Sm Biomed Sdn. Bhd. — EU GMP NCR (EudraGMDP) Findings

Based on the findings of the inspection, supply of falsified API to European customers was identified and were determined to be non-compliant with the EU GMP standards, and with Directive 2011/62/EU of the European Parliament and of the Council of 8 June 2011, amending Directive 2001/83/EC on the Community code relating to medicinal products for human use, as regards the prevention of the entry into the legal supply chain of falsified medicinal products, and it is proposed by consequence to issue a Statement of Non-Compliance for SM BIOMED SDN BHD. Specifically, during the inspection, 10 deficiencies against EU GMP were identified. One critical deficiency relating to supply of falsified API to European customers was identified and two major deficiencies were also observed in relation to risks of contamination and cross-contamination and process validation. In addition, 7 other deficiencies were found. (It should be noted that due to the significant amount of time spent investigating the supply of falsified API to Europe, many elements of the quality system which would normally be covered as part of a routine GMP inspection, were not reviewed on this occasion). Action taken/proposed by the NCA: Requested Variation of the marketing authorisation(s) Assessment of the MA to delete or substitute SM BIOMED SDN BHD should be considered. No new MAs should be approved where APIs / intermediates from this site is used as long as the non-compliance statement is active. Recall of batches already released For Clarithromycin covered by CEP 2006-240 and CEP 2022-483 The need of recall of released batches of finished products where APIs/intermediates manufactured on this site have been used should be considered unless proven risk of shortage. For Erythromycin (CEP 1999-119), Erythromycin base dihydrate (CEP 2020-007), Erythromycin Ethylsuccinate (CEP 1999-121), Erythromycin Stearate (CEP 1999-120), and for substances not covered by CEP Erythromycin Estolate and Erythromycin Lactobionate: If there are alternative suppliers and there is no risk of shortage, recall of medicinal product should be evaluated by involved NCA’s following assessment conducted in conjunction with MAHs. Given the nature of non-compliances, assessment should include a complete retest of all imported batches of active substance. In specific cases of national legislation that require GMP certification for a specific API used in critical medicines with no alternative, each authority may decide, under their own responsibilities, to maintain locally a limited GMP certification of the company SM Biomed in order to guarantee the supply to its market. For other substances covered by CEP (Azithromycin, Betamethasone sodium phosphate, Betamethasone valerate, Deferasirox, Dexamethasone sodium phosphate), or other substances not covered by CEP (Sitagliptin Phosphate Monohydrate, Tadalafil): At that time, it is understood that no such APIs are supplied directly to EU/EEA markets. Nevertheless, if such substances have actually reached the European market through SM BioMed or other providers (manufacturers, brokers, …), similar assessment and decisions should be considered. 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. Given the nature of non-compliances, decision to accept the supply must be based on an assessment that should include a complete retest of all imported batches of active substance. Suspension or voiding of CEP (action to be taken by EDQM) The EDQM had taken the decision to withdraw all granted CEPs and to close all CEP application currently under treatment from SM BIOMED SDN BHD. Withdrawal of the Certificate of Suitability (CEP) : Betamethasone valerate (CEP 1999-118), Clarithromycin (CEP 2006-240), Clarithromycin (Process 2) (CEP 2022-483), Dexamethasone sodium phosphate (CEP 2024-065), Erythromycin (CEP 1999-119), Erythromycin (process 2) (CEP 2020-007), Erythromycin ethylsuccinate (CEP 1999-121), Erythromycin stearate (CEP 1999-120) Certificate of Suitability (CEP) application closing : Azithromycin (CEP 2024-067), Betamethasone sodium phosphate (CEP 2024-470), Betamethasone valerate (CEP 2025-284), Deferasirox (CEP 2024-142)