Embed Size (px)
Citation preview
CMO Oversight: The Role of Quality Susan Kalk
VP Global Quality Assurance
NPS Pharma
NPS Pharma
Common Internal Sponsor Misperceptions
• “The Quality Agreement is signed – now it’s over to them”
• “The CMO QA department reviewed the batch records so we don’t have to”
• “QA oversight is just duplication of effort and resources”
• “ The CMO already release it!”
NPS Pharma
Quality Responsibilities Cannot Be “Outsourced”
• Sponsor QA are accountable for CMO oversight that includes:
– a fully validated process at the CMO
– product release to intended jurisdictions
– compliance to the NDA/BLA/MAA
– compliance to GXP regulations
– compliance to the Quality Agreement
• If CMO is not compliant, FDA will question sponsor oversight
• Consequences of inadequate CMO oversight can have significant business impact
• Effective risk-based CMO oversight is the goal!
NPS Pharma
Quality has End-to-End Responsibilities in CMO Oversight
• Involvement in all phases from due diligence through contract termination
• Establishment of an effective Supplier Quality Management program
• Definition of an appropriate level of quality oversight through ongoing evaluation
• Quality risk management and escalation as required
• Aligned CMO/sponsor quality system interfaces
• Establishing an effective relationship with CMO QA/QP
• Effective resolution of quality issues
NPS Pharma
Case study: The first change control from the CMO………
• Sponsor QA receives proposed change from CMO QA for customer approval in 2 days to allow CMO to update batch records for upcoming campaign
• It’s in German. Send for translation.
• Sponsor QA do not understand the translated change and refer to sponsor technical department.
• Sponsor project manager attempts to schedule a “quick” teleconference with CMO to gain clarification
• Key CMO staff are not available until next week
• Sponsor project management communicate internally that everything is “on track” for campaign start
• Sponsor QA do not understand the classification of the change- it does not match the sponsor internal change classification system
• Sponsor QA require internal regulatory evaluation of the change and forward to sponsor regulatory department. Regulatory need 5 days to review the submission and confirm whether registration relevant.
• Sponsor project manager wants the change approved on time to keep the project on schedule……….
NPS Pharma
CMO Selection: Quality Focus
Does CMO manufacture
their own products at
this site? Regulatory experience in
sponsor jurisdictions?
Does QA have a voice?
Head of Quality/QP experience?
Is technology
current?
Speed Cost
Are Quality systems robust?
What is their reputation?
NPS Pharma
Key “hidden” CMO Selection Factors
• CMO is “sweating the assets”- high volume, infrequent maintenance
• Accept all sponsors → financial concerns
• Culture of complacency
• Cost reducing initiatives are encouraged and rewarded
• Lack of transparency → withholding information
• Metric focused culture
• Backlog?
• High deviation rates →critical deviations → FAR/BPDR’s→ recalls?
