Covis Pharma GmBH – FDA EIR, May 21, 2014

An FDA inspection of AMAG Pharmaceuticals, Inc., located in Waltham, MA, was conducted from April 2 to May 21, 2014. This 'for-cause' assignment, initiated by the Center for Drug Evaluation and Research, followed regulatory guidelines including CPGM 7356.002, 7353.001, and 7356.021 for drug manufacturing inspections, post-marketing adverse drug experience regulations, and drug quality reporting. The inspection identified significant deficiencies primarily related to quality systems and manufacturing controls for their intravenous drug product, Feraheme (ferumoxytol injection). Key violations included inadequate investigations into several critical issues, such as observed white specks on Feraheme vials, out-of-specification results for mannitol content, and unexplained conductivity increases in drug substance batches. Furthermore, the company failed to adequately assess the impact of corrosion on product-contact equipment and microbial byproducts on product quality and patient safety. Analytical methods were found lacking, specifically in the absence of objective acceptance criteria for identity testing and the use of unvalidated reference standards. Concerns were also raised regarding cleaning validation for product-contact equipment, the monitoring of sterilization cycles, and the processing of stoppers. AMAG Pharmaceuticals, Inc. committed to responding to the FDA Form 483 within 30 business days, and was encouraged to provide a scientific explanation addressing the potential association of these observations with adverse events like fatalities or anaphylaxis.