Public Meeting On: Gluten-Free Food Labeling

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Proceedings

Welcome

MS. OLIVER: Good morning. I would like to welcome all of you to College Park this morning for today's meeting on gluten-free labeling. I would especially like to welcome the persons who have celiac disease and their caregivers, and we appreciate your interest and your desire to work with us here today, and we appreciate all of your input.

Our intention is to develop a rule to define the term gluten-free for voluntary use in food labeling. And, as you are all well aware, persons who have celiac disease must avoid all sources of gluten in their diet and we will hear more about that this morning. A standardized definition of gluten-free is going to enable everybody to have more confidence in selecting foods by having a standardized definition on the label. FDA is here to listen today. We welcome your input; we want your input.

We have quite a full program so what I would like to do, without any further introductions, is to turn the program over to Dr. Barbara Schneeman. Dr. Schneeman is our Director of the Office of Nutritional Products, Labeling and Dietary Supplements, which we affectionately call ONPLDS. Barbara joined us last year and she has a distinguished career in nutrition. She came to us from the University of California at Davis. We are all very glad to have her here. Barbara?

[Applause]

Opening Remarks and Introductions

DR. SCHNEEMAN: Thank you, Janice. I am pleased to add my welcome to the Center's welcome. We do, indeed, appreciate your participating in this workshop and your interest in helping the agency meet the requirements of FALCPA around a definition for gluten-free.

As indicated, the purpose of today's meeting is to help FDA better understand how manufacturers make gluten-free foods and the challenges facing them. We are also interested in gaining insight on what consumers, particularly those who have celiac disease and their caregivers, understand the food labeling term gluten-free to mean. As you know, we are in the process of developing a regulation to establish a uniform definition of the term gluten-free for use by the food industry, both domestic and foreign, to label and market foods as gluten-free in the United States.

If you look at our agenda, you see that we divided the agenda into three major topic areas. First will be an industry perspective on gluten-free food labeling standard. The second section is on gluten detection analytical methods, and the third is on the consumer perspective on a gluten-free food labeling standard. These three major themes were in response to the questions that you have in the Federal Register Notice. Certainly, it is our intent to focus on those questions in the Federal Register Notice. Hopefully, you picked up a packet of information when you registered. If not, you can get that information at the registration desk.

Now, after we go through those three major topic areas members of the public who have requested to speak can deliver their statements. I would remind everyone that the maximum amount of time for public comments is five minutes for each speaker. Now, if you did not previously request to make a statement but would like to do so, please let the FDA staff at the registration table know by the end of the second break time. We request that any statement that you make be directly related to the issues and the questions that are outlined in the Federal Register Notice.

As Miss Oliver indicated, we do have a very tight schedule. We have a lot of material to cover in our agenda. We have scheduled two 15-minute breaks and a one-hour lunch period. For those who are thinking about lunch just a few housekeeping details, certainly, the most convenient place for lunch is Cafe Wiley. Keep in mind that once you leave the building you will have to come back through security when you come back into the building. But there are other places up on Highway 1. There is the 94th Air Squadron which is located on Paint Branch Parkway but just keep in mind that we only have one hour scheduled.

I want the speakers to be aware that as I want the speakers to be aware that as (*See errata) get near the end of your talk you will hear a very gentle beep-beep-beep. That means one minute. And, because we are trying to make sure we cover all the topics, please be cognizant of the need to wrap up your comments when you hear that gentle beep-beep-beep, and Geraldine and I will ensure that you are aware of that. I wore my bright red suit today so when you see me stand up you know.

Some other housekeeping details, there are restrooms that are located in the hall leading to this auditorium and also in Cafe Wiley. We do request that you do not bring food and beverages into the auditorium. That is just policy for the Center.

This is a public meeting and the meeting will be recorded and a transcript generated. That transcript will be made available on our website approximately one month after this meeting time.

Because of the transcription, we ask that all speakers use the microphone, state their name and affiliation for the record before sharing their comments, and that will be true for all of you who make comments during the public comment period.

If you have more information than you have time to present or you have additional data in more detail or references, please be sure to submit that information to the FDA's Division of Dockets Management under docket number 2005N-0279. That, again, is described in the Federal Register Notice so it is part of the material you should have received during the registration. All comments on the notice on this meeting are due in dockets by September 19th so you still have time after this meeting to submit additional comments.

We have a distinguished panel here in the front. These are members of FDA, members of the Center for Food Safety and Applied Nutrition, and I want to introduce each of them. They will be in charge of questioning each of the speakers and, again, it is with the goal of making sure we address the issues and the questions that are outlined in the Federal Register Notice.

The first member of our panel is Felicia Satchell. She is the Director of the Food Labeling and Standards Staff. That is one of the divisions within my office.

Next to her is Rhonda Kane. Rhonda is a consumer safety officer on the Food Labeling and Standards Staff and she has been the lead staff writer working on the gluten-free initiative. Rhonda has spent a lot of time and planning to get this meeting to come off so we appreciate all her effort in that regard.

Next is Douglas Park who is the Director of the Division of Natural Food Products within the Office of Plant and Dairy Foods, and is responsible for the gluten detection methods.

Next to Doug is Don Zink, who is a senior food scientist in the Office of Plant and Dairy Foods, with an expertise in Good Manufacturing Practices.

At the end of the table is Stefano Luccioli, who is the senior medical officer in the Office of Food Additive Safety, with a specialty in food allergen and intolerances.

I will then be serving as the panel moderator and the meeting facilitator.

So, our first presentation will be on the FALCPA mandate and the meeting questions, and Rhonda Kane is going to give an overview of the new law that directed FDA to pursue the rule-making to define the term gluten-free and a brief review of the list of questions in the recent Federal Register Notice that announced this public meeting. So, Rhonda?

Congressional Mandate and Federal Register Notice Questions

[See presentation slides for Ms. Kane]

DR KANE: (*See errata) Thank you. Good morning. I wanted to provide you some background information on the reason why FDA will be pursuing a standardized definition for the term gluten-free for use in food labeling. On August 2, 2004 a new law was enacted that is called the Food Allergen Labeling and Consumer Protection Act of 2004. FDA refers to this new law by the acronym FALCPA. It represents Title II of Public Law 108-282.

Now, this new law provided details on the requirements for food labeling if a product is made with ingredients that are or contain a major food allergen as defined by the law. This law also includes a provision that directs the Secretary of Health and Human Services, or FDA by delegation, to consult with appropriate experts and stakeholders to define and permit the use of the term gluten-free in food labeling. We plan to meet this directive by publishing a proposed rule by August 2, 2006. So, next August we have to publish a proposed ruling and two years later, August 2, 2008, come out with a final rule that defines the term gluten-free and identifies the criteria that would enable the food industry to use that term voluntarily for labeling their products.

I want to point out that this law does not mandate that food companies label their products gluten-free. Instead, it mandates that the federal government establish a uniform definition for the term gluten-free that would apply to both domestic and foreign products that are marketed in the United States that voluntarily include this label claim. Once a federal definition for gluten-free is in effect, then any product that included this claim on its labeling would have to comply with the requirements or it would be deemed misbranded under the Federal Food, Drug and Cosmetic Act.

Among the things that FDA has done to meet FALCPA's mandate is to publish a Federal Register Notice, which was published on July 19, 2005, a month ago, that announces this meeting and includes a list of specific questions where we have gone out and asked the general public, but we have targeted food industry and those who have celiac disease and their caregivers, to give us feedback on the questions that would be most helpful to us in defining the term gluten-free.

In the Notice we have used certain terms and they are gluten, grains of concern and gluten-free foods. I want to point out that these terms are not FDA regulatory definitions. Instead, they are terminology that we used to explain the questions in our Notice and to solicit comments. In the Notice we use gluten to refer to proteins found in any grains that can cause harm to persons with celiac disease. Grains of concern refers to wheat, rye, barley and oats and their related species such as durum, spelt and kamut or their crossbred hybrids such as triticale, which is a cross between wheat and rye. Gluten-free foods refers to foods marketed in the United States that are either represented to be gluten-free or include statements or symbols in the labeling of those products that indicate that they are free of gluten.

Now, our questions in the Notice are organized under five major subheadings, and they are definitions of gluten-free; gluten-free product development; Good Manufacturing Practices and analytical methods; foods as gluten-free; and,analytical methods; foods as gluten-free; and (*See errata) lastly, consumer purchasing practices.

Now, I want to review the list of questions that are found in the Federal Register Notice, and copies were available at the registration table. If you didn't get a chance to pick one up, you can do so at the break. The wording that I have used on my slides is not identical to that used in the Notice in all cases; I have had to simplify it to put it onto my slides, however, the essence of what I have displayed is the same. I would like to review those questions one by one.

Question one asks how do food manufacturers define gluten-free? How does the food industry, or does the food industry, have a generally accepted definition of gluten-free? Does any entity certify finished foods or raw ingredients to be gluten-free? And, if so, how is that term defined and how is a food determined to satisfy that definition?

Switching to the subheading of gluten-free product development, question two asks how are gluten-free foods produced and what methods are most commonly used to remove gluten from food?

Under the same subheading, question three asks whether it is technologically and economically feasible to produce two different categories of foods in particular. One is gluten-free flour milled from grains other than those of concern. For example, would it be feasible to mill corn or millet into flour without it containing any gluten from wheat?

The other category is oat-based products that do not contain gluten from grains of concern other than oats. For example, would it be feasible for oat-based products to be produced that do not contain any residual amount of wheat gluten?

If it is feasible to produce such categories of foods, what additional measures in the milling or the manufacturing process would be needed to produce these products and what would be the incremental cost to do so?

Under a different subheading of Good Manufacturing Practices and analytical methods, the first question is four and it asks what measures are in place during the manufacturing, packaging or holding of gluten-free foods to prevent them from coming in contact with any grains of concern?

Continuing, question five asks what analytical methods are used to evaluate gluten-free products? How often are these analyses performed? For example, is every batch of finished product tested or are the bulk containers of each of the ingredients tested? And, what is the cost of such testing?

Question six is a whopper. It contains a series of questions that relate to the types and characteristics of different types of analytical methods or test kits that are designed to detect gluten. Among that long list of questions underneath question six are in what grains can the test kit or method detect gluten? What specific mechanism is used to indicate the presence or absence of gluten? In other words, describe in detail how that method or test kit works. What is the sensitivity or lowest level of detection of that test kit or method?

Continuing under the same question, is the test kit or method qualitative or quantitative? If the latter, what is the test kit's or method's limit of quantification? And, what are the test kit's or method's false positive and negative rates?

Further, question six asks is the effectiveness of the text kit of method itself effectiveness of the text kit of method itself (*See errata) affected by the nature of the processing of the gluten-free food or by the food matrix, and if so, how? The food matrix refers to the total food environment in which gluten is found in that particular product. So, that includes all of the components that make up that food. If the test kit or method has been validated, by whom and at what level, such as parts per million, of detection was it validated?

Further, if the test kit or method has not been validated, have the results of its performance or an evaluation of its performance been published in a peer-reviewed scientific journal? Lastly under question six is the question what is the cost of the test kit or the cost to perform that method of analysis?

Continuing under this same subheading but under question seven are the following questions: What analytical methods are currently available or under development to detect the presence of oat proteins in food? Which oat proteins are detected and what is the cost to conduct this analysis? Have these methods been validated or published in a peer-reviewed scientific journal?

Now switching to a new subheading that relates more to consumer issues is foods marketed as gluten-free. Question eight asks if research data or findings are available on what consumers with celiac disease or their caregivers believe the term gluten-free means. For example, which specific grains or other ingredients should not be in a product that is labeled as gluten-free?

Question nine is under a different subheading, and the last of the five, which is consumer purchasing practices. It asks if research data or findings are available on how do consumers with celiac disease or their caregivers identify packaged foods that don't contain gluten? How much time do these consumers devote to identifying such foods?

Lastly, question ten asks if there is research data or findings available on the following: Are the packaged foods that consumers with celiac disease or their caregivers currently purchase or consume primarily or exclusively those foods labeled gluten-free?

What types of gluten-free packaged foods are purchased or consumed by persons with celiac disease or their caregivers? And, does a gluten-free label influence the purchasing decisions of persons with celiac disease or their caregivers when presented with products having identical ingredient lists? In other words, if two products had identical ingredient lists where one had a gluten-free label claim and the other didn't, would the person who had celiac disease or his or her caregiver choose the one that was labeled gluten-free or choose the other one equally if their ingredients are the same?

I want to remind everybody that we are very interested in receiving your written comments on our Notice about this meeting. The deadline to receive your comments is September 19 so it is one month from today. Please note on any correspondence you send FDA about this meeting or the questions in the Notice to the Docket Number 2005N-0279. Comments can be submitted by one of three routes. You can submit them by land mail to FDA's Division of Docket Management, or to that (*See errata) same division via the internet because they have a website, or via e-mail. The Notice identifies the land mail and website address in it. The one that is not in the Notice that I want to point out to you is the e-mail address I have on my slide, and those addresses are included for your convenience on the slide. I just recently learned that the e-mail address will better accommodate the electronic transmission of comments that have an attachment so you might want to keep that in mind.

Well, in closing I want to thank everyone for attending today's public meeting and I hope you enjoy the rest of the program.

DR. SCHNEEMAN: Thank you, Rhonda. As you can see, we do have an ambitious agenda for today. I want to note also for the people attending this session that we are not going to do lengthy introductions of our speakers. You have the background information for our speakers; we provided the bio sketches, but we want to give our speakers as much time as possible so we won't be going into length introductions. (*See errata)

Our first presentation will be to give us an overview of what celiac disease is, and we have invited Dr. Frank Hamilton who will give this overview, the challenges with treatment of celiac disease and why Congress was prompted to mandate the develop of definitions for gluten-free foods that are marketed in the U.S. Dr. Hamilton is the Chief of the Digestive Diseases Program within the Division of Digestive Diseases and Nutrition at the National Institute of Diabetes and Digestive and Kidney Diseases, which is a part of the NIH. Dr. Hamilton?

Overview of Celiac Disease

[See presentation slides for Dr. Hamilton]

DR. HAMILTON: Good morning. I would like to really thank the organizers for inviting me to be a part of this very important public meeting. I have a history, just like most of the patients who have celiac disease. Twelve years ago we were very concerned about celiac disease being an important area of research at the NIH and 12 years ago we had a public meeting, and about the same number of people are here but it has taken almost 12 years for this to really get on the radar screen.

What I would like to do is to really give an overview of celiac disease, a very common condition. As most of you know, celiac disease is an immune-mediated disorder caused by sensitivity to gluten primarily in genetically susceptible individuals. It occurs in symptomatic patients with gastrointestinal symptoms as well as non GI symptoms and in some asymptomatic patients affected, such as patients with type 1 diabetes, Down syndrome, Turner syndrome and Williams syndrome, which is a congenital disorder with ataxia and neurologic disorders that are seen in young children, and selective immunodeficiency syndromes, as well as first degree relatives of individuals with celiac disease.

As most of you know, clinical manifestations of celiac disease can be very protean. Usually you can have the classical presentation with the GI symptomatology, non-gastrointestinal or the atypical presentation and the asymptomatic individual.

This is a theme that has come out. It is called the celiac iceberg that many of you have already heard about, where there is a small number of people who are identified as having celiac disease but there is a silent number who go around with various manifestations of either GI symptoms or other symptoms. Then there are those patients who have latent celiac disease. These are the patients who may have normal tissue but have positive serology.

The clinical manifestations of celiac disease--this is what we were all taught in medical school--is that it is the most common thing that you see in young children between the ages of 6 and 24 months. The patient is usually a child who comes to the pediatrician complaining of chronic or recurrent diarrhea, abdominal distention, loss of appetite, failure to thrive compared to his other siblings, abdominal pain, nausea, vomiting and irritability and sometimes the parents may present with only one of complaint, that is, irritability or a child who is always so fussy and nothing does anything to improve comforting him.

This is a typical picture of a child that is seen in the pediatrician's office. This is a child with a typical presentation with the abdominal distention. It doesn't project very well but around the rectal area you can see some redness, and this represents the chronic irritation of the perirectal area secondary to chronic diarrhea. Also, you notice that the folds around the buttocks are somewhat not prominent, and this is primarily due to weight loss.

Now the non-GI manifestations, and these are the ones that physicians really don't think about but these are the common presentations that we can see in older children or adults: dermatitis herpetiformis, a skin disorder we will see a picture of. The dentist can commonly see patients who have essentially dental hypoplasia or essentially eroding of the enamel of the teeth. Sometimes patients can present with osteopenia or loss of bone mass density, as well as osteoporosis. One of the most common things that we see in adolescents is short stature or delayed puberty in those kids who, in fact, do have celiac disease. Iron-deficient anemia, especially in a young woman who presents to the physician, as most of you know, most physicians will see a woman who is on her menses and says her disorder is due primarily to menstrual cycle. However, this is commonly seen in women who have iron deficiency anemia who have normal periods. Periodically we see patients with inflammation of the liver, arthritis and epilepsy in young children who may have calcifications on their CT scans.

Dr. Peter Green, of Columbia University, did a very interesting survey of over 1,800 patients who had celiac disease and one of the striking things that came out in his survey was that a number of the patients who had celiac disease--he took a very careful history--from the time of presentation of the symptoms it was a total of 11 years before the diagnosis was finally made. So, there is a long lag phase before the final diagnosis is made and that is primarily due to the fact that many of us don't think, or the clinician or healthcare provider does not think of celiac disease as a potential reason why a patient may be presenting to the office.

This is a typical presentation of a patient with dermatitis herpetiformis. This is a very itchy or pruritic lesion seen on extensive surface of the arms of an individual with the disease. For these patients it may be the only manifestation of celiac disease, the unusual rash.

Again, as I mentioned, there is the silent phase. There are some patients who may never have any symptoms until their fourth or fifth decade of life. However, they may have damaged mucosa and a positive serology. Identified by screening are asymptomatic patients from groups that are at high risk. Again I want to emphasize that first degree relatives of patients with celiac disease have a higher percentage of having the disease. Again, children with Down syndrome, as well as patients with insulin-dependent diabetes will have a high prevalence of celiac disease.

In the latent phase are those individuals who have no symptoms and if you do a biopsy on these individuals, with our present requirements for human research, it is not likely that we can get a normal biopsy on an individual who is asymptomatic. The patient usually has a positive serology and usually these are the patients that are sort of the enigma for the primary care physician who comes in with vague symptomatology. Sometimes it is either a viral illness of a bacterial infection that will trigger the manifestation of celiac disease in this patient and they go on frequently to develop celiac disease.

I will never forget a patient that I had followed at the VA hospital, over in Baltimore. For years this guy had been presenting to the clinic with chronic diarrhea. Our index of suspicion was, you know, that he was just a chronic complainer, and when we finally did a serology--this was in the early '80s and at that time antigliadin antibodies were available--we tested him and he was positive. He was forever grateful because this guy had wasted from about 180 lbs. to about 110 lbs. and he was very emaciated. So, for our physicians we really sort of emphasize in our teaching programs the importance of having a high index of suspicion when anybody presents with an unusual presentation with diarrhea.

Again, this is just the associated symptomatology. As we mentioned before, the patient's first degree relatives, the percentage of them who have celiac disease ranges anywhere from 4-18 percent. In first degree relatives with insulin-dependent diabetes the range can be anywhere from 3 percent to as high as 16 percent who will have celiac disease. Thyroiditis, another condition which is an autoimmune disease, inflammation of the thyroid gland--these patients also have a high prevalence of celiac disease.

Again, this just goes over some of the data on the healthy population and I will show this in the next slide. Some of the major complications of celiac disease that the clinician, hopefully, will not wait until the end when the patient has developed this is that the pediatricians will always--you know, parents will come to the pediatrician and say our son is lagging far behind his brother or sister with this short stature. Again, we have seen more commonly than not that dermatitis herpetiformis will present usually in the fourth, fifth and sixth decade of life.

But the biggest problem that tends to be underestimated is in dental practice, and part of the NIH consensus conference that was held in June, 2004, is emphasizing that the dentist has a primary role. If he has a patient who comes in with recurrent dental hypoplasia or eroding dental enamel, he really should start thinking of celiac disease or have the patient referred to a primary care physician for evaluation. Again, recurrent ulcers within the mouth, stomatitis, is very common.

One of the conditions that we frequently don't think about is women who have recurrent miscarriages. Based on data, there is a great deal of data that show for women who have fertility problems celiac disease is one that we have asked people to really consider, especially in a young woman who may be of European extraction. We will talk about the distribution of the disease later on.

Osteoporosis presenting in women of ages 30-40--osteoporosis, as most of you know, is a disease of older women and very commonly you will see young women who are showing signs of bone mineral loss at the age of either 20, 30 or 40.

We will talk briefly about refractory celiac disease but the thing that we want to stress--and some of the European studies have done an excellent study. There was a cohort study that was done in Sweden that did a very nice population study of 800 celiac disease patients, from 1974 through 1993, and they found that there was an increased mortality of patients who had celiac disease. Whether they were gluten-free or not, or adhering to a gluten-free diet, that was not available in the study that was reviewed.

Again, this is the old paradigm that we thought of before 2004, that this was a rare disease of children. We thought the incidence fluctuated. It was always taught that if you were an Irish Catholic you had 1/400 chance of having celiac disease but that whole paradigm has changed. As most of you know, it was thought to be a disease of Europeans.

This just shows the sources of finding patients with celiac disease. We talked about first degree relatives, patients with short stature, anemia, fatigue and abnormal liver function tests and, again, the autoimmune disorders are a smaller number that should be followed and, again, blood donors, students and general population.

This is a study that Dr. Fasano, at the University of Maryland did. He screened over 13,000 individuals for celiac disease. This was the thing that really sort of changed our thinking about the prevalence of this disease. As you see, in the healthy individuals there were 4,000 that were healthy and, of that number, 1/133 had a positive serology for celiac disease. If you look at the high risk groups, you see that there is a range of 1/40, 1/22 and 1/39. The upshot of this slide is that usually it has been estimated that there are about 40,000 people in the United States who have celiac disease. But Dr. Fasano and others are supporting this hypothesis that the projected number is really about two million individuals in this country who have celiac disease.

I just want to mention the global village of celiac disease. I think this is really how our paradigm has changed in the last few years. It was thought for many years that this was a disease of Western Europeans. However, one thing that has really come out in a lot of the epidemiological surveys is that one percent of the patients in countries like Iran and India have a high prevalence of celiac disease. Also in South American we are finding greater numbers of populations who have celiac disease based on the advent of these new serological tests. As I mentioned, most of these cases escape diagnosis and most people think that it is just a product of what the person has eaten over a period of time. Again, we will talk about the role of screening and whether it is indicated. Again, the impact of this is really remarkable.

One of the things that we really try to emphasize to our physicians, nurses and healthcare providers is to have a high index of suspicion for celiac disease; think beyond the paradigm of what it was 20 years ago. The important thing is to confirm the diagnosis. This is a life-term commitment to celiac disease. Once a patient is screened for celiac disease, really the important thing to do is to do an intestinal biopsy. I underscore that. Although there are a lot of concerns about doing an intestinal biopsy, especially in young children, this is a lifelong term commitment to a gluten-free diet and I think there are some issues of quality of life implications when a patient is placed on this diet, and we will hear from other speakers this morning.

The failure to treat potential long-term adverse health events--I think many people and some of the epidemiologic studies that have been coming out now show that patients who have celiac disease are very prone to develop intestinal lymphoma or specifically non-Hodgkin's lymphoma, and it has been found that these patients have a higher prevalence of this disorder in their 40s, 50s and 60s. The other thing to remember also is that patients with celiac disease in later years of life have a higher prevalence also of cancer of the small intestine as well.

I wanted to mention the role of serological tests. Since the NIH consensus conference and prior to 1995 there was a lot of proliferation of kits to test for serology. The NIH consensus conference had essentially an evidence-based approach to evaluating these tests, and the main reason that we emphasize the types of serology is that there are a lot of tests that are being propagated and promoted to be done for suspected celiac disease that are not warranted and are very costly.

But the main reason that we strongly urge serological testing is to identify the symptomatic individuals who need a biopsy; secondly, screening of asymptomatic individuals that are at high risk, such as those first degree relatives of celiac disease patients, those patients who have insulin-dependent diabetes, as well as those patients who have family members who may have Down syndrome or Turner syndrome, and really to support the diagnosis. One thing that we really stress is the importance of using this marker to follow patients to determine compliance with the gluten-free diet.

The NIH consensus conference last year felt very strongly that the antiendomysial antibody test and the TTG or the transglutaminase antibody tests are, in fact, the only tests that you should order for your patients because these have 95 percent sensitivity and are 95 percent specific for gluten abnormalities. The HLA typing which can be done on some patients is usually done in patients where there is a question about the positivity of these studies. Again, the NIH really stressed this based on the evidence that was in the literature advocating these two tests to be performed.

Most of you know that treatment is a lifelong commitment to a gluten-free diet, and most of you know that there is a strict lifelong commitment of avoiding wheat, rye and barley. Back in the 1960s and '70s there was a concern about are oats safe, and studies from the 1970s really suggested that oats were toxic in patients with celiac disease.

The Agency for Healthcare Policy and Research did a very extensive review of the literature and one of the things they found very striking is that those studies were very small studies. Those studies had as few as 6, 7, 12 patients who were placed on oats. The recommendation from that review that the Agency for Healthcare Policy and Research determined was that those studies were too small to make any statistical statement. Therefore, there was just a better need to really clarify the role of oats in the setting of gluten-free diets.

Oats, as most of you know, contain a protein called avenin. This is a protein that is similar to the wheat gliadin. Both are prolamins which are rich in glutamine and proline which are both amino acids that have the same peptide sequence. As we will hear later on from our chemists here, we will hear about the proportion of proline and glutamine compared to gliadin which is very, very low.

This was a really landmark decision or a landmark article in 2004, by Dr. Hogberg, which was published last May, which really did the first randomized clinical controlled trial looking at gluten-free diets with oats versus gluten-free diets alone. This is a very important study and it was mentioned in the public register also because it was the first to really document large number populations which were fed with oats as well as given a gluten-free diet. They found that patients in this setting had normalization of tissue and the serological markers did not change. Essentially they remained normal when they were placed on oat diets with the gluten-free diet.

There was other supporting evidence that was reported in GUT in January, 2003, where there were patients who had dermatitis herpetiformis and they found that the patients' skin lesions did not worsen with the oats in their diets. Again, this gives other supporting evidence that gluten [sic] is not toxic in patients with celiac disease.

As most of you know, and there are going to be other discussions, these are the sources that all of us sort of ingest: bread, bagels, cakes, you name it, but the other thing that was not mentioned is that periodically cosmetics, lipstick or things in mouth washes as well, have gluten in them as well and some patients are not aware of this. So, I think we have to remember that those things are triggers as well.

