Effective Strategies for the Transfer of an Analytical Method
Xiande (Andy) Wang, Ph.D.
Analytical Development
Janssen Pharmaceutical Companies of Johnson & Johnson
IVT Analytical Procedures and Validation, December 2015, Philadelphia
Ground Rules
• Questions welcome any time!
• Comments are encouraged!
• Contact info:
Outline
I. Life cycle management of analytical methods
II. Method transfer procedure
– Definition of objectives, roles and responsibilities
– Laboratory evaluation
– Draft, review and approval of transfer protocol
– Experiment and data collection/analysis
– Draft, review and approval of transfer report
III. Options of method transfer
1. Comparative testing
2. Co-validation between two labs
– Case study: Extraneous peaks in glass vials
3. Complete or partial method validation
– Case study: Validation of HPLC and UHPLC in parallel
4. Transfer waiver
IV. Summary
Full Life Cycle of Pharmaceutical Products
CMC/R&DSupply Chain/
Operations
Life Cycle of Pharmaceutical Products
1996 2006
Method Development Life Cycle
Planning
Development and Validation Policy
Objectives/Requirements of Method
Information Gathering
Resource Gathering
Method developmentInitital Method Development
Pre-Validation Evaluation
Method Optimization
Robustness
System Suitability
Development
Plan –
Project
Customer Evaluation
Testing Validation
Method Transfer Filed Method in Use
Periodically
Monitoring/Review
of Methods
in Testing Labs
Analytical Procedures and Methods Validation for Drugs and Biologics: FDA Guidance July 2015
Analytical Procedures and Methods Validation: FDA Guidance Aug 2000
Method remediation initiatives
What is New in FDA Guidance July 2015:Life Cycle Management of Analytical Procedures
What is NOT New in FDA Guidance July 2015:Analytical Methods Transfer Studies
USP Chapter <1224>: Transfer of Analytical Procedures
– Focus on risk based approach• previous experience • knowledge of the receiving unit• the complexity• specifications of the product, and • the procedure
– Discussion of 4 types of analytical transfer
– Elements recommended for transfer of analytical procedures
– Emphasizes importance of transfer protocol
– The analytical procedure and report
What Is Analytical Method Transfer
• Protocol driven study with pre-defined acceptance criteria
• Transfer of validated analytical procedures to a new laboratory
• Verification of a method’s suitability for its intended use
• Demonstration of a laboratory’s proficiency in running a particular method
• No official guidelines
Objectives of Method Transfer
• Maintain the validated state of the method and meet all regulatory requirements
• Minimize surprises!
– Open and responsive communication
– Pre-determined expectations
– Clearly documented and communicated technical details
– Pre-transfer evaluation by experienced technical staff at receiving site
– Technical contact available for troubleshooting at transferring site
Occurrence of Method Transfer
R&D Method Development
QC Lab 1QC Lab 2
Occurrence of Method Transfer
• Sponsor company to contract lab
• Analytical development to QC labs
• Across different sites
– The same lab conditions
– Different lab conditions
• Existing to new instrumentation
– With different specifications
– With different technology
• Supplier of material to client
• Transfer to new instruments with different instrument characteristics
Roles and Responsibilities in Method Transfer
Coordinator
Transferring Lab
Receiving Lab
• Project owner• QA• Lab management• Analyst
Roles and Responsibilities in Method Transfer
Coordinator
Transferring LabReceiving Lab
• ID-FTIR
• HPLC (assay, impurity)
• GC-Ethanol
• GC-Residual solvent
• Water content
• Particle size
• Micro
Roles and Responsibilities:Coordinator / Coordinating laboratory
• Sends method validation information, if applicable
• Creates, approves method transfer protocol / report as author
• Provides materials required for execution and associated COA for reference materials
• Provides technical support
• Collects and evaluates all analytical results
• Documents / initiates inter-lab deviations / investigations which occurred during method transfer activities / testing
Roles and Responsibilities:Transferring laboratory
• Is a GMP laboratory that has validated the analytical procedures or is qualified to perform the analytical procedures
• Can also act as the coordinating lab
• Provides materials required for execution and associated COAs for reference materials
• Provides qualified instruments / personnel
• Gives technical support
• Executes analytical testing and shares results with coordinating lab
• Document deviations / investigations related to the transferring lab
• Document / initiate inter-laboratory deviations / investigations which occurred during method transfer activities / testing
• Perform gap assessment:– Does method/validation meet today’s guideline/standard
– Is the method compliant with regulatory approval
Roles and Responsibilities:Receiving laboratory
• Laboratory management reviews and approves for correctness and completeness, and is accountable for analytical test method transfer protocol / transfer report
• Provides qualified instruments / personnel
• Executes analytical testing and shares results with transferring / coordinating laboratory
• Document deviations / investigations related to the receiving laboratory
• Stores a copy of the final version of method validation report, transfer protocol and transfer report, if applicable
Options for Method Transfer
• Comparative testing:A set of samples are tested in both labs and resulting data are compared with predetermined acceptance criteria.
