Method Validation Report for XXX
Report No.: XXX
Prepared by: XXX
Title
Dept
Reviewed by: XXX
Title
Dept
Approved by: XXX
Title
Dept
Approved by: XXX
Title
Dept
TABLE OF CONTENTS
Section Page
1.0 XXXX
2.0 XXXX
3.0 XXXX
4.0 XXXX
5.0 XXXX
6.0 XXXX
7.0 XXXX
8.0 XXXX
9.0 XXXX
10.0 XXXX
11.0 XXXX
1. Validation Background
X Describe the background / intent of this validation X
1.1. Validated Formulations
Method XXX has been validated for the related formulas described in Table X
Table 1: Validated Formulas
Component Level
XXXXXX XX mg per YYY
XXXXXX XX mg per YYY
XXXXXX XX mg per YYY
XXXXXX XX mg per YYY
1.2. Degradation Products Studied
A summary of the degradation products of the active ingredient(s) that is likely to form is
shown in Table X.
Table X Known Degradation Products Observed XXX Dosage Forms
Active Degradation Product Route Comments
XXX XXX Hydrolysis product Validation performed
Will be included in the XXX
XXX Hydrolysis product
method
Method is not specific, but will
XXX Process Impurity
include a retention time marker
XXX Method is specific, and will
XXX Process Impurity
include a retention time marker
Forced degradation studies show
XXX Possible hydrolysis product this is not formed in these
products.
2. Validation Summary
2.1. Validated Ranges
The method has been demonstrated to be validated over the specification range for the
following:
Table 3: Validated Ranges
Analyte Specification Validated Range
Range
XXX XX.X - XX.X% XX.X - XX.X%
XXX XX.X - XX.X% XX.X - XX.X%
XXX XX.X - XX.X% XX.X - XX.X%
Additional Comments for the table here.
3. Deviations During Validation
Description of any deviations here and associated references to approvals.
Table 4: Summary of Deviations
Deviation Attribute Corrective Action Preventative Action
Deviation XXX: XXXX • XXX. • XXXX
• XXXX. .
4. Validation Results for Suitability, Linearity, Accuracy and Recovery
4.1. System Suitability
Table X: System Suitability and System Precision Results
Tailing Factor
System Precision Resolution between xxx
Replicate
(area, height) and xxx xxx xxx
Mean
%RSD
Acceptance Criteria
Pass/Fail
Notebook Reference XXXX
4.2. Linearity, Accuracy and Precision Studies
Linearity, accuracy, and recovery studies for the validated degradation products are
summarized in Tables XXX-YYY.
All results meet the acceptance criteria through the validated ranges presented in Table X.
Table X: Analyte Accuracy, Linearity, Recovery and Precision
Acceptance Mean Acceptance Acceptance
Level Concentration % Recovery Criteria Criteria %RSD Criteria
Recovery
Individuals Mean % RSD
XX.XX%
XX.X% XX.X- XX.X-
XX.X% XX.XX% XX.X x.x% x.x%
XXX.X% XXX.X%
XX.XX%
XX.XX%
XX.X% XX.X- XX.X-
XX.X% XX.XX% XX.X x.x% x.x%
XXX.X% XXX.X%
XX.XX%
XX.XX%
XX.X% XX.X- XX.X-
XX.X% XX.XX% XX.X x.x% x.x%
XXX.X% XXX.X%
XX.XX%
XX.XX%
XX.XX%
XX.X% XX.XX% XX.X- XX.X-
XX.X% XX.X x.x% x.x%
XX.XX% XXX.X% XXX.X%
XX.XX%
XX.XX%
XX.XX%
XX.X% XX.X- XX.X-
XX.X% XX.XX% XX.X x.x% x.x%
XXX.X% XXX.X%
XX.XX%
Parameter Result Acceptance Criteria
Correlation Coefficient X.XX > 0.XX
Slope XXXX NA
Y-Intercept XXX
XXXX
Notes
1. XXXXXXXXXXXXXXXXXX
2. References:
Figure X: XXX Linear Regression
Insert Figure Here
4.3. Range
The validated range was established from the accuracy and precision levels that met the
acceptance criteria specified in SOP XXX and summarized in Section X.X. The
validated ranges are shown in Table X.
