Pharmaceutical Quality System (PQS) – Advantages for a ...c.ymcdn.com/sites/ · PDF filePharmaceutical Quality System (PQS) ... PQS and to using the enablers QRM & Knowledge...
Post on 31-Jan-2018
230 Views
Preview:
Transcript
© 2009 Genentech, Inc.
Joseph C. FamulareSenior Director
Global Quality and Compliance Genentech, Inc.
Pharmaceutical Quality System (PQS) –Advantages for a Global Operation in the Implementation of Q8, 9, and 10
WCBP 2011Sunset Plenary Session
January 10, 2011
Slide 2
© 2009 Genentech, Inc.
Outline
• ICH Vision for Pharmaceutical Quality
• Regulatory Expectations
• Implementation of Q10 at Genentech/Roche
• Conclusions
Slide 3
© 2009 Genentech, Inc.
Existing GMP ss
Management
The RegulatorySystem
Pharmaceutical Quality System / PQS (Q10)
Quality Risk Management (Q9)
PharmaceuticalDevelopment(Q8 & Q8R)
An ICH Vision for Pharmaceutical Quality
Quality System
Existing GMP
Quality Risk Management
Pharmaceutical
Development
Source: Jacques Morénas, ISPE, Nov 2007
Drug Substance Guidance (Q11)Step 2 – Spring 2011?
Slide 4
© 2009 Genentech, Inc.
ICH Guidance History
1. ICH Q8 - Pharmaceutical Development (2006; revised 2009)• describes the suggested contents for the pharmaceutical development section of a
regulatory submission in the ICH M4 common technical document (CTD) format; • indicates areas where the provision of greater understanding of pharmaceutical and
manufacturing sciences can create a basis for flexible regulatory approaches.• Q8(R) includes concepts of Quality by Design (QbD) and examples of design space.
2. ICH Q9 – Quality Risk Management (2006)• provides principles and examples of tools for quality risk management that can be
applied to all aspects of pharmaceutical quality throughout the lifecycle of drugsubstances, drug products, and biological and biotechnological products;
• intended to enable regulators and industry to make more effective and consistent risk based decisions.
3. ICH Q10 – Pharmaceutical Quality System (2009)• intended to provide a comprehensive approach to an effective pharmaceutical quality
system that is based on ISO concepts, includes applicable GMP regulations andcomplements ICH guidance on Q8 and Q9.
Slide 5
© 2009 Genentech, Inc.
Q9 Goal is to reduce patient risk
Q10Q8
Process
Materials
Design
Manufacturing
Distribution
Patient
Facilities
Opportunities to impact risk using quality risk
management Q9
Slide 6
© 2009 Genentech, Inc.
GMP
Pharmaceutical Development
CommercialManufacturing
ProductDiscontinuation
Technology Transfer
Investigational products
Management Responsibilities
Process Performance & Product Quality Monitoring SystemCorrective Action / Preventive Action (CA/PA) System
Change Management SystemManagement Review
PQSelements
Knowledge ManagementQuality Risk Management
Enablers
Q10 Pharmaceutical Quality System PQS
Slide 7
© 2009 Genentech, Inc.
Guidance for Industry: Q10 Pharmaceutical Quality System (April 2009),Process Performance and Product Quality Monitoring System 3.2.1 -
Pharmaceutical companies should plan and execute a system for the monitoring of process performance and product quality to ensure a state of control is maintained.
• Use quality risk management to establish the control strategy.
• Provide the tools (e.g., data management and statistical tools) for measurement and analysis of parameters and attributes identified in the control strategy
• Verify continued operation within a state of control
• Identify sources of variation affecting process performance and product quality for potential continual improvement activities.
• Include feedback on product quality from both internal and external sources, e.g. complaints, product rejections, non-conformances, recalls, deviations, audits and inspection inspections and findings;
Regulatory Landscape and Need for Integrated Product Quality Management
Slide 8
© 2009 Genentech, Inc.
Q10 - Where the PQS Applies
Operations
Make Assess Release
PQS
PharmaceuticalDevelopment
Technology Transfer
Commercial Manufacturing
Product Discontinuation
Product Life Cycle
Pharmaceutical Quality System (PQS)
Slide 9
© 2009 Genentech, Inc.
Q10 PQS
Q10 encompasses the entire product lifecycle and can be applied whether or not QbD is employed.
