GMP for ATMP

Advanced Therapy Medicinal Products

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Content

• Background and regualtory requirements

• GMP Walkthrough

• Quality Risk Management

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Background and regulatoryrequirements

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When???

Medicinal products

• Classification of ATMP’s

• http://www.ema.europa.eu/docs/en_GB/document_library/Regulatory_and_procedural_guideline/2012/04/WC500126681.pdf

• If Medicinal product – GMPs apply

– And more…

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GMP applies!

ATMP withMA

ATMP used in Clinical trial

Hospital exemption

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Permit from LV also needed!

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GMP applies

• GMP Part IV

– (from May 22, 2018)

• Annex 1 (Sterile medicinal products)

– Draft update published

• Annex 11 (Computerised systems)

• Annex 12 (Ionisation radiation)

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GMP Walkthrough

EU GMP Guide, Part IV

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1. Introduction2. Risk-based approach3. Personnel4. Premises5. Equipment6. Documentation7. Starting and raw materials8. Seed lot and cell bank system9. Production10. Qualification and validation11. QP and batch release12. Quality Control13. Outsourced activities14. Quality defects and product recalls15. Environmental control… (GMOs)16. Reconstitution..17. Automated production of ATMPs

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1. Introduction

Scope

• Both commercialand for Clinical trials

• MA/CTA must always be followed

General principles

• Quality System and GMP

• Ensure QS is effective

• PQR for authorised ATMPs

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2. Risk-based approach

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Wait for it….

Risk management and ATMPs

ATMPs

• Complex

• Different risks

• Inherent variability

Innovation

• Rapid changes

• Academic/hospital setting

• Different QS

Flexibility

• Early clinicalphases

• Evolvingknowledge

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Hospital AcademicIndustry

Quality

Safety

Efficacy

GMP compliance

Equal application of RBA = Risk-Based Approach

Flexibility

Necessarycontrols/mitigations

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Level of effort and documentationcommensurate withthe level of risk!

InvestigationalATMP

AuthorisedATMP

Strategy agreed in MA

Protection of subjectsReliable test resultsConsistent with CTA

Examples of RBA

• Raw materials

• Testing strategy

• No ”substantial manipulation”

• Investigational ATMPs

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4. Premises

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Contamination and cross-contamination

Errors

Adverse effect on quality

5. Equipment

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7. Starting and raw materials

Raw materials

• Consider Ph. Eur. 5.2.12

• Ideal – Pharma grade

• May rely on Certificate ifrisks understood

• Biological origin – TSE!

Starting materials

• Tissues, cells – Directive2004/23/EC or 2002/98/EC

• Quality agreements

• May need to audit

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• Properly identified, labelled and stored

• Released by QC before use

• If test takes long time, may be OK to use if risks understood and mitigated

9. Production

Phase I/II

Phase III

Authorisedproduct

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Procedures and instructions more and more detailed as knowledge increases

9. Production

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10. Qualification and validation

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Process

Clean room

Cleaning

Test methods

Transport conditions

11. QP and Batch release

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QP Competence

The release process – 14

items

Products with short shelf life

Unplanneddeviations and OOS

12. Quality Control

Approval of specifications, instructions, procedures

Approvals of outsourced testing

Control of materials

Supervision of reference/retention samples

Ensure testing and evaluation of records

Stability monitoring

Participation in investigations

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13. Outsourced activities

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Contractgiver

Contractacceptor

14. Quality defects and product recalls

CAPA system

Correction

Correctiveaction

Preventiveaction

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17. Automated production of ATMPs

Equipment suitable for intended purpose

CE mark may or may not be relevant

Qualification required

Sufficient data from equipment manufacturer

SOPs, maintenance etc.

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Thank you for your attention!