• Co-validation between two labs:The receiving laboratory is involved in method validation but have to identify which validation parameters are to be generated or challenged by the two labs.
• Complete or partial method validation:A repeat of method validation either completely or partially.
• Transfer waiver (omission of formal validation):Needs justification as to why method transfer was not needed. For example, lab is already testing the product.
Typical Method Transfer Steps
• Discussions Initiated
• Review of Method and Validation
• Laboratory Evaluation
• Gap assessment
• Protocol (Transfer or validation) Written
• Protocol Approved
• Experimental evidence from a transfer study generated
• Report (Transfer or validation) Written
• Report Approved
• Transfer Complete
Preparation for a Method Transfer
• Method
– Details about method
– Specific instrument
• Method development history report
• Training/discussion on the method
• Materials
– Reference Standard
– Samples for Evaluation
– Difficult to purchase supplies
• Specifications
• Technical Contact
• Details about product
Prior to Formal Method Transfer
Receiving laboratory should perform the method
– Helps to determine where there are differences and gaps in documentation
• Lack of detailed test method instructions
– Assay Conditions
– Calculations
– System Suitability
– Differences with instrumentation or reagents
Prior to Formal Method Transfer
• Training of Personnel
– Review of relevant SOPs
– Observation of test procedure
– Performing test procedure
• Helpful to include development, qualification and validation reports to recipient laboratory
Recommendations for Deviations
• If the tests don’t pass acceptance criteria, identify the source of the problem
• Develop corrective action plan– Provide additional training– Use other equipment
• Update the procedure
• Repeat the tests
• If successful, document initial results, corrective actions and final results
• If not successful, develop alternative procedure
Options for Method Transfer
• Comparative testing:A set of samples are tested in both labs and resulting data are compared with predetermined acceptance criteria.
• Co-validation between two labs:The receiving laboratory is involved in method validation but have to identify which validation parameters are to be generated or challenged by the two labs.
• Complete or partial method validation:A repeat of method validation either completely or partially.
• Transfer waiver (omission of formal validation):Needs justification as to why method transfer was not needed. For example, lab is already testing the product.
Option 1: Comparative Testing
• Most frequently used
• The same tests are carried out by both labs
• Should only be performed with validated methods
• Based on pre-approved transfer protocol
• Predetermined number of samples of the same lot
• Well defined test procedures and acceptance criteria, including acceptable variability
• Results are compared with a set of pre-determined acceptance criteria
• Ground rules for OOT/OOS results (preferably expired lot or non-GMP lot)
Steps for Comparative Testing
• Develop and approve a test plan
• Order missing equipment and materials
• Training
• Concurrent execution of the protocol
• Evaluation of test results– Compare with acceptance criteria
• Resolution of deviations, if there are any
• Gather all required documents
• Write method transfer report
Considerations for Testing
• Number of sample batches (1-3)
• One or more concentrations (1-3)
• Number of repetitive analysis / sample (4-6)
• One or more analysts? (1-2)
• One or more days? (2-5)
• Equipment from one or more manufacturers? (1 - all)
Comparative Testing
However, more often than we desire, deviation happens…
Case Study: Extraneous peaks associated with HPLC vialsA
U
0.000
0.001
0.002
0.003
0.004
0.005
0.006
0.007
0.008
0.009
0.010
Minutes
0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 6.50 7.00
3.1
08
3.6
70
RA
PA
MY
CIN
- 4
.133
Polypropylene
Deactivated glass vials
Case Study: Extraneous peaks associated with Glass PipettesA
U
-0.002
-0.001
0.000
0.001
0.002
0.003
0.004
0.005
0.006
0.007
0.008
0.009
0.010
0.011
Minutes
0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00
Unknow
n1 -
1.6
90
Unknow
n2 -
2.5
26
Unknow
n3 -
2.9
77
Unknow
n4 -
3.4
96
Rapam
ycin
- 3
.947
Above: chromatograms of two different lots of glass pipettes .Plastic transfer pipettes, or no pipettes, were recommended.
