Florida Manufacturer Warned for Inadequate Written Procedures

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FDA sent a warning letter to Allay Pharmaceuticals for inadequate written procedures; inadequate out-of-specification testing; inadequate stability testing; and inadequate quality control oversight.

A warning letter sent to Allay Pharmaceuticals by FDA on Jan. 27, 2021 details violations of current good manufacturing practices (CGMPs) found at the company’s Hialeah, FL site during an agency inspection conducted from May 5–15, 2020. Investigators found a variety of quality control failures and a lack of written production and process control procedures.

Specifically, FDA stated in the letter that the company had not adequately validated manufacturing processes. “You lacked adequate data to show homogeneity of your drug product during manufacturing. During your process performance qualification (PPQ), blend samples were (b)(4) before analysis. When samples are (b)(4), it potentially masks the variability of your blend. In addition, you obtained an out-of-specification (OOS) assay result for one of the active ingredients, (b)(4), in your post-compression testing of (b)(4) strength PPQ lot (b)(4).” FDA also found samples collected from the company’s process validation lots to have sub-potent API.

“Your manufacturing failures indicate that you do not have an adequate ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality,” the letter stated. FDA requested the company provide the agency with a “data-driven and scientifically sound analysis” of sources of variability; a summary of the company’s validation program; a process performance qualification timeline for its products; and process performance protocols and written procedures for equipment and facility qualification.

The agency also stated that the company failed to thoroughly investigate out-of-specification (OOS) assay results found after FDA testing of one lot of tablets. “Your investigation into the OOS sample result was inadequate and did not identify CAPA. Furthermore, an investigation was not performed to ensure that previously released lots met your revised assay specifications. FDA investigators found 13 lots within expiry that exceeded your new assay specification during release or stability testing. These lots should have been identified in your investigation,” the agency stated in the letter. FDA requested the company provide a review and risk assessment of products to determine if specifications are appropriate; updated procedures for routine review of product specifications; an independent assessment of its system for investigating OOS results and deviations; and an action plan with timelines and summary results from retain sample testing of product.


In the letter, the agency also stated that the company had failed to establish and follow a written testing program for assessing stability characteristics. The company’s quality control unit also failed to ensure that products were manufactured in compliance with CGMPs, according to FDA. Specifically, according to the agency, the company did not adequately evaluate variability in supplier API assay results compared with the company’s testing. “The variability observed may compromise the assay and content uniformity of your finished product. For example, your firm’s test results for API lot (b)(4), used in the manufacture of (b)(4) tablets (b)(4) lot (b)(4), had a difference of 7.8% from the API manufacturer’s certificate of analysis (COA). Your firm used your assay result to formulate the finished product. Additionally, the FDA sampled lot (b)(4) and the sample results failed to meet the USP assay specification for active ingredient, (b)(4), and for content uniformity.”

Source: FDA