Risk-Based Strategies for Analytical
Method Qualification/Validation Studies
to Support Accelerated
Product Development
Stephan Krause
Principal Scientist, MedImmune
27 January 2014
CASSS CMC Strategy Forum
Washington, DC
2
Outline
Review of Strategic Opportunities to Reduce Analytical Method Lifecycle
Steps for Accelerated Programs for:
– Analytical Platform Technology (APT) methods
– Product and Process Characterization methods
– Product-Specific (‘New”) methods
– Compendial methods
Understand how analytical platform technology concepts can greatly
support accelerated development programs.
Understand how parallel (versus sequential) analytical method lifecycle
steps can further support these programs.
Presentation to Focus on Late-Stage Development Opportunities:
– Mostly Risk(s) to Manufacturer/Sponsor
2 Krause/PDA TR 57 (2012)
3
CQA Development, CMC Changes, and Specifications
FTIH POC BLA
Tox StudiesPhase 1
Phase 2Phase 3
Clinical Resupply
Mfg/Formulation Change(s)
Specifications
Revision(s)
Target Quality Criteria
Commercial
Specifications
Negotiations, Final
Commercial Specifications
QTPP
Final CQAs &
Control Strategy ApprovalPotential CQAs
Product & Process
Design
Life-Cycle
ManagementPOST-APPROVAL
CHANGESPHASE 3PHASE 1/2Pre-IND
CQ
A D
ev
elo
pm
en
t
(Qb
D P
roc
es
s)
Sp
ec
s L
ife
Cy
cle
Mg
mt
CM
C a
nd
Te
ch
Tra
ns
fer
Pro
ce
ss
Analytical
Manufacturing
Strategic or
Tactical Changes
Method
qualification
Dose
change
Delivery
Device
PQ lots
Setting of Initial
SpecificationsSpecifications
Review/Confirmation
Mfg
Transfer
Method
validation
Method
transfer
Formulation
ChangeProcess Verification
Method
Maintenance
Global
Supply
Krause/WCBP January 2013
4
Accelerated CQA Development, CMC Changes, and Specifications
FTIH POC BLA
Tox StudiesPhase 1
Phase 3
Clinical Resupply
Mfg/Formulation Change(s)
Specifications
Revision(s)
Commercial
Specifications
Negotiations, Final
Commercial Specifications
QTPP
Final CQAs &
Control Strategy Approval Potential CQAs
Product & Process
Design
Life-Cycle
ManagementPOST-APPROVAL
CHANGESPIVOTAL PHASE (3)PHASE 1 Pre-IND
CQ
A D
ev
elo
pm
en
t
(Qb
D P
roc
es
s)
Sp
ec
s L
ife
Cy
cle
Mg
mt
CM
C a
nd
Te
ch
Tra
ns
fer
Pro
ce
ss
Analytical
Manufacturing
Strategic or
Tactical Changes
Method
qualification
Dose
change
Delivery
Device
PQ
lots
Setting of Initial
SpecificationsSpecifications
Review/Confirmation
Mfg
Transfer
Method
validation
Method
transfer
Formulation
ChangeProcess Verification
Method Maintenance
Global
Supply
Method
Change
Accelerated Development
5
Analytical Method Lifecycle – Intended Use
Analytical Method
Selection
Pharmaceutical Development Supporting Studies:
Process characterization
Product characterization
Process validation
Routine Testing (registered methods):
Raw materials
In-process
Release
Stability
Intended Use
(defined)
AMD
Studies
AMD
Studies
AMQ ReportAMQ ReportIntended Use
(re-defined)
AMV Report
Identity
Safety
Purity
Quality
Potency
Quality Target Product Profile (QTPP)
Critical Quality Attributes (CQA)
Critical Process Parameters (CPP)
Krause/PDA TR 57 (2012)
6
Retrospective and Prospective Use of Data for AMV Studies from
other Processes Prior to AMV – New Method
Krause/PDA Workshop (2013)
7
Retrospective and Prospective Use of Data for AMV Studies from
other Processes Prior to AMV – Analytical Platform Method
Method
Qualification
(AMQ)
Method Validation
(AMV)
Method Transfer
(AMT)
(Less)
AMQ
Studies
“Verification”
Focus on:
Accuracy,
Specificity
PVFTIH BLA
Historical
Data - SU
Assay
Control
Tech
Transfer
(Less)
Interm.
