Pfizer Inc. – FDA CRL

The Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Pfizer Inc. regarding its Biologics License Application (BLA 761081) for Trazimera (PF-05280014), a proposed biosimilar under section 351(k) of the Public Health Service Act. The BLA, initially submitted on June 22, 2017, cannot be approved in its current form due to several product quality deficiencies. Key issues identified include insufficient stability data for both the Working Cell Bank and Master Cell Bank, requiring further data to confirm stability and qualification of new cell banks for commercial production. The FDA also noted that the drug product's fill weight range does not consistently ensure the 420 mg label claim, necessitating a tighter rejection limit and supporting data. Furthermore, commercial shipping validation data for the drug product was deemed inadequate, requiring real-time or robust simulated studies to demonstrate product quality maintenance during distribution, including specific temperature ranges and shipper performance in actual conditions. The CRL also mandates implementing additional control specifications for Trazimera. These include validated assays and acceptance criteria for Antibody-dependent cell-mediated cytotoxicity (ADCC) activity, iso Asp102 levels, and high mannose species in drug substance release. Additionally, quantitative acceptance criteria for Polysorbate 20 and an "extractable content" test (no less than 420 mg) must be added to the drug product release specifications. The company must also provide sufficient justifications for current drug substance and drug product acceptance criteria.