Adventitious agents,comprising unintentionally introduced microorganisms in the production of biological products,pose a significant challenge in ensuring the safety of gene therapy products.The revised International ...Adventitious agents,comprising unintentionally introduced microorganisms in the production of biological products,pose a significant challenge in ensuring the safety of gene therapy products.The revised International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH)guildline Q5A(R2)from September 2022 highlights the inclusion of viral vector-based gene therapy products in safety discussions,emphasizing controls in material sourcing,testing,and viral clearance[1].Detecting adventitious virus contamination is complex due to the unique characteristics of gene therapy products and the limitations of routine testing methods.The US Food and Drug Administration(FDA)recommends incorporating routine and specific virus detection methods,including those outlined in various pharmacopeias.Existing control methods have limitations,prompting the need for highly sensitive and broad-spectrum detection approaches.Unlike traditional biological products,gene therapy products primarily consist of live viruses,necessitating methods that distinguish between the main virus and adventitious viruses.Current virus detection techniques,such as polymerase chain reaction(PCR),sequencing,mass spectrometry,and DNA microarrays[2e4],have their drawbacks.展开更多
基金financially supported by Beijing Municipal Science&Technology Commission,China(Grant No.:Z221100007922015)Youth Development Research Foundation of National Institutes for Food and Drug Control,China(Grant No.:2020B1).
文摘Adventitious agents,comprising unintentionally introduced microorganisms in the production of biological products,pose a significant challenge in ensuring the safety of gene therapy products.The revised International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH)guildline Q5A(R2)from September 2022 highlights the inclusion of viral vector-based gene therapy products in safety discussions,emphasizing controls in material sourcing,testing,and viral clearance[1].Detecting adventitious virus contamination is complex due to the unique characteristics of gene therapy products and the limitations of routine testing methods.The US Food and Drug Administration(FDA)recommends incorporating routine and specific virus detection methods,including those outlined in various pharmacopeias.Existing control methods have limitations,prompting the need for highly sensitive and broad-spectrum detection approaches.Unlike traditional biological products,gene therapy products primarily consist of live viruses,necessitating methods that distinguish between the main virus and adventitious viruses.Current virus detection techniques,such as polymerase chain reaction(PCR),sequencing,mass spectrometry,and DNA microarrays[2e4],have their drawbacks.
