Author: Amber Hermans, Junior Project Engineer
The pharmaceutical industry is one of the most strictly regulated industries. This is necessary because these extensive measures prevent potential incidents from having a detrimental and even lethal impact. Despite strict regulations and a mandatory quality system things still go wrong. On the one hand, catastrophic incidents that occurred in the past often gave rise to significant quality system improvements and have driven legislation further. On the other hand, minor incidents are often the most interesting, because they highlight possible gaps in a quality system early and thus show where there is room for improvement.
One way to see where things went wrong, is to take a look at the FDA drug recalls. A recall is a voluntary action taken by a company to remove a defective drug product from the market (U.S. Food & Drug Administration, 2018). A product is recalled after a defect or safety issue has been discovered by either consumers, regulators or the manufacturers themselves. This article summarizes the 5 most common FDA drug recalls that occurred in the past 3 years (U.S. Food & Drug Administration, 2021). Advipro, as a GxP-specialist, can support all processes that prevent these recalls.
The sub- or superpotency of a drug refers to the activity of the Active Pharmaceutical Ingredient (API). If this activity is too high (superpotency), patients might risk an overdose. However, if the activity is too low (subpotency), the drug might also have life-threatening consequences to those patients who are depending on the curative effect. Therefore, recalling pharmaceutical products with these defects is crucial. Luckily it does not happen very often. Out of a total of 270 drug recalls in the past 3 years, only 5.6% of all recalls were due to a sub- or superpotent drug.
8.1% of drug recalls are due to incorrectly labelled products. This relates to multiple issues: from less crucial defects like an incomplete printed drug label to more important issues such as the dosage that is incorrect. However, the riskiest type of mislabelling is considered to be a label mix-up, where the drug product has received a label from either a different batch or an entirely different pharmaceutical. As proven in the past, a mix-up can be very hazardous. Even with all the extensive measures taken nowadays to prevent label mix-ups, incidents still occur. This shows how crucial the role of labelling is in the pharmaceutical industry.
Sterility assurance is a somewhat abstract concept. It is the confidence provided by the manufacturer that a product does not contain viable microorganisms. Thus, when a lack of sterility assurance occurs, the product could be sterile, but it is not possible to say with confidence, that it is. This type of recall happens relatively often (9.6%) and thus deserves its spot in the top 3.
All drug components in the product have to be declared. This transparency is needed so no unauthorised products are released to the market. Though, sometimes through analyses performed by the FDA, undeclared amounts of drugs are found and these products are recalled. This unexpectedly turns out to be the second most common drug recall in the past 3 years (13.0%). This high occurrence can be justified by a mass-recall of hand sanitizers with an undeclared amount of methanol from February through August 2020. At that time, there was a high demand for hand sanitizers due to the coronavirus pandemic, which led to the import and production of methanol-tainted hand sanitizers (Holzman et al., 2021). Methanol is highly toxic and additionally, hand sanitizers might be wrongfully ingested as a substitute for alcohol (ethanol). Hence methanol is an unauthorized compound in hand sanitizers and when the manufacturers did not include it on the compound list, they were recalled due to an undeclared amount of drug present.
More than half of the recalls are due to contamination, which can be either microbial (11.1%), chemical (31.9%), physical (9.3%) or from other pharmaceutical products (1.5%). Contamination can be prevented by having Good Manufacturing Practices (GMP) in place. Microbial and physical contamination are prevented by performing the production process in a validated and controlled environment. And chemical contamination or cross-contamination can be prevented by having a validated cleaning process in place, among numerous other GMP measures. Throughout the years Advipro has built an expertise in all GMP-related processes.
Not all drug recalls are product related. Some are related to the packaging of the drug product. For example, besides the previously mentioned mislabelled products, physical packaging defects may also cause a recall as they can raise questions about the sterility assurance of the product. Even the shape and outlook of a packaging can trigger a recall. Recently four different hand sanitizers were recalled because their packaging resembled that of a drinking bottle or food pouch. This defect is completely GMP unrelated, but can cause serious consequences when mistaken for something edible, and thus a recall was requested by the FDA.
Taking a look at some defects in the form of FDA recalls, gave us an small overview of where our colleagues are active:
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Holzman, S. D., Larsen, J., Kaur, R., Smelski, G., Dudley, S., & Shirazi, F. M. (2021). Death by hand sanitizer: syndemic methanol poisoning in the age of COVID-19. Clinical Toxicology, 59(11), 1009–1014. https://doi.org/10.1080/15563650.2021.1895202
U.S. Food & Drug Administration. (2018, July 3). FDA’s Role in Drug Recalls. Retrieved November 4, 2021, from https://www.fda.gov/drugs/drug-recalls/fdas-role-drug-recalls
U.S. Food & Drug Administration. (2021, October 20). Drug Recalls. Retrieved October 22, 2021, from https://www.fda.gov/drugs/drug-safety-and-availability/drug-recalls