1Documentation and records
Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity [21 CFR 211.160(b)]. The review of batch records and procedure QAD-040 titled “Product Release” (Effective date: September 5, 2023) indicate final product testing is limited to sterility testing and endotoxin testing as measurements of product attributes and such testing does not demonstrate, for example, the identity and/or strength of your products.
2Laboratory and QC controls
Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates [21 CFR 211.166(a)]. For example, your firm assigned expiration dates between (b)(4) months to your products without adequate supporting data that conform to appropriate standards of identity, strength, quality, and purity. For…
3Aseptic processing and sterility assurance
Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions [21 CFR 211.42(c)(10)(v)]. For example, your firm has failed to validate your procedure for cleaning and disinfecting the ISO 5 (b)(4) and supporting ISO 7 cleanroom where your products are manufactured. Validation of a cleaning process is needed to verify suitable cleaning and disinfecting agents are used to remove potential microbial contaminants from the critical manufacturing areas where your products are exposed during manufacturing.
4Aseptic processing and sterility assurance
Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas to prevent contamination [21 CFR 211.42(c)(10)(iv)]. For example, a. Your firm has not performed routine (i.e., during every production batch) non-viable particulate monitoring and surface sampling of the critical area (i.e., (b)(4) where your products are exposed to the environment). The environmental monitoring frequencies described in SOP QCD-034 titled, "Environmental Controls and Monitoring Procedure" (Effective date: December 12, 2022) are not sufficient to detect potential environmental contamination risks and demonstrate control inside the critical manufacturing area during manufacturing. b. Your firm does not require microbiological monitoring of operators' arm coverings used in the critical aseptic processing area for manually processing your products.
5Process validation
Your firm failed to establish adequate 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 [21 CFR 211.100(a)]. For example, your firm has not adequately validated your manufacturing processes for your products with respect to identity, strength, quality, and purity. Your testing is limited to (b)(4) . These are not sufficient measures of identity, strength, quality, and purity. Process validation studies determine whether an initial state of control has been established while routine monitoring of process performance and product attributes determines whether control is maintained. Establishment of appropriate attributes relating to identity, strength, quality, and purity of drug products is essential for assuring product quality over the product lifecycle.
