Pharmaceutical cGMP Initiative Questions and Answers

August 21, 2002

1. What did the FDA announce today?

Today the Agency announced that it would be undertaking a significant new initiative concerning regulation of pharmaceutical manufacturing and product quality. The initiative, Pharmaceutical cGMPs for the 21^st Century: A Risk-Based Approach will cover veterinary drugs and human drugs, including human biological drug products.

As we approach the 25^th anniversary of the last major revisions to the drug cGMP regulations, FDA concluded that it was time to step back and evaluate the currency of both the cGMP program and the pre-market review of chemistry and manufacturing issues. The initiative announced today is intended to build on the many successes of the pre-market approval and pharmaceutical cGMP programs. The initiative will help these programs continue to be successful in the future by keeping pace with advances in pharmaceutical science and manufacturing technology.

2. Why is FDA launching this initiative on cGMPs now?

Advances in quality assurance techniques and manufacturing technologies provide an opportunity to evaluate how these advances can be applied to pharmaceutical manufacturing. This initiative will integrate the most current quality systems and risk management approaches and will encourage the adoption of modern and innovative manufacturing technology. In addition, it will better integrate the inspection programs with the review of drug quality that is performed as a part of the pre-approval process. The initiative will also use existing and emerging science and analysis to ensure that limited resources are best targeted to address important manufacturing quality issues, especially those associated with predicted or identifiable health risks.

3. Why is it being called a risk-based approach? Is FDA's current regulation of pharmaceutical products not based on risk?

The initiative is intended to build on the many successes of the cGMP and pre-approval programs and help them continue to be successful in the future by keeping pace with the most up-to-date quality systems and risk management approaches. It will also allow FDA to enhance the scientific underpinnings of cGMPs and to facilitate the latest innovations in pharmaceutical engineering. In addition, the risk-based approach will enhance FDA's ability to focus on identifying and controlling critical factors that effect process and product quality. This enhancement is expected to facilitate targeting of cGMP and application requirements that better reflect improved scientific understanding of product quality.

4. How will the process work?

FDA is forming internal working groups composed of representatives from across the Agency, to begin various projects that are discussed in the concept paper, and there will be ample opportunity for public and stakeholder comment as the process moves forward.

5. How long will it take?

There are a variety of projects that fall within the scope of this initiative, and some will take longer than others. Among the first projects that FDA will take on include:

Holding scientific workshops with stakeholders;
Including product specialists, as needed, as part of inspection teams;
Having FDA's product Centers provide a scientific and technical review of all drug cGMP warning letters; and
Developing a technical dispute resolution process that integrates technical experts from the Centers and addresses perceived inconsistencies between Centers

6. What sorts of things are you likely to do?

The plan calls for various projects to be carried out by FDA's product Centers, the Office of Regulatory Affairs, and other components of the agency. They include such innovations as:

internal and external reviews and analyses of the agency's internal quality-assurance programs, practices, and approaches;
regulatory process changes to encourage manufacturing innovations, emphasize a risk-based approach to quality control, and enhance key aspects of FDA inspections; and
augmented scientific training and communications, both internally and with the regulated industry.

7. How will FDA assess the success of the risk-based cGMP program?

Each project under the initiative will be judged on its own merits, and success will be measured by appropriate outcomes identified during project development. The overall success of the program will depend on its ability to help the agency achieve its mission of public health promotion and protection by ensuring that safe and effective pharmaceutical products are available to the American public. We believe that the success of the initiative will depend on incorporating the following principles:

Risk-based orientation;
Science-based policies and standards;
Integrated quality systems orientation; and
Strong public health focus.

8. FDA's announcement talks about better integrating the pre-approval review and cGMP inspection programs. What does this mean?

FDA ensures product quality by inspecting and evaluating firms' compliance with cGMP requirements and also, as part of the pre-approval review program, by evaluating the chemistry and manufacturing controls associated with drug production. We intend to perform an external review of the two programs, including evaluation of potential inconsistencies and redundancies. Our goal is to ensure that the two programs operate in a fully coordinated and synergistic manner.

