FDA Plans Major Review of cGMP Program

ROCKVILLE, Maryland—The US Food and Drug Administration has announced a major new initiative to revise its regulations governing pharmaceutical manufacturing and product quality. Focused on the agency’s current Good Manufacturing Practice (cGMP) program, the new effort seeks to improve public health promotion and protection. It will apply to veterinary and human drugs, including vaccines and other human biological drug products.

The FDA oversees the quality of drugs marketed in the United States by reviewing the safety and efficacy of drug applications and by inspecting manufacturing plants to ensure they conform to the cGMP requirements.

In a memorandum to all FDA employees, deputy commissioner Lester M. Crawford, DVM, PhD, noted that nearly 25 years have passed since the last major revision of the cGMP program.

The initiative—called "The Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach"—aims at achieving three major goals:

• To focus FDA’s cGMP requirements more squarely on public health by increasing its regulatory activities and resources on aspects of manufacturing that pose the greatest potential risks.

• To ensure that the FDA’s work in establishing and enforcing product quality standards does not slow innovation and the introduction of new manufacturing technologies.

• To enhance the consistency and predictability of the FDA’s approach to assuring quality production and safety among its centers and field components.

"The FDA’s regulatory and quality control systems for pharmaceutical products have become a gold standard for the world," Dr. Crawford said. "Any system can be improved upon, however, and with this risk-based, highly integrative initiative, we intend to do just that."

Three Broad Actions

The agency said it would carry out three broad actions to accomplish the reappraisal: Perform an external review of the existing cGMP program and product review practice, which will include an evaluation of potential inconsistencies in regulations; reassess and reevaluate its product review process and the cGMP program to achieve an integrated systems approach to regulating product quality; and enhance the scientific approach of the cGMPs to emphasize risk-based control point analysis and to facilitate innovations in pharmaceutical engineering.

First Steps

The FDA said it will carry out its review in three steps. The immediate actions include:

• Holding scientific workshops with key stakeholders.

• Enhancing its expertise in phar-maceutical technologies, such as pharmaceutical engineering and industrial pharmacy, by providing its staff with additional training, hiring new employees, and seeking external expertise.

• Encouraging innovation within its existing legal and regulatory structure by allowing certain manufacturing changes without prior review or approval.

• Evaluating the best ways to effectively and efficiently communicate deficiencies to industry.

• Including product specialists, as needed, as part of inspection teams.

• Having FDA centers provide a scientific and technical review of all cGMP warning letters.

• Developing a technical dispute resolution process that integrates experts from its centers and addresses perceived inconsistencies between centers.

• Emphasizing a risk-based approach in the work planning process.

• Improving the operation of Team Biologics—a partnership between the Office of Regulatory Affairs and the Center for Biologics Evaluation and Research (CBER).

The initiative’s intermediate steps will be to use emerging science and data analysis to enhance compliance programs, to target the highest risk areas, and to evaluate the feasibility of establishing dedicated teams of pharmaceutical inspectors, the FDA said.

The long-terms steps envisioned by the FDA will enhance training of the agency’s staff on new scientific approaches and innovative pharmaceutical manufacturing technology; develop and publish policies and procedures that reflect a science-based, risk-management approach to regulation; and educate the industry on new regulatory approaches that encourage innovation.

FDA acknowledges it cannot accomplish its goal alone. Because the pharmaceutical industry is global, the initiative will be undertaken in close collaboration and consultation with FDA’s regulatory counterparts in other countries. In addition, the success of the initiative will depend strongly on the support of quality control experts in industry, academia, government, and consumer groups.

"The globalization of pharmaceutical manufacturing requires a global approach to regulation," the agency said.