The delay in FDA approval of generic versions of Bristol-Myers Squibb's Glucophage (metformin) will reduce Barr's profitability from the product by giving other generic companies time to increase their manufacturing capacity, Barr said.

"The opportunity was the limited capacity to make the product," CEO Bruce Downey told analysts during an Oct. 4 conference call. While the metformin launch "will be good for us," Downey said, "probably the delay will make it a less profitable launch than it might have been four or five months ago."

Barr prefers to focus on patent challenges where it would have the opportunity to launch products with 180 days of exclusivity, Downey noted. Metformin does not fit that profile, but the company was interested because it believed it would have an opportunity to exploit limited generic capacity.

FDA declared nine generic metformin applications "approvable" on Oct. 9. The FDA letter notes that the approval process is awaiting resolution of exclusivity issues raised by pediatric labeling changes for Glucophage.

"The legal basis for withholding approval or not moving forward is shaky, and I think the proper interpretation of the various laws and regulations would compel the approval of a generic product," Downey said.

However, Downey declined to project a timeline for approval. "I'm not making a prediction it's this quarter or the next, but I think it will be fairly soon," he said. The focus of the conference call was on Barr's upward revision in its earnings forecast following the launch of generic fluoxetine in August.

Bristol has three-year Waxman/Hatch exclusivity for a Glucophage pediatric indication that runs until 2004. Bristol argues that FDA cannot approve generics until they are allowed to reference the pediatric labeling (¹ Also see "Bristol BuSpar Pediatric Labeling May Delay Second Round Of Generics" - Pink Sheet, 1 October, 2001.).

Bristol is making a similar argument about the second round of generic versions of BuSpar (buspirone), although the BuSpar pediatric labeling states that the product was not effective in children at the adult dose.

FDA is developing a guidance on allowing ANDAs to use discontinued labeling. The guidance "would have allowed everyone to be on the market within 30 days [of finalization] and so I would hope that would still occur," Downey said. The guidance has "somehow been derailed or at least hung up at the FDA."

FDA's new Chief Counsel Daniel Troy is reviewing the guidance and solicited comments from the generic industry.

The Generic Pharmaceutical Association's Oct. 10 comments argue that safety-related labeling changes are not eligible for exclusivity. In addition, GPhA said, labeling changes for innovator products should not preclude generic approval.

Allowing safety labeling changes to block generic approvals "would create a dangerous incentive to delay safety-related changes in the approved labeling and would put the American people at grave risk," GPhA maintained.

Approving ANDAs without the pediatric labeling would be appropriate, GPhA said. "If a generic drug's label omits pediatric information present in innovator labeling, but if the generics labeling does not otherwise recommend pediatric use, FDA cannot deem the drug to be unsafe based on the arbitrary assumption that it would be used in a manner other than recommended in its own labeling."

FDA has traditionally permitted ANDAs to have different labeling than innovator products to avoid use of protected labeling, GPhA noted. The agency and the courts "have long recognized that the three-year exclusivity is limited to protection of the actual labeling change."

"Significant labeling differences between generic and innovator drugs are permissible under the FD&C Act and FDA's implementing regulations even where such differences directly relate to matters of safety," GPhA concluded.

The generic industry is also pursuing a legislative fix. The House version of the pediatric exclusivity reauthorization bill marked up by the Commerce Committee Oct. 11 would allow ANDAs to omit pediatric labeling language that is protected by exclusivity (² Also see "Pediatric Labeling Would Not Block Generic Approval - House Exclusivity Bill" - Pink Sheet, 15 October, 2001.).

Metformin Generics Are "Approvable"; Barr Says Delay Helps Other Generics

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