A quick trivial pursuit: Which pharmaceutical regulatory body annually performs the most foreign inspections—that is, visits to facilities outside its region of authority? If you said FDA or EMEA, you’re wrong. Japan? No.
Give up? Try Brazil’s ANVISA. According to data compiled by an EFPIA working group of 24 companies, Brazilian regulators performed more drug plant inspections outside Brazilian borders than did any other agency outside its primary area of jurisdiction. While the data is not comprehensive and all-inclusive, it does point to a critical compliance concern among industry representatives: Everybody seems to be inspecting, anywhere.
From that same data set, EFPIA found that total inspection days of foreign inspections for those 24 companies in 2008 to be 3591 days, roughly twice as many as five years before. The number of inspections per site: most sites have 2-3 inspections per year, but one site had 18 in 2008.
“We are seeing an increasing frequency of inspections from FDA and the rest of the world,” says John O'Connor, PhD, senior director of Corporate Inspection Management for Genentech. “The question is, what’s the value of a duplicate inspection? We don’t believe it adds value to the product. But it costs us.”
O’Connor spoke recently at the BIO 2009 meeting in Atlanta.
- Quality risk management based upon risk assessments and QbD
- More reliance on ICH guidelines Q8, Q9, and Q10
- Review of supply chains, especially for materials from China and India
- Documentation review for license renewals in Japan and Canada (an “encouraging” development, since it obviates the need for a site inspection)
Sure, inspectorates need guarantees that regulations are met, and are there to ensure safe medicine for the patient, says O’Connor. But inspections carry not only significant costs to the manufacturer, but to the agencies who perform them as well. “The concern that I have is that these resources aren’t being directed toward other quality efforts,” he says, citing anticounterfeiting as just one area in need of greater support and attention.
O’Connor also shared data on the habits of regulators during their visits. The most intriguing nugget: While FDA spends approximately 75% of its time on site reviewing documentation (and thus 25% touring the facility), EMEA is just the opposite, spending three-quarters of its time touring. Other major global regulatory agencies—Japan, Brazil, Korea, Mexico—spend more time on documentation than touring, O’Connor notes.
FDA’s top areas of focus, O’Connor says, are: deviations/investigations; role of the quality unit; buildings and facilities; raw materials/supply chain; and equipment/cleaning validation.
EMEA’s areas of focus are similar, but also include laboratories and issues of process control.
In the end, O’Connor says we need a global solution to ease the burden. Mutual Recognition Agreements (MRA’s) and the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) are a good start, he says, but it’s just not enough. Could inspection reports be shared? O’Connor asked rhetorically.
He’s not confident that regulatory harmonization will happen quickly or easily. Take the dilemma of global differences in pharmaceutical clean room classifications. “If we’re lucky, my grandchildren will see it harmonized,” he says.