Escolar Documentos
Profissional Documentos
Cultura Documentos
1|
2|
3|
First-time Generic
Information from regulatory agencies (publicly available) & literature data Information from regulatory agencies (publicly available) & literature data
Multisource Generic
Pharmacopoeias
Originators specifications
Pharmacopoeias
Analytical methods
Establish identity, Derive identity, potency, Verify identity, potency, potency, purity of API purity of API and FPP by purity of API and FPP by and FPP by in house methods pharmacopoeial methods in-house methods and in-house methods
4|
5|
IC = PE + BE
6|
Birgit Schmauser | April 2008
Analytical methods must be developed and validated according to TRS 823, Annex 5, Validation of analytical procedures used in the examination of pharmaceutical materials ; ICH Q2 (R1)
To be used within GLP and GMP environments
8|
9|
Man
qualified
Machine
Methods
characterised documented robust
calibrated
qualified
suitable
Vibrations Temperature
Irradiations
Time
Quality
Humidity
Supplies
Material
10 |
Milieu
Management
Method development
Initital Method Development Pre-Validation Evaluation Method Optimization Robustness System Suitability
. From: Analytical Chemistry in a GMP Environment. Edited by J.M. Miller and J.B. Crowther, ISBN 0-471-31431-5, Wiley & Sons Inc
11 |
Validation protocol
Method principle / objective Listing of responsibilities Laboratories involved and their role in the validation Method categorization List of reagents (including test lots) and standards Test procedures to evaluate each validation parameter and proposed acceptance criteria Plan or procedure when acceptance criteria are not met Requirements for the final report
The validation process cannot proceed until the protocol and all parties involved approve the acceptance criteria
13 |
Birgit Schmauser | April 2008
14 |
Impurities
quantitative limit
Assay
+ + + + + + + + +
+ + + + + + +
15 |
&Inaccurate precise
16 |
17 |
for xn = n is described by the erf-function ( = mean): xn P 0.6826895 2 0.9544997 3 0.9973002 4 0.9999366 5 0.9999994
Values
19 |
20 |
21 |
22 |
23 |
mean
24 |
Birgit Schmauser | April 2008
true
25 |
From: Analytical Method Validation and Instrument Performance Verification, Edited by Chung Chow Chan,Herman Lam, Y.C. Lee and Xue-Ming Zhang, ISBN 0-471-25953-5, Wiley & Sons
26 |
Identity testing
To ensure the identity of an analyte
Purity testing
To ensure accurate statement on the content of impurities of an analyte
Assay
To allow an accurate statement on the content of an analyte in a sample
28 |
From: Analytical Method Validation and Instrument Performance Verification, Edited by Chung Chow Chan,Herman Lam, Y.C. Lee and Xue-Ming Zhang, ISBN 0-471-25953-5, Wiley & Sons
29 |
Assure that the API can be assessed specifically in the presence of known and unknown (generated by stress) impurities Assure that known impurities/degradants can be specifically assessed in the presence of further degradants By peak purity assessment and (overlay of) chromatograms
30 |
Birgit Schmauser | April 2008
31 |
32 |
34 |
35 |
37 |
Correlation coefficient (r) Y-intercept Slope of regression line Residual sum of squares PLOT OF THE DATA
r > 0.997
r < 0.997
From: Analytical Method Validation and Instrument Performance Verification, Edited by Chung Chow Chan,Herman Lam, Y.C. Lee and Xue-Ming Zhang, ISBN 0-471-25953-5, Wiley & Sons
39 |
40 |
Test concentration can be used to determine impurities To determine drug substance (assay) the test concentration must be diluted The range is 0 ~ 150% of impurity specification
From: Analytical Method Validation and Instrument Performance Verification, Edited by Chung Chow Chan,Herman Lam, Y.C. Lee and Xue-Ming Zhang, ISBN 0-471-25953-5, Wiley & Sons
42 |
44 |
45 |
A solution containing stavudine spiked with its impurity thymine does not allow to clearly distinguish between degradation and spike A solution containing stavudine of a FPP-stability sample solution does not allow to clearly distinguish between FPPstability degradation and sample solution degradation Should be analysed immediately
46 |
Average peak area % RSD 0.4 Method precision of released API (dissolution) Acceptance criterion % RSD 10.0
47 |
Validation of analytical procedures should demonstrate that they are suitable for their intended use Validation of analytical procedures deserves special attention during assessment of dossiers for prequalification
50 |
THANK YOU
51 |