If there is a surefire way to arouse the concerns of Food and Drug Administration inspectors, try this: take a notebook listing manufacturing problems, place it in plastic bags along with other paperwork, and toss them in a nearby scrap yard where the inspectors can find them.

Here’s another approach: leave “unofficial notebooks,” which are used to track manufacturing activities, lying around an office so the inspectors can read how bacteria is present in the water system, but become puzzled when the problem is not cited in official company records.

These were just two of several “serious breaches” of good manufacturing practices the FDA cited in a Dec. 23, 2015, warning letter sent to Cadila Healthcare, one of India’s largest drug makers. The letter followed agency inspections of two manufacturing plants in India between August and December 2014.

advertisement

What else concerned the FDA?

There were problems with the potency of warfarin made at one plant and Cadila agreed to temporarily suspend production. But after running tests, the company resumed production in November 2014. Yet in June 2015, Cadila acknowledged to the FDA that problems with some lots of warfarin were subsequently found, but had been shipped anyway.

Meanwhile, nine consumer complaints were lodged by way of pharmacies and distributors over potential product mix-ups. But while Cadila conceded some drugs were made on adjacent production lines, the company never completed its investigation. Were mix-ups caused by inadequate cleaning, unsuitable equipment, material flow, or something else? Cadila didn’t know, which made it hard to fix the problem.

There’s more. Several batches of active pharmaceutical ingredients failed an analysis, but Cadila never explored why this occurred. The drug maker also failed to prevent unauthorized access or changes to data. FDA inspectors noted a lab manager could delete data from software and, in fact, one file was deleted. But an audit trail function was never activated and Cadila did not have records of any changes.

For its part, Cadila issued a statement to the Bombay Stock Exchange last week to maintain that it takes “quality and compliance matters very seriously … and is working hard to ensure that the commitments made to the FDA are fully completed.” The drug maker also insisted its products are safe and effective and that no products shipped to the United States are made with ingredients from the plant where the analyses failed.

“This has a theme found in a lot of warning letters, especially warning letters issued to Indian companies,” said Vince Suneja, chief executive of TwoFour Insight Group, a consulting firm that works with Indian drug makers. “There’s a failure to properly investigate problems and a lack of adequate controls for data.”

Indeed, as we have noted previously, this is only the latest instance in which the FDA has scolded an Indian drug maker or ingredients supplier for quality control problems. Over the past several years, in fact, there has been mounting concern over the safety of the pharmaceutical supply chain after the agency cited several companies for production failures.

The most notable example was Ranbaxy Laboratories, which is now owned by Sun Pharmaceutical. The drug maker has been a poster child for manufacturing problems. Last year, Ranbaxy paid a $500 million fine to US authorities as part of a settlement that included pleading guilty to two charges of violating drug safety laws that, for example, involved manipulating data.

Several companies have also been hit with so-called import alerts in which the FDA bans products made at a specific facility. The crackdown, however, has alarmed Indian drug makers. They have complained the FDA has singled them out for especially tough inspections, which occur too frequently and haphazardly, depriving them of the opportunity to make substantive changes.

The ongoing problems prompted several congressional lawmakers last month to ask the US Government Accountability Office to review FDA oversight of foreign manufacturing plants.

Last year, the FDA began considering a new approach to inspecting manufacturing facilities in India. The plan is to “allow our inspectors to document where a firm’s quality management system exceeds what would be required to meet regulatory compliance,” FDA officials wrote in a blog post. “To put it simply: the inspections can yield also carrots, and not just sticks.”

The FDA has also begun working with the Indian government to bolster domestic oversight. Right now, the agency has three inspectors who work in the country, but others regularly travel there as well, so the total number varies. India’s drug makers, however, are angry over the FDA scrutiny, which has led to a series of import alerts that ban products from being shipped to the US.

Leave a Comment

Please enter your name.
Please enter a comment.

