Trends In: Foreign Inspections

How much time does your company spend on regulatory inspections? If your answer included the words "too much" followed by an agonizing sigh, you're not alone.

(DORIANO SOLINAS/GETTY IMAGES)

In today's global marketplace, a single manufacturing site may supply more than 80 markets and spend as many as 137 days working on one inspection, according to the European Federation of Pharmaceutical Industries and Associations (EFPIA). The organization's Foreign Inspections Topic team has conducted surveys annually since 2003 among its members. Last year, 22 big and small companies, representing 644 manufacturing sites worldwide, responded. Of the 644 sites, 211, or 33%, had at least three inspections in 2007; 6 of them had more than 10 inspections.

Some of the most interesting survey results: It typically takes about 137 work days (i.e., 8-hour days, totaling 1096 working hours) to host an inspection. This includes 80 to 100 days for preparation (e.g., reviewing, compiling, summarizing, crafting presentations); about 17 work days per inspection day (accounting for multiple employees) for inspection management during the inspection itself; and 20 days for administrative followup.

The data also show that companies overall spent as many as 106,158 days dealing with inspections by foreign inspectorates, says EFPIA Topic Team Chair Stephan Roenninger, global quality manager at F. Hoffmann-La Roche (Basel, Basel-Stadt, Switzerland). The most active inspectorates in order of activity reported are those from the European Union, United States, Brazil, Japan, Mexico, South Korea, and Uganda.

Considering that the average person in Europe works 220 days per year, this totals about 483 years of employee resources. In turn, inspectors spent 3054 days on foreign inspection activities in 2007 at the sites of the companies surveyed in addition to their local inspection responsibilities.

Overall, inspection numbers are going up on both the manufacturer and regulator side. The number of days that surveyed companies spent on foreign inspections increased by 51% between 2006 and 2007. And even though the number of sites the companies had decreased by 3%, the number of foreign inspections they had increased 34% during the same period. Add to that inspections by local authorities, and there is a 130% increase in the number of inspections between 2003 and 2007, and a 172% increase in the time inspectors spent doing inspections between 2003 and 2007. In fact, many companies participating in the annual EFPIA survey have seen a 16% to 20% increase in inspections every year since 1999.

Fast Facts...

This change may be, in part, because there are now 43 inspectorates conducting inspections outside their own borders, says Roenninger. The following countries reported to EFPIA that they recently started doing foreign inspections: Botswana, Costa Rica, Ethiopia, Morocco, Serbia, and Iraq.

Compare the statistics compiled by EFPIA to those from a typical plant in the United States over a recent calendar year. The Pharmaceutical Research and Manufacturers Association (PhRMA) Quality Technical Group conducted a similar initial survey between 2004 and 2006 focusing on FDA's risk-based inspections. Nine companies reporting for 57 sites participated. Zena Kaufman, divisional vice-president at the Quality Center of Excellence at Abbott (Abbott Park, IL), presented data from the PhRMA group at the 2008 PDA/FDA Joint Regulatory Conference.

A typical US plant experienced 84 days in which an inspection was occurring in one year's time. Considering that the average plant is operational 250 days per year (52 weeks x 5 days -10 holidays), about one third of a plant operations can be tied to inspection activities, not to mention how many persons were involved in inspection activities.

Other early results from PhRMA show that the number of inspections in the Americas increased between 2004 and 2006, but stayed relatively the same for inspections outside the region during the same period. There was a higher reported facility complexity in the Americas and the Asia-Pacific region, as compared with the European Union. The PhRMA Quality Technical Group intends to continue the survey and to possibly expand or work with EFPIA, said Kaufman.

Both surveys beg the question: Given the amount of time and effort that go into foreign inspections, is there a better solution to assuring compliance? Can joint inspections or sharing of knowledge about sites come soon enough in a global supply chain?

"More sharing of assessed risks to GMP and compliance at manufacturing sites between industry and/or regulators is certainly needed," say Roenninger and Kaufman. "Awareness, multi- and bilateral confidentiality agreements facilitated by harmonized training and trust between inspectorates such as membership of inspectorates in PIC/S should also be encouraged."

Adds Roenninger, "In addition, administrative instruments (e.g., the World Health Organization's certification scheme on the quality of pharmaceutical products) providing for governmental regulatory processes for certifying manufacturing sites should be encouraged as well."