at i mps good clinical practice lola briones, phd, mba bio roi consulting sl [email protected] m....

Madrid, 28- Marzo-2012

L.Briones, PhD, MBA. BIO ROI Consulting SL. 1

ATIMPsGOOD CLINICAL

PRACTICE

Lola Briones, PhD, MBABIO ROI Consulting [email protected]. 639 83 31 61

Madrid, 28- Marzo-2012 L.Briones, PhD, MBA. BIO ROI Consulting SL. 2

Detailed EU guidelines on GCP specific to ATMPs ENTR/F/2/SF/dn D(2009) 35810, 2009

04/21/23 Perfil de compañía 2


ATIMPs GCP 2009 Introduction

• Specific ATMPs GCPs required• Regulation(EC) 1394/2007 on ATMPs• Supplements E6-ICH GCP on IMP (1996)

• WMA Helsinki Declaration 1964 (Seul 2008)• Pending final adoption

• ATMPs vs ATIMPs• Advanced Therapies Investigational Medicinal

Product


ATIMPs GCP 2009 content

• Donation, Procurement & Testing

• Tissue/Blood Establishments & Animal Facilities

• Manufacturing & Importation

• Overarching Principles• Traceability• Safety Reporting & Long

Term Follow-up

• National CA• Ethics Committee• Investigator• Sponsor

• Protocol• Investigator Brochure• Essential Documents• Annex-Traceability Records


ATIMPs GCP 2009: regulationsDonation, Procurement and Testing

of ATIMPsClinical Trials with ATIMP

• Sponsor• Investigator• Manufacturer/Importer

+• Tissue/Blood establishment• Procurement organisations• Animal facilities• Donors


ATIMPs GCP 2009: regulationsDonation, Procurement and Testing

of ATIMPs• EU Directive 2004/23/EC, Q&S. ( H. cells &

tissues)– EU Directive 2006/17/EC– EU Directive 2006/86/EC

• EU Directive 2002/98/EC, Q&S (H.blood & comp.)– EU Directive 2004/33/EC – EU Directive 2005/61/EC – EU Directive 2005/62/EC

• Donors– EU Directive 2004/23/EC (H. Cells & tissues)– EU Directive 2002/98/EC ((H. Blood & comp.)– Annex 2 GMP/Vol. 4 (animal origin)– CPWP/83508/2009 (xenogenic cells)


ATIMPs GCP 2009: regulations

Tissue or Blood Establishments and Animal Facilities• Regulations sect. 3

Manufacturing and Importation of ATIMPs• Art. 13, Directive 2001/20/EC


ATIMPs GCP 2009Overarching Principles

• Traceability• Chain of custody bidirectional links• Follow-up : during & after trial end

– long-term follow-up

• Specifics, ie. Embrionic stem cells; viral vectors, etc

• Specifics: tissues/cells of animal origin• Medical care & decisions-> qualified

Physician/Dentist – Experienced /expert sponsor representative role


‘… to locate and identify each individual unit of tissue/cell during any step from procurement, through processing, testing and storage, to distribution to the recipient or disposal and vice versa.

… to identify the donor and the tissue establishment or themanufacturing facility receiving, processing or storing the

tissue/cells,

… to identify the recipient(s) at the medical facility/facilities applying the tissue/cells to the recipient(s)

… to locate and identify all relevant data relating to products and materials coming into contact with those tissues/cells

ATIMPs GCP 2009Traceability: the ability to

…


General requirements• Traceability system in place => bidirectional links

• Accountability• Records: if bankrupct of sponsor ….->-> National

CA• Personal data protection vs subject traceability

Donors code ~ full indentity by tissue/blood establishm. Subject code ~ full indentity by investigator/ institution

ATIMPs GCP 2009Traceability

donoranimal source

donation product subject

Tissue establishmentAnimal facility

Manufacturingsite

Investigator /Institution


Responsibilities• Sponsor: system in place, contractual

agreements,…• Tissue /blood establishment, procurements• Manufacturer of the ATIMP• Investigator/Institution

– Investigator / Pharmacist / others– Traceability system al clinical site

Archiving• All parties• > 30 years ~ through contractual agreements

ATIMPs GCP 2009Traceability


Clinical Trials-> E2a ICH (1994) Clinical Safety Data Management, Def. and Standards for Expedited Reporting Guideline

+ Notification of Adverse Events and Reactions+ SAEs associated with trials procedures+ Significant hazards to the subject

+ Sponsor: information/training to the investigatorAE related to product application processInfectionsRe. to product failure (including lack of efficacy)Unexpected reactions: ie. InmunologicalsRe. to Mandatory concomitant medicationsRe. to Medical devices (combined ATMIP)

+ Causality assesment, protocol, AE Reporting Plan

ATIMPs GCP 2009Safety Reporting & Long-Term

Follow-up


Follow-up ~ sponsor• Need, duration and nature• Risk annalysis strategy• Risks for close contacts and offspring• Follow-up for

– protection of the subject– specific data collection

• Subject Alert Cards, during & after the End• End of Trial definition ~ protocol• Follow-up, part or not of the clinical trial• Subjects withdrawal, follow-up subject to consent

ATIMPs GCP 2009 Safety Reporting & Long-Term

Follow-up


National CA evaluation• + strategy for traceability, Follow-up, End of Trial

definition and risk-assesment

Ethics Committee evaluation• Traceability vs personal data protection• Close contacts and offspring follow-up• Written Informed Consent• Representative of the sponsor in some processes• Irreversible nature of certain ATIMPs • Protection, donor from sibling/parent pressure

ATIMPs GCP 2009National CA - Ethics Committee


• Traceability at clinical site• Keep records of traceability • Specific AE & AR • Knowledge of risk annalysis• ATIMP accountability• ATIMP conditions of use, application, …• Requirements and training of other professionals• Inform the subject /legal representative

– Special ATIMP risks and precautions– Guidance on how to communicate risks to close contacts..– …..

ATIMPs GCP 2009Investigator


• Traceability system• Keep their part of records• Implement AE-AR reporting process• Ongoing risk analysis• Combined products, risks• Identify clinical, safety or efficacy follow-up• Requirement for standardisation of surgical

procedures• Train the investigator:

– ATIMP handling, storage,…– Concomitant therapy, surgical procedures, …

ATIMPs GCP 2009Sponsor


Protocol. Section # 6 ICH GCP + …….• Flexibility: variability in nature of ATIMPs, diseases• Donor type, material suitability• Medical device, if combined therapy• Blinding issues, preparation vs administration • Traceability system // Safety reporting• End of Trial definition // Follow-up strategy• Subject withdrawal• Specifics, concomitant therapies, surgery,• Representative of the sponsor• Gene therapy

ATIMPs GCP 2009Protocol – Investigator

Brochure


ATIMPs GCP 2009 Essential Documents

• Traceability records: > 30 years • Each party, information for bidirectional

traceability– Before the Clinical Phase of the Trial– During the Clinical Conduct– After Completion or Termination of the Trial

Investigator/InstitutionE6 ICH GCP. #8. 3. 21.SUBJECT IDENTIFICATION CODE LIST

ATIMP + records linking Traceable

ATIMP

TraceableATIMP

patient codepatient identificationmedical file


ATIMPs GCP 2009 Annex- Traceability

records

……….Subject Medical Records• product name/code• trial reference code• trial subject code• administration dates and dose


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ATIMPs GCP 2009