Table X: Validated Ranges
Analyte Specification Validated Range
Range Solution
% Analyte
Concentration
XX.XX% - XX.XX-XX.XX XX.XX% -
XXXXX
XX.XX% ppm XX.XX%
XX.XX% - XX.XX-XX.XX XX.XX% -
XXXXX
XX.XX% ppm XX.XX%
Notebook Reference: XXX
In all cases, the acceptance criteria were met for all spiking levels.
4.4. Reproducibility
One analyst from GROUP and one analyst GROUP performed ASSAY analysis on XX
sample preparations as directed in the method validation protocol. All results met the
reproducibility acceptance criteria of each impurity.
Table XX: Reproducibility for Analyte
Replicate ANALYTE Acceptance
Criteria
Analyst 1 Analyst 2
(R&D) (QC)
1 XX.X% XX.X%
2 XX.X% XX.X%
3 XX.X% XX.X%
4 XX.X% XX.X%
5 XX.X% XX.X%
6 XX.X% XX.X%
Mean XX.X% XX.X%
%RSD XX.X% XX.X% <XX%
Relative
difference of X.X +XX%
means
Reference: XX
4.5. Limit of Quantitation (QL) and Limit of Detection (DL) for ANALYTE
The limit of quantitation and limit of detection were determined by checking the S/N
ratios for a series of spiked placebo sample solutions. Each level was prepared in
triplicate to establish accuracy and precision at that level for each known impurity.
Table XX: Low Level Recovery for ANALYTE QL/DL Determination
Reporting Threshold = 0.05%
Input Input Input Input Acceptance
0.005% 0.010% 0.020% 0.025% Criteria
XX.XX XX.XX XX.XX XX.XX
% % % %
% XX.XX XX.XX XX.XX XX.XX XX.X-
Recovered % % % % XXX.X%
XX.XX XX.XX XX.XX XX.XX
% % % %
Level XX.XX XX.XX XX.XX XX.XX
Mean % % % %
RSD X.X X.X X.X X.X NMT XX.X%
XX QL: S/N >10
S/N
(QL) DL: S/N >3
Notes: S/N = Signal to Noise, QL=Quantitation Limit, DL=Detection Limit
Detection Limit is X.XXX%
Reference: XXX
4.6. Linearity for Low Level ACTIVE Analytes
Linearity of response for Analytes has been demonstrated from solutions of these
ANALYTES at a minimum of five levels bracketing the specification levels. The
response of each active is linear over the described range.
Table XX: Linearity of Low Level Analyte
Acceptance
% ANALYTE ppm Area
Criteria
XX.XX XX.XX XXXXX
XX.XX XX.XX XXXXX
XX.XX XX.XX XXXXX
XX.XX XX.XX XXXXX
XX.XX XX.XX XXXXX
Correlation Coefficient XX.XX >0.XX
Slope XXXXX
Y-Intercept XXXXX
References: X
Figure X: Linear Regression for Low Level ACTIVE Analyte
Insert Figure Here
Table X Low Level ACTIVE Analyte Accuracy and Recovery
Acceptance Acceptance Acceptance
% Mean
Level Concentration Criteria Criteria %RSD Criteria
Recovery Recovery
Individuals Mean % RSD
XX.XX
0.XX% XX.X- XX.X-
0.XX% XX.XX XXX.X X.X X.X
(RT) XXX.X% XXX.X%
XX.XX
XX.XX
XX.X- XX.X-
0.XX% 0.XX% XX.XX XXX.X X.X X.X
XXX.X% XXX.X%
XX.XX
XX.XX
XX.X- XX.X-
0.XX% 0.XX% XX.XX XXX.X X.X X.X
XXX.X% XXX.X%
XX.XX
XX.XX
XX.X- XX.X-
0.XX% 0.XX% XX.XX XXX.X X.X X.X
XXX.X% XXX.X%
XX.XX
Reference: XXXXX
RT= Reporting Threshold
5. Relative Response Factors
The Relative Response Factors for the degradation products studied in this report have
been established previously and are summarized in Table XX.
In this work, Relative Response Factors for X degradation products (Analytes) were
determined by performing linear regression analysis on the mean area for each impurity
at each level versus the % label claim and then comparing the slope of the response line
to that of its parent peak obtained under section X.X. The concentration levels used are
given in Table XX, and the calculated RRFs are given in Table XX.
