In 2019, Katherine Eban published a book, “Bottle of Lies”. It tells a convincing story that leaves readers concluding that all generic drugs are bad. But is this cause to abandon generic drugs?
Problems with the quality of generic drugs, from contaminants to subpotency to violations in manufacturing practices, have been hitting the headlines regularly for the last decade and even before. “Bottle of Lies” is one of the latest publications that detailed these problems.
One particularly sore spot is the origin of many generic drugs, India or China, where cheap labor and technology attract generic drug manufacturers hoping to make a quick buck. Facilities in these countries not only produce finished product pharmaceuticals, but also active pharmaceutical ingredients (APIs) that may be exported for use by manufacturers in other countries to make finished products.
One of the most problematic issues relates to FDA inspection and oversight of overseas pharmaceutical manufacturers. Inspections are said to be flawed because the FDA provides advance notice before overseas inspections, leaving time for the companies to destroy or stage evidence in order to “earn” a good score. Another accusation is that inspectors overlook or de-emphasize violations that they encounter, resulting in factories that pass inspection even when their products are inferior.
Brand drugs are subject to quality issues too
Ms. Eban did a great deal of high-quality investigation and it is likely that her conclusions are correct. However, completely abandoning generic drugs in favor of brands will not solve the problem.
It appears that APIs are procured from the same source by both brand and generic manufacturers and only 28 percent of the manufacturing facilities making APIs to supply the United States market are in the United States. By contrast, the remaining 72 percent of the API manufacturers supplying the U.S. market are overseas and 13 percent are in China. If the contamination being found in finished drug products is carried with the API, then brand drugs manufactured in the U.S. may be at as much of a risk of contamination as generics. Many brand name products are manufactured abroad, some in the same factories as generics, exposing the brands to the same manufacturing conditions as the generics.
Generic products are not the only drugs associated with quality issues; many brand products have been the subjects of FDA inspection warnings as well. Federal records show that in 2018 alone, new (brand) drugs for cancer, migraines, HIV and a rare disease were approved by FDA and brought to market — even though inspectors urged FDA to withhold approval. This occurred at least 10 other times in recent years. Kaiser Health News provided the following examples:
- In 2012, FDA inspectors said [Gilead’s Foster City] facility had failed to properly review how the HIV drugs Truvada and Atripla became contaminated with “blue glass” particles; some of that tainted batch was distributed. The company “made no attempt to recover” the contaminated drugs.
- In January 2018, FDA inspectors hit a Korean manufacturing plant that makes Ajovy, a migraine drug, with a warning letter. … Among other problems, inspectors found that glass vials sometimes broke during the manufacturing process and that the facility lacked protocols to prevent the particles from getting into drug products.
- At a Chinese plant making the new HIV drug Trogarzo, employees dismissed ‘black residue’ found to be ‘non-dissolvable metal oxides’, assuming it ‘did not pose a significant risk.’
- When FDA inspectors visited a contract manufacturing facility in Indiana used to make Revcovi, which treats an autoimmune disease, they noted that a redacted drug lot had failed a sterility test because the vials tested positive for a bacterium called Delftia acidovorans, which can be detrimental even in people with healthy immune systems. But the drug-filling machine stayed in use after the contaminant was discovered.
Health Plans, employers and members cannot afford to abandon generics completely
A couple examples of the egregious markup that brand products represent over generics, from Confidio’s book of business (note “IC/claim” is average ingredient cost per claim):
Patients are known to skip or reduce doses of expensive medications because they cannot afford to pay for their complete regimen. This may save money in the short run but raises the risk of expensive medical consequences of drug non-adherence, not to mention the devastating effects of conditions that might have been prevented.
Harvard Women’s Health Watch, affiliated with Harvard Medical School, notes that “It’s estimated that if more prescribers substituted generic for brand-name drugs, drug spending could drop substantially, as much as $5.9 billion by some estimates”.
Some concerns over the safety of generic drug products are legitimate, but branded products are vulnerable to the same issues. Given the price differential between generics and brands, Confidio continues to recommend use of generics in all but a few circumstances (patient allergic to an inactive ingredient in the generic, net cost of brand is less than that of the generic, patient already stabilized on a brand of a narrow therapeutic index drug, etc.). Consider a generics first strategy.
- Eban, K. (2019). Bottle of Lies: The Inside Story of the Generic Drug Boom. New York: Ecco.
- Greene, J. A. (2019, September 12). After a scandal, a one-sided warning against generic drugs. Retrieved from The Washington Post: https://www.washingtonpost.com/outlook/after-a-scandal-a-one-sided-warning-against-generic-drugs/2019/09/12/6a755e48-c50a-11e9-b5e4-54aa56d5b7ce_story.html
- Harvard Health Publishing. (2018, January). Do generic drugs compromise on quality? Retrieved from health.harvard.edu: https://www.health.harvard.edu/staying-healthy/do-generic-drugs-compromise-on-quality
- Lupkin, S. (2019, November 19 ). FDA Keeps Brand-Name Drugs On A Fast Path To Market ― Despite Manufacturing Concerns. Retrieved from Kaiser Health News: https://khn.org/news/fda-keeps-brand-name-drugs-on-a-fast-path-to-market-%E2%80%95-despite-manufacturing-concerns/
- Woodcock, J. (2019, October 30). Safeguarding Pharmaceutical Supply Chains in a Global Economy–Testimony to House Committee on Energy and Commerce, Subcommittee on Health. Retrieved from https://energycommerce.house.gov/subcommittees/health-116th-congress