Precision
& Reprod.
Historical
Data - RU
Assay
Control
“Approved”
Method
Krause/PDA Workshop (2013)
Ideal Analytical Method Lifecycle Clinical Phase 1-2 (prior to transfer from Pilot to Commercial Plant)
8
DS/DP
Specification
Test Methods
for New Method
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
Start PV
Stage 2(PQ Lots)
Completed
In progress
Not started
AMV completed
Maintenance
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
Process Color
Legend:
Method Qualified
(SOP Lock)
Ideal Analytical Method Lifecycle Preparing for Tech Transfer (Pilot to Commercial Plant)
9
DS/DP
Specification
Test Methods
for New Method
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
Start PV
Stage 2(PQ Lots)
Completed
In progress
Not started
AMV completed
Maintenance
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
Process Color
Legend:
Method Qualified
(SOP Lock)
Ideal Analytical Method Lifecycle Preparing for Tech Transfer (Pilot to Commercial Plant)
10
DS/DP
Specification
Test Methods
for New Method
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
Start PV
Stage 2(PQ Lots)
Completed
In progress
Not started
AMV completed
Maintenance
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
Process Color
Legend:
Method Qualified
(SOP Lock)
Ideal Analytical Method Lifecycle Preparing for Tech Transfer (Pilot to Commercial Plant)
11
DS/DP
Specification
Test Methods
for New Method
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
Start PV
Stage 2(PQ Lots)
Completed
In progress
Not started
AMV completed
Maintenance
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
Process Color
Legend:
Method Qualified
(SOP Lock)
Ideal Analytical Method Lifecycle Preparing for PQ (at Commercial Plant)
12
DS/DP
Specification
Test Methods
for New Method
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
Start PV
Stage 2(PQ Lots)
Completed
In progress
Not started
AMV completed
Maintenance
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
Process Color
Legend:
Method Qualified
(SOP Lock)
Ideal Analytical Method Lifecycle Preparing for PQ (at Commercial Plant)
13
DS/DP
Specification
Test Methods
for New Method
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
Start PV
Stage 2(PQ Lots)
Completed
In progress
Not started
AMV completed
Maintenance
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
Process Color
Legend:
Method Qualified
(SOP Lock)
Ideal Analytical Method Lifecycle Executing PQ Studies (at Commercial Plant)
14
DS/DP
Specification
Test Methods
for New Method
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
PQ Lots
Mfg
Completed
In progress
Not started
AMV completed
Maintenance
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
Process Color
Legend:
Method Qualified
(SOP Lock)
Analytical Method Lifecycle APT Opportunities following AMV Study Completion
15
DS/DP
Specification
Test Methods for
Same SOP and
New Product
Robustness
Studies Execution
QCDev.
AMVStudies
(QC-Comm.)
PQ Lots
Mfg
Completed
In progress
Not started
AMV completed
Maintenance
AMM
(QC-Comm.)
Robustness
StudiesMaster Plan
AMT Studies
(QC-Dev. &
QC-Comm.)
SOP-specific
Min/Max Method
Conditions
(for PB Design)
Commercial
Specifications
Not Parallel Step
APT MethodAMV and AMM
(QC)
Analytical Platform
Technology
APT
Method Robustness
and AMT
Process Color
Legend:
Method Qualified
(SOP Lock)
APT
Method AMQ
Analytical Method Lifecycle for Accelerated Programs APT Opportunities following prior AMV Study Completion
16
DS/DP
Specification
APT Test Methods
(not compendial)
APT Transfer
(feasibility only,
no formal AMT)
Partial
AMV Study
Execution
Start PV Stage 2
(PQ Lots)
APT
Maintenance
VMP Analytical
Methods
APT
Qualification
Studies
Commercial
Specifications
APT
Robustness(QC-Dev.)