• Documentation• Training and education• Outsourced activities / purchased materials• Control Strategy
–Use quality risk management to establish using parameters and attributes and related facility and equipment operating conditions
• Monitoring / Handling Quality Defects (CAPA)–The level of effort of the investigation should be commensurate
with the level of risk.–Result should be product and process improvements
Slide 10
© 2009 Genentech, Inc.
Q10 PQS
• Auditing / Inspection–For regulators–For companies
• Periodic review
• Change management / change control–Driven by innovation, continual improvement, the outputs
of process performance and product quality monitoring, and CAPA
–Level and formality commensurate with risk
• Continual improvement – an opportunity to optimize science-and risk-based post-approval change process
11
PQS Management Responsibilities & Expectations
Slide 12
© 2009 Genentech, Inc.
Outline
• ICH Vision for Pharmaceutical Quality
• Regulatory Expectations
• Implementation of Q10 at Genentech/Roche
• Conclusions
13
Performance Expectations of the PQS
Health Authorities expecting ICH Q8-10 implementation
EU moving in direction of making ICH Q10 elements enforceable asdirectivesMore emphasis on role of managementQRM and KM are expected to be integrate in PQSPQS is expected to be applied consistently across a company
Slide 14
© 2009 Genentech, Inc.
FDA Performance Expectations of the PQS
Establish and Maintain State of Control(Systemic, Comprehensive and Global)
• “It is our [FDA] expectation that firms take a systematic approach to correcting and complying with CGMP to ensure the identity, strength, quality, and purity of their drug products.”
• “In your response to this [warning] letter, please include an explanation of how you intend to implement, support, and sustain acomprehensive quality system at your firm that is consistent with CGMP.”
• “It appears that you have not taken a global quality systems approach to corrective actions at your firm…It is your responsibility to review your operations at all facilities and apply appropriate corrective actions to address deficiencies present at multiple sites.”
Source: 2010 FDA Warning Letters, at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm
Slide 15
© 2009 Genentech, Inc.
FDA Performance Expectations of the PQS
Management Commitment
• “It is our expectation that firm’s senior management ensure a systematic approach to designing their products, processes, and quality systems, and require that deviations and flaws are promptly identified and corrected to assure the identity, strength, quality, and purity of their drug products.”
• “Be advised that FDA expects that your corporate management will undertake a comprehensive evaluation of manufacturing operations to ensure compliance with CGMP.”
Source: 2010 FDA Warning Letters, at http://www.fda.gov/ICECI/EnforcementActions/WarningLetters/default.htm
Slide 16
© 2009 Genentech, Inc.
Outline
• ICH Vision for Pharmaceutical Quality
• Regulatory Expectations
• Implementation of Q10 at Genentech/Roche
• Conclusions
Slide 17
© 2009 Genentech, Inc.
Quality PhilosophyQuality is every patient’s right and every employee’sresponsibility. Quality provides a competitive advantage andis engrained in everything we do, from concept throughcontinuous improvement. Because our products touch humanlives, quality is the true measure of our success.
Our Prioritization Principles1. Right to Operate2. Quality Supply to Patients3. Contribution to Target
Our People
Our Patients
Quality Philosophy & Prioritization Principles
Slide 18
© 2009 Genentech, Inc.
South San Francisco
Toluca
RioIsando
Leganés
Mannheim
Basel/KaiseraugstSegrate
Latin America
North America
Europe & Africa
Asia Pacific
Boulder
ClarecastlePenzberg
a
420
Vacaville
Oceanside
Hillsboro
Singapore
ShanghaiFlorence
Small MoleculesDrug Substance
PLUS: Over 200 contract manufacturing organizations (CMOs)
Global Technical Operations
BiologicsDrug Substance
Solid Dosage Drug Product
Sterile Drug Product
Over 20 Plant Operations at 17 sites, about 12,000 employees
Slide 19
© 2009 Genentech, Inc.
Implementation of Modern Quality Systems
Why One Pharmaceutical Quality System (PQS)?
• Health Authority Requirements & Standardization
• LEAN Quality Process Expectations
• One Company…One PQS
• Network Wide Integrated with the Business
• Knowledge Management
• Reduce Product & Patient Risk
• Drive Down Costs
Slide 20
© 2009 Genentech, Inc.
