Foods
FY 1998 Accomplishments:
1) Juice Safety: FDA initiated an inspection and sampling program covering 250 firms producing unpasteurized apple juice and cider products. Data was used to develop FDA's proposed HACCP program for juice manufacturers.
FDA conducted two workshops in the Midwest and Northeast apple growing areas to teach cider and fresh juice producers safety steps to prevent microbial contamination in their products. Also, FDA launched a public awareness campaign on the extra risk that unpasteurized or untreated juices may present to vulnerable populations subgroups (e.g., pregnant women, young children and the elderly) most likely to suffer effects from foodborne infections.
An FDA promulgated rule became effective that requires warning labels on packaged apple juice products that are not pasteurized or otherwise treated to kill pathogens. The regulation became effective in November for all other unpasteurized or untreated juices. Warning labels must state that the product has not been pasteurized, that it could harbor harmful bacteria, and that young children, the elderly and those with compromised immune systems should not consume the product. If labels are not affixed to packages, placards containing this warning are required at points-of-sale of unpasteurized juice products until the fall of 1999. By that point, all packages of unpasteurized or untreated juice products must bear the label warning statement, and the placard option will be rescinded.
FDA launched a research program to determine methods that can effectively prevent contamination of unpasteurized juice. The Agency leased a cider mill in California to operate as a research site in partnership with the California Department of Health Services, the Eldorado County Department of Agriculture, and the National Center for Food Safety and Technology (Moffet Center).
2) FDA's Advisory Panel Reaffirmed the Safety of Olestra: FDA's Food Advisory Committee reaffirmed the safety of Olestra. Olestra is a fake fat that tastes like normal fat, but does not increase the intake of fat calories because it is not absorbed by the body. When olestra was originally approved in 1996, the Agency required that the manufacturer (Procter & Gamble) and the user (Frito-Lay) report any adverse health effects attributed to the product. Moreover, potato chips that contained olestra were required to carry a label warning of possible gastrointestinal effects from eating the product.
The Advisory Committee, which is composed of experts on food safety, evaluated testimony related to potato chips made with olestra. After weighing comments from consumers, scientists and industry officials, the Advisory Committee agreed that there were no new data that raised significant new public health concerns related to the use of the product.
3) FDA Approves Sucralose: On April 1, FDA announced that it had approved sucralose, a new high-intensity sweetener, for use in a wide variety of food products. FDA reviewed data from more than 110 studies on humans and animals in its efforts to determine the safety of sucralose for human consumption. Many of the studies were designed to identify possible adverse health effects of sucralose, including carcinogenic, reproductive and neurological effects. During the Agency's evaluation, no such effects were found.
Based on the Agency's action, sucralose may be used in baked goods, baking mixes, non-alcoholic beverages, chewing gum, coffee and tea products, confections and frostings, fats and oils, frozen dairy fillings, jams and jellies, milk products, processed fruits and fruit juices, sugar substitutes, sweet sauces, toppings and syrups. It can also be used as a table-top sweetener that is added directly to foods by consumers.
4) Red Meat Irradiation Petition Approved by FDA: In December, FDA published a final rule in the Federal Register to amend the food additive regulations to provide for the safe use of ionizing radiation to treat red meat products (i.e., beef, lamb and pork) to control pathogens and extend product shelf life. In making its determination, FDA reviewed the results of a wide range of toxicity studies including previous safety evaluations, an analysis conducted by the World Health Organization, chronic feeding studies, reproduction and teratology studies and genetic toxicity studies. Based on these studies, FDA concluded that irradiation of meat under the conditions set forth in the regulation does not present a toxicological hazard. In the final rule, the Agency noted that results from chemical analyses of irradiated flesh foods established that there would be very small amounts of individual radiolytic product generated by radiation doses comparable to those proposed in the petition. Also, the Agency determined that the nutrient value of macronutrients and minerals is not significantly altered by irradiation at the petitioned dose levels.
5) Foodborne Disease Surveillance: The surveillance of foodborne disease increased significantly through the expansion of Foodnet. Foodnet is a foodborne disease tracking system that CDC, FDA and USDA operate in cooperation with the Council of State and Territorial Epidemiologists. With the addition of two new sites in FY 1998, the program now provides baseline data on foodborne illnesses for seven areas that are representative of geographic and demographic distributions in the U.S. Two important findings already have been established based on FoodNet data. One is that Campylobacter is the most common cause of foodborne disease. The second is that Listeria infections have the highest hospitalization rates and cause more deaths than any other pathogen tracked through the system. These and other findings provided by FoodNet data will help FDA more effectively target its compliance monitoring and research activities.
6) Foodborne Outbreak Response Coordination: On May 22, 1998, Vice President Gore announced the formation of the Foodborne Outbreak Response Coordinating Group (FORC-G), created through a memorandum of understanding between the Department of Health and Human Services, Department of Agriculture, and the Environmental Protection Agency. Members of FORC-G include representatives from EPA, CDC, FDA, FSIS and one state employee each representing the Association of Food and Drug Officials (AFDO), the National Association of City and County Health Officials, Association of State and Territorial Epidemiologists, Council of State and Territorial Epidemiologists (CSTE), and the National Association of State Departments of Agriculture (NASDA). The goal of FORC-G is to improve coordination between federal agencies and state and local agencies in responding to foodborne illness outbreaks which is critical in reducing the number of foodborne illnesses and their associated economic costs.
7) PulseNet: PulseNet combines the latest in microbiology and computer technology to help public health officials more quickly determine whether illnesses occurring in many different locations during the same timeframe are linked to a common food source. This system uses a molecular technology called pulse-field gel electrophoresis (PFGE) to identify distinctive "fingerprint" patterns of E. coli 0157:H7. PulseNet technology permits public health laboratories throughout the country to share information on bacteria subtype patterns via the Internet within 10 to 30 minutes instead of the two days or more required with the previously used mail system.
