Impurities in Generics - New FDA Draft Guidance for Industry

GMP News No. 630

GMP News
24 October 2005

Impurities in Generics – New FDA Draft Guidance for Industry

In August 2005, the FDA published the draft for a new guideline with the title ANDAs: Impurities in Drug Products. This guideline provides advice on the question which CMC (Chemistry, Manufacturing and Control) information on the detection, identification and qualification of impurities classified as degradation products should be listed in an application for a marketing authorisation. This refers both to ANDA (Abbreviated New Drug Applications) applications for generics and to changes in ANDA applications. This guideline will replace the existing draft guidance of the same title dating back to 1998.

The revision of the draft guidance became necessary in order to adapt it to the ICH Guideline Q3B(R) - Impurities in New Drug Products revised in November 2003.

Even though the ICH Guideline Q3B(R) refers primarily to impurities in new drug products (NDA applications), the FDA assumes that many of the requirements laid down in this document should also be applied to ANDAs.

Topics dealt with by the FDA Draft Guidance include:

  • List of degradation products
  • Acceptance criteria for degradation products
  • Qualification of degradation products

A decision tree in the attachment to the draft guidance describes considerations for the qualification of degradation products in case the standard qualification thresholds mentioned in ICH Q3B(R) are exceeded.

The document recommends three methods for the qualification of degradation products:

  • Comparison of the generic drug product's analytical profiles with those of an approved human drug product using the same validated stability-indicating analytical method.
  • Scientific literature and significant metabolites. 
    The degradation product does not need to be qualified if its level is adequately justified by scientific literature. Furthermore, a degradation product that represents a significant metabolite of the drug product is generally considered qualified.
  • Conduct of toxicity studies.
    The text emphasises that this method should only be chosen if qualification cannot be carried out by means of the procedures mentioned above.
  • You can learn everything you need to know about impurities and their specifications at the two ECA top conferences "Setting Specifications" and "Stability Testing" taking place in Barcelona from 28 to 30 November 2005.

    If you are interested in the analytical details of impurity detection by means of gas chromatography, the GMP Education Course "GC in Pharmaceutical GMP Laboratories" (Barcelona, 30 November - 1 December 2005) will offer you a comprehensive overview, the most important topics being consolidated in workshops. Please click here in order to read the programme.

    Dr Günter Brendelberger

    The complete FDA Draft Guidance can be found here:


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