As the generic drug industry faces allegations of data manipulation, headlines about carcinogen-tainted blood pressure medicine, and an intensifying probe by the House Energy and Commerce Committee, whose health subcommittee is holding a hearing on Wednesday on safeguarding our global drug supply, generic drug industry lobbyists are fighting back.

They claim that low-cost drug makers operating overseas — where the majority of our generic drugs are made — follow the same intricate rules as U.S.-based drug makers. They argue that instances of manufacturing fraud or negligent practices are a thing of the past, having ended largely in 2013 when India’s largest drug company, Ranbaxy, pleaded guilty in the United States to seven felonies related to falsifying manufacturing data.

The Food and Drug Administration, also on the defensive, has been quick to reassure consumers and Congress that its regulatory system of data review and inspections is effective regardless of where drugs for the United States are made.

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But our analysis of the FDA’s own records reveals that violations of data integrity are not only persistent and ongoing in overseas drug manufacturing plants, but are happening with greater frequency than in U.S. plants. With the help of FDAzilla, a leading data analytics company, we analyzed 5 1/2 years of FDA inspection records, from 2014 to the present, for four major markets: China, India, Europe, and the United States.

The data show significantly greater falsification or manipulation of manufacturing data in Indian and Chinese drug plants. “Egregious data integrity violations are alive and well, especially in China and India,” said Michael de la Torre, chief executive officer of FDAzilla’s parent company, Govzilla. “While the U.S. and Europe are not immune to serious data integrity violations, China and India are at least twice as likely to have these issues.”

Out of more than 12,000 FDA inspections of drug plants in the United States, about 15% uncovered violations of the FDA’s data integrity rules. These stipulate that all manufacturing data must be preserved — unaltered — and made available to regulators. In India, about 25% of the plants inspected committed some sort of data violation, while in China, that figure hovers just above 32%.

Country Number of inspections Number (percentage) of violation forms (Form 483) issued Percentage of Form 483s that cite data integrity violations Percentage of Form 483s that cite data manipulation
China 916 617 (67.4%) 48% 31%
India 1,693 976 (57.6%) 44% 24%
Europe 2,969 1,445 (48.7%) 36% 18%
USA 13,650 (estimated) 6,794 (49.8%) 26% 7%

While this analysis reflects a serious problem, it likely understates the severity. The FDA is failing to detect a significant amount of fraud in overseas plants because of the way it conducts those inspections. In the United States, FDA investigators show up unannounced for inspections. But abroad, the agency has chosen to pre-announce its inspections, a system that gives plants time to clean up any evidence of unsanitary conditions, wrongdoing, or data manipulation.

In 2014, when the FDA attempted a short-lived experiment of giving Indian drug plants only short or no advance notice of inspections, the serious violations uncovered by its investigators rose by almost 60%.

The glaring shortcomings of the FDA’s decision to pre-announce overseas inspections, exposed in “Bottle of Lies: the Inside Story of the Generic Drug Boom,” which one of us (K.E.) authored with help from the other (S.S.). These inspections are now under review by the House Energy and Commerce Committee’s oversight and investigations subcommittee.

But these numbers tell only part of the story. We also wanted to understand if there is a difference not only in the rate of data violations but in the nature of the wrongdoing. Some practices, like multiple lab technicians using the same log-in information, suggest unprotected computer systems. That might amount to negligence. But other practices, like lab technicians deleting irregular test results or discarding raw data, suggest fraud. Here, too, our analysis shows that data integrity violations in India and China are more egregious than they are in the United States and Europe.

To distinguish negligent practices from egregious ones, we worked with FDAzilla to identify key words in the FDA’s inspection reports, such as falsification, destruction, and backdating. By comparing inspection reports, we discovered that in the United States about 28% of plants cited for data integrity problems exhibited truly deceptive behavior. In India, that number rose to 55%, and in China, to 65%.

