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TABLE OF CONTENTS
Section
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
11.0
Page
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1. Validation Background
Level
XX mg per YYY
XXXXXX
XX mg per YYY
XXXXXX
XX mg per YYY
XXXXXX
XX mg per YYY
Degradation Product
Route
Comments
XXX
XXX
Hydrolysis product
Validation performed
XXX
Hydrolysis product
XXX
Process Impurity
XXX
Process Impurity
XXX
XXX
2. Validation Summary
2.1. Validated Ranges
The method has been demonstrated to be validated over the specification range for the
following:
Analyte
XXX
XXX
XX.X - XX.X%
XX.X - XX.X%
XXX
XX.X - XX.X%
XX.X - XX.X%
Attribute
XXXX
Corrective Action
XXX.
.
Preventative Action
XXXX
Replicate
System Precision
(area, height)
Tailing Factor
xxx
xxx
1
2
3
4
5
Mean
%RSD
Acceptance Criteria
Pass/Fail
Concentration
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
Parameter
Correlation Coefficient
Slope
Y-Intercept
% Recovery
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
XX.XX%
Result
X.XX
XXXX
XXXX
Notes
1. XXXXXXXXXXXXXXXXXX
2. References:
Acceptance
Criteria
Individuals
Mean
Recovery
%RSD
Acceptance
Criteria
% RSD
XX.XXXX.X%
XX.X
XX.XXXX.X%
x.x%
x.x%
XX.XXXX.X%
XX.X
XX.XXXX.X%
x.x%
x.x%
XX.XXXX.X%
XX.X
XX.XXXX.X%
x.x%
x.x%
XX.XXXX.X%
XX.X
XX.XXXX.X%
x.x%
x.x%
XX.XXXX.X%
XX.X
XX.XXXX.X%
x.x%
x.x%
Acceptance Criteria
> 0.XX
NA
XXX
Acceptance
Criteria
Mean
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.
Analyte
XXXXX
XXXXX
XX.XX% XX.XX%
XX.XX% XX.XX%
XX.XX-XX.XX
ppm
XX.XX-XX.XX
ppm
XX.XX% XX.XX%
XX.XX% XX.XX%
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.
1
2
3
4
5
6
Mean
%RSD
Relative
difference of
means
Reference: XX
ANALYTE
Analyst 1
(R&D)
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
X.X
Analyst 2
(QC)
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
XX.X%
Acceptance
Criteria
<XX%
+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.
ppm
Area
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XXXXX
XXXXX
XXXXX
XXXXX
XXXXX
Correlation Coefficient
Slope
Y-Intercept
References: X
XX.XX
XXXXX
XXXXX
Acceptance
Criteria
>0.XX
Concentration
0.XX%
(RT)
0.XX%
0.XX%
0.XX%
0.XX%
0.XX%
0.XX%
0.XX%
%
Recovery
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
XX.XX
Acceptance
Criteria
Individuals
Mean
Recovery
Acceptance
Criteria
Mean
%RSD
Acceptance
Criteria
% RSD
XX.XXXX.X%
XXX.X
XX.XXXX.X%
X.X
X.X
XX.XXXX.X%
XXX.X
XX.XXXX.X%
X.X
X.X
XX.XXXX.X%
XXX.X
XX.XXXX.X%
X.X
X.X
XX.XXXX.X%
XXX.X
XX.XXXX.X%
X.X
X.X
Reference: XXXXX
RT= Reporting Threshold
XXX
Related
Degradation
Product
ANALYTE
ANALYTE
ANALYTE
ANALYTE
RRF
X.XX
X.XX
X.XX
X.XX
Reference
XXXXXXX
Reference: XXX
Table XX: Calculated RRF Values
Name
DEGRADATION
PRODUCT ANALYTE
DEGRADATION
PRODUCT ANALYTE
DEGRADATION
PRODUCT ANALYTE
DEGRADATION
PRODUCT ANALYTE
RRF
X.XX
X.XX
X.XX
X.XX
Reference: XXX
6. Solution Stability
The TEST standard solutions for injection were prepared for XXX. One stock solution was
prepared and a portion was stored at XC 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 XC 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
XC (see Tables XXX).
Table XX: Standard solution stability for ANALYTE
Time Point
0 (Initial)
Day 1
Day 2
Day 5
Day 7
Acceptance
Criteria
% Difference at XC
Freshly
Original
diluted
N/A
N/A
X.X
X.X
X.X
X.X
X.X
X.X
X.X
X.X
% Difference at RT
Freshly
Original
diluted
N/A
N/A
X.X
X.X
X.X
X.X
X.X
X.X
X.X
X.X
<X.X%
<X.X%
<X.X%
Reference
<X.X%
A sample spiked with X.X% of DEGRADATION PRODUCTS was prepared. The spiked
sample was analyzed after X, X and X days storage at XC 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 C (see Tables XX-XX).
Table XX: Solution stability of spiked sample at XC and room temperature (RT)
Time Point
0 (Initial)
Day 1
Day 2
Day 3
Greatest difference
from initial (%)
Acceptance Criteria
ANALYTE
(0.X%)
4C
RT
X.XX X.XX
X.XX X.XX
X.XX X.XX
X.XX X.XX
ANALYTE
(0.X%)
4C
RT
X.XX X.XX
X.XX X.XX
X.XX X.XX
X.XX X.XX
ANALYTE
(0.X%)
4C
RT
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
+ 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
Active
Result
% Placebo
Interference
ANALYTE
Specific
X.XX%
ANALYTE
Not specific
X.XX%
ANALYTE
Not specific
X.XX%
ANALYTE
Specific
X.XX%
ANALYTE
Not specific
X.XX%
Degradation Product
ACTIVE
ACTIVE
Comments
ANALYTE
DETERMINED IN
METHOD YYY.
ANALYTE
DETERMINED IN
METHOD YYY.
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
Time
X
X
X
X
X
X
X
%A Mobile
Phase
100
100
X
X
X
0
0
%B Mobile
Phase
0
0
X
X
X
100
100
100
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
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.
% LC
(XX:XX) at XX
minutes
X.XX
X.XX
X.XX
% LC
(XX:XX) at XX
minutes
X.XX
X.XX
X.XX
Relative
Difference (%)
X.X
X.X
X.X
REFERENCE
8.2.
% LC
(XX:XX) at XX
minutes
X.XX
X.XX
X.XX
% LC
(XX:XX) at XX
minutes
X.XX
X.XX
X.XX
Relative
Difference (%)
X.X
X.X
X.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.
ANALYTE
%
% Diff
X.XX
X.XX
ANALYTE
%
% Diff
X.XX
X.XX
ANALYTE
%
% Diff
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
X.XX
Reference
Stress Condition
Unstressed Control
Heat Stress
X days, XC
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
RRT/(Area %)
Pass/Fail
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
Reference
ANALYTE
ANALYTE
ANALYTE
ANALYTE
ANALYTE
ANALYTE
ANALYTE
1
2
3
4
5
6
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.
.