荷兰药监局公布一家医院药房GMP不合规报告，1项严重缺陷含无菌检测失败仍放行ATMP
彪悍！无菌检测失败，依旧放行产品
荷兰药监局对一家医院药房开展GMP检查并判定不符合GMP要求，不合规报告于2026年10月7日公布在EudraGMDP数据库。检查于2026年2月10日至12日和4月22日至23日进行，结论为1项严重缺陷、7项主要缺陷和14项其他缺陷。
材料转述荷兰药监对一家医院药房的GMP不合规报告，列出1项严重缺陷与7项主要缺陷的具体条目，可供对照缺陷类别查阅。
2026年4月荷兰药监局对荷兰药企Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting进行了GMP检查，检查结束日期为2026年4月23日，相关的GMP不合规报告于2026年10月7日公布在EudraGMDP数据库。
The GMP inspection has been performed on February 10–12, 2026 and April 22-23, 2026. This manufacturer, a hospital pharmacy, is producing multiple type of products: medicinal products for human use with a marketing authorization, advanced therapy medicinal products (ATMPs, investigational) and human investigational medicines. It concerns sterile production of registered products and ATMPs and non-sterile production of registered products. In addition, the activities of investigational medicinal products are manufacturing of tablets/capsules, and relabeling and repackaging. All of the clinical studies are performed in the Netherlands, except one study is performed in Europe (M22BOL EU CT 2023-505039-11-00). The outcome of the inspection was GMP non-compliant, which is based on one (1) critical deficiency, seven (7) major deficiencies and fourteen (14) other deficiencies.
GMP检查于2026年2月10日至12日以及2026年4月22日至23日进行。该生产商为一家医院药房，生产多种产品：已获上市许可的人用药品、先进治疗药品（ATMPs，用于临床研究）以及人用临床研究用药品。涉及注册产品的无菌生产及ATMPs的无菌生产，以及注册产品的非无菌生产。此外，临床研究用药品的活动包括片剂/胶囊的生产，以及重新贴签和重新包装。所有临床试验均在荷兰开展，仅有一项试验在欧洲进行（M22BOL EU CT 2023-505039-11-00）。本次检查结果为不符合GMP要求，依据为1项严重缺陷、7项主要缺陷和14项其他缺陷。
In summary the main inspection findings were as follows: Critical deficiency: 1) The execution of the Out-of-Specification (OOS) process is inadequate. In practice, multiple batches of registered finished products were released even though they did not comply with the specified limits for moisture content or assay. An Advanced Therapy Medicinal Product (ATMP) was released despite a failed sterility test which was performed as an in-process control. In addition, the procedure for OOS is not unambiguous and can lead to batch certification and release without thorough investigation of sufficient justification.
主要检查发现如下：关键缺陷：1）OOS处理程序执行不充分。实际操作中，多批已注册的成品即使未达到规定的水分含量或含量限度，仍被放行。尽管在生产过程中进行的无菌检测未通过，但仍批准放行了一种先进治疗药物产品（ATMP）。此外，OOS的处理程序不明确，可能导致在未充分调查和合理论证的情况下就对批次进行认证和放行。
Major deficiencies:
主要缺陷如下：
1)The control of aseptic practices for both the registered product and the ATMP manufacturing process is insufficient e.g. Annex1 gap assessment and the contamination control strategy are incomplete. Regarding ATMP production multiple aspects are not under control.
1）对已注册产品及ATMP生产过程中的无菌操作控制不足，例如附录1的差距评估和污染控制策略不完整；ATMP生产中多个方面均未得到有效控制。
2)Aseptic process simulation is inadequate for both the registered product and the ATMP process, including the additional media fill.
2）针对已注册产品和ATMP工艺的无菌操作模拟试验不足，包括额外的培养基灌装试验。
3)The design, investigation and trending of microbiological test results are insufficient for example multiple microbial exceedances on the hands of the operators in class A handling the ATMP product.
3）微生物检测结果的设计、调查和趋势分析不充分，例如在A级区域操作ATMP产品的操作人员手部多次出现微生物超标。
4)Operator behaviour in the cleanroom and gowning procedures for Grade B areas are inadequate.
4）操作人员在洁净室内的行为以及B级区域的更衣程序不符合要求。
5)The Pharmaceutical Quality System (PQS) is insufficient. This is shown by deficiencies identified in the management of deviations, CAPAs, changes, complaints, self-inspections, and the Product Quality Reviews (PQRs) that were assessed.
5）药品质量体系不完善。这体现在对偏差、CAPA、变更、投诉、自检以及所评估的产品质量回顾管理中存在的缺陷。
6)The approach to Computerized System Validation (CSV) and data integrity is inadequate.
6）计算机化系统验证和数据完整性的方法不足。
7) Good Documentation Practices (GDocP) are not sufficiently adhered to, as demonstrated for example by the backlog of revisions for multiple documents.
7）未充分遵守良好的文件规范，例如多份文件修订积压的情况即为明证。
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来源：GMP干货 · mp.weixin.qq.com