9. How will consumers and patients benefit from this work? More than 40 years ago, Congress required that all drugs must be produced in accordance with current Good Manufacturing Practice (cGMP). This requirement was intended to address substantial concerns about substandard drug manufacturing practices by applying quality assurance and control principles to drug manufacturing. The last comprehensive revisions to the regulations implementing cGMP requirements occurred almost 25 years ago. In addition, for many years, pre-market approval requirements, pertaining to chemistry and manufacturing controls, have also been in place to ensure quality manufacturing of approved drugs.

The initiative is intended to ensure that FDA resources are used most effectively and efficiently to maximize the public health impact of the agency's actions. The initiative will strengthen the public health protection achieved by FDA's regulation of pharmaceutical manufacturing, and FDA remains committed to strong enforcement of the existing regulatory requirements, even as we are examining and revising our approach to these programs.

10. Many of FDA's major enforcement actions are based on violations of cGMP. Isn't this really just an effort to deregulate the drug making process?

No, this initiative will strengthen the public health protection achieved by FDA's regulation of pharmaceutical manufacturing. Enhancing and reinforcing the scientific underpinnings of our cGMP program will not interfere with our ability to enforce cGMP requirements. FDA remains committed to strong enforcement of the existing regulatory requirements, even as we are examining and revising our approach to the programs.

11. You mention a "risk-based" approach to cGMPs. Does that suggest that the manufacturing process will not be regulated if industry can persuade FDA that there is minimal risk?

No. FDA remains committed to strong law enforcement. FDA has always placed higher priority on legal violations that pose direct and significant safety risks to the public, but FDA also recognizes that enforcement against indirect health risks is important too. Although certain legal violations may not pose direct safety risks, they may, by context or association with other violations or conditions collectively, threaten product quality or the integrity of the regulatory system that serves important public health protection objectives. The cGMP requirements ensure that the American public does not have to wait until there are injuries and deaths before the FDA can intervene to assure drug safety and effectiveness. The cGMP requirements are intended to prevent such harms by building quality into the design and production of pharmaceuticals and thereby reducing the risks that deficient drug products will be produced.

12. Does FDA have evidence of patients actually being harmed because of cGMP violations? If not, why does the FDA take them so seriously? Are they needed at all?

The cGMP requirements ensure that the American public does not have to wait until there are injuries and deaths before the FDA can intervene to assure drug safety and effectiveness. The cGMP requirements are intended to prevent such harms by building quality into the design and production of pharmaceuticals and thereby reducing the risks that deficient drug products will be produced. In addition, there are numerous examples of manufacturing problems--that could have been avoided with full cGMP compliance--that have resulted in the distribution of drug products that needed to be recalled because of compromised safety or effectiveness.

13. Is this initiative reflective that FDA is being overly cautious with its review of drugs and now with its manufacturing standards?

No. The initiative does not represent a ratcheting up of manufacturing standards. It reflects FDA's plan to implement the most up-to-date concepts of risk management and quality systems approaches and ensure that FDA's resources are used most effectively and efficiently to address the most significant health risks.

14. Does this effort mean that current FDA enforcement of cGMPs is inconsistent?

No, the initiative announced today is intended to build on the many successes of the pharmaceutical cGMP programs. This initiative will help this program continue to be successful in the future by keeping pace with advances in pharmaceutical science and manufacturing technology.

15. Will this impose additional costs to industry and patients?

We believe that enhancing the scientific underpinnings of our regulation of drug quality will be more efficient and effective for both FDA and industry because it will better target agency and industry resources to address problems that may adversely affect product quality.

16. Will the cGMP standards be the same for generic and innovator drugs?

Yes

17. Doesn't this initiative suggest that FDA's cGMP regulations are obsolete? Why not simply stop enforcing them until the new ones are in place?

