The Third Annual Regulatory and Compliance Symposium Managing Risks – From Pipeline to Patient Meeting the Goals of the FDA’s QbD Initiative: Risk Management and Pharmaceutical Development Helen N. Winkle Director, Office of Pharmaceutical Science Center for Drug Evaluation and Research Food and Drug Administration Anjali R. Kataria Co-Founder and CMO, Conformia Principal Investigator, FDA-Conformia CRADA Study
26
Embed
The Third Annual Regulatory and Compliance Symposium Managing Risks – From Pipeline to Patient
The Third Annual Regulatory and Compliance Symposium Managing Risks – From Pipeline to Patient. Meeting the Goals of the FDA’s QbD Initiative: Risk Management and Pharmaceutical Development. Helen N. Winkle Director, Office of Pharmaceutical Science Center for Drug Evaluation and Research - PowerPoint PPT Presentation
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
The Third Annual Regulatory and Compliance SymposiumManaging Risks – From Pipeline to Patient
Meeting the Goals of the FDA’s QbD Initiative: Risk
Management and Pharmaceutical Development
Helen N. WinkleDirector, Office of Pharmaceutical
ScienceCenter for Drug Evaluation and
ResearchFood and Drug Administration
Anjali R. KatariaCo-Founder and CMO,
ConformiaPrincipal Investigator,
FDA-Conformia CRADA Study
Actual Focus of Current Initiatives
Implementing changes in how FDA regulates pharmaceutical products – or improvement in our business processes
Necessity as move into 21st century Paradigm shift Evolution – not revolution
State of Pharmaceutical Manufacturing In many cases, not state-of-art as compared to
other industries Able to achieve reasonable product quality – but at
a great effort and cost Little emphasis on manufacturing – mainly on
development although manufacturing is approximately 25% of expenses
Factory/equipment utilization rate about 15% For some products, waste as high as 50% Inability to predict effects of scale up on final
product Inability to analyze or understand reasons for
manufacturing failures Globally fragmented
Consequences High cost for products due to
Low efficiencies in manufacturing Waste Manufacturing time requirements based on
testing, etc. Drug shortages due to manufacturing
problems Lack of improvements based on new
technologies Slowed development/access for
investigational drugs Need for intensive regulatory oversight
State of Regulatory Quality Review Processes Oversight increased – reviewed every change made
– increased number of application supplements Focused on chemistry but not on other important
areas (e.g., engineering) Implemented numerous changes in process to
Issued numerous “how to” guidances (prescriptive) All standards internally developed PDUFA requirements speed up review process More complex products along with new dosage
forms Increased emphasis on focused issues such as
counterterrorism, pandemic, counterfeiting
Consequences Too much work Not enough staff More and more information from sponsors
required (not always relevant) No flexibility in regulatory process Impossible to ensure consistency Discouraged innovation on part of
manufacturer because of need for supplements Assumed all responsibility for product quality
The Desired State: A Mutual Goal of Industry, Society, and the Regulators
A maximally efficient, agile, flexible pharmaceutical manufacturing sector that reliably produces high quality drug products without extensive regulatory oversight.
Janet Woodcock, M.D.
Characteristics of the Desired State Quality is controlled by industry Manufacturers have extensive knowledge
about critical product and process parameters and quality attributes
Knowledge comes from product development, prior experience, studies, scientific and technical literature
Use that knowledge to understand product risk and risk mitigation
Use that knowledge to determine appropriateness to make manufacturing changes
Manufacturers control process through quality systems over life cycle and strive for continuous improvement
FDA’s role is to do initial verification and subsequently audit
Moving Toward the Desired State Philosophy – “Quality should be built
into the product, and testing alone cannot be relied on to ensure product quality.”
