Science and Risk-Based

Commissioning and Qualification

Applied Risk Management
In a 21stCentury GMP Environment
David Dolgin
Senior Quality Program Manager
Global Quality Systems
Abbott
Topics
Introduction and Background
Transition to Science and Risk Based
Approaches
Linking C&Q to the Process
Validation Lifecycle
Recent ISPE Guidance
Agenda
Thursday Morning 19 May 2012
Background (8:30-9:00)
Transitional Approaches (9:00-10:30)
Process Validation and Legacy Systems
(10:45-11:30)
Recent ISPE Guidance Documents
(11:30-12:00)
Science and Risk-Based
Commissioning and Qualification
Introduction and Background
David Dolgin
Senior Quality Program Manager
Global Quality Systems
Abbott
What is a Science and Risk Based
Approach?
A science and risk based approach to
Qualification of applicable systems and
facilities consists of:
The identification and control of risks to product
quality
Formality and documentation commensurate with
risk
The use of Good Engineering Practices (GEP) to
verify installation and operation of systems
Verification that system performance meets product
and process user requirements
A Brief History of C&Q
! Qualification of
Systems and Facilities
! Validation of
Manufacturing and
Supporting Processes
Validation Quality Systems have traditionally described
two separate but related activities:
Qualification A Broken Process
! One-Size-Fits-All Approach
! Emphasis on Documentation Not
Process Requirements
! Absent or Incomplete Assessment of
Risks to Product Quality & Patient
Safety
! IQ/OQ More Intensive Than PQ
! Organizations Refused to Leverage
Commissioning
! Deviations for Trivial Items
! Change-is-Bad Attitude Driven by
Cost / Time Inhibited Innovation &
Continuous Improvement
A Road Forward
! ISPE Baseline Guide 5 (2001)
! Pharmaceutical cGMPs for the 21
st
Century A Risk Based
Approach FDA (2004)
! ISPE White Paper Risk Based Qualification for the 21
st

Century (2005)
! ICH Q9 Quality Risk Management (2006)
! ASTM E 2500 Standard Guide for Specification, Design, and
Verification of Pharmaceutical and Biopharmaceutical Manufacturing
Systems and Equipment (2007)
! ISPE Good Practice Guide Science and Risk Based Approach for
the Delivery of Facility Systems and Equipment (2011)
! ISPE Good Practice Guide Applied Risk Management in
C&Q (2011)
10 Principles for Risk-Based Qualification
1. Focus on that which affects product quality
2. Process User Requirements key to acceptability (IQ/OQ subordinate
to PQ)
3. Risk assessments and process knowledge used to identify critical
elements
4. Only critical features/functions to be qualified
5. All activities must contribute value
6. Risk-based asset delivery not cookbook requirements
7. Value-added documents based on technical merit
8. Use of supplier documentation
9. Test planning (and one-time testing)
10. Foster innovation all change is not bad
ISPE White Paper Risk Based Qualification for the 21
st

Century March 2005
ICH Q9 Two Key Principles
! The evaluation of 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
quality risk management
process should be
commensurate with the
level of risk. (my emphasis)
Think about it:
If everything is treated as critical -
then nothing is!
ASTM E 2500-07
First consensus standard using science and risk-based
approach to verification
Verification is an umbrella term taken from regulation
(verified as fit for intended use) and used to
describe both commissioning and qualification
ASTM does away with IQ and OQ as mechanisms and
goes straight from commissioning to PQ
Redefines Quality and Engineering roles QA is
assurance not control an audit role, not a direct
management or execution role
Design Review
Change Management
Risk Management
Good Engineering Practice
Figure 1 The Specification, Design, and Verification Process
Operation
Product
Knowledge
Process
Knowledge
Regulatory
Company
Quality
Requirements
Specification
and Design
Verification
Acceptance
and
Release
ASTM E 2500-07 Process Flow
Verification as Qualification
Qualied as Suitable
For Intended Use
Basis for Suitability:
Process Requirements,
Risk Control
FAT Verication
Work
SAT Verication
Work
Commissioning Verication
Work
Figure 2 from Solving the Terminology Conundrum
Pharmaceutical Engineering, July/August 2008
Qualification -Traditional vs. RBA
Traditional Approach
User Requirements not
Formally Documented
Protocols Developed from
Templates
IQ/OQ Protocols
Preapproved
Commissioning not Leveraged
Engineering and Validation
Personnel Often Distinct
Emphasis on Documents Not
System Performance
RBA Based on ASTM E 2500
Process Requirements
Documented, Approved
Risk Assessments Determine
Critical Aspects of E/F/U Design
Engineering Testing
(Commissioning) Verification
All Documents with Technical Merit
Used as Evidence of Fitness for
Use
Emphasis on Meeting Process
Requirements
Risk Based C&Q - Challenges and
Opportunities
Opportunities
Cheaper
Faster
Focused on Patient Risk
Resource Reallocation Possible
Foster Innovation
Challenges
ASTM not yet fully vetted with all global
agencies
GEP and ECM are prerequisites
Both Quality and Engineering units must
buy-in
Commissioning documentation Quality
standards must be set and achieved
Pros
Cons
Industry Needs Going Forward
Regulators who walk-the-talk on risk based approaches
Industry that understands the opportunities and responsibilities
not simply viewing RBAs as chance to do more with less
Continued leadership from key industry groups and participation
of big pharma in an evolutionary process
QA units that understand that more is not necessarily better
Good Engineering Practices and Good Engineers
Actual photo of risk based revalidation paperwork for a
legacy control system (on right) vs. previous revalidation
testing everything
Time & $$$
to
Focus on Critical
Quality Issues
Eyes on the Prize
Questions ?