Date post: | 02-Jun-2018 |
Category: |
Documents |
Upload: | hassan-houdoud |
View: | 221 times |
Download: | 0 times |
of 44
8/11/2019 FDAs Draft Process Validation Guidance.pdf
1/44
FDAs Draft Process Validation Guidance
Overview and Implications for C&Q Programs
Alice Redmond, C&Q Technical Director09th March 2010
8/11/2019 FDAs Draft Process Validation Guidance.pdf
2/44
Reviews potential impact onthe current industryapproaches to science andrisk based design and
qualification activities whichsupport the processvalidation program
The key changes inrelation to the 1987guidance
This paper presentsan overview of thedraft FDA PV guidance
Overview Key Changes Impact
8/11/2019 FDAs Draft Process Validation Guidance.pdf
3/44
Guidance for Industry
Process Validation: General
Principles and Practices
DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 60 days of
publication in theFederal Register of the notice announcing the availability of the draft guidance.
Submit comments to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be
identified with the docket number listed in the notice of availability that publishes in the FederalRegister.
For questions regarding this draft document contact Brian Hasselbalch or Grace McNally
(CDER) 301-796-3286 or 301-796-3279, Christopher Joneckis (CBER) 301-827-0373, or
Dennis Bensley (CVM) 301-827-6956.
U.S. Department of Health and Human Services Food and Drug Administration Center forDrug Evaluation and Research (CDER) Center for Biologics Evaluation and Research
(CBER) Center for Veterinary Medicine (CVM)
November 2008 Current Good Manufacturing Practices (CGMP)
1.1.
2.2.
3.3.
FDAs Guidance for Industry on Process Validation has
been welcomed for
The clarity of its integrated3 stage lifecycle process
The elimination of the 3Golden Batches concept.
Its emphasis on the need
for effective scientificknowledge led programs
8/11/2019 FDAs Draft Process Validation Guidance.pdf
4/44
Guidance for Industry
Process Validation: General
Principles and Practices
DRAFT GUIDANCE
This guidance document is being distributed for comment purposes only.
Comments and suggestions regarding this draft document should be submitted within 60 days of
publication in theFederal Register of the notice announcing the availability of the draft guidance.
Submit comments to the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be
identified with the docket number listed in the notice of availability that publishes in the Federal
Register.
For questions regarding this draft document contact Brian Hasselbalch or Grace McNally
(CDER) 301-796-3286 or 301-796-3279, Christopher Joneckis (CBER) 301-827-0373, or
Dennis Bensley (CVM) 301-827-6956.
U.S. Department of Health and Human Services Food and Drug Administration Center forDrug Evaluation and Research (CDER) Center for Biologics Evaluation and Research
(CBER) Center for Veterinary Medicine (CVM)
November 2008 Current Good Manufacturing Practices (CGMP)
Once Published
It will replace the FDAs1987 Guideline on GeneralPrinciples of Process
Validation
It sets out the approachesthat the FDA consider tobe appropriate elementsof process validation
It represents the FDAscurrent thinking in regardto process validation
1.1.
2.2.
3.3.
8/11/2019 FDAs Draft Process Validation Guidance.pdf
5/44
Stage 1 Process Design: The commercial process isdefined during this stage based on knowledge gainedthrough development and scale-up activities
Stage 2 Process Qualification: During this stage,
the process design is confirmed as being capable ofreproducible commercial manufacturing
Stage 3 Continued Process Verification: Ongoingassurance is gained during routine production that theprocess remains in a state of control
3 Stages of Process Validation
1.1.
2.2.
3.3.
8/11/2019 FDAs Draft Process Validation Guidance.pdf
6/44
In
ScopeHumanDrugs
Veterinary
Drugs
APIs
Biologicals
8/11/2019 FDAs Draft Process Validation Guidance.pdf
7/44
Out ofScopeInvestigational
MedicinalProducts
Medical
Devices
8/11/2019 FDAs Draft Process Validation Guidance.pdf
8/44
Effective Process Validation contributes significantly to
assuring drug quality
Basic Principles of Quality Assurance
A drug should be produced that is fit for its intended use;
Quality, safety, and efficacy are designed or builtinto the product.
