Objective: To refine and elaborate on typical types of change-related issues and specific cases, based on China’s post-marketing change management framework for drugs, providing a reference for marketing authorization holders to establish a robust post-marketing change control system and offering guidance for post-marketing change inspections of drugs. Methods: Using a literature review approach,keywords such as drug management, drug change, and post-marketing changes in pharmaceuticals were used to search on the official websites of the National Medical Products Administration (NMPA), the Center for Drug Evaluation (CDE) of NMPA, and provincial medical products administrations. A series of drug change regulations issued in China in recent years were sorted out, and the framework for drug change management in China was summarized. Statistical analysis was conducted on the drug change control deficiencies raised in FDA warning letters from 2021 to 2023. Additionally, based on the author’s recent inspection experiences, typical types of issues and specific cases related to post-marketing change management in China were identified through a survey research method. Results: China’s framework for drug change management is basically well-established. However, inspections of drugs conducted both domestically and internationally have uncovered deficiencies in the post-marketing change management by drug marketing authorization holders. These deficiencies include imperfections in the establishment of a change control management system, inappropriate categorization of change management, failure to submit supplementary applications, filings, or reports as required, exclusion of changes from the change control management system, and inadequate or insufficient research on changes. Conclusion: Marketing authorization holders should establish a scientific and reasonable internal change control system, conduct necessary research on changes, and utilize the communication mechanisms of regulatory authorities to fully discuss uncertain change categories. Drug inspectors should focus on knowledge management and summarizing inspection experience to form a systematic and comprehensive understanding of changes, and conduct targeted analysis of post-marketing change issues encountered during inspections.
Wu Fan
,
Mei Leilei
,
Fu Wenyan
,
Du Chuanlong
,
Sun Xijun
,
Hu Yuan
. Research on Post-Marketing Change Management and Analysis of Common Issues from the Perspective of Drug Inspection[J]. Chinese Pharmaceutical Affairs, 2025
, 39(2)
: 123
-131
.
DOI: 10.16153/j.1002-7777.2024-08-0020
[1] 吴凡,廖辉军,梅蕾蕾,等. 我国药品检查过程中上市后变更风险的研究与控制[J]. 药品评价,2021,18(24): 1481-1486.
[2] 颜若曦,曹轶,李小春. 世界卫生组织药品检查分析[J]. 中国药物评价,2020,37(1): 61-65.
[3] 漆亮,洪玲洁,宋宇. 江西省2022年度药品GMP检查缺陷分析与研究[J]. 药品评价,2023,20(11): 1301-1305.
[4] 江西省药品监督管理局. 关于印发《江西省药品监督管理局药品生产许可关键生产设施变化管理暂行规定》的通知[EB/OL].(2023-06-29)[2024-06-18]. http://mpa.jiangxi.gov.cn/art/2023/6/29/art_37110_4516329.html.
[5] 国家药品监督管理局药品审评中心. 国家药监局药审中心关于发布《药品注册申请审评期间变更工作程序(试行)》的通知(药审业〔2022〕597号)[EB/OL].(2022-11-11)[2024-06-18]. https://www.cde.org.cn/main/news/viewInfoCommon/0d5a8825b3da3461f93de60674100111.
[6] 国家药品监督管理局. 药品上市后变更管理办法(试行)[EB/OL].(2021-01-13)[2024-06-18]. https://www.nmpa.gov.cn/xxgk/fgwj/xzhgfxwj/20210113142301136.html.
[7] 国家市场监督管理总局. 药品生产监督管理办法[EB/OL].(2020-01-22)[2024-06-18]. https://www.gov.cn/gongbao/content/2020/content_5515280.htm.
[8] 国家药品监督管理局. 国家药监局关于印发优化药品补充申请审评审批程序改革试点工作方案的通知[EB/OL].(2024-02-07)[2024-06-18]. https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20240207173908137.html.
[9] ICH. Q12:药品生命周期管理的技术和监管考虑[EB/OL].(2019-11-20)[2024-06-18]. https://www.cde.org.cn/ichWeb/news/getNewsDetail/2/bb27c3d90c540d64d269e6c9da9db061/1.
[10] 国家药品监督管理局. 国家药监局关于发布《药品生产质量管理规范(2010年修订)》临床试验用药品附录的公告(2022年第43号)[EB/OL].
[11] 国家药品监督管理局. 药品监督管理统计年度数据(2021年)[EB/OL].(2022-12-28)[2024-06-18]. https://www.nmpa.gov.cn/directory/web/nmpa/zwgk/tjxx/tjnb/20221228165838115.html.
[12] 国家药品监督管理局. 药品监督管理统计年度数据(2022年)[EB/OL].(2023-04-19)[2024-06-18]. https://www.nmpa.gov.cn/zwgk/tjxx/tjnb/20230419090931121.html.
[13] 国家药品监督管理局. 药品监督管理统计年度数据(2023年)[EB/OL].(2024-05-20)[2024-06-18]. https://www.nmpa.gov.cn/zwgk/tjxx/tjnb/20240520160659160.html.
[14] 袁建龙,张灵娜,陈晴宇,等. 已上市化学药品中等变更的典型问题分析[J]. 中国医药工业杂志,2023,54(10): 1517-1520.
[15] 武海军,周冲,刘福龙,等. 上市后化学药品制剂生产场地变更政策解读与常见问题分析[J]. 中国药学杂志,2023,58(1): 83-86.
[16] FDA. Warning Letters[EB/OL].[2024-06-18]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/compliance-actions-and-activities/warning-letters.
[17] 程立. 美国FDA警告信制度对我国药品监管工作的启示[J]. 行政科学论坛,2022,9(8): 47-50.
[18] FDA. Warning Letter: Spartan Chemical Company,Inc.[EB/OL].(2021-12-28)[2024-06-18]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/spartan-chemical-company-inc-614450-12152021.
[19] FDA.Warning Letter: Syntec Pharma Corp[EB/OL].(2021-08-03).[2024-06-18]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/syntec-pharma-corp-612765-07062021.
[20] FDA.Warning Letter: Health Plus Inc[EB/OL].(2022-01-25)[2024-06-18]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/health-plus-inc-616877-12292021.
[21] FDA.Warning Letter: DuPont Nutrition USA Inc[EB/OL].(2022-12-20)[2024-06-18]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/dupont-nutrition-usa-inc-627211-12022022.
[22] FDA.Warning Letter: Aurobindo Pharmaceutical[EB/OL].(2022-01-25)[2024-06-18]. Limitedhttps://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/aurobindo-pharmaceutical-limited-618091-01122022.
[23] FDA.Warning Letter: Premier Trends LLC[EB/OL].(2022-03-22)[2024-06-18]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-lettes/premier-trends-llc-621313-03142022.
[24] FDA.Warning Letter: Sircle Laboratories LLC[EB/OL].(2021-10-19)[2024-06-18]. https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-lettes/sircle-laboratories-llc-615098-09212021.
[25] 国家药品监督管理局药品审评中心. 已上市化学药品药学变更研究技术指导原则(试行)[EB/OL].(2021-02-10)[2024-06-18]. https://www.cde.org.cn/main/news/viewInfoCommon/4ec3dca752a82347bdf24ad3d3e85113.
[26] 中华人民共和国卫生部. 药品生产质量管理规范[EB/OL].(2011-01-17)[2024-06-18]. https://www.samr.gov.cn/zw/zfxxgk/fdzdgknr/bgt/art/2023/art_d5e1dbaa8f284277a5f6c3e2fc840d00.html.
