Generics made in India have more ‘severe adverse events’
Ohio State University
Generic drugs manufactured in India are linked to
significantly more “severe adverse events” for patients who use them than
equivalent drugs produced in the United States, a new study finds.
Photo Credit: Policy and Medicine
These adverse events included hospitalization, disability,
and in a few cases, death. Researchers found that mature generic drugs,
those that had been on the market for a relatively long time, were responsible
for the finding.
The results show that all generic drugs are not equal, even
though patients are often told that they are, said John
Gray, co-author of the study and professor of operations at The Ohio
State University’s Fisher College of Business.
“Drug manufacturing regulation, and therefore quality
assurance practices, differ between emerging economies like India and advanced
economies like the United States,” Gray said.
“Where generic drugs are manufactured can make a significant
difference.”
“The FDA assures the public that all generics patterned after the same original drug should be equivalently safe and effective, however, this is not necessarily the case when it comes to generic drugs made in India,” added another co-author, George Ball, associate professor of operations and decision technologies at Indiana University’s Kelley School of Business.
Published recently in the journal Production and Operations Management,
the research was led by In Joon Noh, who received his PhD at Ohio State and is
now an assistant professor at Korea University. Other authors include Zachary
Wright, who will receive his PhD from Ohio State and is now an assistant
professor at Brigham Young University; and Hyunwoo Park, a former assistant
professor at Ohio State, now at Seoul National University.
Several of the authors on this paper have worked closely
with the Food and Drug Administration on federal grants and contracts, though
this study was conducted completely independent of the FDA. These authors said
working closely with the FDA gave them a deep appreciation for the importance
of studying generic drug quality.
The study is significant because it is the first to be able
to link a large sample of generic drugs to the actual plant where they were
manufactured. The FDA will not release that information through the
Freedom of Information Act process. But Gray said Noh figured out how to use
what is called the Structured Product Labeling dataset to link drugs to the
factory where they were produced.
“Overcoming this lack of transparency of drug manufacturing
location is one of the major accomplishments of our study,” Gray said.
Another key to the study is that it matched the drugs made
in India to the same drugs made in the United States. The drugs had the same
active ingredients, the same dosage form and the same route of administration.
“That means the drugs are pharmaceutically equivalent and we
are comparing apples to apples,” he said.
The researchers matched 2,443 drugs made in the United
States and in emerging economies. Although the researchers included other
countries in their analysis, 93% of generic drugs from emerging economy
countries are made in India, so India data fully explained the results.
The researchers compared the frequency with which drugs were
associated with adverse event reports for generic drugs made in India versus
the matched drugs made in the United States. These adverse event reports are
available in the FDA Adverse Event Reporting System (FAERS).
Although the FAERS includes all reported adverse events, in
this study the researchers only used those with the most serious outcomes,
including hospitalization, disability and death.
Results showed that the number of severe adverse events for
generic drugs made in India was 54% higher than for equivalent matched generic
drugs made in the United States. That was after taking into account a variety
of other factors that could have impacted the results, including the volume of
drugs sold.
The findings were driven by drugs that had been on the
market for a longer time.
“In the pharmaceutical industry, the older drugs get cheaper
and cheaper and the competition gets more intense to hold down costs,” Gray
said. “That may result in operations and supply chain issues that can
compromise drug quality.”
Gray emphasized that the results shouldn’t be taken as a
reason to stop overseas production of generic drugs.
“There are good manufacturers in India, there are bad
manufacturers in the U.S., and we’re not advocating for ending offshore
production of drugs or bashing India in any way,” Gray said.
“We believe this is a regulatory oversight issue that can be
improved.”
Gray said one key issue is that when the FDA inspects plants
that make generic drugs in the United States, the inspections are
unannounced. But in overseas locations, the inspections are arranged in
advance, which may allow manufacturers to hide problems and make it harder for
the FDA to find those that do exist. Making all inspections unannounced could
make a big difference, he said.
“A key recommendation we make in this study is for the FDA
to make drug manufacturing location, such as the country of manufacture, and
drug quality, transparent for consumers,” Ball added. “This can help create a
market in which drug quality is incentivized more than it is today.”