FDA WARNING_LETTER - Qualiphar Nv - May 07, 2010

An FDA inspection of Qualiphar n.v.'s pharmaceutical manufacturing facility in Bornem, Belgium, from May 3-7, 2010, revealed significant Current Good Manufacturing Practice (CGMP) violations, rendering their drug products adulterated under 21 U.S.C. § 351(a)(2)(B). The firm's May 28, 2010, response was deemed insufficient. Key violations include inadequate written procedures for production and process control (21 CFR § 211.100(a)), particularly for (b)(4) powder and tablet manufacturing, with deficient process validation and undocumented changes. This was a repeat observation from 1998 and 2002 inspections. The firm also failed to follow in-process control procedures (21 CFR § 211.110(a)), releasing an out-of-specification batch without investigation. Established laboratory control mechanisms were not followed (21 CFR § 211.160(a)), with OOS assay/dissolution results for (b)(4) powder batches being invalidated and re-tested without thorough investigation. Inadequate laboratory controls, sampling plans, and test procedures (21 CFR § 211.160(b)) were noted, along with a lack of records for the disposition of rejected drug product containers (21 CFR § 211.184(e)). Written procedures for annual product evaluations were absent (21 CFR § 211.180(e)(2)), another repeat observation. Additional concerns included lack of cleaning validation, unclear dedicated equipment use in batch records, incomplete filling records, and missing sampling records. Furthermore, Qualiphar failed to register and list products distributed in the U.S. (21 CFR § 207.40, 21 U.S.C. § 360(i)). The FDA requires a written response within fifteen working days detailing corrective actions, recurrence prevention, supporting documentation, and completion of registration and listing. Failure to comply may result in withholding new application approvals and refusal of admission for products into the U.S.