Organizational Gaps in Reaching the Desired State

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Organizational Gaps in Reaching the Desired
State

• Helen Winkle

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OPS Organization
Office of Pharmaceutical Science Helen N. Winkle,
Director Ajaz S. Hussain, Ph.D., Deputy
Process Analytical Technologies
New Drug Microbiology Team
Informatic Computational Safety Analysis
Office of Biotechnology Products Keith Webber,
Ph.D.
Office of Generic Drugs Gary Buehler
Office of New Drug Chemistry Moheb M. Nasr, Ph.D.
Office of Testing and Research Ajaz Hussain, Ph.D.
Div. of New Drug Chemistry I John Simmons, Ph.D.
Lab. of Clinical Pharmacology Jerry Collins,
Ph.D.
Div. of Monoclonal Antibodies Steven Kozlowski,
M.D.
Div. of Bioequivalence Dale Conner, Pharm.D.
Div. of Applied Pharmacology Research Jerry
Collins, Ph.D.
Div. of Therapeutic Proteins Amy Rosenberg, M.D.
Div. of New Drug Chemistry II Eric Duffy, Ph.D.
Div. of Chemistry I Rashmikant Patel, Ph.D.
Div. of Pharmaceutical Analysis Lucinda Buhse,
Ph.D.
Div. of New Drug Chemistry III David Lin, Ph.D.
Div. of Chemistry II Florence Fang
Div. of Product Quality Research Robbe Lyon, Ph.D.
Div. of Labeling and Program Support Peter Rickman
Div. of Chemistry III Vilayat Sayeed, Ph.D.
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Organizational Gaps

• Multi-dimensional
• Between organizations
• Within organizations
• Outside of OPS - other parts of CDER organization
• Organizational gap is what we need to consider
  and resolve within our process before we can
  adequately implement regulatory direction and
  support (through applications process and review)
  of the desired state

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What Constitutes the Gap in OPS?

• Appropriate utilization and focus of available
  human resources
• Difference in products and regulatory
  requirements and review processes
• Organizational structure - lack of consistency
  and flexibility
• Process driven, not science driven
• PDUFA
• First in - first reviewed
• Heavy workloads/Backlogs
• Too many supplements
• Interaction with inspection - lack of appropriate
  reviewer involvement - dont get feedback

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What Constitutes Gap?

• Possibility of two-tiered system - how do you
  handle?
• Guidances to accomplish consistency - sometimes
  too prescriptive
• Organizational components too reactive not
  proactive (caused by workload - perpetuates
  problem)
• Use of available scientific expertise and
  scientific collaboration
• Challenge of focusing on appropriate questions
  (based on information received)
• Lack of utilization of appropriate tools (e.g.,
  statistics)
• Lack of good communication between disciplines

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Closing the Gap

• Structural changes needed in some parts of
  organization
• Reviewers on inspections or as consultants to
  inspections so have complete knowledge on product
• Answering questions regarding manufacturing
  science and review including whether or not have
  QOS, what need in way of pharmaceutical
  development information, how does industry
  determine critical attributes, etc., and how we
  will review

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Closing the Gap

• Better understanding of what constitutes design
  space across all products and when notification
  to FDA of change in manufacturing is warranted
• Understanding of what constitutes risk for a
  product - development of a systematic risk-based
  approach to review processes
• Guidances
• Training
• Determining process for working under a
  two-tiered system
• Developing an internal system for handling
  differences in review decisions
• Appropriate metrics

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Current Steps

• Across OPS
• Working group under Manufacturing Subcommittee of
  
• ACPS to address questions
• ICH participation
• Workshop on specification setting - March 2005 -
  broad scope
• Collaboration with academics and PQRI
• Internal review of current guidance
• Developing a program for team interactions for
  inspections
• Training for reviewers (scientific seminars,
  etc.)
• Formation of OPSCC
• Finish guidance on comparability protocol

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Current Steps

• ONDC
• Changing to an assessment program focused on
  quality attributes (chemistry, pharmaceutical
  formulation and manufacturing processes)
• New organization structure (independent
  discipline)
• Proposed QOS
• Team approach
• Establishing a peer review process
• Implementing quality systems approach
• Developing a mock NDA
• Reducing supplement requirements
• OBP beginning to identify where can reduce
  supplements

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Current Steps

• OGD
• Reorganization - additional chemistry division
• Change in supplement review and evaluation to
  determine if some supplements can be eliminated
• Team approach - better application of scientific
  expertise and consistency
• Efficiencies in review - eliminating redundant or
  non-essential review activities
• OBP
• Review of supplement requirements to determine
  where can eliminate or reduce

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Additional Steps

• Involve stakeholders in review of guidances,
  answering manufacturing science issues, etc.
• Determine how to handle a two-tiered approach -
  if at all
• Hold additional external workshops (e.g, QOS)
• Develop a dispute resolution process
• Review how handle PAI process
• Develop appropriate metrics
• Other?

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Observations and Conclusions

• Need to continue to address organizational gap
  issues
• Culture is an important element of change
  management
• Will take time!!
• Depends on resolving some of the science gaps
• Need to include stakeholders in making some of
  the decisions and developing some of the
  procedures
• Training of reviewers important!!
• Will identify more steps as move forward