细胞和基因治疗产品原材料的质量控制.pdf

1、1Pharmaceuticals and Medical Devices AgencyDisclaimer:The contents of this presentation represent the view of this presenter only,and do not represent the views and/or policies of the PMDA.Quality Control of the Raw Materials for Cell and Gene Therapy ProductsAtsushi NISHIKAWAPrincipal Reviewer,Offi

2、ce of Cellular and Tissue-based Products,Pharmaceuticals and Medical Devices Agency(PMDA),JAPAN2Pharmaceuticals and Medical Devices AgencyOutline1.Overview of CAR-T Products2.Quality control of raw materials for each type of modality regulatory situation in JapanControl of starting materialsControl

3、of raw materials(FBS,trypsin,etc.)Control of transgenic reagentsRisk management of adventitious agents3.Regulatory differences between regions3Pharmaceuticals and Medical Devices AgencyCAR-T Therapyhttps:/www.cancer.gov/publications/dictionaries/cancer-terms/def/car-t-cell-therapyCAR:Chimeric Antige

4、n ReceptorExtracellular receptorExtracellular hinge domainTransmembrane domainIntracellular costimulatory domainIntracellular signaling domain4Pharmaceuticals and Medical Devices AgencyApproved auto CAR-T Products in JAPANCarvykti(2022)Multiple myelomaB-Cell Maturation Antigen(BCMA)CAR-T Abecma(2022

5、)CD19 CAR-T http:/www.takara- B-Cell Lymphoma,etc.Kymriah(2019)5Pharmaceuticals and Medical Devices AgencyCurrently approved types of CAR-T productsNovel types of CAR-T cell productsNovel types of CAR-T cell productsAllogeneic CAR-TMethod of CAR gene transferNon-viral vectors(piggy-BAC,etc.)Genome e

6、ditingGenome editing tools are also used to knockout TCR,PD-1,CTLA-4,etc.toenhance CAR-T cell function.Depending on the type of modality,appropriate quality controlshould be considered.Autologous CAR-TGenetically modified with viral vectors(lentiviral vectors,retroviral vectors)6Pharmaceuticals and