Paul D’Eramo—former ISPE chair, a two-decade veteran of FDA, and current head of Quality and Compliance Worldwide for Johnson & Johnson—always has a finger on the pulse of the regulatory environment, and knows that GMPs are fluid, not static. “We are always searching for what the ‘c’ in cGMP is,” he says.
At October’s ISPE 2008 show in Boca Raton, Florida, D’Eramo offered his take on current trends that are shaping GMPs. Though not surprising, his are the words of experience and insight:
1. There’s a new inspection model: FDA has become an international organization, and there is an increasing number of plant inspections being done by many countries’ regulatory authorities, D’Eramo says.
These authorities are sharing inspection, recall and adverse event data to a degree that they never have before. They’re training together, primarily through the PICs sessions that occur two to three times a year. These trends will continue. “Eventually we might see mutual agreements between countries to accept each other’s inspections,” D’Eramo says.
2. Regulators hold manufacturers responsible for quality and safety: Aware of the ever increasingly complex supply chain and the impossibility of keeping track of all plants, regulatory authorities are holding manufacturers—or, to be specific, license holders—ultimately responsible for Quality and Safety. While in the U.S., Congress has allocated more funding for FDA, it has also increased manufacturers’ responsibilities for contamination testing, labeling, and the number of products to which they must apply GMPs.
D’Eramo notes how FDA’s CDER director Janet Woodcock has said that all parties throughout the supply chain have to be responsible for their product. FDA must have the tools to hold these parties accountable, D’Eramo says; in particular, it must build an active, accurate database of pharmaceutical facilities. Yet FDA will continue to be limited in its resources, and thus will wield its authority through legal action. “They haven’t been afraid to do this in the past, but they will do this moreso,” says D’Eramo. “If they feel that management is not taking action [to resolve GMP issues], they’ll go for legal actions.”
In Europe, the EMEA has increasingly placed the burden of drug quality and safety on the “Marketing Authorization Holders,” and the role of the Qualified Person (QP) within each organization. It has also been requiring that drug manufacturers submit their own audit reports to health authorities—for example, EMEA has asked J&J API manufacturers to submit audit reports to verify that they have been visiting suppliers, says D’Eramo.
Japanese authorities are focusing on the Marketing Authorization Holder as well. In addition, Japanese inspectors are starting to inspect facilities outside Japan—and have done this with a few J&J sites, D’Eramo notes.
3. There is the continued trend towards harmonized global standards: This is see chiefly in ICH and its stipulations for GMPs, Quality by Design and Quality Systems. GHTF, ISO, and ASTM are also encouraging this trend. The heparin crisis of the past year has had a broad impact on evolving standards. It caused ICH to beef up sections within Q10 on supplier control and sourcing materials (careful supplier selection, clear documentation, etc.), and has put more of an emphasis on a lifecycle approach to quality within standards.
4. Regulators are promoting innovation . . . and providing regulatory relief: FDA in particular has realized its potential to promote (rather than stifle) innovation, and has made several key changes:
--It has come out with more reasonable Part 11 requirements for electronic documentation.
--New validation guidelines, which are pending approval, will allow manufacturers to facilitate PAT, real-time processing, and other efforts that are being undertaken.
ICH’s focus on Quality by Design will also stimulate new ideas and practices, and the use of tools for risk management, PAT and modern Quality systems.
5. New regulatory/registration requirements are ongoing. One is the trend toward reduced filing requirements for process changes (with fewer supplements)are also a positive sign, D’Eramo says. Merck’s ability to gain approval of Januvia through real-time release data is a great example of what such an environment can enable. “These things are all significant enough to help us all out with the business case” for adapting practices, D’Eramo concludes.
6. There is greater transparency in all manufacturing practices, D’Eramo says. If there are any issues or recalls, “the whole world knows about it.”
--PWT
