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 21st Century – A Risk Based

Approach” – FDA (2004)   ISPE White Paper – “Risk Based Qualification for the 21st

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 21st 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

Qualified as Suitable For Intended Use Basis for Suitability:

Process Requirements, Risk Control

FAT Verification Work

SAT Verification Work

Commissioning Verification 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

Pro’s Con’s

Industry Needs Going Forward

•  Regulators who walk-the-talk on risk based approaches

•  Industry that understands the opportunities and responsibilities – not simply viewing RBA’s 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 ?