China manufacturing-site findings

The inspection team identified 18 deficiencies (grouped) against EU GMP, of which 11 were classified as Major. The major deficiencies were related to: - Inadequacy of Quality Assurance oversight and Quality management system - Inadequate design, poor maintenance/cleaning, lack of contamination control in intermediates manufacturing facilities - Solvent recovery, lack of traceability and risk of cross-contamination - Risk of supplying non-GMP APIs for production of medicinal products for human or animal use - Change control - Data integrity of documentation and records - Traceability and control of material throughout the manufacturing process - Cleaning and process validation - Material management - Insufficient control of analytical methods - Incomplete understanding and incorrect application of fundamental GMP principles Action taken/proposed by the NCA: Suspension or voiding of CEP (action to be taken by EDQM) CEP 2023-042 / Dexamethasone sodium phosphate CEP 2023-086 / Betamethasone CEP 2023-244 / Dexamethasone Crystalline Form-B CEP 2023-305 / Dexamethasone Crystalline Form-A were suspended on July 29, 2026 by EDQM

During the inspection of the manufacturing site, in the frame of EDQM’s inspection progamme, 21 deficiencies against EU GMP were identified. One deficiency was classified as critical due to inadequate control of contamination and cross-contamination risk in shared facilities. The risk assessments and contamination control strategy for Workshop 2 and the dispensing area were insufficiently robust, specific, justified, and effectively implemented, notably for exposed product operations, gowning, area and equipment cleanliness, material entry, dispensing activities, and the use of shared equipment for potentially highly potent products. Furthermore, absence of contraindications between APIs manufactured in the shared facility was not evaluated consistently. These represent a potential risk to patient safety. Five deficiencies were classified as major and were related to the following areas: cleaning validation and cleaning procedures, preventive maintenance and equipment condition, data integrity, change control management, and batch release and compliance to CEP. In addition, 15 other deficiencies were found (i.e. records, quality system, personnel training, calibration, labelling management, equipment qualification). Action taken/proposed by the NCA: Requested Variation of the marketing authorisation(s) For medicinal products containing APIs manufactured by LIANYUNGANG GUIKE PHARMACEUTICAL CO. LTD. in Workshop 2, assessment of the MA to remove or substitute this manufacturer of active substances and intermediates should be considered. In addition, no new MAs should be granted for products relying on this API source while the statement of non-compliance remains in force. Recall of batches already released If there are alternative suppliers and there is no risk of shortage, recall of medicinal product should be evaluated by the involved NCAs following assessment conducted in conjunction with MAHs. Prohibition of supply Due to the nature of the non-compliance, prohibition of supply 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) The EDQM had taken the decision to suspend all granted CEPs from LIANYUNGANG GUIKE PHARMACEUTICAL CO. LTD. CEP 2013-019 Atracurium besilate CEP 2021-236 Cisatracurium besilate CEP 2017-271 Entecavir monohydrate (intermediate)

Laboratory records do not include complete data derived from all tests, examinations, and assay necessary to assure compliance with established specifications and standards.

Backup data is not assured as exact, complete and secure from alteration, erasure or loss through keeping hard copy or alternate systems.

Equipment and utensils are not maintained at appropriate intervals to prevent contamination that would alter the safety, identity, strength, quality or purity of the drug product.

Laboratory Controls do not include the establishment of scientifically sound and appropriate test procedures designed to assure that components, in-process materials and drug products conform to appropriate standards of identity, strength, quality and purity.