New Developments in FDA Biocompatibility Requirements for Personal Lubricants

In FDA, Preclinical, Regulatory, Toxicology by Jennifer Shafer

Personal lubricants are a lucrative portion of the medical device market in the US and elsewhere. In the past, the Food and Drug Administration (FDA) has considered them to be short-term, mucosal contact, and have required the basic four tests for preclinical biocompatibility: cytotoxicity, sensitization, irritation (vaginal in this case) and acute systemic toxicity.

Over the past few years, FDA has become more concerned about the longer-term effects of personal lubricants. Several recommendations have been issued to NAMSA’s clients to perform a combined vaginal irritation/systemic toxicity test with repeated dosing and macroscopic and microscopic evaluation of the animals, similar to a subacute study. A typical study design would be:

  • Five test and five control New Zealand White rabbits
  • Test or control dosed for 10 consecutive days
  • Assessment of loss of material after each dose
  • Daily health observations and body weights
  • Daily detailed observations to include evaluation of discharge, erythema, and edema
  • Blood collected prior to first dose and at termination for hematology/clinical chemistry
  • Gross necropsy
  • Histopathology of the vagina, uterine horns, and cervix
  • Liver, kidneys, adrenals heart, spleen, mesenteric and submandibular lymph nodes, ovaries, thymus and brain collected, weighed and preserved for potential future evaluation
  • Statistical evaluation of blood and clinical chemistry values, body weights and organ weights

Food consumption may also be evaluated in some cases or the in-life period may differ; but in general, this is the type of study the FDA will request.

Several recent 510ks have included the test (for example, see
http://www.accessdata.fda.gov/cdrh_docs/pdf11/K110690.pdf,
http://www.accessdata.fda.gov/cdrh_docs/pdf12/k120650.pdf, and
http://www.accessdata.fda.gov/cdrh_docs/pdf13/K133336.pdf).

Unfortunately, FDA’s interest in this test has not been written up into a formal guidance as of yet. There is no guidance specific to personal lubricants. FDA’s recognition of ISO 10993-10 (#2-174) states that their extent of recognition is:

Complete standard with the following exception:

Annex B.4: Penile irritation test

Annex B.5: Rectal irritation test contact the review division prior to initiating any studies

Annex B.6: Vaginal irritation test; contact the review division prior to initiating any studies

No documentation on the combined vaginal/systemic study has been released to our knowledge. The requests we have seen at NAMSA have mostly been in Additional Information Requests.

However, FDA reviewers are undeniably interested in this test. We recommend that clients beginning their preclinical 510(k) program for a personal lubricant consider changing their test plan from the standard four tests to three: cytotoxicity, sensitization and combined vaginal irritation/systemic toxicity. NAMSA is happy to discuss the testing or facilitate discussion with the FDA concerning it.

Next Steps

Authors:

Jennifer Shafer is a technical adviser with NAMSA, focusing on biocompatibility regulations and requirements across the globe. She holds a master’s degree in neuroscience from Johns Hopkins University and previously worked at a firm studying expertise and decision-making. She has written for an online neurofinance site, business journals, and a site that monitors medical device manufacturing developments.