Implementation of Modern Quality Systems
Product Quality Management
- Deliver an End to End (E2E) view of product quality for all Commercial products
- Critical to:– maintaining quality supply to patients– product consistency across sites– our right to operate
- End to End means that the product quality:– is managed throughout the product value stream– includes both API and drug product– is managed throughout Product Life Cycle (Q10 enabler-
Process Performance and Product Quality Monitoring)- Success requires knowledge transfer from Clinical to Commercial
Slide 21
© 2009 Genentech, Inc.
Product Complaints• Early warning signals of product quality issues in
the field
Product Complaints• Early warning signals of product quality issues in
the fieldProduct Assessment & Trending• Proactive assessment of product quality
attributes across the manufacturing process
Product Assessment & Trending• Proactive assessment of product quality
attributes across the manufacturing process
Product Quality Stewards• Single point of Contact for Quality to key stakeholders• Routine health assessment of product to address trends• Planning provides foresight and proactive approach
Product Quality Stewards• Single point of Contact for Quality to key stakeholders• Routine health assessment of product to address trends• Planning provides foresight and proactive approach
QC testing network support• Harmonized approach to test method execution & support• Scalability & flexibility to balance test workload across network
QC testing network support• Harmonized approach to test method execution & support• Scalability & flexibility to balance test workload across network
Analytical methods managementScientific rigor engrained in analytical method performanceProduct control systems based on scienceSeamless product transfers & assessment of consistency
Analytical methods managementScientific rigor engrained in analytical method performanceProduct control systems based on scienceSeamless product transfers & assessment of consistency
Product Quality Management: Fundamental Elements
Slide 22
© 2009 Genentech, Inc.
Implementation of Modern Quality Systems
Product Quality Steward Model
- Dedicated resources overlooking each product to assurequality integrating activities - across all sites (Mfg, QC, QA, etc)
- Single point of contact: – from raw materials to distribution– across all technical disciplines Quality and the rest of the
organization- Early warning for product quality issues- Quality improvement activities are implemented across the network
Slide 23
© 2009 Genentech, Inc.
Opportunities for Global Implementation
• Better understanding of a company’s capability and profile across a global network i.e., more assurance by regulators of consistentprocesses and global implementation;
• Companies can provide more assurance site to site for producingconsistent products and analytical procedures in a global network environment; and
• Enhanced ability for regulators to leverage shared assessments,inspections based on common standards globally for new products,changes, and site transfers.
24
Design of the PQS
PQS involves IT Tools, business processes and common requirements
described in QRs / GSPs
Proc
ess
Map
s, F
low
Char
ts
and
Visu
al A
ids
Standard Operating Procedures
Global Standards & Processes
Quality Requirements
Quality Policy
Other Document Types
In Alignment with ICH Q10:Four Categories to
Organize PQS Documents
One Document Hierarchy
Slide 25
© 2009 Genentech, Inc.
Cost of Quality
Slide 26
© 2009 Genentech, Inc.
Cost of Quality
• Encompasses the costs of creating a quality product and service
• More importantly it incorporates and focuses on the cost of NOT creating a quality product or service
• Encompasses Right First Time Principles to drive better quality decisions and improve the quality throughout processes
Slide 27
© 2009 Genentech, Inc.
Cost of Quality
• Need to establish metrics including costs:InvestigationsRejects product removal actionsLabor and Time involved
• Too often the focus is on getting the product released, but not enough focus on getting to the root cause and preventing the issues from reoccurring. If conducting multiple investigations to deal with the same issues over and over again, is money really being spent wisely?
• “The Cost of Quality quantification provides a business case for well thought out preventive action."
Slide 28
© 2009 Genentech, Inc. 28
Quality Compliance Risk
Risk Assessment
Mitigation Planning
Reporting
Use of Quality Risk Management to utilize findings from inspections, audits, and trending data and to
eliminate or mitigate risks
29
Conclusion
• PQS is the foundation for quality products
• PQS covers
All of Supply Chain from raw materials to distributionOwn production and outsourcedFrom pre-clinical through commercial to decommissioningGMPs and should be integrated with business processes and supported by tools
• For multi site companies PQS consistency is achieved through standardization, common IT tools and management oversight
• ICH Q10 has increased expectations to Senior Management within PQS and to using the enablers QRM & Knowledge Management
• Quality is an attribute not just a function
Slide 30
© 2009 Genentech, Inc.
Acknowledgements
Stephen Mahoney – Genentech
Jennifer Magnani – Genentech
Ann Gillian – Roche
Deb Bailey – Genentech
Ron Taticek - Genentech
Slide 31
© 2009 Genentech, Inc.
top related