Case Study: Extraneous peaks associated with Extraction Vials
Extraction Vial
Volu
me
(mL)
Number
per case
Price
( $/case)
Price
($/vial) Comments
Nalgene-Teflon 10 10 224.70 22.47 Re usable. VWR Cat# 21009-422
30 10 333.30 33.33 Re usable. VWR Cat# 21009-455
BD Falcon-Poly
Propylene,
snap cap
5 500 160.00 0.32 VWR Cat # 60819-706
14 500 195.30 0.39 VWR Cat # 60819-740
BD Falcon-Poly
Propylene,
screw cap
15 500 220.89 0.44 VWR Cat# 21008-918
Starplex-
Polypropylene
screw cap
5 1500 186.18 0.12 only 2 sizes available VWR Cat#
14216-262
10 1000 135.96 0.14 only 2 sizes available VWR Cat#
14216-266
15 500 192.00 0.38 Sigma Aldrich Cat# Z720461 NUNC Poly
propylene snap cap
Supelco pre-cleaned
clear glass
7 100 92.50 0.93 Pre-cleaned* Sigma Aldrich Cat#
27341
15 100 102.50 1.03 Pre-cleaned* Sigma Aldrich Cat#
27342
22 100 116.00 1.16 Pre-cleaned* Sigma Aldrich Cat#
27343
Supelco Silanized
Clear Glass 4 1000 267.00 0.27
Larger sizes are available upon
request, caps not included.
Sigma Aldrich Cat# 27114
Kimble-glass
8 144 152.49 1.06 Currently being used VWR Cat#
66009-984
16 144 193.44 1.34 Currently being used VWR Cat#
66009-986
Treatment to Glass Extraction Vials
• Rinse with 0.02% formic acid in acetonitrile
• Rinse with acetonitrile
• Wash with a regular washing cycle for other glassware
• Soak with 0.02% acid (formic, acetic or nitric) in water and rinse with DI water
• Soak/sonicate in DI water
•Details are critical to ensure accurate comparison cross labs.
Standard Solution in Unwashed Glass Vials
0.00
0.50
1.00
1.50
2.00
2.50
3.00
3.50
0 1 2 3 4 5 6 7 8
Tota
l Im
pu
rity
Are
a%
Day
Standard Solution in Pre-cleaned Glass Vials
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
5
0 1 2 3 4 5 6 7 8
Tota
l Im
pu
rity
Are
a %
Day
2ml
3ml
4ml
5ml
6ml
7ml
9ml
10ml
Standard Solution in Silanized Glass Vials
Standard Solutions in Glass Vials Soaked and Sonicated in DI Water
Standard Solution in Glass Vials Rinsed with MeCN 3 Times
0
0.5
1
1.5
2
2.5
3
0 1 2 3 4 5 6 7 8
Tota
l Im
pu
rity
are
a %
Day
Direct pour
8ml- std soln-1
8ml- std soln-2
8ml- std soln-3
8ml- std soln-4
8ml- std soln-5
Standard Solution in Glass Vials Rinsed with 0.02% Formic Acid in MeCN 3 Times
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 1 2 3 4 5 6 7 8
Tota
l Im
pu
rity
Are
a%
Day
Direct pour
8ml- std soln-1
8ml- std soln-2
8ml- std soln-3
8ml- std soln-4
8ml- std soln-5
Standard Solutions in Glass Vials Treated with 0.02% Acid (Nitric, Acetic or formic)
Standard Solution in Washed Glass Vials
0
0.02
0.04
0.06
0.08
0.1
0 1 2 3 4 5 6 7
To
tal
imp
uri
ty %
Day
Standard in Washed Extraction Vial
2
3
4
5
6
7
9
10
Standard Solution in BD Falcon Polypropylene Vials
0.00
0.02
0.04
0.06
0.08
0.10
0.12
0.14
0.16
0 1 2 3 4 5 6 7
Tota
l Im
pu
rity
are
a%
Day
Polypropylene Ext vial-Small
small-1
small-2
small-3
small-4
small-5
small-6
small-7
small-8
small-9
Summary to Case Study: Extraneous peaks Associate with Glassware
• Pay attention to the glass grade, vendor and treatment.
• Glass vials vary within the same lot/box.