In several instances during FY 1998, PulseNet demonstrated its value as an effective means for identifying common sources of illnesses and increasing the speed of illness outbreak tracebacks and containment. In one instance, this system was able to connect two seemingly independent E. coli 0157:H7 illness outbreaks to a common source -- alfalfa sprouts. It helped determine that E. coli 0157:H7 illnesses in two different states shared the same DNA fingerprints and accelerated the traceback to a single lettuce packer. The PulseNet system also helped confirm that approximately 50 cases of E. coli in Wisconsin were attributed to cheese curds from a single facility after the initial inspection failed to identify the source of the contamination. In the near future, another pathogen that is an important cause of foodborne illness, Salmonella typhimurium, will be added to PulseNet. Overtime, CDC will set up additional databases of DNA fingerprints for other foodborne bacteria that are important causes of human illness. This information enables a faster response, and as a result, shorter outbreaks and hence, fewer deaths/illnesses.
8) Microbial Pathogen Contamination in Raw Sprout Products: In late August, the FDA reaffirmed health advisories that persons who are at high risk for severe foodborne disease should avoid eating raw alfalfa sprouts. Since 1995, raw sprouts have emerged as a recognized source of foodborne illness in the United States. FDA's reaffirmation of this advisory followed an investigation by the state of California of three Salmonella and E. coli 0157 outbreaks in which sprouts were implicated in illnesses of approximately 60 individuals. Foodborne infections caused by these pathogens can have serious health consequences for consumers, especially those in certain high risk subpopulations. For instance, an E. coli 0157 infection can lead to hemolytic uremic syndrome with resultant kidney failure or death in children, and equally serious complications in the elderly. Salmonella infections can cause serious illness in children, the elderly and the immune compromised. Healthy people infected with these bacteria usually experience less severe symptoms, including diarrhea, nausea, abdominal cramping or fever, that last for several days.
The reaffirmation of the health advisories was an interim measure until intervention methods are in place to improve the safety of these products. FDA and CDC are closely monitoring the occurrence of foodborne illness outbreaks associated with sprouts. Moreover, FDA has worked with other agencies and industry to develop a strategy to enhance the safety of sprouts. This includes the International Sprout Growers Association (ISGA) which is taking positive steps to address the problem of microbial contamination is sprouts. For example, the sprout industry is pursuing a method for soaking seeds prior to germination and growth to substantially reduce the microbial contamination that can be passed on to the growing sprouts. Also, the ISGA is working with FDA and the California Department of Health Services to develop and implement a food safety program for sprout growers. In addition, the industry is actively working with FDA and USDA on other interventions, including irradiation, to address the problem.
FDA has taken a number of other steps to respond more effectively to the health threat posed by pathogen contamination in sprouts. The Agency requested that the National Advisory Committee on Microbiological Criteria for Food (NACMF) investigate sprout contamination. An inspection assignment was issued requiring visits to sprout companies through out the nation before the end of FY 1998 to determine how sprouts are grown and processed, and how to reduce the number of outbreaks tied to these products.
The Agency also has held several public meetings on pathogen contamination on sprouts. FDA met with industry representatives in Chicago to discuss ongoing cooperative research towards ensuring the safety of sprouts. Another public meeting was held in Washington, D.C., which was attended by members of Fresh Produce Working Group of NACMF. NACMF's Fresh Produce Working Group was asked to advise the agency on near-term interventions and controls that should be considered to improve the safety of sprouts.
9) Guide on the Safe Production and Processing of Fresh Produce: DHHS announced the publication of a draft guide on the safe production and processing of fresh produce. The draft guide was developed with public input gathered at a series of six public meeting held around the country during November and December of 1997. Three more public meetings were held in May 1998 following the publication of the draft guide to allow additional public input on the development of the final document.
The guide is a set of voluntary guidelines describing good agricultural and manufacturing practices designed to minimize the risk of pathogen contamination on produce. It addresses key areas where precautions should be taken to ensure safety, including water quality, worker hygiene, field and facility sanitation, manure management and transportation. FDA and USDA will initiate a program of grants, partnerships, and outreach programs to provide technical assistance and education to assist with the implementation of the guide.
The development and implementation of the guide for fresh produce is a key strategy incorporated in the Presidential Initiative announced in October 2, 1997, for increasing the safety of domestically produced and imported fresh fruits and vegetables. This emphasis on improving the safety of fresh produce is critical because more consumers are heeding the advice of the U.S. Government Dietary Guidelines which recommends that most of the calories in a healthy diet come from fruits, vegetables and grain products. Without effective steps to ensure their safety, these products, which are most often eaten fresh or with minimal processing, will pose a greater potential threat to the public health as larger amounts are consumed to establish healthy diets.
10) Implementation of Seafood HACCP: In December, FDA began inspection of the seafood industry to ensure that it had implemented the Seafood HACCP regulation. The Agency committed to inspecting all domestic seafood processors by the end of December 1998. These inspections permit FDA to: review HACCP plans to determine that all the appropriate critical control points are identified and that proper monitoring procedures are established for each; check the processor's operations to ensure that these points are being monitored; and check that the appropriate records are being maintained. By the end of FY 1998, the Agency and states had conducted HACCP inspections in 3,876 domestic seafood establishments. Also, approximately 940 HACCP inspections were conducted of seafood importers. In cases where the plans were found to be inadequate, "untitled letters" were sent to the processor/importer that identified the deficiencies and technical assistance was provided to help them bring their processes in line with the HACCP regulation.
FDA published the second edition of its Fish and Fishery Product Hazard Controls Guide. The Guide contains information on hazards that are likely to occur in fishery products and identifies the appropriate controls for them.
11) Meeting with States and Territories on a Vertically Integrated Food Safety System: In September FDA, USDA, CDC, and others sponsored a meeting attended by over 170 people to determine how federal agencies and states can work together to improve the safety of the Nation's food supply. Attendees included representatives of all 50 states, the District of Columbia and Puerto Rico.
This meeting had two major goals. One was to determine how to best establish a "vertically integrated" food safety system that involves federal and state agencies. The other was to determine how to best coordinate illness outbreak responses among federal, state and local agencies. Some of the participants in the meeting will form workgroups to begin drafting documents that will explain how to begin working towards the goal of a national integrated food safety system. Issues such as capacity, resources, roles and responsibilities, data sharing and collection, communication, flexible and uniform standards, marketing plans, research and development, and training and education will be addressed. Documents that incorporate the results of these work groups are expected to be available early in FY 1999. Participants in the Kansas City meeting expect that the effort to develop an integrated food safety system should begin to show results by FY 2005.
12) Interagency Coordination on Food Safety Research: FDA, USDA and other federal agencies issued a coordinated interagency research plan to guide research directed at substantially enhancing the safety of fresh fruits and vegetables. The interagency plan, which was developed with input from industry, academia and consumers, is designed to make food safety research more effective by targeting efforts to those areas with the most potential for providing real-world food safety benefits and avoiding duplication.
Based on this plan, FDA has developed a three-year plan to guide its research activities. FDA's plan will focus on the microbiological and microbial risk assessment research necessary to support implementation of more effective food safety strategies incorporated in the Food Safety Initiative.
13) Expanded Efforts to Ensure the Safety of Eggs: On May 18, FDA and USDA announced expanded efforts to ensure the safety of shell eggs. (USDA and FDA share federal regulatory responsibility for egg safety though regulation of shell eggs is primarily the responsibility of FDA.)
The Federal Register notice on this effort identified several actions that apply the best science to activities to protect consumers from eggs contaminated with Salmonella enteritidis (SE). These actions include:
14) Workshop Held on Microbiological Risk Assessment: FDA and the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) Risk Assessment Consortium (RAC) sponsored a workshop for regulatory agencies and the scientific community that focused on dose-response modeling for microbial risk assessment. Dose response models describe the relationship between the number of foodborne pathogens consumed and the severity of human illness that is likely to result from their consumption. Dose response is also a key step in formulating an accurate risk assessment for individual pathogens. The workshop was the initial effort to apply the expertise of multidisciplinary groups of scientists from regulatory agencies, academia, private industry and the public to dose-response modeling data needs. In addition, the RAC, in conjunction with the Illinois Institute of Technology, the University of Illinois and the Chicago Public Health Department, have begun development of criteria and protocols for the collection of dose-response data from foodborne disease outbreaks.
15) Raspberries from Guatemala: In April, FDA ordered a seasonal import ban on fresh raspberries from Guatemala. This ban was imposed because Cyclospora, a foodborne parasite, is believed to be most infectious in the spring and early summer. When the ban ended on August 15, FDA allowed raspberry shipments from some Guatemalan farms for the fall season.
FDA is taking several actions to help improve the safety of berries and other fresh produce from Guatemala. Representatives will be sent to the country to teach local inspectors how to check implementation of Guatemala's food safety program for fresh berries. The Agency also expects to evaluate how much progress the Guatemalan berry industry has made in adopting its Model Plan of Excellence and train Guatemalan Ministry of Agriculture inspectors to check for correct implementation of safety measures designed to reduce the risk of Cyclospora contamination. Most growers are now trying to implement the model program in an effort to obtain FDA approval for year-round export of their products.
16) Pilot Food Safety Program for Retail Settings: FDA asked for volunteers from the retail sector of the food industry to participate in a pilot program designed to reduce the risk of foodborne illness. The pilot will test the implementation of Hazard Analysis Critical Control Point (HACCP) in retail settings, which includes restaurants, grocery stores, institutional food service and vending operations. HACCP is a scientifically designed program where manufacturers/food preparers are required to identify points in a process where safety problems can occur and establish measures to effectively prevent those problems. HACCP principles that are built into FDA's Food Code can be integrated into the operating procedures of any size establishment. Participating businesses will partner with interested state and regulatory authorities to implement the volunteer pilot program. Information produced by the retail food industry pilot will permit FDA to fine-tune the guidance and approaches given in the Food Code to help ensure safe preparation, service and sale of foods in retail settings.
17) E. coli 0157:H7 Illness Outbreaks: Several foodborne illness outbreaks occurred during FY 1998 that were attributed to E. coli contamination. These included an outbreak involving 7 children that occurred in Spokane, Washington in February. Test results confirmed that E. coli 0157:H7 was the cause of the illnesses in children aged 18 months to 6 years old. Fortunately, only the18 month old child was hospitalized.
Another outbreak occurred in June, when as many as 4,500 people in the Chicago area became ill after consuming food contaminated with E. coli 0157:H7. The strain of bacteria is believed to have been transmitted by potato salad prepared by a delicatessen that was served at 300 and 500 parties.
18) Vibrio parahaemolyticus in Oysters from Texas and New York: In June, FDA warned consumers not to eat raw oysters from Galveston Bay, Texas. All oysters harvested from Galveston Bay were put under a nationwide recall because they might contain harmful levels of Vibrio parahaemolyticus, a naturally occurring marine bacterium that can cause human illness. The recall initially affected only certain harvest leases in Galveston Bay, but was extended June 30 to cover the entire bay after the illness count climbed from 51 to 128 four days later. Symptoms caused by Vibrio parahaemolyticus infections include watery diarrhea and abdominal cramps, sometimes accompanied by nausea, vomiting, fever and headache, and usually last from one to seven days. The illness is rarely fatal but can be life threatening to persons with liver problems or weakened immune systems.
Another illness outbreak attributed to Vibrio parahaemolyticus occurred in the New York region in August. Illnesses were confirmed in eight people who ate oysters and one person who ate clams in restaurants in Nassau and Suffolk Counties in August. The harvesting areas from which the oysters came were closed, and were to remain closed until samples show that shellfish are not contaminated.