I am just going to give you essentially what the NIH consensus conference mentioned, that these are the six elements in the treatment of patients with celiac disease. It is a lifelong-term commitment to having a multi-disciplinary approach in how these patients are approached. You have to have a skilled dietitian or nutritionist working with you, the family and the caregivers. And, education is essential not only for the patients but for the healthcare provider. We are beginning to do a public awareness campaign at the NIH targeting physicians, primarily family care providers, through the American Academy of Family Medicine, and also through the American College of Physicians, to really educate the healthcare providers about the importance of this disease and consideration when patients come into the office.

Again, the identification and treatment of nutritional deficiencies--as I mentioned before, the many deficiencies that these patients present with, as you well know, are vitamin B deficiency, iron deficiency and thiamine as well as folate. The important thing I want to emphasize about folate, which is so common in our diet, is that a lot of the patients who have celiac disease who present in their 40s and 50s is loss of memory or forgetfulness. It is amazing, when you give them 1 milligram of folate a day, it makes a big difference in how they process, in how they reason and think.

Again, the importance of advocacy groups--I cannot underscore that because these are the people who have made this meeting possible because of their strong commitment to bringing the awareness of the public about this very important public health disease, and a continuous long-term follow-up by a multi-disciplinary group.

The other thing I just want to mention is that people will say why don't we screen for celiac disease at an early age. As most of you know, most of the public health screening that is done in this country is based on the fact that you can detect the disease at the time of birth. If you remember when you had your kids, they all got stuck in the ankle for PKU. This disorder is very rare in this country; it is 1/14,000 births. When you see the number of celiacs in this country, that is far more common than PKU is but the reason that this test is not done routinely is that there are a lot of patients who have celiac disease. The TTG, or the transglutaminase, does not appear until age two or three and that is why there hasn't been a big push to public screening in kids who may have celiac disease.

But, again, we feel this requires knowledge about what gluten-free diet is, and this meeting I think will be very instrumental in really raising our awareness of what gluten-free diets are and understanding the risk and the serious complications of celiac disease.

The other thing is to reinforce how important it is not only for the caregivers but also the family members to support patients with celiac disease and to be a source of support. Again, the advocacy groups have really been very instrumental in helping a lot of patients who deal with the issues of depression and anxiety really cope with their illness because it is an illness that impacts not only the patient but also their families and their colleagues.

Again, I just want to thank the organizers. Really after 12 years of sort of pushing unawareness, it has taken this long for it to hit the radar screen but, hopefully, we will begin to see a difference in how foods are labeled in this country. I was in Canada five years ago or six years ago and I was very struck that most of the Canadian restaurants always label their meals with what is gluten and what is gluten-free. Again, thank you very much for your attention.

[Applause]

DR. SCHNEEMAN: Thank you very much, Dr. Hamilton. I think you have given us the scope of the public health significance of what this requirement means to the American public. I will allow our panel from the FDA--if you have some questions, I think we have a few minutes to address them to Dr. Hamilton. If you would please identify yourself.

Question and Answer Period

DR. LUCCIOLI: Stefano Luccioli. Dr. Hamilton, thank you for a very informative lecture. I just wanted to clarify with you what your feeling is about the two studies, recent studies on oats showing that there are a few individuals who may react to the avenin portion of oats. What is your feeling about these studies?

DR. HAMILTON: Thank you, that is a very good question. I think the evidence is still not in. I think there was some concern raised by some of the reviewers who looked at that article very carefully about the milling and the preparation of those products where there was contamination. I think based on that, the jury is not in. But I think the randomized, controlled study by Hogberg is very convincing in a large number of patients, and I think some issues of milling might have affected those studies.

DR. LUCCIOLI: Also another question, do you know of any definitive study where the risk of mortality is also shown for individuals who have silent disease or latent disease? I believe most of the epidemiological studies have looked at untreated symptomatic patients and I am wondering if you have any insight on whether there is an equal mortality for all groups of celiac disease.

DR. HAMILTON: As I mentioned earlier, the study that was done in Sweden looked at a cohort of patients who had biopsy-proven celiac disease and mortality rates were much higher. That is the only study that I have seen in the literature that looks at that. It didn't specify whether these were latent or typical celiacs. So, the information is very limited at this time.

DR. LUCCIOLI: Thank you.

DR. SCHNEEMAN: Other questions from our panel?

[No response]

So, we are now ready for our first panel. As indicated in the agenda, this is where we would like industry representatives to give us their perspective on the gluten-free labeling standard and the questions that we have raised in the Federal Register Notice. Again, because of the nature of this meeting, with each speaker we will ask our panelists to address questions to each speaker and then there will be a more open time for discussion and comment at the end of the panel.

So, our first speaker is Miss Jane DeMarchi, who is the coordinator for technical and export programs at the North American Millers' Association.

Industry Perspective on a Gluten-Free Food Labeling Standard North American Millers' Association

[See presentation slides for Ms. DeMarchi]

MS. DEMARCHI: Good morning. My name is Jane DeMarchi and, as mentioned, I am the coordinator of technical and export programs at the North American Millers' Association. Thank you for giving me an opportunity to speak to your panel today.

NAMA, or the North American Millers' Association, represents the what, corn and oat Association represents the what, corn and oat (*See errata) milling industry. Our members produce 160 million pounds of milled products daily, which is 96 percent of the milling capacity in the United States. Our members' products are put into a plethora of food products that Americans consume every day--cereal, bread, cakes and cookies, pasta, snack foods and beer.

I have been asked to inform the committee on the processes used by the largest segment of the milling industry, and specifically I will attempt to respond to questions two through five from the Federal Register Notice for the meeting.

The goal of the milling process is to produce a consistent product through blending. Our customers rely on receiving a product that is uniform in performance attributes and appearance. However, a fact of milling is that the grains received in the mill contain trace quantities of other grains in them. The milling process seeks to limit these impurities as much as possible but it cannot extract them 100 percent.

Cross contact begins at the farm. The amount of other grains mixed into product depends on a variety of factors, including what part of the country or Canada it is grown in. Oats are grown in agricultural production regions which are also conducive to the production of wheat, barley, rye and other small grains. Most producers in these areas grow a variety of grain in any given year and typically rotate crop species on a piece of land from one year to the next. Kernels that fall into the ground prior to and during harvest one year often grow as volunteer grain in the next year's crop. For example, if a producer grows barley one year, followed by oats the next year, the oats harvested from the field often contain a small percentage of barley.

In the Illinois corn belt a farmer may just grow corn but in Kansas they may grow corn and wheat. Weather conditions, harvesting practices and other variables lead to inconsistent cereal grain admix from concentrations from year to year. This variability makes it difficult to determine an expected level of the presence of other grains in any given product.

In the corn and oat business some mills have established purchasing relationships with particular farms to guarantee grain quality. This may or may not have an impact on the presence of other grains. Organic millers do contract purchasing almost exclusively and still have issues with cross contamination of grains.

A second source of cereal grain admix is during the handling of cereal grains. Because various crop species are grown in a given region the grain handling systems usually handle multiple grains which can add to the amount of unwanted grain. Since grain handling equipment is expensive and cleaning of equipment is time consuming, different grains are often handled using the same equipment on a farm to minimize capital investment, and the equipment is usually not cleaned out between handling the two different grains.

The trucks and rail cars used to transport grains are also not thoroughly cleaned out between uses. These problems persist to the elevator that receives the grain from the farm. An elevator may receive a load of wheat from a producer then subsequently receive a load of oats from another producer, without bothering to empty the leg boots or clean the tails of drags. Elevators also do not undertake rigorous cleaning of the silos that store the grains when the grains are changed over in part to minimize dust which causes health and safety concerns. These practices I have described introduce additional cereal grain admix to the grain destined for milling.

Grain is inspected and graded prior to delivery and then reinspected when the grain is delivered. The U.S. grain standards, established by USDA and administered by the Grain Inspectors, Packers and Stockyard Administration, allow for other grains to be mixed in. This is considered foreign material and is allowed at up to four percent, depending on the grade and the grain. Mills may buy from the higher grades or require their suppliers to sell them grades at a higher standard. Typically, milling quality oats contain 0.5 to 1.0 percent cereal grain admix. But specifications can allow up to a maximum of 2-3 percent. Standards for grades of corn used in milling generally have 2-3 percent foreign or broken kernels. Similarly, some corn mills may have tighter specifications for 1 percent of other grains, but that is not universal. The U.S. grain standards are based on the realities of production agriculture and the bulk grain handling business, and are not necessarily what the food processing industry would prefer.

The milling process--grain is cleaned prior to milling to remove any foreign material. Part of the objective of the cleaning process is also to remove as much as cereal grain admix as possible. There are three primary technologies that can be used to clean grain: width grading, and this technology is the basis of most screening applications and typically relies on the fact that narrower kernels will fall through a slotted or punched sieve while the thicker kernels will remain on the top of the screen or sieve. Length grading, which is the concept of segregating kernels by length, is usually achieved using rotating drums with indented pockets into which the kernels fall. Shorter kernels fall deeper into the rounded pockets, allowing the drug to remove them from the (*See errata) longer kernels that can not fall as deeply into the pockets. Density segregation uses moving air streams or vibration as a basis to separate kernels based on their density.

Concentrations of wheat, barley and other cereal grains in oats and corn can be used with the appropriate combination of the above three principles. But these three concepts do not allow for the complete removal of all admixed grain. The success of these mechanical measures is based on the difference in size and shape of the desired grain and the unwanted grain. Wheat and corn are more easily separated because they are quite different.

However, on this slide you can see pictures that depict how close various grains that are of concern in oats are in appearance to one another. Oats, wheat, barley and rye have some difference in average kernel length, width and density but the natural variation between crop kinds, crop varieties and individual kernels means that significant overlap exists between any two populations.

While width grading can be used as the basis of removing many of the larger barley kernels from an oat sample, and length grading can remove many of the shorter wheat kernels, thin barley kernels and long wheat kernels will remain in an oat sample.

Density separation similarly can be used to remove some of the wheat due to its high bushel weight, but the best milling oats are close to the same density as barley and diseased or shrunken wheat kernels are often no heavier than oats.

Some of the newest color sorting or optical sorting technology holds the promise of being able to remove individual kernels of grain admix by evaluating each kernel under various light conditions and comparing to a reference or standard. Kernels failing to match the standard closely enough are removed from the stream typically by a small blast of compressed air. However, the technology is expensive and it is generally of low capacity, and not yet reliable enough to guarantee the level of accuracy needed to be considered an allergen control due to the small difference in the color of the grains that are trying to be sorted. If the mill adheres too tightly to a standard in mechanical cleaning procedures, they run the risk of rejecting too much of the desired grain along with the additional grain that they do not want.

Reducing cross contact at the mill is also important. Mills follow Good Manufacturing Practices that require regular cleaning and inspection of equipment. It is critically important to mills that product dust not be allowed to gather in the equipment or outside for sanitation purposes. In many cases today mills are dedicated to one grain line. In those instances, which is typically just a portion of the mill, where more than one grain is handled mills undertake a rigorous cleaning protocol when switching between grains. This includes opening the equipment and dry-wiping it down and vacuuming it as necessary after all of the first grain runs through. At the start-up of the next grain a certain amount is run through the line and then discarded. The grains themselves are abrasive and assist with the clean-out procedures. After these procedures the mill is considered saturated with the new product.

Corn and wheat mills do not generally conduct tests to determine levels of other grain mixed into the final product. There are several reasons for this. The mills use all of the available technology to separate out the unwanted grain. However, once the grain is milled the presence of other grain is not evenly distributed throughout the product. There are no reliable tests that accurately determine the amount of unwanted grain overall in any given lot.

ELISA tests are still fairly new and do not have a long history of being used for allergy detection in mills. They test a very minute amount of grain and individual test results are greatly skewed by the presence of one fraction of an unwanted grain. Without thresholds or standards, mills also do not have a target number which they are trying to achieve.

Oat mills do have a process they have used for establishing the levels of cereal admix in finished product. This is possible because of the greater size of an oat flake. Representative samples are taken from a lot and then composited. After mixing, a representative 200 gram sample is withdrawn from the larger sample. Each individual flake in the sample is separated by hand and visually inspected in an in-house lab. From there, a concentration of cereal admix in the lot can be derived.

Economics of grain milling is another consideration. The high volume and low cost of milled products has an impact on the type of screening and testing that mills are able to do. Mills operate as close to 24/7 as possible. Like most food processors, they seek to avoid shut-down time. An average mill may produce a million pounds a day, seven days a week. If they shut down for a day it will have a significant impact. The mills emphasize mechanical means as the best method to address the presence of other grains. Testing every bag of product is not practical. Mills cannot control the fact that product comes to the mill with traces of other grains mixed in.

Research has not been conducted on an industry-wide basis to quantify the levels of cereal admix in oats or corn. In some instances a customer may specify what level they are willing to accept and the mill will operate accordingly for those lots, however, this is not common.

As previously mentioned, variability of admix from year to year is great. Weather is a large factor in this and the effects of the weather are felt far into the future. Herbicide application may also have an impact.

It is important to note that generally the levels are in the low parts per million range on all products. However, our members are conscious that without a threshold, gluten-free means zero. For the oat millers zero is, frankly, not achievable both due to the presence of gluten in oats and because of the small presence of other gluten-bearing grains. Currently, corn millers do consider their corn products to be gluten-free. Corn is not gluten-bearing and can more easily be sorted from gluten-bearing grains. The presence of admix in oat products varies depending on product and portion size. Concentrations of wheat protein in oat flour will be higher than those in oat flakes due to the milling process.

Although industry-wide research has not been done, I have analyzed an example of what could be considered realistic for the presence of wheat and barley in a sample of oats. In my example a 28 gram serving of instant oatmeal with a .03 presence of wheat at 15 percent protein and a barley presence of 0.16 percent at 14 percent protein content, this serving would have approximately 7.5 milligrams of wheat and barley protein, approximately 40 percent of which, or 3 milligrams, would be gluten.

In conclusion, I would like to say it is not a perfect world. The farming system allows for a certain level of mixed grains. The technology is not available currently to separate grains 100 percent in the milling process. In an effort to protect the most sensitive members, celiac support groups recognize this situation and do not endorse the consumption of oats.

However, there is more work to be done to better understand the relationship between oats and celiac disease. If gluten-free means a zero tolerance level that places the threshold at zero we run the risk of turning products that had been previously been considered safe for celiac sufferers to not be considered gluten-free. Corn millers who to date have considered their products to be gluten-free may reevaluate that determination at a zero threshold. As we like to say at NAMA, zero is a very small number.

Thank you for allowing me to address this group and I would be happy to answer any questions that I can.

[Applause]

DR. SCHNEEMAN: Great! Thank you very much. I will turn to our panel to see if we have some questions. If you will just use the hand mike that is right here, and be sure and identify yourself.

Questions and Answers

DR. ZINK: Don Zink, with FDA. Do you in these mills typically use pneumatic systems for moving milled flour, and are these runs of piping fairly long and, if so, how do you go about cleaning them, or can you?

MS. DEMARCHI: Yes, they do use pneumatic systems, and the pipes are somewhat long. Mills operate on several levels so they are not extensively long pipes; they tend to be broken up but it would be a series of shorter pipes. The cleaning process for the pipes is basically when the grain runs through, it is allowed to completely drain through.

DR. SCHNEEMAN: Other questions?

DR. PARK: I am Doug Park. I am with FDA. I have actually several questions and they are kind of in sequence a little bit as you go through your processing and product movement. Early on, when you are doing your inspection, I assume this is in conjunction with U.S. federal inspection of the grains. What do you do individually as an industry to supplement and to identify whether there may be cross contamination of the different types of grains?

MS. DEMARCHI: Different mills and different companies, depending on the grain, have different systems. There is certain reliance on the grading and the inspection that is done at the elevator level. In most situations it is reinspected on arrival. In some cases the elevator will take a sample and send it to the mill for testing, and it is laboratory tested to evaluate the presence of other grains. Usually the process is taking a variety of samples and then compositing them, mixing them and then extracting a smaller sample that is then tested.

DR. PARK: Does it take into account the damaged kernels or the percent, because your cleaning is based, obviously as you described, by size, and weight and length, and so forth? Does it take into account the damaged kernels that may be affected?

MS. DEMARCHI: In terms of the damaged kernels of the ones you desire or the ones that you don't?

DR. PARK: Both, exactly, the ones that you desire and the ones you are trying to avoid.

MS. DEMARCHI: I know part of the corn specification does take into account damaged kernels. I don't know about the oats.

DR. PARK: Okay. You talked about the HACCP programs. What do you go through there with respect to sampling and then, obviously the analytical testing of that product?

MS. DEMARCHI: In terms of the HACCP program, I think for the mills it is identifying the areas that are at the greatest risk for cross contact. If you are in a dedicated mill, and if you are doing a HACCP evaluation for allergen control, there is going to be less risk of cross contact so it would generally be following normal cleaning procedures. Where there are areas where there would be some different grains used in a bagging line, or something like that, they would probably more closely evaluate the cleaning procedures that they are using. But at the moment in mills they don't do things like swabbing and testing in that way.

DR. PARK: My final question will be dealing with the sampling. Do you have in-line sampling procedures set up, or are you addressing the bulk? Your comment is very correct and it is very difficult to sample bagged product.

MS. DEMARCHI: Yes, we do have in-line sampling procedures. At the moment though they are not used for allergen characteristics. We use NIRs, the light reference testing generally for performance characteristics but we have not done that type of sampling for allergen, and I don't know actually how long it takes to do the allergen analysis but my guess is it is something that would take a while to get your results.

DR. PARK: Some of our speakers will address that very appropriately, but they are not an immediate response. There is a time lag. Have you as an industry and as a group addressed that, how then to do the appropriate sampling and testing specifically for the allergen issues? It is kind of a challenge out to you that has to be addressed.

MS. DEMARCHI: I think that is something that we are still considering, and I think at the moment it is being done on an individual company basis.

DR. PARK: Thank you.

MS. SATCHELL: Felicia Satchell, FDA. I guess I just wanted to hear maybe a little more, if you could expound, on this new technology, the one that you talked about on differentiation based on color or optical sorting machines. I guess, is there research ongoing to improve this method, to bring the cost down for using it? Is there any manufacturer that is trying to use it or any mill trying to use it in their process?

MS. DEMARCHI: My understanding is that it is being used but not--I think it is being used in corn mills, but I don't think it is prevalent in the industry. I think when you talk about the expense, it is largely related to the capacity issues. The mill would have to slow down to a large extent and also the reject level is so high that it is difficult also to put it back into rework stream. There are other issues not just related to the cost of buying a piece of equipment because I would imagine that that is something that could be handled. But it is how to actually work it back into the manufacturing system, and I think that equipment hasn't been refined for the milling industry enough.

DR. SCHNEEMAN: Thank you. A lot of questions. One more.

DR. ZINK: Don Zink, with FDA. Just a quick question. Is it common in the milling industry to try to validate cleaning to some particular degree of cleanliness? And if they do validate cleaning methods, say, between grains, what sorts of methodology do they use to measure that degree of cleanliness?

MS. DEMARCHI: I am on thin ice a little bit here but, you know, I think that the mills use the FDA--you know, everything they do is based on FDA guidelines and then they are regularly audited. So, I would say probably it is whatever is generally accepted.

DR. ZINK: What I was getting at for example, after they have cleaned up a line, would they go back and test for residue of the previous grain?

MS. DEMARCHI: No, they don't do that testing currently.

DR. SCHNEEMAN: We will have time with the panel also later. We don't want our first speaker to carry the burden of all the questions. Our next speaker is Mr. Dennis Gilliam. He is the vice president of sales and marketing for Bob's Red Mill Natural Foods, Inc. Do you have slides?

MR. GILLIAM: No, no slides.

DR. SCHNEEMAN: No slides?

Bob's Red Mill Natural Foods, Inc.

MR. GILLIAM: Panel members, you may want to avail yourselves of the packet that I left for you because I will be referring to a piece or two that is in there, and it is up here on the table. It has the assembly of wine in the heart of France, where they are assembling millstones on the cover.

Dennis Gilliam, Bob's Red Mill Natural Foods, partner, executive vice president, sales and marketing. It is a pleasure to be here and to share. Our company has also brought three other representatives who will speak this afternoon.

Just to give you the lay of the land with our company, Jane was mentioning the 96 percent of the millers that come under her umbrella. We do not fall under her umbrella. We are a tiny part of the four percent. All right, how we became stakeholders here I believe is relevant so I would like to begin with that.

At Bob's Red Mill we set up initially, over 30 years ago, with the intention of milling the widest variety of grains available, and we do that. It soon surfaced though that some of these grains were appealing--not only appealing to but being used by a very unique segment, celiacs and those adverse to gluten. We became a stakeholder in gluten-free more than 10 years ago, and here is how we went about it.

After fielding gluten-free questions and comments from our customers, we invited a number of experts into our plant, research scientists, some of whom we have spoken about this morning, gluten-free cookbook authors, lecturers, spokespeople for the celiac community to tour our facility and make recommendations. Based on their assessments and recommendations we then dedicated stand-alone milling and packaging rooms for gluten-free production; implemented a testing protocol. And, to assist consumers in their pursuit of the gluten-free products, and this is what you will find in our packet, we drafted a statement. We created a gluten-free logo for our package labels; placed gluten-free product advertisements in diverse publications; implemented a program of gluten-free shelf talkers that pop into the clip strip at the grocery store to identify gluten-free products; created, shared and posted on the internet many gluten-free recipes; published a mail order catalog featuring gluten-free and soon found that to be the shining star of our entire mail order catalog; exhibited at gluten-free and diabetic conferences.

I also feel it is significant to share that since we also market in Canada our testing protocol, gluten-free statement and gluten-free logo were carefully designed to meet their specifications and stand the scrutiny of the Canadian food inspection agency. They do not insert a certifying agency into the process but their rules are stringent. They are practical and they are fair. They do random testing of products and occasionally issue warning letters, and in rare, rare cases they will remove non-compliant products or products that fail the random testing from store shelves. All of our products withstood the test of that protocol for several years.

Based on those experiences, I would like to share with you how we define gluten-free. Now, in the process of defining gluten-free--well, we from time to time do this but we recently gathered gluten-free foods from 14 manufacturers and examined each package to see how they were handling the claims. This wasn't done with a critical eye at all; this was done with an informative eye. We found that five speak of dedicated gluten-free environment; seven speak to being wheat and gluten-free; one says simply ELISA and GF/CF, which I am sure means gluten-free/casein-free; one says 100 percent dedicated machinery; and three state they also are free of other allergens.

In our business we define gluten-free as a product that does not contain in any form or derivation wheat, rye, barley, triticale, spelt, eye corn and kamut grain. To this list, until they can be proven by rigorous cleaning and testing as has been previously mentioned, to be free from other contaminating grains, we have added oats even though we believe oats to be inherently gluten-free. The statement on all of our packages reads, and you will see labels in our packet that will bear this out, quote: Products labeled gluten-free are batch tested in our quality control laboratory. We use an ELISA gluten assay test to determine if a product is gluten-free, end of quote.

Along side this statement we place a gluten-free logo of our design, and you will see an 8.5 X 11 copy of that in our packet. There is nothing unclear or contradictory in what we do or say. However, I think as you can see as a group, these 14 manufacturers, based on the 14 products we recently reviewed, we manufacturers are all over the board in our approaches to communicating to consumers that we are gluten-free.

How gluten-free foods are processed in our plant is what I would like to deal with next. The gluten-free foods we manufacture are stone ground on quartz millstones. While these millstones grind a multitude of products, the only products ground on these dedicated mills in a dedicated mill room are inherently gluten-free. In our gluten-free manufacturing process we use only grains, beans and seeds and ingredients that are inherently gluten-free. We manufacture and package over 50 gluten-free products.

For over 30 years we have used French burr stones to grind all of our products. These have been in production around the world commercially since the 14th century. Our stones easily mill nearly every grain, bean and seed grown. They make flour, meal and cereal that incorporate the bran, germ and endosperm. We currently mill various beans, various types of rice, buckwheat, flax seed, peas, millet, kimwa, sorghum, and teff into gluten-free flours. All are verified gluten-free by testing, and more about that in a moment.

Future increases in gluten-free production are absolutely assured. We have mills and capacity to satisfy production far into the future. But as your question properly asks, is this technology feasible for others? Well, remember, we are one of the four percent not in Jane's umbrella so we are fairly small. But I am not sure, precious few I surmise, have indicated an interest in pouring over old milling journals to learn how to set up and sharpen millstones the way we do. And, there may be a limit to the number of manufacturers willing to implement the necessary control over cross contact and testing protocols. Different milling systems, as we have just heard, are capable of producing flour and cereal from some non-glutinous grains and I am not sure if they can also grind beans and seeds. Others may speak to that later.

I would like to share with you measures we employ to prevent cross contamination. We purchase all of our gluten-free grains, beans and seeds, precleaned. Upon receipt of each shipment our laboratory does a random sampling ELISA gluten assay test. After incoming products are tested and verified gluten-free, they are moved about in super-sacks or one-ton totes. Each tote is clearly marked gluten-free. These containers, and all containers used for the storage or transportation of gluten-free products are never used to store or transport grains of concern or products containing grains of concern.

We utilize a dedicated room to house our gluten-free ingredients, and the milling, mixing and packaging equipment used to manufacture them into marketable products. No grains of concern are ever introduced, processed, mixed or packaged in that room. That dedicated room also has its own desk control system. There is no shared desk control.

After each batch of products is milled in that dedicated room our laboratory performs another ELISA gluten assay batch test. After being verified to be gluten-free the product proceeds to the mixing, blending and then to packaging. During packaging our laboratory does another random sampling gluten assay test. After being verified gluten-free, finished case-packed products are transported about two miles to our distribution warehouse where they are placed in a segregated area for gluten-free products.

Analytical methods that we use: Our plant uses an enzyme-linked immunosorbent sandwich assay test method, and it is made by the R-Biopharm Company to determine whether gluten is in our products. This gluten test allows us to measure the gluten quantitatively. The lowest detection level of the test is 10 parts per million gluten. All raw commodities and ingredients destined for products marked as gluten-free are tested before entering our system. Additionally, we test every batch of products prior to their packaging runs.

Because batch testing is performed in-house, the costs associated with samples are relatively low. The equipment and the tools that allow us to do the testing were purchased for just under $10,000. Supplies needed to process and test each sample cost less than $15 per sample. Labor per test is about $10 per sample. The testing kits and the supplies we use are readily available to the public from the manufacturer. As I am sure you are aware, the technical details and tests are available from that manufacturer.

Now I would like to close by sharing what some of our expectations are and hopes are to roll out of all of this. We really do need the total scrutiny and thoroughness for the issues that I am sure are going to roll out of these hearings. We also would like to offer, if it is appropriate, our trademark logo as the gluten-free symbol should one be incorporated into a voluntary protocol. We have a trademark, but under these conditions of uniform nationwide use directed by the FDA, we would waive all of our trademark rights to that logo, and you will find a copy of that in your packet, as you will find many other pieces that we use as we deal with taking gluten-free foods to the consumer. Thank you for the invitation to be here.

