ESGCT/ICH Workshop on Viral Vector Shedding€¦ · Langen • Dr. S. Simek ... EMEA/ICH WORKSHOP ON VIRAL/VECTOR SHEDDING Tuesday 30 October 2007 (11.00-18.30) in conjunction with:

PaulPaul--EhrlichEhrlich--InstitutInstitutFederal Agency for Sera and VaccinesFederal Agency for Sera and Vaccines

CHMP GTWPCHMP GTWP

• Introductory notes:

What is vector shedding?

Why is it important?

Klaus Cichutek

Chair, CHMP GTWP at EMEAPaul-Ehrlich-Institut, 63225 Langen, Germany

E-mail: [email protected], 30 October 2007

ESGCT/ICH Workshop on Viral Vector SheddingESGCT/ICH Workshop on Viral Vector Shedding


CHMP GTWPCHMP GTWP

• Dr. M. Papaluca-Amati and Dr. O. Maki-Ikola, European Medicines Agency

• Prof. G. Dickson, ESGCT President, and the ESGCT Board

• Prof. G. Wagemaker, Rotterdam, and the local Organizing Committee of the XVth Annual Congress of the European Society of Gene and Cell Therapy (ESGCT)

• Dr. Odile Cohen-Haguenauer, Coordinator, and Clinigen Network of Excellence, a European Network for the Advancement of Clinical Gene Transfer and Therapy


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ICHICH--Gene Gene Therapy Therapy

DiscussionDiscussion GroupGroup

/EFTA


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• Update from the ICH Regions

• Issues

• Harmonisation of technical requirements


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Mr. Takeo OzawaPresident & CEOPOC Clinical Research, Inc.Tokyo

Dr Daisuke MaedaReviewerOffice of BiologicsPharmaceuticals and Medical DevicesAgency (PMDA)Tokyo 100-0013

Dr Teruyo AratoReview DirectorOffice of BiologicsPharmaceuticals and Medical Devices AgencyTokyo

Dr Teruhide YamaguchiHeadDivision of Biological Chemistry and BiologicalsNational Institute of Health SciencesTokyo

Ms. Maki TanakaProject ManagerResearch and Development DivisionM's Science CorporationKobe

Dr. Yoshiyuki TanakaDirectorClinical Science Planning and DevelopmentClinical Development InstituteBanyu Pharmaceutical Co., Ltd.Tokyo

Dr Andreas MartiHead Gene Therapy Clinical Trials & ProductsDivision Biotechnology MedicinesSwiss Agency for Therapeutic ProductsSwissmedicBerne

Dr Anthony RidgwaySr. Regulatory ScientistOffice of the DirectorCenter for Evaluation of Radiopharmaceuticals and BiotherapeuticsBiologics and Genetic Therapies DirectorateHealth CanadaOttawa, Ontario

Dr Beth HutchinsDirectorBioanalytical & Protein Chemistry Dept.Schering Plough BiopharmaPalo Alto

Dr Stephanie SimekDeputy DirectorOffice of Cellular, Tissue & Gene TherapiesFood and Drug AdministrationCenter for Biologics Evaluation and ResearchRockville, MD

Dr Daniel TakefmanChief, Gene Therapy BranchOffice of Cellular, Tissue & Gene TherapiesFood and Drug AdministrationCenter for Biologics Evaluation and Research1401 Rockville PikeRockville, MD

Dr Alex KutaVice PresidentRegulatory AffairsGenzyme Corporation500 Kendall StreetCambridge, MA


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Dr Richard PilsudskiDirecteur Scientifique et Affaires Réglementaires AstraZeneca 1, Place RenaultRueil-Malmaison

Dr Sharon LonghurstMedicines and Healthcare products Regulatory AgencyLondon

Dr Outi Maki Ikola instead of Dr Marisa Papaluca AmatiScientific secretary of Gene Therapy Working Party (GTWP)Safety and Efficacy of MedicinesEuropean Medicines Agency – EMEACanary Wharf, London E14 4HB

