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Advisory Committee for Pharmaceutical Science
April 13, 2004
OPS Update
Helen WinkleDirector, Office of Pharmaceutical ScienceCenter for Drug Evaluation and Research
Food and Drug Administration
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Outline of Presentation
• OPS Mission, Vision and Goals• Developing a new paradigm for CMC review
in ONDC– Building on the Pharmaceutical Quality Initiative
for the 21st Century• New Personnel in OPS• Meeting Agenda
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Mission Statement To ensure timely availability of high quality
drug products to the US patients through
– effective and efficient scientific assessment of relevant pharmaceutical and biotechnology information in regulatory submissions and
– by facilitating those scientific and technological innovation that improve understanding of product performance, quality and efficiency of development, manufacturing, and quality assurance processes
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Vision
OPS is an international champion and leader in regulatory application of contemporary scientific knowledge of design, development, manufacture, and clinical performance of pharmaceutical and biotechnology products
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Goals and Objectives OPS programs and projects will support the
achievement of the following attributes of drug products: Drug quality and performance is achieved and assured
through design of effective and efficient development and manufacturing processes
Regulatory specifications are based on a mechanistic understanding of how product and process factors impact product performance
Continuous "real time" assurance of quality
http://www.fda.gov/cder/gmp/21stcenturysummary.htm
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Goals and Objectives OPS will implement a review quality system and
procedures that will: Recognize the level of scientific knowledge supporting
product applications, process validation, and process capability
Apply a risk based regulatory scrutiny that will relate to level of scientific understanding of how formulation and
manufacturing process factors affect product performance, and the capability of process control strategies to prevent or mitigate risk
of poor product performance
http://www.fda.gov/cder/gmp/21stcenturysummary.htm
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Setting the Stage For the
Future
• FDA Strategic Action Plan• Pharmaceutical Quality for the 21st
Century• Resources• Other Influences
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FDA Strategic Plan - Responding to Challenges and Opportunities• Efficient risk management - the most public
health bang for our regulatory buck• Empowering consumers - improving health
through better information• Improving patient and consumer safety• Protecting America from terrorism• More effective regulation through a stronger
workforce
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FDA’s Initiative on Pharmaceutical Quality for the 21st Century
FDA Unveils New Initiative To Enhance Pharmaceutical Good Manufacturing Practices http://www.fda.gov/bbs/topics/NEWS/2002/NEW00829.html (August 21, 2002 )
Strong Public Health
Protection
Integrated quality systems orientation
Science-based policies and standards Risk-based orientation
International cooperation
Time
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Directional Vectors
• Ensure regulatory review and inspection policies are based on state-of-the-art pharmaceutical science
• Encourage new technological advances• Encourage risk-based approaches that focus both industry and
Agency attention on critical areas • Facilitate modern quality management techniques, including
implementation of quality systems • Enhance the consistency and coordination of FDA's drug quality
regulatory programs, in part, by integrating enhanced quality systems approaches into the Agency's business processes and regulatory policies concerning review and inspection activities
Second Progress Report and Implementation Plan. http://www.fda.gov/cder/gmp/2ndProgressRept_Plan.htm (September 3, 2003)
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Covering the Space Defined by the Directional Vectors
Risk
Science
Preapproval Inspection Compliance Program
Dispute Resolution Process
Comparability Protocol
PAT PAT
Pharmaceutical Inspectorate
Product Specialists on Inspection Process
Aseptic Processing
Guidance on CFR Part 11
Systems/
Integrat
ion ICH P2, QbD, & Risk ICH P2, QbD, & Risk ManagementManagement
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Opportunities• Develop strategy for ensuring product quality • Revisit processes - all aspects of pharmaceutical quality - incorporate best
practices• Focus more on manufacturing and associated issues relating to quality of
products• Focus both review and inspection more on science• Enhance interactions between review, inspection and compliance• Foster communication with industry
– Early discussion of CMC questions– Dispute resolution
