Study finds significantly higher adverse events in generic drugs imported from India into US

By Rosamma Thomas* 

It was not so long ago that Dinesh S. Thakur and Prashant Reddy T. published their book The Truth Pill: The Myth of Drug Regulation in India, showing how poor regulation of drug manufacturing in India was causing the market to be flooded with subpar prescription medicines.

Thakur was a whistleblower who exposed poor practices at Ranbaxy, once one of India’s largest pharmaceutical companies. By 2018, the company had ceased to exist.

Now, a new study raises questions about the safety and efficacy of generic drugs made in India.

The study, recently published in the journal Production and Operations Management, was conducted with a grant from the Korea University Business School. It is authored by five researchers from the US and Korea; its lead author, Joon Noh, is affiliated with the Korea University Business School.

The article, titled "Are All Generic Drugs Created Equal? An Empirical Analysis of Generic Drug Manufacturing Location and Serious Drug Adverse Events," cites anecdotal evidence pointing to manufacturers in countries designated as "emerging economies" by the International Monetary Fund (IMF)—particularly India—"producing in ways that do not consistently result in truly interchangeable drugs" (Eban 2019, Martinez et al. 2019, White 2020). 

For example, a Cleveland Clinic cardiologist believed that a switch from one generic manufacturer based in an advanced economy to another based in an emerging economy led to the deterioration of a patient’s health (Edney 2019)—one of many such anecdotes he observed after beginning, several years ago, to pay closer attention to which drugs his patients were being administered by pharmacies and where they were made (Lever 2020).

The authors note that understanding systemic quality differences between generic drugs produced in advanced and emerging economies is important because generic drugs consumed in the US are increasingly manufactured in emerging economies, with the majority coming from India.

The location where a drug is manufactured is considered confidential information and is not disclosed under the Freedom of Information Act in the US.

The researchers thus used a dataset known as Structured Product Labeling data, which provides information for all drugs marketed for sale in the US, including the name of the manufacturer and details of the manufacturing plant.

The measure the researchers used to compare quality was data on serious adverse events (SAEs). An adverse event is considered "serious" if it results in the patient being hospitalized, disabled, or dying.

The FDA in the US operates under the assumption that drugs sharing key aspects of their design are pharmaceutically equivalent—regardless of by whom or where they were manufactured.

"The core finding that emerges from this set of empirical tests is of concern both for consumers and the FDA: generic drugs made in India, where the majority of emerging economy generic drugs are produced, experience significantly more SAEs than equivalent generic drugs made in the US. … Further, this difference is entirely explained by those generic drugs that are most susceptible to operational and supply chain cost-reduction efforts: mature generic drugs that have been on the market for several years," the article states.

Generic manufacturers compete on price, and consumers and their doctors often cannot identify differences in quality. In the US, FDA approval functions as the sole mark of quality.

Post-approval quality checks of drugs arriving from "emerging economies" in the US are not as rigorous, as the authors explain.

Drug inspection strategies were developed between nations of the First World, with the US and Europe having agreements in this regard.

Such harmonization has not proven possible with countries like India, where regulatory bodies are "less mature and less resourced." Additionally, the US FDA notifies foreign plants before conducting an inspection, while its own manufacturers are subject to surprise checks.

The researchers matched 2,443 drugs that were made in the US and India. The authors note that 93% of the emerging economy drugs in the sample were from India, and 81% of the advanced-economy drugs originated in the US. India-made generic drugs that have been on the market for a long time were more likely to cause higher rates of serious adverse events.

What is significant for India is that the researchers suggest these findings likely apply to other industries as well, where consumers cannot easily detect product quality. This is a damning indictment of manufacturing standards and regulatory oversight in India.

As the government of India promotes its "Make in India" campaign, it would do well to take note of this research—for the sake of the health of ordinary citizens.

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*Freelance journalist