1Laboratory and QC controls
Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)). Before beginning distribution, you did not adequately study antimicrobial effectiveness in your…
2Equipment and facility
Failure to adequately establish schedules for the adjustment, cleaning, and other maintenance of equipment (21 CFR 820.70(g)). Specifically, the (b)(4) Sanitization system of the (b)(4) water system was not part of a maintenance schedule. The system included three gauges that measure the (b)(4) in the system to verify that the sanitization process and the storage tank control are acceptable. There was no documentation that gauges ( (b)(4) ) had been calibrated.
3Other quality system
Failure to adequately establish procedures for design input (21 CFR 820.30(c)). Specifically, the design for Hydral Spray failed to include Burkholderia cepacia as a challenge in (b)(4) although Burkholderia cepacia was included in the (b)(4) challenge for other products to include the (b)(4) toothpaste in June 2017. The risk management file of the Hydral Spray was not updated to include these objectionable organisms and any controls necessary to mitigate the risks as part…
4Deviation, CAPA, and investigation
Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192). Your water system was subject to microbiological contamination and numerous deviations from operating parameters since validation. Many of these deviations were either not investigated or did not result in implementation of CAPA. • No investigations were…
5Other quality system
Your failed to adequately establish procedures for corrective and preventive action to include the documentation of such activities (21 CFR 820.100(a) & (b)). Refer above to the discussion of 21 CFR 211.192 violations.
6Quality unit oversight
Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)). You did not adequately exercise your responsibility to ensure all drug products manufactured by and for your firm possessed appropriate quality attributes, antimicrobial properties, or preservative systems to ensure…
