FDA Faces Many Challenges in Auditing Foreign GMP Sites

A GAO report on FDA’s foreign inspections paints a very dire picture for the current status of inspections. There are about 5000 manufacturing sites registered with FDA of which 3000 are located outside of the US; about 1000 of these foreign sites have never seen an FDA audit. With about 40% of finished products and 80% of API manufactured at locations outside the US, GAO raised concerns about the effectiveness of FDA’s resources to monitor quality of the US drug supply chain. FDA has made huge strides in ramping up its foreign inspections over the last 6 years. It audits almost the same number of foreign sites as domestic sites and focuses its resources in countries that have bulk of the non-US FDA-registered manufacturing sites, namely India and China. Sites in India get audited at rates more than double that of those in China. That said, the majority of sites that have never been inspected by FDA are also located in India, China and South Korea. About 33% of FDA-registered sites in India, 45% of those in China and 90% of those located in South Korea have never been inspected by FDA. Practically every one of the 150 countries with FDA-registered manufacturing facilities has sites that have never been visited by FDA but actively export finished drugs or API to the US. Since 2008, FDA has established offices in 7 countries to better coordinate its in-country inspections but over time it has faced numerous challenges. FDA is finding it hard to fill vacancies in foreign offices with about 46% vacant positions. There are several reasons for this. An FDA official can only be stationed at a foreign office for 2 years, extendable annually to up to a total of 6 years in one country. After that personnel can rotate to another country but the total time out of US cannot be more than 12 years. In addition, FDA inspectors can do short stints of 30-, 60-, 90- or 120-days at the foreign offices. It could take up to a year to get security clearance for FDA personnel to be stationed in another country. After return, these personnel face uncertainty in reintegrating into FDA’s domestic offices. There is practically no debriefing of the returning inspectors so most of the skills and relations developed by an individual inspector are not leveraged for future growth of the office or the personnel. In addition, inspectors face numerous financial, personal, security, environmental and administrative hardships making it very unattractive for domestic inspectors to volunteer for foreign deployment leading to a huge gap in the demand and supply of skilled inspectors at FDA’s foreign offices. The GAO report sites numerous instances where FDA inspectors found egregious violations thanks to their presence and relationships with local regulators in a foreign country but these incidences highlight the gaps rather than calm the concerns as these events were likely happening undetected at other uninspected locations. FDA assured GAO investigators that its plans to visit every single registered drug manufacturing site in the World in the next 3 years. FDA also assured that it is formulating measures to recruit inspectors to foreign offices and address the deficiencies identified by GAO. GMP issues were the primary reason for delays in new drug approval in 2016 which means more organizations failed to meet the minimum standards for GMP when audited. Last few years have seen numerous reports of shocking violations at foreign manufacturing sites but also a resulting improvement in the quality as the violators rectified the errors and passed subsequent inspections. With more sites getting audited, we can expect further improvements in the quality of the supply chain.