Biogen MA Inc. – FDA 483, Aug 2, 2013

This FDA Form 483 document details observations from an inspection of manufacturing and control operations for the APIs Tysabri (natalizumab) and Avonex (Interferon Beta 1a).

**Observation 1:** The firm lacks assurance that it consistently challenges the validity of testing results provided in container-supplier's certificates of analysis as part of supplier qualification. Specifically, bulk bags used for Tysabri API, certified as sterile and endotoxin-free, have never had these results challenged or verified by the firm.

**Observation 2:** The firm fails to adequately and/or completely document the execution of control procedures in equipment logbooks and/or production records, raising questions about adherence to procedures. Examples include: * Logbooks for biosafety hoods in Avonex and Tysabri production rooms do not document cleaning/sanitizing agents used or contact times. * The logbook for the Bio-Reactor # used in Tysabri API production lacks documentation of buffers used to standardize pH-measuring probes. * The logbook for the chromatography column skid in Tysabri API purification does not document values obtained during standardization of UV and conductivity probes. * The Tysabri API batch production record only states the UV meter of the System was standardized, without documenting the value obtained as per procedure PRCD-19494. * Questionable logbook entries were found for biosafety hood #, where entries