Assessment and control of DNS reactive in pharmaceuticals Flashcards
what are the three major endpoints of genetic damage associated with human disease?
Gene mutation, clastogenicity and Aneuploidy
What is mutagencity?
the induction of permanent transmissible changes in stucture of genetic material of cells or organism
What are the guidelines?
S2(R1) genetoxicity testing and data interpretation
M7(R1) assessment and control of DNA reactive (mutagenic) impuries in pharmaceuticals
Mutagenic impurities?
An impurity that has been demonstrated to be mutagenic in an approprite mutagenicity
TTC
Threshold of toxological concern
What are cohort of concern
Group of high potency mutagenic carcinogens such as n-nitroso and alkly-azoxy compounds
Imurities can be classified as?
actual and potential impurities
actual and potential impurities
actual impurities (where structures where known) and potential impurities should be evaluated for mutagenic potential
threshold outline in ICH Q3A/B
Does not apply to products in clinical development
ICH M7
guidance on how to assess potential mutagenicity of identified and relevant degradtion products
Clastogenicity
structural chromosome changes
DNA reactive substance assay
example
Bacterial reverse mutation (mutagenicity)assay
Ames test
aim of ICH M7 guideline
to ensure that mutagenic impurities are controlled to safe levels
where are the threshold listed for drug substance and drug product
Q3A (R2) drug substance Q3B/R2 for drug product
