Upload
vokiet
View
225
Download
0
Embed Size (px)
Citation preview
Dr. Jean-Louis ROBERTChair CHMP/CVMP QWP
Luxembourg
Evolution règlementaire de l’approche qualité
opportunité et challenge
Plan de gestion du cycle de vie d’un
médicament (ICH Q12)
Aperçu
• Cycle de vie d’un médicament et changement
post-autorisation (variation)
– Acquis, situation actuelle
– Comment améliorer le futur?
2
Medicines and Regulation
• Highly regulated area
• Lifecycle of a medicine
– Development incl. technological transfer
– Application for a marketing authorisation
– Commercialisation
• Knowledge gain on process and product
• Continuous improvement
• Post approval changes
– Discontinuation
3
Pharmaceutical Quality: New Paradigm
• Described in ICH Q8, 9, 10 and 11
• Depending on the level of development (scientificunderstanding) achieved and an adapted quality systemin place, opportunities exist to develop more flexibleregulatory approaches, for example, to facilitate
• Risk-based regulatory decisions (reviews andinspections);
• Manufacturing process improvements, within theapproved design space described in the dossier,without further regulatory review
• Reduction of post-approval submissions;• Real-time release testing, leading to a reduction of
end-product release testing
4
Change Management
• Definition “Change Management” (ICH Q10)A systematic approach to proposing, evaluating,approving, implementing and reviewing changes
• Types– GMP related (well implemented in manufacturing
site)– Assessment related or regulatory changes
• Variation Regulation• Post Approval Change Management Protocol
(PACMP)• Verification Protocol (e.g. for design space not fully
established at commercial scale) mix possibilities
5
Regulatory Change Management
Situation in EU
• Mainly based on EU Variation Regulation
• The revised variation guideline is based on risk
• Q8, 9, 10 and 11 concepts have been taken into
account
• It should also provide a flexible and risk based
system for managing changes post approval
6
Reminder - Types of Changes/Variations
Changes not requiring
any prior approval
Changes requiring
prior approval
Do and tell
Variations
Immediate
notification
Annual
report
Evaluation Procedure adapted to the level of risk
Type IA Type IB Type II Extensionwithin a Design space
7
8
Reminder - Guideline Content – General principles
• Changes are classified as:
– Type IA variations (IA and IAIN) with conditions and documentation
requirements
– Type II (specific scopes, No conditions or documentation requirements)
– Examples of Type IB with documentation requirements
Post Approval Change Management
Protocol (PACMP)
• A PACMP describes specific changes (upfront) that the MAH would like to implement during the lifecycle of the product and how these would be prepared and verified
• This procedure (or tool) allows a faster and more predictable implementation of the change.
Concept introduced in EU through The Variations Classification Guideline that supports Variations Regulation EC (1234/2008)Further guidance Q&A
• Not to confuse with GMP change management!
9
+
Strategy
• Planned
studies
• Acceptance
criteria
• Methods
Results +
Strategy
• Planned
studies
• Acceptance
criteria
• Methods
Results
Traditional
Evaluation of a proposed
variation as a ‘whole’
(Strategy + Results)
Early Step 1:
Submission of aChange
Management Protocol
Fast Step 2:
Reporting of implementation of a change in accordance
with an approved protocol
Principle of PACMP
Type II Variation
Type IA or IB Variation10
Content of a PACMP: Amount of data
• Such a protocol would include for instance
– Justification for the need of a specific change
– A detailed description of the proposed change
– Risk assessment of the impact of the change on product quality.
– Adequacy of the approved control strategy to identify and manage these risks
– Description of additional controls which might be needed
– Description of the studies to be carried out and the acceptance criteria based on which the effect of the proposed change will be evaluated
– Commitment to update the approved protocol if needed
– Justification for submission of multiple changes
11
PACMP
• Advantage: Downgrade of type of variations:– Type II Type 1B– Type IB Type 1A
• Examples:– Change of API SM suppliers– Change of manufacturing site (biologicals)
• Experience so far: – Not very much used by Industry (bio more than chem)– Too product specific
• Full benefit achieved?
12
New Paradigm: next step
• LifeCycle Management (LCM): ICH Q12
Will solve all our problems?
• ICH guidelines on LCM
– Q10: Pharmaceutical Quality System
– Q11: Development/Manufacturing APIs
– Q3D: Residual elements
– M7: Genotoxic impurities
13
Scope Life Cycle Management (ICH Q12)
• “….to facilitate the management of post approvalchanges in CMC in a more predictable and efficientmanner across the product lifecycle”
• Optimization of resources for assessment and inspection
• Confidence and trust in the firm’s pharmaceutical qualitysystem (PQS)
• Scientific basis: Q8, Q9, Q10 and Q11
Address mainly early stages of product lifecycle(development)
• LM will focus on commercial phase
• Ultimate goal: better use of:
From “Tell and Do” to “Do and Tell”
14
LCM: Identified Key Elements
• Regulatory dossier/commitment
• Knowledge management
– How to share with Regulators
• Change management and Quality System
• Tools for LCM:
– Post Approval Change Management Protocols
– Comparability protocol
– Others………….?
15
Knowledge Management (KM): Key issue
• Implementation of changes to rely on company’s
product/process understanding
• How to manage KM (general sharing, communicating…)
• Knowledge
– At time of submission
– During commercialisation
• How to transfer KM
– Industry Regulators
– Regulators Industry?
• Inspectable?
16
Conclusion
Q12 discussion at a very early step
• How to keep track of the regulatory dossier?
• Information on site and/or in the dossier?
• Need for change in legislation?
• Eligibility for Q12:
– PQS
– How to manage knowledge
– Control strategy in place
– ………….
17