[Applause]

Questions and Answers

DR. SCHNEEMAN: So, we have some time for questions.

DR. PARK: Douglas Park, with FDA. I had quite a list of questions that I was going to ask you and you systematically answered those during your presentation.

MR. GILLIAM: That is a real compliment. Thank you.

DR. PARK: So, I have no further questions.

MR. GILLIAM: What?!

[Laughter]

DR. SCHNEEMAN: Dr. Zink?

MR. GILLIAM: All right, you will fill in the blanks.

DR. ZINK: Don Zink, with FDA. Speaker DeMarchi talked about the problems with inherent contamination of the grain supply with grains of concern for example, and the difficulties with removing those with cleaning. Are you using a different source of supply where you have less likelihood of such contamination and how are you doing that? Or, how are you dealing with that problem where others may find that difficult to deal with?

MR. GILLIAM: Since no grains of concern ever enter our gluten-free mill room--most of the other grains, the non-gluten containing grains are of distinctly different shapes. The teff grain, for instance, is a tiny grass seed. It would take about 50 pieces of teff to equal the size of a wheat berry. Now, we buy all of those precleaned from specialty growers who have specialty cleaning equipment so we have a certain comfort level in knowing that they are completely different sizes from the other grains that have been shown on slides. Beyond that comfort level, you just heard of the testing protocol we use also. Did that help or have I been evasive?

DR. ZINK: Yes, that helps. Do you encounter a situation where your raw material testing shows it to be acceptable, yet, after it goes through a milling process and you do your final test for gluten contamination, have you ever had situations where one turned up positive? In other words, I am trying to get at problems where sampling plans, non-random distribution of contaminants, might result in a negative test one time and a positive test the next. Does that situation occur, and how do you recover from it?

MR. GILLIAM: What I would like to do with that question, doctor--we brought along as part of our team the head of our lab and he deals with those questions daily and would have a better sense of that. You have the sales and marketing guy here, and I don't always get every piece of information so I am unable to answer that. Roger, if it is appropriate, would you approach that question in your five minutes this afternoon? Thank you.

DR. LUCCIOLI: Stefano Luccioli, FDA. I am wondering what kind of system you have available for consumers to report any adverse events? Obviously, you don't use grains of concern but I would be curious to know if individuals have called you up to question whether they have had a reaction. Maybe there are some other grains that are concerning to individuals who are reacting. I don't know if you have that information or what you do to acquire that information.

MR. GILLIAM: Yes, to a certain extent we do. Since we have mail order, and have had for a number of years a very thriving mail order program, we do get a lot of calls and we have four people staffing the lines. And, there is never--well, never--never say never--there is rarely an on hold situation that would cause a consumer to hang up. So, we field all questions. Matt, I am going to ask you, if it is appropriate, to touch on that. Matt is my associate and has his ear, because he is part of the mail order team also, to questions and concerns that come in.

One that I am very much aware of that comes in is they look through our catalog and they will not find a gluten-free symbol by corn, and they say, "well, what's the problem? Corn's gluten-free." And we say to them that because corn is a grain of such high usage in our plant at this present time with our present equipment, it would swamp our gluten-free mill room with production. So, it is produced in a gluten-containing mill room. Now, under our scrupulously clean environment and on our scrupulously clean set of stones--but because in our mind's eye we are aware, and in very real terms we are aware that cross contamination means dust particles in the air, and because of that possibility of triticale dust particle connecting with the corn we are voluntarily choosing not to put the gluten-free mark on corn yet.

Let me add just one caveat to that. There is one product in our catalog that is corn-based that does carry the gluten-free symbol, and that one is scrupulously isolated and milled only in our gluten-free mill room. So, if you scoured that catalog that would be contradictory unless I clarified.

DR. PARK: Douglas Park, with FDA. My focus obviously, as you may surmise, is methodology, sampling, reliability of the analytical result, and so forth. Your comments concerning the corn-based brings a whole litany of questions that would come to mind. What is your sampling procedure; your sample preparation; the reliability of the analytical result that deals with those products since they are not in a dedicated environment and run the potential of having cross contamination? What have you set up for those particularly?

MR. GILLIAM: I believe it is very, very thin. Remember now, we are one of the four percent and of that four percent we are one of the small ones. I believe it is very thin but, again, I will attempt to lean on Roger Farnnen for a more definitive answer to that in his five minutes.

DR. SCHNEEMAN: One more question.

MS. SATCHELL: Felicia Satchell, FDA. My question really deals with the Canadian requirement, I think it is anything below 20 parts per million, and the statement that you made regarding the use of the ELISA R-Biopharm kit at a detection of 10 parts per million. In your product testing do you allow products to go on the market that are below 20 or are you aiming for the 10 parts per million?

MR. GILLIAM: We are aiming for the 10, and--well, we just simply are aiming for the 10. Now, to better clarify the Canadian position, in reality, if you read their position or the government mandate, it is zero. But it is impractical--impossible at this point because there are no tests that will take it down to zero. Beyond being impractical and impossible, it may--may, what do I know?--it may eliminate so many foods from the food chain if it were to take it down to zero that none of us know what would happen under that scenario because we have been limited to experience with tests that only take it to 10.

DR. SCHNEEMAN: Great! Thank you very much. Mr. Gilliam made reference to the packet of material that he had provided at the front desk. If any of you want to see some of the material in that packet, I will make my packet available during the break if someone would like to take a look at that.

I know this is not a major problem with our computer here, but it just guarantees that no one can steal information from an FDA computer and our technical person is here. So, let me go ahead with introducing our next speaker, Miss Jay Berger, who is the vice president and co-owner of Miss Roben's, Inc.

Miss Roben's Inc.

[See presentation slides for Ms. Berger]

MS. BERGER: Well, scaling further down into the food production chain, we are a very small manufacturer and I am here to present a small manufacturer presentation of gluten-free foods. My company is Miss Roben's. We are also known as the Allergy Grocer online.

If you notice, on most of my slides I reference the questions that were asked of us. So, who is Miss Roben's? Basically, we are a dedicated gluten-free manufacturer with over 50-plus mixes of our own. We cater both to celiac and those with multiple food allergies and intolerances. So, we are a little different than the mainstream group that caters just to celiacs.

We are a dedicated plant. There is no wheat, gluten, dairy, peanuts, tree nuts, eggs, soy except for the lecithin in one of our pre-made chocolate chips, shell fish, fish or sesame found in the plant. We are also a national mail order business for over a thousand other select gluten-free products.

As a family owned business, just basically my husband and I, we basically self-educated ourselves to gluten-free and food manufacturing. We didn't have the money or means for outside help or consultants. We wear multiple hats so we do research and development; we do overseeing plant production and operations; and also answer the phone when we are short staffed. We have always had less than 15 employees so with one operation site we are able to change on the fly and get rid of a lot of red tape that some corporations have to go through to make changes.

We also provide extensive assistance over the phone and the internet to the consumer, and sometimes the physician and dietitian who call in. We constantly redirect and network customers to the more appropriate resources that we know of, whether they be medical or dietary or national or local support groups. We will distribute other manufacturer contact information so that they can further follow-up and clarify information. We also provide extensive baking assistance, even if it is not for our own product. I also belong to over 30 different celiac and associated e-mail news groups and that allows me somewhat of a bug's eye insight to what is being discussed about celiac disease.

Just based on this anecdotal experience, it really appears to me that customers rely very heavily on labels for processed foods. They seek out gluten-free on the label and they will often have complaints about multiple extra hours of time spent on both label reading, shopping, and follow-up calls to the manufacturer just to clarify information. Typically, it is sad to say that I think a lot of them have poor knowledge of both the manufacturing process and the terms used in the industry, and also the terms defining gluten-free. We will get a call about once a week because they misunderstood or misinterpreted the information that was possibly disseminated to them, possibly not. They often inadvertently purchase unsafe products. They will purchase spelt more commonly in a health food store if somebody unknowingly directs them to such, and calculations are needed for them to be helped for nutritional analysis if it is 100 gram analysis. The European products often come in with labeling and they don't understand how to break it down per serving.

In defining gluten-free for the general industry, it is no wheat, barley, rye, oats, spelt triticale or kamut; no derivatives, extracts or processing aids from any of the above that would be used in the processing of the foods, with the exception of distilled vinegar, the caveat being malt vinegar. Then, there is anything from 10-200 parts per million testing procedures done on ingredients or the finished product ranges that I have seen in the industry.

Most of the references for gluten-free to the industry that I am aware of come from either Don Kasarda, who is a great scientist who I think is retired by now. The national celiac support groups provide most of the education and the American Dietetic Association and some of the medical journals that have been publishing. The issue with oats has been for the most part, as far as I know, mostly cross contamination.

Additionally, at Miss Roben's we also define gluten-free to be that whenever possible, over 90 percent come from a dedicated single source ingredient supplier, straight from the farm that makes their own product and does all aspects of the production. So, this helps us provide the least possible risk of cross contamination. The ingredients that come possibly from a distribution, which is less than 10 percent of our products, must come from a supplier that individually farmed the entire product and processed it, and it must come sealed and pre-packaged before they receive it. We request that on their own documentation or company letterhead they give us product specifications; 100 gram analysis; a processing condition statement which I will refer to in the next slide; if possible, a written certification from a third-party lab of testing, and what I have found is that if testing is done in the lab the testing procedures vary greatly; and further certification for kosher, organic and vegen, again tangential to gluten-free but who we do business with. The product label, the website and the catalog explain in detail to the consumer how we are defining gluten-free and what our processing conditions are.

For each product that we supply or ingredients that we utilize we send out this exhaustive, somewhat irritating check list to the company, the actual manufacturer, requesting a quarterly check of both potential allergens, gluten being considered as an allergen and gluten being defined for them. It also allows us to then tell the processing conditions to help define for the customer what we know at the time we made the request, and ask for testing procedures and what part per million they test down to.

It also allows us a chance to identify any red flags. If a customer states something contradictory in that we may choose not to use them because we feel that they don't truly understand gluten-free correctly. They will say spelt is in their products but it is gluten-free. That is kind of a red flag to us. Then, the other is in their cleaning and processing. Sometimes we will find that the final product may not comprise gluten in it but how they came about it may be somewhat intriguing.

Some of the challenges to defining gluten-free as a manufacturer, especially a small one like us, since there is no standardized definition the manufacturer then has to decide, by educating themselves and their staff, what the definition is. The current definition can be confusing and vague, especially as a lay person. I mean, my background is more medically oriented and, still, I really struggled to understand the definition. Then you have to decide are oats okay, and when is it gluten-free enough. Then you have a customer who calls in who is also possibly misinterpreting, who is basically saying how could you sell this product that has guar and canola in it, which are the two most common questions that come up, and you have to then redirect them without offending them back to appropriate sources.

Current gluten-free production, as was suggested by Dennis earlier, is an extremely wide continuum both in the food production and in the plant itself, and it goes anywhere in the entire spectrum from what I would call suspicious to excellent. In Europe, where some of our products come from, wheat starch is considered acceptable although it is not acceptable in the States, so you need to make sure that you are not bringing in products that are not acceptable by our standards. In most companies of my size, a lot of times just no gluten in the actual ingredients but no concern for where the ingredient came from and no issues to prevent cross contamination, all the way up to dedicated plants with excellent procedures in place and well-written protocols and testing down to three parts per million.

The production also varies. Sometimes it will be done in somebody's home. Oftentimes a celiac or a consumer decides I am just going to do this myself and starts their own business. Sometimes it happens that production will be in a shared bakery which is not cleaned between runs and washed down. Sometimes it happens that it is in a dedicated plant so it goes the whole continuum.

Some specific challenges to the production of gluten-free foods from my perspective are that, for one, a lot of the flours that we use are lighter and starchier in texture. They have a finer mesh. So, in using a form fill and seal machine, a lot of times they tend to poof. The components of xanthan and guar, which are considered somewhat of a gluten replacer, are a very minute portion of the product but they have to be thoroughly blended in order to get a final mix that is adequate. By the flours poofing, the bags have a harder time sealing unless you have the proper mechanisms to throw the flours back down.

Also, too, the grains vary from year to year. Even in the rice farming industry, for example, each year the lot may be slightly different. In a wheat environment I know there is a lot more variability also but there is more flexibility in the baking of the product. In a gluten-free environment there are exquisite differences, and I will get into that in a second. Also, too, washing down equipment and floors with these very slippery substances of xanthan and guar can make life a little challenging.

For the mix preparation, both for the plant and the consumer, as I am sure Lee Tobin will get into more, most of the flours are more sensitive to environmental conditions. Breads, particularly, are more prone to failure. The exact liquid content you need to add varies from lot to lot, which is different than picking up General Mills Brownie Mix that you just throw in and it always seems to work. The raw dough batter is stickier and looser which can change your production. I have helped with some of the productions for finished products and I know one guy was having trouble dropping his donuts because they would fall apart.

Also, in order to be successful to the consumer, the label has to be much more exhaustive in terms of explaining how to proceed and make this product, and you have to factor in the costs associated with that replacement.

For methods most commonly used to remove the gluten from foods, predominantly in the United States it is the absence of gluten in the ingredient. That is the most common practice. Sometimes the gluten proteins have been processed or denatured out, such as the distilled vinegars and in wheat starch in the European conditions.

Is technologically feasible to produce gluten-free products given the potential for grain cross contamination? I think yes. I think if you select ingredients from dedicated grain suppliers, and they are out there, and dedicated gluten-free mills that are using good HACCP, Good Manufacturing Practices and allergen protocols in the plant, and also doing that in your situation, providing education to your staff about what gluten-free means and cross contamination, and if you are utilizing shared lines or non-dedicated ingredients performing a universally accepted enzyme-linked immunosorbent assay test, an ELISA test, to confirm potential cross contamination, those would be my suggestions.

Is it economically feasible? Again, I think yes. I mean, here I am, a small manufacturer, and we have been viable for 12 years. I think the biggest investment is the time required to source out the ingredients and the appropriate equipment. The ingredient supplier distributors are successful even to small businesses with poor purchasing powers now. We used to buy our ingredients in 50 lb. bags, 100 lb. bags and drag them in. Now we do it by pallet. And, I can sympathize with those who are still doing what we used to do because their buying power is far less, and some companies won't even break a pallet down to sell to you. So, you have to factor these things into price, and also the customer failures that you are inherently going to have.

Manufacturers can also outsource and utilize co-packers. They exist with dedicated gluten-free rooms and equipment. Or, they could utilize dedicated gluten-free manufacturers like ourselves that would benefit from decreasing our operational and ingredient costs. It seems like the customer buying power and interest is already there. There is already 1/133, the last citing for celiac disease. If you consider also the wheat allergic consumer who would have different demands, there is a huge demand for a gluten-free product. Then, there was a recent survey put out by Mantel that basically suggested to the industry that there is excellent potential.

As the gluten-free industry grows, the ingredients and production costs would further decline and make the availability increase, which would make it even more affordable to small industry. And, if oats were allowed to be considered and we were able to find dedicated suppliers, you know, personally I feel it would enhance both the product taste and texture and the structure, and expand the product line. The question then becomes is it worth it to a large manufacturer to produce.

The measures and costs that we use to prevent cross contamination at Miss Roben's include using a dedicated plant where no gluten is used in-house; dedicated equipment--we purchased ours new so we didn't have to worry about any risk of potential cross contamination with anything prior; exhaustive research to find the ones that will blend, disperse, seal and clean without any caking or crevices with minimal downtime and waste; and handling the volume runs and wash downs needed to maintain and efficient and economical production.

We do use dedicated single ingredient suppliers with a written certificate of analysis, and do quarterly routine checks with the suppliers. If a concern is raised by a consumer, for whatever reason, we then source out that ingredient and/or the ingredients within that mix and follow up. We also do written employee allergen training and potential methods of cross contamination regularly and review that. We go over with our staff Good Manufacturing Practices and HACCP. Even the phone staff understands that. And, we have internal policies and procedures for any type of manufacture recalls for products that we do sell that aren't ours, as well as customer complaints.

In the winter we hope to do more testing and analytical methods, and are hopeful to have the celiac branding which will be discussed later; and in-house ELISA testing each batch for a quantitative sandwich ELISA test of less than 10 parts per million, and a quarterly quantitative test done outside by the University of Nebraska which I have been told costs $80 if you are not a member, $55 if you are for each mix. They use two sandwich ELISA tests for gliadin, the Neogen Veratox test and the Biopharm test, testing down to three parts per million. My limited knowledge of this is that fermented and hydrolyzed samples would require special ELISA testing however.

In conclusion, my personal suggestions for manufacturers, should the definition for gluten-free exist, would be to still try to obtain dedicated ingredient suppliers who can provide written certification of analysis and analytical testing with the parts per million or testing procedures based on what the FDA recommendations are; provide ongoing in-house education to the staff using the universally agreed upon gluten-free definition; and easy to follow written education tools for the staff to refer back to; to test for gluten quarterly quantitative analysis outside lab testing and, if shared lines, in-house every batch.

The last thing I wanted to mention that is somewhat tangential but related to this, is if more of the educators could be educated to what gluten-free means so that when a patient is diagnosed they are not calling a manufacturer like us to define it for them. Thank you.

[Applause]

Questions and Answers

DR. SCHNEEMAN: Thank you very much. Do we have some questions? Rhonda?

DR KANE: (*See errata) Thank you, Jay, for that very informative presentation. I had a quick question about your check list that you use for your suppliers and your criteria. You mentioned that you use the Neogen and the R-Biopharm ELISA tests for your own in-house testing. Do you ask the suppliers which methodology they use, or do you require them to use certain methodology? And, do you know what they are using for testing? Because you ask them to report what is it in parts per million, so what is it that they are using to analyze their products, and is there any consistency across your suppliers of using the same test kits you do? Are they using other kits? Are they using other methodology? What are they doing, do you know?

MS. BERGER: Well, first to clarify, we hope to test in the fall; we don't currently. That is where I feel we are not where we should be, and that was economic really more than anything.

Secondarily, the testing that we know of that other companies do, they do not share information. The gluten-free is an interesting industry. I think we all know each other but I don't think manufacturers like to share what is considered trade secrets, and that is considered possibly a trade secret. I have asked for a parts per million and I don't really know that I could evaluate it if I got the information, to be honest, to say one is better than another. So, a lot of what we do is really a compilation of, you know finding out. Sometimes somebody will say they have tested down to one part per million, and that is like a red flag right there, you know, because I know they don't test down that far for gluten. So, sometimes it just gives us more information about what the manufacturer may know. You know, even me as a lay person, I can see some red flags.

Then, I think to answer your question do they use consistently the same ones, no. Again, we also ask for food allergens as well so, besides gluten where we may not look at it in terms of, you know, do you test down to this level and such, for allergens we look at it a lot differently, and part of it is just to see what lengths they are going to; how concerned are they; how scrupulous they are. So, some of it is qualitative in the results and how forthcoming they are about the information.

DR KANE: (*See errata) I just want to make sure I understand. So, you do not ask the manufacturer what methodology they are using. You ask them for the parts per million but you don't know how they arrive at that, what test kit or methodology they are using. Is that correct?

MS. BERGER: No, if they have tested we have that certificate and that certificate says on there what they have used. But my ignorance would be I would look at it and I would have to call somebody else, like Steve in Nebraska, and say what does this mean to me? You know, I just don't have the knowledge to evaluate it critically.

DR KANE: (*See errata) Thank you.

DR. PARK: Douglas Park, with FDA. Thank you for your presentation. I do have some questions I would like to pose to you. One of them basically is a follow-up a little bit to what Dr. Kane was asking you. On your certification on your products do you do follow-up confirmations of your own when you receive a product, whether it is done on a random basis or whether it is done with each batch of the product that you receive?

MS. BERGER: When you say follow-up--

DR. PARK: Do you follow up testing?

MS. BERGER: Call the person that did the test?

DR. PARK: No, do you do follow-up testing your own? Within your own organization do you have a quality assurance/quality control program that provides you assurance that the product that you are receiving, your raw product, is in compliance and your in-line production is in compliance, as well as your final product?

MS. BERGER: We came about how we are doing it now somewhat deductively and not as analytical as I would like, and part of the fall testing is not just for gluten but it is going to be for all of the allergenic proteins. Part of how we--I wouldn't say side-stepped, but part of how we tried to stay as scrupulous as we can to our own mixes, which are our products, is to get ingredients from people who only do one thing. So, the sorghum supplier we use, they only grow sorghum; they mill their own sorghum and they package their own sorghum. The rice we have to get all the way from California to get a dedicated farm that does those things. The products that we carry from other companies, which is somewhat separate because we don't have a lot of control over that--I don't do in-house testing on those at all but I do pay attention to customer complaints and we have had to follow-up with a voluntary recall and decide not to carry a product that the company still lists as gluten-free on their website today.

The plan is to do this fall in-house testing on our own ingredients. Even though we know inherently that they are gluten-free because they have been farmed as such, I still want that level of assurance for myself--you never know--and test each thing to all the eight major allergens plus gluten in particular so that I can feel the best level of comfort that what we say we do, we do. But the problem really has been mostly cost and actually too my educational process to understanding because, again, I put my research hat on and actually had--I mean, I bugged University of Nebraska and called people that are dietitians that are friends of mine and just plugged them for questions.

So, we are not where I want to be and where I would like to be and comfortable to be to give a true sense of self. So, we are very clear with the consumer, particularly the food allergic consumer. Here is what we do; here is how we do it. We challenge you at any time, please call the manufacturer; please let us know if something has changed; please let us know if you ever have an issue with us. And, we do testing; we take ingredient lot numbers and then we take a mix and we make a lot number out of that, and we will go back to every single ingredient and check, even though we do a quarterly, and just second-guess the supplier. So, yes and no.

DR. PARK: Do you anticipate setting up in your process a HACCP program which would be then also tied in with an in-house quality assurance/quality control program?

MS. BERGER: Definitely. That is, again, the goal with the ELISA testing, not only to have fail-safe mechanisms to prevent but, if they should occur, how would we handle it and, actually most importantly to me is how do we let the customer know? Because we are a national mail order, we go overseas and how do I let this person know? So, we have a database that can tell us a customer has purchased a product but we don't know what lot number it has come from to re-reference it, and how do you communicate to people who don't necessarily have e-mail; you don't have a phone number sometimes, and how to do it adequately? So, we have discussed with food allergy and anaphylactic networks to help us. Then, being part of these e-mail news groups you can kind of get the word out. I mean, part of how we did the pasta was to politely let everybody know that our comfort level exists such that we would like to retract the product without trying to inflame the company.

DR. PARK: In the meantime, do you envision using an outside organization to do your testing for you on a regular basis--

MS. BERGER: Yes, in the fall.

DR. PARK: --and not necessarily quarterly--

MS. BERGER: No, I want to do quarterly--

DR. PARK: --I am talking about daily?

MS. BERGER: I want to do quarterly. I would feel more comfortable with quarterly because we do change suppliers regularly. You know, we will have to change a rice supplier because they are now doing something besides rice, or whatever. Maybe this is overkill but I would like to test every batch in-house that we do. Then I would like to use an outside independent lab by University of Nebraska, which is what I have chosen so far, to double check my procedures and have it more honest. And, part of the celiac branding that I am looking forward to is, again, an outside body like the kosher certification that comes in and says you are doing what you are supposed to be doing. They have more knowledge than you, and they see things that you may not see.

DR. PARK: Along that line, have you looked at the economic impact of doing that?

MS. BERGER: Yes. I have 53 mixes and if my husband stops me now we will stay at 53, but I figure 53 mixes times 80 per quarter. But I don't think that is unreasonable to provide the level of safety I want to provide considering what I want to do. And, I want customers to feel that, to the best we possibly can do it, it is as clean as they possibly can get.

DR. PARK: Thank you.

DR. LUCCIOLI: Stefano Luccioli, FDA. In your talk you referenced that you often look for grains in Europe, which I think is a very good idea since Europe has a much longer history of dealing with celiac disease and I am sure that they have tackled a lot of these problems. What are things that you have learned that maybe the American market could improve on in milling their grains? For instance, I understand that countries such as Scandinavia produce oats without wheat so that is never a problem. Is it economically feasible to do that in this country?

MS. BERGER: I don't know if I am your bird of choice. I know more about the actual finished product than the raw ingredients. We do get raw ingredients from overseas. The corn starch that we get that only does corn can comes from (*See errata) overseas sometimes because it is not as prevalent in this country, that you can find corn where they are only growing corn and they are only milling corn.

As far as economics and their knowledge, I think they are ahead of us in a lot of ways. I am not really sure if it is just that--like Dr. Shar for an example that has been around for years. In the pharmacies for years you have been able to purchase gluten-free products and it has been identified for you so the consumer would walk somewhere and they would go get their prescribed diet. It may be more limited. It may be not as appealing but they felt safe that somebody had given them what they needed to work around instead of setting them loose in the Giant to try to figure out for themselves this pile of paperwork that they have compiled.

I can't really speak intelligently. I mean, I can tell you off the top of my head but I can't really tell you intelligently. I know that there are a lot of manufacturers out there overseas that are trying to bring products in, and there is a huge industry. I get letters almost monthly asking me if I want to be an importer or the retailer in this industry for it.

DR. SCHNEEMAN: For some of those questions we might be able to come back to the general panel too if there we have time. Was there anything else from the panel?

[No response]

Great! Thank you very much. Our last presentation for this panel is Mr. Lee Tobin, who is the team leader for the Gluten-Free Bakehouse at Whole Foods Market.

Gluten-Free Bakehouse, Whole Foods Market

[See presentation slides for Mr. Tobin]

MR. TOBIN: Thank you. The last audience I spoke to I think was a little more challenging than the FDA. I did a cooking demonstration for some group of children at the GIG celiac camp in North Carolina, and the six year-olds sat in the front row.

[Laughter]

I can assure you that celiac children are very well behaved, especially when you feed them. I wanted to start out by thanking the FDA for inviting me and Whole Foods Market to participate in these meetings. I would like to thank Jill Kuzo who is our research and consumer relations coordinator at the Bakehouse and Joe Dixon from Whole Foods quality standards offices, both of whom helped to prepare this presentation.

The Whole Foods Market Gluten-Free Bakehouse is a dedicated facility that grew from a dedicated production run which I developed in one of our in-store bakeries after my diagnosis with celiac disease in '96.

We opened our new bakehouse--it is a fairly new facility, we opened less than a year ago in Morrisville, North Carolina last October. We produce 27 different baked goods from scratch. We are packaging everything in pallet size quantities and distributing them to approximately 170 of our stores throughout the U.S.

In this presentation I will be covering sections A, B and C of the Federal Register Notice; discuss our framework for defining gluten-free; and the Good Manufacturing Practices and the analytical methods we use to ensure that our products meet these standards.

Our stake in decisions involving gluten-free labeling is three-fold. Our primary concern is the confidence of our customers. They trust that an item labeled gluten-free meets their expectations. Secondly, it is consistency. We need to assure that other products labeled gluten-free are set to the same or similar standards as those we have set for ourselves. Last, any standards set by the FDA of labeling of gluten-free products will necessarily impact our production and the measures we take to exclude gluten.

