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FDA to Prescribe New Drug Manufacturing Standards

Keith Larson, Vice President of Content

First top-to-bottom review in 25 years to emphasize risk management principle

U.S. Food and Drug Administration (FDA) caught many drug makers by surprise when it announced in late August a broad-ranging initiative to overhaul how it regulates pharmaceutical manufacturing operations.

The announcement comes at a time when a significant number of major drug makers have struggled to meet the FDA's current Good Manufacturing Practices (cGMP) standards. For example, Schering-Plough in May agreed in a consent decree to pay $500 million for shortcomings identified in inspections of its plants in Puerto Rico and New Jersey. Eli Lilly, Abbott Laboratories and Wyeth are among other drug makers that have recently had to delay or withdraw new drug introductions because of FDA inspection problems at their factories.

Administration officials are quick to point out that the new initiative is not a response to the spate of enforcement actions announced in recent months. Rather, officials say, the current cGMPs have worked quite well to protect the public health--and this initiative is intended to make them even more effective.

"FDA's regulatory and quality control systems for pharmaceutical products have become a gold standard for the world," says FDA deputy commissioner Lester Crawford.`"Any system can be improved upon, however, and with this risk-based, highly integrative cGMP initiative we intend to do just that. We know we can make a good system better. Publicizing this blueprint for action is just the first step."

"For years, the FDA and industry have engaged in an ongoing dialogue on cGMP standards and agree that they're pretty good--even if there were a few rough edges," adds Jeff Trewhitt, spokesman for the Pharmaceutical Research and Manufacturers Assn. (PhRMA). "But now, instead of periodic, ongoing conversations, there will simply be a more organized, consistent review with industry feedback."

Indeed, pharmaceutical cGMPs have continued to evolve since Congress first mandated the application of quality assurance and control principles to drug manufacturing 40 years ago. (After all, the "c" does stand for "current.") But the last top-to-bottom review of the requirements occurred almost 25 years ago.

"The time has come to step back and evaluate the currency of both the cGMP program and the pre-market review of chemistry and manufacturing issues," FDA's Crawford says.

But other industry observers see the timing as more than just a coincidence. "Some senior FDA officials must have been asking themselves, 'Why are these well-financed companies continuing to have basic GMP problems? '"contends Gordon Richman, vice president of strategic consulting and general counsel for EduQuest, an FDA regulatory consulting firm in Hyattstown, Md.

Pharmaceutical manufacturers, meanwhile, have just begun to interpret the FDA's ambitiously titled guidance document, Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach. "It's really too early to tell just what it will mean," says David Adler, a senior engineering consultant for Eli Lilly in Indianapolis. Other pharmaceutical manufacturers contacted for this story were similarly reluctant to speculate on specific implications of the initiative.

The initiative outlines immediate, near and longer-term steps that FDA believes will take two years to fully unfold. "This is a long-term, science-driven process that will take time to develop and implement," says Crawford.

FDA also stresses that enforcement of existing cGMPs will continue during this review process and that it will continue to work with other regulatory bodies worldwide in developing standards applicable to the increasingly global pharmaceutical industry.

On the technical side, FDA outlines three overarching concepts that will guide the reevaluation process: advances in risk management science, advances in quality management science and advances in pharmaceutical science and manufacturing technology.

In broad strokes, the three stated goals of the initiative are to: