By Douglas B. Farquhar –
In a long-awaited ruling, a federal judge has upheld FDA’s decision to grant approval to the generic version of Xibrom®, an ophthalmic product for treatment after cataract surgery (active ingredient: bromfenac).
The opinion was issued Monday by Judge James Gwin of the Northern District of Ohio (substituting for Judge Emmet Sullivan in this case, which was brought in the U.S. District Court for the District of Columbia). The decision disposes of a challenge brought by ISTA Pharmaceuticals, Inc. to FDA’s grant of approval to an Abbreviated New Drug Application (“ANDA”) filed by Coastal Pharmaceuticals. In the litigation, our firm represented Metrics, Inc., doing business as Coastal Pharmaceuticals, and Mylan Pharmaceuticals Inc., which markets the generic product.
Bromfenac had an unusual approval history. After securing approval for and marketing a twice-a-day brand product, which was called “Xibrom,” ISTA sought and secured approval for a product administered once a day, called “Bromday®.” Xibrom and Bromday have the same indication, the same active ingredient, and the same dosage strength. Prior to the approval of Bromday, Coastal filed its ANDA seeking approval of a twice-daily product. ISTA then filed a Citizen Petition with FDA seeking that any generics for the twice-daily product should be denied on the grounds that labeling for the new product, Bromday, replaced the labeling for the older product, Xibrom (see our previous post here). ISTA argued that the ANDA could not be approved unless it included labeling that was identical to the current labeling of the product, and ISTA claimed that the “current labeling” for the product was the once-daily instructions for use, for which ISTA had an exclusivity period.
FDA disagreed. On May 11, 2011, FDA granted approval to the Coastal ANDA, and denied the ISTA Citizen Petition. FDA, in its response to the Citizen Petition, stated that Xibrom and Bromday are two different products, and, although ISTA had withdrawn Xibrom from the market, the product was not withdrawn for reasons of safety or efficacy, which would have prohibited its use as the “Reference Listed Drug” for an ANDA.
ISTA then promptly filed a lawsuit seeking a Temporary Restraining Order (“TRO”) that would have prohibited the generic product from being distributed. Mylan and Metrics intervened as parties in the litigation. ISTA failed to secure a TRO, and filed an Amended Complaint that added allegations related to FDA’s discussions about whether an ophthalmic product could safely treat two eyes with the same bottle, because of concerns about cross-infection if the dropper touches the eye’s surface. Coastal’s generic product was approved in two sizes, 2.5ml and 5ml, with the larger size containing enough medication to treat two eyes twice a day for the prescribed period.
Judge Gwin addressed each of ISTA’s arguments in his 9-page opinion. He pointed to ISTA’s public statements that implied that Xibrom and Bromday were two different products, and noted that Xibrom and Bromday were both on the market for a period of months. He also found that, although ISTA argued in the litigation that Xibrom was removed for reasons of safety and efficacy, ISTA “never indicated that Xibrom was unsafe or ineffective” while the agency was considering whether to grant Coastal’s ANDA. He noted that FDA has requested some manufacturers of ophthalmic products to “voluntarily change their labels” to address “some ongoing concerns about improper consumer usage and cross-contamination of post-operative eyes,” but FDA has not yet required such changes to be made. Copies of the ISTA and FDA briefs are available here and here.