PT Novell Pharmaceutical Laboratories — EU GMP NCR (EudraGMDP) Findings

The production of sterile products at the facilities of PT Novell Pharmaceutical Laboratories in NBL-1 and NBL-2 is considered not compliant with Annex 1 EU GMP as listed in the deficiencies raised in the inspection report as well as the gaps identified in the CCS which was submitted in the response on 08 March 2024. The following products were in scope of the inspection: Tranexamic acid 500 mg/5ml Solution for Injection (Tranexamsäure Medicamentum 25 mg/ml Injektionslösung) in NBL1 1st floor line 2, NBL2 2nd floor line 1; Esketamine 25 mg/ml Solution for Injection (Esketamin Medicamentum 25 mg/ml Injektionslösung) in NBL1, 1st floor line 3; Midazolam 1 mg/ml Solution for Injection (Midazolam Medicamentum 1 mg/ml Injektionslösung) in NBL1, 1st floor line 3; Amiodarone 50 mg/ml Solution for Injection (Amiodaron Medicamentum 50 mg/ml Injektionslösung) in NBL1, 1st floor line 3; Dexmedetomidine 100 mcg/ml concentrate for Solution for Infusion (Dexmedetomidin Medicamentum 100 mcg/ml Konzentrat zur Herstellung einer Infusionslösung) in NBL-1, 2nd floor; Vitamin B1 100 mg/2ml and 50 mg/2ml Solution for Injection (Vitamin B1 Medicamentum 100 mg/2ml bzw. 50 mg/2ml Injektionslösung) NBL1, 1st floor line 3; The implementation of suggested actions in order to solve the raised deficiencies needs to be reevaluated during an on-site inspection. A paper-based evaluation of proposed actions is considered not adequate. Furthermore, the company intends to move the production of EU products from NBL-1 to NBL-2. A marketing authorization variation for transfer of the production to NBL-2 should be submitted and accepted prior to start EU production. The approval of the variation should be submitted to the respective EU authority. Following points addressed, but not limited to these points, need to be implemented and reevaluated on-site before starting the production of sterile products: - The continuous monitoring of alarm differential pressure of clean rooms including a pressure alarm system. - Smoke studies of clean rooms and filling lines - Cleaning validation of aseptic filling lines - Integrity test validation for vials - Sterile filtration system: o allow sterilization in place o allow integrity testing after assembling as closed system o allow integrity testing pre-use post sterilisation and post use (PUPSIT) o allow filter in line testing o product specific filter validation o single use of the bioburden and sterile filter - The access of technical area of the oven and the autoclave from clean room - The manual transfer of washed equipment from CRC C to CRC A via trolley - Suitablity of epoxy coating of clean room walls and floors. - Suitability of Clean rooms for sterile production in general - Distinguishability of cleanroom garments of production and cleaning personnel - Clear pressure difference of clean rooms to adjacent area - Clear requalification requirements and implementations for clean rooms, filling lines and autoclaves For details also refer to response of the inspectors in the final report INS-484367- 101052478-19224178. Action taken/proposed by the NCA: Others -Restriction of current valid GMP certificate -Suspension/revocation/requested variation/ refusal to grant * of Marketing Authorisation(s)