• Rinse with 0.02% acid (formic, acetic, nitric) acid in water is effective for this method.
• Wash the glass vials with acidic detergent is effective.
• Use of polypropylene vials eliminates the problem.
• It is critical for multiple labs to be involved, to carry our experiments and share data with details.
Method Transfer Option 2: Co-validation
Analytical Method Validation Characteristics
• Accuracy
• System repeatability
• Analysis repeatability
• Intermediate precision
• Reproducibility
• Specificity
• Forced degradation study
• Linearity
• Limit of quantitation (LOQ)
• Limit of detection (LOD)
• Range
• Robustness
• Stability of solutions
• Filtration study
• Method comparison
Option 2: Co-validation
• Receiving lab is part of original method validation• Transferring and receiving lab conduct the same validation
experiments• Useful for methods not (fully) validated• Must be based on pre-approved validation protocols and
acceptance criteria• Should challenge all USP or ICH validation parameters• Include receiving lab in validation through inter-laboratory
tests.• Ensures harmonization of method at both sites
A site that performs validation studies
is qualified to run the method
Definition of Method Validation Characteristics –Precision
• The precision of an analytical procedure expresses the closeness of agreement (degree of scatter) between a series of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions.
• The precision of an analytical procedure is usually expressed as the variance, standard deviation or coefficient of variation of a series of measurements.
• Precision may be considered at three levels: repeatability, intermediate precision and reproducibility.
Definition of Method Validation Characteristics –Precision (Cont.)
• Repeatability expresses the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision.
– System repeatability expresses the precision of an analytical instrument under the same operating conditions in a short time interval, e.g. the precision of multiple analysis of a single sample or reference preparation.
– Analysis repeatability expresses the precision of an analytical method, by the same analyst, under the same operating conditions over a short interval of time, e.g. the precision of the results for multiple sample preparations.
Definition of Method Validation Characteristics –Precision (Cont.)
• Intermediate precision expresses within-laboratory variation: different days, different analysts, different equipment, etc.
• Reproducibility expresses the precision between laboratories (collaborative studies, usually applied to standardization of methodology).
Validation Methodology and Acceptance Criteria –Precision/Intermediate Precision
• Acceptance criteria for API:
For drug product, the mean % label claim (% LC) results generated by each analyst can differ by not more than 3.0% (absolute difference). The precision for each analyst should be no more than 2.0%. For drug substance, the mean results generated can differ by NMT 2.0% (absolute difference) and the precision for each analyst should be no more than 1.0%.
• Acceptance Criteria for impurities:
Conc range Relative Diff between means of each analyst
Precision for each analyst
1.0 – 2.0 X RT 60% 25%
2.1 – 10 x RT 40% 15%
11 – 20 x RT 30% 10%
21 – 100 x RT 20% 5.0%
Validation Methodology and Acceptance Criteria –Precision/Reproducibility
• Acceptance criteria for API:
For drug product, the mean % label claim (% LC) results generated by each lab can differ by not more than 3.0% (absolute difference). The precision in each laboratory should be no more than 2.0%. For drug substance, the mean results generated can differ by NMT 2.0% (absolute difference) and the precision in each laboratory should be no more than 1.0%.
• Acceptance Criteria for impurities:
Conc range Relative Diff between means of each lab
Precision for each lab
1.0 – 2.0 X RT 60% 25%
2.1 – 10 x RT 40% 15%
11 – 20 x RT 30% 10%
21 – 100 x RT 20% 5.0%
Option 3: Full or Partial Revalidation
• Received lab repeats some or all of the validation experiment
• Done after initial method validation
• Validation parameters depend on the method
Method Transfer and Validation
Method Transfer• Can be part of the validation
• Protocol driven study with pre-defined acceptance criteria
• Transfer of validated analytical procedures to a new laboratory
• Verification of a method’s suitability for its intended use in a new laboratory
• Demonstration of a laboratory’s proficiency in running a particular method
• No official guidelines
Method Validation• Protocol driven study with pre-defined
acceptance criteria
• Validation of analytical procedures in a laboratory
• Verification of a method’s suitability for its intended use
• Demonstration of a laboratory’s proficiency in running a particular method
• http://www.ich.org/LOB/media/MEDIA417.pdf; http://www.fda.gov/cder/guidance/2396dft.pdf
Case study: Validation of HPLC and UPLC Assay & CU Method Side by Side Chromatograms of the Final Methods
HPLC
UPLC
AU
-0.004
-0.002
0.000
0.002
0.004
0.006
0.008
0.010
0.012
0.014
0.016
0.018
0.020
0.022
0.024
0.026
0.028
Minutes
1.00 2.00 3.00 4.00 5.00 6.00 7.00 8.00 9.00
2.1
81
2.5
77
3.0
59
3.3
90
3.5
95
RA
PA
MY
CIN
- 4
.055
4.9
79
BH
T -
7.1
96
AU
-0.002
0.000
0.002
0.004
0.006
0.008
0.010
0.012
Minutes
0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00
RA
PA
MY
CIN
- 2
.358
BH
T -
4.2
02
Case study: Validation of HPLC and UPLC Assay & CU Method Side by Side Chromatograms of the Final Methods
• Scenario:– HPLC assay & CU method was transferred before, but was modified
after the transfer.