Quality cannot be adequately assuredmerely by in-process andfinished-product inspection or testing
Each step of a manufacturing process is controlled to assure that
the finished product meets all design characteristics and qualityattributes including specifications
Ref : Guidance for Industry Process Validation: General Principles and Practices (Nov 2008)
8/11/2019 FDAs Draft Process Validation Guidance.pdf
9/44
Guidance is Intended to Promote
modernmanufacturing
principles
processimprovement& innovation
soundscience
ProductProduct
LifecycleLifecycle
ApproachApproach
8/11/2019 FDAs Draft Process Validation Guidance.pdf
10/44
ProductProduct
LifecycleLifecycle
ApproachApproach
Emphasizing the importance of the links between
Product and processdesign and development
Qualification of thecommercialmanufacturingequipment andprocess
Maintenance of theprocess in a state of
control during routine
commercial production
8/11/2019 FDAs Draft Process Validation Guidance.pdf
11/44
Validation of the process is not aone off event but represents anongoing continuum of scientific
knowledge development andongoing assurance.
Ongoing Continuum.
8/11/2019 FDAs Draft Process Validation Guidance.pdf
12/44
Key Definition : Process Validation
The collection and evaluation of data,from the process design stage
throughout production, which establishesscientific evidencethat a process is
capable of consistently delivering quality
products
Ref : Guidance for Industry Process Validation: General Principles and Practices (Nov 2008)
8/11/2019 FDAs Draft Process Validation Guidance.pdf
13/44
Key to this Success
0
50
100
150
200
250
2004 2005 2006 2007 2008 2009 2010
Description A Description B Description C
25
30
2512
55
Description A Description B
Description C Description DDescription E
60%
30%
10% Description C
Description B
Description A
100%
5 7
2
4
2
3
7
9
56
8
6
5
3
Company A Company B
Proficiency in thecollection and
evaluationof information and dataabout the performance of the
process
8/11/2019 FDAs Draft Process Validation Guidance.pdf
14/44
Importance of making the entire process validationprogram more effective and efficient
General Considerations for PV
Good project management Robust scientific knowledge collection, management and
archiving
Uniform collection and assessment of information methods Reducing the burden of redundant information gathering
Use of an integrated team approach
Appropriately documented Project Plans
The support of senior management
Statistical assessment of data
8/11/2019 FDAs Draft Process Validation Guidance.pdf
15/44
3 Stages of Process Validation
Process
Design
ProcessQualification
ContinuousProcess
Verification
ProductProduct
LifecycleLifecycle
ApproachApproach
8/11/2019 FDAs Draft Process Validation Guidance.pdf
16/44
Key tenets of the lifecycle approach
Gain a high degree of assurance in the performance of theprocess before distribution
Based on objective information from lab, pilot, and/or
commercial- scale studies Success relies on skilled interpretation of the information
and knowledge gained
Understanding sources of variation, their impacts andassociated risks
Establishing appropriate control strategies
This scientific knowledge is verified by testing
(in-process, release, characterization) of each significantstep of the commercial manufacture process
8/11/2019 FDAs Draft Process Validation Guidance.pdf
17/44
Key Tenets of the Lifecycle Approach 2
Ongoing data analysis of both intra-batch and inter-batchvariability
Appropriate provisions to address deviations andnonconforming data
Importance of both QA and Operators in providingfeedback for continued process verification
Emphasis is on maintaining the process in astate of control
It provides a strong lead in acknowledging thatqualification programs devoid of process understandingwill not guarantee the assurance of quality required
8/11/2019 FDAs Draft Process Validation Guidance.pdf
18/44
Stage 1Process Design
Design a process suitable for routine commercial manufacturing thatcan consistently deliver a product that meets its CQAs
a. Building and Capturing Process Knowledge and Understanding
b. Establishing a Strategy for Process Control
DOE
GMP/NonG
MP
PAT
CommercialScale
Functionalityand
Constraints
Variability
8/11/2019 FDAs Draft Process Validation Guidance.pdf
19/44
Stage 2Process Qualification
Process design is confirmed as being capable of reproduciblecommercial manufacturing
a. Design of a Facili ty and Qualification of Utili ties and Equipment
b. Performance Qualification Approach
c. Performance Qualification Protocol
d. Protocol Execution and Report
Fit for Intended UseQualification
Productsmanufactured
duringthisstage,ifacceptable,canbereleased
Role of QA EnhancedMonitoring
8/11/2019 FDAs Draft Process Validation Guidance.pdf
20/44
The decision to begincommercial distribution should
be supported by data fromcommercial batches
Released
Product and
ContinuedProcess
Verification
Batch
C
Batch B
Batch
AFacility and
Equipment'Qualified
How Many ?
