Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting — EU GMP NCR (EudraGMDP) Findings

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. 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. Major deficiencies: 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. 2) Aseptic process simulation is inadequate for both the registered product and the ATMP process, including the additional media fill. 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. 4) Operator behaviour in the cleanroom and gowning procedures for Grade B areas are inadequate. 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. 6) The approach to Computerized System Validation (CSV) and data integrity is inadequate. 7) Good Documentation Practices (GDocP) are not sufficiently adhered to, as demonstrated for example by the backlog of revisions for multiple documents. In conclusion: the impact of the GMP non-compliance on registered products, ATMPs and most of the investigational medicinal products is exclusively national, except for one clinical study (EU CT 2023-505039-11-00)(see paragraph: suspension of clinical trials). Action taken/proposed by the NCA: Suspension of clinical trials For the EU only one product is impacted: M22BOL study (EU CT 2023-505039-11-00). The activities relabeling and repackaging of DS-8201a (trastuzumab deruxtecan). All the other products are solely present on the Dutch market. Impact: The impact of the inspection findings for EU CT 2023-505039-11-00, where a registered product will be relabeled and repacked by NKI/AVL, will be limited. This is an existing and released medicinal product. The critical shortcoming plus four major shortcomings regarding sterile manufacturing and aseptic production do not affect this investigational medicinal product. However, major shortcomings regarding the Quality Management system, Computer System Validation and Good Documentation practice could affect this investigational medicinal product. Recommendations: Up to this moment, four patients out of the expected total amount of 72 patients have been treated since the start of the clinical trial May, 2, 2024. Those four patients were treated in the Netherlands. It is up to the concerned Member States to make a decision regarding their market taking into account the legal frameworks. Others Withdrawal of GMP certificates NL/H 24/2051740A, NL/H 24/2051740B, NL/H 24/2051740C and NL/H 24/2051740D. A re-inspection will be performed on the basis of the company's plan of action to address the deficiencies (currently not scheduled yet). After a positive result following the re-inspection an new GMP-certificate will be issued and this non-compliance statement will be withdrawn.