FDA strives for more efficient drug regulation

It's almost as if the U.S. Food & Drug Administration just got back from a stint in a self-help program to deal with its regulation of drug manufacturing. Within the drug industry, if drug makers use technology with which FDA is not familiar, that can be bad. If, on the other hand, industry is shy about using newer technology on the theory that FDA will best accept the old and familiar, that's also bad. If FDA's own practices and priorities don't match the size of the risk involved, that can also be bad.

FDA is saying it recognizes the problems and is working on solutions. Because of problems like these, as well as others, a couple of years ago, FDA realized it needed to re-think its whole approach to the regulation of drug manufacturing in order to keep up with industry advancements and find a way to encourage the use of the best technologies while still enhancing quality.

The agency's final report on drug manufacturing practices emerged in September after a two-year effort targeting a variety of goals all at once, but summarized as modernizing the regulatory controls over drug manufacturing. The key concept in this effort was to align the agency's efforts and resources with the relative degree of risk posed by specific products and processes (see PD, Oct. '02, p. 28 or visit www.packagingdigest.com/Legal/ 1002legal.php).

FDA regulates all aspects of drugs, requiring premarketing confirmation that a drug is safe and effective and properly labeled, and also elaborately regulating the process of drug manufacturing, aiming to assure that drugs are made right the first time and every time.

The conceptual foundation of the agency's program of "Current Good Manufacturing Practices (CGMPs)" is all about following recipes for how to make products, handle them, move them and package them. You might well be able to eyeball and surmise your way to a finished drug product of the correct safety, strength, quality and purity each time, but FDA says that's not good enough. You must have control over your process, and you must be able to prove it. And that goes well beyond merely proving that you have a properly made, finished product. You must also be able to demonstrate that you followed each established step of your manufacturing process.

Then, in 2002, it announced its overhaul of these regulatory requirements, FDA said it wanted to do a lot of different things, but the most important was to change the system to align risks with resources. That is, the agency wanted to ensure that its efforts are being weighted toward the hazards and products that present the greatest risks, rather than mechanically applying all requirements equally. They also want the CGMPs to be better guided by science, integrated systems, international cooperation and, of course, protection of the public health.

While this is a final report, and some interim steps have already been taken, the report is more likely the start to a future effort, for which a Council on Pharmaceutical Quality has been formed and will undertake implementation of the many complex recommendations. Some of this stuff is best left to the organizational junkies. For example, the agency says it already has adopted a "quality systems approach" to improving drug regulation, even adopting the approach to improving its own internal operations. FDA's staff manual notes: "The FDA Quality System Framework is organized into four main components built upon a fifth Quality System Infrastructure component. The four components, or areas of responsibility, are Strategic Management, Resource Management, Lifecycle Management and Quality System Evaluation."

FDA has also developed a guidance document to help industry design its own CGMPs from a quality systems perspective that incorporates the risk-based assessment system.

And how does this risk-based assessment system translate into action? Well, for one thing, FDA has commissioned a study of 13 years' worth of data from inspections. Reports of more than 38,000 inspections of 3,700 manufacturing facilities are being reviewed in order to generate a statistical analysis of factors that relate to inspectional outcomes. They will examine which types of products, processes, facilities, manufacturers and even FDA characteristics tend to be associated with different types of violations or inspectional observations.

FDA is also about to start testing a "risk-based model for prioritizing sites for manufacturing inspections"-a model that the statistical study of inspections will enhance. Another conceptual underpinning of this effort is found in FDA's determination to make its regulatory decisions based on sound science as a way of keeping pace with industry advancement. FDA says in its final report, "As pharmaceutical manufacturing evolves from an art to a science and an engineering-based activity, application of science and engineering knowledge in regulatory decision-making, establishment of specifications and evaluation of manufacturing process should improve the efficiency and effectiveness of both manufacturing and regulatory decision-making."

Undeniably, any government body whose goals are to be led by sound science in an effort to more fairly and effectively oversee and enhance the development of an industry is on the right track. The continuing implementation of these CGMP enhancements will reveal if FDA is true to its word.

Eric F. Greenberg is Of Counsel to the Chicago and Washington, DC, law firm of Ungaretti & Harris, where his practice is concentrated in food and drug law, packaging law and litigation. Contact Eric by e-mail at efgreenberg@ uhlaw.com; by phone at 312/977-4647; by fax at 312/977-4405; or write Ungaretti & Harris, 3500 Three First National Plaza, Chicago, IL 60602.

The key concept in this effort was to align the agency's efforts and resources with the relative degree of risk posed by specific products and processes.