The bitter side of India’s pharma story

Katherine Eban’s Bottle of Lies: The Inside Story of the Generic Drug Boom is a well-researched, if stinging, indictment of at least a couple of major pharma companies of India whose exports make a big slice of India-made generics consumed in the US and elsewhere. The author does not soft pedal her narrative, and calls out companies indulging in fraudulent practices. In the process, the book also casts doubt on the India-as-pharmacy-of-the-world story. Nor does the book spare the USFDA which has had its quota of rule-bound bureaucrats, unwilling to act with needed alacrity.

Evasive, dishonest practices

The book documents the allegedly evasive, dubious practices of, among others, Ranbaxy, Wockhardt, Mylan, the CRO Vimta Labs, and GVK Biosciences — and to a smaller extent Zydus and Dr Reddy’s — in manufacturing, documenting and exporting medicines to the US. Some of these companies were/are big names. The USFDA has admittedly stricter standards.

If you are exporting to any country, you need to comply with that country’s regulatory requirements. Going by the narration in the book, documentation at the manufacturing sites of these companies was cooked up, tests for dissolution and stability, and chromatograms were not done but copied from that of the reference drug and recorded as having been done, blue glass shards were found in the bulk drug atorvastatin but this was sought to be hidden and tablets made of such a faulty bulk drug were exported, unhygienic/unsafe practices of workers/staff were common, etc.

Even after being given a chance to rectify the mistakes, it was not done. Data integrity was sorely lacking. Medicine batches, that did not comply with GMP and quality requirements, were considered fit for export to Africa instead of being destroyed. “Indian executives approached the regulatory system as an obstacle to be gamed”. All these even by capitalist standards of maximising bottomlines, is reckless.

If big Indian pharma companies with billion dollar sales can play hard and fast with quality and manufacturing practices for products for a country with the most (grudgingly) admired drug regulatory agency in the world, what could our pharma companies be doing with products for the domestic market with decidedly less effective regulation?

It is easy to blame the tyranny of documentation, but it is insisted upon so that it is a double-check on whether the approved process and the SOPs are indeed followed. The other damage dishonest behaviour and shoddy manufacturing practices does is that it reinforces the stereotypical India script: decrepit, developing country, no ethics, poor documentation, poor hygiene (“employees failed to wash their hands after using the toilet”).

Brands the solution?

By the end of the book, the author has managed to alarm, if not convince, the uninitiated reader that generics and especially if Made in India, tend to be bad and therefore the answer is to go for brands, preferably made in the US. This point is made repeatedly at several places in the book.

However, this is neither correct nor logical. Brands will not solve the problem. And this is why.

Brand names in the author’s telling means innovator company’s brands. Generics are drugs not under patent, or medicines with patents expired. The author does not elaborate — when she advocates brands over generics — how a branded medicine, even if made by the innovator, is superior ipso facto to an unbranded equivalent. Both can be quality medicines if made scientifically and ethically, and both can fail if made badly.

The other misleading message of the author is that only the original innovator of, say, atorvastatin (brand Lipitor of Pfizer), can make the medicine of acceptable quality; and generics can seldom match the originator in quality. If that were the case, we would not be able to run any health programme. It is also an argument for a monopoly in perpetuity, by other means, for the innovator — which in turn will make universal availability, affordability and access to healthcare impossible.

Thirdly it is a bit late to restrict manufacture to the originators as most useful products have been out of patent for decades.

Issues in bioequivalence

The author also chooses to underplay the nuances of the debate on bioequivalence of generics and the innovator product. A generic is bioequivalent to a brand or innovator’s product if the two products behave about the same in the human body. Most regulators insist that first time generic manufacturers of a drug show bioequivalence to the innovator’s drug.

There are also criteria — called biowaivers — by which bioequivalence testing requirements, especially involving human participants, can be waived safely. And these waivers are applicable for many of the generic drugs in common use. In addition, there are at least a dozen other parameters on which quality is to be established.

Quite a few manufacturers in India comply with these quality requirements. In particular, making atorvastatin and most essential medicines, as in the WHO Essential Medicines List, given competence and ethics on the manufacturer’s part, is a task that is being routinely accomplished.

Quite a few also don’t comply, including some big names. For instance, the National Drug Survey 2014-16 showed 26 of the 46 samples picked up from retail outlets in India and that were manufactured by Pfizer Maharashtra, or almost 57 per cent of the samples, to be NSQ — Not of Standard Quality — well above the national retail average of 3 per cent.

Big pharma of the West has anything but clean slates. Think Vioxx (rofecoxib) and Merck, or more recently think J&J and its carcinogenic talcum powder and its faulty hip implants that killed patients. In the rofecoxib issue, the USFDA too was considered derelict.

In India, most foreign and Indian companies are also complicit in making products that are irrational, useless and harmful. However, any amount of wrongs of Big Pharma and MNCS do not right the wrong of the Indian companies making substandard products for any market.

The whistleblower

The book is also the story of Dinesh Thakur, the Indian American who left his relatively secure job in Bristol-Myers Squibb in New Jersey to join Ranbaxy in India only to find there the worst of manufacturing and data integrity practices. Thakur’s admirable sense of moral rectitude, eventually leading to his whistle-blowing on Ranbaxy, where many others in his place would have quit for safer pastures, or fallen off the map, must be seen as a signal service to the Indian pharma industry.

The book also narrates the dedication of several individuals in the USFDA who had to ferret out fraudulent practices — in India’s pharma sector — at great personal risk.

The then Health Minister Dr Harsh Vardhan did not give a proper hearing to Thakur’s suggestions. Now that Dr Vardhan is back in the saddle and even if he had previously called the CDSCO, India’s top drug regulatory agency, as a “snake pit of vested interests”, after calling his job a “poisoned chalice”, he may consider giving a second hearing to the likes of Thakur and others.

Bottle of Lies needs to be read with due diligence.

The reviewer is affiliated with All-India Drug Action Network and LOCOST, Vadodara; thanks to Anant Phadke, T Srikrishna for comments

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