Process Validation
“The Science and Risk-Based Approach”
CARLO L. PERETE, [Link].
President, ISPE Philippines
Technical Services Lead, GSK Philippines
Is the Philippine Pharmaceutical Industry
Ready for the Future?
Pharmaceutical Engineering
will focus on
Risk Management in 2015.
Quality Risk Management (ICH Q9)
PRINCIPLES of Quality Risk Management
•the evaluation to the risk to quality should be based on
scientific knowledge and ultimately link to the protection
of the patient
•the level of effort, formality and documentation of the
QRM should be commensurate with the level of risk
Quality Risk Management (ICH Q9)
Quality Risk Management (ICH Q9)
TOOLS of Quality Risk Management
• Basic risk management facilitation methods (flowcharts,
Ishikawa diagram, process maps, etc)
• Failure Mode Effects Analysis (FMEA)
• Failure Mode Effects Criticality Analysis (FMECA)
• Fault Tree Analysis (FTA)
• Hazard Analysis & Critical Control Points (HACCP)
• Hazard Operability Analysis (HAZOP)
PRODUCT Life Cycle – ICH Q10
Product
Discontinuation
GMP, ICH Q8, Q9, Q10 and PROCESS VALIDATION
Quality Risk
Management
Statistics
Process QTTP, CQA,
CPP, Design
Validation Space
Quality
Management
System
US FDA Guidance for Industry – Jan. 2011
PROCESS VALIDATION
- the collection and evaluation of data, from the
process design stage through commercial
production, which establishes scientific evidence
that a process is capable of consistently delivering
quality product.
PIC/S – Guide to GMP of Medicinal Products
All the critical steps in the different
manufacturing processes should be subjected to
validation
In theory, the number of process runs carried
out and observations made should be sufficient
to allow the normal extent of variation and trends
to be established and to provide sufficient data
for evaluation
Process Validation: the new concept
Process Validation:
from documentation to science . . .
US FDA 1987 PV Guideline US FDA 2011 PV Guideline
Documented evidence Scientific evidence
IQ, OQ, PQ prior to Covers process design , tech
commercialization transfer and commercial
manufacture (product lifecycle)
3 batches From One to many batches
Process Validation Lifecycle Overview
A FINAL WORD on Process Validation STAGE 1 . . .
Stage 3 - Continuous Process Verification: a new concept
WORKSHOP No. 1:
Identifying CQAs, CPPs and
Product Control Strategy
WORKSHOP No. 1 MECHANICS
INSTRUCTIONS TIMINGS
1. You will be divided into 3 groups 5 mins.
2. Your group will be assigned to work on a particular dosage form, and you will be 5 mins.
issued with a product formulation, process flow diagram and equipment manuals
3. Conduct a process FMEA using the severity, probability and detectability scales 40 mins.
discussed in the lecture
4. Identify the CRITICAL PROCESS PARAMETERS (CPP) 10 mins.
5. Assign personnel who will report the Process FMEA to the PLENARY 30 mins.
Quality Risk Management:
Process FMEA Example...
Quality Risk Management:
Examples of Severity Scales
RANK SEVERITY CRITERIA
No impact of this process variable / operating parameter
1 Not Severe
on product quality
Large deviation from this process variable / operating
4 Slightly Severe parameter, in conjunction with other factors, have a
significant impact on quality
Large deviation from this process variable / operating
Moderately
7 parameter have a significant impact on quality
Severe
Extremely Small to moderate deviation from this process variable /
10
Severe operating parameter have a significant impact on quality
Quality Risk Management:
Examples of Criteria to Assess Probability
Probability
RANK Occurrence Description Failure Rate
of Failure
5 Very High Failure is almost inevitable ≥ 1 in 2
4 High Failure commonly occurs 1 in 20
3 Moderate Occasional Failures only 1 in 100
2 Low Failure is unlikely – isolated incidents only 1 in 10,000
1 Very Low Failure is extremely unlikely ≤ 1 in 1,000,000
Quality Risk Management:
Examples of Criteria to Assess Detectability
RANK SEVERITY CRITERIA
Control Systems exist which and will almost certainly detect
1 Almost Certain a potential cause/mechanism and subsequent failure mode in a
preventative manner
Control systems exists with a high chance that it will detect a
4 Highly Likely potential cause / mechanism and subsequent failure mode in a
preventative manner
Control systems exists with a moderate chance that it will
detect a potential cause / mechanism and subsequent failure
7 Moderate
mode in a preventative manner
No control systems exists OR a control systems exists that
will not detect a potential cause / mechanism and subsequent
10 Impossible
failure mode in a preventative manner
Thank you!
