17 Issues In Invitrx Inspection

A 3/25-4/3/19 FDA inspection at Invitrx Therapeutics, Lake Forest, CA, documented 17 issues in the firm’s processing of products for allogeneic use. A 3/16 Warning Letter lists 17 significant deviations from current good manufacturing practice (CGMP) regulations applicable to the firm’s products as well as significant current good tissue practice (CGTP) deviations applicable to the firm’s human cells, tissues, or cellular or tissue-based products (HCT/Ps). Specific deficiencies were: 

•          failure of a responsible person to determine and document the eligibility of a cell or tissue donor based upon the results of donor screening and testing;
•          failure to determine a donor to be ineligible whose specimen tests reactive on a screening test for a communicable disease agent;
•          failure to screen a donor of human cells or tissue by reviewing the donor’s relevant medical records for risk factors for, and clinical evidence of, relevant communicable disease agents and diseases;
•          failure to establish and maintain procedures for all steps performed in testing, screening, and determining donor eligibility, and complying with all other donor eligibility requirements in regulations;
•          failure to retain the accompanying records with the HCT/Ps at all times following a donor eligibility determination including a statement whether, based on the results of screening and testing, the donor has been determined to be eligible or ineligible, and a summary of the records used to make the donor eligibility determination;
•          failure to establish and follow appropriate written procedures to prevent microbiological contamination of drug products purporting to be sterile, including procedures for validation of all aseptic and sterilization processes;
•          failure to reject drug products that do not meet established standards or specifications and any other quality control criteria;
•          failure to establish and follow written procedures for cleaning and maintenance of equipment used in the manufacture, processing, packing, or holding of a drug product;
•          failure to thoroughly investigate any unexplained discrepancy, or the failure of a batch or any of its components to meet any of its specifications;
•          failure to establish written procedures for production and process control designed to assure that the drug products have the identity, strength, quality, and purity they purport or are represented to possess;
•          failure to have separate or defined areas or such other control systems for operations as are necessary to prevent contamination or mix-ups during the course of manufacturing and processing operations;
•          failure to have an adequate system for monitoring environmental conditions in an aseptic processing area;
•          failure to test the Invitra AT and Invitra WJ products, non-penicillin drug products, for the presence of penicillin although a reasonable possibility exists that the non-penicillin drug products have been exposed to cross contamination with penicillin;
•          failure to establish and follow written procedures describing the handling of all written and oral complaints regarding a drug product;
•          failure to establish and follow a written testing program designed to assess the stability characteristics of drug products and to use results of such stability testing to determine appropriate storage conditions and expiration dates;
•          failure to establish and follow written procedures describing in sufficient detail the control procedures employed for the issuance of labeling; and
•          failure to withhold from use each lot of components, drug product containers, and closures until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.

Invitrx was told to respond with a list of specific steps it has taken or plans to take to correct the violations and prevent their recurrence with the documentation necessary to show that correction has been achieved and a timetable for completion of all the steps.