Today's discussion is analytical method validation parameters as per USP, EP, BP and ICH. For a personalized solution towards your own needs, please contact us: https://lnkd.in/dyY-249

1. QualityControl
Performanceparametersin
analytical validation
Dimitris Papamatthaiakis
Pharma Life-cycle Consultancy

2. Outline
 Precision
 Accuracy
 Linearity
 Specificity, LOD & LOQ
 Robustness

3. Performanceparametersin
analyticalvalidation
Precision

4. Performance
parametersin
analytical
validation
Precision
Validation
parameter
Procedure Suggested
Acceptance criteria
System
precision
(injection
repeatability)
Assay (API)
Assay (FP)
Impurities
RSD <1%
RSD<2%
RSD<2-5%
Repeatability Assay
Impurities
RSD<1-2%
RSD<10-20%,
at LOQ calculation
from specs
Intermediate
precision /
Reproducibility
Assay RD<3-5%
Intermediate
precision
(matrix)
Assay
Impurities
RD<2%
RD (or AD)<10%
Target
Measurement
Uncertainty
Assay
Impurities
RSD<2%
RSD<5%

5. Performanceparametersin
analyticalvalidation
Accuracy

6. Performance
parametersin
analytical
validation
Accuracy
Validation
parameter
Procedure Suggested
Acceptance criteria
Compare with a
reference
Assay (API) (n=6)
Assay (FP) (n=6)
Impurities (n=6)
<1-2%
<2%
<10%
Recovery Assay (FP) (n=9)
Impurities (n=9)
98-102%
80/90-110/120%
Statistical
evaluation
95% confidence
interval of the mean
includes 100%
95% confidence
interval within 96 –
104%
Relative
standard
deviation
Assay (FP) (n=9)
Impurities (n=9)
<2%
<10-20%
t-test No significant
difference between
the means (95% level
of significance)
Relative bias Assay
Impurities
<2%
<10%

7. Performanceparametersin
analyticalvalidation
Linearity

8. Performance
parametersin
analytical
validation
Linearity
Validation
parameter
Procedure Suggested Acceptance
criteria
Corelation
coefficient
Assay
Impurities
and low level
depends on number of
values and concentration
range
R>0.9999
R>0.999
Single point
or
Regression
95%CI of y-intercept bracket
zero
Limit of linearity Slope of assay & impurities
should be very similar
p-value > 0.05
Bias of y-
intercept
<3%
Residual sum of
squares
Report
Random scatter

9. Performanceparametersin
analyticalvalidation
Specificity
LOD & LOQ

10. Performance
parametersin
analytical
validation
Specificity
LOD&LOQ
Validation
parameter
Procedure Suggested Acceptance
criteria
Specificity Resolution >2
Purity angle < Purity
threshold
MS
LOD Unknown
impurities
(or low level)
0.05% or 0.1%
Precision on
LOQ
Impurities
Cleaning
validation
methods
RSD<10-20%

11. Performanceparametersin
analyticalvalidation
Robustness

12. Performance
parametersin
analytical
validation
Robustness
Validation
parameter
Procedure Suggested Acceptance
criteria
Recovery Assay
Impurity
98-102%
90-110%
Resolution
critical pair
>2
RSD At LOQ Impurity >0.05%
Tailing <2
Plates >5000
API = Active Pharmaceutical Ingredient
FP = Final Product
RSD = Relative Standard Deviation
RD = Relative Difference
AD = Absolute Difference
LOD = Limit Of Detection
LOQ = Limit Of Quantitation
MS = Mass Spectrometry

13. Are you looking for a personalized solution towards your own needs?
Please contact us: https://pharmalifecycle.kartra.com/page/contactus