Table XX: RRFs Previously Determined
Related
Active Degradation RRF Reference
Product
ANALYTE X.XX
ANALYTE X.XX
XXX XXXXXXX
ANALYTE X.XX
ANALYTE X.XX
Table XX: Linearity of Low Level DEGRADATION PRODUCT ANALYTE
ANALYTE
% Area
X.XX XXX
X.XX XXX
X.XX XXX
X.XX XXX
X.XX XXX
X.XX XXX
Reference: XXX
Table XX: Calculated RRF Values
Name RRF
DEGRADATION X.XX
PRODUCT ANALYTE
DEGRADATION X.XX
PRODUCT ANALYTE
DEGRADATION X.XX
PRODUCT ANALYTE
DEGRADATION X.XX
PRODUCT ANALYTE
Reference: XXX
Figure XX: Linear Regression for Low Level DEGRADATION PRODUCT
INSERT FIGURE HERE
6. Solution Stability
The TEST standard solutions for injection were prepared for XXX. One stock solution was
prepared and a portion was stored at XºC as well as room temperature. Freshly diluted
standard solutions for injection were prepared at X and X days from the initial stock solution
at room temperature. The refrigerated stock solution was used to prepare standard solutions
for injection at X, X, X, and X days.
Both original preparations and freshly diluted standard solutions from XºC and room
temperature conditions were analyzed up to X days. These solutions met the acceptance
criteria given in the method validation protocol for X days at room temperature and X days at
XºC (see Tables XXX).
Table XX: Standard solution stability for ANALYTE
% Difference at XºC % Difference at RT
Time Point Freshly Freshly
Original Original
diluted diluted
0 (Initial) N/A N/A N/A N/A
Day 1 X.X X.X X.X X.X
Day 2 X.X X.X X.X X.X
Day 5 X.X X.X X.X X.X
Day 7 X.X X.X X.X X.X
Acceptance
<X.X% <X.X% <X.X% <X.X%
Criteria
Reference
A sample spiked with X.X% of DEGRADATION PRODUCTS was prepared. The spiked
sample was analyzed after X, X and X days storage at XºC and room temperature. The
acceptance criteria given in the method validation protocol was satisfied for all known
impurities for X days at room temperature and X days at X ºC (see Tables XX-XX).
Table XX: Solution stability of spiked sample at XºC and room temperature (RT)
Time Point ANALYTE ANALYTE ANALYTE
(0.X%) (0.X%) (0.X%)
4ºC RT 4ºC RT 4ºC RT
0 (Initial) X.XX X.XX X.XX X.XX X.XX X.XX
Day 1 X.XX X.XX X.XX X.XX X.XX X.XX
Day 2 X.XX X.XX X.XX X.XX X.XX X.XX
Day 3 X.XX X.XX X.XX X.XX X.XX X.XX
Greatest difference
X.XX X.XX X.XX X.XX X.XX X.XX
from initial (%)
Acceptance Criteria + X% + X% + X% + X% + X% + X%
REFERENCE
Figures XX-XX show representative chromatograms of a spiked sample solution analyzed at
initial and Xdays.
Insert figures here.
7. Specificity
The method is specific for the compounds listed in Error! Reference source not found.
Table X: Specificity
Result % Placebo
Active Degradation Product Comments
Interference
ANALYTE Specific X.XX%
ACTIVE ANALYTE
ANALYTE Not specific X.XX% DETERMINED IN
METHOD YYY.
ANALYTE
ANALYTE Not specific X.XX% DETERMINED IN
METHOD YYY.
ACTIVE ANALYTE Specific X.XX%
Forced degradation studies
ANALYTE Not specific X.XX% show this is not formed in
these products.
Insert Figures Here
Figure X: Overlay of 10x Placebo and Spiked Sample
8. Robustness
Discuss robustness parameters evaluated. For Example: The effect of changes in the
gradient program and composition of mobile phase were evaluated.