There are three methods we use to support our claim of gluten-free status. We gather testaments from ingredient suppliers. We perform ELISA testing on our ingredients and finished products, and we dedicate our entire facility to production of gluten-free with the exclusion of gluten from the premises. In the future we would consider participating in a third-party certification program, one that follows FDA guidelines, perhaps modeled after kosher or organic certification which Whole Foods has considerable experience with.

In addition to screening our ingredients for gluten, we also exclude artificial colors, flavors and preservatives. In most cases Whole Foods Market support of minimally processed ingredients has made searching for gluten-free ingredients easier. Virtually all of our ingredients, with the exception of extracts and emulsions, are inherently gluten-free and not rendered gluten-free through processing.

We made a concerted effort to educate our suppliers and manufacturers about hidden gluten and sources of gluten cross contamination issues with shared lines or concurrent production. Once we have determined that each ingredient is gluten-free we gather statements from suppliers that express understanding of the term gluten-free and give assurance that their ingredients are free of gluten.

In addition, our facility employs a lot tracking system. We record lot numbers of each ingredient used in each batch and each recipe produced. This system traces all ingredients used from their origin to each batch of our finished product and allows us to initiate recall procedures as a safeguard should gluten, or any other form of contamination, be discovered in our ingredients.

This screen illustrates points in the processing of ingredients that farmers, manufacturers and suppliers should be aware of to prevent gluten contamination. It refers mainly to grain and flour production which are higher risk ingredients but could be applied to other ingredients as well.

Crops should not be rotated with any form of wheat, rye or barley and should be harvested, stored, transported, milled and packaged with gluten-free equipment or in a gluten-free environment. We have always excluded oats from our production due to concerns about cross contamination, and we will continue to do so until the safety of oats can be consistently confirmed through the process.

Gluten testing--testing protocols are challenging to establish because there is no one method we can use to test 100 percent of our products. Samples must be taken at key points in the process and the number of samples needed depends on the level of risk of contamination. We use the BioKits rapid gluten test from Tepnel Biosystems. It costs about $16 per test. This is a qualitative stick test that detects the presence of gliadin as low as 50 parts per million and yields results in about five minutes. We chose this test because it is fairly simple to use.

All testing is done at the bakehouse by our quality control person. We looked into sending out samples to a lab for testing but, as Jane mentioned, the costs are prohibitive. We currently test all new ingredients and a new source of an existing ingredient if we are to change suppliers since this is the best point in the process to exclude gluten from our bakehouse.

We also test random samples of finished products for additional verification. Finished products need to be sampled carefully so that particulates in the sample do not obscure test results, which has required us to do additional tests when we have had inconclusive results. Our sampling plan continues to evolve as we grow and increase our production volumes.

We are in the process of developing a HACCP program which will include screening for gluten as a critical control point. With this program we intend to test samples from each lot of all high risk ingredients coming into the bakehouse and one finished product sample from each of our production runs. This testing program could be part of a possible third-party certification program, as I mentioned earlier.

Our decision to dedicate our entire bakehouse and work staff exclusively to gluten-free production was made primarily on the basis of minimizing the risk of contamination. Facilities that process wheat or gluten ingredients will always run a higher risk if they also choose to process gluten-free products.

This screen illustrates levels of dedication that food processors can use to reduce risks. Some dedicate production run and clean equipment thoroughly between runs. Some dedicate certain pieces of equipment or an entire line of equipment, and some dedicate their whole facility to gluten-free production. Each higher level eliminates more points of potential contamination.

Cross contamination within our facility--there are some steps that we take to reduce contamination risks at the bakehouse and at our stores as well. We provide full uniforms for all of our employees and replace them daily. We also provide them with shoes and aprons. The aprons are worn over the uniforms but remain in the work area during work breaks as a protective barrier for any gluten that might be on their clothing. Visitors to the bakehouse are supplied with lab coats if they enter our production areas. We share our building with a warehouse that the company runs and there are several employees; people are coming in an out so we require those lab coats. We also signage throughout the facility to (*See errata) alert anyone who is coming in and our employees as well that it is a gluten-free production area and we need to exclude wheat, rye, oats and barley.

We employ strict cleaning procedures between production runs to prevent any allergen cross contamination. I should mention that we are not an allergen-free bakehouse. We use dairy, soy, nuts and some of the other allergens but we do not promote our products as being allergen-free, just gluten-free.

At the store level we have initiated training programs that stress cross contamination issues with gluten and other allergens when employees in our store are either serving or sampling our products. We feel that education of all our employees is key to reducing potentials for cross contamination.

Any standards that are set for gluten-free labeling must meet the expectations of our customers. Customers must have the confidence that food labeled gluten-free is safe for them to consume and will not make them ill. In addition, standards must be feasible for producers to meet. Feasibility is determined by relative difficulty to implement, reliability of results and, of course, the cost. There also needs to be consistency in definitions so that fair comparisons between brands of products can be made, and these definitions must be easy for the general public to understand. Education of consumers, manufacturers and lawmakers is essential to create a label that easily distinguishes gluten-free foods for celiacs who are medically required to be on a gluten-free diet. Thank you.

[Applause]

Questions and Answers

DR. SCHNEEMAN: First, why don't we take some time to see if there are some specific questions for Mr. Tobin, and then we will have time I think for more questions to be addressed to the panel speakers. So, do we have some specific questions?

DR. PARK: Thank you. This is Douglas Park, with FDA. You indicated, and correct me if I am wrong, that for many of your raw products you obtain certification that they are gluten-free. Is that correct?

MR. TOBIN: We obtain letters from our suppliers and manufacturers claiming gluten-free status, yes.

DR. PARK: And I will ask you the same question that I asked the previous speaker, do you confirm in your own testing in your own laboratory that they are, in fact, gluten-free?

MR. TOBIN: Yes, we have done a limited amount of testing to confirm that. Our intention is to ramp up our testing once we have our HACCP program developed.

DR. SCHNEEMAN: Excuse me, let me interject. Do you have a certain expectation of what kind of test they would use in order to certify to you that they are gluten-free?

MR. TOBIN: No, we have not questioned our suppliers whether they have used testing procedures.

DR. PARK: That is a good follow-up question. You indicated that you are developing a HACCP program. Would you share with us a little bit your initial ideas as to what you would consider an appropriate HACCP program for a gluten-free plant?

MR. TOBIN: I can't give you specifics because it is still under development and I am not the person who is working on it. We actually run two bakehouses. Our gluten-free facility is umbrella'd under an existing bakehouse that has been in operation for a number of years. It is located a quarter mile away and we have a quality control person who does work for both of our bakehouses and is working on developing that program. But the gluten testing will be a significant part of that program.

DR. PARK: In your dedicated facility you prepare only products that fall under your gluten-free assurance and label? Is that correct?

MR. TOBIN: That is correct. All of the wheat-based products are made at our other bakehouse.

DR. PARK: What about other cereals, other than just wheat-based?

MR. TOBIN: I am not sure I understand.

DR. PARK: Well, we are concerned not only just with wheat; we are concerned with oats and some of the hybrids and specialty grains. Are those brought into that gluten-free area?

MR. TOBIN: No, not at all. Our warehouse that shares the facility primarily stores equipment, coffee and drinking water, firewood, pallets, that sort of thing. There is nothing stored on the premises, or processed.

DR. PARK: Those are all my questions.

DR. LUCCIOLI: Stefano Luccioli, FDA. I just wanted to follow-up. Did you define what you consider gluten-free? Do you consider oats in that definition?

MR. TOBIN: Not at this time, to deal with the cross contamination issues.

DR. LUCCIOLI: So, basically what all the other presenters have said, that is what your definition of gluten-free is?

MR. TOBIN: For the most part, yes.

DR. SCHNEEMAN: I was going to suggest why don't we have the panel come up? Don, go ahead and ask your question and then we can raise other questions for other speakers. Go ahead, Don.

DR. ZINK: Don Zink, with FDA. Have you had situations where a supplier has certified that they are gluten-free and you have tested it and found it to contain gluten? And, have you had a situation where your raw materials passed muster but then, when you produced the finished product and ran the test, you had a positive gluten? I asked this question earlier. I am just trying to get a feel for the synchrony of claims of gluten-free with the actual test, as well as possible lot sampling and non-random distribution of contamination issues.

MR. TOBIN: To the first part of your question, we have not had any of our own in-house testing that conflicted a supplier's claim of an ingredient being gluten-free. With the finished product, we had a couple of tests that were inconclusive due to our inexperience with the testing method. The samples were shaken a little too much and rendered the inconclusive results, and we retested the samples of the same product and that was confirmed gluten-free to greater than 50 parts per million.

Questions the FDA Panel

DR. SCHNEEMAN: Can the panel come up? Thank you very much. Stefano, you had a question of the last speaker about import, and I am wondering if Miss DeMarchi might be able to address the nature of the question that you had. So, I was thinking you might want to restate the nature of the question you were getting at. We will give you a microphone to respond.

DR. LUCCIOLI: Yes, Stefano Luccioli. I guess as a follow-up I have a question about oats. Why do we have a problem with oats contaminated with wheat? Is there just not demand for gluten-free oats, and why maybe in other countries are they able to supply these grains? Obviously, maybe it is an economic issue.

MS. DEMARCHI: This is Jane DeMarchi from the North American Millers' Association. I think I would caution you about cross contamination. Although wheat contamination may be our greatest problem in the U.S. and Canada with oats, rye and barley are the grains of concern in Europe. I think in Ireland there are problems with rye contamination. I don't know as much about Scandinavian countries. I think that they may have a greater level of purity but I am not totally sure about that.

In reference to an earlier question you had asked about products coming from Europe, and I don't know if this is true but if they have a different type of identity preservation system that is used on grains in Europe, in part because of concerns about biotechnology, that may impact the level of grain mixture not just in oats but in other grains in the grain system in Europe.

MS. BERGER: Just in addition, as a manufacturer, if we were to find for an example a source that we felt to be clean, like I have heard McKane's oats hypothetically has been touted (*See errata) clean and, yet, there was another one that disputed it--I think right now, if we were to take oats in, because there is so much in the understanding of what is gluten-free to the community, we would basically be discrediting ourselves as a gluten-free supplier because there controversy is (*See errata) so great about it that even if we were to obtain it, until the definition is laid out that everybody is in consensus, I think everybody is very cautious to want to even introduce it anyway.

DR. LUCCIOLI: That is a good point. That is my feeling, that the demand, since you are going to have to include it in gluten-free anyway, then maybe there is not the demand to find a more purified form.

MR. GILLIAM: I totally concur with that statement. There is a real hesitancy within our company to put something in a package and put it in the marketplace and be labeled and in whatever percent, 50 percent of the celiacs' minds it is now being possibly tainted. We are just staying away from that.

DR. SCHNEEMAN: Please identify yourself.

MR. TOBIN: Lee Tobin, from Whole Foods Market. I just wanted to add that I agree with what these folks are saying. We were approached about eight months ago by a woman representing a group of farmers, I believe in Montana, who were interested in growing dedicated gluten-free oats. I don't know how far along they are in the process of bringing a product to market, but we would certainly be interested if they could confirm gluten-free status of the products.

DR. SCHNEEMAN: Great! Thank you. Felicia?

MS. SATCHELL: Felicia Satchell, FDA. My question is for Mr. Tobin. I just want to make sure I am clear on your testing, and you are testing at 50 parts per million?

MR. TOBIN: That is correct.

MS. SATCHELL: So, for products that are below 50 parts per million, they proceed through production and distribution channels. Do you have any type of system set up where you get adverse event reports? Have you gotten any? Do you have a system that allows you to trace back to any particular product that might have been the subject of an adverse event?

MR. TOBIN: Good question. Yes, we do get a tremendous amount of feedback from our customers, mostly through e-mail. We have someone working full time answering e-mail for us. We get phone calls as well. We have been growing out our product region by region and most of the issues we get, phone calls or e-mails we get from customers, are from customers who are new to our products as we have just rolled out to their local store. I would say all cases of customers claiming to have a reaction, we have not found that to be the case. They were either not diagnosed with celiac--we sell to customers who are celiac and customers who are on a gluten-free diet for whatever reasons, and some of them have various reactions, maybe caused by consuming gluten or consuming something else. We have never been able to confirm any contamination with our products. As I mentioned, we do have lot numbers. We track lot numbers with ingredients and we date code all of our products so when they are at the store and a customer has a complaint or an issue with a specific product, we can track the date of production. We have actually had samples sent back to us and we have sent them out for testing, and we have not had any issues, no confirmed issues.

MS. SATCHELL: Thank you.

DR KANE: (*See errata) Rhonda Kane, FDA. Lee, just to follow-up about your definition of gluten-free specifically, could you list the different grains that you exclude, and do they include spelt and kamut and triticale? Could you just state what the grains are that you do not use?

MR. TOBIN: Sure. For the most part, what everyone else had mentioned. We exclude all varieties of wheat. We are using sorghum flour, soy flour, rice flour of course, tapioca starch, potato starch, bean flours, kimwa flour (*See errata) and buckwheat and millet in their whole grain form. I think that is everything, and there are other grains that we would consider to be gluten-free that we are not using currently.

DR KANE: (*See errata) You didn't mention rice.

MR. TOBIN: Yes, we use rice, quite a bit of it.

DR. LUCCIOLI: Stefano Luccioli. How about corn?

MR. TOBIN: Oh, yes, corn. Absolutely. We use corn meal in our cornbread and corn starch as well.

DR KANE: (*See errata) Rhonda Kane, FDA. In the different grains that you use, do you ask the suppliers if they are dedicated, or do you only deal with dedicated suppliers? Or, is it up to them but you ask them to provide some sort of certification that their product is gluten-free? What type of suppliers do you deal with, with these other grains?

MR. TOBIN: We deal with a variety of suppliers. Bob's Red Mill is actually one of our suppliers. Most of our flours are brought in pallet size quantities, but we do ask for letters of certification, and we don't specifically ask for their testing methods, no.

DR KANE: (*See errata) And they are not all dedicated facilities? Correct? Is that true?

MR. TOBIN: The millers are, yes.

DR. KANE: The millers?

MR. TOBIN: They claim to be.

DR. SCHNEEMAN: I am going to ask the panel if there are just some last questions that you might have.

DR. PARK: Douglas Park, FDA. The question which just came across my mind is, is there such a thing as a gluten-free alcoholic beverage, such as beer and that type of thing? If so, what grains are used in those?

MS. BERGER: Jay Berger. Yes, there are two. One is using sorghum and I have forgotten what the other is--honey. One is a honey lager. So, yes. There has been a big interest. I don't know how it fares, to be honest, but there has been a big interest.

DR. SCHNEEMAN: Felicia, did you have a last question?

MS. DEMARCHI: Just as a follow-up to the oats discussion also, I think the demand of interest to purchase is tremendous. I think the hesitation is, okay, when is it going to be considered safe enough that we all can bring it in comfortably and feel confident that we are providing something that isn't contradictory to what they are hearing otherwise.

MR. GILLIAM: Dennis Gilliam, Bob's Red Mill. Tangential to that, I would say if oats are determined to be safe or found to be uncontaminated, being in marketing, I have a sense that taking out full page ads in "Living Without" and other publications similar to that, it would take a six-month campaign of full-page ads to educate the celiac community to the fact that they are, in fact, acceptable.

DR. SCHNEEMAN: I think I am going to close this morning's session. I want to start by thanking our panel. These have been excellent presentations. I appreciate, number one, your sticking to the time but, number two, really focusing in on those questions and issues that FDA had put in the Federal Register. I think you have provided us a wealth of information and your responsiveness to the questions has been very helpful as well. We are going to take our first break. I know many of you are probably anxiously waiting for that. It is 11:15.

There are restrooms. As you leave the auditorium, if you head back toward where you came in, there are restrooms along that corridor. Again, I would remind you that if you do leave the facility to go out to Cafe Wiley you will have to come back in through security. So, just keep that in mind if you are coming back in. Also, I would remind some of you who would like to add to the public comment period this afternoon, it you would (*See errata) like to do that please be sure and pre-register for that with the registration desk that is out in the foyer. So, with that, we will take a 15-minute break and we will reconvene promptly at 11:30. Thank you.

[Brief recess]

DR. SCHNEEMAN: I think it is going to be time to reconvene. Knowing that we have a lot to cover in a short amount of time, I want to keep us on time as much as possible. The next panel, of course, has the challenge that they are the panel between you and lunch so I know they will want to make sure we keep to the schedule here. We are going to do a little bit of a switch. The panel members can sit in the front row for the presentations but then we will want our speakers to actually be in the front for the question period.

Our next section of the agenda is to address questions around the gluten detection analytical methods. We have two speakers for this particular section. Our first speaker is going to be Dr. William Hurkman, who is a plant physiologist with the Pacific Western Regional Office of the Agriculture Research Service of the U.S. Department of Agriculture.

Gluten Detection Analytical Methods Detection of Cereal Proteins and DNA Using MS, ELISA and PCR

[See presentation slides for Dr. Hurkman]

DR. HURKMAN: Well, thanks for inviting me here. It has been a pleasure listening to the presentations this morning, and my presentation will be a little bit different. I am Bill Hurkman, from Western Regional Research Center in Albany, California, and my topic will be detection of cereal proteins and DNA using mass spectrometry, ELISA and PCR.

DR. SCHNEEMAN: Excuse me, Bill, could you move the microphone?

DR. HURKMAN: Is this better? I always have a problem standing close. So, I will take a different approach. I am a plant physiologist and I like to see how things work and take them apart. I like to look at assays and understand what is going on.

So first of all I thought, not to insult the audience but I thought I would start out defining some of these terms because they can be confusing. Wheat flour, when you combine it with water, forms a dough, as you all know, and it makes many nice things, some of which you may have eaten for breakfast this morning. If you knead it with excess of water you can get rid of the starch granules and you are left only with the protein portion, and that is called gluten. Now, gluten consists of two protein groups, the gliadins and the glutenins, and these can be separated from each other by mixtures of water and alcohol.

So, that is all well and good but then you come across this term prolamins and gliadins, and (*See errata) glutenins are also called prolamins, and together they make up gluten. So, it can be slightly confusing. Then to add to this, there are prolamins in other cereals besides wheat. I am going to focus today on the gliadins, so the wheat prolamins are called gliadins. In barley they are called hordeins; in rye, secalins; and in oat, avenins. So, I thought with that introduction, maybe as I mix these terms I won't lose you; I will try not to do that.

The topic of today's talk is detection methods, and there are several analytical tools available for detecting the presence of cereal prolamins in food products. Today I will just cover three of them. They are the ones that are used principally. They are mass spectrometry, monoclonal antibodies and polymerase chain reaction, abbreviated as PCR almost by everyone.

Now, the first topic I am going to cover is the use of mass spectrometry for protein identification. The schema you see here is the one I use in my laboratory for identifying the many proteins present in wheat endosperm. Essentially, what you are doing is isolating proteins from the seed, and we focus on endosperm so we isolate endosperm, extract the proteins and run them in a two-dimensional gel so the net result is a 2D gel.

Now, what that is, it is a separation of proteins in a first dimension gel by charge, and then that gel is laid on top of a second gel--the rectangle you see on the screen there--which separates them by size. Once we have done this, we visualize the proteins with a blue stain. That is why the protein spots are blue. Then we scan the gels to get a digital image.

This digital image is used to match spots between different gels, for example, for comparing different samples grown under different conditions. Once this gel is scanned, we then cut out the spots and we add trypsin to the spots to break them into fragments so that the mass spectrometer can handle them. The fragments are created by an XY robot. In this case we have one made by Digest Pro. Then these fragments are analyzed by the mass spectrometer which is a rather large instrument, about 8 ft. by 3 ft. and about as high as the podium.

What you end up with is data like this. To the uninitiated that doesn't look like much, but what that represents is the size of these fragments in their amino acid sequence. With that information, you plug it into a computer and check databases and you can come out with the identity of the proteins. This has really been a marvelous piece of equipment in my research. I always like to tell the story that when I identified my first protein it took two years. Now we can do 50 a day using this technology.

Here is an example of two fractions of proteins from wheat endosperm, the gluten proteins and the albumins and globulins. What you see is that there is a whole bunch of proteins in these fractions. There are several hundred here and over a thousand proteins in this fraction. What we have attempted to do using mass spectrometry is to identify all these proteins.

On the slide I haven't done that but since this meeting is basically to talk about wheat allergen proteins, I thought I would show a few on the slides. The gluten proteins contain the omega, alpha, gamma gliadins and the high and low molecular weight glutenins. So, that is quite a few proteins that celiac patients can be allergic to or react to.

In the albumin and globulin fraction I have just labeled areas in the gel where these other known allergens, IgE allergen proteins are located. They include the serpins, glyceryl aldehyde 3-phosphate dehydrogenase, the GAPDH on the slide, peroxidase and also alpha trypsin inhibitors of which there is a large number in the low molecular weight region of the gel. So, this technology is wonderful in that, if you can separate the proteins either on a gel or using HPLC, you can identify and separate specific proteins out of all the proteins present in wheat endosperm.

Advantages of the mass spectrometer identifying proteins are that, as you saw in the previous slides, it can separate and visualize many proteins at once. Protein identification is relatively rapid. Proteins can be quantified. Another useful thing about this technology is that proteins that you separate can be used to make antibodies against specific proteins of interest. One thing I didn't point out on this slide is that you can use this technology also in combination with antibodies and Western Blots to identify, for example, wheat allergy proteins.

The limitation to this method is that you can only visualize the most abundant proteins, but this can be overcome to some extent by fractionation, which I showed on the previous slide where I used KCl to separate the two protein fractions. Also, the method is technically demanding. You need skilled people in your laboratory to do the protein separations and the mass spectrometry. Also, the equipment and the associated software is quite expensive.

Another one you have heard a lot about today is the ELISA, and that is short for enzyme-linked immunosorbant assay. This assay takes advantage of the ability of antibodies to recognize and bind to specific proteins which are termed antigens. It is more rapid and less expensive than mass spectrometry and is highly specific through the use of monoclonal antibodies.

On this slide is an outline of how monoclonal antibodies are made. First, the antigen is injected into a mouse to stimulate the production of antibodies. The antibodies are made in specific cells in the spleen called lymphocytes. These then are isolated and fused with myeloma cells to produce antibody-producing hybrid cells.

If you look at the slide you can see that the little lines on each of the cells are different. What that is showing is that each of these cells make different antibodies. So, you can screen for the antibody of interest, and once you find that cell line you can clone it to produce unlimited amount of antibody for future studies.

What do we do with this antibody? We use it in what is called a sandwich ELISA. This is done in 96 well plates. The blue cylinder there is representative of one well and a plate. The first thing that needs to be done is to bind the monoclonal antibody to the wells of the plate. Then you add the sample and you also compare the sample with the standard so you can quantify the results. You incubate for a time and wash the sample to remove excess antigens. Then you add a conjugate. Now, what a conjugate is, it is another antibody that recognizes the antigen that is connected to an enzyme. Later I will tell you what that is about. Then you again wash it so that you have just your antigen in a sandwich. That is where the name comes from. It is a sandwich between an antibody and a plate and an antibody connected to an enzyme. Then you add the substrate, and what happens is that the conjugate has the enzyme which utilizes the substrate and alters its color. After a certain time you stop the reaction with a stopping reagent and the color that is in the well is correlated with how much of the antigen is present. So, I thought it is an interesting assay and it is nice to know how these things work.

With respect to gluten proteins, what has become available in recent years is the R5 monoclonal antibody. This was produced by Mendez and his collaborators in Spain, and the reference is at the bottom of the slide. This antibody detects gliadins, hordeins and secalins but not the avenins. You might wonder how is this possible.

Well, the way this works is that the antibody recognizes the five amino acid sequence, QQPFP, and for those who aren't familiar with the shorthand, it is at the bottom of the slide and it stands for glutamine-glutamine-proline-phenylalanine-proline. If you look at this sequence, this is a sequence of a wheat gliadin and I said that it is a prolamin because it has a lot of glutamines and prolines. If you look in there you see a whole lot of Ps and Qs so that is where that name comes from.

What you will see in this wheat gliadin is that that five amino acid peptide is in there 14 times. So, that is why this assay works because processing it this peptide gets fragmented and there are 14 chances that you can detect this particular protein using the antibody. It is a pretty cool method. Now, this sequence is found also in the hordeins and secalins but not avanins. So, that is why you have the specificity.

The advantage of the ELISA assay is that, as you saw, it detects wheat, barley and rye but not oat prolamins. It works well for a variety of processed and unprocessed foods. It is relatively rapid. The R-Biopharm assay literature says that it can accomplish this in an hour and 30 minutes--not too bad but not fast enough for assembly line production. In a laboratory setting it is sensitive down to 1.5 parts per million, and it is available in several commercial kits.

Two of these kits were tested by 20 laboratories in a study that came out in a symposium proceedings by the Prolamin Working Group last year, and the conclusion was that it was rapid and reliable, and that statistically reproducibly it was quite good. This assay has been temporarily endorsed by the Committee on Methods of Analysis and Sampling, which is part of the Codex Alimentarius Commission. The reason it is temporary is that they would like to see more data; they would like to see more samples tested, and so forth. Anyway, it is a good start for that.

The disadvantage is that it does not distinguish between wheat, barley and rye so if you have all three contaminants in one sample all you know is that it is contaminated, but not with what and in what proportion.

Another issue is that it detects only gliadins in wheat. Some celiac patients also react to high and low molecular weight glutenins. So, this may not be a major issue in ingredients that contain gliadins and glutenins but some, most notably starch, preparations don't always have gliadins associated with them and they have glutenins. So, it is something to be aware of.

The last assay I want to talk about is PCR amplification. Essentially, this is a method to amplify a specific segment of DNA to levels high enough to detect by assay. The reaction consists of three parts. The first is to denature or unwind the DNA template so you go from this helix to double strands. What this does, it allows the primers to anneal or bind to the DNA segment for which they are directed. Once the primer is annealed onto the DNA, then you can have the synthesis of the peptide of interest.

Now, what you need are forward and reverse primers, which is indicated here, to carry out this reaction, and when you want to extend these polymers you need DNA polymerase and nucleotide bases. You have probably heard of a thermal cycler. It is how this assay is done. What it does, it cycles through this a number of times to increase the DNA to high enough levels to work with.

Now, what I did, I took from this publication by Sandbert et al. some data to show you how PCR works and why it is so specific. The red boxes indicate the forward primers; the blue boxes the reverse primers. This sequence, here, is specific to wheat gliadin. In other words, it is not found in rye, barley or oat. Similarly, this sequence is specific only to rye and is not found in wheat.

Again, just to show this for hordein, the same thing. Here is the specific sequence and this is the specific sequence for avenin. What this means is that, unlike the ELISA assay, you can tell which of the cereals are within your sample by doing this DNA detection.

