CDER s Office of Pharmaceutical Quality (OPQ): Delivering on the 21 st Century Quality Goals

Transcription

1 CDER s Office of Pharmaceutical Quality (OPQ): Delivering on the 21 st Century Quality Goals Lawrence X. Yu, Ph.D. Director (acting) Office of Pharmaceutical Science Food and Drug Administration IFPAC Annual Meeting, Jan Jan. 24, 2014 Arlington, VA (Washington DC), U.S.A 1

2 Quality Regulation is the Basis of Drug Regulation Initial impetus came from bad quality products being foisted on the American public Harvey Wiley and the poison squad The earliest drug regulators were chemists Focused on impurities and toxic substances Quality remains the foundation of assurance of drug performance 2

3 20 th Century Saw Development of Standards for both Manufacturing and Testing GMP regulations published in 1978 Evolution of CMC filing and submission requirements Beginning in 1990s, ICH sought international standardization of requirements, including many CMC areas; common technical document Ongoing reliance on USP and other national pharmacopoeias for public standards 3

4 21 st Century Initiative Succeeded at many levels: Introduction of QbD Facilitated use of modern technology Updates to GMP regulations Multiple ICH documents: Pharmaceutical Development; Quality Risk Management; Quality Systems Focus on manufacturing science Formation of pharmaceutical inspectorate 4

5 Early 2000s: FDA Embarks upon Pharmaceutical Quality for 21 st Century Initiative Vision: A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drugs without extensive regulatory oversight. 5

6 21 st Century Quality Goals Encourage the early adoption of new technology advances by the pharmaceutical industry. Facilitate industry application of modern quality management techniques Encourage implementation of risk based approaches Ensure that regulatory review, compliance and inspection policies are based on state-of-the-art pharmaceutical science Enhance the consistency and coordination of FDA s drug quality regulatory programs 6

7 We Aren t There Yet. 7 CMC Supplements Total Product Recall Calendar Year Calendar Year Calendar Year Total Product Shortage

8 Current Problems Drug shortages, recalls, and lack of indicators of quality cross-industry Can we predict these problems? Generic drug application backlog and large number of manufacturing supplements Time required for regulatory go-ahead holds back or blocks facility improvements, e.g., site changes, major upgrades Manufacturers with robust quality systems should be able to manage such changes without regulatory oversight Need for ongoing innovation in manufacturing Regulatory oversight one factor in lack of industry adoption of modern manufacturing technology 8

9 FDA Commissioner Margaret A. Hamburg, Feb. 22, 2013 The Food and Drug Administration's Center for Drug Evaluation and Research is working on creating a new office of pharmaceutical quality 9

10 As Proposed, OPQ Consists of Eight Offices Office of Operations Office of Policy Office of Biotechnology Products Office of New Drug Products Office of Lifecycle Drug Products Office of Process and Facilities Office of Surveillance Office of Testing and Research 10

11 OPQ: One Quality Voice Mission: The Office of Pharmaceutical Quality assures that quality medicines are available for the American public. Vision: The Office of Pharmaceutical Quality will be a global benchmark for regulation of pharmaceutical quality. 11

12 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 12

13 OPQ: One Quality Voice Value Statements (cont) Enhance quality regulation by developing and utilizing staff expertise Encourage innovation by advancing new technology and manufacturing science Provide effective leadership by emphasizing crossdisciplinary interaction, shared accountability, and joint problem solving Build collaborative relationships by communicating openly, honestly, and directly 13

14 Integrated Team-based Review Pilot Evaluate the feasibility, effectiveness, and efficiency of OPQ s vision for integrated team-based quality assessment Optimize the process and practice of integrated team-based quality assessment 14

15 Risk-based Review FDA is planning to implement formal risk assessment for its drug product review functions 15

16 CMC Review Template We are presently making improvements to the CMC review template to incorporate aspects such as: question-based review risk assessment lifecycle knowledge management Ongoing discussion on regulatory commitments 16

17 Clinical Relevance Definition of adequate quality: delivers clinical performance described in drug label and is not contaminated Clinically relevant specifications: based on risk to clinical performance, not what can necessarily be achieved by process Clinically relevant manufacturing standards: deviation should have clear link to risk of substandard clinical performance Standards should include human factors analysis end user is very important for medicines 17

18 cgmp Standards and Inspections Clear, written standards and inspectional procedures Industry quality management system must be the mainstay of maintaining adequate quality Use of quantitative metrics should help in assessing and signaling which facilities are potentially at risk, and which are operating in control based on a strong QMS Hope to evolve towards new approaches with manufacturing supplement requirements 18

19 We Are Moving to Performance-based Regulation Stage of Production Type of Regulation Coglianese, Cary and Lazer, David, "Management-based regulation: prescribing private management to achieve public goals" (2003). Computer and Information Science Faculty Publications. Paper

20 Quality Metrics An objective measure of the quality of a product or process An objective measure of the quality of a site An objective measure of the effectiveness of systems associated with the manufacture of pharmaceutical products, including the pharmaceutical quality system Performance-based Quality Assessment and Inspection 20

21 Potential Quality Metrics Right First Time Batch Rejection Rate OOS / Laboratory Failure Investigation Rates Process Capability/Performance Product Quality Complaint Rate, etc. We would like to hear from you! lawrence.yu@fda.hhs.gov 21

22 Role of Industry FDA has been and will continue to be transparent and engage external stakeholders as we initiate changes Technical experts in industry and professional societies have been and will continue to be consulted We are interested in your ideas This is likely to be a multi-year process; there will be ample opportunity for input 22

23 Summary FDA has made some progress in improving its overall approach to regulating pharmaceutical quality, but major challenges remain We are looking at this again, and taking a comprehensive approach to change We are planning to make coordinated organizational, process, and policy changes that will move us more towards our articulated vision 23

24 A MAXIMALLY EFFICIENT, AGILE, FLEXIBLE PHARMACEUTICAL MANUFACTURING SECTOR THAT RELIABLY PRODUCES HIGH QUALITY DRUGS WITHOUT EXTENSIVE REGULATORY OVERSIGHT. 24