American Specialty Pharmacy, Inc. dba ASP Cares — FDA Warning Letter Findings

Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.

Your firm failed to validate your (b)(4) to ensure it can maintain adequate temperatures to achieve required depyrogenation.

Your firm has not addressed the steps of remediation for positive environmental results found in environmental monitoring reports. In addition, your firm failed to conduct investigations into the impact of these environmental excursions on your sterile products.

Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).

Your firm failed to validate your (b)(4) by ensuring your process can detect the highest and lowest temperature spots within the (b)(4) which provides valuable information on where to place your (b)(4) to ensure sterility of your products is achieved through the (b)(4) .

Your firm failed to document and measure pressure differentials during operations to demonstrate proper airflow. Therefore, this indicated a lack of assurance that your firm can aseptically produce drug products in an environment that may not provide adequate protection against the risk of contamination. The FDA investigator also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example…

Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and your firm’s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)).

Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)). Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21…

Your media fills were not performed under the most challenging or stressful conditions such as failing to simulate the largest batch size produced at your firm. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.

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 firm caulked the loose ceiling tile noted on inspection and repeated the cleaning procedure for the cleanroom with a sporicidal agent. We are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation…

Your firm’s facilities where sterile drug production occurs is not maintained in an adequate state of repair. For example, the investigator noted a crack in the caulking around the HEPA filter inside the ISO 7 cleanroom ante of Modular 1. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.

You state that you have hired a contract laboratory to develop a validated potency test method for your taurine injection, but you have not provided any timeline for implementing this test method and interim steps that your firm is taking to ensure the potency of your taurine injectable product. Additionally, your firm provided no information on how you will ensure the products produced and released by your facility will be tested for identity, potency and any other release testing requirements for each individual product produced at your firm. Some of your corrective actions appear deficient…

Your firm stated that the (b)(4) testing result for your sterile products was set below the product specification without providing any scientific rationale to support this interim passing result. In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501…

Your firm revised and updated Master Production Records to include intermediate hold steps for any batches that are not immediately sterilized or filled into their final container.