cGMPs back under FDA microscope

Agency initiative will give manufacturing and product quality regulations much needed revamp due partly to globalization

By Mark A. DeSorbo

ROCKVILLE, MD-In a move that will revamp regulations for pharmaceutical manufacturing and product quality, the FDA has launched an initiative, Pharmaceutical cGMPs for the 21st Century: A Risk-Based Approach, an intended “step back,” the agency says, to “evaluate the currency of both the current good manufacturing practices (cGMPs) program and the pre-market view of chemistry and manufacturing issues.”

At a late August press conference, Janet Woodcock, director of the agency's Center for Drug Evaluation and Research (CDER), told re porters that significant changes in the pharmaceutical industry have occurred over the last two decades, resulting in incremental adjustments to FDA regulatory approach to quality. Those changes include the globalization of the pharmaceutical industry; advances in the science and management of quality; advances in the pharmaceutical sciences and manufacturing technologies; application of biotechnology in drug discovery and manufacturing; and decreased inspection as a result of fewer agency resources.

The FDA science and risk-based approach to cGMPs could prove to be a shot in the arm for the pharmaceutical industry. (Photo courtesy of Genzyme Corp.)
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“We are approaching the 25th anniversary of cGMPs,” she says. “There have been a lot of changes in that time, and it's time for a re-evaluation.”

The initiative focuses on the cGMPs program and will cover veterinary and human drugs, including human biological drug products such as vaccines. This initiative, according to the FDA, is designed to improve public health promotion and protection by focusing on three major goals that will augment its pharmaceutical product quality assurance programs across the board.

The first goal is to enhance the focus of the agency's cGMP requirements more precisely 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. The second goal will be to help ensure that FDA's essential work in establishing and enforcing pharmaceutical product quality standards does not impede innovation and the introduction of new manufacturing technologies in the pharmaceutical industry. The third goal will be enhancing the consistency and predictability of FDA's approach to assuring production quality and safety among the FDA's centers and field components.

“Our presence in [pharmaceutical] facilities has decreased,” Woodcock says, adding that in 1980, 4,300 manufacturers of human drugs were inspected, while less than half, 1,600, were evaluated by the agency in 2002.

Mark Ellengold, deputy director of the agency's Center for Biologics and Research (CBER), says the initiative has numerous long- and short-term goals. Among the first projects the FDA will take on, he says, 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 view of all drug cGMP warning letters; developing a technical dispute resolution process that integrates technical experts from the centers and addressing perceived inconsistencies between centers.

“We're going to recruit from the industry just like the industry recruits from the FDA,” Ellengold adds.

Intermediate steps include using emerging science and date analysis to enhance compliance programs to target the highest risk areas and evaluate the feasibility of establishing “dedicated cadres” of compliance officers, says Linda Tollefson, deputy director of the FDA's Center for Veterinary Medicine.

“One of the goals is to enhance compliance programs and target the highest risk areas,” she adds.

Long-term goals include enhanced training of agency staff on new scientific approaches and innovative pharmaceutical manufacturing technology; developing and publishing policies and procedures reflecting a science-based, risk management approach; and educating the drug industry on new regulatory approaches that encourage new developments.

“The impetus for this initiative is independent of public comment and higher profile cases,” says David Horowitz, director of CBER's Office of Compliance. “We want to build upon our successes and encourage innovation in the pharmaceutical industry.”

FDA cannot accomplish these goals alone, says John Taylor, director of the Office of Enforcement.

“We'll need international cooperation,” he adds. “FDA will be collaborating with other regulatory authorities to ensure public health protection.”

Given the global nature of pharmaceutical production today, the agency says it fully intends to undertake this initiative in close concert and consultation with its regulatory counterparts internationally.

“Regulatory safety standards are needed to form a safety net,” Woodcock adds.

In addition, the success of this initiative is strongly dependent on active participation and input from manufacturing quality control experts from industry, academia, government, and consumer groups, and FDA will be actively soliciting such participation as the initiative progresses.

“Americans expect that their medicines will be of the highest quality, and assuring that quality is one of FDA's core missions,” says FDA deputy commissioner Lester M. Crawford. “FDA's regulatory and quality control systems for pharmaceutical products have become a gold standard for the world, and we Americans should be proud that the quality of the medicines we have available to us and our animals is second to none. 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 even a very good system better. Publicizing this blueprint for action is just the first step.”



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