19) Food Safety Priority Setting/Meeting Held with Food Safety Stakeholders: in June, FDA hosted a priority setting meeting for foods and cosmetics with consumers and industry. A number of industry associations and consumer groups participated in the two-day meeting. These included representatives of the Association of Food and Drug Officials, International Shellfish Sanitation Conference, American Frozen Food Institute, Grocery Manufacturers of America, National Fisheries Institute, Center for Science in the Public Interest, Enzyme Technical Association, Calorie Control Council, Alliance of Food Additive Producers, International Dairy Foods Association, In Flight Food Service Association, International Sprout Growers, Council on Responsible Nutrition, Nutrition Network, Inc., National Nutrition Foods Association, National Food Processors Association, The Society of Plastics Industry, Inc., Apple Processors Association, American Heart Association, American Dietetic Association, and the Viskase Corporation. Cosmetics representatives included Cosmetic, Toiletry and Fragrance Association, and Independent Cosmetic Manufacturers and Distribution Association. Participants at the meeting addressed several questions related to program, regulatory and research priorities for food and cosmetic safety. Information gained from the two-day meeting as well as any written comments submitted in response to the Public Notice on the meeting were used to help the Agency establish more relevant and realistic priorities for activities to enhance the safety of foods and cosmetics.
20) Other Food Safety Activities/New Rules Established for Health Claims on Foods: In February, FDA published a final rule to allow foods containing psyllium to make health claims on reducing the risk of heart disease. Under the Nutrition Labeling and Education Act (NLEA), FDA can only authorize health claims if, based on the totality of publicly available scientific evidence, there is significant scientific agreement that the claim is true. Scientific studies consistently showed significant blood total- and LDL-cholesterol lowering effects of psyllium seed husk (PSH). The new regulation permits labels on certain foods containing soluble fiber from PSH -- such as certain breakfast cereals -- to claim that these foods, as part of a diet low in saturated fat and cholesterol, may reduce the risk of coronary heart disease.
In June, FDA published in the Federal Register nine interim final rules denying notifications for health claims based on an authoritative statement. The Food and Drug Administration Modernization Act of 1997 (FDAMA) amended the FD&C Act to permit distributors and manufacturers to use health claims if such claims are based on current published, authoritative statements from federal scientific bodies or the National Academy of Science. FDAMA further provides that, if FDA has taken no action on the notification within 120 days, the requested claim may be used on food labels. In seven cases, the claims were prohibited because the statements were judged not to be authoritative. Others were prohibited because they either did not relate to a diet/disease, or because an existing health claim addressed the same diet/disease relationship identified in the notification.
21) FDA Established Rule on Health Claims for Dietary Supplements: In response to recommendations by the Commission on Dietary Supplement Labels, FDA issued a proposed rule to provide consumers better information about dietary supplements by requiring that labeling of these products be more reliable and uniform. This Commission was an independent panel of experts mandated by the Dietary Supplement Health and Education Act of 1994 (DSHEA).
Under DSHEA, dietary supplements may carry claims that a product may effect the structure or functioning of the body (structure/function claims) but may not claim that the product can treat, diagnose, cure or prevent disease. The proposed rule attempts to clarify for manufacturers what types of claims can or cannot be made on a dietary supplement label. The improved labeling will also help consumers make more informed choices.
Examples of the structure/function claims that will be permissible under the proposed rule include statements that the product "promotes regularity," "helps maintain cardiovascular health," "supports the immune system," "is an energizer," or "promotes relaxation." The proposal also identifies many "disease claims" that are prohibited under DSHEA. These include claims for dietary supplements that expressly or implicitly claim to diagnose, treat, prevent, or cure disease. Examples of prohibited disease claims for dietary supplements include "protect against cancer," "treats hot flashes," "lowers cholesterol," "reduces joint pain," or "reduces nausea associated with chemotherapy." These claims are reserved for drugs, which must meet safety and effectiveness standards under the FD&C Act.
22) FDA Issued Warning On Potentially Hazardous Dietary Supplement: In March, FDA issued a notice warning consumers not to buy or consume a dietary supplement identified as Sleeping Buddha. Sleeping Buddha is marketed in capsule form as a product of China and is promoted as an herbal alternative to prescription sedatives for insomnia and restlessness. FDA determined that the product contains the prescription-strength drug ingredient, estazolam, which is a sedative of the benzodiazepine family and is known to have serious side effects, including the potential to cause fetal damage in pregnant women. Also, because the product contains a sedative, its poses a special risk to consumers who take it while driving, while operating heavy machinery, or while taking other sedative drugs or alcohol.
FDA also prohibited the interstate shipment of a dietary supplement containing a mixture of lectins from pokeweed plants (phytolacca americana). FDA informed the manufacturer -- Advanced Plant Pharmaceuticals, Inc. -- that the lectins contained in pokeweed plants are believed to be one of the primary biochemical contributors to pokeweed toxicity. The Agency further indicated that dietary supplements containing a mixture of the lectins cannot reasonably be expected to be safe. Some of the serious health effects of pokeweed poisoning include stomach cramping, nausea, vomiting and diarrhea, dyspnea, spasms, hypotension, heart block, convulsions and death.
23) FDA Confirms the Presence of Impurities in Some L-tryptophan Products: FDA confirmed the presence of impurities in some 5-hydroxy-L-tryptophan (5HTP) products that are marketed and widely promoted as dietary supplements. The 5HTP products are being used as aids for insomnia, depression, obesity, and for children with attention deficit disorder. FDA's analytical results were consistent with those obtained and published by researchers at the Mayo Clinic.
One of the impurities found in 5HTP is known as "peak X." "Peak X" was identified in one case of eosinophilia-myalgia syndrome (EMS) associated with 5HTP in 1991. EMS is a serious systemic illness characterized by elevations of certain white blood cells and severe muscle pain. CDC has identified more than 1,500 case of EMS, including at least 38 deaths associated with the use of L-tryptophan. The medical literature reports approximately 10 pervious cases of EMS worldwide associated with use of products containing 5HTP. FDA has worked closely with its colleagues at CDC and NIH and counseled professional and patient groups to closely monitor this situation.
