Title: Pharmaceutical Quality in the 21st Century An Integrated Systems Approach
1Pharmaceutical Quality in the 21st Century An
Integrated Systems Approach
- Janet Woodcock, M.D.
- Deputy Commissioner/Chief Medical Officer
2October 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
3October 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
4The 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
5Consequences 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
6Characteristics 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)
7Current 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
8Critical 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
9Desired 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
10Desired 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
11Prerequisites 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
12Desired 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
13Prerequisites 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
14Desired 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
15Prerequisites 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
16Desired 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
17Getting 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
18Summary
- 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
19Incorporation 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
20Summary
- 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
21Summary
- 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