FDA Rejects Approval of Pfizer's Epoetin Alfa Biosimilar, Again

The FDA rejected, for a second time, Pfizer’s application for approval of its biosimilar epoetin alfa (Epoetin Hospira), a colony-stimulating factor indicated for anemia, biosimilar to Epogen (Amgen) and Procrit (Janssen).

The FDA issued a complete response letter (CRL) to Pfizer citing its continuing concerns about the company’s plant in McPherson, Kansas, where the biosimilar will potentially be manufactured. The FDA’s rejection, however, was a surprise, as the agency’s Oncologic Drugs Advisory Committee (ODAC) voted 14-to-1 only a month ago to recommend its approval based in part on its conclusion that the biosimilar is highly similar to its reference products and has demonstrated that there are no clinically meaningful differences in terms of safety, purity, and potency of the biosimilar product.

The CRL relates to matters noted in the FDA’s February 2017 Warning Letter to Pfizer in which the agency documented problems observed during a routine inspection of the facility, which was listed as the potential manufacturing site in the Biologics License Application for Pfizer’s proposed epoetin alfa biosimilar. According to Pfizer, the issues noted in the Warning Letter do not relate specifically to the manufacture of epoetin alfa, and no additional clinical data was requested in the CRL at this time to support a future approval. (The FDA had asked Pfizer for more data when it rejected the drug in 2015.) Pfizer said it submitted a corrective and preventive action plan to the FDA in March 2017, and had been “diligently working to address the items in the Warning Letter,” providing regular updates to FDA on the status of the action plan, and remaining dedicated to addressing all concerns with the said manufacturing facility.

The plant in question was the same Hospira unit plant that was responsible for the FDA’s rejection of Glatopa, a long-lasting generic version of Teva’s multiple sclerosis drug, Copaxone (glatiramer acetate), developed jointly by Momenta and Novartis (Pfizer bought Hospira in 2015). Those companies were told that the approval of Glatopa is dependent on Pfizer resolving issues at the Hospira plant at which Pfizer was handling fill-finishing on a contractual basis for Momenta and Novartis’s Sandoz unit. The problems at the plant were enumerated “in a scathing warning letter that chastised Pfizer for repeated failings through the Hospira manufacturing unit,” which stated that Pfizer should have recognized issues that needed attention much earlier, because the agency had cited 5 other Hospira plants for similar problems in 4 warning letters, from 2012 through 2015.