Benefits of New Paradigm to FDA
1. Enhances scientific foundation for review2. Better coordination across review,
compliance and inspection3. Improvement in what is required for
regulatory submissions4. Better consistency5. Improved quality in review (establishing a
QMS for CMC)6. More flexibility in decision making7. Decisions made on science and not on
empirical information 8. Involves various disciplines in decision
making9. Uses resources to address higher risks
Benefits to Industry1. Design better product with less problems in
manufacturing 2. Reduce number of manufacturing supplements required
for post market changes – rely on process and risk understanding and risk mitigation
3. Allow for implementation of new technology to improve manufacturing without regulatory scrutiny
4. Possible reduction in overall costs of manufacturing – less waste
5. Less hassle during review – reduced deficiencies – quicker approvals
6. Better interaction with FDA – deal on a science level instead of on a process level
7. Allow for continuous improvements in products8. Better understanding of how APIs and excipients affect
manufacturing9. Relate manufacturing to clinical during design10. Better overall business model!
Next Steps Evolution There are definitely obstacles to change and a
lot to learn – gaps in science, knowledge, risk and risk mitigation
Need to determine the applicability to risk management to manufacturing process
What is appropriate information to submit in application based on current product development data?
Need appropriate guidance to guide industry and FDA staff
Training, training, training Will continue to work with industry and others
to learn – CRADA with Conformia is a perfect example of how this is being done
Company Confidential to Conformia, Inc
FDA – Conformia CRADAFindings from Part 1
Opportunities, Priorities and Challenges in Implementing FDA’s Desired State
August 23, 2007Anjali Kataria
Principal InvestigatorFDA-Conformia CRADA
Company Confidential to Conformia, Inc
CRADA Is Focused on Manufacturing Aspects Drug Development
Analyze Root Cause: Identify existing root causes of bottlenecks in drug development resulting in inefficiency
Assess Guidelines: Describe gaps, perceptions, and usefulness of existing guidance related to pharmaceutical development.
Describe Current State Practices: Summarize current state of pharmaceutical development, challenges, opportunities, and top of mind issues facing development organizations.
Identify Potential Future State: Define requirements needed for companies to implement Quality by Design (QbD) closed-loop, continuous improvement, process understanding approach to new drug development.
Educate: Increase familiarity of key initiatives, new technologies and future state possibilities
Company Readout: Identify current state practices / top of mind issues internal to participating companies.
Final Report / Benchmarking Briefing: Roll up results of all preliminary phase company participants ( Phase 1 )and loose comparison
FDA Briefings: Communicate to FDA current perceptions in understanding, expectations of future agency guidance; opportunities for streamlining guidance.
FDA Reaction: Conformia to share FDA’s feedback with participating companies.
FDA Workshops: Conduct Internal FDA Seminars to educate FDA on key areas: Development Process, QbD, Design Space, PAT.
At Present 9 participating companies. (Will expand to 25 companies.) 7 of these have a biotech division participating in the study or are a standalone
biotech company. Designated by: Collectively:
350+ commercial products to market Parallel and multi-site development activities occurring at all 9 companies All 9 companies using CMOs in Development process / tech transfer
Smaller LargerRelative Company
Size*
*Based on 2005 Annual Revenue, # of Employees, Number of Development Sites, Number of Commercial Sites
Most companies had well documented development processes (roadmaps, technical briefs etc.)
Though few companies had aligned these development process maps with the FDA’s QbD approach such that key decision points encompassed/aligned with QbD goals
Top obstacles include: Poor information management supporting product/process lifecycle across
development FDA’s perceived commitment to drive QbD across reviewers, inspectors and
policy team Harmonization across PMDA, EMEA, FDA.
Dialogue between industry and agency is helping companies translate concepts into practice / develop more case studies
FDA-Conformia-PhRMA Workshops for Cross Functional Senior Leadership OPS Pilot Programs /Industry Meetings (ISPE, AAPS, PhRMA etc.)
More communication between FDA and Industry regarding FDA’s implementation plans to support training of Reviewers and Inspectors in this new paradigm will help move QbD forward