• Leverage resources to get “best bang for buck”• Simplify regulatory requirements and reduce regulatory burden• Eliminate “check box” approach
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More Opportunities• Enhance training opportunities
– Plant residency – Cross training opportunities– Pharmaceutical inspectorate
• Enhance FDA’s knowledge regarding new technologies in manufacturing and encourage innovation
• Develop processes which are more focused on product risk• Revisit how quality of product relates to ensuring safety and efficacy - ensuring clinical relevance• Alleviate industry’s concerns regarding “reprisal”• Enhance international involvement
– Pharmaceutical Development– Risk Management
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Resources
• CMC Workload for FY 2003– 159 NDAs (103 originals and 56 resubmitted)– 342 commercial INDs– 507 research INDs– 1858 CMC supplements, not including efficacy
and labeling– 1132 annual reports
• Fewer review staff
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Other Influences
• 1995 - ONDC established - collocated with clinical divisions
• Shorter PDUFA deadlines• FDAMA• Harmonization/globalization• SUPAC, BACPAC • New technologies in pharmaceutical
manufacturing
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Other Influences• PAT• Counterterrorism• Counterfeit products• BSE• Focus on generic products• Changes in industry - more global, mergers, etc.• Electronic submissions• Focus on risk management and quality systems
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How to Achieve the Future CMC Review Paradigm
• Develop risk-based CMC review• Establish quality systems which help set framework
for ensuring dynamic organization• Focus resources towards efforts that improve quality
- not hinder or interfere with innovation• Focus on all aspects of CMC - chemistry -
manufacturing - controls
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Advantages of New Paradigm in CMC Review
• FDA– More product and process knowledge shared by
industry for a better understanding of products and where manufacturing processes are in control
– More efficient resource allocation for review and inspection
– Increased trust and understanding of industry decision making
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Advantages - cont.
• Industry– Fewer, more efficient, science based inspections– Faster, more consistent reviews– Potential for reduced regulatory burden– Manage changes with less FDA oversight– Focus resources on critical issues– Flexibility to focus on what should be done, not what
can be done– Improve communication with FDA
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Advantages - cont
• Ultimate beneficiary - The public– Increased availability of drugs on the market– Faster approval of new products– Continued assurance of high quality products– Increased confidence– {And hopefully, reduced costs}
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What the New Paradigm Will Include
• Develop strategies to recruit and train reviewers with expertise in drug discovery, analytical chemistry, pharmaceutical engineering, etc.
• Build a learning organization“A learning organization is an organization skilled at creating, acquiring, and transferring knowledge, and at modifying it behavior to reflect new knowledge and insight”
• Set specifications based on science and process understanding• Reengineer process
– Best practices– Metrics– Customer oriented
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New Paradigm• Increase emphasis on manufacturing science - ask the “right”
questions at the “right” time• Implement peer review by FDA scientists and clinicians• Establish a program to better integrate review and inspection -
team approach - product specialists on inspection• Develop processes which ensure regulatory relief based on:
– Process understanding and control– Quality systems in manufacturing processes– Continuous improvement
• Create better work environment and promote job satisfaction
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Challenges to Moving Ahead
• Current culture - both inside and outside of FDA• Hiring• Establishing performance metrics• Identify gaps in requirements• Reevaluate review process to determine right questions to ask to
ensure product quality• Understanding what is relevant science• Determine what needed from pharmaceutical development data to
assist in better understanding of manufacturing process• Develop a science-based risk model• Integrate better into inspection process including participating on
inspections
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OPS New Additions
• Dr. Vincent Lee (OPS)• Dr. Mansoor Khan (DPQR/OTR/OPS)
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ACPS Meeting Topics• Day 1
– Subcommittee Report– Proposal for PTIT (Parametric Toleerance Interval Test for
Dose Content Uniformity)– PAT Update and PAT for Office of Biotechnology
Products• Day 2
– Bioequivalence topics (highly variable drugs, bioINequivalence, and topical products)
– Awareness topic - Nanotechnology