8.1. Effect of Change in the Gradient Program
The original method gradient conditions are listed below:
Table XX: Original method gradient
%A Mobile %B Mobile
Time
Phase Phase
X 100 0
X 100 0
X X X
X X X
X X X
X 0 100
X 0 100
X 100 0
The gradient composition at X minutes was changed from XX:XX to XX:XX. The
XX:XX ratio is too extreme for accurate peak identification.
One prepared sample containing X.X% levels of the known impurities was evaluated by
two analysts from different labs on different days using different HPLC systems and
different solution preparations
An example chromatogram showing the affected region is presented in Figure XX.
Insert Figures HERE:
The % label claim results are summarized in Tables XX-XX.. The results are well within
the listed acceptance criteria showing that either gradient program can be used for regular
testing provided system suitability is met.
Table XX: Effect of change in gradient composition-Analyst 1
% LC % LC
Relative
ANALYTE (XX:XX) at XX (XX:XX) at XX
Difference (%)
minutes minutes
ANALYTE X.XX X.XX X.X
ANALYTE X.XX X.XX X.X
ANALYTE X.XX X.XX X.X
REFERENCE
Table XX: Effect of change in gradient composition-Analyst 2
% LC % LC
Relative
ANALYTE (XX:XX) at XX (XX:XX) at XX
Difference (%)
minutes minutes
ANALYTE X.XX X.XX X.X
ANALYTE X.XX X.XX X.X
ANALYTE X.XX X.XX X.X
8.2. Effect of Change in Composition of Mobile Phase X
The mobile phase composition consists of an A and B preparation. Mobile phase A is a XX:XX
ratio of CONCENTRATION OF buffer, pH X: solvent, and mobile phase B is XX:XX buffer
CONCENTRATION OF X,, pH 3.0: solvent.
The composition of SOLVENT in mobile phase B was changed by ±X%. One prepared sample
containing 0.X% levels of the known impurities was evaluated by one analyst
Representative chromatograms are shown in Figures XX-XXX.. The % label claim results for
each known spiked impurity are presented in Tables XX-XX. The acceptance criteria for
robustness was met for all ANALYTES.
The method is robust with respect to +2% changes in buffer percentage of mobile phase B.
Insert representative chromatograms here.
Table XX: Effect of Change in Mobile Phase X Composition
Composition of Mobile ANALYTE ANALYTE ANALYTE
Phase X % % Diff % % Diff % % Diff
(XX:XX) X.XX X.XX X.XX X.XX X.XX X.XX
Buffer :Solvent
(XX:XX) X.XX X.XX X.XX X.XX X.XX X.XX
Buffer :Acetonitrile
(XX:XX) X.XX X.XX X.XX X.XX X.XX X.XX
Buffer :Acetonitrile
Reference
9. Forced Degradation Studies
Table XX: Forced Degradation Studies for Placebo
Stress Condition RRT/(Area %) Pass/Fail
Unstressed Control
Heat Stress
X days, X°C
Photolysis
2xICH Option 2
Oxidation
Xx% H2O2 for xx hrs
Acid
x.x N HCl for xx hrs hrs
Base
x.x N NaOH for xx hrs
Insert Figures Here
Table XX: Forced Degradation Studies for SAMPLE
Stress Condition RRT/(Area %) Pass/Fail
Unstressed Control
Heat Stress
X days, X °C
Photolysis
2xICH Option 2
Oxidation
Xx% H2O2 for xx hrs
Acid
x.x N HCl for xx hrs hrs
Base
x.x N NaOH for xx hrs
Insert Figures Here
10. Filter Study
Describe filter study (different brands or volume discarded)
Volume Discarded ANALYTE ANALYTE ANALYTE
Control
(centrifuged)
x mL
%diff. from control
x mL
%diff. from control
x mL
%diff. from control
Pass/Fail
Reference
11. Method Equivalency
Describe the two methods and the differences between them.
Table 1: Method Equivalency Results
Test Method No. Test Method no. (with revision) Test Method no. (with revision)
Replicate # ANALYTE ANALYTE ANALYTE ANALYTE
Mean
%RSD
% Difference
Reference
11.0 CONCLUSION
The test method for the analysis of XXXXXX in XXXXXXXXXX, has been validated
according to Protocol XXXXXXXXXXX. The data in this report were compared to the protocol
requirements, and the protocol requirements were met. The method is considered suitable for
intended use.
.
