Viral Shedding Viral Shedding <in hospital> <in - PowerPoint PPT Presentation

ICH WORKSHOP: Viral Shedding Review of experience of shedding data for in vivo gene therapy Teruhide YAMAGUCHI

Viral Shedding Viral Shedding <in hospital> <in hospital> into Patients' ??? ??? Blood, Urine, Gene Therapy Products Gene Therapy Products Feces, Sputum... ??? ??? ??? ??? patients patients <into the environment > <into the environment >

Impact of Viral Shedding • Viral shedding risk – Depends on biodistribution and the biological activity of each vector – Depends on the route of administration, dose and so on • How to test for viral shedding • Risk of vector/virus from patients to 3rd-party should be dependent on: – biological activity of virus shed – viability of virus in the environment • Measures to minimize the risk of viral shedding

Should all Viral Vectors be treated in the same way in relation to shedding? Review of experience of shedding data for in vivo in vivo gene therapy gene therapy Review of experience of shedding data for Impact of viral shedding is dependent on: viral shedding is dependent on: Impact of � Property of virus � Property of virus � Biodistribution Biodistribution � � Route of administration � Route of administration � Systemic or local administration Systemic or local administration � Adenovirus Adenovirus � Ex vivo Ex vivo or not or not � Ｖ Ｖ � Dose � Dose � High or low High or low � Adeno- -Associated Associated Adeno � Single dose or repeat doses Single dose or repeat doses � virus virus Seneca Valley virus (Picornavirus Picornavirus) ) Seneca Valley virus (

How to detect viral shedding How to detect viral shedding How to detect viral shedding How to detect viral shedding sputum sputum sputum sputum Detection of viral shedding Detection of viral shedding � Detection of viral shedding Detection of viral shedding � � PCR PCR PCR PCR � � sensitive and accurate sensitive and accurate sensitive and accurate sensitive and accurate � � no correlation of infectivity no correlation of infectivity no correlation of infectivity no correlation of infectivity � � Infectivity assay Infectivity assay Infectivity assay Infectivity assay � � less sensitive less sensitive less sensitive less sensitive � � New method New method New method New method Blood Blood Blood Blood � � Infectivity PCR Infectivity PCR Infectivity PCR Infectivity PCR �

Measures to minimize the risk of Measures to minimize the risk of Measures to minimize the risk of Measures to minimize the risk of viral shedding viral shedding viral shedding viral shedding � Patients in quarantine Patients in quarantine Patients in quarantine Patients in quarantine � � Study design of viral shedding Study design of viral shedding Study design of viral shedding Study design of viral shedding � � How long viral shedding is How long viral shedding is How long viral shedding is How long viral shedding is � detected detected detected detected � Follow Follow Follow- -up up up Follow up �