Transcript Diapositiva 1

ATIMPs
GOOD CLINICAL
PRACTICE
Lola Briones, PhD, MBA
BIO ROI Consulting SL
[email protected]
M. 639 83 31 61
Detailed EU guidelines on GCP specific to
ATMPs ENTR/F/2/SF/dn D(2009) 35810, 2009
Madrid,
21/07/2015
28- Marzo-2012
L.Briones, PhD,
Perfil
MBA.
de compañía
BIO ROI Consulting SL.
2
ATIMPs GCP 2009
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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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
3
ATIMPs GCP 2009
content
• Donation, Procurement &
Testing
• Tissue/Blood Establishments &
Animal Facilities
• Manufacturing & Importation
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National CA
Ethics Committee
Investigator
Sponsor
• Overarching Principles
• Traceability
• Safety Reporting & Long Term
Follow-up
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Protocol
Investigator Brochure
Essential Documents
Annex-Traceability Records
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
4
ATIMPs GCP 2009: regulations
Donation, Procurement and Testing of ATIMPs
Clinical Trials with ATIMP
• Sponsor
• Investigator
• Manufacturer/Importer
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Tissue/Blood establishment
Procurement organisations
Animal facilities
Donors
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
5
ATIMPs GCP 2009: regulations
Donation, 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
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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)
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
6
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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
7
ATIMPs GCP 2009
Overarching 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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
8
ATIMPs GCP 2009
Traceability: the ability to …
‘… 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 the
manufacturing 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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
9
ATIMPs GCP 2009
Traceability
General requirements
• Traceability system in place => bidirectional links
Tissue establishment
Animal facility
donor
animal source
Manufacturing
site
donation
Investigator /
Institution
product
subject
• 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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
10
ATIMPs GCP 2009
Traceability
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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
11
ATIMPs GCP 2009
Safety Reporting & Long-Term Follow-up
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 investigator
AE related to product application process
Infections
Re. to product failure (including lack of efficacy)
Unexpected reactions: ie. Inmunologicals
Re. to Mandatory concomitant medications
Re. to Medical devices (combined ATMIP)
+ Causality assesment, protocol, AE Reporting Plan
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
12
ATIMPs GCP 2009
Safety 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
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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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
13
ATIMPs GCP 2009
National CA - Ethics Committee
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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
14
ATIMPs GCP 2009
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Investigator
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..
– …..
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
15
ATIMPs GCP 2009
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Sponsor
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, …
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
16
ATIMPs GCP 2009
Protocol – Investigator Brochure
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
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
17
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/Institution
E6 ICH GCP. #8. 3. 21.SUBJECT IDENTIFICATION CODE LIST
ATIMP + records linking
Madrid, 28- Marzo-2012
Traceable
ATIMP
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
patient code
patient identification
medical file
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ATIMPs GCP 2009
Annex- Traceability records
……….
Subject Medical Records
• product name/code
• trial reference code
• trial subject code
• administration dates and dose
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
19
ATIMPs GCP 2009
THANKS
BIO ROI Consulting
Strategy & Education
[email protected]
T. + 34 639 83 31 61
Madrid, 28- Marzo-2012
L.Briones, PhD, MBA.
BIO ROI Consulting SL.
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