The cGMP program has been extremely successful, and pharmaceuticals produced for Americans are widely recognized for their safety and effectiveness. This initiative is intended to build on the successes of this program to ensure that the program continues, in the future, to achieve this level of success. FDA remains committed to strong enforcement of the existing regulatory requirements, even as we are examining and revising our approach to these programs.

18. Will FDA continue to enforce its existing GMP regulations?

While FDA is examining and revising its approach to the pharmaceutical cGMP program, the agency will continue to enforce its cGMP regulations. FDA believes that the regulations provide ample flexibility to incorporate the central principles underlying this initiative.

19. The FDA announcement talks about major changes in science, technology, and manufacturing methods. Does this mean that the pharmaceutical industry is not keeping up?

Pharmaceuticals produced for Americans are widely recognized for their safety and effectiveness. The initiative intends to build on these successes and facilitate the adoption of advances in pharmaceutical science, manufacturing technologies, and quality systems approaches.

20. Is industry involved in this re-evaluation?

As discussed in the announcement, there will be ample opportunities for industry to participate in this initiative.

21. Are consumer and patient groups involved?

As discussed in the announcement, there will be ample opportunities for consumer and patient groups to participate in this initiative.

22. What is the bottom-line message for industry? For patients and consumers?

This initiative will strengthen public health protection achieved by FDA's regulation of pharmaceutical manufacturing. It will also allow FDA to enhance the scientific underpinnings of the regulation of pharmaceutical quality and to facilitate the latest innovations in pharmaceutical engineering.

FDA remains committed to strong enforcement of the existing regulatory requirements, even as we are examining and revising our approach to these programs.

23. Will this initiative have an impact on other on-going revisions to the drug cGMPs and guidances?

The Agency will continue and expand efforts to provide cGMP guidance that is consistent with this initiative, and, if necessary, to reevaluate such guidance on a case-by-case basis.

24. What kind of impact will this have on the blood GMPs?

We have been evaluating our regulation of blood and are revising our regulations and policies as part of our Blood Action Plan. While the GMP regulations specific to blood are not the focus of the initiative to reexamine pharmaceutical GMPs, what we learn in our evaluation of pharmaceutical GMPs generally can be used in our efforts in other areas.

25. What kind of impact will this have on the proposed tissue good tissue practice (GTP) regulations?

The Agency has a comprehensive approach to the regulation of human tissues. One part of the approach is the proposed GTP regulations. The effort to reexamine pharmaceutical GMP regulations is not intended to cover the tissue regulations; however, what we learn in our evaluation of pharmaceutical GMPs generally can be used in our efforts in other areas

26. As far as a risk-based approach, does it mean it is more likely that efforts will be concentrated on human pharmaceuticals rather than veterinary?

This initiative is consistent with the agency's current approach that ensures that adequate resources are provided to address safety risks to humans associated with pharmaceuticals. However, FDA's statutory mission requires appropriate regulation of veterinary pharmaceuticals, including those intended for companion animals.

27. The FDA initiative covers veterinary drugs. Does this mean that Type A medicated articles and medicated feeds are included in the initiative?

While the cGMP regulations specific to medicated articles and medicated feeds are not the focus of the initiative to reexamine pharmaceutical cGMPs, what we learn in our evaluation of pharmaceutical cGMPs generally can be used in our efforts in other areas.

28. What does this initiative means for foods and medical devices and the Centers that regulate these products?

These products are the subjects of recent initiatives that incorporate many of the same principles, including an emphasis on quality systems regulation with strong scientific underpinnings.

29. Are there any international implications associated with this initiative?

This initiative is focused on FDA programs to assure the quality of drugs available to the American public. These include drugs produced domestically and in foreign countries for the U.S. market. Given the global nature of pharmaceutical production today, FDA fully intends to undertake this initiative in close concert and consultation with its regulatory counterparts internationally.

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