– UPLC method was validated recently but was not transferred
– Receiving lab only qualified UPLC instrument and trained analysts recently
– UPLC method is the preferred method
• Decision:– Receiving lab performs the side-by-side validation of the revised
HPLC and UPLC method, on following parameters:• Accuracy
• Precision
• Linearity
Case study: Validation of HPLC and UPLC Assay & CU Method Side by Side Final Method Parameters
HPLC UPLCParameter Value
HPLC Column Agilent Zorbax Eclipse XDB-C18, 100 mm x 4.6
mm, 3.5 µm
Flow Rate 1.0 mL/min
Injection Volume 20 µL
Column
Temperature 45
oC 2C
Detection
Wavelength
Assay Identification
278 nm Note: If using an Agilent DAD
detector, set the bandwidth to 4 nm and
the reference wavelength off.
200 to 400
nm
Mobile Phases A: (20:80)THF: Formate Buffer
B: (75:20:5)ACN:THF:Formate Buffer
Gradient
Program
(Linear
Gradient)
Time (min) % Mobile
Phase A
% Mobile Phase
B
0.0 47 53
3.0 47 53
5.0 20 80
6.0 2 98
7.5 2 98
7.6 47 53
10 47 53
Parameter Value
UPLC
Column AgilentZorbax Eclipse XDB-C18, 100
mm x 3.0 mm, 1.8 µm
Flow Rate 0.7 mL/min
Injection
Volume 5 µL
Autosampler
Temperature
10 o
C
Column
Temperature 45
oC 2 C
Detection
Wavelength
Assay Sampling
Rate
278 nm
Note: If using an Agilent
DAD detector, set the
bandwidth to 4 nm and
the reference wavelength
off.
20
(points/sec)
Mobile
Phases
A: (20:80)THF: Formate Buffer
B: (75:20:5)ACN:THF:Formate
Buffer
Gradient
Program
(Linear
Gradient)
Time (min) % Mobile
Phase A
% Mobile
Phase B
0.0 47 53
2.0 47 53
3.5 20 80
4.2 2 98
5.2 2 98
5.3 47 53
6.5 47 53
Run Time 6.5 minutes (Retention time is ~2.5 min
for sirolimus, ~4.3 min for BHT.
