Lube Maker, PETA At Odds With FDA Over Animal Testing

Personal lubricant products–lube for short–are medical products intended to facilitate vaginal or anal intercourse and masturbation, with others or with sex toys, by reducing friction and minimizing trauma to delicate tissues. Personal lubricants are also commonly used to manage the symptoms of vaginal dryness and vulvovaginal atrophy of menopause, especially for women where the use of estrogen-containing creams are contraindicated.

Lubricants also have important health promotion effects. The CDC recommends that water- or silicone-based lubes be used with condoms to prevent breakage as a prevention strategy against HIV transmission. According to the World Health Organization, the condom breakage rate without lubricants in men having sex with men is 21.4%, but only 3% when using a personal lube product. The use of lubricants for receptive anal intercourse has led to testing of products containing antiretroviral drugs for the prevention of HIV infection.

In the vernacular of the U.S. Food and Drug Administration, lube is classified as Class II medical device, the same category as that for powered wheelchairs and some pregnancy test kits. The convoluted reasoning for this can be attributed to 1) the original development of patient lubricants for gynecological examinations and 2) the original packaging of condoms with lubricant and/or spermicidal agents (a condom is also a Class II medical device). The official FDA definition is:

This device is a personal lubricant, for penile and/or vaginal application, intended to moisturize and lubricate, to enhance the ease and comfort of intimate sexual activity, and supplement the body's natural lubrication. This product may or may not be compatible with natural rubber latex, polyisoprene, and/or polyurethane condoms.

Yet until recently, lube was not explicitly required to undergo mammalian safety testing.

But the FDA's Center for Devices and Radiological Health (CDRH) informed personal lubricant industry stakeholders last year that 100% of products would be required by December 31, 2015 to submit premarketing notifications that would include irritant and hypersensitivity safety testing in rabbits and guinea pigs.

In response, the regulatory department of People for the Ethical Treatment of Animals (PETA) and product manufacturers have registered their objections to the FDA, saying that less expensive testing methods with cultured human cells are as predictive, or more predictive, of human safety than animal tests.

These critics point to CDRH's expressed commitment to minimizing animal use. But the CEO and founder of Good Clean Love, Wendy Strgar, told me that the agency only accepted one of their four proposed substitute testing models. The FDA marketing approval letter (PDF) to Good Clean Love confirms these CRDH requirements.

An FDA spokesperson responded to my request for comment by email, writing that "CDRH accepts in vitro testing to assess the cytotoxicity and acute systemic toxicity potential of personal lubricants. Regarding vaginal irritation and sensitization, at this time, we are not aware of any validated in vitro models for those tests."

Why doesn't the FDA just require human safety testing? This 510(k) notification–so named for the section of the Food, Drug and Cosmetic Act governing medical devices–doesn't require human clinical trials if the manufacturer can demonstrate that their product is "substantially equivalent" in safety and effectiveness to a product already on the market (a "predicate product") or has been in commercial distribution before 1976. Human testing is also more expensive than animal studies.

"Iso-osmolar" lubricants are the safest

I first wrote about lube safety when a December 2012 article in Chemical & Engineering News (C&EN) shed light on research showing that some types of lubricants can cause cellular damage and disrupt the protective Lactobacillus bacteria that populate the vagina.

The C&EN article, by Lauren K. Wolf, PhD, assistant managing editor for science and technology at the American Chemical Society's weekly magazine, focused specifically on a chemical characteristic of lubricants called osmolality. (Disclosure: I have been a paid contributor to the magazine and their former blog network, CENtral Science.)

Osmolality is a chemical term that describes the number of dissolved particles in a defined volume of liquid. When the osmolality of a lubricant exceeds that of normal vaginal secretions and the epithelial cells lining the vagina, water passes out of the cells, causing them to shrivel or even die. This significance of this quality was tested in 2012 by a group led by Charlene Dezzutti, PhD, at the Magee-Womens Research Institute at the University of Pittsburgh and published in the journal PLOS One.

Dezzutti and colleagues tested 14 commercially available brands of personal lubricants for toxicity to human cervical or rectal epithelial cells, three types of Lactobacillus bacteria that maintain the acidic pH of the vagina, and cellular susceptibility to HIV infection in vitro. The products causing the least damage were those that had osmolality within a factor of two from normal vaginal secretions or semen. (None of the lubricants enhanced HIV infection in culture and some even had anti-HIV activity.)

The best of these iso-osmolar lubricants were Good Clean Love and PRÉ. Dezzutti's team also found that silicone-based lubricants like Female Condom 2 lubricant and Wet Platinum were also safest in their in vitro tests.

But she cautioned in an interview with Wolf, "This is just a model in a test tube, and it’s hard to equate that with real-life activity."

What are valid, "real-life" tests?

Dezzutti's cautionary note is at the heart of PETA's beef with the FDA. Jeffrey Brown, a scientist in PETA's Regualtory Testing Department, provided me with the letter the organization sent to CDRH Center Director Jeffrey Shuren, MD, JD, noting that the maker of Good Clean Love did provide equivalence data to the agency on in vitro and animal tests.

One might be surprised to learn of PETA's work with human tissue research. Eric Boodman at STAT News wrote last week on PETA's investment in scientific research and support of external scientists to study methods that would spare the use of lab animals.

One of these PETA-supported tests is a 3D human vaginal epithelial model sold by MatTek, a spinoff of two MIT bioengineering professors. The cell biology company produces a range of testing systems designed to recapitulate the histological organization and diverse cell types of specific human tissues. The EpiVaginal assay system has been used by University of Utah researchers to validate the safety of an intravaginal ring designed to release the HIV reverse transcriptase inhibitor dapivirine.

Good Clean Love's Strgar holds that these such complex, multicellular assay systems from human donor tissues are far more relevant than instilling rabbit vaginas with lube and killing them to examine their histology.

"There is no other animal in the kingdom that has the same kind of vagina as humans," said Strgar. In fact, the rabbit vagina contains less specialized cells than the human vagina and their increased susceptibility to irritation is why they were originally adopted as a toxicology model.

During a June 2015 conference call with the agency to discuss the tests necessary for a 510(k) submission, she was struck by CDRH's reticence to accept cellular tests and the possibility that the objections were not entirely scientific.

"One of the things that came up continuously in this whole negotiation was like, 'Oh, you don't want to include PETA - that will put you on the bad side of FDA,'" says Strgar. "You can't even mention that you're working with PETA if you want to get a 510(k)."

Strgar's Good Clean Love has European Union medical device authorization with in vitro tests that cost less than $10,000. She says that the additional animal testing required by CDRH cost at least $50,000. The company did finally receive their 510(k) authorization on November 19, 2015 (PDF). As an established company, Strgar says that she's less concerned about the money she spent.

Strgar says, "I never wanted to test on animals and I'm angry that I was forced to do it. And, in the end, animal testing doesn't even tell us about toxicity."

"That's the most stupid and tragic part of the whole thing."