Approved for Commercial Distribution
8/11/2019 FDAs Draft Process Validation Guidance.pdf
21/44
Batch
C
Batch B
Released
Product and
ContinuedProcess
Verification
Facility and
Equipment'Qualified
Approved for Commercial Distribution
The decision to begincommercial distribution
should be supported by datafrom commercial batches
How Many ?
8/11/2019 FDAs Draft Process Validation Guidance.pdf
22/44
Batch B
Released
Product and
ContinuedProcess
Verification
Facility and
Equipment'Qualified
Approved for Commercial Distribution
The decision to begincommercial distribution should be
supported by data fromcommercial batches
How Many ?
8/11/2019 FDAs Draft Process Validation Guidance.pdf
23/44
Stage 3Continued Process Verification
Continually assure that the process remains in a state of control (thevalidated state) during commercial manufacture
Detection of Process Drift
Ongoing program to collect and analyze product andprocess data that relate to product quality
Statistician led analysis Detection, control, and/or mitigation strategies
Continued enhanced monitoring
Process Optimization Maintenance
8/11/2019 FDAs Draft Process Validation Guidance.pdf
24/44
Overview Key Changes Impact
Reviews potential impact onthe current industryapproaches to science andrisk based design andqualification activities whichsupport the processvalidation program
The key changes inrelation to the 1987guidance
This paper presentsan overview of thedraft FDA PVguidance
8/11/2019 FDAs Draft Process Validation Guidance.pdf
25/44
to is controlled to assure.Wording revision from maximize
the probability that
to is designed or built.Principles of quality assurance
wording revision from designed
and built into the product
to cannot be adequately assured
merely by in-process and finished
product inspection or testing
Principles of quality assurance
wording revision from cannot be
inspected or tested into the finished
product
Defines validation in terms of
establishing scientific evidence
Defines validation as establishing
documented evidence.
2008 Draft1987 PV Guidance
Key Changes between 1987 PV Guidance and 2008 Draft
8/11/2019 FDAs Draft Process Validation Guidance.pdf
26/44
New Guidance in 2008 Draft
2008 Draft1987 PV Guidance
Emphasizes the use of qualitative
statistical methods to monitor,
evaluate and justify assurance of
process performance
Emphasizes Science Based
Knowledge development
Removes validation information for
medical devices;
Introduction of root cause
(e.g., review of customer
complaints and impact on process)
Introduction of Process Analytical
Technology (PAT) concepts for PV
exclusion of revalidation and
retrospective process validation.
