The viability of time and extent applications as a route to market for new OTC ingredients continues to wane in light of new final guidance on the process.

“The TEA route is not an expedited process for revising OTC drug monographs or for getting a particular OTC drug to market,” FDA says in industry guidance published Sept. 28.

The guidance clarifies how to submit a TEA to show a drug ingredient is eligible to be in an OTC monograph by showing a product was marketed “to a material extent” and “for a material time.” If eligible, FDA reviews the safety and efficacy data, which is where the two-step process appears to break down.

Frederick Stearns, a partner at Keller and Heckman in Washington, maintains “the view of the TEA process as a route to get a new OTC to market in the U.S. … seems to have dimmed.”

“There is not a whole lot of interest in it,” Stearns said. Firms submitted a number of TEAs “early on in the process in 2003, 2004 and 2005,” that FDA found eligible, and while the sponsors presumably filed safety and efficacy data, “FDA still hasn’t acted on any of those,” he said.

“We are working as expeditiously as possible to complete our review of data for all the ingredients found eligible under the TEA process,” an FDA spokeswoman said. However, it is only after “the review for other actions is completed,” that “the lengthy clearance process begins, and it is at this point that the first projections of final publication can be made to the Unified Agenda.”

A Consumer Healthcare Products Association spokeswoman said the trade group hopes FDA “can accelerate the approvals in order to encourage industry to take advantage of this pathway.”

FDA indirectly explains the delay in the guidance by noting it “cannot specify a typical timeframe for completion of our evaluation because it is dependent on FDA resources and priorities.”

Agency resources are stretched and it must first address other higher priority rulemakings, such as emerging drug safety issues, the FDA spokeswoman said.

In addition, the agency’s priorities are mounting as Congress heaps on new responsibilities, like regulating tobacco products, and demands action in other areas, like the new dietary ingredient guidance.

Competing priorities likely prompted the agency to push back action on TEAs for sunscreen ingredients, which purportedly is the first product on which FDA will act.

The agency aims to address TEAs for sunscreen in a new proposed rulemaking by April 2012 (Also see "FDA Adds Targets To Semi-Annual Regulatory Agenda, Pushes Some Back" - Pink Sheet, 11 July, 2011.).

An FDA spokeswoman declined to discuss when the reviews of the other ingredients might be finished. She said only rulemakings projected for publication in the agency’s semi-annual regulatory agenda can be publically discussed. The most recent agenda was published in July (Also see "FDA Adds Targets To Semi-Annual Regulatory Agenda, Pushes Some Back" - Pink Sheet, 11 July, 2011.).

The industry’s waning interest in TEAs as a way to expand OTC monographs is reflected in FDA’s dwindling estimates for new TEAs. The agency said in 2010 it expects to receive only two TEAs annually. This is down substantially from a predicted 50 applications estimated in 2002 (“FDA shrinks TEA estimate,” “The Tan Sheet” Oct. 11, 2010, In Brief).

The failure of TEAs as an efficient route to the OTC market leaves the industry with limited options for introducing new OTC ingredients, Stearns said.

Stearns dismissed new drug applications as a viable alternative route for OTCs because “it is a tremendously expensive process,” and nonprescription status does not offer the same high margin as prescription products.

Ingredients Deemed Eligible Via TEAs

FDA determined the following ingredients were eligible to be in a monograph via TEAs:

Amiloxate: sunscreen monograph, July 2003
Bemotrizinol: sunscreen monograph, December 2005
Bisoctrizole: sunscreen monograph, December 2005
Climbazole: dandruff monograph, December 2005
Diethylhexyl: sunscreen monograph, July 2006
Drometrizole trisiloxane: sunscreen monograph, June 2010
Ecamsule: sunscreen monograph, September 2008
Enzacamene: sunscreen monograph, July 2003
Octyl triazone: sunscreen monograph, July 2003
Piroctone olamine: dandruff monograph, February 2004
Sodium picosulfate: laxative monograph, June 2006
Sodium shale oil sulfonate: dandruff monograph, April 2009
Triclosan: acne monograph, December 2005
Triclosan: antigingivitis/ antiplaque monograph, July 2004

Environmental Assessment Could Pose Hurdle

A “substantive” change between the draft guidance, issued in 2004, and the final guidance also could discourage firms from filing TEAs.

FDA clarifies firms must submit data in their TEA on the environmental impact of adding an ingredient to the monograph.

“The legal requirement to take [the environmental impact] into account is not new,” but explicitly noting it in the guidance is new, Stearns said.

FDA says firms “should submit an estimate of the expected introductory concentration of the eligible active ingredient in the aquatic environment.”

FDA will use this information to determine if the ingredient qualifies for a categorical exclusion for the environmental assessment requirement.

An eligible ingredient could qualify for environmental assessment exclusion if the addition of the ingredient to the monograph does not increase the estimated concentration of the active ingredient in water beyond one part per billion, according to the guidance.

The agency “sort of points you in the direction of being able to hopefully qualify for this exclusion” by directing firms to related guidance that outlines how to estimate the concentration in water, Stearns said.

FDA asked firms with TEAs for ingredients already deemed eligible to submit information on environmental impact in February 2010, so this addition to the guidance is not a complete surprise.

By Elizabeth Crawford

Guidance Underscores FDA Practice Of Letting TEAs Steep

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