“Perhaps the most important line in this entire statement is: ‘It is important to note that USP standards are applicable during the entire shelf life of the product, not just at the time of release,’” said Bunick. “The problem with the USP statement is that the FDA already rejected their methods as not being good enough, and you wouldn’t know that unless you read the FDA’s statement.”
In 2020, the FDA rejected USP’s method of gas chromatography–flame ionization detection for benzene analysis, which is a method that has less precision and accuracy.7
The FDA elected the industry standard of gas chromatography–mass spectrometry (GC-MS), which is more accurate, and is the method Valisure chose to use in its recent petition.
Validating Valisure’s Findings
The findings of benzene in BPO products were independently validated by 3 different labs using 3 different technology platforms, including GC-MS, GC–high-resolution mass spectrometry, and selected-ion flow-tube mass spectrometry. Bunick shared updates that CBS News followed up with the labs, and 2 of the 3 responded and confirmed Valisure’s results when contacted.
“There have been concerns that, superficially, when you look at the petition, that it’s all about elevated temperatures. That is not true. Benzene was also found extensively at room temperature on the shelf and off the shelf. This important fact cannot be overlooked. The focus of the petition is stability studies,” said Bunick.
Of the 66 products tested at day 0 at room temperature, 10 of the products had more than 10 ppm of benzene and 19 products had more than 2 ppm of benzene. According to Bunick, the biggest problem with BPO is degradation, not contamination. He also reminded attendees that although the FDA permits up to 2 ppm of benzene, that is only if it is absolutely necessary to manufacture said product and that product represents a major medical advance. Bunick added that with so many other acne treatments available, it is not absolutely necessary to manufacture BPO with unsafe levels of benzene, even at 2 ppm.
Stability testing is not meant to replicate consumer use or real-world use; it is intended to evaluate the full 3-year product life cycle. Three-year stability at room temperature is equal to 169 days at 50 °C (122 °F), which is based on industry standards. It is a regulatory requirement to perform stability testing on products and should be conducted on products under normal storage conditions, or, preferably, under exaggerated conditions, according to the FDA.
However, in some cases, stability testing does overlap with real-world outcomes. Bunick shared new data for the first time at AAD 2024 that demonstrated that of 5 BPO products tested at 37 °C (98.6 °F), or human body temperature, 1 product had more than 10 ppm of benzene, and all 5 had over 2 ppm of benzene. This 37 °C data was published shortly after the AAD in a peer-reviewed journal, Environmental Health Perspectives; Bunick is a co-author along with the Valisure research team.8
When considering Valisure’s testing, Bunick pointed out that every time Valisure has detected a carcinogen in consumer products, some form of a recall followed.
Bunick noted that some individuals and organizations have questioned Valisure and its credibility. Valisure is a company hired by the US Department of Defense to check the quality of drugs for the United States military. Their No. 1 clients are drug purchasers, according to Bunick, because these companies want to know what they are buying is safe.
Lastly, Bunick concluded his session by reviewing recent benzene studies and news items, all of which called out benzene’s associated risk with various cancers such as leukemia. Regulatory agencies such as the CDC, the World Health Organization, the Environmental Protection Agency, and the National Institute for Occupational Safety and Health have all made similar statements that benzene is a known human carcinogen.
Additionally, in December 2023, the FDA released new guidance for industry for the reformulation of drug products containing carbomers manufactured with benzene.9
“So, what does this all mean, and what am I going to advise for patients? I will say, we as a community have to see what is validated.I do not necessarily think at this moment that no one should use benzoyl peroxide. I think there has to be a proportional response until more data comes out,” said Bunick.
“With Valisure’s agreement, for those providers and patients who wish to continue using benzoyl peroxide–containing products, a proportional response at this time would be to keep the product refrigerated at all times, renew the medicine every 3 to 6 months, and avoid heated storage. This will not necessarily eliminate all benzene but should slow its decomposition. This measure gives the medical community a chance to await further investigation and recommendations,” Bunick told Dermatology Times.
READ MORE: Dermatology Resource Center
This article originally appeared on Dermatology Times.
References
4. Bunick CG. Discussion of new findings of benzene in BPO-containing products. Presented at: 2024 American Academy of Dermatology Annual Meeting; March 8-12, 2024; San Diego, CA.
7. FDA. Direct injection gas chromatography mass spectrometry (GC-MS) method for the detection of listed impurities in hand sanitizers. August 24, 2020. Accessed March 14, 2024. https://www.fda.gov/media/141501/download
8. Kucera K, Zenzola N, Hudspeth A, et al. Benzoyl peroxide drug products form benzene. Environ Health Perspect. 2024;132(3):37702. doi:10.1289/EHP13984
9. FDA. Reformulating drug products that contain carbomers manufactured with benzene: guidance for industry. December 27, 2023. Accessed March 14, 2024. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/ reformulating-drug-products-contain-carbomers- manufactured-benzene
