FDA Foreign Inspection Programme under Review

GMP News
30 January 2008

FDA Foreign Inspection Programme under Review

FDA's Foreign Inspection Programme deals with inspecting manufacturers outside the USA. Many of the manufacturers of medicinal products and active pharmaceutical ingredients are located in Europe and Asia. The five countries with the largest number of inspections are (in this order): India, Germany, Italy, Canada, and the UK. Interestingly, this does not correspond to the number of production sites in these countries. China, for example, has 714 sites delivering products to the USA and is thus the by far most important exporter of medicinal products and APIs. Yet, China does not rank higher than 7th among the most frequently inspected countries (88 inspections since 2002). In comparison, India has 410 sites, and Canada and Germany rank 3rd and 4th with only 288 and 199 sites to be supervised respectively. The same lack of correlation can be observed with regard to Italy, the UK, France, Japan, Switzerland, and Ireland.

Click for a larger version.

The US Government Accountability Office (GAO) supports the US Congress in supervising federal institutions with regard to their efficiency ("investigative arm of Congress"). As long as 9 years ago, the GAO found out that the FDA must improve its programme for inspecting manufacturing companies outside the USA. Now a new study has again found weaknesses. The following text is an excerpt from the report:

FDA’s effectiveness in managing the foreign drug inspection program continues to be hindered by weaknesses in its databases. FDA does not know how many foreign establishments are subject to inspection. Instead, FDA relies on databases that were not designed for this purpose. Further, these databases contain inaccuracies that FDA cannot easily reconcile. One database indicates there were about 3,000 foreign establishments registered to market drugs in the United States in fiscal year 2007, while another indicates that about 6,800 foreign establishments actually imported drugs in that year. FDA recognizes these flaws. Further, because the databases cannot exchange information, any comparisons of the data are performed manually, on a case-by-case basis. FDA officials told GAO that they have not generated an accurate count of foreign establishments whose drugs are imported into the United States.

FDA inspects relatively few foreign establishments. Data from FDA suggest that the agency may inspect about 7 percent of foreign establishments in a given year. At this rate, it would take FDA more than 13 years to inspect each foreign establishment once, assuming that no additional establishments require inspection. However, FDA cannot provide an exact number of foreign establishments that have never been inspected. Most of the foreign inspections performed are conducted as part of a review associated with processing an application to market a new drug, rather than inspections for monitoring the quality of marketed drugs.

Inspections by Type.

Although FDA uses a risk-based process to develop a prioritized list of foreign establishments for inspections to monitor the quality of marketed drugs, few are completed in a given year. This prioritized list was used to select foreign establishments for inspection in fiscal year 2007. According to FDA, about 30 such inspections were completed in that year and at least 50 are targeted for inspection in fiscal year 2008.

The foreign inspection process involves unique circumstances that are not encountered domestically. For example, FDA relies on staff that inspect domestic establishments to volunteer for foreign inspections.

Click for a larger version.

Unlike domestic inspections to monitor the quality of a marketed drug, FDA does not arrive unannounced at a foreign establishment. It also lacks the flexibility to easily extend foreign inspections if problems are encountered, due to the need to adhere to an itinerary that typically involves multiple inspections in the same country. Finally, language barriers can make foreign inspections more difficult than domestic ones. FDA does not generally provide translators to its inspection teams. Instead, they may have to rely on an English-speaking representative of the foreign establishment being inspected, rather than an independent translator.

The complete recording of the US Congress Hearing on the FDA Foreign Inspection Programme can be found here.

Prepared by:
Oliver Schmidt
On behalf of the European Compliance Academy (ECA)

Go back

GMP Conferences by Topics