Seal Wash Acetonitrile
Weak Wash Acetonitrile/water: 50/50, 600 µL
volume
Case study: Validation of HPLC and UPLC Assay Method Side by Side Accuracy (spiked recovery)
~Level
Actual
Concentration
(μg/mL)
Individual %
Recovery
Mean %
Recovery
%
RSD
40% 67.4
99.9
99.9 0.1 99.7
99.9
100% 151.7
99.5
99.6 0.2 99.8
99.5
160% 242.7
100.6
100.5 0.2 100.6
100.3
~Level
Actual
Concentration
(μg/mL)
Individual %
Recovery
Mean %
Recovery
%
RSD
40% 67.4
100.9
101.0 0.1 101.0
101.1
100% 151.7
99.4
99.6 0.2 99.6
99.8
160% 242.7
99.3
99.0 0.2 98.9
98.9
HPLC
UPLC
Validation of HPLC and UPLC CU Method Side by Side:Accuracy (spiked recovery)
HPLC
UPLC
~Level
Actual
Concentration
(μg/mL)
Individual
%
Recovery
Mean %
Recovery % RSD
40% 12.1
100.6
100.4 0.4 100.7
100.0
100% 30.3
98.9
98.9 0.1 98.8
99.0
160% 48.5
99.6
99.8 0.2 100.0
99.6
~Level
Actual
Concentration
(μg/mL)
Individual
%
Recovery
Mean %
Recovery % RSD
40% 12.1
100.9
101.2 0.3 101.6
101.3
100% 30.3
100.4
100.0 0.4 100.0
99.5
160% 48.5
100.4
101.3 0.9 102.2
101.5
Validation of HPLC and UPLC Assay Method Side by Side:Intermediate Precision
HPLC
UPLC
Determination %LC Analyst 1 %LC Analyst 2
1 103.1 103.4
2 101.9 102.6
3 101.4 103.0
4 101.6 103.0
5 102.4 103.4
6 102.2 104.0
Mean (n=6) 102.1 103.2
%RSD (n=12) 0.8
Determination %LC Analyst 1 %LC Analyst 2
1 103.8 101.3
2 101.8 102.1
3 100.9 102.3
4 100.6 102.2
5 101.8 102.7
6 102.2 102.9
Mean (n=6) 101.9 102.2
%RSD (n=12) 0.5
Validation of HPLC and UPLC CU Method Side by Side:Intermediate Precision
HPLC
UPLC
Determination %LC Analyst 1 %LC Analyst 2
1 101.5 102.7
2 102.0 104.2
3 101.0 102.3
4 103.4 102.3
5 105.1 102.3
6 101.3 101.7
7 103.1 102.6
8 103.1 102.7
9 102.1 102.7
10 102.9 102.0
Mean (n=10) 102.6 102.6
%RSD (n=20) 0.9
Determination %LC Analyst 1 %LC Analyst 2
1 102.0 103.4
2 101.6 103.7
3 101.3 103.4
4 100.4 102.7
5 102.6 102.2
6 101.0 101.7
7 101.7 103.6
8 100.8 102.6
9 101.6 102.9
10 101.4 102.2
Mean (n=10) 101.4 102.7
%RSD (n=20) 0.9
Validation of HPLC and UPLC Assay Method Side by Side:Linearity
HPLC
UPLC
R=0.9997
Validation of HPLC and UPLC CU Method Side by Side:Linearity
HPLC
UPLC
R=0.9997
R=1.0000
Summary of Case Study
• Partial validation proved to be most efficient and effective
• The same solutions were used in validating two methods side by side
• The knowledge of both methods were exchanged during the process
Option 4: Transfer Waivers
• Method is used without dedicated transfer testing
• Reasons should be well justified and documented
– The new product’s composition is comparable to that of an existing product and/or the concentration of active ingredient is similar to that of an existing product and is analyzed by procedures with which the receiving unit already has experience
– The analytical procedure transferred is the same as or very similar to a procedure already in use(ex. changes in calculations, volume ratios)
– The personnel in charge of the development, validation or routine analysis of the product at the transferring unit are moved to the receiving unit
– Transfer of compendial methods (refer to USP <1226>)
– Method validation package encompasses the new methods
Waiver should be well justified and documented
Method Development Life Cycle
Planning
Development and Validation Policy
Objectives/Requirements of Method
Information Gathering
Resource Gathering
Method developmentInitital Method Development
Pre-Validation Evaluation
Method Optimization
Robustness
System Suitability
Development
Plan –
Project
Customer Evaluation
Testing Validation
Method Transfer Filed Method in Use
Periodically
Monitoring/Review
of Methods
in Testing Labs
• Is the method inadequate by today’s scientific standard or regulatory requirement?
• Is sufficient data available to permit simplification of the method?
• Does monitoring of laboratory deviation suggest a need for method improvement ?
• Do newer method for similar products significantly outperform?
• Is the volume of testing justify further method optimization or automation?
Periodically Monitoring/Review of Methods in Testing Labs
Analytical Procedures and Methods Validation for Drugs and Biologics: FDA Guidance July 2015
Analytical Procedures and Methods Validation: FDA Guidance Aug 2000
Method remediation initiatives
What is New in FDA Guidance July 2015:Life Cycle Management of Analytical Procedures
• Method transfer is a critical milestone in the life cycle of analytical methods
• Method transfer is a team effort which needs strategic planning, adequate communication and flawless execution.
• Four options of method transfer:
1. Comparative testing - Most popular
2. Co-validation between two labs - team up for trouble shooting
3. Complete or partial method validation – Two birds with one stone
4. Transfer waiver – Justification and documentation
• Method transfer should be a two-way, dynamic process.
Summary
