Valisure's David Light Shares Insights Into Newly-Published Benzene and BPO Data

In March 2024, Valisure, LLC, an independent testing lab, first raised alarms about elevated benzene levels in certain benzoyl peroxide (BPO) acne products, urging the US FDA to investigate.

Now, a new study published in the Journal of Investigative Dermatology confirms these findings, showing significant benzene contamination in BPO products from major US retailers—this time with testing conducted at room temperature.

To explore the clinical implications of these data, Dermatology Times spoke with Valisure's president and co-founder, David Light.

Transcript

David Light: My name is David Light. I'm the co-founder and president of Valisure.

Dermatology Times: What is the significance of detecting benzene in BPO products at room temperature, especially compared to previous studies conducted under elevated temperatures?

Light: It's definitely a significant finding, and one that we did see evidence for even when we were looking at stability testing. In the previous studies that came out in March, we did have room temperature analysis in those day 0 figures. But obviously, the focus was the stability over time, accelerated stability, which has various levels of heat. We did a lot of work at 50 degrees Celsius, but also a lot of work at 37 degrees Celsius, and actually, the peer-reviewed paper in the Environmental Health Perspectives journal included a lot of data on 37 degrees Celsius, which is the temperature of the human body, and we were seeing evidence, even then, of a variety of products that had benzene in them at room temperature and above the conditional limit of 2 parts per million.

But to the question, we did a lot deeper dive of that with this study. There's over 100 drug products from a variety of different states, and we saw, effectively, the the same thing that we've seen before, where quite a number of them had concerningly high levels of benzene. Again, the 2 parts per million is a conditional limit from the FDA. It really only applies if the drug product is a significant therapeutic advance and benzene is required for its manufacture, which we don't believe any of that applies to benzoyl peroxide product. Ostensibly, the limit is 0. The FDA says just don't use it because it's unacceptably toxic. We definitely see it quite extensively in about a third of the products over that 2 PPM conditional limit just at room temperature buying the products off the shelf.

Dermatology Times: The study found that 34% of tested BPO products exceeded the FDA's conditional limit. How significant or concerning is this finding given the wide use and accessibility of BPO products?

Light: This is certainly concerning in general. Benzene is not a potentially dangerous chemical; it is well known to cause cancer in human beings, and there's been studies on it for over 100 years. It's extremely well-accepted, and that's why there's law around it. People are considering toxins like endocrine disruptors and others, and a lot more research is needed, but the research is extremely strong on benzene. Really, any amounts are concerning, and there are regulatory implications and laws around even these trace levels at 2 ppm or higher.

But I think it's especially concerning for something like benzoyl peroxide acne treatments that can be used over the counter; there's obviously a lot of people using them, and can be used in high quantities. I think anything, especially in the world of dermatology, it's not just a small pill that you're taking. We're talking about concentration limits, which, if you take 100 times more of the product, and are putting it, let's say, over a patient's back, perhaps daily, not just a spot treatment that gets used maybe a few times a year, that could be 1000 fold or more difference in how much somebody is actually using. Again, what we're talking about are these conditional limits, are just concentrations, not total amounts. That's one element that we've been petitioning the FDA for, is to better quantify what a daily limit is, not just a concentration limit, and we've seen that with other drug products like Zantac, metformin, balsar and Losartan, a variety of different drugs that got recalled for these carcinogenic contaminants, was not just a concentration limit: It was also a total daily amount limit. I think that is especially concerning in dermatology products, because you could literally be using it at 1000 fold or higher amounts than, let's say, a small tablet.

Dermatology Times: In the study, benzene concentrations varied based on the formulation. Why might certain formulations or brands may be more prone to benzene formation than others?

Light: The fact that you do certainly see some correlations based on formulation or brand is really very much in line with what we've been saying the whole time, that this is an instability problem. It's not just contamination; obviously, the room temperature data showed very clearly that it is also a contamination issue. But broadly speaking, the benzoyl peroxide molecule is known to be unstable. Our tests were the first test in drug products that showed this is happening and that benzene is forming and present at concerningly high levels in drug products. But it's been known in the world of chemistry, there's actually a lot of problems with plastics and the resins and other industries where benzoyl peroxide is used on purpose because it is unstable and forms radicals, and of which one of the end products is benzene. The fact that you have different levels of benzene on the shelf, different levels of stability, or instability, as we've seen with previous studies, makes a lot of sense, because it is an unstable molecule that, depending on what kind of environment it's in, will break down slower, faster, as we showed. Things like lowering the temperature, refrigeration, temperature slows it down pretty substantially, but it is unstable.

