Clinical Relevance Context, Connections and...
Transcript of Clinical Relevance Context, Connections and...
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FDA/PQRI Conference March 22, 2017
Sarah Pope Miksinski Director (acting), Office of Surveillance Director, Office of New Drug Products
Clinical Relevance
Context, Connections and Collaboration
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2 www.fda.gov
CDER’s Office of Pharmaceutical
Quality (OPQ)
January 11, 2015
Advances FDA’s Quality Initiative to the next level
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The link to the patient/consumer...
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Office of Pharmaceutical Quality
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Office of Program and Regulatory Operations
Director: Giuseppe Randazzo
Immediate Office Director: Michael Kopcha
Deputy Director: Lawrence Yu
Office of Policy for Pharmaceutical Quality
Director: Ashley Boam
Office of Lifecycle Drug Products
Director: Susan Rosencrance
Office of Testing and Research
Director: Lucinda Buhse
Office of New Drug Products
Director: Sarah Pope Miksinski
Office of Biotechno-logy Products
Director: Steven Kozlowski
Office of Process and Facility Director:
Robert Iser
Office of Surveillance Acting Director:
Sarah Pope Miksinski
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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
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Clinical Relevance
• Product quality is the foundation upon which the clinical safety and efficacy assessment rests
• A product is “fit for use” if it meets the established quality attributes
– purity, potency/strength, identity, bioavailability/delivery, labeling/packaging, performance, etc.
• Strive to establish appropriate correlations between quality attributes and clinical performance
Adapted from M. Nasr’s “Setting Specifications in the 21st Century”/PQRI Workshop, March 16, 2005
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Applying Clinical Relevance to Quality
• A high quality drug product is a product that reproducibly delivers the therapeutic benefit to the patient/consumer as stated in the label, is free of defects, and presents no undeclared risk (e.g., is not contaminated)
• Attributes – Beginning with the end in mind – designing the product to meet
patients’ needs and the intended product performance – Developing the Quality Target Product Profile (QTPP)
• A prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the drug product (ICH Q8 (R2))
– Identifying “clinically relevant” CQAs – those characteristics having an impact on product quality
• Specifications, such as: – Dissolution, Impurities, Size/Shape/Delivery/Design
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Clinical Relevance - The Continuing Dialog
• How much is enough? • Need to know vs want to know • Risk communication • Uncertainty/Risk-Informed • Multidisciplinary interactions • Efficiency of interactions/discussions • Stakeholder feedback • Timeframes (including expedited) • Seeing the “big picture”
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Clinical Relevance – Specific Discussions
• Clinically relevant specifications – Impurities – Dissolution, IVRT – …
• Emerging technologies • Effective risk communication • Policy/guidance development • Benefit-Risk • Breakthrough Therapies • …
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The Risk/Benefit Balance…
www.fda.gov
Availability to patients
Risks to Quality
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Clinical Relevance – Context
• Clinical relevance is not only about clinical data – Patient/consumer-focused – Links quality to clinical performance – Involves pertinent multidisciplinary data/dialog – Helps to ensure that drug products will perform as
indicated in the label
• Clinical relevance is more than specifications – More than dissolution or IVIVC – CRS are just part of clinical relevance – Clinical relevance is not owned by a single discipline – Not a “cookie-cutter” approach
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Clinical Relevance – Connections
• Clinical relevance is just as much about what we don’t know vs what we do know – Risk involves uncertainty – Need to know vs want to know in our communication to
stakeholders – Timely engagement of internal and external stakeholders
• Clinical relevance is a balanced conversation – Not a “magic bullet” – Balanced within quality, multidisciplinary, and/or
Agency/industry
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Technical Dossier & Prior
Knowledge
A Balanced Conversation
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Clinical Relevance – Collaboration
• Clinical relevance is just as much about HOW we work vs WHAT we do – More than a single discipline/not owned by any single
discipline – Based on robust internal/external discussions and solid
collaboration – Based on concept of building mutual understanding and
benefit/risk-based decision making – Striving to identify potential efficiencies and continuous
improvement
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Clinical Relevance – Selected Initiatives
• Breakthrough Therapies – lessons learned • Quality Overall Summary
– Risk communication – Review efficiency
• Review process innovations • Product Quality Benefit Risk Framework
– Started in 2014 – Developed framework for consideration of quality
deficiencies within clinical context of proposed product
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Risk Communication
www.fda.gov
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Excerpts from ICH Q9
“…risk is defined as the combination of the probability of occurrence of harm and the severity of that harm.
However, achieving a shared understanding of
the application of risk management among diverse stakeholders is difficult because each
stakeholder might perceive different potential harms, place a different probability on each harm
occurring and attribute different severities to each harm.
...there are a variety of stakeholders…the protection of the patient by managing the risk to quality should be
considered of prime importance.”
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Risk Communication (ICH Q9)
www.fda.gov
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Risk Communication/General
• Frequent interfaces of risk communication in all stages of quality risk management
• Similarly true for various stages of review and assessment
• Various types of risk communication • Dossier • Dialog • Information available on site
• From a practical standpoint (e.g.) • Risk identification and assessment • Risk communication
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Effective Risk Communication
• Confirms high-level alignment first • Builds common understanding • Considers the needs of parties in discussion
• What happens after the discussion?
• Balances technical debates with overall goals • Timeframes – “Right conversation, right time” • Allows time for idea generation and/or information
digestion • Considers the intended output of the dialog
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21 www.fda.gov
Patient-Centric Assessment
Regulatory Outcome (approval if sufficient)
Post approval experience
Patient (QTPP) expectations
Clinical Relevance - A Lifecycle Approach
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• Our primary stakeholder – the patient/consumer • Supporting OPQ organizational constructs and
initiatives • Various objectives in 2017 heavily support clinical
relevance, effective risk communication, and enhanced collaboration/integration
• Additional opportunities may exist to align objectives with meaningful outcomes for industry
• Appropriate context, robust connections, and effective collaboration are crucial to progress
Moving Forward…
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Thank You!
www.fda.gov