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Lester M. Crawford, Jr., D.V.M., Ph.D. - FDA/PDA Conference

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.

FDA/PDA Conference
Remarks by
Lester M. Crawford, Jr., D.V.M., Ph.D.
Deputy Commissioner
U.S. Food and Drug Administration,
September 24, 2002

Thank you for the generous introduction, and good morning. As you just heard, I first joined the FDA 27 years ago, and now that I am back on my fourth tour with the agency, I find that having that long view is sometimes helpful. It puts things into perspective.

For example, I remember the collective shudder that went through the agency many years ago when a former general counsel of the FDA called it a "slow-moving elephant that bleeds profusely when pricked." The agency produced statistics to show that the shoe did not fit -- as indeed, it did not, although the part about easy hemorrhaging was not, (if I may mix the metaphors) completely out of the ballpark.

The reason I mention this bit of FDA lore is to point out how times have changed -- how different is our environment from what it was only 10-15 years ago -- and, to add the obvious corollary, how it is incumbent upon us to respond in kind. No one who knows anything about our agency would even think of comparing it to a slow-moving animal -- not in the recent years, and most definitely not since that terrible morning in September a year ago.

We've heard and read recently a great deal of commentary on how much -- or how little -- we have changed as a nation as a result of the attack on the World Trade Center and the Pentagon. Well, there is no question about that ordeal's profound impact on the FDA. Practically overnight, our agency, the traditional protector of consumers against largely unintended public health risks, found itself on the front lines of the war against terrorism, with the added top-priority assignment of helping shield the country from intentional mayhem. We've been designing, building, and reinforcing our part of that shield ever since.

Sometimes the FDA has acted on its own: for example, after the discovery of the letters with anthrax, our agency assured the public that doxycycline and penicillin G procaine are approved and effective for treating anthrax infections.

Sometimes we acted together with industry: as you know, we've been trying to stimulate development of new drugs to counter the effects of potential weapons of terrorism, and to ensure adequate supply of vaccines against smallpox and other substances that could be used against us.

And most of the time we've been implementing the mandates of Congress, which has appropriated special funds and passed a major law -- the Public Health Security and Bioterrorism Preparedness and Response Act -- to turn the FDA into a bulwark against potential attempts to contaminate the products we regulate.

As a result, we're in the process of hiring and training more than 800 additional employees, two thirds of whom will focus on our biggest counter-terrorism job, which is to protect the security of the 80 percent of our national food supply -- practically everything but meat and poultry -- that's in FDA's purview.

Most of these new employees are being assigned to our field offices and to the 150-odd ports of entry that process eight million shipments of food and other regulated imports we receive in a year. We are also drafting rules and guidances for implementing a broadly based program of firms registration, records keeping, advance import notification and administrative detention -- measures that have been primarily designed to safeguard the security of seafood, fresh produce and other imported food. We are also adding to the network of laboratories that will enable us to detect and counter outbreaks of food-borne disease.

In addition to this top-priority, truly massive undertaking, we have to carry out FDA's routine workload, including our substantially strengthed drug program. PDUFA -- the Prescription Drug User Fee Act -- as you know, was extended for another five years by the Bioterrorism Preparedness and Response Act, and the FDA has been authorized to hire additional 450 employees to make up for the resource shortages that have affected the program during the last five years, and to increase the surveillance of the safety of drugs during their early years on the market, when we're best able to detect and counter side effects that had not appeared during the clinical trials.

These are just the highlights of the biggest FDA expansion in at least 30 years, most of which is being carried out with an urgency that has no precedent in the agency's 96 year-old history. In addition, we are preparing to consolidate the oversight of certain types of pharmaceutical products from CBER, our Center for Biologics Evaluation and Research to CDER, the Center for Drug Evaluation and Research.

The goal is to bring under one roof reviews of products that are similar in clinical development, clinical data analysis, and use in medical practice, and to allow the biologics center to focus its expertise on vaccines and blood products -- which are critical for our homeland defense -- and on such issues as gene therapy and tissue transplantation. These technologies, as we all know, which are likely to be the great vehicles of medical progress in this new century.

The consolidation is a very sensitive undertaking, and we're still in the planning stage -- so until you hear more from us, sometime next year, please continue dealing with CBER on the same issues as you had before.

So, we're very busy. And yet, on top of this formidable workload, we have just launched yet another demanding initiative -- a major overhaul of our system of current Good Manufacturing Practice, or cGMP, for human and veterinary drugs, and biological products.

This is the main subject I've been asked by your organizers to discuss today, and I can understand, why. The cGMPs are the backbone of product quality: they're the instrument on which the FDA and your firms rely most heavily for assurance that pharmaceutical products are safe and effective. For millions of people, drug quality can make the difference between well-being and misery, or life and death. Moreover, the pharmaceutical cGMPs have been hardly touched in the last 25 years, and they still do the job, and have no major flaws that demand urgent attention.

