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Method Validation and Transfer

  • Frank J. Diana

Abstract

Analytical methods used in testing pharmaceutical stability samples need to be validated to the current standards. Often the same methods are employed for release and stability testing which facilitates method validation and allows for the use of initial release data for time zero stability as long as samples are packaged and placed on stability in a reasonably short period of time (typically 30 days). Transfer of these methods between laboratories is also facilitated by the development and validation of the same methods for release and stability testing. Stability testing will typically include appearance and a test for assay and degradation products for all dosage forms. The assay method is typically proven to be stability indicating and specific, meaning that all degradation products and synthetic impurities, known or unknown, as well as inactive components are separated from the active ingredient thereby allowing for the accurate measurement of the strength/potency of the dosage form. Similarly, to accurately measure a degradation product level in finished product, all other degradation products and synthetic impurities should be resolved from the peak of interest. Additional tests are typically performed depending on the dosage form, for example dissolution or drug release for solid dosage forms, pH, preservatives and anti-oxidant content for liquid, topical or parenteral dosage forms.

Method validation is covered in the current Good Manufacturing Practices (cGMPs) under section 211.165(e) which indicates that “The accuracy, sensitivity, specificity, and reproducibility of tests methods …shall be established and documented”. Such validation and documentation may be accomplished in accordance with 211.194(a) (2) which includes the need to “indicate the location of data that establish that the methods used in the testing of the sample meet proper standards of accuracy and reliability as applied to the product tested”. Methods included in recognized standard references such as the current USP/NF are understood to be validated. “The suitability of all testing methods used shall be verified under actual conditions of use” (211.194). For new products for which methods are developed, analytical method validation as described in this chapter will be necessary; for methods already included in the USP, method verification will suffice.

Keywords

Dosage Form Acceptance Criterion Method Transfer Force Degradation Study Analytical Method Validation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    International Conference on Harmonization (ICH) (November 2005) Guideline Q2(R1), Validation of analytical procedures: text and methodologyGoogle Scholar
  2. 2.
    Food and Drug Administration (FDA) (August 2000) Draft guidance for industry, analytical procedures and methods validation: chemistry, manufacturing, and controls documentation (CMC)Google Scholar
  3. 3.
    United States Pharmacopeia, 30th rev, <1225> Validation of compendial methods, pp 680–683Google Scholar
  4. 4.
    Center for Drug Evaluation and Research (CDER) (November 1994) Reviewer guidance, validation of chromatographic methodsGoogle Scholar
  5. 5.
    Green JM (1996) A practical guide to analytical method validation. Anal Chem 68 (9),pp 305A–309AGoogle Scholar
  6. 6.
    Snyder LR, Kirkland JJ, Glajch JL (1997) Practical HPLC method development. 2nd edn,pp 685–713Google Scholar
  7. 7.
    Layloff T, Nasr M, Baldwin R, Caphart M, et al (2000) The FDA regulatory methods validation program for new and abbreviated new drug applications. Pharm Technol 24, pp 30–42Google Scholar
  8. 8.
    International Conference on Harmonization (ICH) (November 1996) Guideline Q1B, Photostability testing of new drug substances and productsGoogle Scholar
  9. 9.
    Olsen BA, Gavin PF, Wozniak TJ (2007) Quality by design considerations for analytical methods. AAPS News Mag 10, pp 16–22Google Scholar
  10. 10.
    Quarry MA, Sebastian, DS, Diana F (August, 2002) Investigation of 4,5-epoxymorphinan degradation during analysis. J Pharm Biomed Anal 30, pp 99–104Google Scholar
  11. 11.
    United States Pharmacopeia, 30th rev, <621> Chromatography, pp 243–256Google Scholar
  12. 12.
    FDA/CDER (November 1995) Guidance for industry, content and format of investigational new drug applications (INDs) for phase 1 studies of drugsGoogle Scholar
  13. 13.
    FDA/CDER (May 2003) Guidance for industry, INDs for phase 2 and phase 3 studies CMC informationGoogle Scholar
  14. 14.
    Boudreau SP, McElvain JS, Martin LD, Dowling T, Fields SM (2004) Method validation by phase of development: an acceptable analytical practice. Pharm Technol 28, pp 54–66Google Scholar
  15. 15.
    Sixsmith DG (2001) Outsourcing resources: third-party technology transfer. Pharm Tech,pp 58–62Google Scholar
  16. 16.
    Scypinski S, Roberts D, Oates M, Etse, J (March 2002) PhRMA acceptable analytical practice for analytical method transfer. Pharm Technol 26, pp 84–88Google Scholar
  17. 17.
    ISPE (2003) Good practice guide: technology transfer, analytical methods pp 23–34Google Scholar
  18. 18.
    Swartz M, Krull I (November, 2006) Analytical method transfer. LCGC N Am vol 24 (11),pp 1204–1214Google Scholar
  19. 19.
    FDA/CDER (April 1998) Guidance for industry post-approval changes – analytical testing laboratory sitesGoogle Scholar
  20. 20.
    FDA/CDER (November, 1995) Guidance for industry scale up and post-approval changes: immediate release solid oral dosage formsGoogle Scholar
  21. 21.
    FDA/CDER (September, 1997) Guidance for industry scale up and post-approval changes: modified release solid oral dosage formsGoogle Scholar
  22. 22.
    FDA/CDER (May, 1997) Guidance for industry scale up and post-approval changes: nonsterile semisolid dosage formsGoogle Scholar
  23. 23.
    FDA/CDER (April, 2004) Guidance for industry changes to an approved NDA or ANDAGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Endo PharmaceuticalsChadds FordUSA

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