the office of pharmaceutical quality: an update on team...
TRANSCRIPT
The Office of Pharmaceutical Quality:
An Update on Team-Based Review and
One Quality Voice
DIA Annual Meeting 2015/Washington DC
June 16, 2015
Sarah Pope Miksinski, Ph.D.
Giuseppe Randazzo, M.S.
Objectives of OPQ
• A single unit in CDER
dedicated to drug product
quality
– Across all drug product areas
• new drugs, generic drugs,
biotechnology products, and
over-the-counter drugs
– Across all sites of manufacture
• domestic and foreign
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Objectives of OPQ
• The creation of ‘one quality
voice’ streamlining quality
oversight throughout the
lifecycle of a drug product
– Aligns review, inspection, and
research functional areas
– Spans pre- and post-approval for
brand and generic drugs
– Strengthens surveillance and
inspections of facilities globally
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Objectives of OPQ
• Encourages use of modern,
more efficient manufacturing
technologies
• Establishes consistent
quality standards and clear
expectations for industry
• Balances potential quality
risks with the risk of a
patient not getting a drug
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Objectives of OPQ
• Anticipates quality problems
before they develop to help
prevent drug shortages
• Emphasizes quality metrics and
surveillance techniques to help
monitor quality across facilities
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OPQ
Office of Process
and Facilities Acting Director:
Christine Moore
Office of Surveillance Acting Director: Russ Wesdyk
Office of Testing
and Research Director:
Lucinda Buhse
Office of Program and
Regulatory Operations Acting Director:
Giuseppe Randazzo
Office of Lifecycle
Drug Products Acting Director:
Susan Rosencrance
Immediate Office Acting Director: Janet Woodcock
Deputy Director: Lawrence Yu
Office of Policy for
Pharmaceutical Quality Acting Director:
Ashley Boam
Office of New Drug
Products Acting Director:
Sarah Pope Miksinski
Office of Biotech
Products Director:
Steven Kozlowski
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• Performing team based quality assessments of applications inclusive
of drug substance, drug product, manufacturing, and facilities
Seamless Integration of Review, Inspection,
Surveillance, Policy and Research
Drug Substance
Experts
Product
Experts
Process
Experts
Facility
Experts
‘One Quality Voice’
Technical Advisors
OTR OPPQ
OS Others as needed
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One Quality Voice is:
• Patient-centric
• Clear and Unified
• Efficient
• Transparent
• Collaborative
• Concise
One Quality Voice is not:
• Just a saying
• Confrontational
• Polarized
• Territorial
• Siloed
• Slow
What is One Quality Voice?
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Expectations for Quality
Patients and caregivers assume that their drugs:
Are safe, efficacious, and have the correct identity
Deliver the same performance as described in the label
Perform consistently over their shelf life
Are made in a manner that ensures quality
Will be available when needed
The Link to the Patient - Considerations
• “Why does it matter to the patient?” or “What is the impact on overall quality?”
• Effective discussions are timely, transparent, and robust
• Multiple collaborators involved (e.g., clinical review division, Applicants, other offices)
• Can be framed by any review discipline
• Occurs within the appropriate regulatory framework (e.g program deliverables, application urgency)
• End result – using sound science and technical expertise to identify/discuss major risks to quality, with effective communication to stakeholders regarding risk and the resulting impact to the patient
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One Quality Voice – Where We Are
• OPQ review process – Integrated Quality Assessment
– Builds on previous adaptations of team review
– Team touchpoints based on program deliverables
• Exploration into additional review paradigms
• Flexible use of teams – Expertise-based
– Strategic/case-specific
– Cross-office
• Stakeholder input
• Continuous improvement/learning 12
Team-based IQA (OPQ)
• Team-based Integrated Quality Assessment – Maximizes team expertise
– Provides aligned patient-focused and risk-based quality recommendations
• An IQA team/original NDAs – Application technical lead (ATL)
• Responsible for overseeing the scientific content of the assessment
– Regulatory business process manager (RBPM) • Responsible for process and timeline
– Discipline reviewers • Drug substance, drug product, process, facility, microbiology,
biopharmaceutics, and Office of Regulatory Affairs (ORA) investigators.
– Other members (as needed) • FDA laboratories (e.g., Office of Testing and Research), policy,
surveillance, and other offices
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How is IQA different from previous process?
