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
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

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
XXXXXX

Level
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

XXX

Hydrolysis product

XXX

Process Impurity

XXX

Process Impurity

XXX

Possible hydrolysis product

XXX

Will be included in the XXX

method
Method is not specific, but will
include a retention time marker
Method is specific, and will
include a retention time marker
Forced degradation studies show
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:

Analyte
XXX

Table 3: Validated Ranges

Specification
Validated Range
Range
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
Deviation XXX:
XXXX.

Attribute
XXXX

Corrective Action
XXX.
.

Preventative Action
XXXX

4. Validation Results for Suitability, Linearity, Accuracy and Recovery

4.1. System Suitability
Table X: System Suitability and System Precision Results

Replicate

System Precision
(area, height)

Resolution between xxx

and xxx

Tailing Factor
xxx

xxx

1
2
3
4
5
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

Level

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

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.

Analyte

Table X: Validated Ranges

Specification
Validated Range
Range
Solution
% Analyte
Concentration

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%

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

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.

Table XX: Low Level Recovery for ANALYTE QL/DL Determination

Reporting Threshold = 0.05%
Acceptance
Input
Input
Input
Input
Criteria
0.005% 0.010% 0.020% 0.025%
XX.XX XX.XX XX.XX XX.XX
%
%
%
%
%
XX.XX XX.XX XX.XX XX.XX
XX.XRecovered
%
%
%
%
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

% ANALYTE

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

Figure X: Linear Regression for Low Level ACTIVE Analyte

InsertFigureHere

Table X Low Level ACTIVE Analyte Accuracy and Recovery

Level

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

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
Active

XXX

Related
Degradation
Product
ANALYTE
ANALYTE
ANALYTE
ANALYTE

RRF
X.XX
X.XX
X.XX
X.XX

Reference

XXXXXXX

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
DEGRADATION
PRODUCT ANALYTE
DEGRADATION
PRODUCT ANALYTE
DEGRADATION
PRODUCT ANALYTE
DEGRADATION
PRODUCT ANALYTE

RRF
X.XX
X.XX
X.XX
X.XX

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 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.

Forced degradation studies

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
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

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

ANALYTE
ANALYTE
ANALYTE
ANALYTE

% 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

Table XX: Effect of change in gradient composition-Analyst 2

ANALYTE
ANALYTE
ANALYTE
ANALYTE

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

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
Phase X
(XX:XX)
Buffer :Solvent
(XX:XX)
Buffer :Acetonitrile
(XX:XX)
Buffer :Acetonitrile

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

9. Forced Degradation Studies

Table XX: Forced Degradation Studies for Placebo

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

Insert Figures Here

RRT/(Area %)

Pass/Fail

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
Control
(centrifuged)
x mL

%diff. from control

x mL

%diff. from control

x mL

%diff. from control

Pass/Fail

Reference

ANALYTE

ANALYTE

ANALYTE

11. Method Equivalency

Describe the two methods and the differences between them.
Table 1: Method Equivalency Results
Test Method No.
Replicate #

Test Method no. (with revision)

Test Method no. (with revision)

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.
.