A CGMP Makeover

FDA's review of CGMPs focuses on introducing new technologies and developing a more consistent approach to evaluating quality systems.

Erik Swain, Senior Editor

The regulation of the pharmaceutical packaging process in the United States is about to change significantly. FDA has announced an initiative to improve its current good manufacturing practice (CGMP) program.

Precisely how this will affect pharmaceutical packaging operations is not yet known. The agency plans to perform an external review of the CGMP program and product review practices, reassess and reevaluate its current scientific approach to CGMPs and product reviews, and do what it can to "facilitate the latest innovations in pharmaceutical engineering." FDA will also hold scientific workshops with industry and other stakeholders.

The CGMP program will be adjusted to focus more on the products and packages that pose the greatest risk to public health. This philosophy is consistent with other recent regulatory initiatives from FDA, including the 1999 guidances, "Container Closure Systems for Packaging Human Drugs and Biologics" and "Changes to an Approved NDA or ANDA." The former classified drugs by dosage forms and routes of administration and asked for more information for those that posed more risk. The latter made it easier to change the packaging for drugs whose package format, dosage forms, and routes of administration pose little risk. The adjusted CGMP program is also consistent with the agency's new inspection format, which gives inspectors the discretion to inspect just two of six systems per visit, except in cases involving firms with poor recent histories of regulatory compliance.

The mantra behind these policies and others was "risk-based assessment," and that will also be true for the CGMP overhaul. The agency says its first goal is to "focus [its] CGMP requirements more squarely on potential risks to public health, by providing additional regulatory attention and agency resources on those aspects of manufacturing that pose the greatest potential risk." It must also "match its level of effort against the magnitude of risk" because "resource limitations prevent uniformly intensive coverage of all products and production."

Other goals include trying not to "impede innovation and the introduction of new manufacturing technologies in the pharmaceutical industry," and improving "the consistency and predictability of FDA's approach to assuring production quality and safety among the FDA's centers and field components."

The evaluation of quality systems ios expected to undergo a significant overhaul. FDA intends to evaluate new approaches to manufacturing and packaging quality for applicability, and then use those applicable approaches to evaluate CGMP requirements and related preapproval requirements. By integrating inspection programs with preapproval reviews, the agency hopes to "ensure that limited resources are best targeted to address important manufacturing quality issues, especially those associated with predicted or identifiable health risks."

The agency will further its commitment to using science-based policies and standards and will undertake "a thorough evaluation of the science base to ensure that product quality regulation not only incorporates up-to-date science, but also encourages further advances in technology."

Because of the global nature of the pharmaceutical industry, the agency intends to collaborate with regulatory authorities in other nations to achieve these goals. These efforts will occur through the International Conference on Harmonization and other venues.

Other potential reforms include hiring new employees and training others to enhance expertise in pharmaceutical technologies, allowing more changes in the manufacturing process without prior approval, better communication of deficiencies to industry, including product specialists as part of inspection teams, providing scientific and technical review of all CGMP warning letters, and developing a dispute resolution process that addresses perceived inconsistencies between centers.

The Product Quality Research Institute (Arlington, VA), a consortium of industry, academia, and government devoted to developing scientific knowledge to help spur regulatory changes, strongly endorsed FDA's initiative and said it hopes its manufacturing technical committee can be of help in the process.

More information on the initiative can be found at http://www.fda.gov/oc/guidance/gmp.html and http://www.fda.gov/oc/guidance/qsas.html.

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