Introduction of
product lifecycle concept
Introduction of
integrated team approach
8/11/2019 FDAs Draft Process Validation Guidance.pdf
27/44
Overview Key Changes Impact
Reviews potential impact onthe current industryapproaches to science andrisk based design andqualification activities whichsupport the processvalidation program
The key changes inrelation to the 1987guidance
This paper presentsan overview of thedraft FDA PVguidance
8/11/2019 FDAs Draft Process Validation Guidance.pdf
28/44
Key Definition : Qualification
Activities undertaken todemonstrate that utilities and
pieces of equipment are suitable fortheir intended use and performproperly is referred to in this
guidance as qualification
Ref : Guidance for Industry Process Validation: General Principles and Practices (Nov 2008)
8/11/2019 FDAs Draft Process Validation Guidance.pdf
29/44
Fundamental Change Needed
Current premise: Did we meet the
design (design is presumed to be
perfect)?
Future premise: Have we metprocess requirements, and have we
controlled risks to quality?
8/11/2019 FDAs Draft Process Validation Guidance.pdf
30/44
Page 30
C&Q Model
Traditional V Model or Risk Based Verification
Lean Thinking is Equally Relevant
related to
SystemBuild
related to
related toUser
RequirementsSpecification
PerformanceQualification
FunctionalSpecification
OperationalQualification
InstallationQualification
DesignSpecification
Good Engineering Practice
Requirements Specificationand Design
VerificationAcc eptan ceand Release
Operation &
Continuous
Improvement
ProductKnowledge
ProcessKnowledge
RegulatoryRequirements
CompanyQuality Reqs.
Risk Management
Design Review
Change Management
Figure 1 The Specification, Design and Verification Process
8/11/2019 FDAs Draft Process Validation Guidance.pdf
31/44
Process - The New V Model
Reference: Figure 1: ASTM E2500-07 A Standard Guide for the Specification, Design, and Verification
of Pharmaceutical and Biopharmaceutical Manufacturing Systems and Equipment, pg 3
GOOD ENGINEERING PRACTICE
OPERATION &
CONTINUOUSIMPROVEMENT
RISK MANAGEMENT
DESIGN REVIEW
CHANGE REVIEW
PRODUCT
KNOWLEDGE
PROCESS
KNOWLEDGE
REGULATORY
REQUIREMENTS
COMPANY QUALITY
REGULATIONS
REQUIREMENTS SPECIFICATIONS& DESIGN ACCEPTANCE& RELEASEVERIFICATION
8/11/2019 FDAs Draft Process Validation Guidance.pdf
32/44
ASTM Process Flow
Subject Matter Experts (SMEs) following GEPs
Verification
Plan
List of
Critical
Aspects
(CQA, CPP)
Verification Testing (Design to Performance)
to confirm Critical Aspects andmeet Acceptance Criteria
Acceptance
and
ReleaseFactory Acceptance Test
Site Acceptance Test
Installation VerificationFunctional Verification
Performance
Testing
Verification Phase
Acceptance
and
Release
Approved by
Quality Unit
Approved by
Quality Unit
Review all completed verification test
documentation by a second, independent SME
Approved by
Quality Unit
Operation
Continuous
Improvement
8/11/2019 FDAs Draft Process Validation Guidance.pdf
33/44
Principles
Risk-Based Approach
Science-Based Approach
Critical Quality Attributes
Quality by Design
Good Engineering Practices
Subject Matter Experts
Use of Vendor Documentation
Continuous Improvement
8/11/2019 FDAs Draft Process Validation Guidance.pdf
34/44
MOC, operating principles & performance characteristics
Verifying built as designed;
Verifying operation (comparable load / interventions /
durations)
(1) Tests
(2) Criteria(3) Timing
Summary report with conclusions that address criteria in
the plan
Qualification
IncludeInclude
Q PlanQ Plan
Q ReportQ Report
(4) Responsibilities
(5) Procedures(6) Changes
Approved
Approved
