Spurred by a March 5, 2024 citizen petition to the Food and Drug Administration (FDA), a flurry of class action complaints have been filed claiming that drug makers failed to warn consumers about the presence of benzene in popular acne products.

The citizen petition submitted by Valisure LLC alleges that dangerous levels of the chemical benzene—a carcinogenic material at certain concentrations and exposures—are present in benzoyl-peroxide-based acne products under certain storage conditions.

Valisure, an independent laboratory that conducted lab tests on the degradation of benzoyl peroxide (BPO) in over-the-counter (OTC) and prescription products, calls upon FDA to commence a broad recall of the acne products, restrain their sale, and issue heightened regulations and guidance to protect consumers.

FDA will carefully consider these allegations and study the test results, conduct its own testing, and communicate with industry trade associations and individual companies who may have contradictory data that refutes Valisure’s test results.

HISTORICAL REGULATION OF BENZENE BY FDA

Over the last several years, FDA has focused on the existence of benzene as an inactive ingredient or residual solvent in certain drug products, with a particular focus on propellants. In 2021, FDA requested recalls of various drug products due to the presence of benzene contaminants, including product lines such as OTC antifungal sprays, aerosol deodorant and antiperspirant sprays, hand sanitizers, hair and scalp sunscreen sprays, and topical anesthetic sprays. FDA also published a web page for consumers on benzene contamination in drugs.

Although the March 5 petition is the first instance in which Valisure has raised concerns regarding benzene as a degradant rather than benzene as a contaminant or impurity, the organization is no stranger to citizen petitions. According to its website, Valisure is a company that sells its “independent product testing” to fill a “gap in the healthcare supply chain.”

In doing so, Valisure has focused on benzene contamination through a series of citizen petitions earning FDA attention:

• March 24, 2021: Concerning the levels of benzene in hand sanitizer
• May 24, 2021: Concerning the levels of benzene in sunscreen and after-sun-care products
• November 3, 2021: Concerning the levels of benzene in antiperspirant body sprays
• October 31, 2022: Concerning the levels of benzene in dry shampoo

In each instance, FDA issued an Interim Response Letter, primarily concluding that it could not reach a decision on the petitions within the first six months because they raise complex issues requiring extensive review and analysis. On December 27, 2023, however, FDA separately issued an alert to manufacturers regarding the risk of benzene contamination from drug components and other potential risk factors.

NEXT STEPS FOR FDA

At present, FDA guidance requests that manufacturers avoid use of benzene in any quantity in the manufacture of drug products. If the use of benzene is unavoidable, FDA’s standard is that no more than 2 ppm of benzene be present during the entire shelf life of a drug product.

Although Valisure’s March 5 petition alleges that the instability and degradation of certain BPO products at certain temperatures can lead to benzene levels in excess of the limit, Valisure’s lab tests did not review the extent of benzene formation at room temperature storage nor the effects on consumers of prolonged benzene exposure or absorption.

FDA has cautioned that the Valisure data must be verified as accurate and reproducible before the agency will take action against BPO products. Additionally, the US Pharmacopeia separately raised concerns on the testing methods and procedures used to generate the Valisure findings. These concerns, if substantiated, could lead to disqualification of the Valisure testing data.

In either case, FDA is likely to face mounting public pressure to investigate and respond to Valisure’s allegations given the size of the market and the number of consumers, including adolescents, that may be impacted by an FDA action—whether FDA permits continued marketing or requests a market withdrawal of BPO acne products.

Currently, there are 31 active New Drug Applications and Abbreviated New Drug Applications for prescription BPO products listed in FDA’s Orange Book, with hundreds more BPO products in the OTC market. If the benzene exposure levels are validated by further investigation, FDA will carefully weigh the risk-benefit calculus of and medical need for the BPO acne treatments, while exploring labeling revisions, usage limitations, and storage directions to minimize risks.

TAKEAWAYS

Prescription and OTC drug manufacturers are already responsible for monitoring the stability of samples from each lot of their drug products to ensure the quality lasts through the labeled expiration date. However, all sellers of BPO products may be impacted by the class action litigation arising from the Valisure tests and should take steps to review their batch release and stability data to prepare a scientific defense to a variety of potential claims, if need be. They should also take proactive steps to prepare for litigation involving multiple plaintiffs, defendants, and jurisdictions.

Manufacturers may wish to review their policies and procedures and internal supervisory roles to ensure compliance with and impact on regulatory obligations related to good manufacturing practices, adverse event reporting, drug shortage notifications, and drug application requirements. They can also confirm or tighten internal product specifications and analytical testing procedures and scrutinize third-party raw materials and formulations.

As noted above, there are still many questions left open by the Valisure petition, including the applicability of the lab test results to products merely stored at room temperature. Accordingly, affected manufacturers should consider a thoughtful, measured approach to this petition as we await further guidance from FDA.

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