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Since 2007 my colleagues and I have been collecting and testing samples of essential medicines from around the globe. India is the largest producer of generic drugs in the world, providing over 40 percent of our samples across the 21 countries studied. India has also received more complaints from the FDA than any other producer nation, epitomized by the underhand nature of the operations at Indian company Ranbaxy, which resulted in seven felony counts and $500m in fines and penalties against the company from a US court. But most of the substandard products Ranbaxy made were for emerging markets. As a result, we decided to assess whether some Indian drug manufacturers cut corners and made substandard drugs for markets with non-existent, under-developed or emerging regulatory oversight, notably Africa.
In 2014 we published a working paper with the National Bureau of Economic Research, which was subsequently published in the American Journal of Health Economics (2016 Volume 2, Issue 3, p.373-398). The paper assessed the quality of 1,470 antibiotic and tuberculosis drug samples that claim to be made in India and were sold in Africa, India, and five mid-income non-African countries. Roughly 11 percent of those products had insufficient active pharmaceutical ingredients (API), and the vast majority of the failures were substandard (not counterfeit) as they contained the correct API and the packaging looked correct.
In other words while a few products were falsified medicines, counterfeits of legitimate Indian generics, most of the quality failure was not due to criminal counterfeiters. The distribution of these substandard products was not random: they were more likely to be found as unregistered products in Africa than in India or non-African countries. Since this finding is robust for manufacturer-drug fixed effects, one likely explanation is that Indian pharmaceutical firms and/or their export intermediaries do indeed differentiate drug quality according to the destination of consumption.
The reaction from Indian industry and the Indian government was very hostile. Amongst other complaints, the Commerce Ministry threatened to sue us for criminal defamation, until cooler heads prevailed and showed they had no standing and no case.
But the fact that the Indian government would threaten four academics (including an Indian national) with a crime punishable by up to two years in jail, shows their willingness to silence critics. And criticism like this has a chilling effect on those seeking to work in India.
Our data were not conclusive, merely indicative. Cost prohibited a more thorough analysis of all samples, but a representative sample of 100 antibiotic and tuberculosis products from West Africa were subjected to Raman spectroscopy and 14 percent were identified as being substandard. Raman spectroscopy can be used to identify the components of drugs by measuring wavelengths sent through compounds. In this case, we used it to measure the level of active pharmaceutical ingredients (API) in the sample to assess their quality.
More importantly, the Raman spectra of the good products could be used for a new and more rapid assessment in the same regions, targeting the same products at a later date.
And that was the aim of this paper. We used those spectra to test newly procured products and see whether quality has improved in the past five years since the products were first procured.
Has quality of Indian medicine improved?
Using the Raman spectra of good quality medicine created in 2014, 100 of exactly the same antibiotic and tuberculosis medicines (ciprofloxacin and rifampicin) were sampled from the same places in Nigeria and Ghana. In 2014, 14 percent failed, with several others being borderline passes. In 2019, 15 percent failed with fewer borderline passes. As can be seen in the graphic below, a comparison of the p values (presented from lowest to highest) from 2014 and 2019 shows a very strong correlation.
In simple terms, the quality of Indian-made products was virtually identical in 2019 as compared with 2014. Most of the products were fine, but a sizeable minority (around one in seven) was inferior. As in 2014, most of the problem is due to substandard production.
No change in quality
At first glance the data are unsurprising since the situation has not changed in the past five years — one in seven of these medicines in West Africa do not work. But over the past five years much light has been shed on the quality problems of Indian medicine. Dozens of FDA sanctions, major media coverage of the Ranbaxy fiasco, and more importantly, the problems with Indian medicine has received significant media and political coverage in West Africa.
A prime example of this was following a report from US Pharmacopeia (USP). USP is very active with regulators in emerging markets, and it demonstrated that uterotonic medicines from India and China failed most of the time in Ghana. Unfortunately USP redacted the report, which originally named offending Indian and Chinese manufacturers, and even covered it up when pushed. The original report can be found on the internet archive.
In my next post I will attempt to explain why quality has still not improved despite the actions taken against drug manufacturers.
A sizeable minority of Indian drugs exported to Africa (around one in seven) is inferior, mostly due to substandard production processes.
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