Professor Dr Klaus CichutekVice PresidentPaul-Ehrlich-InstituteLangen

• Dr. S. Simek, CBER-FDA, Prof. K. Cichutek and the ICH Gene Therapy Discussion Group(EU, US-FDA, MHLW/JPM, Health Canada, EFTA)


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What is Gene Therapy?What is Gene Therapy?

viral or non-viral vector/DNA

transgene/vector

gene product

therapeutic

(preventive)

in vivodiagnostic


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What is Shedding?What is Shedding?

therapeutic

(preventive)

in vivodiagnostic

shedding

release of product from

subject/patientto whom theproduct has

beenadministered

product in gene therapy:- vector

or- cell


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What may be shed in gene therapy?What may be shed in gene therapy?

therapeutic

preventive

in vivodiagnostic

shedding

release of product fromsubject/patient to whomthe product has been

administered:

- viral or non-viral vector particle/micro-organism

- vector nucleic acid- genetically modifiedcell

- virus derived from/ mobilising/ recombined with vector

product in gene therapy:- vector

or- cell


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in vivo

1) local or systemic application

2) biodistribution

InIn--vivo vivo genegene transfer transfer usingusing vectorsvectors


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in vivo• biodistribution into bodily fluidsincluding excreta

• infectious or non-infectious agent

• transmission to third parties:humans, animals

• recombination with other agents:viruses, micro-organisms, TSE agents

• spread in humans

InIn--vivo vivo genegene transfer transfer usingusing vectorsvectors

1) local or systemic application

2) biodistribution


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Which shed products/organisms pose a risk?Which shed products/organisms pose a risk?

shedding

release of product fromsubject/patient to whomthe product has been

administered:

- viral /non-viral vector particle/m.-org.

- vector nucleic acid- genetically modifiedcell

- virus/micro-organismderived from/ mobilising/ recombined with vector

- infection of other human beings or animals:

- risk to individual:adverse effects

- risk to public:new pathogenic organism


CHMP GTWPCHMP GTWP

What may be the result of shedding? What may be the result of shedding?

shedding

release of product fromsubject/patientto whom theproduct has beenadministered

transmission to other human beings

transmission to animals

transmission (from reservoirs) to micro-organisms, viruses, TSE-agents, plants


CHMP GTWPCHMP GTWP

Definition of Definition of sheddingshedding in in genegene therapytherapy

• Shedding in the field of gene therapy

may be defined as

• dissemination and/or transmission of

• gene therapy product or product-related vector or infectious agent

• from bodily fluids and excreta of the treated subject or patient

• to humans other than the patient.


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ConsiderationsConsiderations withwith respectrespect to to sheddingshedding in in genegene therapytherapy

• What is shed?

• How and whereto is something shed?

• Does shedding lead to dissemination/transmission?

• What are the consequences of dissemination/transmission?

• How can the risk of shedding be assessed• in non-clinical studies,• in clinical studies• in post-marketing studies?

• What kind of measures can be recommended to• assess shedding and/or• to reduce harmful consequences of shedding?


CHMP GTWPCHMP GTWP

EMEA/ICH WORKSHOP ON VIRAL/VECTOR SHEDDINGTuesday 30 October 2007 (11.00-18.30)

in conjunction with:The XVth Annual Congress of the European Society of Gene and Cell Therapy

27-30 October 2007 Rotterdam, The Netherlands

European MedicinesAgency (EMEA)

European Society of Gene and Cell Therapy (ESGCT)

European Network of Excellence in Gene Therapy


CHMP GTWPCHMP GTWP

• Introductory notes:

What is vector shedding?

Why is it important?

Klaus Cichutek

Chair, CHMP GTWP at EMEAPaul-Ehrlich-Institut, 63225 Langen, Germany

E-mail: [email protected], 30 October 2007

ESGCT/ICH Workshop on Viral Vector SheddingESGCT/ICH Workshop on Viral Vector Shedding

Documents

ESGCT/ICH Workshop on Viral Vector Shedding€¦ · Langen • Dr. S. Simek ... EMEA/ICH WORKSHOP ON VIRAL/VECTOR SHEDDING Tuesday 30 October 2007 (11.00-18.30) in conjunction with: