GMP Compliance at Indian Drug Manufacturers Questioned by RAPS

Two weeks ago, I wondered if Indian GMP manufacturers are indeed as bad as one would be led to believe based on the constant headline news of FDA’s audit notices to manufacturing sites in India. A review of FDA’s inspections database shows that the truth may be somewhere in the middle. Indian GMP sites are found to have issues but more often these issues are minor and get addressed voluntarily by the manufacturers when pointed out. This week, Regulatory Affairs Professionals Society (RAPS), the largest US-based organization of regulatory affairs experts, published an interesting analysis of the 483s issued to manufacturing sites located in India. On its face value the article seems very critical of GMP compliance of manufacturers in India. It picks some egregious findings to highlight cases of blatant non-compliance. Review of 483s is obviously a much better way to critique the quality of sites. While I applaud the effort by RAPS, an interview with the author of the RAPS article points some issues that must be considered when reading it. The analysis is based on review of about 50 audit letters given to about 20 companies. According to the author of the RAPS article, these 483s spanned about one year period, between July 2013 and July 2014. These 483s were obtained from FDA under Freedom of Information (FOI) request and there were no primary selection criteria for these 483s, except for the location of the audited site, which obviously was in India. Many of the findings listed on these 483s were relatively minor and could have been readily addressed by the companies. There were no obvious trends in these findings. Based on this new information, we went back to our analysis of FDA’s inspectional findings. Every year FDA audits about 2300 manufacturing site audits and issues FDA 483 forms to about 1150 of these sites, hence roughly about 50% of sites audited by FDA get 483 Forms. In the period reviewed by RAPS (July 2013 to July 2014), FDA conducted 114 audits in India, 68 of these audits led to Form 483s, but only 10 of these were OAI (Official Action Indicated). Going back to basics, it seems India sites have on an average similar rate of findings as all FDA inspected sites. As the review of 483s by RAPS pointed out, some of the audit findings are certainly outrageous and should never happen but a review of FDA’s Warning Letters shows that outrageous findings are not India’s monopoly. Unfortunately, it seems the article by RAPS still leaves many questions unanswered and concerns of negative media bias towards manufacturers in India unaddressed. The issue of quality of drugs, extrapolated to safety to consumers, is a critical topic and must be discussed fairly. RAPS for examples has not yet conducted a similar review of 483s issued to manufacturers in China (the other country with as many FDA-approved sites at in India), and other countries that we compared in our article. We re-emphasize that the ratio of compliance to non-compliance in Indian companies is no different than companies in rest of the World. Our aim is not to defend the perpetrators of fraud and malpractice, but painting with a broad brush only sensationalizes the topic without giving it the credibility this discussion deserves. Manufacturing sites in India supply 40% of the generic drugs to the US consumer. There are no known trends for safety concerns related to the drugs manufactured in India. With 2 out of 5 generic drugs coming from India, if there is a systematic problem with GMP compliance at Indian manufacturing sites, it is not known to regulators in the West. FDA plans to double its auditors in India so we should get better data about GMP compliance in India. Or maybe this extra negative publicity has made Indian sites more diligent to avoid past mistakes. Either way, we should find out soon. Till them let’s stop the anecdotes and collect more data to support the truth. The discussion is certainly not over.