Here is sort of a summary table showing how specific these primers are. The wheat primers detect only wheat, not rye, barley or oat and all of these types of wheat make that selected DNA sequence. In other words, whether the sample contains winter wheat, spring wheat, durum wheat, spelt, kamut or triticale wheat, it detects that. The rye primer only detects rye; barley, only barley; and oat only detects oat.

So the advantage of PCR is that it is species specific. In any given sample you can tell whether or not it has any wheat, rye or barley within it. It is sensitive and rapid. It complements ELISA results. In other words, the disadvantage is that it detects DNA rather than protein. ELISA detects protein but if there is contamination, say, from rye the ELISA shows that this test is contaminated. The PCR probe with tell you that the contamination is due to rye. So, that is kind of a nice thing.

In summary, mass spectrometry is an excellent tool for protein identification. It is sensitive but not really rapid when you compare it to ELISA and PCR. It is expensive and technically demanding. The ELISA works well for a variety of unprocessed and processed food. It is sensitive and rapid. The main advantage of PCR is that it is species specific, complements ELISA and it also is sensitive and rapid.

What I have to say is that, as a user of mass spectrometry, I think that if you want to confirm absolutely results of ELISA it is the way to go. So, that is all I have to say today.

[Applause]

Questions and Answers

DR. SCHNEEMAN: We will take some questions right now from the panel. Also, if some of the other speakers are trying to get some questions, please alert one of the panel members that you have a question. I think it is the easiest way to get recognized. We know Doug will have questions.

DR. PARK: Douglas Park, with FDA. Considering the viewpoint of the individual that is susceptible to gluten, is it crucial that you know exactly which allergenic protein is present?

DR. HURKMAN: I would say the answer to that is no as long as they know that it is contaminated with wheat--

DR. PARK: Or one of the others.

DR. HURKMAN: --or one of the others, yes.

DR. PARK: So, then going the next step and saying if we try to set up a two-tier testing system, first with ELISA as you have presented here and then a confirmation with either PCR or mass spec., throwing away your bias for mass spec., which would you recommend would be a confirmation?

DR. HURKMAN: I think you answered that it is PCR because of its specificity and it is a lot less work than mass spec., for sure. But if you run into a question that you can't answer maybe mass spec. might be--

DR. PARK: Three-tier testing. Relative cost--I know you indicated that this is very expensive, and also relative time for both the mass spec. and the PCR. Could you elaborate on that a little bit?

DR. HURKMAN: I will try. Mass spectrometry, if you want to use a company that provides that service, runs about $150 to $200 per sample. That means that you are preparing this sample and giving it to them, which can take some time. The samples that we prepare take roughly a day and then with the mass spectrometer you can do 50 samples in a 24-hour period. So, that is where I got that it is relatively slow and expensive.

On the ELISA, I can only tell you that a kit is roughly $300 for 42 assays and it takes about an hour and a half. I was asking Jupiter about that timing. That includes the pipetting of the sample into the wells through reading the final results.

For PCR I don't quite know. In our laboratory we often start PCR the night before and get the samples the next morning. We can do a 96-well plate and machines can do, of course, more than one plate. Its cost is mainly for kits. Again, they are roughly $200 or $300 for a kit that can keep you happy for about a week or two.

DR KANE: (*See errata) Rhonda Kane, FDA. Thank you, Bill, for your presentation. On one of your slides you mentioned that some ingredients have glutenins and not gliadins. Can you give me any examples where you would have a food ingredient that would not come with both proteins together?

DR. HURKMAN: We are doing a project looking at various manufactured starches, and those are what I am referring to. The starches are relatively free of protein, low protein content, and of the proteins that are there, they are glutenins and not gliadins. Along with other cellular proteins, they seem to be a magnet for cell proteins. They are like a non-specific column for endosperm proteins.

DR KANE: (*See errata) Is this wheat protein that you are talking about?

DR. HURKMAN: Yes.

DR KANE: (*See errata) That only has the glutenins and not the gliadins? Is that correct?

DR. HURKMAN: No, it has the glutenins--

DR KANE: (*See errata) I am sorry, glutenins and not the gliadins?

DR. HURKMAN: And this is wheat starch.

DR KANE: (*See errata) And it is wheat starch. I had another question about the ELISA method that was mentioned by Jay Berger, where she said that the University of Nebraska mentioned that hydrolyzed protein and fermented proteins require a special ELISA--

DR. HURKMAN: Right.

DR KANE: (*See errata) --could you elaborate on that? What is so problematic about detecting those types of proteins?

DR. HURKMAN: What happens is that on processing with heat, whether wet or dry, the proteins denature and once they are denatured you can't solubilize and assay them. So, it is interesting. One objection I have to R5 monoclonal antibody is that it is patented and not anybody can do this so you have to run around and either create antibody yourself because they won't sell it to you and it only comes in a kit, or you figure out how to do it. In this case, it is very funny--I always try to find out how to do things and there is a patented solubilization buffer exactly for those types of proteins that they either include in the kit or you buy separately. That kit contains agents that denature the proteins so that when they go into solution you can assay them. Of course, the ingredients are secret. But in one publication I read it includes beta mercapito ethanol and, of course, it would. I mean, that is a standard component for doing that sort of thing.

DR KANE: (*See errata) I have one last question and that goes back to the starch. Do you know anything about modified food starch and how it may differ from just regular wheat starch--

DR, HURKMAN: No.

DR KANE: (*See errata) --and if the proteins in that are--

DR. HURKMAN: No. Unfortunately, I haven't read up on that yet.

DR KANE: (*See errata) Thank you.

DR. ZINK: Don Zink, with FDA. Is this R5 monoclonal antibody the one that is used in all of the commercial test kits now? What I am getting at is do these commercial test kits suffer from an inability to detect glutenins?

DR. HURKMAN: You could ask Jupiter. He can shake his head. But my feeling to your answer is yes. Is that correct? I am not sure about that because the Mendez kit is from Spain and I have no idea how many kits--at least two or three use them and I don't know how many kits are out there. DR. YEUNG: This is Jupiter Yeung. Actually, I am going to talk about three different kinds of antibodies that are used in the commercial market. The Mendez kit uses a different polyclonal antibody made by themselves.

DR. SCHNEEMAN: It would probably make sense to go ahead and have Dr. Yeung give his presentation.

DR. ZINK: Actually, I have one more quick question. On the refined starch do you consistently have enough DNA there to make the PCR reliable?

DR. HURKMAN: That is a good question and I think the only way it could be answered is by someone that has done it. We have not done that in our lab so I can't answer that. But it is a good question because it is not clear always that there will be enough DNA in your particular samples.

DR. SCHNEEMAN: Great! Thank you very much. Our next speaker in this section is going to be Dr. Jupiter Yeung, who is going to talk about some of the commercial test kits and methods.

Commercial Gluten Test Kits and Methods

[See presentation slides for Dr. Yeung]

DR. YEUNG: My name is Jupiter Yeung. I am the principal scientist with the Food Products Association.

There are three different test methods, as has been alluded to previously, and I am concentrating on just the commercial test kits based on the immunochemical methods, the ELISA and the lateral flow device that is the dipstick. The mechanism has been alluded to so I am going to skip it.

In the commercial world for the gluten test there are three different antibodies that are being used. The first one is the skerritt monoclonal antibody which recognizes the omega gliadin. Although it is a monoclonal antibody, it has also been identified that this antibody, also recognizes the R5 gliadin. So, the reactivity towards three different varieties of grains are different, with the wheat being 100, rye 120 sensitivity and barley only 5. The monoclonal antibody has been available for a long time, since 1991, and is the AOAC approved official method, in '95.

The other kind of monoclonal antibody commonly being used is the Mendez R5 which recognizes the five amino acid sequence and that recognizes R5 beta, gamma and omega gliadins and they are supposedly equally sensitive to wheat, rye and barley. Both antibodies recognize raw and cooked prolamins.

Here are the commercial test kits available in the U.S. market. There are six companies. Neogen is a U.S. company. R-Biopharm is from Germany. Tepnel and Hallmark are from the U.K. Diffchamb is from Sweden and Morinaga, a new company currently just getting into the market, is a Japanese company. Only the first one, the Neogen Alert is a qualitative test. The rest of the test kits are all quantitative.

The limit of detection and limit of quantitation and the range are all in ppm gliadin. So, if you want to convert it to gluten you have to X 2. Within this box you insert how many mcg/ml or ng/ml so I converted it to ppm to make it a little bit easier for everybody to compare. But recognize that for the Japanese one--actually, I should have two stars there because the reporting unit is different from anybody else. It is not just gliadin but, rather, a wheat protein. So, when you do the interpretation, they are not the same. If it is a quantitative analysis, once you look at the error kill, the error kill is from 1 ppm to 50 ppm detection limit.

The Tepnel and the Hallmark, although they are two different companies from the U.K., are essentially the same product because the owner, originally from Tepnel, developed all the test kits for Tepnel and now has his own company so they are essentially the same. So, all the companies Neogen, R-Biopharm--they use the R5 monoclonal antibody. Tepnel and Hallmark and Diffchamb use the skerritt antibody. With the skerritt antibody, they always have two different analyses, the regular one and the sensitivity is 50 ppm of gliadin but they all have a high sensitivity protocol that includes Tepnel, Hallmark and Diffchamb.

The high sensitivity assay will give you 5 ppm of gliadin so, depending on which method you use, you have different sensitivity and this is how many replicates you have to do per sample. The cost is here. But recognize that for the cost you can not just divide it by how much money and how many samples you have to run. Every time you run an assay you have to run the standard curve; you have to run your quality control samples so one cannot just say because they charge you $15, it is $15 a sample. It is not that cheap actually. But then one has to also recognize that they spent hundreds and thousands of dollars to develop the test kit so those are factored into your final product. Like the mass spec. you have an expensive instrument that you have to outlay.

Here, is the validation of the test kits. The RidaScreen was validated by the Ring trials of the Prolamin Working Group. For the BioKits and the HAVen one they used the AOAC method but original protocol was verified by the AOAC but not the test kit itself. All the test kits would have the validation data either internally or neutral site testing. If you ask the company, I think they will share with you--I don't know if they will share with everybody but I have all the validation data.

They have two different kinds. One uses the skerritt antibody, the other uses the R5 antibodies. So, the first one was validated actually by Sweden, the national food authority administration, the government agency. Morinaga was verified by the National Institutes of Health Sciences in Japan. I haven't seen the data yet but they are going to present in the AOAC meeting this month. From what I heard, it satisfied the government.

Here is one of the ELISA tests we use. This is the standard curve we use, and in all the samples you compare the color intensity with the standard curve. But this is not exactly that all commercial kits use this color scheme so it is different and another company product will give you a different color scheme, but it is all based on comparison with your controls.

If you look at the lateral flow device, the dipstick, there are primarily two different companies providing it. The R-Biopharm gives you 10 ppm of gluten. This time it is gluten because that is what the company insert declared. The Tepnel uses 100 ppm of gluten. Although it is two different kinds, essentially they are the same sample; everything is the same except they don't have the controls for the home test kit.

The mechanism is exactly the same as the ELISA test. It is a sandwich mechanism. So, if you have the antibody labeled and the antibody trapping in your sample in here and the control antibodies here when you dip into the sample, the sample containing gliadin, for example, will pull up and will bind with the antibody and will be trapped by another antibody for the test, and will give you a sandwich and will give you a color, and the control will be trapped here and give you a different color. So, it is essentially the same use. It will give you a few minutes for the reaction and for the whole thing to occur, but you have to wait until it dries up. So, in a total of about five minutes you will have your result.

So, if you have two lines it is positive according to this company's product, the control and the test line--so positive two lines, negative one line, and if there is no line it means something is wrong. Either your sample is not meant for this method. In fact, it happened. Then you have to do it again. Sometimes it is your problem; sometimes it is your sample's problem.

But most of the dipsticks are two lines. So, if you use a different company product--this one actually is the Tepnel one--two lines is negative; three lines is positive. If it is only one line your sample is overloaded. So, one has to recognize which commercial dipstick you are using so your interpretation will be different.

But also recognize here when they say 10 ppm or 50 ppm, when you see the line it does not mean it is 10 ppm or 50 ppm. It can mean much less than that. And we also have data to show that even if the detection is 10 ppm, you can see it; 5 ppm, can see it, depending on how strong the line is. If you are color blind you may not see it, but if you are not you can see it.

So, there are different issues with the gluten test kits. Depending on which test kit you are using and depending on whether it is the skerritt antibody or the R5 antibody the reactivity is different and the extraction media is also different depending on methods. Some use 40 percent, some use 60 percent alcohol and some use cocktails and some don't; whether it is cooked or not; or if you don't know whether it is processed or not processed. And there are also different standards being used in different kits. Most of the European test kits use the Prolamin Working Group standard now with the IRMM-480, but then the 480 is not commercially available yet to the market. Some use the AOAC standard. All the standards are not identical.

If you have a false positive and false negative in the ELISA, it is very, very difficult to confirm it because most of the alternative confirmatory methods, like mass spec. or PCR, are not available to most food companies, although one can use the antibody based Western Blot to confirm it but it is still the same mechanism.

Obviously, same as any other allergens or other contaminants, there are no official or no recognized sampling plans so random testing--what is random testing mean? I can get a positive sample and I can get a negative sample very easily if you know what you are doing.

Extraction media--there are different extraction media and cocktails, and also either alcohol or the cocktail and in the cocktail some ingredients are not known, and some we know interact with the antigens and antibodies and the mechanism is the antigen/antibody reaction.

The cocktail is also known to interfere with some of the complex matrices and it is reported in the Prolamin Working Group proceedings. Another thing is that when samples have a high polyphenol, tannins or syrups, that kind of thing, your recovery tends to be very, very low if you don't take care of it. Some have additives in. Some people add fish gelatin to improve their recovery.

Here is some of the information that we know. Here is R-Biopharm data. Here is 40 percent and 60 percent ethanol, 40 percent ethanol here, and the cocktail here. One can see from the same sample, the same homogeneous sample, that it will give you all different numbers. Usually the cocktail will give you quite a bit higher number. But are these high numbers the true numbers or not? One has to ask the question. The previous speaker, Bill, mentioned these 14 repeating units in the DNA sequence. So, is the antibody recognizing one unit or recognizing multiple units?

This is the PCR and it can differentiate or speciate in a different one but not for the antibody-based methods. For the partial hydrolysis from the syrup if you use the sandwich-based ELISA your recovery will be low so the Mendez group actually has an alternative method. Instead of a sandwich ELISA, they have a competitive ELISA to, so-called, better quantify the hydrolyzed product, and it has been published. But it still depends on whether you have access to the antibodies or not so it really doesn't help too much.

Reference material--IRMM and TLC in Europe have the 480 for wheat gliadin but, unfortunately, it is still not available. The nice thing about is it is fully characterized and also it is soluble. If you use the reference material, there are different kinds and they are not identical so what do you choose? Alternatively, you can buy from Sigma, you can buy from any other companies but they are not the reference material and they are not identical either as far as a confirmation method goes, and I think the previous speaker, Bill, has already mentioned this and discussed it with you.

Here is the information for the three different methods. These numbers are the ELISA quantitation numbers. If you mass spec. you can see all the alfa, beta and gamma gliadins using the mass spec. method. You can use the immunoblot of the antibody here, at the R5 antibody gel, and it will tell you which proteins will be recognized. This is the PCR for two different samples. So, mass spec. and the PCR methods would be a good marker to identify the allergens.

For detection and speciation, the antibody-based method can give you a summation of all the different kinds of grains--wheat, rye and barley. But the PCR and the mass spec. will give you alternatives or speciate which grain may be involved. If Health Canada is going to require speciation of source labeling of the wheat for celiacs, then we need an alternative method to tell whether it is wheat, rye, barley or oat. That is all for me now.

[Applause]

DR. SCHNEEMAN: Thank you very much. We will take some specific questions. Dr. Hurkman, do you want to come up to the front and we can have some specific questions for you right now and we can address the panel as a whole? Rhonda?

Questions and Answers

DR KANE: (*See errata) Thank you, Jupiter. I had a question so I understand one of your slides. It is the fourth one in your series where you have gliadin antibody specificity, and you have wheat 100 percent. Is rye 120 or is it 20?

DR. YEUNG: It is 120 because the antibody was originally starting from rye so it is more reactive to rye than wheat.

DR KANE: (*See errata) Can you explain what those percentages actually mean?

DR. YEUNG: It is the cross reactivity of the antibody. So, if you plot an inhibitory curve, the IC50, then you know that rye is more reactive so it is more to the left than wheat and than barley.

DR KANE: (*See errata) Thank you. I have just one more question. You mentioned, I thought, that there were three types of antibodies.

DR. YEUNG: Yes.

DR KANE: (*See errata) What is the third?

DR. YEUNG: The third one is Morinaga's polyclonal antibody. They make it themselves. They did not get a license from any of the producers.

DR KANE: (*See errata) So, that is not on that slide? Is that correct?

DR. YEUNG: It is not on the slide because Morinaga just came to the U.S. market and at this point in time they are trying to evaluate the test kits.

DR KANE: (*See errata) Thank you, Jupiter.

DR. YEUNG: You are welcome.

DR. PARK: Doug Park, FDA. Thank you very much for a very comprehensive summary of the methodology. I do have some questions and to some of the questions we already know the answer but I think we need to have that brought out. You pointed out and discussed briefly standards, the availability of standards and so forth. Would you address the composition of the standards that you listed and the potential availability to any organization that would want to have the standard for confirmation of their testing program?

DR. YEUNG: The reference material from NIST and IRMM, for that matter, too, they are the official reference material organization, and it is (*See errata) available to the whole world. It doesn't matter who buys it or where you buy it, it would be the same material, unlike if you buy it from Sigma; it would not be the same. All the NIST materials are available. The IRMM-480 are not officially available yet but 480 is an alcohol soluble protein and is meant for this kind of work. The NIST reference material, the different varieties of wheat, was not originally meant for allergens. So, for characterization it is different. You look at how much percent protein, carbohydrate, minerals--all the basic quantitative data that you can get from NIST.

DR. PARK: Thank you.

DR. YEUNG: The reason why we always push on reference material, the same as FDA--we worked together for a long time, pushing for the reference material because if you use different reference materials you would get different numbers that you would generate, different numbers from your test kit, and if you used it for your quality control samples they would also give you a very, very different number than what you are going to see, and your recovery would be different because you use a different standard so you are comparing a little bit different--it is not the difference between oranges and apples but it is definitely a different species so you will get a different result.

DR. PARK: Thank you. Also, on your slide where you showed the various levels of quantitation, and so forth, the Tepnel method has 50 parts per million. Does that mean that is the lowest you can go with that or are there other options?

DR. YEUNG: The Tepnel one originally was based on the skerritt procedure, the AOAC official method, '95. Because it is the official method it has been used for a long time but for the last couple of years, with everybody looking at the Codex number pushing down to 20, they are pushing it down to 20 ppm, so-called, the high sensitivity procedure. Then they put in a factor of 2 and made it 10 ppm.

DR. PARK: You also mentioned the matrix effect of some of the extraction procedures, in particular the cocktail. Are there issues where that can be addressed as well?

DR. YEUNG: Issues have been reported but because we do not know exactly what is in the cocktail--we know it is there--and some companies use it so you can imagine what would be there but we do not know exactly what kind of issues there are. But in our hands, when we use the regular procedure for testing and also when you add the cocktail in the numbers are different, substantially different. So, as a scientific organization, we probably want to take a closer look at these issues.

DR. PARK: You identified in your slide for instance milk but do you have that same effect with the cereal grains?

DR. YEUNG: I do not have experience in it but that has been reported by the European group in the 2004 proceedings.

DR. PARK: Was that the cocktail that was used for the validation study in Europe?

DR. YEUNG: That is right.

DR. PARK: And the data there suggests that it is fairly consistent and acceptable for those commodities that were tested.

DR. YEUNG: Are you talking about the Ring trial?

DR. PARK: The Ring trial.

DR. YEUNG: All the data reported from the Ring trial is consistent with all the other multi-lab validation procedures.

DR. PARK: This is my last question, and you will never be able to answer it because it is one of the biggest challenges. You did point out the difficultly with sampling, sample preparation, and so forth. I would like you to just take a minute longer and point out some of the difficulties associated with sampling as it deals with potentially allergenic products, dealing with the raw product as well as the finished product.

DR. YEUNG: I think everybody is trying to look at FDA and trying to get a guidance document to see what FDA's guidance is as far as sampling is concerned. I know you guys had an extensive look at this and we were told before that the guidance document will come out soon. I don't know if it will be soon or not. But I think most people still want to have guidance from the regulatory agencies so what we do can reflect that the inspector who comes to the plant and takes a sample will be consistent with what a company would want to do. Of course, the problem of allergens is that the contamination is heterogeneous and it is very sporadic, and also the sample would be very--you can have contamination at one portion of the process in-line or during the production cycle. So, sampling would be the biggest challenge. At the same time, because of the expense of the testing and the time involved with the testing, one cannot over-test during production.

DR. PARK: In your opinion, when you look at the analytical result which is a sum of errors associated with sampling, sample preparation and analytical, where is the largest error associated with those three categories?

DR. YEUNG: I think Whitaker presented and published in the journal of OAOC recently, in 2004 (*See errata) and if my memory serves me right, which doesn't happen very often, it is the sampling that gives you the highest variability, not the analytical method. Actually, the analytical procedures gives you the least uncertainty.

DR. HURKMAN: I think you asked a good question, and that is what about different samples--flour versus process? To me, and the work that I do, that is the critical point. Unfortunately, what we find is that for every sample we do we optimize the extraction methods and I think it is going to take quite a lot of work to categorize samples and how to extract them for best results or reproducible results.

DR. LUCCIOLI: Stefano Luccioli, FDA. I guess with the availability of some confirmatory tests like PCR or mass spec., do we have preliminary data on false-negative rates for the ELISA kits or is that something that we just don't have data on? I mean, how many times can one of these tests be falsely negative and it has been confirmed with a PCR?

DR. HURKMAN: I don't have a full answer. The Ring study is the only study I know with that sort of data. Right? If it even has it, and this was published in the symposium proceedings. That is hard to get. I have a copy back at the lab. So, that hasn't been directly addressed and I think that is why the assay is temporarily recommended rather than fully endorsed.

DR. LUCCIOLI: Thank you.

DR. PARK: I would like to comment on that, and I am going to put on my FDA hat. This is Doug Park. That is the reason why it is crucial that methods are validated because that is the type of data that you get from a validation study. The Ring trial is an example of that. The AOAC harmonized protocol is an example of that, where you have 95 percent confidence in the analytical result, and that addresses your false positives, false negatives.

DR. YEUNG: This is Jupiter Yeung. I think for the false positives and false negatives, from the Ring trial there is information--I don't have the exact data with me, but the challenge is on the actual sample. It would be very, very difficult to prove if it is a false positive or false negative from a real sample because all the test kits are meant for all food matrices. Obviously, everyone is going to spend a little bit of time in the lab. You know, it is not possible; it is all matrix dependent.

DR. SCHNEEMAN: Do you have one last question?

DR. LUCCIOLI: Yes, a follow-up to that. I guess we could be able to get information on which matrices may be more difficult to detect, and so forth. So, I mean, some information. I don't know if it is available but I was just curious, I think Miss Berger talked about how she sent samples to labs, to Steve Taylor's lab and the University of Nebraska, and I am just curious to know what has been the lowest level of detection, parts per million, of a consumer complaint, if that data is available.

DR. YEUNG: If you are looking at the company claim for the limit of detection, the lowest one is the R-Biopharm RidaScreen, which is 1.5 ppm of gliadin. That is 3 ppm of gluten. That is the lowest one. The rest are all 10 ppm and gluten.

DR. SCHNEEMAN: Did you want to comment on that question? Identify yourself.

MS. BERGER: Jay Berger, Miss Roben's. I was just wondering, you know, as a manufacturer of the products trying to come up with the appropriate testing for celiac disease and allergens, will the summation of this discussion evolve into specific procedures, specific tests and how to go about doing them so that we can provide the best accuracy to the product for the consumer?

DR. SCHNEEMAN: FDA is certainly in the process of gathering as much information as we can. So, we can make decisions within what we are charged to do under the law. So, you know, at this point we are trying to learn where we can go with the information, and that is really the purpose of this particular session, to learn as much as possible so that we can then make some regulatory decisions.

I think at this point we will need to break for lunch. I do want to again thank our two speakers for excellent presentations.

[Applause]

We really do appreciate your looking at the questions and issues we have and helping us get the information out that we need.

Again, we have an hour scheduled for the lunch break so I would like to see everyone back here at 1:35 for our next panel. The most convenient place is the Wiley Cafe but you will be exiting security. For those that are more adventuresome, certainly there are some areas in College Park that are possible too but just keep an eye to the time. Thank you.

[Whereupon at 12:35 p.m., the proceedings were adjourned for lunch, to reconvene at 1:35 p.m.]

AFTERNOON PROCEEDINGS

DR. SCHNEEMAN: Well, I think we had better get started. We are ready for our third panel and I do want to comment. I know we kept telling you that Cafe Wiley may be your best and simplest option, and I understand that there were some problems with the delivery and food service. We thought that we had sufficiently prepped them for having the public meeting and having the types of food that would be appropriate. So, I apologize if any of you were inconvenienced. We are going to follow-up to see where the gap was. It is embarrassing to us to have you here as our guests and not be able to offer the service that we thought we had prepared for. I hope that wasn't a hardship for anyone in particular and, please, accept our apology.

As I said, our next panel will be to focus on the consumer perspective on a gluten-free food labeling standard. We will follow exactly the same format that we have been following so far where we will have the three presentations and some questioning of each of the presentations and then, hopefully, we will have enough time at the end to have questions to the panel as a whole.

So, our first speaker is Miss Mary Schluckebier, who is the executive director of the Celiac Sprue Association, and I hope I pronounced that close to the way you like it pronounced.

Consumer Perspective on a Gluten-Free Food Labeling Standard

[See presentation slides for Ms. Schluckebiers]

MS. SCHLUCKEBIER: Good afternoon. I want to thank you again for the opportunity to be here. I am Mary Schluckebier from the Celiac Sprue Association, and I think it is really kind of an interesting opportunity to get to share with you some of the things that are happening with our members, or what our members share with us 24 hours a day sometimes. It is very nice to have answering machines, and e-mail and calls. There are just a lot of people being diagnosed now that have more questions, and those are the ones really asking the questions of the manufacturers so that they are now looking to help us by ways of communicating with each other.

At time of diagnosis--Dr. Hamilton did a very good job talking about the diagnosis and all that stuff as kind of a clinical thing. You have to think about it as this is a person. You have been eating a normal diet for years and they tell you these couple of things, first of all, about the disease itself; that there is no known threshold at this point that will create an immune response in people with celiac disease. There is no way to measure the presence of the offending amino acid sequences, and it shows in research that if you don't adhere to a strict diet you are going to get sicker--you know, that whole list of all the complications that can happen.

