Regulatory News

Allergan urges FDA to revise, replace bioequivalence guidelines for generic drugs

In a letter to the U.S. Food and Drug Administration, Allergan requested that the agency revise and replace bioequivalence draft guidelines issued on June 20. The FDA accepted public comment on the proposed guidelines until Aug. 19.

Richard Spivey, Allergan’s senior vice president for global regulatory affairs, objected to a proposal in the draft guidance that in vitro analysis alone may establish the bioequivalence of a generic drug to Allergan’s Restasis (cyclosporine ophthalmic suspension 0.05%).

As proposed, the FDA guidelines may enable companies to base applications for generic drugs on laboratory studies and not in vivo clinical trials with living human subjects.

“For the reasons set forth in this comment, FDA should replace the draft guidance with revised guidance that makes clear that a proposed generic referring to Restasis must demonstrate bioequivalence through comparative clinical trials to show equivalent safety and effectiveness based on clinical endpoints,” Spivey wrote.

Spivey termed the draft guidance a “sharp and unjustified break from FDA’s consistent past practice.”

“Until now, FDA has recognized that the only scientifically valid way to demonstrate that a proposed generic drug is bioequivalent to an ophthalmic emulsion such as Restasis is to conduct comparative clinical trials to demonstrate equivalent safety and effectiveness based on clinical endpoints,” he wrote.

Proposed in vitro measurements would not show sufficient evidence of a generic emulsion’s bioequivalence to Restasis. The draft guidance would risk patients being exposed to products of unknown safety and efficacy, Spivey wrote.

The patent on Restasis is scheduled to expire May 2014. The FDA approved Restasis in 2002.

In a letter to the U.S. Food and Drug Administration, Allergan requested that the agency revise and replace bioequivalence draft guidelines issued on June 20. The FDA accepted public comment on the proposed guidelines until Aug. 19.

Richard Spivey, Allergan’s senior vice president for global regulatory affairs, objected to a proposal in the draft guidance that in vitro analysis alone may establish the bioequivalence of a generic drug to Allergan’s Restasis (cyclosporine ophthalmic suspension 0.05%).

As proposed, the FDA guidelines may enable companies to base applications for generic drugs on laboratory studies and not in vivo clinical trials with living human subjects.

“For the reasons set forth in this comment, FDA should replace the draft guidance with revised guidance that makes clear that a proposed generic referring to Restasis must demonstrate bioequivalence through comparative clinical trials to show equivalent safety and effectiveness based on clinical endpoints,” Spivey wrote.

Spivey termed the draft guidance a “sharp and unjustified break from FDA’s consistent past practice.”

“Until now, FDA has recognized that the only scientifically valid way to demonstrate that a proposed generic drug is bioequivalent to an ophthalmic emulsion such as Restasis is to conduct comparative clinical trials to demonstrate equivalent safety and effectiveness based on clinical endpoints,” he wrote.

Proposed in vitro measurements would not show sufficient evidence of a generic emulsion’s bioequivalence to Restasis. The draft guidance would risk patients being exposed to products of unknown safety and efficacy, Spivey wrote.

The patent on Restasis is scheduled to expire May 2014. The FDA approved Restasis in 2002.