A coalition led by Center for Responsible Science (CRS) has submitted a citizen petition urging the FDA to issue broad guidance communicating clearly with drug and device sponsors that the Draize rabbit test for skin and eye irritation is no longer required and that human relevant in vitro tests will be accepted. To assist FDA with this request, CRS has submitted a proposed draft guidance.

CRS President Dr. Neil Wilcox states, “Unless FDA issues broad guidance for drug sponsors on irritation testing, drug developers will not have the assurance that FDA does not require Draize data. Failure to issue guidance for primary skin and eye irritation testing results in sponsors continuing to waste time, money and animals for data which is not useful—and data which the FDA does not want.”

The Draize test is an acute toxicity test devised in 1944 to test for irritancy in cosmetics, but subsequently became the most common method for assessing skin and eye irritancy in pharmaceuticals. It has remained the traditional test for over seven decades, despite scientific studies for the last 40 years showing deficiencies with Draize in predicting human response.

Since 2005, FDA has informally stated that Draize test data are not required for primary skin and eye irritation testing, but drug sponsors continue to provide Draize test data—despite the prevalence of other primary skin and eye irritation methods that are more predictive.

When asked in 2014 if FDA would issue formal guidance on irritation testing to clarify there is no need for Draize, FDA responded that it was unlikely due to a backlog of guidance documents, limited resources, and narrow application of irritation testing.

However, in 2015, a CRS and Safer Medicines Trust article was published revealing that a review of all New Molecular Entities (NMEs) approved by FDA between the years 2011-2014 confirmed the Draize test was used in 94 percent of all skin irritation and 60 percent of all eye irritation tests. Of these drugs for which the Draize test was conducted, 76 percent were for systemic, not topical, administration; thus no irritancy testing of any type was necessary.

It wasn’t until publication of CRS’ research regarding the use of Draize in drug development that FDA, for the first time, issued narrow guidance to industry, stating the Draize test was no longer recommended in some circumstances and that in vitro testing would satisfy regulatory requirements in those cases.  Unfortunately, this new guidance does not go far enough. It is limited in scope, and merely covers reformulated products and new routes of administration.

“The unnecessary use of the Draize tests for skin and eye irritation potential should be resolved by FDA issuing broad guidance, which will encourage companies to use more reliable human-relevant tests” said Kathy Archibald, director of Safer Medicines Trust.

The Center for Responsible Science is a non-partisan, nonprofit advocating for more modern and predictive test methods in drug development.

The coalition includes Center for Responsible Science, Safer Medicines Trust, MatTek and Invitro International.

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