8/11/2019 FDAs Draft Process Validation Guidance.pdf
35/44
Summary FDA Draft PV vs. ASTM E2500
YYFlexibility on how effort is structured
YYRisk assessment to scale effort
YYQA approves
[qualification]/[verification] report
N* Acceptance
Criteria only
YQA approves
[qualification]/[verification] plan
YYEquipment and facilities suitable for
intended use
YYFocus on science-based process
understanding and meeting process
requirements
ASTMFDA PVQualification vs. Verification
Aspects
8/11/2019 FDAs Draft Process Validation Guidance.pdf
36/44
Summary FDA Draft PV vs. ASTM E2500
NYSpecific aspects to check for spelled
out
YNACritical aspects defined from riskassessments and process
requirements
YYUse of project change management
YYUse of subject matter experts: how
to verify, adjudicate minor
departures from specification for CQ
YNAUse of vendor documents
YYDesign of facility, process,
equipment based on process
understanding
ASTMFDA PVQualification vs. Verification
Aspects
8/11/2019 FDAs Draft Process Validation Guidance.pdf
37/44
Impact on Design & Verification
Endorses an Integrated LifecycleApproach
Seeks early alignment of product& process requirements
Requires Multi Disciplined Teams
Welcome avoidance of tradit ional,prescriptive terminology such as
DQ,IQ and OQ
Necessary from start of ConceptDesign
Requires access / engagement ofR&D
Impacted by Contracting Strategy
Offers Opportunities to reallyimprove the CQ process
Real opportunities to look behind the prepared templates and
execute qualification and validation programs which arenot only valid but valuable
to the ongoing operation and continuous improvement
O h D i
8/11/2019 FDAs Draft Process Validation Guidance.pdf
38/44
ISPE Singapore - C&Q Workshop 2009Page 38
Other Drivers
ISPE Product Quality Lifecycle Implementation (PQLI) Initiative
- Practical Implementation of ICH Guidance and Quality by Design
ASTM E2500 Standard Guide for Specification, Design, andVerification of Pharmaceutical and Biopharmaceutical Manufacturing
Systems and Equipment GAMP 5 Guidance
ISPE GEP best practise guide
ISPE Draft C&Q best practise guide
ISPE Baseline Guide 12 Draft Verification guide FDA: Quality Systems Approach to Pharmaceutical cGMP
Regulations 2006
EU Annex 20, Quality Risk Management March 2008
ICH Q8 Pharmaceutical Development - Nov 2005 ICH Q10 Quality Systems June 2008
F f B li G id 12
8/11/2019 FDAs Draft Process Validation Guidance.pdf
39/44
Focus of Baseline Guide 12
The Guide focuses on the process and facilitating the
translation of the scientific knowledge about the product and
process into good design of equipment, systems, and
facilities which:
meet documented process requirements
control documented risks to the patient
produce life cycle evidence which verifies that the as-installed
implementation of the design meets the above two objectives
Link From Baseline Guide 5 to New Baseline Guide 12
8/11/2019 FDAs Draft Process Validation Guidance.pdf
40/44
Concepts
Pro
duc
t/
Process
Know
ledge
Requ
iremen
ts
De
fin
ition
Risk
Assessmen
t
Des
ign
Rev
iews
Ver
ifica
tion
Accep
tance
an
dRe
lease
Qua
lity
Managemen
t
Sys
tems
Ch
ange
Ma
nagemen
t
Ro
les
&
Re
spons
ibilities
Th Ch ll g
8/11/2019 FDAs Draft Process Validation Guidance.pdf
41/44
The Challenge
NEW GUIDANCE NEW IDEAS
TIME TO APPROVAL
8/11/2019 FDAs Draft Process Validation Guidance.pdf
42/44
Alignment
Questions and Answers
8/11/2019 FDAs Draft Process Validation Guidance.pdf
43/44
Questions and Answers
8/11/2019 FDAs Draft Process Validation Guidance.pdf
44/44
Questions Tomorrow ?
Alice RedmondC&Q Technical Director, PM Group
+353 21 452 2916
+353 86 8385088