FDA CRL - Sandoz Inc

Sandoz Inc. received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA 761045) for LA-EP2006, a proposed biosimilar under section 351(k) of the Public Health Service Act. The FDA could not approve the application in its current form due to several deficiencies in clinical pharmacology and product quality.

Key issues in clinical pharmacology included a failure to demonstrate pharmacokinetic (PK) similarity between LA-EP2006 and US-licensed Neulasta, and an inadequate scientific bridge due to lack of PK similarity across LA-EP2006, US-licensed Neulasta, and EU-approved Neulasta. The agency requires root cause analyses and recommends considering a new, adequately designed 3-arm crossover study to establish PK and pharmacodynamic similarity and the scientific bridge.

Product quality concerns involved unvalidated maximum filling duration, insufficient data for a requalification strategy and microbial challenge studies, an inadequate container closure integrity test method for prefilled syringes, and insufficient data from simulated air transportation studies. Sandoz must provide media fill data, address data gaps, conduct a new prefilled syringe CCI qualification, and provide comprehensive air transportation study details.

Additionally, the FDA requires a comprehensive safety update, including detailed analysis of new safety data, comparisons to original BLA data, case reports for serious adverse events, and an updated worldwide safety experience summary. Comments on prescribing information and labeling are reserved until these deficiencies are addressed.