NPS Pharma
Establishing the Quality relationship
• Take the time to meet CMO QA counterparts face-to-face
• If possible negotiate Quality Agreement in person
• Establish communication strategy between QA organizations
• Discuss Quality system interfaces
• Agree on quality escalation process
• Be transparent about expectations and concerns
• Situations will arise that require compromise on both sides to achieve a compliant path forward
• Establish joint metrics acceptable to sponsor and CMO
NPS Pharma
The Complex CMO/Sponsor Hybrid Quality System
Regulatory requirements
CMO Quality System
Sponsor 1 Corporate
Quality System
Sponsor 2 Quality System
Sponsor 3 No Quality
System
CMO Corporate Quality System
Sponsor 1 Quality System
NPS Pharma
The Challenges of Establishing a Sponsor/CMO aligned Quality System
• CMO may not readily share internal SOP’s and processes
• Sponsor cannot share SOP’s for proprietary reasons
• Sponsor has well defined internal expectations driven by Corporate standards
• CMO cannot and will not modify quality systems for each sponsor
• Quality system interfaces are rarely evaluated and discussed upfront
• Project timeline often too aggressive to accommodate this step
NPS Pharma
Ensuring CMO and Sponsor Quality Systems Interface Effectively
• Quality Agreement is the foundation for Quality Systems
• Process mapping of key quality systems is recommended
• Determine key interface points in Quality Systems and ensure responsibilities are clearly understood
• Be clear on what documents need notification to, or review and/or approval by sponsor
• Ensure timelines for internal reviews by other departments are considered and understood
• Ensure internal communication within CMO and sponsor QA organizations
• Establish regular sponsor QA/CMO QA meetings or teleconferences to discuss quality documents and issues
• Ensure effective escalation process to VP level within sponsor and CMO organizations
NPS Pharma
The Person-in-plant (PIP)
Benefits
• Validation campaign presence
• Campaign-based manufacturing
• Faster visibility to issues
• Immediate decision making and approvals
• Liaison between sponsor and CMO departments
• Can build a strong long term partnership with CMO
Risks
• May not make sense for low volume products
• Does not prevent deviation events (reactive)
• On site presence may not result in quicker visibility to issues
• Must have authority to make product related decisions
• Must involve QA at sponsor
NPS Pharma
Key Competencies of Person-In-Plant
• Effectiveness depends on skills and experience of individual
– cultural fit with CMO
– credentials and technical expertise
– ability to influence without authority
– trusted by sponsor and CMO
– ability to build and balance relationships with sponsor and CMO
– ability to facilitate resolution of issues
– has authority to make decisions on behalf of sponsor
– know which side of the fence they are on
NPS Pharma
Sponsor, CMO and Joint Quality Metrics
CMO Metrics
Sponsor Metrics
Joint performance
metrics
Time from filling to CMO disposition Time from deviation event to first draft provided to sponsor
Time from CMO disposition to sponsor disposition Time from first draft of deviation to sponsor approval
Overall disposition cycle time Deviation cycle time
NPS Pharma
Quality Risk Management of CMO’s
Identification of risks
Mitigation of risks
Enhanced monitoring
Evaluation and Escalation
Justification for continued
use/exit strategy
NPS Pharma
Quality Risk Management: Identification of Risk
• Regulatory action
• Process compliance with filing
• Delay in product approval
Compliance Risk
• Reportable events (BPDR/FAR)
• Product recalls
• Batch rejects/losses
Product Quality Risk
• Single source
• Supply Impact
• Low inventory levels
Business Risk
NPS Pharma 17
Data used to Evaluate CMO risk
Regulatory Inspection Outcomes
Audit results Compliance to BLA
NPS Pharma
CMO Data Drives Level of QA Oversight
• Batch record review
• Frequency and focus of CMO audits
• Metrics
• Product and process data analysis
• On-site presence
• PAI/inspection readiness activities
• Steering Committee meetings (Sr. Management involvement)
• CAPA follow-up and effectiveness checks
18
NPS Pharma
Common Sponsor QA /CMO QA Failure Modes
• Communication failure: sponsor QA ↔CMO QA or within organizations
• Sponsor and CMO not aligned on level of acceptable risk
• Try to get CMO to modify Quality System for product
• Sponsor inability to make a decisions or “flip-flopping”
• Multiple changes
• Unrealistic timelines
• Internal pressure to release every batch
• Lack of transparency
• Delays in scheduling audits
• Failure to adhere to Quality Agreement requirements e.g. notifications, cycle times
19
NPS Pharma
Quality Relationships are Essential for an Effective CMO Partnership
• Relationships at all levels – junior staff through Executives
• Aligned quality approach
• Willingness to reach common ground
• Mutual respect for CMO and sponsor perspectives
• Sponsor trusts CMO expertise
• CMO earns sponsor trust by delivering on commitments
• Transparency in communication
• Desire to facilitate and improve relationship across all functional areas
