1. Reduced number of inspections by FDA: Obtaining the approval of FDA involves visits of the production facilities by FDA's own inspectors. Whilst the number of approved generics increased (for meeting the election promise of the current Trump administration), the number of FDA inspections (both international and domestic) dropped in the fiscal year of 2018. In the 2018 fiscal year, FDA inspections in China (having a market share of around 8% in the US) decreased by approx. 11%. On the other hand, FDA inspections increased by 18% in India (having a market share of 38% in the US and is the world's largest exporter of generics).
This reduction-increase was justified by the FDA as the strategic targeting of facilities that had a certain risk score based on past inspections. Furthermore, FDA's agreements with EU counterparts ensure there is no duplication of work. However, the agreement does not cover India and China.
2. Production of substandard active ingredients: In May 2017, an FDA inspector pointed out the production of substandard active ingredients at the Linhai (China) factory of Zhejiang Huahai Pharmaceutical Co. Ltd, a supplier of active ingredients to big pharma and generic pharmaceuticals (e.g. Teva). These active ingredients did not meet FDA's criteria.3. Malpractice by manufacturer: The manufacturer had obtained results showing that some batches did not meet the FDA's criteria and contained unknown contaminants. Their responses were to ignore the results, omit the results from the official records, and record falsified data that indicated the products meeting FDA's criteria. Regarding the contaminants, they are supposed to attempt at identifying and rectifying these and communicate the presence of such contaminants to the FDA. The FDA inspector discovered these faux pas and noted that this was not the first time they did so. Furthermore, in 2016, Chinese regulators directed Zhejiang Huahai to withdraw applications for selling new drugs, should the application be based on false or incomplete data. Consequently, Zhejiang Huahai withdrew its applications for epilepsy, blood pressure, and depression generics and blamed flawed testing by a local contract research organisation.
4. Questionable decisions by FDA: The FDA inspector recommended penalising the manufacturer by making the approval of the sale of new drugs/active ingredients in the US contingent on the inspected products and manufacturing facility addressing the shortcomings or meeting quality criteria. However, FDA managers decided not to follow the recommendations of the FDA inspector, claiming that previous inspections of the facility came up with nought.
The end result of these manufacturing and regulatory pitfalls is the consumption of contaminated medicines by patients for at least four years. No one would have been any wiser had not a company who purchased valsartan from Zhejiang Huahai spotted the contamination.
My next post will disentangle the implications of such manufacturing and regulatory pitfalls.
References:
All of Bloomberg's investigative pieces listed below:-
https://www.bloomberg.com/news/articles/2019-03-27/tainted-generic-drugs-force-fda-to-tighten-safety-regulations
https://www.bloomberg.com/news/articles/2019-03-01/third-potential-carcinogen-found-in-blood-pressure-drugs
https://www.bloomberg.com/news/features/2019-01-31/culture-of-bending-rules-in-india-challenges-u-s-drug-agency
https://www.bloomberg.com/news/features/2019-01-30/chinese-heart-drug-valsartan-recall-shows-fda-inspection-limits
https://www.bloomberg.com/news/features/2019-01-29/america-s-love-affair-with-cheap-drugs-has-a-hidden-cost
https://www.bloomberg.com/news/articles/2018-08-09/red-flags-raised-at-chinese-heart-drug-maker-year-before-recall
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