In 2018, the FDA reported that some generic versions of the angiotensin II receptor blocker (ARB), contained nitrosamine impurities that didn’t meet safety standards. As a result, the generic versions of valsartan were recalled. Sadly, these types of product recalls due to tainted drugs appear to be on the rise – more than 45 generic blood pressure medications have been recalled since last summer.
A recent spotlight from NBC News highlighted these concerns in a conversation with an ex-FDA inspector who sounded the alarm about the FDA’s struggles to properly inspect the growing number of overseas drug manufacturers. He said that these firms may not be maintaining proper records or fully disclosing problems in their own production lines. According to the article, “the valsartan case underscores a new reality in the pharmaceutical industry — a growing reliance on foreign manufacturers to provide the raw ingredients for drugs sold in the U.S. “ It also points out that it’s not only foreign manufacturers, but also domestic ones that are not being properly inspected simply because of overburdened inspectors working to keep pace with the industry’s rapid growth. According to the news story, the FDA also inspected only about one in five domestic drug manufacturing facilities last year.
Another article in The New York Times re-affirmed concerns over deceptive practices in overseas drug manufacturing. The article shared problems exposed by an FDA inspector in Indian and Chinese plants, where he uncovered fraud or deceptive practices in almost four-fifths of the drug plants he inspected over a five-year period. These practices included tampering with or falsifying reports, re-testing drugs to get the desired results and operating within unsterile environments. According to the article, the FDA, which approved more than 1,000 new generic drug products last year, faces a vast challenge in safeguarding these medications.
Based on FDA data, roughly 85 percent of the facilities manufacturing the ingredients in American drugs are located overseas, and nearly 40 percent of all our generic drugs are made in India.
These recent revelations and growing recalls of generic drugs point to growing concerns that the FDA cannot properly monitor operations in foreign facilities manufacturing life-saving drugs that are being sold in the U.S., despite user fees and updates to the Generic Drug User Fee Amendments II (GDFUA II). This revised act was created to help ensure that quality is maintained globally. Under GDUFA II, the FDA committed to updating the inspection classifications database by January 1, 2019 and to continue to update it every 30 days.
Part of the lack of quality control is insufficient funds, but it’s also a question of logistics. Surprise visits to overseas facilities can be difficult to arrange without advanced preparation, and often times, contrived data can be difficult to prove.
Meeting the Need for More affordable Generic Drugs
Despite these challenges, U.S. and European-based manufacturers are scrambling to develop generic drugs to treat a growing base of citizens with chronic conditions, at costs they can afford. And in reality, the use of offshore manufacturing plants to supply the raw materials or manufacture end-products more cheaply than would ever be possible in the U.S. or Europe has proven to be a good solution.
The key is for sponsors and Contract Development & Manufacturing Operations (CDMOs) in the U.S. to take matters into their own hands and conduct their own proper and vigilant monitoring when doing business with offshore partners or suppliers. Consider the following ways this can be accomplished:
- Ask the tough questions up front. Before you even start working with an overseas supplier, ask it about its project management processes, its reporting structure, or how it handles and report problems.
- Conduct regular meetings or have an onsite advocate. It’s important to have boots on the ground at best, and conduct regular phone meetings at the least to ensure you are aware of any issues, concerns or project updates that may be occurring.
- Ask for references. Speaking with customers is probably the most important thing you can do to vet an offshore partner, but don’t settle for the company’s customer poster child. Ask to speak to a customer that ran into problems so you can hear how they handled them. Also, do your own research to uncover any deficiencies at the plant.
- Ask what percentage of the business is with U.S. companies. This question will give you a good idea of how experienced the company is in terms of navigating FDA guidelines and policies, as well as how they are able to assimilate to the U.S. business culture and quality standards.
As the demand for generic drugs increases, the use of offshore suppliers to provide more affordable sources of critical raw materials and manufacturing is meeting a great need. Yet more affordable sourcing strategies can never compromise the safety of the life-saving drugs patients rely on. Greater oversight and collaboration is needed to ensure that product defects, such as the valsartan one, is addressed before they have a chance to cause physical harm.
For related articles, please read: Generic Drug Makers Continue to Face Hurdles to Make Drugs More Affordable, or Soaring to New Heights with Quality Control Checklists in API Manufacturing.