So, then you are told eliminate all foods and medications that are derived from wheat, barley, rye and oats at this time--I am going to abbreviate these as WBRO from now on--any of these foods that have the amino acids that evoke an immune response in people with celiac disease, which is what we mean. We mean that whole basket but we are going to call it WBRO. For the remainder of your life do this and then you will be healthy.

That is exactly what happens for most people. After a few weeks on a gluten-free diet people are feeling really great and then they get into something that has wheat in it, and they want to avoid this if at all possible. Now that people are taking less than 11 years to be diagnosed, we are finding people who have basically no symptoms at all when they consume some wheat, rye, barley or oats.

That makes it even a little more confusing and they begin to rely more on information from food manufacturers. So, again, from this time on what you put in your mouth is your responsibility and the consequences are really up to you, and how successful you are in reading labels, gathering information and making your decisions.

I would like to say that all of us process this information. We don't All of us who have (*See errata) celiac disease set up some type of way we make a decision multiple times a day on whether we are going to consume a product or not consume a product. Most people will seek information of one kind. Now, knowing that all information is not equal and that we all can't absorb everything the first week you are diagnosed and that it is a life-long disease, your decision-making process changes over the years.

But you seek out information and you have coping techniques. So, people with celiac disease often have a very broad-based knowledge about the disease and food. As a support group, we do have some help in helping people learn to do a self-management guide which has three stages. The initial stage is really looking at what you are eating right now and how can that be adapted to meet a gluten-free lifestyle so you don't have to make major changes immediately, and then slowly adding and evaluating foods that you want to change and adapt your diet and expand it to greater and greater food choices.

One of the things that we have published--we are now getting ready for the tenth edition--is a 375-page resource for people with celiac disease where manufacturers have given us permission to put in print their products that they consider to be gluten-free or they consider appropriate for people with celiac disease and dermatitis herpetiformis.

We do spot-check some of these and have an ELISA test done on them, usually at 10 parts per million. Most companies' products always test below the level of detection of these. There are a few that do not, and a few that have surprised us, like beer. We tested three kinds of lite beer with an ELISA at 10 parts per million and they all came out below level of detection. We tested another product that had barley as a second ingredient, and the company gave us the test and it had been tested with one of the older ELISAs that was only sensitive for the gluten. So, we tested it at 3 parts per million in one that was cross-reactive; 3 parts per million barley, the second ingredient, below level of detection.

We are not sure why for some of these things, but what we do is we take the information back confidentially to the manufacturer and see if they can help us understand it. Often then they make changes that make it more appropriate for people with celiac disease if it is over, or they feel great because they are doing what they think they are doing.

To make an informed decision you need to know what is present in a product and where it really came from. Natural flavorings has been a problem for people with allergies and celiac disease, and it is one of the really good examples though it is really hard to know, especially since barley is a very common flavor enhancer.

So, in a person with celiac disease the ingredient list gives you a good idea of what is in the product. Calling the manufacturer on processing and packaging is sometimes necessary if, in your decision-making process, when you have tried the product something isn't working and you are trying to eliminate which product of all the 20-something you ate during the last little bit. Then you often call the manufacturer and find out a little bit more about the product's processing and packaging and see if there is any other way that this could be cross contaminated, or if you can eliminate that this is not the problem food.

But when you eat 20 or 30 things a day--just think of how many things you eat--trying to figure out which one created a problem--now, we are doing this on symptoms, and all of you know that symptoms are not a good indicator of what is going on and they are very misleading. The symptom really may be that I am catching a cold so I am reacting to something that may be totally unrelated--maybe catching a cold isn't a good idea.

So, people use their decision-making process and try and ferret out what is good for their diet. That is why this meaning, full verifiable and consistent, is really what we are trying to pull together, and this meaningful thing is when I say gluten-free it can mean so many things to all of us. I am glad we use the definition--you know, we kind of came up with definitions of how we are going to talk today but when I am newly diagnosed and somebody says you are giving up gluten and you have never even heard of gluten, it is really hard and there is a learning curve. Again, as consumers, often our manufacturer consumer service groups have been the educators of our members.

Verifiable--we were talking again about the ELISA or being consistent. So, when I see gluten-free on one label it should mean the same as everything else. And, generally on gluten-free our members said they want it to mean the absence of wheat, barley, rye and oats and that whole basket of other things. But generally if you have any of those other items on a food label they are going to be in the label because they are a selling point and a marketing point for the manufacturers.

These are some of the things that people develop in their decision-making process. The cross contact--now, again, that can go from the field to the fork and often, as a home economist, I watch people prepare something and it often happens right there in the kitchen. It happens when somebody dips into the peanut butter jar and puts it on the bread and goes in again and then gives it to the person who is trying to avoid a wheat product. It is very difficult to explain to people that a person with celiac disease may have to watch and be cognizant of all these potentials for their entire consuming life. And, I am thinking why I gained weight. Sometimes I wonder if we just shouldn't eat just a few things and then there would be a lot less to figure out and we wouldn't gain weight, and it would be a weight loss program and it would be easier to sell.

The cross contact begins at the farm, and I am a farmer. This was near our farm. Harvesting of summer wheat, spring wheat, winter wheat and oats often in the Midwest is within two or three weeks of each other. They are always going out to harvest just before a rain because it is coming, and you have to get it out and you know if you let it go--so it is always under pressure. I have been married 30-some years and it is always under pressure. We don't do this anymore. We don't do the wheat anymore. But this one is near our farm. There is no fence. There is no buffer zone. And there is not, at this time, any regulation that would call for that. But here the wheat has already been cut. If you notice, there is a green tinge to the oats. It is not quite ready but there is wheat growing in the oats and oats growing in the wheat. But we don't have to worry about cross pollination because these are not cross pollinating crops but they are harvested and handled in much the same manner and through the same harvesting equipment, and they are a consideration.

Now, I said my husband used to be a wheat grower. We don't do wheat anymore. But there is a quality control that I think about applying--olives, the olives for the olive oil, they go through and they separate them by grades. Maybe we just need a few more grades so that a pharmaceutical grade would be adequate for people with allergies and gluten-free. As a farmer, I think this kind of sounds good because we maybe could get more money for our crops. But right now it is not even a near possibility.

So, when we ask our members across the country about oats, right now eliminating oats from their diet, 151 said they ate it and 22 had no answer to the question. When we asked how would you like to have gluten-free defined, the first time we asked that a few years ago we said so many parts per million and gave them checks. They basically said, "don't tell me the parts per million, I want it absent of wheat, barley, rye and oats. I don't know what these numbers mean."

I think there is a potential for oats here. It shows that there are people who really don't know what it is and are eating. It is totally inconclusive on oats from everything I have read. When I became a celiac in 1986 they were questioning oats, whether or not to have oats. We had 1,101 define gluten-free as the absence of WBRO and 77 others who said they would like to see it that way but they don't know whether oats should be included or not be included in the definition.

At the threshold meeting, Dr. Colin presented the fact that in the study that they did 10 percent of the participants with CD did get immune symptoms and 19 percent of DH, and I just think that maybe we need to look into this subset and see if it is a real subset of people with celiac disease who can or cannot ingest oats without any immune response.

On packaging, if it could be that gluten-free means the absence of all wheat products in the product itself and then be verified with testing, we would avoid things like this. Both of these gravy mixes are marked gluten-free. One has hydrolyzed wheat protein, and then it says ELISA tested and gluten is removed, There is no standardization for any of this and it is confusing for a consumer.

The other package has rye malt extract as a seventh ingredient, again, you saw gluten-free on the other side. We had this one tested at the University of Nebraska with the RidaScreen and it tested 3,630 parts per million and we were talking 10 and 3 earlier. When we have tested things there isn't a real consistency, and I wish there were.

One of the things is we have to have all the ingredients on the product label. This is candied walnuts. This one has wheat starch in with the walnuts. Some of the food processing people can help me a little bit with this, but I think wheat starch is one of the wonderful coatings you can use to help keep things fresh. That also then creates a problem for a person with celiac disease. They learn to read labels even when you think you don't need to read labels. One manufacturer said since I started working with people with celiac disease I have learned about a new technique. Celiacs pick up a package and give it the celiac twist, they turn it and look at the ingredients. If you want to know anything about any ingredient you would probably ask the person with celiac disease. They probably know that food and nutrition label better than anyone else because they have practiced a lot.

Also things that are a little confusing on labels are wheat fiber that is certified gluten-free and we don't know what the certification program for it is. Wheat grass, again, wheat grass has not been really tested because the people who test wheat test it as it is emerging and then as it is a mature crop, and as a grass there is no research. Hydrolyzed wheat protein, again, is one of those where the ELISA test is not the most effective way of recognizing it. So, this is an area that requires a little more research before we really know how to even deal with these. So, again, a definition that just says the absence of anything from wheat, barley, rye and oats is probably the most conservative at this point.

When we ask manufacturers whether they have these ingredients in their products, "well gluten is not present in oats and barley because we use only the outer portion of the grain kernel and that is gluten-free." "Wheat fiber is certified to be gluten-free." "We adhere to the Codex definition of gluten-free." "And it tested below the level of detection for gliadin so it is gluten-free." When they were talking about the testing, there are some that are just specific for gliadin and some that do a crossover for the other prolamins.

If you want to know what our group looks like that were in the last two surveys, we are mostly women. We are over 45 that stay members of CSA. One of the things that happens with membership in an organization like a support group is that as soon as people become very comfortable in their decision-making process they are like butterflies and they fly off and go do their own, and feel like they can manage their own disease, which is good but it means that often we don't have everybody who is a celiac as part of our organizations. In Europe, if you are diagnosed you automatically become a member of organizations, such as in England.

This is the one that always surprises me. When you ask the educational level, the education level of our members--those last three columns--is some college, college and postgraduate. I don't know if it takes somebody really smart to get diagnosed or, like one of my medical advisers said, you can't make any kind of claim on those. But it does mean that we do have people who are readily reading labels. But we also have people who are celiacs that are blind, they can't hear, and we have those who have below 100 in mental capacity, and we have had social workers call and say, "how am I going to protect the child that has a mother who is not functional in the grocery store and at reading labels?" The one to the right is to show you that most people who have celiac disease are just normal people with all the other problems that we can have, including other food concerns and you will notice that milk is the most common. When we ask how many food concerns do you have, or allergies, or whatever, it was real interesting that almost half of us have something else we are looking at that label for. So, just marking gluten-free, if this is indicative and you can use this small group to predict the larger group, there will be at least half the people who have to read the label for something else.

But when we ask them what do you consider your greatest challenge as a person with celiac disease, the top one, overwhelmingly the top one is lack of good food labeling. Now, I don't know how you evaluate this part but they put avoiding cross contamination along with concerns with traveling and making decisions when you are eating out. They weigh both about the same.

Where do you go to purchase your products? People overwhelmingly say health food stores, followed by grocery stores, mail order, internet and super stores. When we ask them also where do you think other people with celiac disease go to buy their foods--grocery stores.

We ask people to rate themselves with how sensitive they thought they were to food, medications, the skin, contact of medications, hair products, detergents and lotions and soaps, you will see that it is kind of all over the place.

People all say that their food concerns are the highest. They are most sensitive to food. But notice that there are people from very highly sensitive to those that are hardly sensitive at all.

Then we ask them how will you rate your risk of choosing a product if you have incomplete information. Will you take a risk? What is your risk management technique? No matter where they were on that sensitivity curve, we don't repeat the same one here. It is almost overwhelmingly that they are adverse to risk. They will take as little risk as they need to, to continue on their diet.

So, what else do you look at when you are looking at a label to purchase something? First of all, most people are going to look at the ingredients even if there is a marking that says gluten-free. Then, after that, will they buy a product with a seal or something that says it is gluten-free? Most people will buy it at least once.

This is what we are doing as part of our program to recognize those companies that are utilizing the WBRO and have given us good documentation that there are procedures in place that will assure a person with celiac disease that they are making a choice by purchasing this product, that it is free of wheat, barley, rye and oats and everything else.

These are the general terms of the license. We say that it is generally free in product, processing and packaging. Everything is kept confidential. Confidentiality I think is very important in this type of communication between consumer and the company. And, this is the seal of agreement.

Questions and Answers

DR. SCHNEEMAN: Maybe we will take just one or two quick questions, if there are some, and then we will save the others for discussion.

DR KANE: (*See errata) Thank you very much. Rhonda Kane, FDA. Mary, with your certification program do you ask them what parts per million their products have to stay below for any sort of test for gluten, or do you require them to have a test with the results shared with you? What is the scoop there?

MS. SCHLUCKEBIER: We require them to submit some product and we will go pick things up from the grocery store periodically. Depending, again, on the processing, they are assured that it is in place. If it is a dedicated plant and they have only two products our testing requirements are a lot less than if they have 20 products. They have dedicated lines but in a somewhat segregated area. So, it really depends on the company itself and what procedures they already have in place and they may already be testing. If they are, then we do ask for copies of those and we do also do our own independent testing. We will also do on-site if the situation is one where that looks like a prudent choice for helping people with celiac disease that it is a product that is staying consistent with no WBRO.

DR KANE: (*See errata) Do you have a cut-off point though? In other words, do you use 10 parts per million or below as receiving permission to use your seal? Or, can it go higher?

MS. SCHLUCKEBIER: I really don't see any time when it would go higher than 10 parts per million. It often might be lower. Many of the products that we are testing where we have tried at 3 parts per million, they are doing beautifully. It is not detectable at all at 3 parts per million.

DR KANE: (*See errata) Thank you.

MS. SATCHELL: Felicia Satchell, FDA. I wanted to ask about your CSA gluten-free product testing and if there are any criteria that manufacturers have to meet in order to get their manufacturing information or products listed in the manual.

MS. SCHLUCKEBIER: Right now, because there is no FDA definition, we send the manufacturer our list of what we consider necessary to assure people that it is a product that is free of wheat, barley, rye and oats. Most companies are very, very good at voluntarily saying which of their products are the best choices. We can't test all of them and we don't; we take their word for it. Often when we get communications from a manufacturer who wants to be in it, you can kind of tell--again, those red flags. There are some things that just don't seem right here. So, we will do some extra checking and we will ask for more documentation.

MS. SATCHELL: A follow-up question, do you know if these products that are included in your manual labeled as gluten-free are actually on the product package?

MS. SCHLUCKEBIER: Probably very, very few of those are marked gluten-free. Those companies that do provide it are basically a niche market to those who are trying to stay free of wheat, barley, rye and oats for any reason. We do have an area in the back that is a vendors' section where we give the company an opportunity to share a few paragraphs about their company that helps provide the people with celiac disease additional information to make their decisions.

DR. SCHNEEMAN: Can you hold your question for later discussion, please? Our next speaker will be Miss Pamela Cureton, who is a dietitian who works at Celiac Research Center which is affiliated with the University of Maryland, located in Baltimore, Maryland, Celiac Research Center.

[See presentation slides for Ms. Cureton]

MS. CURETON: Good afternoon. I happen to be one who had a great lunch this afternoon so I thank you. It was delicious. My name is Pam Cureton. I am a dietitian at the Center for Celiac Research at the University of Maryland.

Recently, in July, we presented a conference. We did a conference for both professionals and patients. It was about a day before the conference was scheduled and we were running around, extremely busy, trying to get ready to put on the conference, when we got an e-mail from Rhonda saying, by the way, do you have any questionnaires, surveys, any information that we might be able to use in helping us answer our questions? So, I got an e-mail from Dr. Fasano saying, hey, this is a great opportunity. I said, well, I had a couple of hours slated for a little sleep; I can forego those. So, quickly we put together a survey trying to look at some or the questions that the FDA is looking at in the Federal Register.

So, this is just a quick summation of what that survey was. Taking a look at who completed our survey in demographics, you can see that these are all members of CSA because they meet the same profile. The sample size was about 57, mainly female. People completing the survey were aged in a range from 11-78 years old. Actually, a person on a gluten-free diet ranged from 3-78. They are of a higher income level and had at least some college. They are predominantly European American. And, about a half of them had at least two years on a gluten-free diet but some were just newly diagnosed, less than a month, and some for more than five years.

I wanted to know how carefully they thought they were following their diet, how strictly did they follow that diet and how compliant were they. About 53 percent said that they never ingest gluten. As part of the question we asked are you concerned about questionable ingredients or cross contamination? And, these people felt that they did not ingest any gluten and there was no concern for ingredients or cross contamination. Thirty-seven percent, however, were trying hard to follow their diet but weren't sure about these questionable ingredients or if they were getting cross contamination in their diet. Five percent actually knowingly ingest gluten.

In trying to answer question number eight talking about ingredients that should not be present in gluten-free foods, I also found this one interesting when we just listed ingredients that somebody with celiac disease might question. So, there are a lot of things on this list that are perfectly safe and really don't need to be questioned. But you can see that a lot of our respondents were concerned. Overall, it shows that people are very confused about ingredients, what goes into ingredients, and whether it contains gluten or not. For example, starch, as this committee is well aware--if the word starch appears on a food label, it is from corn, therefore, it is completely safe to eat.

Also, some known gluten-free or non-gluten-containing grains like millet and buckwheat, again, are of concern to some of our respondents. Things like distilled alcohol and vinegar are still concerns. So, people have a lot of questions about what is on that food label and what is in those food ingredients.

So, we asked what does gluten-free mean. Are we talking about no detectable levels? Are we talking about trace amounts that are probably safe to eat? Or thought to contain gluten and definitely contain gluten.

There is no surprise here. Seventy-one percent of the respondents felt that a food item labeled gluten-free should have no detectable gluten. There should be no detectable gluten in the product. A few responded that there could be trace amount and they would consider that safe to include. Only two percent said it may contain gluten.

Again, the same question was asked, what should it mean? You have your perception of what you think it means; what should it mean? Again, very much similar response and 83 percent reported it should mean no detectable gluten; 17 again reported that they would consume it if it had trace amount and feel that it would be safe to consume. So the perceptions of what people think gluten-free means and what it should mean are virtually the same. An overwhelming amount say that there should be no detectable gluten.

At looking again at trying to identify foods with gluten, and I think it was question number nine, we asked how consumers identify packaged foods that do not contain gluten. When you are reading labels how do you identify those foods? Of course, reading labels was number one. Our respondents could check more than one answer so they could check from a list of questions which ones they would use. Thirty-two would rely on the food labeling gluten-free; 25 would call the manufacturer. Other choices which were not selected would include asking healthcare professionals, like dietitians and physicians--that made me feel good! We also asked about risks and product guides. Those were other selections that people used to find out if their food had gluten.

Question number ten refers to packaged foods like consumers with celiac disease purchase or consume are primarily or exclusively those foods labeled gluten-free, so kind of what influences the purchase. Only 24 respondents reported that they would rely on those gluten-free foods, while others would rely on the manufacturer or, again, rely on the safe food lists that are published or on the internet. They would use those as reference.

We did ask how likely they were to purchase the food if the food was gluten-free, if there was nothing on the label that indicated that it contained gluten but it was manufactured in a plant that also manufactures other foods that do contain gluten. So, how likely were they to purchase that food? They were evenly divided on either extreme. Only nine percent said they absolutely would and only nine percent said they absolutely would not. So, the majority of the people were in the middle and would probably purchase the food if the food was gluten-free but still was manufactured in a non-dedicated plant or where other gluten-containing grains are.

Obviously, there are limitations to this study. It may not generalize well to all of our celiac patients. It was a sample of convenience and, again, these were predominantly high income, well educated Caucasian Americans participants with an average age of 47. So, it was a small sample size and based on self-report. Thank you.

[Applause]

Questions and Answers

DR. SCHNEEMAN: Do we have some questions? Yes?

DR. LUCCIOLI: I have a question on a slide where you say what does GF mean. You have a trace amount of gluten and in parentheses you have less than 10 mg.

MS. CURETON: It should be 10 parts per million

DR. LUCCIOLI: Okay, that answers that. What does the consumer understand? Do they understand the significance of the level 10 mg/kg or that it also is a factor of how much they eat?

MS. CURETON: Based on clinical experience in a clinic when I instructed patients, they basically have no clue as to what a part per million is, what a milligram is, how much you can eat, that there is anything in the foods that they eat that is listed gluten-free. They are assuming there is nothing there; that they are getting any source of contamination when they are reading their labels and following the recommendations, and how much they can eat. This doesn't enter into their thought process.

We have patients who are more sensitive to gluten and we have a hard time getting the antibody levels down to normal. So, some patients can do the basic diet, follow it carefully, read the labels and do quite well. But there are those that are more sensitive and we have a hard time getting their levels down. Those are the patients that I spend more time with talking about those types of issues--how much of the gluten-free products they are getting. I try to explain to them there could be some contamination or low levels of gluten that they are very sensitive to, and they are very surprised when they hear me say that.

DR. LUCCIOLI: Thank you.

DR KANE: (*See errata) Rhonda Kane, FDA. Thank you very much, Pam. I had a question about gluten-free. You talked about no gluten, but as far as the grains that they consider being sources of gluten, are they the typical ones we have heard about from others, and what about oats? Could you elaborate, please?

MS. CURETON: They would be the typical grains. Again, the patients that we see are well aware of wheat, rye, barley. I am questioned frequently on oats. But wheat, rye and barley are the standard grains that they are well aware of.

DR KANE: (*See errata) And does that include the crossbred hybrids like triticale and also other varieties or other species within the triticum genus with kamut, spelt durum wheat, etc.? Are they including those too?

MS. CURETON: I think a lot of them, like me, didn't even know what triticale is--I can't even say it--before I started looking into celiac disease, and kamut and all of these things. I don't think most people knew what they were. Those things they are less aware of, and spelt is still a big one, as we commented on earlier. Health food stores are promoting gluten-free diet being okay to have spelt and a lot of people are very confused about that.

DR KANE: (*See errata) What about the oats issue? Are they including oats or not?

MS. CURETON: They are not including it; they are asking. They are asking for permission. When they come to see us they are asking for permission. At this point we do not allow oats at our center. There are other centers that do. I basically give them that information. I tell them that we are not recommending at this time and I tell them other centers are, and they are okaying it, and what I ask them to, if they do decide to make a decision to try oats, to please let me know so we can then follow their antibody levels to make sure that they are doing it safely. So, we would just follow those patients if they choose to do that. We, again, present them with the latest and what our opinions are and just ask them to tell us if they are going to try oats and then we will follow them for their antibody levels.

DR. SCHNEEMAN: Thank you very much. Our third speaker for the panel is Miss Anne Lee, who is a nutritionist who works with the Celiac Disease Center which is affiliated with Columbia University located in New York City, Celiac Disease Center.

[See presentation slides for Ms. Lee]

MS. LEE: I want to thank you for inviting me. I am very honored and, indeed, pleased to be part of this momentous occasion in helping the FDA determine what should be included in gluten-free labeling and to help direct that.

Today we are going to be talking about different topics that need to be addressed. Actually, Tricia Thompson's name is on the program also. She is the lead author on a diet survey that we will be looking at. What we have done is combine Tricia Thompson's article on the survey of gluten-free food consumption, in addition to surveys that we are doing ongoing at Columbia which look at consumption patterns, the price of gluten-free food, in order to pool the latest research information that we have together to better address the various questions the FDA has asked us to look at.

In the gluten-free diet survey we reviewed the food records for 47 adults, 39 females, 8 males. Again, this seems to be representative of the population of people with celiac disease. It was interesting in this population that as we looked at their consumption patterns and the types of foods that they ate that across gender they tended to eat the same types of foods.

What was also very interesting is that the largest group of foods that they tended to eat were the prepackaged, pre-prepared foods that were labeled gluten-free. The patterns also noted that there was a large influence of corn-based products, particularly snack type corn-based products, like the chips, the savory snacks, and only two participants out of the 47 actually consume the other gluten-free safe grains. There were two that use bean flour or millet on a routine basis.

So, when we look at these consumption patterns, we are finding that many people relying on the labeling of gluten-free and relying on things that are safe. And, I think that is an important thing to note.

The other thing we found is that the type of food groups, whether it be sandwich bread and pastas or corn tortillas, also had a determining factor on whether or not the product they consumed had a gluten-free label, and it was depending on the particular groupings of food whether or not those foods were labeled.

The foods that are in the sandwich bread group, which included muffins, pizza crust, pretzels and those things predominantly, these foods were all well labeled gluten-free and participants overwhelmingly chose the ones that were labeled gluten-free over those that were not labeled gluten-free, and the labeling was prominent on the packages, as you can see. It was front and center and highlighted, which we feel was an added bonus of security to the patients buying these products.

In the pasta group, again, we find the same sort of purchasing patterns. Again, these foods tend to be specialty food items. They were done in designated facilities. They were prominently labeled as gluten-free, and most were labeled gluten-free, not all, but the list of ingredients was the second determining factor in this group. Again, the labeling tended to be prominent rather than being small or on the back of the package, which was an influencing factor, and it was everything from saying gluten-free in the middle of the bag to just the universal symbol that is often used on the European products.

In the pasta and ready-to-eat cereal, the group of products in this main category that were not as prominently labeled were those that we call more ethnic type foods, like the Asian rice noodles, and these foods tend to be naturally gluten-free. They are only made with rice or buckwheat so, therefore, are gluten-free. These were the products in this main heading that were not labeled and these were the ones that the participants used the list of ingredients to determine their safety.

The next group of foods is snacks and crackers, and this was a product area that actually presented some problems. This was a group that was one of the largest food consumption groups overall. When we look at all the different products that our patients and clients were, consuming, the snacks and crackers and these prepared foods actually comprised over 50 percent of their daily intake.

Now, as a dietitian, you know, red flags start going up, and when we see that someone's grain and carbohydrate intake is over 50 percent of snack foods, it makes me be very concerned about the nutritional content of the diet overall. Indeed, Tricia had done other work that notes that the nutritional intake and nutritional value of someone on a gluten-free diet is not meeting the standards we need.

One of the things too in this area of products is that we find much mislabeling. As you can see, one brand of the rice crackers was labeled "no gluten added" on the front and on the back it says it contains trace amounts of wheat. What is a consumer to do? Which side of the package do you believe? So, standardized labeling would help alleviate a lot of that.

As we said, the corn products were one of the areas that were heavily relied on. Again, it was a lot of the pre-prepared snack types of foods that, again, raise some concern. As many of these products are considered naturally gluten-free--a corn tortilla for the most part is corn and a little bit of salt so it is generally safe. However, the heavy reliance on corn-based products also has a negative impact on the nutritional quality of the person's diet. We are missing fiber; we are missing the iron; we are missing other B complex vitamins.

The other area besides the corn and snack food, as we said before, is the large selection of frozen prepared foods that many of the participants use. The good piece of information on this is they chose foods that were clearly labeled gluten-free but, again, there are so many questions about nutritional density of those choices.

