Pharmaceutical Quality in the 21st Century An Integrated Systems Approach

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Pharmaceutical Quality in the 21st Century An
Integrated Systems Approach

• Janet Woodcock, M.D.
• Deputy Commissioner/Chief Medical Officer

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October 5, 2005 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

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October 5, 2005 The Current State of
Pharmaceutical Manufacturing

• Not state-of-art compared to other industries
• Achieve reasonable quality but at great effort
  and cost
• Manufacturing is 25 of expenses equal to RD
  investment
• Factory/equipment utilization rate about 15
• Product waste up to 50 for some products

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The Current State of Pharmaceutical Manufacturing

• Inability to predict effects of scale-up
• Lack of agility usually takes years to bring up
  a new production site
• Operations fragmented around globe
• Inability to understand reasons for manufacturing
  failures

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Consequences of State

• High cost and low efficiency of manufacturing
• Drug shortages due to inability to manufacture
• Slowed development/access for investigational
  drugs
• Partly due to lack of clarity about IND stage
  regulatory requirements
• Need for intensive regulatory oversight

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Characteristics of Desired State

• Manufacturers have extensive knowledge about
  critical product and process parameters and
  quality attributes
• Manufacturers control process through quality
  system over life cycle and strive for continuous
  improvement
• FDA role Initial verification, subsequent audit
• No manufacturing supplements needed (may need for
  formulation change)

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Current Question How Much Have
We Progressed Towards Desired State?

• Development of ICH Q8 and Q9
• ICH Q10 and FDAs Quality System Guidance
• Development of concepts of quality risk
  management for pharmaceutical quality
• Impact of regulatory changes
• QbDfacilitated by cGMP initiative and CMC pilot
  program
• QbR--generics initiative
• QbDfor biotech
• Formation of pharmaceutical inspectorate
• Impact of technology initiatives PAT

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Critical Factor Importance of International
Harmonization

• Manufacturing environment is global
• ICH partners plus many other countries
  inspectorates
• Global regulatory approach must span wide range
  of technical/regulatory levels of sophistication
  and resources
• Disparate requirements/interpretations serve no
  one, certainly not the patient

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Desired State Harmonization

• Pharmaceutical regulators (review/inspection)
  working from common set of concepts and standards
• Harmonized dossier in CMC area
• Harmonized quality system standards
• Regulatory stipulations compatible
• Inspectional expectations uniform

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Desired State Pharmaceutical Development

• Quality by design concepts well articulated,
  successful, and widely adopted by industry and
  regulators
• Regulatory CMC submissions focus on process and
  product understanding as they relate to critical
  material characteristics and product attributes
• Review process assesses level of understanding
  and acceptance criteria for design space

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Prerequisites to Desired State Pharmaceutical
Manufacturing

• Generalized, accepted knowledge is available
  about performance characteristics of excipients,
  equipment, impact of process changes
• Manufacturers build on accumulated knowledge of
  own processes
• General, mechanistic approach to common active
  ingredient characteristics available
• Sound manufacturing control program

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Desired State Quality Risk Management

• Industry uses quality risk management to set
  level of control and respond to ongoing findings
  during manufacturing
• Regulators use risk based approach for standards
  development, regulatory review decisions,
  inspection choices, investigational findings and
  enforcement priorities
• Widespread use of quality risk management ensures
  that resources are targeted towards the highest
  risk areas, improving quality

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Prerequisites to Desired State Quality Risk
Management

• Develop agreement on risk based approaches to
  management of manufacturing issues
• Regulators have common understanding of risk
  management in inspectional findings
• Regulators develop (consensus not required) risk
  based internal models

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Desired State Quality Systems

• World-wide regulatory community embraces a common
  model of an adequate quality system for
  pharmaceutical manufacturing
• Global industry implements modern quality systems
  that are compliant with various GMP requirements

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Prerequisites for Desired State Quality Systems

• Regulators adopt common standards for quality
  systems
• Work to common understanding of
• State of control
• Change control process
• Process validation
• Life cycle approach
• Role of management in quality

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Desired State Technology

• Technology will help!
• System facilitates and enables new technology
  introductions
• PAT of various types is common
• Statistical process control
• Continuous processing is utilized routinely

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Getting to Desired State Technology

• PAT initiative needs to continue uptake by
  industry
• Encourage and get funding for academic base for
  pharmaceutical manufacturing science and
  technology
• Standards development (external to FDA)
• Innovation in industrial sector

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Summary

• We all can visualize the desired state
• We all see the many steps necessary to achieve it
• Progress will be assessed during this
  workshopparticularly around Q8 and Q9
• However, need to continue forward movement on all
  fronts

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Incorporation of Quality by Design

• Submissions provide opportunity to assess firms
  incorporation of QbD into process development
• Review process provides a prediction of process
  capability
• Process experience, however, is the proof of
  concept
• CGMP program ensures that processes were designed
  for quality

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Summary

• We can visualize the desired state and the many
  steps necessary to achieve it
• Progress has been assessed during this workshop
• Identify gaps and action items for each sector
• Need to continue forward momentum all on fronts

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Summary

• Product Quality Initiative poised to take next
  steps into 21st century
• Will require movement onto unfamiliar ground for
  all of us
• Tremendous benefits to public, industry,
  regulators await
• We must be guided, as always, by rigorous science