FDA outlines new risk-based strategy on GMP

The FDA's reputation has been dented in the wake of high-profile drug safety cases such as Merck & Co's withdrawal of the painkiller Vioxx (rofecoxib), and it emerged last month that drug complaints filed with the agency reached a record high in 2004 - up 14 per cent from the previous year to 422,500.

But Steve Niedeleman, assistant commissioner for regulatory affairs at the agency, told the FDLI​ meeting that risk-based management is helping to identify and target violations that have the greatest potential public health impact, so that the agency can focus inspections in areas of the greatest need.

Risk-based management is being applied to the areas of good manufacturing practice (GMP) compliance - timely given the recent problems at Chiron Vaccines and GlaxoSmithKline - as well as supply chain integrity and counterfeiting and safeguarding FDA-regulated goods from perceived terrorist threats.

In the area of GMP compliance, the FDA has set up a pharmaceutical inspectorate consisting of specialised teams that are experts in drug manufacturing technologies, boosting the agency's ability to conduct high-risk inspections that are technologically challenging. The team will carry out both foreign and domestic inspections, focusing on facilities that use complex technologies.

The FDA's efforts to update its guidance on GMPs, started in 2003, continued last year with the start of a domestic pilot programme to implement the draft guidelines. The agency is currently working towards finalising this guidance document.

The theme of GMPs was taken up later in the meeting by Douglas Throckmorton, acting deputy director of the FDA's Center for Drug Evaluation and Research (CDER).

He told the meeting that the rationale underlying the guidance is a a shift from an assessment and development model to one focused on implementation and actualisation. This can best be accomplished, he added by: encouraging best practices in manufacturing through providing greater flexibility based on the understanding of manufacturing processes; encouraging risk-based approaches; enhancing coordination, consistency and predictability in the process; and getting international cooperation.

In fiscal 2005 the FDA will begin a pilot programme that deals with risk-based approaches, he said, adding that the agency will also work on improving its own internal policies and programs for regulating drug quality, and training staff. The new pharmaceutical inspectorate will be akey element in this strategy, said Throckmorton.

Also, he noted that to improve cross-agency coordination, a Council on Pharmaceutical Quality has been set up to collaborate with other regulatory bodies. The FDA is seeking membership in the Pharmaceutical Inspection and Cooperation Scheme to add to its involvement in the International Conference on Harmonisation (ICH) process.

Drug safety​

While there are concerns about drug safety and the integrity of the FDA process, there are also those who fear that an overemphasis on safety will adversely affect the development of new products, according to Throckmorton.

The FDA's bid to find a new path to restore confidence in this area was kick-started by acting commissioner Lester Crawford in November 2004, who put forward a plan to revamp the drug safety reporting system, appoint an Office of Drug Safety director, and publish risk management guidelines.

In addition to the drug safety oversight board, the FDA also is setting up a drug watch website page and will provide drug safety sheets for medical to provide earlier communication on emerging safety concerns.

Imports and Fakes​

On the issue of drug importation, Niedelman said that ensuring safety of these products was a major challenge for the FDA because it simply does not have the resources to inspect incoming products.

On the other hand, the agency believes it cannot simply adopt a 'buyer beware' attitude given the potential risk to consumers of expired, counterfeit, subpotent or mislabelled drugs entering the marketplace.

This means the FDA has to use a risk-based approach here as well, targeting its efforts on areas perceived as the greatest threat. So, the emphasis is on battling counterfeiting, which is a growing problem because the fakers are becoming increasingly sophisticated and well-organised.

He pointed to the 2004 FDA task force report encouraged the development of new technology to deal with counterfeiting, such as track-and-trace technology, and the education of both consumers and health professionals. Foreign stakeholders have been increasingly cooperating with the FDA on this issue, he added.