| This text contains Dr. Crawford's prepared remarks. It should be used with the understanding that some material may have been added or deleted during actual delivery. |
Good afternoon, and thank you,... for the introduction.
I am doubly pleased and honored to have been invited to this meeting. It gives me an opportunity, as a representative of the Food and Drug Administration, to bring you the greetings of our new Commissioner, Dr. McClellan, and to express his and our agency's appreciation of the support your organization has given to our scientific programs.
And on a personal level, I am happy to be here and discuss microbiology, a fascinating subject that has a long tradition at the FDA, and to which I've devoted much of my professional work.
Ever since our agency was founded -- microbiology research has been one of the FDA's essential tools for making sure that food is safe, and that vaccines and treatments for infectious diseases are safe and effective.
It's always been a basic means to the accomplishment of our public health mission.
Then came the attacks on the World Trade Centers and the Pentagon, the FDA became one of the leading agencies in the defense against bioterrorism, and our microbiologists were charged with the top priority task of helping to develop, and make available, treatments and vaccines for pathological agents that could be used by terrorists. So in my overview of today's microbiology research at the FDA, I will give you a few examples of the more traditional type of work we're advancing to protect our public against infectious diseases, and then I'll describe some of our scientific efforts to protect our public health against the potential hazards of bioterrorism.
In addition, I am told that you are interested in the coming consolidation
of the product reviews carried out by our centers for drugs and for biologics,
and in the general directions
of our agency.
I will address those topics as well.
There is no area where we used microbiology more extensively than in the protection of the food supply, 80 percent of which is in FDA's purview.
Most of this work is done by our Center for Food Safety and Applied Nutrition -- CFSAN -- through microbiological surveillance and monitoring.
Our CFSAN scientists develop and validate microbiology-based methods that are used to detect, enumerate and identify pathogens in food.
CFSAN also conducts microbiological research to support FDA's regulatory policies and delineate microbial risk.
The Center studies bacterial genetics and molecular virology, new pathogens, and the reasons for increased pathogenic resistance to such traditional barriers as acidity.
CFSAN has also a special program that investigates technologies -- such as irradiation, heat and high pressure -- to improve microbiological safety of food.
Our Center for Veterinary Medicine (CVM) contributes to this part of our mission by studying methods to prevent animal pathogens from causing harm to humans and economic damage.
One example is CVM's current research on how to best prevent the spreading Chronic Wasting Disease, which is affecting wild and farm elk and deer in the north of the United States.
This work, which has been very successfull, is focused on developing a rapid method for identifying prohibited rendered materials in feed, and is based on the detection of prions.
CVM also runs numerous projects, both in-house and in cooperation with others, that are designed to develop and implement methods to limit the emergence and spread of antimicrobial resistance in hospitals, communities, farms, and the food supply.
For example, the Center runs several studies exploring the dissemination of antimicrobial resistance among both zoonotic foodborne pathogens and commensal bacteria of food animals.
One of these studies is testing the hypothesis that the use of growth promoting antibiotics fed to chickens will result in the selection of multiple-resistant enterococci from the benign chicken microflora that can contaminate chicken carcasses destined for human consumption.
In addition, CVM has several projects focused on the genetic characterization of novel and emerging antimicrobial resistant determinants such as efflux pumps and integrons among both zoonotic and animal health pathogens including Campylobacter, E.coli 0157:H7, Salmonella, Enterococcus, and Staphylococcus aureus.
We're also learning a lot about the mosquito-borne West Nile Virus, which has spread all over the country.
Our specialists at CBER -- the Center for Biologics Evaluation and Research -- have developed an "infectious" cDNA copy of the West Nile virus genome, which can be used to construct novel RNA genomes of the same virus by side-directed mutagenesis.
The "infectious" cDNA has already been used to study the role played in virus replication by a conserved nucleotide sequence in the 3'noncoding region of the West Nile Virus genome.
The resulting family of mutant viruses have altered growth properties in various tissue culture cell lines, and one of them is host range-restricted in that it fails to replicate in mosquito cells.
It replicates normally in other tissue culture substrates.
Since our previous work has shown that a dengue virus mutant bearing similar properties was attenuated and immunogenic in a monkey model for dengue virus infection, we're planning additional experiments.
They will test the host range-restricted West Nile virus mutant, and other mutant West Nile viruses with altered growth properties derived in the same study, using a mouse model for West Nile virus neurovirulence.
But the biggest microbiological research at CBER is dedicated to biodefense -- to support the development, availability, and maintenance of products for the protection against, or the treatment of, injuries caused by potential agents of bioterrorism.
