According to the Letter, the violations are related to the combination products “Enbrel [etanercept] lyophilized vial and diluent with vial adapter, and Enbrel prefilled syringe with ‘Sureclick 1.5’ auto injector,” as well the production of another MAb, Prolia (denosumab), with prefilled syringe and manual needle guard, and was sent following an inspection by the FDA in June last year.
Three specific violations were cited by the regulators: failure to establish and maintain design validation procedures to ensure that devices conform to defined user needs; failure to establish and maintain the requirements that must be met by suppliers, contractors, and consultants; and failure to establish and maintain procedures for the identification, documentation, validation, review, and approval of design changes before their implementation
“Your firm failed to implement its established procedure for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, for the device constituent part of the Enbrel with vial adapter,” the letter stated in one example.
According to Amgen’s end of year report for 2013, Thousand Oaks houses 36 buildings – five of which it leases out – and performs “substantially all of the bulk manufacturing and formulation, fill and finish, and packaging for product candidates to be used in clinical trials.”
Most of the commercial manufacturing for Enbrel is done at its facility in Juncos, Puerto Rico, which also does the entire formulation and fill and finish for other biologics in Amgen’s portfolio, including Prolia, Epogen (epoetin alfa) and Neulasta (pegfilgrastim).
2012 worldwide sales of its blockbuster MAb rheumatoid treatment Enbrel totalled $41.bn (€3.1bn), according to the report, whilst Prolia clocked $1.2bn of revenue.