Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 2 de 2
Filter
Add more filters










Database
Language
Publication year range
1.
Regul Toxicol Pharmacol ; 110: 104524, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31734179

ABSTRACT

Regulatory Guidance documents ICH Q3A (R2) and ICH Q3B (R2) state that "impurities that are also significant metabolites present in animal and/or human studies are generally considered qualified". However, no guidance is provided regarding data requirements for qualification, nor is a definition of the term "significant metabolite" provided. An opportunity is provided to define those categories and potentially avoid separate toxicity studies to qualify impurities. This can reduce cost, animal use and time, and avoid delays in drug development progression. If the concentration or amount of a metabolite, in animals or human, is similar to that of the known, structurally identical impurity (arising from the administered test material), the qualification of the impurity on the grounds of it also being a metabolite is justified. We propose two complementary approaches to support conclusions to this effect: 1) demonstrate that the impurity is formed by metabolism in animals and/or man, based preferably on plasma exposures or, alternatively, amounts excreted in urine, and, where appropriate, 2) show that animal exposure to (or amount of) the impurity/metabolite is equal or greater in animals than in humans. An important factor of both assessments is the maximum theoretical concentration (or amount) (MTC or MTA) of the impurity/metabolite achievable from the administered dose and recommendations on the estimation of the MTC and MTA are presented.


Subject(s)
Drug Contamination , Pharmaceutical Preparations/metabolism , Animals , Biotransformation , Humans , Toxicity Tests
2.
Nat Rev Drug Discov ; 16(12): 811-812, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29026211

ABSTRACT

The sharing of legacy preclinical safety data among pharmaceutical companies and its integration with other information sources offers unprecedented opportunities to improve the early assessment of drug safety. Here, we discuss the experience of the eTOX project, which was established through the Innovative Medicines Initiative to explore this possibility.


Subject(s)
Drug Evaluation, Preclinical/methods , Drug Industry/methods , Drug-Related Side Effects and Adverse Reactions , Information Dissemination , Humans , Risk Assessment/methods
SELECTION OF CITATIONS
SEARCH DETAIL
...