BEBAC  Ing. Helmut Schütz

Questions & Answers on the Bioavailability and Bioequivalence Guideline

EU – EMEA

On 27 July 2006 a Questions & Answers Document (EMEA/CHMP/EWP/40326/2006) to the current European NfG on BA/BE was published by the ‘Therapeutic Subgroup on Pharmacokinetics’ (EWP-PK).

An overview of the document is given below:

  1. Introduction
  2. Assessment of Cmax in bioequivalence studies.
    In which cases is it allowed to use a wider acceptance range for the ratio of Cmax?
  3. Outliers.
    When can subjects classified as outliers be excluded from the analysis in bioequivalence studies?
  4. If one side of the 90% confidence interval of a pharmacokinetic variable for testing bioequivalence lies on 0.80 or 1.25, can we conclude that the products are bioequivalent?
  5. In which cases may a non-parametric statistical model be used?
  6. When should metabolite data be used to establish bioequivalence?
  7. When using metabolite data to establish bioequivalence, may one use the same justification for widening the Cmax acceptance criteria as in the case of the parent compound?
  8. What is a ‘highly variable drug or drug product’?
  9. When testing for bioequivalence of a product with a non-linear PK, how should one select the strengths with the largest sensitivity to detect differences in the two products?
  10. What are the conditions for using urinary pharmacokinetic data for bioequivalence assessment?
  11. Standardisation of bioequivalence studies with regard to food intake.
    How strictly should the Guideline be interpreted?

Although no draft version was published, according to the Monthly Report from CHMP’s Plenary Meeting (24 – 27 July 2006), and the Clinical Efficacy and Safety Guidelines the document is adopted by the EMEA and effective with July 2006.

Update

This document is superseded by the new Guideline on the Investigation of Bioequivalence with 1 August 2010 and was removed from EMA’s site.
A copy of the document ( 36kB PDF) is available from our site for informational purposes only.