24) Action on Milk Adulteration in Puerto Rico and Texas: FDA held a number of meetings with the Puerto Rico Department of Health (PRDH) and the Puerto Rico Department of Agriculture (PRDA) to discuss the results of an investigation of milk adulteration. FDA's investigation showed that dairy farmers were watering raw milk at their farms before shipment to dairy processing plants. Under the Pasteurized Milk Ordinance (PMO), milk that has been adulterated with water does not meet the Grade A standard and cannot be delivered to any Grade A processing plant. The two Puerto Rican agencies agreed to develop a plan of action for dealing with this problem and submit it to FDA. The Agency urged PRDH to create and fill a position for a milk-sampling officer and fill the vacant position of Director of the Milk Hygiene Program. FDA also offered to provide support and training to PRDH for those conducting inspections and laboratory analyses.
Also, eight dairy farmers, 20 tanker truck drivers and one employee of a milk processing plant were indicted in Fort Worth, Texas, for watered down milk. The indictment stated that farmers allegedly paid truckers to add water and salt to milk sold to a processor. According to the 112-count indictment, more than nine million pounds of water (which cost an estimated $1.22 million) were added to the milk.
25) New Technique Approved for the Elimination of Salmonella Bacteria in Poultry: In March, FDA approved the use of Preempt, a product that is designed to reduce the risk of foodborne illness from Salmonella contamination in chickens. Preempt, which was developed at the Department of Agriculture and licensed to a private company for marketing, is a culture of 29 harmless bacteria isolated by researchers that can prevent Salmonella from taking root inside a chicken. The technique involves spraying newly hatched chickens with a solution containing 29 Agood@ bacteria. The chickens ingest the solution while pecking at their wet feathers. The cultures then grow inside the chicken and shut out other more harmful bacteria.
26) Enforcement Action: FDA undertook a number of enforcement actions to protect consumers from potentially hazardous food and cosmetic products, including 11 seizures, 5 injunctions, and 42 warning letters. There were over 17,800 detentions of imported foods and cosmetics. Also, there were approximately 657 recalls of potentially hazardous food products. Of these, about 208 were Class I recalls, 276 Class II recalls and the remaining 173 recalls were Class III. Recall actions, which are voluntarily undertaken by the manufacturer, are one of the quickest and most effective ways to remove potentially hazardous foods/cosmetics from the marketplace
27) Nutrient Content and Labeling Claims: FDA issued a final rule that amended the definition of the term "healthy" for food labels. The amendment permits labels of certain processed frozen and canned fruits and vegetables and enriched cereal grain products that conform to a standard of identity to bear the Ahealthy@ designation. This action is designed to encourage consumers to use more foods whose consumption is recommended in the U.S. Dietary Guidelines as important for the maintenance of good health.
FDA also completed several actions required to bring policies related to nutrient content and health claims in line with requirements of FDAMA, including:
28) Expanded Web Pages to Make Food Safety Information More Accessible to Consumers and Industry: Education and information dissemination activities on food safety are among the most cost effective means to improve the safety of foods and reduce foodborne illnesses. Using Web pages, food safety education and other food safety information can be placed virtually at the fingertips of industry and millions of consumers. The following improvements were made in Web sites in FY 1998 to make food safety information more accessible to the public:
29) JIFSAN is Designated a WHO Collaborative Center on Food Contamination: The Joint Institute for Food Safety and Applied Nutrition (JIFSAN), was designated as a World Health Organization (WHO) Collaborative Center for Mycotoxin Analysis and Contamination in Foods. JIFSAN is a joint venture between FDA and the University of Maryland. This designation will give JIFSAN the leverage to acquire resources from such entities as the World Bank, International Life Science Institute and others to pursue projects that cannot be done through FDA. Through training and other outreach activities, JIFSAN hopes to share its expertise and encourage more non-government entities to share the resource burden of supporting research needed to keep abreast of emerging food safety issues.
STATUS OF PROGRAM
FY 1998 Accomplishments:
1. FOOD AND DRUG MODERNIZATION ACT OF 1997 (FDAMA):
FDA began implementing the FDAMA initiatives in FY 1998. FDA met nearly all of the FDAMA deadlines and in many cases, completed some projects ahead of schedule. The law required FDA to complete 17 regulations, 11 guidance documents, six regulatory notices, nine reports and 18 other tasks.
FDA has issued 16 final rules, nine proposed rules, 36 guidance documents, 11 regulatory notices and one report. Numerous important issues are addressed in these documents, including pediatric studies of drugs; data requirements; antibiotic and insulin requirements; approval of supplemental applications for approved products; streamlining clinical research on drugs; requirements for radiopharmaceuticals; elimination of certain labeling requirements; pharmacy compounding; dissemination of information on new uses for marketed drugs; dispute resolution; mutual recognition agreements and global harmonization; and national uniformity for nonprescription drugs.
A. FDA Plan for Statutory Compliance. FDA met its November 1998 deadline for publishing the 406(b) plan for implementing the 1997 FDA Modernization Act. Section 406(b) requires the Agency to maximize the availability and clarity of information for consumers and patients concerning new products. The plan is designed to bridge the gap between what FDA is required to do by law and what it is able to get done with current resources. The plan identifies six strategic directions for the Agency, working with the Agency's stakeholders to achieve improvements in processes, addresses the objectives mandated by Congress and outlines emerging challenges that are creating a gap between expectations and performance.
FDA has utilized a number of means of communicating with consumers and patients including giving seminars on new drug therapies and labeling; publishing brochures for consumer and patient use; making information available via the Internet; establishing programs to make promising investigational drugs and therapies available to patients with serious and life-threatening diseases; assuring that patient representatives are included on advisory committees considering products for HIV/AIDS, cancer and other serious diseases; and disseminating information about new and existing products.
B. Pediatrics. FDA implemented the pediatric exclusivity provisions of section 111 of FDAMA and is drafting a proposed rule entitled "Regulations Requiring Manufacturers to Assess the Safety and Effectiveness of New Drugs and Biological Products in Pediatric Patients" (62 FR 43900) . This new rule grants additional marketing exclusivity to sponsors of drugs who conduct studies that allow drugs to be adequately labeled for use in children.
