Quality by Design, Clinical Relevance & Lifecycle Considerations Robert Iser Acting Director Office of Process & Facilities / OPQ / CDER IFPAC 2016 1
FDA Quality Related Guidance and Initiatives Initiatives Critical Path Initiative ONDQA CMC Pilot Program 21 st Century Initiative Final Report OGD QbR Announced ICH IWG formed OBP Pilot Program OPQ 2015 2004 2005 2006 2007 2008 2009 2010 PAT Guidance ICH Q8 Finalized ICH Q9 Finalized Quality Systems Guidance Finalized ICH Q11 (Concept Paper) ICH Q10 Finalized ICH Q8(R1) Finalized ICH IWG Q&A s 2011 2012 2013 2014 Guidance/Guidelines Modified from Dr. Christine Moore 2
FDA 21 st Century Initiative (2004) September 2004 Objectives: Encourage the early adoption of new technological advances by the pharmaceutical industry Facilitate industry application of modern quality management techniques, including implementation of quality systems approaches Encourage implementation of risk-based approaches Ensure that regulatory review, compliance, and inspection policies are based on state-of-theart pharmaceutical science Enhance the consistency and coordination of FDA's drug quality regulatory programs
Office of Pharmaceutical Quality (OPQ) Mission The Office of Pharmaceutical Quality assures that quality medicines are available to the American public Vision The Office of Pharmaceutical Quality will be a global benchmark for regulation of pharmaceutical quality LINKING QUALITY TO SAFETY AND EFFICACY QbD CLINICAL RELEVANCE LIFECYCLE 4
OPQ: One Quality Voice Value Statements Put patients first by balancing risk and availability Have one quality voice by integrating review and inspection across product lifecycle Safeguard clinical performance by establishing scientifically-sound quality standards Maximize focus and efficiency by applying riskbased approaches Strengthen the effectiveness of lifecycle quality evaluations by using team-based processes 5
OPQ: One Quality Voice Value Statements Enhance quality regulation by developing and utilizing staff expertise Encourage innovation by advancing new technology and manufacturing science Provide effective leadership by emphasizing cross-disciplinary interaction, shared accountability, and joint problem solving Build collaborative relationships by communicating openly, honestly, and directly 6
What is QbD? (to me) A philosophy A type of application Enhanced process / product development and understanding Linking product to desired outcome (a safe and effective (quality) drug for the intended patient) 7
Linking QbD to Clinical Relevance A QbD approach seeks to build quality into the final product by understanding and controlling formulation and manufacturing variables. Formulation attributes and manufacturing processes can affect the bioavailability. Application of QbD principles helps sponsors ensure that a formulation and the associated manufacturing process routinely yields product that meets the desired performance (quality).
What is clinical relevance (to me)? Beginning with end in mind TPP & QTPP* QbD Link - Safety and Efficacy Linkage to QUALITY Clinically Relevant Specifications: Biopharmaceutics Dissolution / IVIVC What about others? Impurities / Degradation? Content? Size/Shape/Delivery/Design? ICH Q8 (R2) - 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. 9
What about Lifecycle Considerations? 10
Linking QbD & Clinical Relevance to Product Lifecycle Linking development throughout lifecycle of product Continuously gaining knowledge and understanding & evaluating risks Product / Process quality monitoring Surveillance of safety and efficacy Continual Improvement Considering impact of changes
Changes - ICH Q10 Change Management and Product Lifecycle Quality risk management to evaluate proposed changes. Proposed changes should be evaluated relative to the approved application. Evaluate change to ensure the change is technically justified. Post-implementation, confirm the change objectives were achieved and that there was no deleterious impact on product quality (and safety and efficacy).
ICH Q12 Concept Paper Established Conditions Links to Quality / Safety / Efficacy Knowledge and Change Management (and PQS aspects Harmonized, risk-based change management system based on product, process and/or clinical knowledge, that effectively evaluates the impact of change on quality, and as applicable to safety and efficacy.
Summing Up Examples of FDA Activities Understanding the link from product to patient Challenges of low solubility drugs Linking biopharmaceutics and development Understanding complex products and processes Biotech products, transdermal patches, inhalation products, complex APIs Modern manufacturing and control strategies PAT Automation Continuous pharmaceutical manufacturing (DS, DP) Emerging Technology Team (ETT) 14
Summing Up - (from ICH Q8(R2)) Product profile CQAs Risk assessment Design space Control strategy Continual Improvement Target the product profile Determine critical quality attributes (CQAs) Link raw material attributes and process parameters to CQAs and perform risk assessment Develop a design space (if appropriate) Design and implement a control strategy Manage product lifecycle, including continual improvement 15
Questions? OPQ Questions? CDER-OPQ-Inquiries@fda.hhs.gov 16