Last week, independent research organization Valisure submitted a formal report. Citizen applicationThe company acknowledged that recent test results indicate that “benzene, a known human carcinogen, may form at elevated levels in benzoyl peroxide (‘BPO’) acne treatment products.”
“Laboratory testing of dozens of prescription and over-the-counter benzoyl peroxide products shows that currently prescribed BPO drugs are fundamentally unstable and resistant to high temperatures,” Valisure said in a company press release. It has been suggested that if handled or stored, it may produce unacceptably high levels of benzene.” Product may be exposed during consumer handling. ”
The company’s civil application to the FDA, filed on March 5 of this year, includes a historical study of the classification of benzene as a known carcinogen, an overview of Valisure’s testing and analysis of results, and information to address the issues. outlines the actions FDA should take. Risk of potential consumer exposure to benzene through benzoyl peroxide acne products.
Benzene and BPO
As stated in Valisure’s citizen filing with the FDA, “Epidemiological studies have long shown that benzene has been directly associated with cancer in humans following sustained exposures as low as 0.8 ppm.” I am.
The application further states that research into benzene’s carcinogenic properties dates back more than a century, citing the “1939 benzene study.” [which] “Long-term exposure to benzene at any concentration above zero is not safe,” a comment reiterated in a 2010 review of benzene research, specifically stating that “long-term exposure to benzene at any concentration above zero is unsafe.” There is probably no safe level of exposure.” And all exposures constitute some risk in a linear, if not superlinear, additive manner. ”
The filing also cites information from the American Cancer Society, stating that the risks of benzene exposure include “sufficient evidence that benzene causes acute myeloid leukemia (AML)… ALL), chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin’s lymphoma.
Regarding FDA’s current regulatory actions regarding benzene in consumer product formulations, the filing states: “The FDA now recognizes the dangers of benzene and, as a result, maintains that it should not be used in the manufacture of any drug ingredient, and only when use is ‘unavoidable’ “Strict concentration limits should apply,” Valisure said.
Valisure states in its filing that “the specific issue with benzene in benzoyl peroxide products is not an issue of contamination with a specific ingredient, but with degradation, and this is due to the It is a key element of an organization’s case for action.
Additionally, Valisure said in its filing that the organization is “not aware of FDA guidance regarding the total amount or permissible daily exposure limits for benzene in pharmaceuticals and cosmetics containing benzoyl peroxide products, and We are demanding urgent action on their behalf.” “We called on FDA to issue guidance to fill this gap,” the agency said, adding that it is a priority for FDA to address the issue of benzene contamination in older products such as hand sanitizers, sun care products, body care products, and dry shampoo. He pointed out that he was doing so.
Test results supporting Valisure’s Citizen’s Application
As detailed in the filing, Valisure’s initial analysis was conducted on 175 acne treatment products, of which “99 products contained BPO as at least one active ingredient; 58 products contained BPO as at least one active ingredient; contained the active ingredients individually or in combination with salicylic acid (46 of 58)” 18 The product contained no pharmaceutical ingredients and contained sulfur, adapalene, azelaic acid, niacinamide, and zinc. 83 of the BPO products are OTC and 16 are prescription purchased from licensed wholesalers.
Importantly, “native benzene analysis was performed on 99 BPOs, including acne treatment products, and benzene was detected in 94 products. It was well over 2ppm.”
As a result, “particularly because of the high content of benzene in BPO acne treatment products and the discovery of studies in the academic literature as early as 1936 concluding that BPO can break down directly to benzene.” , Valisure will conduct high-temperature stability studies targeting various markets for BPO products and formulations.[and] 50°C (122°F) was selected as the stable temperature for an extensive study of 66 BPO products. ”
The filing goes on to report that “the results of this 50°C stability study demonstrated significant instability of BPO and a tendency to produce significantly higher levels of benzene in just 18 days.” This is said to be an important discovery. (122°F) is the appropriate temperature “to which the product may be exposed by consumers during distribution and handling,” as well as for conducting accelerated stability studies over a period of at least three months. It is also an accepted incubation temperature used in the pharmaceutical industry. ”
Additionally, during its testing, Valisure found that the packaging of some BPO-containing acne treatment products may be porous to benzene, and that some of the benzene contained in the product or “We have observed evidence that some of the benzene formed within the product may leak into the skin, environment or air surrounding the package,” the filing states.
Therefore, further testing was carried out to “assess the levels of benzene in the air surrounding the BPO product during incubation” and the results showed that “high levels of gaseous benzene are produced from the BPO-containing product and may be used for consumption such as outdoors.” This suggests that there is a possibility that it may be dissipated into the personal environment. It confirms that in a hot car or in the bathroom during a hot shower, “benzene can escape from unopened BPOs containing worryingly high levels of acne treatment products.”
Measures required to address benzene contamination of BPO acne products
In its filing, Valisure requested a set of nine actions or interventions by the FDA to address “serious concerns about the safety of BPO-prescribed drugs,” particularly the laboratory’s “current evidence.” . [which] “Commercial BPO products produce large amounts of benzene when stored at temperatures above ambient, specifically 37°C (98.6°F), 50°C (122°F), and 70°C (158°F). This suggests that it may be generated.
One of the actions requested to address benzene contamination in BPO acne products is that a citizen petition states that “consistent with FDA’s obligation to ensure safety, the Secretary and FDA recommend that the active pharmaceutical ingredient contain benzoyl peroxide.” We are requesting that the product be recalled and discontinued.” We manage prescription and over-the-counter drugs in the United States. ”
The filing goes on to say that “such action is critical to public safety,” and that “removal of benzoyl peroxide from the market would not harm the U.S. health care system or the current use of this drug.” “It is not expected to have a significant impact on patients.” The fact that many alternatives exist for the treatment of acne vulgaris”, “Valisure specifically tested other medications such as salicylic acid and found no evidence of benzene formation.”
Other requests in the petition include that “FDA promulgate regulations requiring robust independent chemical testing and verification of drug products” and that “for the foreseeable future while these regulations are pending, FDA “Issuing formal guidance recommending appropriate testing and verification,” the application states.