On May 20, 1998, a list of approved drugs for which additional pediatric information may produce health benefits in the pediatric population was published. To further foster the development of drugs to treat illnesses in children, in June 1998, FDA published its guidance for industry entitled, "Qualifying for Pediatric Exclusivity under Section 505A of the Federal Food, Drug, and Cosmetic Act".
A Final Rule was published in November 1998 which requires labeling information for the safe pediatric use of new drugs and biologics that are therapeutically important for children or will be commonly used in children. The new rules make it more likely that children will receive improved treatment because doctors will have more complete information on how drugs affect children and at what age appropriate doses are needed. The rule also allows FDA to require pediatric testing of already-marketed products in certain compelling circumstances such as when a drug is commonly prescribed for use in children but the absence of adequate labeling could pose significant risks.
C. Pregnancy Labeling. FDA has reviewed its current system of labeling products for use in pregnant women and is developing an improved, more comprehensive and clinically meaningful approach to this process that integrates input from multiple government agencies, consumer groups, medical experts, and the pharmaceutical industry.
D. Pharmacy Compounding. A guidance document was published in the Federal Register on pharmacy compounding. This will ultimately result in a comprehensive list of bulk drugs that may be used in pharmacy compounding.
E. Radiopharmaceuticals. Section 122 of FDAMA requires the issuance of new regulations for diagnostic radiopharmaceuticals. The proposed rule, "Regulations for In Vivo Radiopharmaceuticals Used for Diagnosis and Monitoring," was published in the Federal Register on May 22, 1998. Efforts are underway to finalize the rule. Closely related to this FDAMA provision on diagnostic radiopharmaceuticals is the FDA published "Draft Guidance for Industry on the Development of Medical Imaging Drugs and Biologics." This document represents several years of work with the pharmaceutical industry and the Medical Imaging Drugs Advisory Committee. The notice of availability for this draft guidance was published in the Federal Register on October 14, 1998.
F. Outreach. FDA's CDER organized a satellite presentation for industry on FDAMA working with a major scientific trade organization. There were 61 down link sites and an estimated 8,000 - 10,000 individuals, representing a cross section of the industry, who heard this broadcast. Issues included updates on Pharmacy Compounding and the Agency's progress in developing a model MOU for use in partnering efforts with States. The MOU will address the distribution of inordinate amounts of compounded drugs in interstate commerce and provide the conditions and responsibilities for state investigations.
2. APPLICATION REVIEW: NEW DRUGS
A. Prescription Drug User Fee Act of 1992 (PDUFA). Under PDUFA, specific performance goals require the prompt review of four categories of submissions: original new drug applications (NDAs), resubmissions of original NDAs, efficacy supplements and manufacturing supplements to already approved marketing applications. FDA's Center for Drug Evaluation and Research (CDER) achieved remarkable success in far exceeding the progressively more stringent PDUFA performance goals agreed to for each successive fiscal year. This success occurred even with unexpected, continued growth in the number of marketing applications filed for review from FY 1992 through FY 1997. In recognition of this performance, Congress, in November 1997, reauthorized PDUFA for another five years.
In FY 1997, 121 original NDAs were filed by the FDA for review. One hundred percent of these NDAs were reviewed on-time. In the FY 1998 submission cohort of original NDAs filed for review, to date, all applications that have been reviewed were reviewed on-time.
In FY 1997, 87 resubmissions of original NDAs were filed for review. Of those, 87 resubmissions, 97 percent were reviewed on-time. In FY 1998, 53 resubmissions were submitted for review by the FDA. Final on-time performance for this cohort will not be known until April 1999.
In FY 1997, 146 efficacy supplements were filed by the FDA for review, and 99 percent were reviewed on-time. In FY 1998, 121 efficacy supplements were filed. Final determination of on-time performance for the FY 1998 submission cohort will not be possible until October 1999.
In FY 1997, 1,262 manufacturing supplements were filed, and 98 percent were reviewed on-time. In FY 1998, 1,468 manufacturing supplements were filed for review. Final on-time performance for this cohort will not be known until April 1999.
B. Pharmacology/Toxicology. FDA is working with academia, industry and the international community to improve drug development processes, evaluation procedures and review times. This cooperative effort will facilitate improved guidance for industry and reviewers in the conduct and evaluation of modern toxicological programs to support rapidly progressing clinical trials and drug reviews. FDA is exploring a formal collaboration with industry and academia to advance the development process for pharmaceutical and biopharmaceuticals.
C. FY 1998 New Drug Evaluation Highlights. FDA took 217 actions on NDAs, 107 of which were approvals. The median approval time was 12.0 months, a 24 percent decrease in median approval time compared with FY 1997. Sixty-three of these NDAs were approved in 12 months or less. Of these 107 approvals, 38 were for new molecular entities (NMEs) -- drugs that are chemically different in structure from those already on the market. Of the 38 NMEs, 17 were drugs given a priority review (products offering a significant improvement over currently marketed drugs).
Two drugs were approved under accelerated approval (Subpart H). Xeloda (capecitabine), approved in six months, is for the treatment of metastatic breast cancer resistant to other types of treatment. Thalomid (thalidomide) is indicated for the treatment of cutaneous manifestations (erythema nodosum leprosum) of leprosy. Unprecedented controls were applied to the distribution of this product to minimize the unique teratogenic risk (phocomelia) posed by the drug.
Thirty-four priority applications (17 NMEs, 10 non-NMEs, and seven efficacy supplements) were approved in FY 1998.
In refusing to approve several applications, the FDA may have prevented significant harm to the public. Sertindole was submitted to the FDA with an indication for the treatment of the manifestations of psychotic disorders. Because it prolonged the QT interval of the electrocardiogram, the FDA was concerned about Sertindole's capacity to cause serious cardiovascular events, including death. Another example is an angiotensin-II-receptor blocker deemed not approvable because of potential hepatotoxicity.
