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2015 - GMP - Validation - Forum - D1.T4.2.2 EMA and FDA Approaches To Process Validation PDF
2015 - GMP - Validation - Forum - D1.T4.2.2 EMA and FDA Approaches To Process Validation PDF
Approaches to
Process Validation
Presented by Ashley Isbel and Marc
Fini
4 July, 2016
Agenda
A quick overview of the new FDA and EMA
process validation approaches
• How you can develop a single approach to be compliant across both regulators
Objective
To understand and control input variability impact and
manufacturing process to assure consistent product quality and
reliable supply.
Continuous Process
Improvement Qualification
Continued
Process
Verification
• Science-Based
• Risk-Based
• Cost Effective approach
Enhanced approach:
Risk management and scientific knowledge are
used more extensively to identify and understand
process parameters and unit operations that impact
critical quality attributes (CQAs) and develop appropriate
control strategies applicable over the lifecycle of the
drug substance which may include the establishment of
design space(s).
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Define the
Quality Target
Product Profile
(QTPP)
Define the
Quality Target
Product Profile
(QTPP)
Define the
Quality Target
Product Profile
(QTPP)
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Qualify Facility,
Implement the Process
Stage 2 Control
Utilities,
Validation
Systems and
Strategy (PPQ)
Equipment
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Identify the
CQAs
Safety &
Efficacy
Morphology
Drug Release Particle Size Distribution
Potential CQAs
Delivery Degradation
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Qualify Facility,
Implement the Process
Stage 2 Control
Utilities,
Validation
Systems and
Strategy (PPQ)
Equipment
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Compression
Granulation
Lubrication
Dispensing
Blending
Packing
Milling
Drying
CQA
Identity
Appearance
Assay
Content Uniformity
Purity
Hardness
Friability
Dissolution
Known or Potential Potential impact to No impact to CQA
impact to CQA CQA
Define Process
Steps & CPPs
Process
Input
YES NO
Potentially Potential
Potentially
Impact to
a CPP CQAs? NOT a CPP
Key Process
NO Parameter
Critical Process YES Risk
Assessment. OR
Parameter
CPP?
Non-Key Process
Parameter Define Process
Steps & CPPs
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Qualify Facility,
Implement the Process
Stage 2 Control
Utilities,
Validation
Systems and
Strategy (PPQ)
Equipment
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Create a
Control
Strategy
Create a
Control
Strategy
Create a
Control
Strategy
• Defined CQAs
• Risk Assessments
• Process Information (Inputs & Outputs)
• Parameters and Ranges
• Design Space Information (if applicable)
Create a
Control
Strategy
Control of Variability
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Qualify Facility,
Implement the Process
Stage 2 Control
Utilities,
Validation
Systems and
Strategy (PPQ)
Equipment
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Implement the
Control
Strategy
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Qualify Facility,
Implement the Process
Stage 2 Control
Utilities,
Validation
Systems and
Strategy (PPQ)
Equipment
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Qualify Facility,
Utilities,
Systems and
Equipment
Qualification PPQ
• Requirements • Evaluate Results
• Acceptance • Evaluate • Approve FSE
Criteria Commissioning • Release FSE
• Control Strategy • Leveraging
• Testing
Protocols Reports
Qualify Facility,
Utilities,
Systems and
Equipment
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Qualify Facility,
Implement the Process
Stage 2 Control
Utilities,
Validation
Systems and
Strategy (PPQ)
Equipment
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Process
Validation
(PPQ)
Prior
Process Design PV
Knowledge
Process
Validation
(PPQ)
Process
Validation
(PPQ)
• For validation:
Test results…
Pass Fail
Process is In spec Correct Type I Error
really… (1-)
Manufacturer’s Risk
Out of spec Type II error Correct
(1-)
• For validation more interested in TypeConsumer’s
II Error Risk
• Need to prove that the process is good – detect problem processes in validation
• “Guilty until proven guilty”
• Type II error usually = 0.2, 0.1, or 0.05
• = 0.1 90% confidence an out of spec process will fail the process validation
acceptance criteria
Process
Validation
(PPQ)
• Raw materials
• Different plants of manufacture
• Different process equipment for use with same
processes
• Different process operators
• Different lab facilities and analyst capabilities
Process
Validation
(PPQ)
Define the
Create a
Stage 1 Quality Target Identify the Define Process
Control
Product Profile CQAs Steps & CPPs
Strategy
(QTPP)
Qualify Facility,
Implement the Process
Stage 2 Control
Utilities,
Validation
Systems and
Strategy (PPQ)
Equipment
Continued
Stage 3 Process
Verification Science and Risk-based Approach at
all Stages of Lifecycle
Continued
Process
Verification
Continued
Process
Verification
Continued
Process
Verification
Continued
Process
Verification
Continued
Process
Verification
Continued
Process
Verification
Ashley.isbel@pharmout.net
www.pharmout.net
Marc Fini
Lead Consultant
marc.fini@pharmout.net
www.pharmout.net