The Center's research is focused on such pathological agents as smallpox, anthrax, botulism, tularemia and viral hemorrhagic fevers, alphaviruses, salmonella, and shigella. The research priorities are the development and validation of assays; understanding the pathogenesis of the threat agents; and development of animal models to assess the safety and effectiveness of new biologic products and the potency of assay methods and standards.
A big job: the Center, with fewer than 160 researchers, handles more than 90 biodefense-related research projects, in addition to product reviews and the investigation of new biotechnologies, including gene therapy, xenotrasplanatation, human tissues and cell products, as well as transgenics.
A good example of the work our scientists have done is the development of a new FDA Vaccinia Immunoglobulin Standard.
To prepare for large-scale smallpox vaccination, clinical trials of new vaccines and new vaccinia immune globulin (VIG) products, we had to develop new assays to measure immune responses in pre-clinical and clinical studies.
The classical assay to measure vaccinia neutralization, the Plaque Reduction Neutralization Test, or PRNT, is slow, labor intensive, and difficult to validate and transfer to clinical laboratories.
Our Center for biologics therefore developed a novel vaccinia neutralization assay based on the expression of a reporter gene, beta-galactosidase. The CBER assay takes just 24 hours, is sensitive, reproducible, and the read-out is automated.
It is easy to transfer, and its results for several VIG products are very similar to those obtained in classical PRNT assays.
Speaking about the research at our Center for biologics, we expect it to be bolstered in a collaborative, constructive manner by Dr. Kathryn Zoon's recent return to NIH, where she will be in an excellent position to contribute to CBER's scientific work.
FDA generally does not engage in basic research, but it is renown for its capacity in the field of applied research that's usually referred to as regulatory research. I understand that you are interested in our decision to transfer the review and approval of therapeutic biologics to the Center for Drug Evaluation and Research (CDER).
First of all, why did we do it:
In other words, we believe the consolidation will contribute to the strengthening of the FDA's science, increase the timeliness of biological product reviews, and contribute to greater uniformity of regulations, policies and practices involving all therapeutics.
The project is not yet completely ready for a roll-out, but the general outline is clear.
What's planned for a transfer to CDER are cytokines, growth factors, enzymes and interferons -- including recombinant versions -- plus proteins for therapeutic use that are extracted from animals or microorganisms, and other therapeutic immunotherapies.
What will stay in the Center for biologics, or CBER, are gene therapy; products composed of human or animal cells or from physical parts of those cells; plasma expanders; allergen patch tests; allergenics; antitoxins, antivenins, and venoms; in vitro diagnostics; vaccines, and toxoids and toxins intended for immunization. The overall responsibility for therapeutic vaccines will remain in CBER, with the understanding that the clinical review of therapeutic vaccine-associated new drugs or biologics will be fully coordinated with CDER.
CBER will be free to concentrate on its core strengths:
Altogether, we estimate that about 34 percent of CBER's human drug review workload
will be transferred to CDER, and to account for that change, we plan to transfer
just under $33 million from CBER's budget to CDER, together with about 208 employees.
We are convinced that the results of this initiative will be what we intend
them to be, which is a stronger and more competent protection of the public
health.
If I can put this project into a larger perspective:
I've been working for the FDA --on and off -- since 1975, and I've seen it go through periods of innovationand periods of adherence to the status quo.
This is phenomenon that's familiar, I believe, to most organizations,in and out of the government.
Our agency is now, has been for the past year, and will continue to be in a highly creative and innovating stage.
In part, this is connected with the expansion and other changes that have had to take place in response to the new threat of terrorism; in part with the need to accommodate and keep abreast of the scientific progress in the regulated industries;but perhaps most of all because new conditions have inspired and made necessary new regulatory ideas that are now ready to be implemented.
Secretary Thompson, Commissioner McClellan and the whole leadership of our agency are closely attuned to this change in the regulatory climate, and we are most interested in exploring new directions and approaches to deal with public health issues.
Which brings me to the last subject I was asked to address, and that is what is to be expected from the FDA in the future.
Expect a lot of initiatives to reduce the risks to the public health; to promote faster access to new medical technologies and products; to prevent and prepare for bioterrorist attacks; to help reduce adverse events; and to bring better and more helpful product information to consumers and patients.
All of these areas in FDA's purview are wide open for new departures and new enterprise.
What will not change is our mandate for, and dedication to, the best public health protection for the American people.
With your continued help, and with the help of other stakeholders, we will fulfill that mandate, and do the job that's been entrusted to us.
Thank you.
FDA/Website
Management Staff
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2003-FEB-07