Even if it was entirely clean, let's say, if you were applying it on your face and go outside and get exposed to UV. UV also destabilizes, and again, very well-known in the chemistry literature, but this is the first time that it's actually been looked at in drug products. Certainly, a very important component of trying to work on these in the future is: Can these formulations be stabilized? Until that's really figured out, I think it's a big, broad concern that changes a lot with with the environment and with the formulation. We don't know what parts of the various formulations may accelerate or decelerate this kind of benzene formation, but it's very hard to know that, because actually, even when you have ingredients listed on a product, you can look at the inactive ingredients, but you don't know how much of any of them have. You could have an ingredient that's a 100th of 1%, and you could have an ingredient that's 50% of the entire product. You don't necessarily know what the total amounts are, and you can even find ingredients that don't help you very much. From a chemistry perspective, it might say fragrance, but that could be a whole variety of different molecules from a chemistry perspective. I think that time will tell how or what makes for a more or less stable formulation, but certainly it makes sense that it tracks with formulations and brands in terms of how much is already there and how much might form over time.

Dermatology Times: The findings showed that benzene formation increases with higher temperatures, particularly during incubation at 50°C. How might this impact storage of BPO products?

Light: We certainly saw that the variety of of dermatologists, and I believe the American Acne & Rosacea Society, had put out a press release at some point in when the first studies came out in March, recommending refrigeration. We did look at that in this study, as well, a particular product that had micro-encapsulation technology, which did not appear to stabilize it when exposed to elevated temperatures over a couple weeks, and the refrigeration at least over the 2 weeks that we analyzed, did seem to stabilize the product somewhat. But again, that's only looking at it for 2 weeks, and it could be the amount that could be formed there are going to be within the noise of the detection and instrumentation.

One element that wasn't looked at specifically was also outside of the products themselves. That's actually another important point, even for the different formulations that you were asking about; there are also different packaging of different products, and one of the things that we showed in our first studies was that the benzene can leak outside of the packaging. You can imagine that it could be certain packaging where you leak a lot of the benzene. It might actually leave less benzene in the product itself, and vice versa. It's a really complex problem, of which are obviously high level of concern, is the instability of the product, but also very well-known and understood in chemistry, is that the colder you keep something, the more stable it'll be. We definitely see that a number of dermatologists are recommending, if you're going to store it, store it in a refrigerator, perhaps, and the current data certainly suggested that that will slow down the formation of benzene.

Dermatology Times: What is the status of Valisure's petition to the US FDA to recall BPO products with levels of benzene exceeding 2 ppm?

Light: An important point on recalls is that it really has to come from the industry. It's not commonly known, but in the United States, the FDA actually doesn't have mandatory recall power on drug products. They can ask a manufacturer to perform a recall, but it's really up to the manufacturers. As the FDA has said many times, the manufacturers are responsible for the safety and purity of their products, so I would hope that this is being followed up on, and that companies are determined that recalls are appropriate, they get done expeditiously.

Dermatology Times: Is there anything else you feel is particularly important for clinicians to know or consider?

Light: I think it's important that, although we had a lot of focus on the on the shelf room temperature, and that was a lot of the questions that was received after the last studies, that this is a problem that we see quite broadly. Even if you had an entirely clean product off the shelf, it can form over time. It's not at all like the situation we saw with benzene and sunscreens and hand sanitizers and body sprays, dry shampoos. All of these were quite clearly raw material contaminants that would get into the product, unfortunately, and then stay the same amount, or at least not very substantially, and not being formed by the active ingredients in these products, where that is the case with benzoyl peroxide. That really gives a lot of concern over the drug product as a whole. It certainly does change from formulation to formulation, but we obviously can't test every single possible environment, and we do see that it is a broad issue with benzoyl peroxide products. I think that's important to keep in mind. If there are recommendations made, dermatologists might want to think about it broadly, not just specific on certain products or brands.

[Transcript has been edited for clarity.]