山东省已上市生物制品备案变更的典型问题和风险分析

Typical Problems and Risk Analysis of Post-Approval Changes of Biological Products in Shandong Province

生物制品上市后变更是生物制品全生命周期中不可或缺的重要一环,对生物制品安全性、有效性和质量均可能带来风险。为帮助和指导药品上市许可持有人高效、规范地开展研究验证、提交申报资料,本研究通过梳理山东省2023年已上市生物制品的备案申报情况,总结归纳了备案申报资料中存在的典型问题,包括备案内容不规范、备案申报资料不齐全、变更等级判定不合理、申报延长有效期但未完成产品注册批件中的研究、变更可比性研究不全面等,并针对相关问题存在的风险进行分析,建议药品上市许可持有人应依据相关法律法规要求加强上市后药品的管理,科学合理地判定变更类别,加强与药品监管机构的沟通交流,有效识别、评估并管控变更可能导致的风险,进一步强化并落实持有人作为药品全生命周期质量保证和持续研究的主体责任;药品监管部门应加大对上市后变更的监管力度,在技术审评过程中对上市后的变更备案严格把关,确保备案后生物制品的有效性、安全性和质量可控性不因变更而受到不良影响。

The post-approval change of biological products is an indispensable part of the whole life cycle of biological products,which may bring risks to the safety,effectiveness and quality of biological products.In order to help and guide drug marketing authoriza‐tion holders(MAH)to carry out research validation and submit declaration materials efficiently and normatively,this study summarized the filing application situation of markted biological products in Shandong province,summed up the typical problems existing in the filing materials,including non-standard content of record,incomplete data of record and declaration,unreasonable determination of change grade,apply for extension of validity period but not complete the study required in product registration and approval,incomplete study on comparability of changes,etc.In view of the risks of the related problems,it is suggested that MAH should strengthen the management of post-approval produts according to relevant laws and regulations,determine the types of changes scientifically and rationally,and strengthen the communication mechanism with drug regulatory agencies,to effectively identify,assess and control the risks that may result from the changes,not arbitrarily reduce the types of changes,and further strengthen and implement MAH responsibilities as the main body of drug life-cycle quality assurance and ongoing research.The drug regulatory authorities should strengthen the supervision of post-approval changes,strictly check the record keeping of post-approval changes in the course of review,and resolutely refuse to record those that do not meet the requirements,ensure that the effectiveness,safety and quality controllability of the biological product after fil‐ing is not adversely affected by the change.