For example, a January 2019 FDA inspection at Indoco Remedies in Goa, India, uncovered that the manufacturing plant had faked the data in its batch production records to justify the release to market of its diabetes drug glimepiride. By contrast, the raw testing data showed that the drug did not meet quality standards and therefore should not have been released to patients.

While data integrity violations may sound minor and technical, for patients they can mean the difference between a safe, effective generic drug that functions just like the brand and a drug that is not equivalent to the brand, or that may contain toxic impurities or foreign particulate matter. In short, a difference between life and death.

At the Cleveland Clinic, as “Bottle of Lies” chronicles, heart transplant patients whose anti-rejection medication was working fine ended up suffering organ rejection after taking an ineffective Indian-made immunosuppressant.

At the manufacturing plants themselves, data integrity violations can mean profound deceit: tearing up records of failing drug tests and smuggling them from the plant; or inventing data to indicate that a plant is sterile, without actually doing the required microbial testing of the surfaces, air, and water.

The FDA recently announced what appeared to be great news: It had approved 1,171 new generic drug products for fiscal year 2019, a new record. But this week, as congressional leaders hold yet another hearing on the safety of our drug supply and the adequacy of the FDA’s regulatory system, they need to consider an unpleasant truth: The overseas manufacturers that are ostensibly saving us from runaway drug prices are actually exposing us to growing risk of getting drugs with undetected impurities or faked results.

There is no question that Americans need more affordable medicines. But to ensure high quality, the FDA needs to overhaul its overseas inspection program — and it should start by ending the practice of the advance-notice inspections for which plants prepare. In March, for example, an FDA investigator inspecting the NingBo Huize Commodity Co., in Zhejiang, China, found that the plant had falsified all sorts of documents: cleaning validation reports, batch records, and annual reports. Under questioning, the plant’s general manager confessed that the documents had been faked “for the purpose of this inspection,” according to an August warning letter.

In today’s interconnected, global drug supply chain, the FDA’s regulatory honor system — which relies on company-submitted data and pre-announced inspections and does not systematically test drugs to verify their contents — is no longer adequate. Americans should demand that the FDA and its investigators police overseas manufacturing plants and their drug products with the same rigor — and using the same standards — as they do domestic ones.

Katherine Eban is an investigative journalist and the author of “Bottle of Lies: The Inside Story of the Generic Drug Boom” (HarperCollins, 2019). Sony Salzman is a freelance science and medical journalist who worked as a researcher on “Bottle of Lies.”

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  • I’ve sustained serious, catastrophic & personal injuries (brain & other organ damage)! 7/31/17 I was diagnosed with cerebellar atrophy (brain damage)! I’m not sure how/when the injury occurred since nothing traumatic has happened (stroke, accident, concussion etc.)! This ordeal has affected my vision, speech, mobility & extremities! I’m permanently disabled! 4/18 I went to the Mayo Clinic (for additional test) my test results revealed my condition is advanced, non-treatable or irreversible! This has taken a toll on my life in many ways!
    I did research into the causes of brain damage(open/closed)! Those listed that pertain to me was toxin or exposure to toxins. The only source of toxin I was exposed to was the medicine(lisinopril) I was prescribed for my HBP!
    I’ve done research into lisinopril for three years. I read of how the medicine works in the body & its hidden dangers! I also have other organ damage, consistent with lisinopril!
    The book Bottle of Lies exposes revelations of the generic drug industry(fraud, false data, poor oversight, greed /a culture of corruption etc.) have raised questions & concerns of safety & effectiveness of generic drugs! The illegal practices, limitations & restrictions imposed aren’t fair nor right to consumers, yet benefits the pharmaceutical! I read of how pharmaceuticals put profits over safety or how they spend billions on advertising their product and less on safety or how the pharmaceuticals rush the products to market without proper testing!( Being that lisinopril is a generic drug fits into that category/there’s other generic medicines too)! Couple together, I’m convinced that lisinopril & the manufacturer are the cause of my injuries & others! I’ve seen several videos , post & reviews about lisinopril deaths, injuries etc. As of December 2019.231, 436 consumers have reported to the FDA side effects from lisinopril among those 32 consumers have reported to the FDA brain damage from lisinopril! Being that lisinopril is the third most prescribed medicine is the cause of an unrecognized epidemic across America!
    I’ve put the pieces to this puzzle together & lisinopril is a BIG piece (it’s the only logical conclusion & the reports of the generic drug industry)!
    Sorry this is rather lengthy, but I wanted to give more insight into my (this) situation!
    Attention & Awareness needs to be brought to this is a public health crises & those responsible for this crises should be held liable!