D. Chemistry, Manufacturing and Controls (CMC). Along with their contributions to the success of the Center in meeting the PDUFA goals for original NDAs, resubmissions of original NDAs, efficacy supplements, and manufacturing supplements, chemists and microbiologists in the Office of Pharmaceutical Science continued to develop and implement guidance documents for industry. Some guidances issued in FY 1998 include: SUPAC-IR Immediate Release Solid Oral Dosage Forms Manufacturing Equipment Addendum and SUPAC-MR Modified Release Solid Oral Dosage Forms Scale-Up and Post-Approval Changes.
E. Over-the-Counter (OTC) Drug Products. The OTC program approved 12 new drug products and/or new indications for OTC marketing in FY 1998. These included Rogaine as a brand new product and, for new indications, the approval of Famotidine for the prevention of heartburn and Excedrine Migraine for the pain of migraine headaches. The other new OTC products were switched to OTC use from prescription use.
The OTC program published 15 monograph-rule making documents in the Federal Register, including the proposed rule for alcohol warnings on anti-pyretic/analgesic products and the notice of availability of draft guidance for labeling of products for the treatment of vaginal yeast infections.
F. Prescription Drug Advertising and Labeling. FDA continued to regulate prescription drug advertising and labeling by monitoring all prescription drug promotions, enforcing laws and regulations, developing new guidances, and conducting research to support the program.
FDA received 14,764 submission packages from pharmaceutical companies in compliance with the Federal Food, Drug, and Cosmetic Act and applicable regulations. These packages contained approximately 30,000 prescription drug advertisements and labeling pieces.
Under Section 401 of FDAMA, the Agency developed and issued final regulations on the dissemination of off-label information. The Agency is developing procedures to implement these regulations.
G. Antibiotic Resistance. FDA has developed an Antibiotic Resistance Coordinating Committee through the Center for Drug Evaluation and Research, in coordination with the Office of the Commissioner, to address the growing problem of antibiotic resistance and its effects on drug development and regulation. To date, activities of the Committee have included the conduct of a public forum meeting with industry and academia, attended by over 200 individuals, to identify specific issues of mutual concern; establishment of contact points across FDA Centers and initiation of cooperative planning in this area with the Center for Disease Control, the National Institutes of Health and the American Academy of Pediatrics. The Committee also held a two-day Advisory Committee meeting to seek comment and foster discussion in the public domain on the clinical development and use of antibiotics to treat resistant organisms.
H. Outreach. FDA's CDER made significant accomplishments in getting easy to read user-friendly information to the consumer. Some recent examples include data on new and innovative drugs approved by FDA since January 1998 via its consumer new drug information page (www.fda.gov/cder/consumerinfo/default.htm); the reporting of adverse reactions and other problems with products regulated by FDA (www.fda.gov/cder/drug.htm); an OTC Drug Page which provides information for consumers and industry about non-prescription drugs (www.fda.gov/cder/index.htm) and a consumer brochure distributed as a public service by FDA and the Nonprescription Drug Manufacturers Association that provides consumers with information on the safe, effective and proper use of OTC medicines. The Agency also instituted a pharmacist education outreach program to help pharmacists better explain the drug approval process to consumers. FDA has updated its publication "From Test Tube to Patient: New Drug Development in the U.S." (www.fda.gov/fdac/special/newdrug/ndd_toc.html) which describes the drug development process in lay terms for the public. Additionally, the CDER Fax-on-Demand system which contains hundreds of documents for consumers, industry, Federal, state and local agencies and foreign government representatives has been established and can be reached on 1-800-342-2722.
I. Information Technology. One of FDA's goals is to have the capability and capacity for electronic regulatory submissions and reviews by FY 2002. This includes INDs, NDAs, and ANDAs, as well as Annual Reports, OTC monographs, drug registrations and product listings, etc. To meet this goal, FDA initiated the Electronic Regulatory Submission and Review (ERSR) Program and established a 5-year plan for moving the Agency from today's environment to the paperless environment envisioned for FY 2002. In September 1997, FDA published guidance for industry on "Archiving Submissions in Electronic Format - NDAs". This guidance provided information for the receipt and archive of electronic Case Report Forms and Case Report Tabulations without an accompanying paper copy. An Electronic Document Room was established to manage the receipt and handling of all electronic submissions. Workshops were conducted to assist industry in preparing their electronic submissions and classes were developed for FDA reviewers to train them on how to use the electronic documents. During FY 1998, FDA received 46 electronic submissions in lieu of paper, or the equivalent of 7.5 million pages. In addition to electronic submissions for archive, FDA continued to pursue a program of structured data submissions, particularly in the areas of chemistry, manufacturing, and controls and biopharmaceutics. FDA is in the second year of its ANDA electronic submission program, which is centered on the concept of structured data. This program is being evaluated for new drug review with the intent of augmenting the electronic submission of NDAs with structured data.
The Agency also implemented enhancements to its corporate management information system to support new requirements identified in FDAMA and converted all of its corporate databases and applications to be Year 2000 compliant.
J. Bioterrorism. FDA has provided extensive input to the National Institutes of Health, the Centers for Disease Control and Prevention and the Department of Defense in development of a research agenda in the general areas of emerging infectious diseases and biological agents and treatments for these that may be used in bioterrorist activities. FDA has also provided expert advice in an ongoing manner to these Agencies in the development of treatment and prevention guidelines related to the clinical management of bioterrorist threats and/or attacks.
3. APPLICATION REVIEW: GENERIC DRUGS
A. Generic Drug Review. FDA continues to support an active generic drugs program with a focus on expanding the availability of high-quality generic drug products to the public.