Feasibility
Testing
(QC-Comm.)
Simultaneous ?
Simultaneous ?
Completed
In progress
Not started
AMV completed
Not Parallel Step
Analytical Platform
Technology
Process Color
Legend:
Analytical Method Lifecycle for Accelerated Programs Additional APT Opportunities
17
Qualification of
Test Methods
Process and/or
Product
Characterization
Representative
Samples
Available (Dev.)
Execution Reqs: (1. IOQ Instrument)
(2. Analyst Training)
3. Final SOP version
QC Dev. or
QC Comm.
Confirm
Method
Suitability
Start PV
Stage 2(PQ Lots)
Qualify (as relevant):A. Accuracy/Matching
B. Precision/Reliability
C. Specificity
D. DL or QL
Qualification
Report(s)
Method
Qualification
Master Plan
Final PV Process Ranges and/or
Analytical Control Strategy
APT (Reduced)
Qualification
Opportunity
Completed
In progress
Not started
AMV completed
Not Parallel Step
Analytical Platform
Technology
Process Color
Legend:
Analytical Method Lifecycle for Accelerated Programs Limited APT Opportunities
18
DS/DP
Specification
Test Methods
Compendial
Representative
DS/DP Samples
(from QC-Dev.
or QC-Comm.)
Execution Reqs: 1. IOQ Instrument
2. Analyst Training
3. Qualified Material
4. Final SOP version
Start PV
Stage 2(PQ Lots)
Completed
In progress
Not started
AMV
completed
Verify (as relevant):A. Accuracy/Matching
B. Precision/Reliability
C. Specificity
D. DL or QL
Verification
Report(s)
Method
Verification
Master Plan
Commercial
Specifications
Not Parallel Step
Process Visual Legend:
QC
Comm.
Risk/Uncertainty Levels and Risk-Based Opportunities (Typical) (Analytical Method Lifecycle Steps in Typical Order)
19
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) No. Analytical
Method
Product /
Process
Sample
A New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
B New Old
(Validated) 3-4(1)
Full
Qualification
Plus AMC(2)
Studies
Full
Robustness
Studies
Full AMT
Studies
Full Validation
Plus AMC(2)
Studies
C
Analytical
Platform
Technology
New 1-2 Qualification Robustness
Studies AMT Studies Validation
D Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
E
Product/Process
Charaterization
Tests
New 2-3 Qualification N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk/Uncertainty Levels and Risk-Based Opportunities (Typical) (Analytical Method Lifecycle Steps in Typical Order)
20
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) No. Analytical
Method
Product /
Process
Sample
A New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
B New Old
(Validated) 3-4(1)
Full
Qualification
Plus AMC(2)
Studies
Full
Robustness
Studies
Full AMT
Studies
Full Validation
Plus AMC(2)
Studies
C
Analytical
Platform
Technology
New 1-2 Qualification Robustness
Studies AMT Studies Validation
D Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
E
Product/Process
Charaterization
Tests
New 2-3 Qualification N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk/Uncertainty Levels and Risk-Based Opportunities for APT Methods (Analytical Method Lifecycle Steps in Typical Order)
21
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) Analytical
Method
Product /
Process
Sample
New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
Analytical
Platform
Technology
New 1-2
APT
(Reduced)
Qualification
APT
(Reduced)
Robustness
Studies
APT
(Reduced)
AMT Studies
APT
(Reduced)
Validation
Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
Product/Process
Charaterization
Tests
New 2-3
Reduced
Qualification
(if APT)
N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk/Uncertainty Levels and Risk-Based Opportunities for APT Methods (Analytical Method Lifecycle Steps in Typical Order)
22
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) Analytical
Method
Product /
Process
Sample
New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
Analytical
Platform
Technology
New 1-2
APT
(Reduced)
Qualification
APT
(Reduced)
Robustness
Studies
APT
(Reduced)
AMT Studies
APT
(Reduced)
Validation
Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
Product/Process
Charaterization
Tests
New 2-3
Reduced
Qualification
(if APT)
N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk/Uncertainty Levels and Risk-Based Opportunities for APT Methods (Analytical Method Lifecycle Steps in Typical Order)
