Method validation
Under method validation in analytics is defined as the formal and documented proof that a chemical, physical or biological analysis method is suitable for their intended purpose and meets the requirements placed on them. Method validation is an important tool in quality assurance and is required by authorities in the context of accreditation and approval procedures. Particularly in the area of drug approval , method validation is essential due to the requirements of the approving authorities (such as the American FDA or the German Federal Institute for Drugs and Medical Devices , BfArM). But also in many other areas such as water analysis, environmental analysis or trace analysis it is an important instrument for ensuring the quality of analysis.
Guidelines
Method validation
The following standards and guidelines deal with the scope and implementation of method validations:
- DIN EN ISO / IEC 17025: "General requirements for the competence of testing and calibration laboratories"
- EURACHEM Guide: “Guide to Quality in Analytical Chemistry (2002)”
- International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH), Guideline Q2 (R1)
- Federal Environment Agency : Guideline for method validation
- United States Pharmacopeia , Chapter <1225>
statistics
The following standards deal with the statistical evaluation of characteristics of methods:
- DIN ISO 5725: "Accuracy (trueness and precision) of measurement methods and results" (correctness and precision)
- DIN 32633: "Standard addition method", s. also standard addition method
- DIN 32645: "Detection, detection and determination limits"
- DIN 38402-41: “German standard methods for water, waste water and sludge analysis; General information (group A); Round robin tests, planning and organization "
- DIN 38402-42: "German standard methods for water, waste water and sludge testing - General information (Group A) - Part 42: Round robin tests for process validation"
- DIN 38402-51: “German standard methods for water, waste water and sludge analysis; General information (group A); Calibration of analytical processes, evaluation of analytical results and linear calibration functions for the determination of process parameters "
- DIN 55350: "Terms of quality assurance and statistics"
electronic data processing
The following requirements apply to the electronic processing and storage of measured values, validation plan data or reports in connection with the approval of a drug for the US market:
scope
Depending on the purpose and type of analytical method, various key figures and evidence may be required to validate a method. In most cases, the suitability of the method is demonstrated by specifying statistical parameters (e.g. mean values , standard deviations and correlation coefficients ) or evaluating statistical tests such as B.
- Test for homogeneity of variance ( F-test , Bartlett, Cochran)
- Test for normal distribution ( Kolmogorow-Smirnow , Shapiro-Wilk)
- Linearity test (almond)
- Outlier tests (Dixon, Grubbs )
- Trend tests (Neumann)
provided. But also a graphic such as B. a chromatogram can provide evidence of a required characteristic. In the case of statistical values and tests, target values, limit values and significance levels must be defined in advance . These depend on the area of application and the procedure and are partly determined by guidelines and regulations.
The above guidelines essentially name the following characteristics that have to be examined and evaluated for a method within the framework of method validation (see ICH Q2 (R1)):
- accuracy
- precision
- robustness
- Specificity / selectivity
- Detection and quantification limit
- Linearity , sensitivity
- Repeatability , comparative precision , and possibly laboratory precision
- Workspace
literature
- Federal Association of Drug Manufacturers eV: Validation of analytical procedures for drug production. 2., revised. u. exp. Edition. BAH, Bonn 2004.
- Werner Funk, Vera Dammann, Gerhild Donnevert: Quality assurance in analytical chemistry. 2., completely revised. and exp. Edition. Wiley-VCH Verlag, Weinheim 2005, ISBN 3-527-31112-2 .
- Stavros Kromidas: Manual of Validation in Analytics. Wiley-VCH Verlag, Weinheim, 2001, ISBN 3-527-29811-8 .
- James M. Miller, Jonathan B. Crowther (Eds.): Analytical Chemistry in a GMP Environment. John Wiley & Sons, New York 2000, ISBN 0-471-31431-5 .
- J. Ermer, JH McB. Miller (Ed.): Method Validation in Pharmaceutical Analysis. A guide to best practice. Wiley-VCH, Weinheim 2005, ISBN 3-527-31255-2 .
- Jörg Wellmitz, Michael Gluschke: Guideline for method validation . In: Umweltbundesamt (Ed.): Texts . No. January 1 , 2005 ( PDF - free full text).
- B. Magnusson, U. Örnemark (Ed.): Eurachem Guide: The Fitness for Purpose of Analytical Methods - A Laboratory Guide to Method Validation and Related Topics . 2nd Edition. 2014, ISBN 978-91-87461-59-0 ( online - free full text).
- Vicki Barwick (Ed.): Eurachem / CITAC Guide: Guide to Quality in Analytical Chemistry - An Aid to Accreditation . 3. Edition. 2016, ISBN 978-0-948926-32-7 ( online - free full text).
See also
Web links
- Validation of Analytical Procedures: Text and Methodology (PDF; 184 kB), ICH Q2 (R1), November 2005
- Analytical Procedures and Methods Validation for Drugs and Biologics (PDF; 134 kB), US-FDA , July 2015
- Guidance for Industry - Bioanalytical Method Validation (PDF; 65 kB), US-FDA, May 2001