Thus the first question I need to address is, what has made the FDA take on this big additional job, despite a workload that's without a precedent in the agency's 96 year-old history?

The answer is -- as I pointed out earlier -- that our environment is changing, and we need to respond accordingly, or else we'll eventually lose our effectiveness. As I said, the cGMP system still performs well, but in recent years, it has required incremental adjustments because of significant changes, including the following:

  • Growing # of pharmaceutical products play greater public health role (7,3411 approved Rx drugs in Dec. 82 v. 11,721 in Sep. 02);
  • Resource constraints have reduced the frequency of FDA's domestic cGMP inspections of drug establishments (4,266 in FY80; 1,505 estimated in FY03);
  • Advances in pharmaceutical sciences and manufacturing technologies;
  • Application of biotechnology in drug discovery & manufacturing;
  • Advances in the science and management of quality;
  • Globalization of industry.

Together, these developments have transformed the environment in which we -- your industry as well as the FDA -- protect the quality of pharmaceutical products. We can't ignore the implications of this new landscape, which warrants a systematic reappraisal of our approaches to product quality regulation. We must make sure the cGMPs continue to protect the public health. The next questions that I am sure you're asking, are not so easy to answer as the first one. How is this overhaul to be carried out? How is it expected to give the cGMPs a new lease on life, and make them serve better our public, industry, and the FDA? We've been considering these questions carefully and in depth, and our conclusion is that we need to achieve integrated quality systems that are based on the principles of science-based risk management. Here are the three major steps we plan to take in the next year or two:

  • We will perform an external review of our cGMP program and product review practices, including evaluation of potential inconsistencies in their implementation;
  • We will reevaluate the consistency of our scientific approach to both product review and cGMPs; and
  • We will adopt solutions that will emphasize risk-based, critical process control point analysis, and facilitate innovations in pharmaceutical engineering.

Designing effective, risk-based, and innovation-friendly cGMPs is a major undertaking that requires careful planning, and we have therefore drawn up a fairly detailed road map we intend to follow. In the first place, in order to identify changes that would be most helpful in adjusting the cGMP system to our new environment, we'll have to study how the trends I mentioned a while ago impact on, and are affected by, the FDA's approach to product quality regulation.

We will then evaluate the cGMPs and our policies and approaches for their compatibility with certain principles and factors that should be the underpinning of an efficient, up-to-date quality control system: These considerations include:

  • One, risk-based use of FDA's limited resources, in order to bring our efforts into a balance with the magnitude of risks;
  • Two, policies and standards that incorporate the latest science to encourage advances in drug manufacturing and technology;
  • The third principle is the need to integrate quality system into cGMP and related pre-approval requirements. We must achieve coordination and synergy of the submission review and inspection programs;
  • Next, we have to consider the opportunities presented by the International Conference on Harmonization and other cooperative forums for addressing cGMP challenges posed by globalized production; and, last but far from the least,
  • we have to continue vigorous enforcement of existing regulatory requirements, to provide strong public health protection until the new system is launched.

In case this plan strikes you as too general, we have prepared a long list of specific steps we will take immediately and in the near future as we translate intentions into actions. Here are the top items:

We will hold scientific workshops with key stakeholders to learn more about their processes and their concepts of dependable, science-based cGMPs;

  • We will hire and train more specialists, and work with external experts, to enhance our knowledge of such technologies as pharmaceutical engineering and industrial pharmacy;
  • We will allow certain changes in the manufacturing processes that do not impair product quality without prior review and approval, by using such regulatory tools as the comparability protocols. The purpose is to encourage innovation within the existing framework of statutory provisions and regulations;
  • We will identify the optimal means for effective and efficient communication to firms about their cGMP deficiencies;
  • We will shift the agency's lead on implementation of electronic record-keeping to our drug Center, while maintaing the involvement of other FDA product Centers and the Office of Regulatory Affairs;
  • We will include product specialists, as needed, in our inspection teams; o We will have our Centers carry out a scientific and technical review of all drug cGMP Warning letters; and
  • We will develop a technical dispute resolution process that integrates technical experts from the Centers and addresses perceived inconsistencies between Center.

That's not the entire list of immediate and short-term measures we're taking or are about to take as part of this initiative. We are also considering several intermediate and long-term steps -- such as establishing dedicated cadres of pharmaceutical inspectors -- that might take more definite shape as our initiative progresses. But I believe that I've said enough to indicate both the thrust and the pace of the coming changes in the cGMP universe.

We want our programs and policies to be in harmony with scientific and technological progress, in order to help strengthen your industry's capacity for producing high-quality drugs while increasing the efficiency of our agency's operations and, above all, continue to safeguard the public health. I think we can all agree that these are achievable and highly desirable goals, and I hope that I can count on your help in reaching them.