AMES test modifications FDA & EMA instructions

Guidance, Documents, Resources
1

Hi,

There is some talk, that the FDA is working on a new document in which some new testing rationale for the conductance of the AMES test will be presented.

  • Preinbcubation time of 30 min or 60 min (standard plate incorporation test used only as backup)
  • Limit solvent concentrations to <3.6% with the prefered solvents : water, acetone, methanol and DMSO (what about acetonitrile?)

The solvent concentration is very low, and prone to test item precipitation. Any thoughts on this?

Has anyone here any information that similar recommendations will be also included by EMA. Will this be the AMES test ā€˜specificationsā€™ needed for it to be accepted by regulatory authorities?

Thanks!
Filip

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2

@trust_user_a @trust_user_b
Hi,

There is some talk, that the FDA is working on a new document in which some new testing rationale for the conductance of the AMES test will be presented.

  • Preinbcubation time of 30 min or 60 min (standard plate incorporation test used only as backup)
  • Limit solvent concentrations to <3.6% with the prefered solvents : water, acetone, methanol and DMSO (what about acetonitrile?)

The solvent concentration is very low, and prone to test item precipitation. Any thoughts on this?

Has anyone here any information that similar recommendations will be also included by EMA. Will this be the AMES test ā€˜specificationsā€™ needed for it to be accepted by regulatory authorities?

Thanks!
Filip

1 Like
3

Thanks, Filip, for sharing this update.

In regard to EMA, all i know is attempts being made to convince EMA to accept Ames as valid assay with plate incorporation method. There were also few publications made to make this point.

This might not fly because the proof of burden increases to prove a cohort of concern as non-mutagenic.

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4

@AndyTeasdale @conudel have you hear anything on your side?

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5

The situation around the Ames test is fluid and complex. In my mind on-going discussion through HESI around possible modifications to the Ames protocol may provide a way forward but I donā€™t anticipate a breakthrough regarding this in the short term. What is vital is establishment of realistic interim AIs. Limits that will permit continued access to critical medicines in the short term while progress in made. Without this we risk loss of access to both individual medicines and whole classes.

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