  • I have been buying Medicines from Costco for a few years.

    Two weeks ago they gave me the wrong dosage of Atorvastatin Prescription #
    RX#6458923 . The dosage was supposed to be 80 mg one a day and they have been giving me 80 mg but this one was for 20 mg. When I called them , they said that they cannot take it back and there is nothing that they can do. I find it appalling as you guys cannot take responsibility for your mistake ?

    Luckily I am an MD and realized that. I dont know what is your Corporate Policy for this kind of mistake.

    I also want to bring your attentions to the quality of products you are supplying to consumers. Cheap Chinese and Indian made products which are hurting American Public. I have been supplied with Losartin 100 mg with HCTZD 25 mg made by Camber Pharma. Please read below.

    I intend to blog and if any one has developed Cancer due to this cheap drug, I will gather people and sue Camber and Costco as there is no quality control and it is all about how much money you guys can make.

    https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/camber-pharmaceuticals-inc-issues-voluntary-nationwide-recall-losartan-potassium-tablets-usp-25-mg

    it should be your job and research this and keep us protected and not the other way around. Innocent people dont know about this.

    Please take some action to protect Costco. I like to go there but your job should be done properly as well.

  • The week in May that your article about tacrolimus came out, my daughter was prescribed it by her bone marrow transplant doctor bat Dana Farber. He was not phased by the knowledge of potentially dangerous impurities and ineffectiveness. He said he knew of the problems but not to worry. The health teams/clinicians need to play a larger role in affecting change for these types of generics manufacturing. They perhaps need more education and advice on how and who to fight for their patients.

  • Prior announcement of inspections is (very obviously given the data presented in the article) a gigantic flaw that utterly defeats the purpose of catching unscrupulous cheaters. It is ridiculous to measure generic maker’s integrity by different stanards. And of course by now cyber integrity should be a logial part of the inspection. And a solution such as producing generics for the USA in the USA would alleviate a lot of FDA pain and errors …………..

    • FDA must do periodic inspections to protects as cheap Indian and Chinese Medicine has flooded the market and no one cares. Here is what I wrote to Costco today.

      I have been buying Medicines from Costco for a few years.

      Two weeks ago they gave me the wrong dosage of Atorvastatin Prescription #
      RX#6458923 . The dosage was supposed to be 80 mg one a day and they have been giving me 80 mg but this one was for 20 mg. When I called them , they said that they cannot take it back and there is nothing that they can do. I find it appalling as you guys cannot take responsibility for your mistake ?

      Luckily I am an MD and realized that. I dont know what is your Corporate Policy for this kind of mistake.

      I also want to bring your attentions to the quality of products you are supplying to consumers. Cheap Chinese and Indian made products which are hurting American Public. I have been supplied with Losartin 100 mg with HCTZD 25 mg made by Camber Pharma. Please read below.

      I intend to blog and if any one has developed Cancer due to this cheap drug, I will gather people and sue Camber and Costco as there is no quality control and it is all about how much money you guys can make.

      https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/camber-pharmaceuticals-inc-issues-voluntary-nationwide-recall-losartan-potassium-tablets-usp-25-mg

      it should be your job and research this and keep us protected and not the other way around. Innocent people dont know about this.

      Please take some action to protect Costco. I like to go there but your job should be done properly as well.

      FDA approves once and then no one gives a damn til people get cancer due to impurities or the manufactures recall like I have included url above. No one can ever know if they got cancer from impure drugs or not and no one is caring or watching as it is ALL ABOUT MONEY.

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