  • I didn’t really finish my first line of previous email. I am trying to find out if there has been a recall or issues reported with the generic drug Pivasta 2 which is manufactured by Zydus Cardiva.

  • I am trying to find out if a drug I am taking which IS manufactured by Zydus Cardiva. I obtain it thru Canada Drugs online. It is the generic form of Livalo, which is called Pivasta 2 for cholesterol. I am having some issues with breathing. I’ve had to undergo expensive cardiac testing and now am facing pulmonary testing as well. This generic drug is not distributed in the US at this time. But the Livalo is so expensive I cannot afford it. My doctor knows I bought this drug thru the Canada Online Pharmacy and she writes the prescriptions for me to send to them. I do not know how to navigate the internet to find out this information. Any help you offer would be appreciated.

  • My pharmacy WALGREENS changed drug manufacturers to CADILA HC LTD, dist by ZYDUS PHARMA.. My medication is Pramipexole Dihydrochloride 1.5mg.
    Every time I take one tab at bedtime it makes me sick. I did report this to Walgreen twice. They 1st told me it was me it was because I was taking Cipro and the twp do not mix. I stopped the AB for 7 days and this med still made me sick. I called Walgreens again and they said they need a Dr. order to change to a different manufacturer. My Dr. is from India. What can I do? I feel like my body has been compromised from this drug as I’m now feeling sick on and off through out the day. I have not stopped the drug because was not advised by Walgreens , so I decided to check out this company myself. Now I see what the problem might be and I am NOT taking this med again.. Please help what should I do? Thank you, Judy

    • Hi Judy

      I’m not a physician and do not give medical advice, but I would suggest you do speak with your doctor and explain the reaction to the medicine and request another prescription and also discuss this, again, with your pharmacist so that you obtain a pill made by another company.

      Best of luck,
      ed at pharmalot

  • Hello, I am really having problems with my meds , they are coming from zydus pharm. I take trazadone, the problems with this new generic is that half of them do not work. I take this medicine for major depression and now my ailment is not preventing my depression from engulfing me. I purchase my meds from rite aid, they used to give me a generic from or by plavix, but they started purchasing from this other company. I have spoke to rite aid and they said there’s nothing they can do.what is your suggestion on this problem?

  • Hello, I am really having problems with my meds , they are coming from zydus pharm. I take trazadone, the problems with this new generic is that half of them do not work. I take this medicine for major depression and now my ailment is not preventing my depression from engulfing me. I purchase my meds from rite aid, they used to give me a generic from or by plavix, but they started purchasing from this other company. I have spoke to rite aid and they said there’s nothing they can do.what is your suggestion on this problem?

  • Walgreens just switched my Cholestyramine (powder for controlling cholesterol) from Sandoz to Zydus and there is a huge difference in how it (dissolved in water) feels in my throat and stomach. It has been very uncomfortable to the point, where I cannot drink it. Am returning to the drug store.

    • I have just started trying to use the Cholestryramine from Zydus and find that it does not dissolve in water. What can we substitute?

  • I am currently taking a generic form of oxycodone manufactured by Zydus that sometimes is NOT EFFECTIVE. I also have noticed that the adjuvant used can give me an odd reaction ie headache and and nausea. I wish I could obtain a different generic as I have in past that works much more effectively. I began to suspect that this was perhaps a company NOT LOCATED IN THE US after this began to be a problem. After seeing the complaints my suspicion is correct. When are we consumers going to be LISTENED TO. I complained to my pharmacy at one point and received a different generic that actually worked as it should have . This company is ripping off the American consumer. WHAT A THE FDA DOING??????

  • Cadilla (Zydus CND) product Zytanix (metolazone IP) produces no therapeutic response, yet their previous USP-approved product (Zytanix-metolazone USP) did produce a therapeutic response. I believe this company knows very well that its IP approved pharmaceuticals are substandard, but does nothing about it because they can get away with it and it means higher profits.

Your daily dose of news in health and medicine

Privacy Policy