US data shows a 50% higher rate of adverse events. The TGA says its processes are different from the FDA’s.
An American study has found that prescription generic drugs made in India are associated with significantly more unexpected severe adverse events than generic drugs made in the US.
The problem is in drugs that have been on the market for years, where manufacturers are competing on price, rather than quality, the study finds.
The FDA does not reveal which factories manufacture each generic drug sold in the US.
But five researchers, from business colleges at Korea University, Ohio State University, Indiana University, Brigham Young University (in Utah) and the Graduate School of Data Science at Seoul National University, found a way to identify where the drugs came from and compare the adverse events associated with each location.
“We find that generic drugs manufactured in India, where a majority of emerging economy generic drugs are made, are associated with significantly higher instances of serious adverse events than equivalent generic drugs made in the US, where a majority of advanced economy generic drugs are made.
“We further show that this key result is explained by mature generic drugs, which are particularly susceptible to operations and supply chain cost reduction efforts – efforts that unfortunately may compromise drug quality. Our study finding leads to implications for the FDA in their regulation of generic drugs.”
About 90% of drugs dispensed in the US are generics, the authors say, which are interchangeable and bioequivalent at the time of approval by the FDA. Ongoing manufacturing quality is supposed to be monitored through plant inspections.
But the authors note “growing anecdotal evidence” that oils ain’t oils, and that patients are feeling the effects.
“We believe that the premise of generic drug interchangeability remains unchallenged by careful academic research for several reasons,” they write.
Top of those reasons is that the FDA says they’re bioequivalent, they said. And it’s hard to know which factory makes what drug because that information is considered commercial in confidence and not released even in response to a Freedom of Information request.
“Overcoming this lack of transparency of drug manufacturing location is one of the major accomplishments of our study,” they write.
To do so, they exploited “a previously unused source” of drug labelling data called the Structured Product Labeling dataset.
The study compared unexpected serious adverse events reported in the US for 1284 drugs manufactured in emerging economies, mainly (93%) India, and 1159 equivalent drugs manufactured in advanced economies. Equivalent meant, according to FDA criteria, that they had the same active pharmaceutical ingredients, dosage form and route of administration.
They found that the number of unexpected severe adverse events associated with generic drugs made in emerging economies was 54% higher than the number associated with the equivalent generic drugs made in advanced economies.
“This difference is entirely explained by those generic drugs that are most susceptible to operations and supply chain cost reduction efforts: mature generic drugs that have been on the market for several years,” they said.
The differences in quality could come about after approval because of where supplies are sourced and how they’re managed, manufacturing processes, equipment, workforce and distribution methods, and profit motives could incentivise cutting corners, “even if it is inadvertent”, said the authors.
On top of that, the FDA’s site inspections in the US are unannounced, but it usually flags forthcoming inspections at plants in emerging economies, including India.
In the EU and the UK there are agreements in place to ensure the same kinds of quality control. That’s not so in emerging economies, the authors say.
The authors make two recommendations: more transparency about the quality and location of manufacture of specific generics so the market can reward those of higher quality, and for the FDA to stop announcing its quality inspection visits in factories outside the US.
Rheumatology Republic asked the TGA, which monitors the safety of therapeutic goods for use in Australia, about adverse events associated with generic drugs sold here.
“At present, the TGA has not detected any safety issues associated with a single generic product,” a spokesperson for the TGA said.
And when asked if the TGA, or its partner agencies, conduct surprise inspections on both local and overseas generic drug manufacturers, they responded, “yes, the TGA and partner agencies do conduct unannounced inspections within their jurisdictions”.
