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Perfect Solution not only for small compound quantities: AMES MPF test – meets ICH M7 requirements

The AMES test is an internationally accepted screening test for mutagenicity detection of potential carcinogenic DNA reactive impurities (see ICH M7 guideline – Assessment and Control of DNA reactive (mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk).

Although the FDA Guidance for Industry M3(R2) (Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals) recommends testing genotocity potential only before starting clinical developments, it is highly advisable to investigate the genotoxicity earlier in the drug development process. Genotoxicity is a knockout criterion and developing a compound with genotoxic potential would be a waste of money. Ideally, such a test should be low-cost, very sensitive and require less compound. [1]

For limited compound quantities, the guideline ICH M7 recommends a miniaturized test method such as the AMES MPF test [2]. The AMES MPF assay has the required proven high concordance with the ICH-compliant agar plate test. Today, Ames MPF is even preferred by the pharmaceutical industry due to its low consumption of compound and high sensitivity. Due to the minimized format also the amount of S9 enzymes required to mimic the hepatic metabolisation is reduced.

The AMES MPF test offers the following advantages

  • Liquid low-volume format
  • Use of microplates and multichannel pipettes
  • Colorimetric read-out
  • Less test sample – up to 4 fold – Very important when compound quantity is limited!
  • Less S9 – up to 12 fold – Reduced number of sacrificed animals!
  • Higher throughput
  • 1 plate = 24 measuring points (cf. agar plate test: 1 plate = 1 measuring point)
  • Simoultaneous handling of several replicates (cf. agar plate test: individual handling = 1 plate requires mixing of 1 compound, agar and plating)

Following increasing demand, Pharmacelsus has now added the AMES MPF to its in vitro toxicity portfolio. A method sheet on the assay can be downloaded here. We would be happy to perform this in vitro toxicity testing for your compound including the AMES test. Please contact us for your individual study at info@pharmacelsus.de!

By the way: Did you already know that Pharmacelsus provides a broad range of services for exploratory toxicity in 2D as well as 3D testing systems? For more information, please contact us at info@pharmacelsus.de.

Literatur

[1] (“ … An assay for gene mutation is generally considered sufficient to support all single dose clinical development trials. To support multiple dose clinical development trials, an additional assessment capable of detecting chromosomal damage in a mammalian system(s) should be completed. A complete battery of tests for genotoxicity should be completed before initiation of phase 2 trials…”)
[2] (“…… bacterial mutagenicity testing could be carried out using a miniaturized assay format with proven high concordance to the ICH-compliant assay….”)

We are looking forward to support your project!