During FY 1998, FDA approved 354 abbreviated new drug applications (ANDA's) and abbreviated antibiotic applications (AADA's) (together referred to as abbreviated applications). Of the FY 1998 approvals, 45 represent the first time a generic drug was available for the brand name product. Examples of first time approvals include: (1) an H2 receptor histamine antagonist used in the treatment of ulcers, over-the-counter cimetidine tablets (generic for Tagamet, SmithKline Beecham), and (2) a smoking deterrent, nicotine transdermal systems (generic for Habitrol, Novartis Consumer Health, Inc.). The approval of generic versions of these two drug products could save the American Public and Federal Government hundreds of millions of dollars.
Regarding the electronic submission initiative, 24 electronic submissions of bioequivalence data and 21 submissions of chemistry, manufacturing, and controls data were received during FY 1998 for this program. For comparison, only nine bioequivalence submissions were received prior to FY 1998.
As a result of FDA's initiative to contact applicants that undergo two or more major deficiency cycles, the Agency has seen a drop in the number of review cycles needed to approve abbreviated applications. In FY 1998, the average application required 2.7 cycles before being approved. This is down from 3.7 cycles in FY 1995 and 2.9 in FY 1997.
B. Post-Market Drug Risk Assessment. FDA's Post-Marketing Drug Risk Assessment program is the program within CDER that evaluates the ongoing safety profiles of drugs available in the U.S. using a variety of tools and disciplines. This program has undergone many changes in FY 1998 including: the expansion of the Division of Pharmacovigilance and Epidemiology (DPE) into the new Office of Post-Marketing Drug Risk Assessment (OPDRA) within the Office of Review Management and the organization of drug risk assessment teams serving the drug review divisions and providing specialized attention to high risk drug areas; initiation of regulatory changes to bring FDA into harmonization with the ICH initiatives including Adverse Drug Reaction (ADR) elements of the M1, M2 and E2B workgroups; rollout of the Adverse Event Reporting System (AERS), a state-of-the-art information technology system for receiving, storing, and analyzing the 250,000+ individual reports of suspected drug-related adverse events the Agency receives each year; initiation of the electronic submission of ADRs to AERS; and the exploration of new databases, such as hospital audit systems and Medicare databases, for the potential to provide good scientific support for regulatory decisions in the drug safety area.
C. Information Technology. A powerful tool used by OPDRA is the computerized spontaneous reporting evaluation system, formerly called SRS, which has been replaced by the new, client server oracle based system - The Adverse Event Reporting System (AERS). This system contains the ADR reports obtained from FDA's MedWatch program and required reporting by manufacturers as well as therapeutic biologic reports. In FY 1998, in excess of 250,000 ADR reports were received. These reports often form the basis of various "signals" that there may be a potential for serious, unrecognized, drug-associated events. After the signal is generated, further testing of the hypothesis is undertaken using various epidemiological and analytic databases, studies and other instruments and the other resources of OPDRA.
Calendar year 1998 has been the initial production year for AERS, with CDER, CBER, the Office of Compliance brought on line and the involvement of 13 drug firms in pilot electronic submission of adverse event reports.
D. The Product Quality Research Initiative. FDA continues to strengthen its science base by working with academia and industry to develop an efficient mechanism to conduct research for improving the quality of pharmaceutical products available to the U.S. public. FDA entered into two partnership agreements with industry and academia to improve the drug review process. The Product Quality Research Initiative will bring together research scientists from academia, industry, and the FDA to conduct research in the areas of pharmaceutical chemistry, biopharmaceutics, and science management to identify better test methods for assessing quality of products, identify optimal manufacturing and management processes. This collaboration will enable consistent and reasonable requirements for all product quality information submitted in a regulatory filing and will streamline the drug development and approval processes for industry and FDA.
In addition, FDA's Collaboration for Drug Development Improvement supports scientifically sound approaches for expediting drug development. Also being developed by CDER are feedback mechanisms, such as formalized round tables, to involve the public, health professionals, Congress and industry to address changing public health needs, and to establish priorities for early and continuous involvement with drug development in all therapeutic areas. International harmonization efforts demonstrate that FDA will reach agreement on having the same new drug documents submitted to the regulatory authorities of Europe, Japan and the United States by the turn of the century. FDA has expanded its efforts to obtain outside expertise and opinion to help formulate policies and procedures that affect the Center's application review processes. Panels of outside experts often confer with FDA about difficult scientific issues, and the Agency has expanded its use of open public meetings to obtain input on important public health policy issues. Recent collaborative efforts between FDA and academia, industry, professional societies and health care organizations are making progress toward the promise of finding scientifically sound ways of expediting drug development and making it easier to take advantage of newer technologies.
FDA chemists and microbiologists participated in numerous workshops, training programs and conferences sponsored by organizations such as the American Association of Pharmaceutical Scientists, the Parenteral Drug Association, AOAC International, the Regulatory Affairs Professional Society, the Pharmaceutical Education and Research Institute, the Drug Information Association, the Food and Drug Law Institute, and the Pharmaceutical Research and Manufacturers of America. Participation in these meetings is designed to present both the CDER position and viewpoints on specific topics and to gather information to assist in the guidance development process.
E. Compliance/Surveillance. FDA participated in various workgroups that address FDAMA requirements in the areas of labeling (Section 126), registration of foreign firms (Section 301(1), insulin certification (Sec 125), and pharmacy compounding (Section 127).
FDA's Offices of Compliance, Generic Drugs and review divisions within CDER worked to coordinate responses to a wide variety of drug shortage situations. These have ranged from treatments for tuberculosis and AIDS to therapy for serious varicose veins to multi-vitamins used for nutritional support in hospitalized patients.
F. Information Technology. During FY 1998, FDA implemented a searchable, web-based publication of the Approved Drug Products with Therapeutic Equivalents (Orange Book). This publication serves as a national reference for drug product selection and as a reimbursement guide for Medicare and DOD purchase programs. The web-based Orange Book results in substantial reductions in publication costs to the Center. One area of technology that has not been fully exploited is electronic mail for communication with regulated industry. During FY 1998, FDA defined requirements for secure e-mail use during regulatory review and will conduct a pilot during FY 1999.