“Bottle of Lies: The Inside Story of the Generic Drug Boom,” by Katherine Eban, Harper-Collins, NY, 2019. This 482-page hard back tells the story of generic drugs. Generic drugs came about with the passage of the Hatch-Waxman act in 1984. It allowed other companies to manufacture off patent drugs using the efficacy data of the brand name filing provided they could demonstrate equivalent bioavailability and stability. In recent years competition has driven the acceptance of generics made in Asia–especially in India and China–where costs are low. The book addresses the problem of FDA inspection of facilities in these countries. Much of the book tells the story of Ranbaxy, a company in India.
The US is one of the most profitable markets for generics. Ranbaxy set out to grow its US business. To do so it hired native Indians who had worked at major drug companies in the US giving them experience dealing with FDA requirements. They were recruited to return to India to assist Ranbaxy. Over time they realized that the data Ranbaxy used in filing for FDA approvals were fabricated. One was forced to resign and became a whistleblower to the FDA. India is a country where local regulatory problems can usually be addressed by connections. FDA is rigid and uncompromising. The whistleblower feared for the safety of his family. The book traces the history of its case before finally Ranbaxy agreed to a consent agreement and paid a $500MM fine. The whistleblower received $15MM.
In the US, FDA inspections are unannounced. They check for well run facilities and look for deviations from Good Manufacturing Practices. In foreign countries, the FDA inspection is prearranged months ahead and the company often arranges hotel and transportation for the FDA team. Traditionally inspectors get a guided tour of the facility and see what the company wants them to see. To keep costs down the company often hires poorly trained, even illiterate workers. The language barrier can make interviews difficult.
Eventually one FDA inspector learned to seek out the details. FDA requires quality testing at each step. Any anomaly in the data must be recorded, investigated and resolved. High performance liquid chromatography (HPLC) is a common analytical tool. The machines are connected to computers that record findings making it difficult to hide a sample with an unexpected impurity. In the US as many as 25% of batches might require action. In India such batches are rare. The inspector learned that often off computer equipment was used to pretest and adjust to pass the official test.
Similarly we learn of multiple levels of quality. Lower quality materials may used to cut costs. Rejected batches are shipped to countries that have less rigorous or no testing. Hence in Africa, some drugs are counterfeit with no active medication. Others can be low in activity. Physicians find some drugs that should have cured a condition ineffective. Buying brand name rather than generics is safer. Quality varies widely.
With better inspection methods FDA learned to identify manufacturers who did not comply with the requirements and blocked their products from US markets. But at times this resulted in drug shortages. Eventually FDA backed off on the rigor of its inspections.
This does caution readers to be aware of drug quality issues. Drugs ordered on line may be counterfeit or contaminated. Buying from responsible organizations with the ability to verify quality is a logical follow-up.
Eban is detailed in her reporting. And cuts a wide swath. Glossary. References. Index.
“Eban has given a lopsided gift to the well-funded lobbyists of the drug industry trade group, the Pharmaceutical Research and Manufacturers of America (PhRMA), and the biotech trade association, the Biotechnology Innovation Organization (BIO). The book paints an uneven picture for readers, who should know that the willingness of pharmaceutical companies to promote substandard and potentially harmful agents is not limited to Indian or Chinese firms; it can be found just as readily among European and North American brand-name manufacturers.”
One has to be careful about making decisions about meds based on “problems uncovered”.
The issues found have often been addressed since the publication and going to all
“brand name” manufacturers will not prevent “problems” from developing. The solutions
will uniformly increase the cost of generics - which may be necessary. But paying the
cost of increasingly pricey and smaller market based medications will continue to be a
problem that folks will have to learn to handle.
A key word for drugs in the US is “pedigree” - as in, dog show - but with medications the word is analogous to the “provenance” from reputable antique dealers: a seamless thread from A to B to C, attested to in writing.
Otherwise, figuring out efficacy is tough (and nonexistent for naturopathic remedies).
An exception is generic WARFarin (Wisconsin Alumni Research Foundation). The relevant test (the “prothrombin time”, or PT) is actually a measure of the efficacy of the drug and won’t be inaccurate
Howie’s comment is valid. The whistleblower Ranbaxy case gave the author ample documentation for the book. That made research much easier and provided numerous names to interview.
The book is mostly about India for that reason. Other generic suppliers may be just as bad in a highly competitive industry. But low labor costs (and well educated professionals) make India and China key players in the industry.
Personally i use generics with no problems so far. But mine are purchased from US suppliers with the ability to monitor quality.
"This is extremely concerning. Makes me wish I had an HPLC at home to analyze all my meds.
You might find that you don’t have the time to test every medicine and check quality of
foodstuffs and make meals and eat meals and lord knows what else as well as earn a living for
for yourself and your family.
Separation and specialization are drivers of human evolution. Humans make mistakes - even when
highly trained and motivated. The more regulations used to “control” or “limit” mistakes
eventually creates a need for people in the loops because one person can never retain the
regulations in their mind - thus eventually recreating automation and controls.
However, the automation and controls are both programmed as well as the hardware is installed
by humans - who also make mistakes and require inspections, reviews, testing, testing-in-place.
Then add in cleaning, inspection of cleaning and cleaned hardware.
There has to be sufficient trust in your fellow humans, the agencies performing testing and
monitoring of processes and production, and manufacturers. Basically, you have to have faith
that folks are not actively trying to kill others and that operations are designed to provide
a minimum chance of errors that can produce fatal results.