Is the FDA at Fault for Allowing Drugs Made in India Despite Multiple GMP Violations?
[Posted on: Thursday, November 19, 2015]

It seems we stirred the hornet’s nest when we posted that Indian drug manufactures are not as bad in GMP compliance as the prevailing perceptions the media would have us believe. A review of the FDA’s Inspections database indicates that auditors find similar numbers of major and minor findings in India as at sites located in other countries. We received more than 100 comments that our analysis was too generalized, and that the actual citations of non-compliance point to a trend for more serious violations. One commenter claimed that in his experience, 95% of Indian manufacturers are non-compliant; it is just that FDA is not able to catch them. A few more commented that Indian companies have a culture of deliberate non-compliance, and one poster even stated that perhaps FDA should ban all drugs manufactured in India altogether.

Overall, most readers confirmed the strong negative perception regarding GMP compliance at Indian drug manufacturing sites based on public information and/or  personal experiences. By serendipitous luck, a week later RAPS published its own review of 483s issued to Indian drug manufacturers which highlighted some atrocious findings. The RAPS article attempted a deeper review of the 483s to find trends, but did not present any statistical analysis to further educate the reader about the rate of occurrence; repeatability of similar violations; responses to FDA findings; or the impact of these findings on the safety of the drugs manufactured at the violating organizations.  The article pointed out that several Indian manufacturers had been cited to import alerts but did not address if these number of alerts showed a higher, lower, or similar trend per number of registered sites compared to other exporters of drugs to the US.
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The same week a large Indian manufacturer, Dr. Reddy, received a Warning Letter for GMP violations at three of its sites in India. When very resourceful Indian multinational companies are caught with such serious and blatant GMP violations, it is an inherent natural response for a reader to extrapolate that all others behave the same. The incidences of non-compliance at sites in India highlight a major problem.
 
Let’s clarify a few things. According to the FDA, approximately 50% of all audits in India lead to no findings. 40% of these audits lead to findings that are minor or moderate and can be easily remedied by the manufactures. In 10% of the cases with major findings, the FDA has issued several Warning Letters and Import Alerts (IA). The findings at Indian manufacturers mostly show ignorance of best practices or blatant risk taking. FDA has published these findings and enforced its rules, where violations were found. But is that enough to protect the US consumers? Should FDA take these trends into consideration and bad drugs from the entire country? A review of FDA’s Import Alerts show that manufacturers in practically every country in the World have been subject to import alerts of one kind or the other. The FDA has not announced any broad action against Indian companies other than doubling the number of auditors in India. Even in the case of GVK Bio, when European countries banned products tested at GVK Bio, the FDA refused to enact a similar ban for the same products. Indian companies deal with a non-competent local regulatory body that is ill-equipped to enforce GMP standards. Indian regulators have been repeatedly challenged to enforce GMP standards in vain. Indian regulators seldom conduct GMP audits or accompany FDA auditors on FDA audits. With lax local enforcement, India is a fertile ground for manufacturers self-interpreting the international rule, and only later discovers their interpretations are faulty when audited by an FDA or European auditor. Many readers commented that the main reason for manufacture non-compliance is lax enforcement of the laws. With this background, the FDA has little option but to increase its enforcement activities in India and take strong action against the violators.  One thing we have learned from the reader comments is that if the FDA were to increase its enforcement activities in India, it will have a lot of supporters and sympathizers in the Indian regulatory community. Over the last few years, the FDA has steadily increased its audits in India, and this is expected to have the desired impact on quality of drugs manufactured in India.

Expert Opinion: Mukesh Kumar
VP, RA, Amarex Clinical Research