FDA Warning Letter with Supplier Qualification Observations

CMO and Supplier Qualification in outsourcing activities are always hot topics in inspections. The U.S. Food and Drug Administration (FDA) recently posted a Warning Letter sent to the pharmaceutical company AACE Pharmaceuticals in the US, criticizing their CMO qualification procedures. The inspection was scheduled because of problems at the company's contract manufacturer (CMO), where "multiple CGMP violations" were revealed, resulting in an Import Alert and drug product recalls.

The CMO manufactures ophthalmic products for AACE. Although AACE identified several CGMP deficiencies at this CMO, the CMO was qualified as approved. Furthermore, it was even re-qualified three years later, "without evaluating whether subsequent corrective actions and preventive actions adequately addressed the identified deficiencies". So AACE released products for distribution "without adequate procedures to ensure that the ophthalmic drug products (…) met appropriate quality attributes".

As a consequence, AACE has revised its procedures to ensure that GMP deviations at a CMO and the associated CAPA plans are assessed accordingly. This was not sufficient for FDA. The agency requires details on how to assess the deviations, how to disqualify CMOs and how to evaluate qualification status of other CMOs.

Before releasing a product, AACE was comparing certificate of analysis (COA) data against the pre-approved specification. FDA clearly states, that this does not overcome the "responsibility to evaluate, qualify, audit, and monitor" CMOs. A firm "should have a robust qualification process" of CMOs, based on quality risk management principles.