Based on these findings. we were concerned that with this type of an intake and with knowing that gluten-free labeling was an important factor in these consumption patterns, we wanted to look at the next step. What is it that makes a consumer or a client determine whether or not to buy a product? So, again as Pam had done, we did a survey of about 57 people who came to see us at the office and the Celiac Disease Center and asked them--we gave them a short, little survey--what was it that made them decide to buy one product over another.

One of the outstanding pieces of information we got from this is that 100 percent of the participants, 57/57, said that if there were two products side by side with identical ingredients and one was labeled gluten-free and one was not, they would purchase the one that is gluten-free, which is a wonderful endorsement for the labeling. However, it also brings to mind the concern of does that make one had of broccoli safer (*See errata) than the next? So, I think we need to keep in mind that there is an overwhelming need for labeling, but labeling of the appropriate product.

I had one woman tell me, well, I know that this can of tomatoes is okay and it is better than the other one because it says it is gluten-free. There is really no foundation for that. A can of tomatoes is a can of tomatoes. So, we know that there is a drive by the consumer, by our patients, to look for that safety in the labeling but we, as the industry and we as the professionals in the health field, need to also direct them and teach them which way to go.

We did find that the presence of the gluten-free label did, indeed, have a very huge impact. When a label was not available on those products--again, the savory snacks, the crackers, the naturally gluten-free products--the second thing that the clients look for, in a 2:1 ratio, was the list of ingredients. They will look down the list of ingredients and try to determine from that whether or not the product is gluten-free.

What we found, however, is that there are many questions. Is spelt, indeed, what or not? What is triticale? And, where does kimwa fall into (*See errata) place? So, they try to decide from the label but more information is needed there.

Now that we are going to be better understanding what is influencing our patients' and clients' practices, we also need to know how to teach them well. For this part of the presentation I wanted to highlight the ADA, the American Dietetic Association, manual and the client education material that is available for all dietitians because I think not only do we need to educate the consumer, but we need to educate ourselves so that we also know the grains and things that we are going to be teaching them about.

However, at the time of this presentation the 2004 ADA manual is the one that we are showing you here. The 2005 edition, which will reflect the 2004 food allergen labeling law is in the last stage and may be ready for the September 19 docket deadline, but at this time it is not. That one would give a better picture of what we really need to teach our clients and how we really need to direct them and steer them through the food labeling and the ingredient list.

We would be able to say that malt is still something to worry about because it is barley based, whereas the modified food starch is going to be corn based and it will say it so that we will be able to better teach them things to look for there.

As we said, barley and rye will continue to be an issue in the 2005 edition, but that is something that we will make sure that our client is educated on. The ADA manual does tend to be client-centered so that we give them the tools that will be able to give them that shopping list, that hand-held kind of piece of paper to take to the store so they can make those informed decisions and can maneuver through the various products, with it be a rice cake, the kind of thing that might not be currently labeled and the ingredients may be difficult to get through.

In all of this, we realize that we are purchasing many products, that we have increased availability of food, increased availability of labeling and increased availability of foods in the various vendors, whether it be a supermarket, a health food store.

But we found, as we are looking at different patients and they are reporting back to us, that in what was influencing their purchasing practices there was an underlying tone of "but I can't find it" and "I can't find that." If you started asking them where they shopped and how they purchased their food, we found overwhelmingly that they tended to do it in the grocery store, the health food store, online or through specialty vendors. But this raised the question to me--and we actually did a survey of the difference in cost of the products in these four different spaces. The regular grocery story availability depended upon where they were. We surveyed stored in Portland, Oregon, Rapid City, South Dakota, Chicago, Illinois, New York and Atlanta, Georgia. What we found is that depending upon your location--and I can guarantee you know exactly which store had products and which one didn't--that determined what that client was able to obtain. The patients who were looking for things in the Midwest, in the Rapid City are, they had to go online. That was the only choice they had. That brought up the question to me, because the online products tend to be more expensive than those products, if you can find them, in the local health food store or grocery store.

So, in addition to the labeling that our clients have to decipher, we also have the additional burden of finding the food and the economic cost of it. So, maybe if the foods were labeled in the regular grocery store, those rice crackers and things, it may increase the availability of food to these people in these other locations. We are fortunate on the East Coast to have a great availability of food but that is not true for many people across the country. And, we get calls frequently at the Center from people in Iowa, in South Dakota asking is it safe to eat X, Y, and Z product? And, we have to try and direct them as best we can through those ingredients because that may be all that is available to them.

We looked at two different groups because those tend to be the largest consumed products, the gluten-free pastas, as we have seen, and the gluten-free bread, and in both cases there was an increased price for buying the product online. What we did is we took two products and looked at them both in the health food store and online, and this was the difference in cost even before we added in shipping and handling. So, the concern is that for those consumers where the market may not have quite caught up to them yet there is not only the burden of reading those labels but the economic one, as we said.

The final thoughts are that for our clients with celiac disease we do want to encourage them to consume a wide variety of foods. They do include many various products, both labeled gluten-free and not. Those that are not labeled gluten-free, they try to obtain those that are manufactured in dedicated facilities. That is not always possible. There is a strong preference to purchase the foods that are labeled gluten-free when available and when possible. Many have reported that it is difficult to determine the gluten-free status of a product that is not clearly labeled. Thank you very much.

[Applause]

Questions and Answers

DR. SCHNEEMAN: We will have some specific questions for Anne. Then, if the other panel members could come up we will have the general panel immediately following. So, if we have some specific questions right now? I will let Don go first.

DR. ZINK: Don Zink, FDA. You talked about looking for products made in dedicated facilities. How frequently do manufacturers label or indicate if a product is made in a dedicated facility, and how do they do that?

MS. LEE: Often through advertising. There are certain manufacturers that do state it is a dedicated facility. It may be on the label. It may be in the advertising in various magazines and journals. But, again, the consumer is left to try and find that out before they can even purchase the product.

DR. ZINK: I guess a follow-up, is it desirable? If you have gluten-free labeling, is it desirable to also have some sort of labeling if it is in a dedicated facility or not? Does that improve comfort level?

MS. LEE: It would improve comfort level but, indeed, if we had uniform gluten-free labeling, my understanding would be that it would meet those standards and the additional labeling that it is a dedicated facility would not need to be on it because it is already going to meet the standards of being gluten-free.

DR. PARK: Doug Park, with FDA. I noticed oats is missing in your presentation. Would you like to explain that?

MS. LEE: We say that oats are okay, with this caveat, because oats are a wonderful grain and scientifically it is gluten-free. It is the milling, the handling, that cross contamination that is an issue. From work that was done by Colin (*See errata) and Thompson who have looked at the issue of gluten contamination in oats, there are a couple of oats that are available that we feel do meet those standards. We have looked at the research out of Europe and we really feel that including clean oats in the diet enhances the diet. It helps add those nutrients back that right now are sorely missing. However, we beat our patients up a little bit.

They can't start oats until they are symptom free. We are not going to add a new twist into the diet unless we know that their antibody levels have come down; they are symptom free. Then if we add oats we know the variable we are adding. We add oats in from the two different providers that we say are safe and then we follow up with them both with antibody testing as well as symptoms. If there are any changes there are no more oats. We instruct them very, very carefully. It doesn't mean oats on any label; it is specifically the can of oats that are clean, designated oats.

DR. PARK: Thank you.

MS. LEE: You are welcome.

DR KANE: (*See errata) Anne, I have a question. You said several times in your slides that the presence of a gluten-free claim or symbol strongly influences purchasing choices of people who have celiac disease. Is that correct?

MS. LEE: Absolutely correct. Specifically on the two products side by side that were identical based on the ingredients, if one is labeled gluten-free and one is not, in our survey 100 percent of the respondents picked the one labeled gluten-free.

DR KANE: (*See errata) Okay, I am going to take you to the next step because you gave a very good example about canned tomatoes--

MS. LEE: Yes.

DR KANE: (*See errata) --say, all canned tomatoes, if they are strictly canned tomatoes with tomatoes and salt and possibly another second ingredient but it is tomatoes, period--

MS. LEE: Right.

DR KANE: (*See errata) --if they are all inherently gluten-free and one has a gluten-free claim and the other doesn't, just because they don't choose to put it on there, not that it isn't; it is identical--

MS. LEE: Right.

DR KANE: (*See errata) --in your opinion, what would be a way to make it less confusing for consumers who are looking to make the right choices and not being concerned that one brand is okay but the other brand isn't, and get the message across that all of the same type or category of food is gluten-free whether they have a claim or not? So, what would be your suggestion if somebody used a claim of gluten-free to kind of rectify that?

MS. LEE: What we do, and I am sure Pam does something similar with her patients too, we try to educate the patient, because we start there, that there are certain foods you need to be careful of. Things like your fruits and tomatoes, if they are just inherently that product--the can of tomatoes, the head of broccoli, the frozen carrots--that naturally is gluten-free. It does not need a label. What we would recommend is that the manufacturing community follow the same thing. There is no need to say a tomato is gluten-free. It is gluten-free.

Where the labeling would help is on those grain products that do present a question as to whether or not they are gluten-free. If we could recommend that the law would include those products that would raise a question--the pastas, the breads, the cereals, the crackers--because those are the things that we need to help identify for our patients. A broccoli is a broccoli, is a broccoli. It doesn't matter whether it says it is gluten-free or not.

DR. SCHNEEMAN: If I could maybe just clarify what I think Rhonda is getting at, so, if a person still chose to do label their broccoli or tomatoes because they feel it is a truthful statement, is there other information that should go on that product to help consumers or the clients that you are concerned about, or is it okay for them just to do it that way?

MS. LEE: It is not false labeling. It is okay for them to label it. It may be misleading in that it may make the product appear enhanced even though it is still the same product. I don't know how you would, you know, differentiate on that.

DR KANE: (*See errata) Are there any different ways that a product could include a gluten-free claim but the way it is worded, would that help? And, do (*See errata) you have any ideas of how additional wording should be added or, in other words, word it one way if there is a potential that it could contain gluten and this is special because the processing is there, versus all of the same foods in the same category is gluten-free--all milk? So, what would you get across to let people know that all milk is gluten-free and not just certain brands?

MS. LEE: Naturally gluten-free. I think the terminology that this food is naturally gluten-free, just by the nature of its composition, may be the way to go. Whereas, a rice cracker or a pasta is not naturally gluten-free and that is a special manufactured product. So, if it is labeled that this is a gluten-free grain or this is a gluten-free product versus a naturally gluten-free product may be the way to differentiate that the tomato is the tomato but the pasta is a rice-based pasta and, therefore, a different type of product.

DR. SCHNEEMAN: Would that help?

DR KANE: (*See errata) Yes, that is very helpful. Thank you.

DR. SCHNEEMAN: We can have your question but if we can get the other two panel members to come up? Felicia, do you want to go ahead?

MS. SATCHELL: Felicia Satchell, FDA. Actually, this question is directed at both Tricia [sic] and Pam. It goes back to the statements that you made about patients who are eating oats. I think in your case, Pam, you advised that if they do that to let you know and that you would continue to monitor their levels. I guess I just wanted to know in cases where you have patients that have eaten oats, have they had any problems as you have monitored their levels? Have they been able to maintain the oat diet? And, in your case, Pam, the oat products that they ate, were they shelf products or were they specially marketed products, similar to the ones that Tricia's patients have consumed?

MS. CURETON: Generally our patients don't. I don't see a lot of patients who do eat oats. Our patients are asking permission before they would do that. I have seen so few that I don't think it is really significant. I have had I think one patient in the last six months that came to us already on oats. It so happened that their antibody levels were normal and there were no symptoms. It was a child and they were growing well. I did not pull them off the oats. They were using I think McKane's oats, but not another product.

MS. LEE: Anne, from Columbia University. When a patient comes and requests oats there are a couple of types of patients in whom we actually encourage the inclusion of oats. Our patient population is predominantly adults. We have several males. As a normal male, we have cholesterol issues and we find that including the higher fiber grains--oats, kimwa, buckwheat, (*See errata) millet--that is a way to help enhance the nutrient density and fiber content of the gluten-free diet. But, again, we only recommend two types of oats. It is not the commercially prepared oat bars or oat cookies. And, we do closely monitor them.

DR. LUCCIOLI: Stefano Luccioli. What percentage, would you say, of your patients eventually have to drop oats from their diet, or haven't you had really anybody?

MS. LEE: We have had one or two people that have not tolerated them well but it is really few. Interestingly, it was two adults. The kids that we have that are doing oats, as Pam's patient also--they are thriving; they are thriving, which is one gentleman and one female. So, it didn't seem to be a gender issue, just an individual tolerance. Again, when we introduce oats we do things, as we do with any trial type of a diet, we don't let them go gang-busters. I feel that many patients do react to oats initially if they go from a very low fiber diet, which the traditional gluten-free diet can be, very devoid of fiber, and if they add a lot of the alternate grains that are very high fiber, you can get a reaction. Anyone would get a reaction to that dramatic increase in fiber. So, we instruct them to add the oats slowly and monitor. They even do it as an alternate day until we establish the tolerance for the oats and the other grains also.

DR. LUCCIOLI: And does your clinic have a policy on the wheat starch since that was also another issue that in Scandinavia they tend to recommend as well?

MS. LEE: They do. We don't recommend wheat starch at this time.

DR. LUCCIOLI: Is there a particular reason for that?

MS. LEE: We feel that for oats there has been enough documentation for that to be considered safe. The wheat, starch we don't feel we have enough information on that as yet.

DR. LUCCIOLI: Just one more question probably for the panel. I think we had a recent meeting on thresholds, about a month or so ago. And, it was proposed that maybe a two-tier labeling method could be used, kind of what Rhonda was saying before, where maybe, you know, where you could have gluten-free and really gluten-free--I mean that kind of jokingly, but do you think that your patients or members would appreciate something where a strong statement would say that this will not have gluten, whereas another statement would say, well, we can't guarantee that this doesn't have traces of gluten. Do you think that that is something that consumers with celiac would want?

MS. LEE: Anne Lee. I think generally our patients are looking for any definition on the packaging of the foods that they purchase. If it is a two-tiered effect, with the understanding--and we can instruct them as to what is really gluten-free and what is gluten-free but in a non-dedicated facility, I think that gives them the information so they can make an educated choice. I think they are clamoring for that type of information and for that security even if it is on a two-tier or three-tier basis that this is absolutely gluten-free; this is gluten-free but not in a dedicated facility; and these tomatoes are perfectly fine because they just are perfectly fine, they would love it. And, I think that it would enhance their comfort level and their ability to expand their diet from where they are at this point in time.

MS. SCHLUCKEBIER: This is Mary Schluckebier, from CSA. I think that an area where you could absolutely be sure that this product is totally, unequivocally absent of any barley, rye, oats, or anything, would be in a hospital when you aren't choosing your own food and you are already under a stress condition. I think many of our patients express that their experiences in hospitals, working with a dietitian and someone else as a caregiver, either hospital staff, training table person, a child care facility, for those people to be able to make choices that they know are unequivocally very precisely meeting the prescription of the diet, I think is a place for that.

DR. SCHNEEMAN: Actually, I would like you to also comment--I was curious about your certification system, do you also get reporting from consumers about adverse events, about things where it was certified but they had some sort of reaction? Do you get that information from them?

MS. SCHLUCKEBIER: Right now there is very little certification program out there anywhere except companies doing some ELISA on their own. Yes, we do get information from members who tell us that they have had a bad experience with something. What we do, we have them send the product. We will have it examined. What we try and do, if they have used some of the product, we do also ask them if they could go and purchase a product with the same oat in it or we try and purchase one locally that is the same company to see what kind of results we are getting, and we do pay for that. Generally, the products have come out with a low level of detection. There are a few cases. There was a loaf of bread and it came out over 5,000 parts per million, which means basically a wheat bread.

DR. PARK: Douglas Park, with FDA. This is for Mary. I am glad you had your previous question because that is a segue back to what I wanted to go into, your certification presentation, part of your presentation. In your certification do you actually visit the facilities and conduct an inspection to confirm that it is either dedicated or addressing the issues of trying to avoid contamination?

MS. SCHLUCKEBIER: It depends on the product. We can have a representative of CSA, because we have chapters and members all over the United States, so generally we can have a team with a check list go in and to an on-site observation. There are times when we have had the company make photographs for us to have on file. We do have a relationship with a company that does certification for some other areas that has agreed to go in and follow our protocol to do on-site visits.

DR. PARK: Along that same line, do you audit the companies on a regular basis, annually, semi-annually, whatever, to confirm that they are still preparing a product and then follow-up with actually testing of the product?

MS. SCHLUCKEBIER: Absolutely. Again, the calendar of those events does depend on how much flexibility they have; if they have changed suppliers. Yes, some of those things would create a testing earlier than would be normally scheduled.

DR. PARK: Thank you.

DR. LUCCIOLI: As a follow-up, I guess I want to get a little bit more insight on quality of life of celiac patients. I have read some studies where there supposedly is no change in their quality of life, where it seems like once a celiac patient knows what they need to do they are content. Do you get a sense that this is not the case? That they are screaming to you to have more products available, or is there a subset of people who would be willing to take some risks just to have more products to consume?

MS. SCHLUCKEBIER: This is Mary, at CSA. I will tell you, it depends on age. It depends on how long they have been diagnosed. We have an 86 year-old member. I think she was number 16 at NIH when she was in her 30s and just had a child, and was in Japan and was diagnosed with celiac disease, as was the child later. She is 86. She gets very unhappy when the 40 year-olds no longer ask her to play tennis with them. She would love to have oats back in her diet. She would love to be able to take some risks, and she probably takes more risks than I do. She has had over 50 years on the diet. She is very comfortable with what she can eat and she probably has a more varied diet than most non-celiacs in the U.S.

DR. SCHNEEMAN: Do you want to comment?

MS. CURETON: I would say, based on the time that I have been working in this area for the last 12 years, when I first started so few were diagnosed 10, 12 years ago I think your diet would be very limited and there wasn't a lot to chose from. The products today are far beyond what was available 10 years ago. So, somebody diagnosed today I think has wonderful choices, and we supply them with a list of manufacturers and vendors so the quality of their products is equal to what we would use for wheat products. So, I have been very pleased with the products. You have wonderful tasting products. Probably the area that is a problem is the cost and convenience. They are usually mail order and there are not a lot of times you can get them right off the grocery store shelf.

You have to make a separate trip to the grocery store or you have to order them by mail. But the quality of the products is just phenomenal. So, I think those who are diagnosed today I think are having a better quality of life of life and it is easier to follow the diet because of what is available.

MS. LEE: If I may--it is Anne Lee from Columbia University. We are actually finishing up a huge quality of life study based on the impact of symptoms as well as the gluten-free diet. What we have found does concur with that, that in that first year from the onset of diagnosis and the first year on a gluten-free diet there is a wonderful increase in quality of life, and people feel better; they are symptom free; they feel that they are going to live. So, there is a very huge upturn in their perception of general health and quality of life.

In two to five years since diagnosis it tends to drop back down both in males and females. The feeling is that at that point they now have gotten to the point where they know they are going to live. They know they feel better, but the routines of daily life become more of a burden. It is that extra trip to purchase the loaf of bread.

Travel and business meetings are one of the major complaints and issues for the males in the population group. Females have found that traveling and dining out was just a burden where 30-40 percent, depending on age category, of females with celiac disease would choose not to dine out because it is too much of a burden.

So, there is an issue with quality of life. Labeling will, indeed, help some but, hopefully, down the road not only will we get labeling under control but maybe even get menus and things done because these are the areas of their life that people without celiac disease don't think twice about, for stopping for the coffee and something but for someone with celiac disease it requires thought, preplanning and purchasing that product and, hopefully, that product is appropriately labeled.

So, there are studies on quality of life. The ones out of Europe tend to have a better rate overall of quality of life on a gluten-free diet, but the question that comes up with that is, is it because they allow the oats, the wheat starch and the labeling is better? We don't know. So, we are hoping to so some studies with Colin to compare the (*See errata) two populations.

MS. CURETON: This is Pam. The other thing too, we talked about patients earlier that took 11 years to diagnose, those patients are very sick and felt very bad. Once they started the gluten-free diet it was a huge change in their life. Those patients would not take a risk. They would not add anything back to their diet because they know how sick they were. But with better diagnosis or screening and a person who is asymptomatic, that is the type of person who would have a much harder time with the quality of life and issues that they are faced with, but those that were very sick would not touch gluten in any shape, form or for any reason.

DR. SCHNEEMAN: We need to start finishing up this panel so I am going to have one more question. Felicia?

MS. SATCHELL: Felicia Satchell, FDA. This question is really not meant to put you on the spot but, just in your professional opinion and experience, a definition for gluten-free should or should not include oats?

MS. LEE: Anne, from Celiac Disease, Columbia. I will start. I think it should, but it should define what the level is and it should define that the oats need to be clean. So, I think if we can define gluten-free with the appropriate level of parts per million, and we can have oats labeled as clean I think it would enhance the gluten-free diet and alleviate some of that burden of illness for those patients. I know that is out on a limb but I honestly believe it makes a difference to our patients.

MS. CURETON: This is Pam. I think at this stage there is a lot of confusion still, and I do agree they are technically gluten-free from the standpoint of the oats themselves. But with the contamination issues and some of the other tolerance issues, at this point I would not include them.

MS. SCHLUCKEBIER: Mary, at CSA. At this time I wouldn't include them. If oats are in a product at some later date, again, they are probably going to be clearly labeled as oats, and at some point when there is a standard, to add oats if it has passed all the rigors of study, I don't think it would be difficult to add that. For the first few years it may need to have some additional notes on labels with oats that would also include a gluten-free label so that people would not be confused. But at this time I just think it is premature to add oats in with gluten-free.

DR. SCHNEEMAN: Of course, some of our panels may not understand the difference between difficulty from a scientific point of view and difficulty from a rule-making regulatory point of view. There is a difference. I have only been here a little bit over a year and I have learned that lesson.

Again, thank you very much. This has been a wonderful panel and really helped address many of the questions that we have.

[Applause]

Now it is time for our afternoon break, which is scheduled for 15 minutes. We are going to ask you to be back as close as possible to 3:15. I will give you two extra minutes. I do want to make sure that anyone who has signed up to speak, you need to do something during the break. So, if you pre-registered to speak before the meeting today, please see Jean Latham. Jean is right back here (*See errata) with her hand up. For those who registered on-site please see Lauretta Carey. Lauretta is right back there (*See errata), waving her hand. So, we can get it set up to start right after the break. Thank you.

[Brief recess]

DR. SCHNEEMAN: I think we really need to get started. We have several individuals who have asked to provide comments so we want to make sure that we allow time for that. I am asking our FDA panel to take a seat at the front so that we can hear the comments. As indicated before, each of you will have five minutes to make the presentation. It is very important that you identify who you are and if you are representing a group or speak on behalf of a group. Please identify that affiliation. We will keep track of the time here and, hopefully, we can keep it well within the time. I think we are going to start with the group here.

Public Statements

MS. HOPKE: My name is Maryrose Hopke, and I am representing the Celiac Disease Foundation. CDF is a national organization that strives to promote awareness and build a supportive community for celiac patients, families and healthcare professionals. The information we provide is evidence-based, not anecdotal. On behalf of CDF, we thank members of this FDA committee for the opportunity to express our opinion on this important subject, gluten-free labeling.

We all understand that celiac disease is a life-long disease that has no cure. Yet, as we are also aware, it can be effectively controlled through a gluten-free diet. Confirmation by the NIH that 1/133 individuals in the United States are affected means that, consequently, two to three million consumers will have to watch everything they eat and drink and every medication they take.

The celiac community is at a distinct disadvantage at this time to properly answer the questions posed by this committee: What should gluten-free mean on a food label? How does the celiac identify foods that do not contain gluten? How much time do we spend identifying foods? What percentage of the foods purchased and what type of foods are marked gluten-free? How are the buying practices of the celiac community influenced by the word gluten-free on a label as opposed with a product with the same ingredients without the words gluten-free?

These questions are just beginning to be asked in our community. The major grassroots efforts of the celiac community to get the word wheat included in FALCPA and the subsequent conditions of that bill have brought about these meetings. In the past sufficient data has not been available to intelligently answer the questions posed. This information has to be accurate, not anecdotal, and it is just now being collected.

On July 27, in a newspaper article, "Gluten-Free Market Goes Mainstream," it stated that gluten-free products will now be available at Walmart. That is good news. But who made the determination that these products are, in fact, gluten-free? This false sense of food safety is misleading and unfortunate for people who rely on the truthfulness and scientific accuracy of a label.

When a celiac eats a product that is assumed to be gluten-free because the manufacturer says so, without any regulation from the FDA, the results can be great physical distress, as well as emotional upset because what the consumer believed to be safe has now harmed them.

Those in the celiac community are devoted label readers. Labels that carry the statement that the product was produced in a facility that also makes products containing other allergens as well as wheat is most helpful, calling the consumer to make an informed decision before purchasing the product. Products that are naturally gluten-free do not require the GF label. But all foods that have been processed, blended, combined and determined to be gluten-free must meet the criteria to be set by the FDA.

The FDA has always been a champion in its responsibility for the safety of food products to the public. This is why the FDA unequivocally must be the regulatory agency determining what is gluten-free. It will be the FDA seal that celiacs will trust and depend on when selecting appropriate gluten-free foods. Thank you.

DR. SCHNEEMAN: Thank you, and exactly on time! Good model, folks! The next person?

MR. SULLIVAN: Good afternoon. My name is Thomas Sullivan. I have the honor of being the president of the Celiac Sprue Association for this year.

I am not myself a celiac. I have a wife who is, a son who is and a great-niece who is. However, if you were to come into our house you would effectively find a gluten-free house. Now, there are four items in the house that are not gluten-free. One is the toaster. There are two toasters on the counter because there is no way in the world that you can avoid cross contact by putting two different types of bagel, bread or anything else in a toaster. So, there is a GF toaster and another. That other one is mine. The two never coexist. There are three other food products in the house that are non-gluten-free. They are bread, cookies and cereal. They don't exist out front. They are underneath the stove.

There is a very simple reason. It isn't that I don't enjoy eating gluten-free; I do, very much so. But products now, compared to ten years ago, are phenomenal. If you were to take the arena of foods non-gluten-free ten years ago and gluten-free, they didn't meet. If you take those two universes now and overlap them, the center where products are available to both sides are much, much larger than ever existed. So, the gluten-free diet itself is improving.

One quick example, the no-bun button for low calorie products and fast food markets was done by celiacs years before because we came in to say I want that hamburger with lettuce and tomato, no bun. How do we do it? You put it in a box. You give it to me with a knife and a fork and I can eat! That is how it happened. Now you just go in and say low calorie--no problems. So, we had to do what is coming along automatically and this is how the two universes of foods are overlapping.

The thousands of celiac patients that have been involved with CSA over the last 20 years have, in fact, defined gluten-free. When they started out they started to ask the manufacture do you have gluten in your product? Yeah. Okay, I can't have your product. No problems. Then they started to ask the question do you have gluten in this product specifically? Yeah. Now, wait a minute, you don't make it with corn, you make it with rice. Why are you saying yes? Because that is corn gluten or rice gluten. Okay, let's ask the question the other way. So, they did. What is the source ingredient for your modified food starch? What is the source ingredient for your enzymes? Those questions started to come through and the answers started to become easier for the patients very quickly.

