Indeus Life Sciences Private Limited — EU GMP NCR (EudraGMDP) Findings

A routine GMP inspection was carried out by the Dutch Health and Youth Care Inspectorate (IGJ) from 2 to 5 June 2025. The product in scope was LOPERAMIDE/SIMETHICONE TABLETS 2mg/125mg, that were to be reintroduced to the Dutch market. The inspection resulted in 7 (seven) Major deficiencies and 10 (ten) Other deficiencies. IGJ concluded that the Company is not in compliance with GMP, based on the amount and severity of the deficiencies. The Major deficiencies were the following: 1. The storage and retention of documents, obsolete artwork, reference samples, spare parts and other waste is inappropriate. Two rooms with severe issues were found: a ‘document room’ with heavy mold and humidity stains on walls, chaotic storage of documents and unidentified drums (presumably development batches); an adjacent room with scrapped GMP documents, obsolete artwork, obsolete reference samples and other debris, uncategorized and chaotically stored, with the room as well being used as dressing room for contract workers. 2. The quality system functions insufficient. Many issues were found in the management and investigation of deviations, changes and OOS. PQR and management review were incompletely executed. 3. Outsourced activities are not sufficiently defined, agreed and/or controlled. The requalification of all suppliers of the product in scope were overdue; API suppliers were not audited as of 2018; significant lapses in the requalification procedure and incomplete supplier agreements were observed. 4. The reintroduction of Loperamide/Simeticone tablets onto the Dutch market is not controlled. The applied assay limit specification was lower than the specification as laid down in the Marketing Authorization; averaging into compliance of analytical results for these tablets was allowed; agreements with the MAH were lacking. 5. Contamination control is insufficient, as was shown by many issues in cleaning, environmental monitoring and water monitoring. Examples were seen in missing cleanliness labels, improperly stored hoses, dirty cleaning clothes and gowning, incomplete cleaning procedures, missing preventive maintenance and checks on equipment; missing QRM principles and justifications in environmental monitoring, EM measurements that were not representative for daily practice, EM and HVAC procedures not being followed; infrequent water measurements and incomplete trending. 6. Validation and qualification are structurally inadequately performed, assessed and reviewed. Severe issues were found in cleaning and process validation, analytical method validation and room qualification; mostly related to missing (crucial) elements, but also not procedures not being followed, incomplete reporting and interpretation of results. 7. Lapses in Good Documentation Practices and control of documents. A wide range of issues were found; among others uncontrolled documents, incomplete and incorrect documents, and registrations. Furthermore, unexplainable data and missing data entries and signing were observed. Action taken/proposed by the NCA: Recall of batches already released Consideration of recall, following NCA assessment of potential quality defects vs. supply restriction. A direct product risk could not be identified, however the nature of the Major deficiencies and the cumulative risk of the deficiencies combined could lead to an inferior product. Based on the information received from the company, as of 2021 only LOPERAMIDE/SIMETHICONE TABLETS 2mg/125mg have been manufactured for the EU; 24 batches in 2022 and 12 batches in 2024. Based on the small scale of manufacturing (max. 100.000 tablets/batch) IGJ expects that only a limited number of tablets will still be on the market. To current knowledge, marketing authorizations are applicable in The Netherlands and Poland; further distribution to other countries is unknown. Prohibition of supply The company should not supply to the EU market whilst the NCS in is force. A successful reinspection is recommended before market supply is resumed.