abbie gentry method validation report

7/24/2019 Abbie Gentry Method Validation Report

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Method Validation Report for XXX

Report No.: XXX

Prepared by: XXX

Title

Dept

Reviewed by: XXX

Title

Dept

Approved by: XXXTitle

Dept

Approved by: XXX

Title

Dept


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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 Level

XXXXXX XX mg per YYY





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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

XXX Hydrolysis productWill be included in the XXX

method

XXX Process Impurity Method is not specific, but willinclude a retention time marker

XXX Process ImpurityMethod is specific, and will

include a retention time marker

XXX Possible hydrolysis productForced degradation studies show

this is not formed in these

products.


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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 SpecificationRange

Validated Range

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.


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Table 4: Summary of Deviations

Deviation Attribute Corrective Action Preventative Action

Deviation XXX:

XXXX.

XXXX XXX..

XXXX

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

4.1.System Suitability

Table X: System Suitability and System Precision Results

ReplicateSystem 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.


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Table X: Analyte Accuracy, Linearity, Recovery and Precision

Level Concentration % RecoveryAcceptance

Criteria

Individuals

Mean

Recovery

Acceptance

Criteria

Mean

%RSDAcceptance

Criteria

% RSD

XX.X%XX.X%

XX.XX%XX.X-

XXX.X%XX.X

XX.X-

XXX.X%x.x% x.x%XX.XX%

XX.XX%

XX.X%XX.X%

XX.XX%XX.X-

XXX.X%XX.X

XX.X-


XX.XX%

XX.X%XX.X%

XX.XX%XX.X-

XXX.X%XX.X

XX.X-


XX.XX%

XX.X%XX.X%

XX.XX%

XX.X-

XXX.X%XX.X

XX.X-

XXX.X%x.x% x.x%

XX.XX%

XX.XX%

XX.XX%

XX.XX%

XX.XX%

XX.X%XX.X%

XX.XX%XX.X-

XXX.X%XX.X

XX.X-


XX.XX%

Parameter Result Acceptance Criteria

Correlation Coefficient X.XX > 0.XX

Slope XXXX NA

Y-InterceptXXXX

XXX

Notes

1. XXXXXXXXXXXXXXXXXX

2. References:


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Figure X: XXX Linear Regression

Insert Figure Here


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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 SpecificationRange

Validated Range

Solution

Concentration% Analyte

XXXXXXX.XX% -

XX.XX%

XX.XX-XX.XX

ppm

XX.XX% -

XX.XX%

XXXXXXX.XX% -

XX.XX%

XX.XX-XX.XX

ppm

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.


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Table XX: Reproducibility for AnalyteReplicate ANALYTE Acceptance

Criteria

Analyst 1

(R&D)

Analyst 2

(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%


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

Reporting Threshold = 0.05%

Input

0.005%

Input

0.010%

Input

0.020%

Input

0.025%

Acceptance

Criteria

%Recovered

XX.XX%

XX.XX%

XX.XX%

XX.XX%

XX.X-XXX.X%

XX.XX%

XX.XX%

XX.XX%

XX.XX%

XX.XX

%

XX.XX

%

XX.XX

%

XX.XX

%

Level

Mean

XX.XX

%

XX.XX

%

XX.XX

%

XX.XX

%

RSD X.X X.X X.X X.X NMT XX.X%

S/N XX(QL) QL: S/N >10DL: S/N >3Notes: 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 AreaAcceptance

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


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Figure X: Linear Regression for Low Level ACTIVE Analyte

InsertFigureHere


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Table X Low Level ACTIVE Analyte Accuracy and Recovery

Level Concentration%

Recovery

Acceptance

Criteria

Individuals

Mean

Recovery

Acceptance

Criteria

Mean

%RSD

Acceptance

Criteria

% RSD

0.XX%

(RT)0.XX%

XX.XXXX.X-

XXX.X%XXX.X

XX.X-

XXX.X%X.X X.XXX.XX

XX.XX

0.XX% 0.XX%

XX.XXXX.X-

XXX.X%XXX.X

XX.X-

XXX.X%X.X X.XXX.XX

XX.XX

0.XX% 0.XX%

XX.XXXX.X-

XXX.X%XXX.X

XX.X-

XXX.X%X.X X.XXX.XX

XX.XX

0.XX% 0.XX%

XX.XXXX.X-

XXX.X%

XXX.XXX.X-

XXX.X%

X.X X.XXX.XX

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

Active

Related

DegradationProduct

RRF Reference

XXX

ANALYTE X.XX

XXXXXXXANALYTE X.XX

ANALYTE X.XX

ANALYTE X.XX


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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

PRODUCT ANALYTE

X.XX

DEGRADATION

PRODUCT ANALYTE

X.XX

DEGRADATION

PRODUCT ANALYTE

X.XX

DEGRADATION

PRODUCT ANALYTE

X.XX

Reference: XXX


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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 knownimpurities 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 ANALYTE

(0.X%)

ANALYTE

(0.X%)

ANALYTE

(0.X%)

4C RT 4C RT 4C 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



Greatest difference

from initial (%)X.XX X.XX X.XX X.XX X.XX X.XX

Acceptance Criteria + X% + X% + X% + X% + X% + X%

REFERENCE

Figures XX-XX show representative chromatograms of a spiked sample solution analyzed atinitial and Xdays.

Insert figures here.


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7. Specificity

The method is specific for the compounds listed in Error! Reference source not found.

Table X: Specificity

Active Degradation ProductResult % Placebo

InterferenceComments

ACTIVE

ANALYTE Specific X.XX%

ANALYTE Not specific X.XX%

ANALYTE

DETERMINED IN

METHOD YYY.

ACTIVE

ANALYTE Not specific X.XX%ANALYTE

DETERMINED IN

METHOD YYY.

ANALYTE Specific X.XX%

ANALYTE Not specific X.XX%

Forced degradation studies

show this is not formed in

these products.


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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 thegradient 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%A Mobile

Phase

%B Mobile

Phase

X 100 0

X 100 0

X X X

X X X

X X X

X 0 100

X 0 100


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X 100 0

The gradient composition at X minutes was changed from XX:XX to XX:XX. TheXX: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 regulartesting provided system suitability is met.


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Table XX: Effect of change in gradient composition-Analyst 1

ANALYTE

% LC

(XX:XX) at XX

minutes

% LC

(XX:XX) at XX

minutes

Relative

Difference (%)

ANALYTE X.XX X.XX X.X



REFERENCE

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

ANALYTE

% LC

(XX:XX) at XXminutes

% LC

(XX:XX) at XXminutes

Relative

Difference (%)




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 bufferCONCENTRATION 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 forrobustness 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.


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Table XX: Effect of Change in Mobile Phase X Composition

Composition of Mobile

Phase X

ANALYTE ANALYTE ANALYTE

% % Diff % % Diff % % Diff

(XX:XX)

Buffer :Solvent

X.XX X.XX X.XX X.XX X.XX X.XX

(XX:XX)

Buffer :Acetonitrile


(XX: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, XC

Photolysis

2xICH Option 2

Oxidation

Xx% H2O2for xx hrs

Acid

x.x N HCl for xx hrs hrs

Base

x.x N NaOH for xx hrs

Insert Figures Here


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Table XX: Forced Degradation Studies for SAMPLE

Stress Condition RRT/(Area %) Pass/Fail

Unstressed Control

Heat Stress

X days, XC

Photolysis

2xICH Option 2

Oxidation

Xx% H2O2for xx hrs

Acidx.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


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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

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 protocolrequirements, and the protocol requirements were met. The method is considered suitable for

intended use.

.

abbie gentry method validation report

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