So, the concept of gluten-free is now wheat, barley, rye and oats in a product or in any of their derivatives. By definition and by actuality that has evolved to what is the current definition. No wheat, barley, rye or oats or any other derivatives means gluten-free. I can use it. I have no problems. And, the quickest way and why you have the celiac patient pick up a product and flip it to the ingredients, go down the list--do I see something I don't recognize the ingredient source on, I put it down and I get another product.

If I see the term wheat, barley, rye or oats, I put it down. That is the quickest way.

There are examples of where that occurs with a newly diagnosed patient. We see them all the time, hear them all the time, and I get calls from all over the world. When you start with a newly diagnosed celiac patient, they are in absolute terror. That is this overwhelming wall of don't each anything with wheat, barley, rye and oats. Okay, what do I do? So, you give them three words and one direction. Your direction is read the label. The words, starch, vinegar, malted extract. Well, what do you mean? Malted extract has malt in it. By definition of the federal government malted extract is from potatoes, rice or corn. It is good for you. Starch, corn. Vinegar, single word vinegar, apples. Life is great. You have three defined words, three source ingredients. If I see them on a label, no problem.

DR. SCHNEEMAN: Tom, your time is up.

MR. SULLIVAN: I do thank you. It has been a great day.

DR. SCHNEEMAN: Thank you so much.

MR. COX: Hello! My name is Matthew Cox and I am a representative of Bob's Red Mill Natural Foods. I want to thank you all for your endeavors, and thanks for the opportunity of letting us come here and give our point of view.

I wanted to clear up one of the questions that was posed to Dennis Gilliam by the panel regarding how we deal with the consumer that has reported to us that a product that we have marketed as gluten-free, they suspect, is contaminated with gluten, and how we deal with that. It is really a pretty simple process. We take it very seriously though and what we do is we communicate with the consumer directly and try to get as much information from them as we can. We want to find out where did they buy the product, what product is it. We definitely want to get the lot numbers because all the products are identified with a lot number that we can track and, you know, look back at the sourcing, and all those sort of relevant details. We get other information from the consumer, like what other ingredients did you use? You know, we primarily manufacture baking ingredients. So, what did you combine with this flour to make your baked goods? You know, we have no idea how to gauge how well informed they are. Maybe they are using ingredients that they are not aware contain gluten, like an extract, malted barley, or something like that.

After getting as much information as we can, we provide a report to our quality assurance department and that report is then evaluated and, if necessary, we try to acquire a sample from the consumer, maybe a sample of their product so we can compare that with the product that we have in-house. If it is warranted, we also audit the manufacturing process. Again, it is visual inspections and, you know, just a basic run-through to see if there is anything that we are missing, any gaps that have been left open leading to some potential for contamination.

We have only had reports like this--in four years I can only recall maybe a dozen people reporting that products that we market as gluten-free have caused a reaction in them, and none of them have ever resulted in a recall, or anything like that, which we could implement if we needed to. We would just simply track the entire lot and get all that product back, and that is what we would do if there was such a case. So, I hope that that answers the question for you.

I also wanted to mention that I have talked to a lot of our consumers. We have lots of calls to action, inviting our consumers to give us feedback if they have any questions or concerns at all, and all our literature, all our products are widely open for them to contact us. As a result, we have had many, many conversations with our celiac consumers. I know personally that labeling products gluten-free does make a difference for them. It does make it easier for them to shop for products they need to eat and enjoy life.

We also use a symbol on our products. Yes, it is a marketing device but it also helps consumers. We have many products and many of them are not gluten-free and we want to make it easy for them to tell which products are gluten-free. So, this symbol that they can notice on the packaging is very useful to them and I have had reports on that from consumers.

I would like the FDA, if possible in the final ruling, to allow for the use of symbols that imply that a product is gluten-free. Also, I might ask that the FDA ban or bar companies from using a symbol that imply gluten-free when that product contains gluten in it. One example might be a manufacturer that makes a spelt bread and might use a symbol that has a grain shaft that is crossed out, which we use and I know other organizations use similar symbols. So, just to limit the level of confusion, and there is plenty of that already for celiac consumers, I might ask the FDA to address those issues. That is it. Thank you.

DR. SCHNEEMAN: Great! Thank you. That was another star performance, within five minutes!

MS. FENSTER: Hello! My name is Carol

Fenster, and I am president and founder of Savory Palate, Inc. For the past ten years I have been providing a cookbook and publishing and consulting information on the gluten-free diet. As the author of six of those cookbooks on gluten-free cooking and developer of gluten-free products for manufacturers, including Bob's Red Mill who is present here today, the importance of correct, consistent labels is critically.

When I formulate a recipe for one of my cookbooks I rely on the ingredient label. When I search the grocery stores or health food stores or go online for hard to find items, I look to see if the ingredient is labeled gluten-free somewhere on the package. I have learned that this label can be very large on some products, even incorporated into the overall design of the package. On other products I have to search very hard for the words gluten-free and sometimes I find them on the back of the package in tiny, little letters. Even then I look at the list of ingredients just to be sure because I know that not all companies use the same criteria, and I have learned to take nothing for granted.

As I read through the list of ingredients, sometimes I don't even recognize the words and for help I consult a book that has kind of become my bible, "The Consumer's Dictionary of Food Additives: Descriptions in Plain English of More than 8,000 Ingredients, Both Harmful and Desirable, Found in Food." It is kind of a long title to begin with. It is by Ruth Winters. This book does not address gluten-free in any way, shape or form but at least it gives me a working knowledge of what this rather strange ingredient is. Then, for help with other ingredients that I wonder if they are gluten-free or not, I turn to publications like "Gluten-Free Living" which carefully researches many suspect foods, or the "Quick-Start Diet Guide," or all the other manuals that things that were mentioned today. I reference all of those. I also consult lists and where there are constant changes.

Once I have all the information I decide with that ingredient is appropriate to use in my recipes in my cookbooks. If I decide that it just doesn't meet my criteria, then I simply don't use it. When in doubt, don't use it.

Now, the same process I use for my own recipes and my own cookbooks becomes even more complex when you develop products for corporations because of what we call the sourcing issue. Sometimes the ingredients I must use are not available to me as a general consumer, and I don't have access to the label to read it, or the manufacturer of a consumer ingredient that I buy on the store shelf is not quite the same as the one manufactured by the commercial provider which only other corporations can buy. In other words, certain products out there only other corporations can buy wholesale and have the whole issue of labeling all over again. Whereas, I am a consumer, and I am gluten-free, by the way also, I have learned to rely on very specific lists.

This means that my client needs to source out or to research on my behalf the right sources for ingredients, and not always having access to all the relevant information, the sources may not be required or may downright refuse to disclose exact ingredients because of proprietary issues. Since many of these sources provide a myriad of products, some gluten-free and some not, there is always the risk of whether there is a cross contamination. So, this all has to be considered.

My concern with these ingredients is only amplified when we talk about more complex processed foods such as certain dairy products, whether yogurt, sour cream or Worcestershire sauce. By the way, I had an interesting thing happen to me. I was very confident that a certain brand of Worcestershire sauce, here in the U.S., was gluten-free. I specified that brand in my cookbook, only to learn that in Canada that brand is not gluten-free. So, there we are with issues of labeling for us internationally.

At any rate, in summary, I think a standardized set of guidelines about what is gluten-free will help me make recipes that I know are safe for my customers. It will help my customers locate the same safe ingredients that I specify in my recipes. And, it will give manufacturers guidance in selecting gluten-free ingredients for their products whether they are developed in-house or by consultants such as me.

It is time that we all agree on what gluten-free means and what is not, and implement guidelines that assure a correct, consistent label. Thank you very much.

DR. SCHNEEMAN: Thank you.

MS. ASHWORTH: Hello! My name is Anna Ashworth and I am the vice president of business and administration for the Gluten-Intolerance Group, and I am also a representative for the Gluten-Free Certification Organization. I also have celiac disease.

Cynthia Cooper, the Executive Director for (*See errata) the Gluten-Intolerance Group, conducted an online consumer survey to get the gluten-free consumers' perspective on issues of labeling, purchasing decisions and determination of what gluten-free means to them. This survey, which was sent to the FDA on August 15, had nearly 2,100 responses worldwide and confirmed what we already knew, that gluten-free consumers want products that are clearly labeled to be gluten-free and that they know to be free of cross contamination.

Gluten-free consumers would benefit from a gluten-free certification program and manufacturers would benefit from their consumers' increased confidence in their products. To meet these needs, over the past two years the Gluten-Intolerance Group, in conjunction with a committee of scientific advisers, has worked to develop an independent certification program for gluten-free food processing. This program, the Gluten-Free Certification Organization, or GFCO, is the first program of its kind in the world. GFCO was developed in cooperation with Food Services, Inc., a subsidiary of the Orthodox Union, the world's largest and oldest kosher certification agency, with food inspection agents all over the world.

Key elements of the GFCO process will include the following: Individual ingredients will be reviewed down to the original supplier. There will be on-site inspections by independent, experienced, specially trained field inspection agents provided by the global resources of Food Services, Inc., a subsidiary of the Orthodox Union. Products and ingredients will be tested using scientifically proven AOAC approved test methods.

There will be regular spot plant visits and product testing by field inspection agents. The GFCO certification mark will appear on product packages for easy identification. The manufacturer and the Gluten-Free Certification Organization have a written agreement that states what can go into the product and how it is produced. The GFCO must be consulted in advance of any ingredient or processing changes to ensure that the product's gluten-free status is not affected. As a global program, the GFCO uses the highest standards for gluten-free ingredients and a safe processing environment based on a continual review of the current scientific and testing methodologies, existing global standards such as Codex in Canada, and balanced by reasonable application by the manufacturer.

A new Gluten-Free Certification mark on food labels will allow gluten-free consumers to eat easily and confidently, identify safe food that has been independently verified to meet the highest standards for gluten-free. We already have food manufacturers who have signed on with the GFCO program and we have received enthusiastic interest from many more. We are providing this program on behalf of the community who have voiced their strong interest in having gluten-free certification. Our standards are always available for public inspection on our website, www.gfco.org. Thank you.

DR. SCHNEEMAN: Thank you.

MR. BROWNE: Hello there! Thank you for allowing me to speak. My name is David Browne. I work for a company called SPINS. We are a San Francisco-based organization. I am the director of content services there.

SPINS is a leading provider of information to the natural products industry. Specifically what we do, we track the sale of bar coded products moving through natural supermarkets, including Whole Foods and Wild Oats and many independent stores. We also track the sale of natural and organic products moving through conventional supermarkets such as the Safeway and other drug stores.

Through this, in the last several months we started tracking gluten-free products specifically and flagging them in our database of over 400,000 products. I wanted to use my time today to provide some top-line information, statistical information on what we found with gluten-free products.

First of all, my team calls manufacturers and checks product websites to identify products that are marketed and claim on their labels that they are gluten-free. In instances where it is not labeled, we are still talking to the manufacturer to ask some other information. Generally, we found that there are about three buckets that companies that are making gluten-free products fall into. One is that their product is gluten-free and it is labeled as such. Two, the product is gluten-free but it is not labeled as such and in general the reply is that with the new labeling that they are going to be generating, new labels will have that but they have to go through their existing labels before they move forward. Thirdly, the product is gluten-free but they will not guarantee it, for all the reasons that we talked about earlier today as far as cross contamination and manufacturer warehousing where they are storing these goods. In the case of that, we are only coding items that are actually labeled as gluten-free at this point.

First off, I just want to summarize what we have found. We have researched over 10,000 products that fall into food categories where gluten-free products are known to exist, categories like bread and baked goods, cookies, cereals, frozen entrees, and other categories such as soup and candy where product labeling for gluten-free is common. At this point we have identified over 2,000 products moving in the U.S., with sales over 600 million dollars. This is a growth of 1.6 percent year over year, and that is both channels, both natural supermarkets and conventional supermarkets combined.

As far as UPC codes go, the vast majority of the are still moving in natural supermarkets. There are over 2,000 that are moving in natural supermarkets at this point. That is an increase of 9 percent over last year when there were over 1,965 items that were labeled as gluten-free. In the conventional channel there are about half, there are only about 1,200 items at this point that are labeled as gluten-free but, because of the volume of sales that occur in conventional, that 600 million dollar figure is broken down into being 400 million approximately moving in conventional supermarkets and 200 million moving in natural supermarkets.

For today's session I tried to encapsulate just about 9 categories where there is a lot of activity both in volume and quantity of UPCs. The 9 categories include, as I say, chips and snacks, puddings and desserts, entrees and mixes, cookies, soup, baking mixes and supplies, bread and baked goods, frozen entrees and candy. In the natural channel sales are growing for these gluten-free products at 12 percent. In the conventional channel they are growing at 17.8 percent. That may seem ironic but, in fact, as a lot of us know, gluten-free products have long been available in natural product supermarkets and what is happening over the last several years is that they are migrating into the conventional channel. Because of that, their growth rates are much larger and their volume.

One of the other interesting points that I want to mention today is that when you take some of these categories as a whole and look at their growth rates, and then look at the gluten-free products that are labeled within that and look at their growth rates, the gluten-free products far exceed the growth of the category as a whole. Essentially, they are driving the growth of the category.

Take a category like candy for example, which had a lot of up and down last several years due to low carb diets and products like Atkins bar on the market which were essentially candies but they were sugar-free version, the category is still showing positive growth in the natural channel at about 22 percent, but gluten-free candy is growing at 47 percent. Take a category like baking mixes and supplies, the category is relatively flat in the natural channel about 5 percent growth; gluten-free products are growing at 18.6 percent growth.

DR. SCHNEEMAN: We do need you to wrap up, but this sounds like the kind of data that would be great to submit to us.

MR. BROWNE: I have already submitted it, yes. I just want to say one last thing. Another important element of the growth of gluten-free products is that the share of the total sales for gluten-free products within a category is increasing year over year. If you take a category like baking mixes and the share of total sales within that category for gluten-free products went from 36 percent last year to 39 percent this year. So, more consumers are buying baking mixes and supplies that contain gluten-free products in volume than they were a year ago. Thank you very much.

DR. SCHNEEMAN: Thank you.

MS. WHELAN: My name is Ann Whelan, and together with Amy Rettner I have published "Gluten-Free Living," a national magazine for people who have celiac disease, for the last ten years. Over those years we have concentrated our research efforts on ingredients and their relation to celiac disease.

I was asked to respond to questions eight, nine and ten. Question eight, are there available research data or findings on what consumers with celiac disease or their caregivers believe the term gluten-free means? For example, do the research data or findings show consumers' belief as to what specific grains or other ingredients are not present in foods labeled gluten-free?

I believe there are at least two ongoing research studies as we speak, and from what I have heard today there are probably more. We did a survey nine years ago and some of the results of that survey are relevant to question nine. But we are planning on another survey which will probably be presented in our next issue, and in the new climate of celiac disease which is much different than it was nine years ago, I am very curious to see what we will find out.

You ask what people think the term gluten-free means. In the current climate it would be difficult for people to explain what they think gluten-free means. The reason it would be difficult is found in the second part of your question, meaning disagreement within the celiac community over specific grains and specific ingredients that are gluten-free. The specific grains part of the question is more easily addressed, and you have heard it today. Everyone agrees on wheat, rye and barley as grains not being found in foods marketed as gluten-free and, as everybody else said, at this point I think people expect oats to be in that category too. We have spelt, kamut and triticale that aren't found that much. Spelt is a problem. In the past, and you have heard this, some spelt companies have said spelt is safe for people who are sensitive to gluten, and it is still not clear, at least on one spelt site, that spelt is not safe for anybody who has celiac disease. So, any definition of gluten-free would have to emphasize that the product does not contain spelt. Most celiacs recognize corn, rice, potatoes and tapioca as being gluten-free. Uneasiness about some of the alternative grains like buckwheat and kimwa seems (*See errata) to have been addressed now and everybody is cool I think on that issue.

The ingredients portion is much less easily resolved. First, many celiacs do not know who to believe. There is a lot of information out there that seems to have been put forward on the basis of no evidence whatsoever. Some of our readers ask us you say this, but I read that elsewhere. At this point I explain to them how we do our research and recommend that they go back to the other source and find out how they do their research. For the record, we do our research by querying the people who should know the answers to the questions. We include the FDA, the USDA grain scientists, ingredient makers, food processors, food companies and other relevant sources of that ilk. Over nearly ten years we have developed a relationship with these groups and, therefore, have a place to start when we begin researching something new.

Second, people do not understand what certain ingredients are, and for good reason. For example, malt comes from barley and, therefore, would not be included in a product labeled gluten-free. Dextran can be derived from several (*See errata) grains, one of which is wheat. So, a product labeled gluten-free wouldn't contain dextran (*See errata) derived from wheat. Malt dextran, on the other (*See errata) hand, as you heard, is gluten-free. However, it if comes from outside the United States, and even sometimes from inside the United States, it may contain wheat but it will be wheat malt dextran or (*See errata) malt dextran wheat (*See errata).

Now, I can explain that quickly because I have done in-depth research on many ingredients. But when you are used to picking up a product off a shelf and throwing it into your shopping cart, and on top of that you know that some of these products and ingredients are going to make you sick, the learning curve required to be comfortable and efficient and effective with the diet is daunting. We are currently working on a booklet of ingredients and I hope that will help people make safe decisions.

We work very hard to explain ingredients as clearly as possible but ingredients are what they are and some explanations are complex. In fact, I suspect the complexity of the diet is the main reason why most people we ask say just tell me if the product is gluten-free. Just tell me what can I eat. We asked over the last two weeks what people would like to see and everybody told us some version of the same thing. Make it easy to read. I hate to have to read a label forever. I want the label to specifically say gluten-free. I don't want to have to assume it is gluten-free just because it doesn't contain wheat. Just tell me plain and simple gluten-free.

Third, people are afraid of what they don't know, especially if they have been very sick. That is understandable. The fear is amplified by misinformation that suggests molecules of gluten are dangerous or tries to define the diet by brands versus ingredients, and that is kind of a complex issue that I won't go into. But an acceptable agreement on what gluten-free means when it appears on the label would solve that problem.

Fourth, people perceive some ingredients as being gluten-free some of the time and not gluten-free other parts of the time, and that is truly confusing. Starch is a good example. Starch and food starch on a food label mean corn starch. Modified food starch may, and usually does mean modified corn starch. The FDA regulation on this ingredient is currently understood as saying modified food starch could be modified anything starch.

DR. SCHNEEMAN: Ann, we need to finish up.

MS. WHELAN: Okay. I think that it is doable right now for us to define the gluten-free diet and to solve all of these ingredient problems. It is my humble opinion that we need a better agreement on the specific grains and ingredients that would be excluded from a product label of gluten-free before you can regulate the use of the term gluten-free on a food label. I offer our ten years of research to anybody that would like it in order to determine this.

DR. SCHNEEMAN: That would be great, and I hope you do submit that to the docket.

MS. WHELAN: Fine. Thank you.

DR. SCHNEEMAN: Thank you.

MS. BAST: My name is Alice Bast and I am the founder and the executive director of the National Foundation for Celiac Awareness. I want to say that Ann Whelan has incredible information. The information I am presenting today is customer surveys. Her information is scientifically vetted.

On behalf of the of the Americans who suffer from celiac disease, I appreciate the opportunity to provide information on consumer understanding of the term gluten-free and the purchasing practices of celiac patients and their caregivers in the public meeting on gluten-free labeling.

The National Foundation prepared a short survey which was posted on our website and was e-mailed to support group members around the country. We received informative and heartfelt responses to the seven questions that were developed based on questions eight, nine and ten in the Notice for today's public hearing. We will submit the full responses in part of our written comments and I will summarize the results today.

The respondents are educated consumers that spend considerable time and effort in educating themselves and researching the contents of the food they buy in stores and eat in restaurants. They rely on the gluten-free label and express to us and the food manufacturers who have policies not to hide allergens and gluten. When given a choice, they buy products that are labeled gluten-free over those that are not. They are thrilled that the food labeling will soon be improved because it will save time, reduce frustration and provide a measure of confidence that they and their families are eating foods that are safe.

The following are the questions we asked and a summary of the responses we received. What does the term gluten-free mean to you? The overwhelming response was that gluten-free means gluten-free, that is, the product contains no wheat, barley, rye and related grains and derivatives. A few mention above a safe threshold but the general respondents expressed an understanding that no gluten is present in the food product either directly or as a result of cross contamination and, again, there was confusion over spelt and oats.

How do you identify foods that do not contain gluten? The primary response was read the label, followed by calling or e-mailing manufacturers, food lists from select support groups, reference provided by medical providers, newsletters and the internet. Often people read labels and call manufacturers to confirm, having learned about cross contamination potential and changing manufacturing practices as the hidden source of gluten. Many mentioned calling the manufacturer in the grocery store in order to be able to make a safe purchase. Respondents expressed the need to look for ingredients which are derivatives of wheat, barley and rye and other ingredients which contain these in reality but not in their names. Also, many said fear played a role. They are worried about buying products when they didn't recognize the name so they would automatically not buy those products because they weren't sure whether they contain gluten or not. Many mentioned the difficulty in eating out safely because restaurants don't always know whether gluten is contained in the bulk ingredients that they buy.

How much time to you spend identifying gluten-free foods? The response to this question varied. Some folks indicated that they are educated and they carry lists with them and just buy the same foods again and again. Others spend 30 minutes extra each week reading labels and researching ingredients. Others said that grocery shopping takes twice as long as normal.

Many have come to rely on the current gluten-free label as a time saver and seek out brands from companies who have voluntarily made allergen and gluten information available in their packaging. Most expressed the need for a uniform label so it would be faster and easier for them to obtain the information.

Four, when you purchase packaged foods, do you purchase foods that are primarily or exclusively labeled gluten-free? Many respondents indicated that they do prefer to purchase products that are labeled gluten-free if available. They also indicated that they must purchase products that are not labeled and, in order to do so, must read the ingredient lists. Many mentioned the added expense of products that are labeled gluten-free.

Five, if so, what types of packaged foods that are labeled gluten-free do you purchase? For example, breads, dairies, canned vegetables, and there is a whole list of a variety of products that they do purchase.

Does a gluten-free label influence your purchasing decision when you have a choice among products having identical ingredient lists? The overwhelming response was yes. People indicated they felt confident that the food was safe for them to eat if it had a gluten-free label.

Seven, would you like to share any other thoughts about a need for accurate understanding of food labeling in your experience with food labeling? The overwhelming response was that people are looking forward to having clear, unambiguous food labeling so they could be sure the food they were planning to eat was, in fact, gluten-free and, therefore, safe. Many expressed the challenge of complying with the gluten-free diet when labels do not clearly indicate whether gluten is present.

In conclusion, as the NFCA analyzed the responses to our survey, we reinforced our own belief that clear, unambiguous labeling of food is a win-win for everyone-- celiac disease patients and food providers throughout the food chain. People with celiac disease will save time and will greatly improve their ability to select foods that are safe to eat. Food providers, by clearly indicating whether gluten is present in the foods they produce or serve, will engender the trust of celiac sufferers and, therefore, create loyal consumers for their brands. Thank you for the opportunity to speak with you today.

DR. SCHNEEMAN: Great! Thank you.

MS. KUJO: Hi! My name is Jill Kujo. (*See errata). I am here representing Whole Foods Market. My official title is research and customer relations coordinator. That means I answer the phones, answer all the e-mail and I also talk to our ingredient suppliers. I collect the letters of certification.

I really wanted to bring out that while we focus a lot on the breads and cakes and desserts that celiacs can't eat, there are a lot of general grocery products that people don't think of right away as containing gluten, deli meats, snack foods, spices, mixes. A lot of times when I am getting initially diagnosed people write to me, I inform that these products are available in our stores and it is more often the smaller producers that will make products, like potato chips, that don't have gluten in the spice mix that goes on them.

I think that although perhaps our ignorance in this country about celiac disease may be a reason why there are cross contamination issues, especially in oats. I also think it might be because I get the general impression that we process our foods a little bit more than the rest of the world and gluten is really useful in processing, not only to tie things together like in baking but also to keep spices from clumping in production. I think that is it. Thank you.

DR. SCHNEEMAN: Great! Thank you.

MR. BLANK: My name is James Blank. I am a member of CSA. I just wanted to bring out that the gluten-free labeling is going to help some people that are very vulnerable, and those are the very elderly people and the very young. Most of the time that has to do with the caregivers and families that have to try to figure out this whole thing about gluten-free or not.

I was diagnosed 12 years ago and I was doing fine. Eight months ago my father was diagnosed with celiac disease. Now I have to teach my family and, you know, his wife how to look for gluten-free products and it is very difficult, especially when you have some family members that don't understand celiac disease and how difficult it is and how dangerous it can be for people. When I was diagnosed I lost 50 lbs. and I almost died from this disease. I think that is the thing, and when you are diagnosed with something and you get very sick from it, you know, it really matters. Now, with my father, 78 years old now, it is hard. I have to train him, 78 years old and now he has to learn how to eat all over again.

I think these are the people that the gluten-free labeling is going to help. Those and also people in hospitals. You know, people are afraid. They are afraid to go to the hospital because they don't know what they are going to eat. So, that is all I have to say and I just want to thank the FDA for having this meeting.

DR. SCHNEEMAN: Great! Thank you. Do we have any other presenters?

[No response]

Again, on behalf of FDA, I want to really sincerely express my appreciation to all of you who have been here today for your participation and involvement. I appreciate the fact that you have respected our time schedule; you have respected the fact that we had very specific questions that we are trying to address and I think you have provided us with a real wealth of information. Again, hearing from both the industry as well as consumers, plus the analytical piece of it, those are all important inputs for our decision-making.

Before we adjourn, I do want to remind everyone of the docket number, 2005N-0279 that corresponds to this meeting. The ten questions that we cited in the Federal Register Notice will remain there and that docket is open until September 19. Obviously, we have heard in just short presentations that some of you do have additional data, references, reference material and perhaps some additional comments. So, we encourage you to submit material to that docket and that is one of the best ways to make sure that FDA considers your input in its decision-making as it goes forward with this very important initiative.

So, again, thank you for being here. Thank you for sticking to the very end so that we had the opportunity to hear everyone who wanted to make a comment. I just want to express my sincere appreciation to the staff at FDA who really worked hard to put all of this together, to gather the speakers, arrange the meeting. I know that Rhonda Kane has spent a substantial amount of time, and Geraldine June has also put in a huge effort to make sure that this meeting would come off very well and that FDA would be able to gather the type of information that is most useful to us. We had a lot of volunteers from our office who have helped with the registration desk. That is just extra effort on their part because they view this information as important. So, again, thank you for being here.

[Whereupon, at 4:08 p.m., the proceedings were adjourned.]

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(See Errata Sheet)

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