FDA 483 - Grifols Therapeutics LLC - May 06, 2022

During an inspection conducted from April 28 to May 6, 2022, the FDA issued a Form 483 to Grifols Therapeutics LLC, a biologic drug manufacturer located in Clayton, North Carolina. The inspection revealed two significant observations related to the firm's manufacturing processes.

Firstly, procedures intended to prevent microbiological contamination of sterile drug products were found to be inadequately established, documented, and followed. Specific concerns included incomplete documentation of "Integrity Rejects" vial reconciliation in media fill batch records, indicating a lack of accountability for all filled units. Additionally, the Quality Unit did not periodically review all intrusions into the aseptic filling line to assess their impact or incorporate them into media fill simulations. Discrepancies were also noted in media fill batch records regarding the alignment of operator activities and personnel monitoring sample times.

Secondly, bioburden monitoring of manufacturing processes for pre-sterile bulks was deemed inadequate or inconsistent. The firm had not established definitive action limits for certain clarified bulk materials and failed to consistently perform speciation of all bioburden samples, even when required by internal procedures. Investigations into microbial detections, such as Trichoderma and Pseudomonas species, were often limited to identification at the genus level, neglecting the use of more robust testing to determine specific species and fully understand potential sources of contamination.

These observations, issued under Section 704(b) of the Federal Food, Drug, and Cosmetic Act, require Grifols Therapeutics LLC to address the identified deficiencies in its quality systems and manufacturing practices to ensure compliance and product integrity.