Advisory Committee for Pharmaceutical Science October 25-26, 2005

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Advisory Committee for Pharmaceutical
ScienceOctober 25-26, 2005

• OPS Update
• Helen N. Winkle
• Director, Office of Pharmaceutical Science

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Outline

• CDER objectives and goals
• Move to White Oak
• Current management structure in OPS
• Reorganizations in OPS
• Important Initiatives for OPS
• Pharmaceutical CGMP for the 21st Century
• CMC Review
• Field and Review Interaction
• Drug Safety Initiative
• Critical Path Initiative
• Follow-on Proteins
• Importance of this meeting
• Agenda for meeting and what hope to accomplish

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CDER State of the Center Dr. Galsons Vision
for CDERs Future

• CDERs leadership
• International scientific leader in drug
  development and innovative regulatory science
• Many active, robust, productive scientific
  partnerships with outside groups
• Regulatory programs are consistent, efficient and
  transparent

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Vision

• CDERs Organization
• Quality Systems throughout our organization
• Improve communication with the public and
  health-care community about the risks and
  benefits of pharmaceutical products
• Electronic vs. paper environment for submission,
  review, post-marketing surveillance
• Respect and tolerance for differences of opinion
• More mechanisms for involving stakeholders in
  peer review
• High degree of professionalism in resolving
  disputes

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Supporting the Vision

• Enhance the ability of the Center to respond to
  challenges of Critical Path (CP) initiatives and
  improve regulatory and drug development science
• Locus needed for ownership of CP activities
• Reflect the commitment of CDER to sustain a
  multi-disciplinary, cross-Center approach to drug
  safety
• Placement in organization must reflect level of
  commitment
• Need focus and consistency and improvement in
  communication about drug risks and benefits
• Need focus for cross-center policy development

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White Oak
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White Oak Offers Opportunity

• Allows for flexibility to reorganize
• Brings OPS together in one location
• Provides opportunity to work closely with all
  review groups
• Potential for better interaction when rest of
  CDER moves

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Management Structure

• Deputy Directors
• Ajaz Hussain
• Keith Webber
• Associate Directors
• Nakissa Sadrieh
• Jon Clark
• Office Directors
• Office of Generic Drugs Gary Buehler
• Office of New Drug Quality Assessment Moheb
  Nasr
• Office of Biotechnology Steve Kozlowski, Acting
• Office of Testing and Research Cindy Buhse,
  Acting

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Reorganizations

• Have had several reorganizations in OPS during
  the past few months
• OGD new chemistry division
• ONDQA
• Change in organizational structure
• New division
• Other reorganizations in Center that affect OPS

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Pharmaceutical CGMP for the 21st Century

• What is current status?
• Set direction for modernization of pharmaceutical
  regulation
• Continue to focus on pharmaceutical quality
  issues through Council on Pharmaceutical Quality
• Still implementing various recommendations

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CMC in OPS Three Pronged
ONDQA
OGD
CMC
OBP
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Changing the CMC Review Processes

• Office of New Drug Quality Assessment
• Question-based review
• Integration of biotech products into new paradigm
• All come together as one

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Benefits of Changes to CMC Review

• Quality-by-design and performance-based
  specifications enhance product quality
• Understanding of product and process leads to
  reduced CMC supplements
• Focused review on highest risk products
• Risk assessment facilitates continuous
  improvement
• Standardized review enhances the quality of CMC
  evaluation
• Better applications and focused questions reduce
  review time

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CMC Workshop

• Held October 5, 6, and 7
• Over 600 in attendance
• Focused on new paradigm for CMC review
• Discussed quality-by-design (QbD), design space,
  pharmaceutical development data (PD), continuous
  improvement (CI) and quality overall summary
  (QOS)
• Set stage for moving forward with the new
  processes

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Agreements Reached at Workshop

• Support concept of QbD built into PD
• PD to illustrate product/process understanding to
  serve as the basis of science and risk-based
  assessment
• Regulatory flexibility predicated on scientific
  knowledge and process understanding and is
  welcomed by industry and regulators
• Concept of regulatory agreement supported
• Improved, streamlined, frequent communications
  required - We must partner!!
• Specifications tied to clinical safety/efficacy
• Guidances and training will need to be different

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Challenges Realized as Result of Workshop

