As drug recalls increased over the past 12 months, questions regarding FDA oversight of drug manufacturing are triggering questions involving IVD oversight by the federal agency and potential implications for clinical laboratories

Pathologists and clinical laboratory managers are following the recent recalls of popular blood pressure medications in the past six months. These issues once again placed the spotlight on failures in the US Food and Drug Administration’s (FDA’s) drug safety oversight processes.

With the global supply chain—and a large amount of secrecy—involved with manufacturing modern pharmaceuticals, maintaining standards and enforcing safety requirements appears to be challenging the FDA’s monitoring capacity. In November 2018, Scott Gottlieb, MD, then commissioner of the FDA and current resident fellow at the American Enterprise Institute, told USA Today, “We put out very big guidance on this—it’s a known risk. It’s a place where there’s been a significant increase in focus in recent years.”

Despite the increase in focus, Kaiser Health News(KHN)recently highlighted potential concerns not shown in the headlines of mainstream media outlets—both for the public and for medical laboratories that rely on FDA oversight in other areas, such as in vitro diagnostics (IVD).

“Since the start of 2013, pharmaceutical companies based in the US or abroad have recalled about 8,000 medicines, comprising billions of tablets, bottles, and vials that have entered the US drug supply and made their way to patients ….” KHN reported. “Over the same period, 65 drug-making facilities recalled nearly 300 products within 12 months of passing [an FDA] inspection ….”

Data published by Stericycle Expert Solutions, a global B2B services company, offers deeper insight into forces driving recalls in Q3 of 2018. “Pharmaceutical recalls increased 19% to 92—the second highest quarter since Q3 2013,” they note. “Failed specifications were the top reason based on recalls for the ninth consecutive quarter.”

Current Good Manufacturing Practices (CGMPs) ranked second, accounting for 23.9% of recalls in their study. The same data shows medical device recalls also increased across 2018 compared to the prior year.


In an e-mail to Kaiser Health News, FDA spokesman Jeremy Kahn said, “While the FDA would prefer that no drug be distributed that later is recalled, we do not think that a recall indicates a failure of FDA inspection and surveillance programs.” He continued, noting that inspectors “may not uncover all issues or practices that may eventually result in a problem leading to a recall” and that “not all recalls are the result of poor manufacturing practice.” (Graphic and caption copyright: Kaiser Health News.)

Issues now presented as “shortcomings” with pharmaceutical oversight could one day present serious concerns for pathology groups, clinical laboratories, and other service providers using IVDs.

In a field requiring precision, quality, and accuracy to provide reliable results for an ever-growing portion of modern healthcare’s questions, quality control of testing materials and devices is critical—particularly when dealing with the increasingly smaller samples and sensitive reagents used today.

Enforcing Standards Around the World

Despite today’s CGMPs and myriad regulations designed to ensure pharmaceuticals are safe, KHN notes that the FDA struggles to stay ahead of manufacturers and suppliers who might violate regulations. Even when FDA inspectors discover issues, they have little means of enforcing standards and encouraging change.

“A KHN review of thousands of FDA documents—inspection records, recalls, warning letters and lawsuits—offers insight into the ways poorly manufactured or contaminated drugs reach consumers,” KHN notes. “Inspectors miss serious hazards. Drug makers fail to meet standards even after the FDA has taken enforcement action. Hundreds of plants haven’t been inspected for years, if ever.”

However, no amount of protective regulations or standards can make a significant impact without proper enforcement. In October 2017, the FDA announced they would recognize the European drug regulatory authorities of eight countries to help reduce duplicative inspection. “By partnering with these countries,” said Gottlieb, “we can create greater efficiencies and better fulfill our public health goals, relying on the expertise of our colleagues and refocusing our resources on inspections in higher risk countries.”

Nonetheless, statistics indicate that the FDA’s ability to support global inspections is still stretched thin. More than 2,500 foreign and domestic facilities have not received a drug-quality inspection in more than five years, according to KHN. Additionally, 1,200 domestic facilities and 400 foreign facilities were found to have no drug-quality inspection records dating back 10 years, KHN reported.

While Gottlieb hopes to “clear the backlog” by the end of September 2019, the fact that such a backlog exists at all is cause enough for concern—particularly in light of Gottlieb’s April 2019 resignation, KHN noted.

Lack of Effective IVD Manufacturing Oversight Affects Medical Laboratories

Even with an effective inspection system, the FDA’s options for bringing manufacturers into compliance are limited. KHN points out that over the past decade, 70 plants in their data sets received citations for the same violation four or more times. The FDA cannot issue mandatory recalls, and while it can seize drug products, it has only exercised that right 23 times in the past decade. This shows how few options the FDA has for ensuring contaminated or otherwise defective medications do not reach patients, hospitals, and other part of the healthcare industry.

For anatomic pathologists, clinical laboratories, and other diagnosticians relying on the FDA to be the gatekeeper of quality and safety—as well as ensuring IVDs provide accurate, reproducible results—these trends in pharmaceutical oversight should be cause for concern.

Worse still, the lack of effective enforcement options available to inspectors and oversight committees—alongside the sheer scale of a global manufacturing chain—offer few easy answers for reversing the trends making headlines today.

—Jon Stone

Related Information:

When Medicine Makes Patients Sicker

FDA Chief: Blood Pressure Medicine Recalls Reflect Increased Scrutiny on Drug Safety

Recall Index Q3 2018

FDA Takes Unprecedented Step toward More Efficient Global Pharmaceutical Manufacturing Inspections