• OPQ process uses:
– expert teams
– concurrent assessment
– single review template
– Predictable, scheduled team meetings
• Pre-OPQ process uses:
– “one application, one reviewer”
– independent assessment
– separate templates
– Inconsistent communication between disciplines
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IQA Team Roles
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Role / Task Responsible* Scientific Content / Initial Risk Assessment ATL
Process and Timeline RBPM IQA Executive Summary ATL / IQA Team
Assessment of Drug Substance DS/DP Reviewer
Assessment of Drug Product DP Reviewer
Assessment of the Manufacturing Process Process Reviewer
Assessment of Facilities Facility Reviewer
Assessment of Biopharmaceutics Biopharm Reviewer Assessment of Microbiology Micro Reviewer
Assessment of Environmental Analysis EA reviewer
Labeling & Package Insert DP Reviewer
Facility Inspections ORA Leads / SMEs participate
FDA Labs OTR and/or OBP
Others as needed OS, OPPQ, etc
Lifecycle Knowledge Management ATL/ IQA Team
* Represents General Cases
Team Review (OPQ) - Observations
• Proactive meeting framework essential to
alignment and communication (CMC pilot)
• Meeting timeframes most effective when aligned
with PDUFA deliverables (filing, midcycle, etc)
• Various review templates considered
• Effective team leadership essential to outcomes
and progress
– One Quality Voice (technical, regulatory)
– Risk-based conversations (technical)
– PDUFA deliverables (regulatory)
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IQA Template (OPQ) - Highlights
• Structured in CTD format
• Uses guiding questions & reviewer guide
• Clear delineation of roles / responsibilities
• Executive Summary
• Initial and “Final” Risk Assessment
• Lifecycle Communication
• Consolidated Comments
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IQA – Continuous improvement
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• Integrated Product Process/Facility Review Committee – Meets weekly to assess current process and make interim
improvements
– Representatives from all OPQ sub-offices
• Continuous feedback from end users – Retreats for ATL/Secondary reviewers
– Retreat for reviewers and RBPMs
– Additional feedback vehicles (e.g. end of cycle surveys)
• IQA document to be evaluated on a predictable cycle with new
version rolled out periodically
• IT enhancement to facilitate review process, collaboration and
knowledge management
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IQA can be broken down into modules for authoring by owners
Integrated
Quality
Assessment
(IQA)
Quality Review Data
Sheet and Executive
Summary
Owner: Application
Technical Lead
Assessment of the
Drug Substance
Owner: Drug
Substance Reviewer
Assessment of the
Drug Product
Owner: Drug
Product Reviewer
Assessment of
the Process
Owner: Drug Process
Reviewer
Assessment of the
Facilities
Owner: Facility
Reviewer
Assessment of the
Biopharmaceutics
Owner: Biopharm
Reviewer
Assessment of
Microbiology
Owner: Microbiology
Reviewer
Appendices
Owner: All
Reviewers
Read access for all other parties involved and IT solution to consolidate
Formal Risk Assessment
• Provides a consistent understanding of the inherent risk of different types of products
• Establishes a common platform for risk communication and knowledge retention
• Enables a more efficient review processes – Focus on the most critical aspects
• Supports more efficient and targeted inspections
– Focus on the most critical processes and facilities
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• How do we intentionally and explicitly link the
risks identified in our quality assessment to
patient outcomes?
• How do we communicate our findings and
recommendations to our stakeholders outside
of OPQ?
– Internal: OND, OGD
– External: e.g., industry, patients
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Risk Communication - Considerations
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Additional Review Considerations
• Are we having the right conversation at the right time?
• Determining communication gaps and clarification needs from actual scientific disagreements
• Generating One Quality Voice within the appropriate regulatory framework
• Embracing a “culture of curiosity”
• Utilizing resources effectively (e.g. consolidated IRs)
• Building proactive communication into review process
• Building formalized risk assessments into review process and team staffing decisions
• Integrating review and inspection
• Improving overall risk communication to stakeholders 24
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Conclusions
• Patient/caregiver expectations of quality – Safe, effective, high quality, correct identity, perform as labelled,
available
• Multiple OPQ drivers/values based on risk benefit balance
• Team based IQA currently in use within OPQ – Based on historical team review experience
– Incorporates risk-based elements in review process
– Continuously improving based on internal and external feedback
– Evolving IQA template
• Additional ongoing initiatives – Risk communication
– Knowledge transfer
• All on behalf of the ultimate stakeholder – the patient