23
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) Analytical
Method
Product /
Process
Sample
New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
Analytical
Platform
Technology
New 1-2
APT
(Reduced)
Qualification
APT
(Reduced)
Robustness
Studies
APT
(Reduced)
AMT Studies
APT
(Reduced)
Validation
Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
Product/Process
Charaterization
Tests
New 2-3
Reduced
Qualification
(if APT)
N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk/Uncertainty Levels and Risk-Based Opportunities for APT Methods (Analytical Method Lifecycle Steps in Typical Order)
24
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) Analytical
Method
Product /
Process
Sample
New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
Analytical
Platform
Technology
New 1-2
APT
(Reduced)
Qualification
APT
(Reduced)
Robustness
Studies
APT
(Reduced)
AMT Studies
APT
(Reduced)
Validation
Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
Product/Process
Charaterization
Tests
New 2-3
Reduced
Qualification
(if APT)
N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk/Uncertainty Levels and Risk-Based Opportunities for APT Methods (Analytical Method Lifecycle Steps in Typical Order)
25
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) Analytical
Method
Product /
Process
Sample
New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
Analytical
Platform
Technology
New 1-2
APT
(Reduced)
Qualification
APT
(Reduced)
Robustness
Studies
APT
(Reduced)
AMT Studies
APT
(Reduced)
Validation
Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
Product/Process
Charaterization
Tests
New 2-3
Reduced
Qualification
(if APT)
N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk-Based Opportunities for New Methods
(Analytical Method Lifecycle Steps in Typical Order)
26
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) Analytical
Method
Product /
Process
Sample
New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
Analytical
Platform
Technology
New 1-2
APT
(Reduced)
Qualification
APT
(Reduced)
Robustness
Studies
APT
(Reduced)
AMT Studies
APT
(Reduced)
Validation
Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
Product/Process
Charaterization
Tests
New 2-3
Reduced
Qualification
(if APT)
N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
Risk-Based Opportunities for New Methods
(Analytical Method Lifecycle Steps in Typical Order)
27
AMQ-Robustness-AMT-AMV
Class Description Typical
Risk /
Uncertainty
Level
(1=Low,
5=High)
Suggested
Prospective
AMQ Studies
(QC-Dev.)
Suggested
Prospective
Robustness
Studies
(QC-Dev.)
Suggested
Prospective
AMT Studies
(QC-Dev./ QC-
Comm.)
Suggested
Prospective
AMV Studies
(QC Comm.) Analytical
Method
Product /
Process
Sample
New New 4-5 Full
Qualification
Full
Robustness
Studies
Full AMT
studies Full Validation
Analytical
Platform
Technology
New 1-2
APT
(Reduced)
Qualification
APT
(Reduced)
Robustness
Studies
APT
(Reduced)
AMT Studies
APT
(Reduced)
Validation
Compendial New 1-2
Verification
per USP
<1226>
N/A N/A
Verification
per USP
<1226>
Product/Process
Charaterization
Tests
New 2-3
Reduced
Qualification
(if APT)
N/A N/A N/A
(1) If a new analytical method (forced method replacement) is needed due to supply reasons, the risk level can be generally considered higher
because no other option may exist. Unforced test method replacements can be considered to be a lower risk level as more time may be available
to optimize the method performance.
(2) AMC = Analytical Method Comparability: A study to confirm that a new analytical method can perform equally or better than the existing one.
Krause/PDA-DHI Publications, 2007, PDA TR 57 (2012)
28
Summary
Opportunities exist to reduce typical analytical method lifecycle
steps for accelerated programs.
Use of (analytical) platform technology can greatly support
accelerated development programs.
Reduction and/or use of “parallel” analytical method lifecycle steps
during later-stage development (prior to PV stage 2) results in risk(s)
mostly to manufacturer/sponsor and not the patient.
28