ALI Pharmaceutical Manufacturing, LLC – FDA Warning Letter, Oct 3, 2022

On March 30, 2023, the FDA issued a Warning Letter to ALI Pharmaceutical Manufacturing, LLC, following an inspection from September 26 to October 3, 2022. The inspection revealed significant deviations from current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (API), rendering their API adulterated under the FD&C Act.

Key violations include: 1. **Failure to demonstrate reproducible manufacturing processes:** The company failed to adequately validate its porcine thyroid API manufacturing processes, including intermediates. The process validation was not representative of the current manufacturing process, which is critical for products with narrow therapeutic ranges like those for hypothyroidism. The company's response regarding retrospective evaluation and interim sampling was deemed inadequate, lacking sufficient rationale for sample size and not addressing the impact on other distributed API. 2. **Failure to establish and follow written procedures for investigating critical deviations or OOS results:** The company failed to adequately investigate Out-of-Specification (OOS) results. While revised procedures were mentioned, the response was inadequate as it did not address the failure to evaluate the manufacturing process, commit to evaluating retain samples, or provide evidence for further investigations into microbial and other OOS results. 3. **Failure to ensure API lots meet specifications prior to blending:** The company failed to perform analytical testing prior to the final blend of intermediate lots, potentially leading to blending non-conforming lots and unreliable finished API results. The proposed sampling plan for