Renan GoisHealth Regulatory Expert
Office of Evaluation of Post-approval Changes for Small Molecules
ICH Q12: Perspectives on Post-approval
September 6th 2016 Ciudad de México
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Disclaimer
This presentation does not necessarily reflect the policiesand views of Anvisa.
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Outline
• Introduction;• Perceived problem;• Intentions;• Lifecycle:
o Risk Management;o Established Conditions.
• Challenges.
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Application of scientific
approaches and quality risk management
Greater understanding
of pharmaceutical
and manufacturing
sciences
Basis for flexible
regulatory approaches
Innovation and continual
improvement
ICH Q8: Pharmaceutical Development
Introduction
ICH Q9: Quality Risk Management
Brazilian Health Regulatory Agency - Anvisa
ICH Q10: Pharmaceutical Quality System (PQS)
Agência Nacional de Vigilância Sanitária - Anvisa
Introduction
Review timeline
Stability requirements
Post-approval regulation
Dossier format
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Drug Substance Drug Product
Labeling/PackagingDistribution
IntroductionBrazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Drug Substance
Drug Product
Labeling/Packaging
Distribution
IntroductionBrazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Drug Substance A
Drug Substance B
Drug Product
Labeling/Packaging
Distribution
IntroductionBrazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Drug Substance A
Drug Substance B
Drug Product A
Drug Product B
Labeling/Packaging
Distribution
IntroductionBrazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Perceived problem
lack of a harmonized approach on lifecycle management
confusion on the necessary information and level of detail in the dossier
post-approval flexibility not achieved
hinder innovation and continual improvement
post-approval tools
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Intention
• Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management
ICH Q12
• Pharmaceutical products, including currently marketed chemical, biotechnological and biological products
SCOPE
• Lifecycle of the product, focusing particularly on the Commercial Manufacturing phase
APPLICABILITY
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
lack of a harmonised approach on lifecycle management
confusion on the necessary information and level of detail in the dossier
post-approval flexibility not achieved
hinder innovation and continual improvement
post-approval tools
Intention
ICH Q12 Lifecycle Management
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Intention
ICH Q12
ICH Q10
ICH Q9
ICH Q12 Lifecycle Management
Brazilian Health Regulatory Agency - Anvisa
ICH Q8
ICH Q11
Agência Nacional de Vigilância Sanitária - Anvisa
Intention
• Development of a harmonized approach to “regulatory commitments”• Delineate the appropriate level of detail and in the dossier
Regulatory Dossier
• Establish criteria for a harmonized risk-based change management system
• Clarify expectations and reinforce the need to maintain a knowledge management system
PQS
• Proactively identify post-approval changes• Mechanism to submit and assess these changes by regulatory authorities• Establish criteria for post-approval tools that can be adopted by the ICH
regions
Post-Approval Change
Management
ICH Q12 Lifecycle ManagementIssues to be Resolved
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Intention
• Complement the existing ICH Q8 to Q11 Guidelines
• Facilitate the management of post-approval CMC changes in a more predictable and efficient manner across the product lifecycle
• Promote innovation and continual improvement
Desired Outcomes
Brazilian Health Regulatory Agency - Anvisa
ICH Q12 Lifecycle Management
Agência Nacional de Vigilância Sanitária - Anvisa
Definition
All phases in the life of a product from the initial development through marketing until the product’sdiscontinuation.
(ICH Q8)
LifecycleBrazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Pharmaceutical Development
Technology Transfer
Commercial Manufacturing
Product Discontinua
tion
Lifecycle
Based on ICH Q10
• Drug substance development; • Formulation development; • Manufacturing process development;• Analytical method development.
• From Development to Manufacturing; • Transfers within or between manufacturing sites
• Acquisition and control of materials; • Provision of facilities, utilities and equipment; • Production; • Quality control and assurance.
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
Diffe
ring
Appr
oach
es to
Pha
rmac
eutic
al D
evel
opm
ent
ICH
Q8,
App
endi
x I
Agência Nacional de Vigilância Sanitária - Anvisa
Product Development Design Space
Risk Management Effective PQS Regulatory
Flexibiity
Lifecycle: Established ConditionsBrazilian Health Regulatory Agency - Anvisa
?
Agência Nacional de Vigilância Sanitária - Anvisa
Lifecycle: Established Conditions
ECCritical elements which assure process performance and product quality across the lifecycle
Legally binding information
Proposed in the Application
Approved by Regulator
Changes are reported using relevant post-approval submission
Brazilian Health Regulatory Agency - Anvisa
Agência Nacional de Vigilância Sanitária - Anvisa
PQSScientific- Risk-based
PharmaceuticalDevelopment
Manufacturing Experience
Brazilian Health Regulatory Agency - Anvisa
CQA
material attributes
process parameters
Design Space
Specifications
Manufacturing Controls
ProductQuality
ProcessPerformance
PRODUCT PERFORMANCE
EstablishedConditions
• Risk-based regulatory decisions• Adjustment within design space• Reduction of post-approval submissions
Regulatory Flexibility
Lifecycle: Established Conditions
Agência Nacional de Vigilância Sanitária - Anvisa
EC
Post-approval Regulatory Submission
(different reporting levels)
non-EC
Solely in PQS
CMC
Lifecycle: Established ConditionsBrazilian Health Regulatory Agency - Anvisa
Science Based
ProductUnderstanding
Agência Nacional de Vigilância Sanitária - Anvisa
Challenges
• Harmonization among different countries and regulatory contexts• Application to small and large molecules• Application to currently marketed products• Measurement of PQS effectiveness • Regulatory flexibility tools through non-ICH members• Product-by-product science- and risk-based approach• Definition of EC within CMC elements and location in the dossier• Assessment of EC• Different ECs approved in different regions
Brazilian Health Regulatory Agency - Anvisa
Renan GoisHealth Regulatory Expert
Office of Evaluation of Post-approval Changes for Small Molecules
www.anvisa.gov.br
Thank you for your attention!