Hebei Shengxue Dacheng Pharmaceutical Co. Ltd. — EU GMP NCR (EudraGMDP) Findings

During the joint Swissmedic / EDQM inspection at manufacturing site (LOC ID LOC-100069397) 4 critical, 12 major and 23 other deficiencies were identified. The critical deficiencies and 9 of the major deficiencies are related to an insufficient implementation of annex 1 requirements, thus constituting a potential risk of producing non-sterile products which could be harmful to patient/treated animals. The company failed to establish an adequate Quality Risk Management to ensure product sterility. Several deficiencies were found for the execution of aseptic process simulation as well as for the sterilization of the spray dryer and filling system. Furthermore, the company was not able to establish an appropriate endotoxin control strategy which could also potentially impact non-sterile APIs. The firm's approach to environmental monitoring, aseptic behaviour in clean rooms, container closure integrity, cleaning, gowning and protection of sterile garment is contributing to an overall risk to the quality of the product and the sterility cannot be guaranteed. The design and maintenance of the clean rooms and equipments in grade A, B and C is insufficient to maintain an adequate environment for the manufacture and aseptic filling of sterile APIs. Additionally, the company failed to establish an appropriate change control management, adequate cleaning and process validation, as well as an overall insufficient preventive maintenance strategy. During the inspection it was found that the level of GMP compliance is insufficient, specifically for Annex 1 requirements it can be stated that knowledge at the site is limited. Action taken/proposed by the NCA: Requested Variation of the marketing authorisation(s) This manufacturer should not be authorised in any new/ongoing marketing authorization or variation application. The submission of a variation application for introducing alternative manufacturers of the active ingredient is recommended Recall of batches already released The decision to be made by NCA, following an assessment between the NCA and MAH, whether to recall a batch of a particular product or not should be based on a risk assessment and on the criticality of the product. Prohibition of supply After issuance of the non-compliance report and as long as it remains active, prohibition of supply of sterile APIs is recommended, unless there are no alternative suppliers and there is a risk of shortage. Suspension or voiding of CEP (action to be taken by EDQM) Suspension of sterile CEPs is recommended. EDQM suspended on 12/01/2026 the following sterile CEPs: CEP 2018-146, Dihydrostreptomycin sulfate for veterinary use, Sterile and CEP 2019-246, Colistimethate sodium, Sterile