Accreditation and Quality Assurance

, Volume 17, Issue 2, pp 139–146

The estimation and use of measurement uncertainty for a drug substance test procedure validated according to USP <1225>

Practitioner's Report

Abstract

The vision for metrology at the United States Pharmacopeia (USP) is for international recognition, harmonization, and official acceptance of all USP reference standards that are based on sound, scientific, metrological principles, such as measurement uncertainty (MU). Pharmaceutical testing laboratories will need to estimate the MU for their test procedures. This paper demonstrates how to estimate MU for a test procedure validated following the requirements in USP General Chapter <1225>, Validation of Compendial Procedures. The test procedure determines the assay and impurities for a pharmaceutical drug substance. Pharmaceutical manufacturing companies are required to test the drug substance used in their drug products. In this example, a new test procedure was developed and validated following the requirements in USP <1225>. The MU was estimated using the data from the test procedure validation. The MU estimate determined that the test procedure was fit for use with one determination, avoiding the expense of duplicate determinations. The MU estimate was used to set up decision rules for comparing test data to the assay and impurity specifications. The information from the MU estimate was used to monitor the routine use of the test procedure using control charts that assess accuracy and precision of each run based upon actual test procedure performance capability.

Keywords

Drug substance Estimation Reporting United States Pharmacopeia 

References

  1. 1.
    Hauck WW, Koch W, Abernethy D, Williams RL, USP (2008) Making sense of trueness, precision, accuracy, and uncertainty. USP Pharm Forum 34(3):838Google Scholar
  2. 2.
    Byrialsen K, Soerensen EM, Riber UM, Redder T, Jespersen AM, Zeuthen N (2008) Novo Nordisk A/S, Krogshøjvej 51, KD-2880 Bagsværd, Denmark. Uncertainty statement regarding USP reference standards. USP Pharm Forum 34(2):477Google Scholar
  3. 3.
    Small Molecules Collaborative Group, Williams RL, Abernethy DR, Koch WF, Hauck WW, Cecil TL (2009) Performance-based monographs. USP Pharm Forum 35(3) May-June 2009Google Scholar
  4. 4.
    Pappa HN (2011) General chapter <1225> validation of compendial methods. USP34-NF29, p 778Google Scholar
  5. 5.
    International Conference On Harmonisation Of Technical Requirements For Registration Of Pharmaceuticals For Human Use (2005) Validation of analytical procedures: text and methodology Q2(R1). http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf
  6. 6.
    BIPM, IEC, IFCC, ILAC, IUPAC, IUPAP, ISO, OIML (2008) International vocabulary of metrology—Basic and general concepts and associated terms (VIM) 3rd edn. JCGM 200:2008. http://www.bipm.org/en/publications/guides/vim
  7. 7.
    ISO (1995) A Guide to the Expression of Uncertainty in Measurement, 2nd edn. ISO, Geneva, JCGM 100:2008. http://www.bipm.org/en/publications/guides/gum.html
  8. 8.
    Ellison SLR, Rosslein M, Williams A (eds) (2000) EURACHEM/CITAC Guide: quantifying uncertainty in analytical measurement, 2nd edn. LGC, TeddingtonGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Quality Analysis ConsultantsWinnipegCanada

Personalised recommendations