• Lack of adequate scientific understanding of
  products and processes both by FDA industry
• Implementation devil is in the details
• Setting specifications
• Legacy products
• Culture change
• Industry buy-in for new processes (in many cases
  industry resistant to make changes)
• Global harmonization

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Integration of Field and ReviewThe submission
review program and the inspection program operate
in a coordinated and synergistic manner
Compliance - Sets standards for quality systems
and reviews inspectional findings
Review - Sets standards for product quality
Field - Inspects against standards
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Roles and Responsibilities

• Review side (lead)
• Scientific assessment of product and process
  design
• Evaluate product quality in light of established
  FDA standards (e.g., impurities, stability, etc.)
• Set and maintain product quality standards

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Roles and Responsibilities

• Field (lead)
• Evaluate implementation of process design
• Evaluate quality system
• Implement enforcement actions
• Set certain compliance policies

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Roles and Responsibilities

• Compliance Offices (lead)
• Establish and maintain quality system standards
  for cGMPs
• Establish and maintain risk management system for
  inspections
• Establish and maintain compliance policies and
  standards

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Drugs Safety and How it Relates to Product Quality

• Many issues related to drug safety are caused by
  product quality problems (e.g., alcohol-induced
  dose dumping)
• Safety is an important aspect when focusing on
  product risk
• CMC specifications linked to safety and efficacy

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Drug Safety How Focused in Center

• Drugs safer than they have ever been
• FDA as organization learns well from experience
  with large number of products
• What weve heard
• More info address gap between FDA and others
• Improve internal processes to manage safety
  issues
• Involve outside experts more
• Secretary Leavitt recently announced a new drug
  safety initiative
• Promote a culture of openness and
• Enhanced oversight within the FDA

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Drug Safety Initiative

• New drug safety information initiative
• Proposed Drug Watch Program
• Patient Information Sheets
• Healthcare Professional Sheets
• Drug Safety Oversight Board
• Focus on product quality

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Critical Path Initiative
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FDAs Role in Critical Path

• FDA has a significant role in enhancing product
  development and manufacturing
• We are involved in review during product
  development -- they see the successes, failures,
  and missed
• opportunities
• We have no preconceived thoughts on how products
  need to be developed and manufactured - we are
  not a competitor, but instead can serve a crucial
  convening and coordinating role for consensus
  development between industry, academia and
  government
• We set the standards that need to be met
• Critical Path research can make a difference in
  how we regulate CMC

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Examples of Critical Path Projects Focused on CMC

• Proposed CRADAs to collaborate with industry and
  academia to better understand manufacturing
  science and new technologies and their
  application
• Determining how PAT can be applied in product
  manufacturing to improve efficiencies
• Gathering information on determining critical
  product and process parameters and quality
  attributes - CMC pilot
• Other

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Follow-on Proteins

• Moving toward follow-on proteins, but there are a
  lot of issues to address
• Terminology
• Legal
• Science
• Administrative/process
• We need to be more open in our thinking and not
  have preconceived ideas as to how follow-ons
  should be regulated
• Process will evolve as we learn more and we
  will incorporate into regulatory processes

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Follow-on Proteins (cont.)

• We need to incorporate thinking from the new
  paradigm looking at early on in developing
  regulatory framework
• Finalizing guidances to help lay the path for
  moving forward
• It will take all of us working together to make
  this happen successfully

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Importance of this Meeting

• Step closer to understanding quality-by-design
  especially as it relates to dissolution
• Showcasing the progress that has been made in
  changes to CMC review
• Introducing several new topics
• Saying farewell to Dr. Ajaz Hussain

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Advisory Committee Meeting Topics

• Quality-by-Design and control of drug dissolution
• Continuation of discussion from May
• Several presentations from outside organizations
• FDA presentations on tactical plan
• Update from PTIT working group
• Fact finding group on dose content uniformity for
  inhalation products
• Alcohol-induced dose dumping
• Awareness topic
• Basis of concern and our current thinking on
  regulatory approach

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Advisory Committee Meeting Topics

• Transitional changes in CMC review
• Presentations by all three OPS CMC programs
• Implementation of risk-based approach
• Laboratory research - developing peer review
  program
• How best to handle scientific peer review for
  all laboratory research
• State of US pharmaceutical science and
  engineering education
• Important as we move toward new paradigm