FDA 发布两封新警告信，聚焦 OOS 调查缺陷

On 29 September 2026, the U.S. Food and Drug Administration (FDA) published two new Warning Letters that, among other issues, identify significant deficiencies in out-of-specification (OOS) investigations. Both underline that retesting, procedural changes or revised specifications cannot replace scientifically sound investigations, robust root cause analysis and an assessment of the potential impact on other batches and products.Delayed OOS Investigation and Batch Release During an Open InvestigationAlthough the first Warning Letter was published only at the end of September 2026, it relates to an FDA inspection of a finished-drug manufacturing site in Rocklea, Queensland, Australia, in 2025.A contract testing laboratory reported an OOS result in August 2024. The Phase II investigation did not begin until December 2024, several months later. While the investigation remained open, the quality unit (QU) released the batch. The batch was subsequently shipped to the United States after a retest produced passing results. The investigation was eventually closed without determining the root cause of the original OOS result.The FDA considered the response inadequate. It did not explain the nearly 11 month investigation, and the stated breakdown in the product release procedure did not establish the cause of the OOS result. The FDA also found that no comprehensive assessment had been provided to determine whether other OOS investigations had been adequately handled.The affected firm now faces a considerable amount of work: FDA requested an independent retrospective review of all invalidated OOS results, including in-process, release and stability results, for U.S. products that were on the market and had not yet expired as of the date of the letter. The authority also requested a comprehensive review and remediation of the OOS investigation system, including QU oversight of laboratory investigations, identification of adverse laboratory trends, investigation of potential manufacturing causes where no conclusive laboratory cause is found, appropriate investigation and CAPA scope, and revised procedures.Stability OOS Results Inadequately InvestigatedThe second Warning Letter followed an FDA inspection of a drug manufacturing site in Edison, New Jersey, in March 2026.The FDA cited several examples of inadequate OOS investigations. These included an assay OOS result at the 24 month stability time point for which the root cause was not scientifically established and the impact on products already on the market was not adequately assessed. A separate OOS pH result at the 36-month stability time point was also inadequately investigated. As CAPA, the pH specification range had been widened without scientific justification.The response attributed the investigation deficiencies to weaknesses in procedures, but the FDA found that the firm had not committed to revising those procedures to require root cause assessment for OOS results. The FDA requested a comprehensive, independent assessment of the overall system for investigating OOS results, discrepancies, complaints and failures, followed by a detailed remediation plan. The authority also requested independent assessments of the CAPA and change management systems, together with an action plan addressing product quality or patient safety risks for products distributed in the United States, including customer notifications and recalls where appropriate.For further information and the full list of findings in other areas, please refer to the full Warning Letters issued to VeganicSKN Limited and Bentley Laboratories LLC on the FDA website.