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

Integrated Quality Assessment

(IQA)

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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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How does it link to the patient?

Quality information

Technical Assessment

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