- OBJECTIVE
This guidance is intended to describe concerns relevant to chronic toxicity testing in rodent and non-rodent in the context of the safety evaluation of a medical product. As guidance is not legally enforceable, an applicant may provide justification for an alternative method.
2 SCOPE
This guidance has been put together for the development of medicinal products other than those covered under ICH Guideline on Safety Studies for Biotechnological goods e.g. Monoclonal antibodies, recombinant DNA proteins.
- BACKGROUND
During the 1991 International Conference on Harmonisation, a review of chronic toxicity testing practices in the EU, Japan, and US established a consensus on a 6-month testing duration for rodents. However, non-rodent testing durations varied, resulting in pharmaceutical companies conducting duplicative studies for both 6 and 12 months. To avoid this redundancy and optimize resource use while ensuring public health safeguards, regulatory authorities explored identifying a single non-rodent testing duration. Their analyses revealed that in 16 cases, further evaluation of data from both durations was necessary, but findings were inconsistent, with some studies showing no additional information gained from the 12-month period and others lacking agreement on the comparability of study designs.
In some cases, findings were observed at 12 months but not at 6 months, suggesting that a study of 9 months could have detected them. Concerns arose regarding differences in findings across studies of varying durations, and no consensus on their clinical relevance was achieved. Generally, studies lasting 12 months are unnecessary, and shorter studies of 9 months may suffice. In the EU, 6-month studies in non-rodents are acceptable per Council Directive 75/318/EEC, and prior longer studies eliminate the need for additional 6-month studies.
4. GUIDANCE ON DURATION OF CHRONIC TOXICITY TESTING FOR TRIPARTITE DEVELOPMENT PLAN
Arising from the extensive analysis and review of the above mentioned data in non rodents and based upon the achievements of ICH1 for testing in rodents, and so as to avoid duplication and follow a single development plan for chronic toxicity testing of new medicinal products, the following studies are considered acceptable for submission in the 3 Regions: 1) Rodents: a study of 6 months duration; 2) Non-rodents: a study of nine months duration.
Reference:
Dr Subramanian S Iyer
