BASF AG’s time and extent application does not support adding octyl triazone to the OTC sunscreen monograph, FDA says in its third finding this year that a TEA for sunscreen ingredients is inadequate.

FDA’s decisions on the three TEAs could concern advocates on Capitol Hill and in the industry who want to use the TEA process to expand the OTC sunscreen monograph. However, drug industry stakeholders have told FDA the TEA process does not work and should be changed to function as intended (see story this issue, [A#05140630009]).

In a June 23 letter, FDA’s Center for Drug Evaluation informed BASF counsel at Morgan, Lewis & Bockius LLP in Washington that the data and other information the firm submitted, initially in 2003 and following agency requests in 2004 and 2006, is not sufficient to establish that octyl triazone, which also is known as ethylhexyl triazone and which BASF markets as Uvinul T 150, is generally recognized as safe and effective.

In February, FDA submitted rejection letters to diethylhexyl butamido triazone TEA sponsor 3V Inc. and amiloxate application sponsors [Symrise AG] and Ego Pharmaceuticals Pty. Ltd. Also see "MHRA on herbals" - Pink Sheet, 31 July, 2006..

CDER posted each of the letters in its sunscreen monograph docket and requests that the firms and other parties submit additional data on the ingredients’ use in OTC sunscreens.

Tests Inadequate, Data Lacking

FDA faulted BASF in each area of information the agency requests in a TEA, including for not providing pharmacokinetic studies on octyl triazone “in response to our call for data.”

Data currently available are from studies not designed to detect or quantify the ingredient in subjects’ blood or other bodily fluids, providing “no useful information about systemic exposure,” CDER said.

However, “another important safety concern” is whether dermal application of octyl triazone-containing sunscreens “may result in skin penetration and systemic exposure” to the ingredient, according to the letter.

BASF advised FDA the firm did not submit information on adverse event reports associated with the ingredient because sunscreens are considered cosmetic products in countries where the ingredient already is used and AERs generally are not required for cosmetics in most of those countries.

With no AERs available, the global chemical firm said it could not review adverse event information to support an evaluation of octyl triazone’s safety for use in sunscreens.

However, FDA says TEA sponsors should “either supplement the information already submitted with adverse events or other safety-related data derived from commercial marketing experience, or explain why such information cannot be provided.”

Additionally, the two skin-irritation studies that BASF submitted had adequate numbers of subjects and appeared “to support that octyl triazone does not cause irritation, but neither study was optimally designed as both lacked appropriate controls,” according to the letter.

FDA also noted that non-clinical studies, with animals as test subjects, are needed in areas in addition to those included in BASF’s TEA.

The firm submitted information from non-clinical studies on:

actual and repeat dose toxicities
genetoxicity and mutagenicity assays
reproductive and developmental toxicity
photocarcinogenity.

Based on assessment of all available information on octyl triazone and on studies currently recommended for sunscreen development, FDA recommends these non-clinical studies addressing ingredient’s safety:

dermal and systemic carcinogenicity
fertility
prenatal/postnatal toxicity
toxicokinetics.

Summaries Not Enough

BASF’s information on octyl triazone’s effectiveness was limited to summary data for studies that did not report outcomes for testing that was described in the study designs. The summaries did not “provide adequate information to demonstrate that octyl triazone is effective for use as a sunscreen,” CDER stated.

“Were complete study data provided … allowing the agency to verify the validity and accuracy of the summaries, these studies might be sufficient,” CDER added.

The center also pointed out that BASF submitted information on skin-irritation studies conducted with 3% and 10% octyl triazone, but FDA guidance suggests human pharmacokinetics and bioavailability studies for applications “be conducted under maximal use conditions” with ingredient concentration up to 5%.

CDER asks BASF for “two adequate and well-controlled [sun-protection factor studies] conducted according to established standards to demonstrate that the lowest selected concentration provides an SPF of 2 or more,” according to the letter.

FDA’s most recent regulatory update for sunscreens was a June 2011 final rule requiring products that fail “broad spectrum” tests or have an SPF less than 15 to warn that they have not been shown to prevent cancer or early skin aging Also see "FDA Strengthens Sunscreen Testing And Label Requirements" - Pink Sheet, 20 June, 2011..

FDA Faults BASF Sunscreen Ingredient Data In Latest TEA Rejection

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