EMEA Publishes Concept Paper on Single Dose / Acute Toxicity

The Drug Regulators, EMEA, have published a concept paper on the Non-Clinical Safety studies needed to support human clinical trials of a given scope and duration as reflected in the ICH M3 guideline. Currently, this guideline recommends that the single dose (acute) toxicity for a pharmaceutical should be evaluated in two mammalian species prior to the first human exposure but that a dose-escalation study is considered as an acceptable alternative to simple dose design. Directive 2003/63/EC states that the singledose toxicity test must be carried out in accordance with the relevant guidelines published by the EMEA. The currently available guidance addressing marketing authorisation states that single dose toxicity testing must be conducted on at least two mammalian species and that two routes of administration should be use.

Problem to be addressed

The usefulness of specific acute (single dose) toxicity studies for the conduct of clinical studies has been questioned. In a recently published survey, it has been shown that data from acute toxicity studies are not used to support the planning and conduct of early clinical studies. It was found that data from acute toxicity studies were never used to select doses for first time in human studies, nor to determine parameters to monitor or for identification of target organs of toxicity. Furthermore, no additional information was gained from acute toxicity testing in a second species or via a second administration route. Data from short term repeated dose toxicity studies, which should be undertaken to support clinical studies in humans, were more informative and fulfilled the purposes of providing data for an adequate risk assessment and mitigation for participants in clinical studies.

New Guidelines Are Needed

The CHMP Safety Working Party recommends revising the existing guideline on single dose toxicity, to reflect conclusions based on currently available data on the limited usefulness of acute toxicity studies for the safety assessment of medicinal products. The pharmaceutical industry, animal welfare organisations and national competent authorises involved in safety assessment of pharmaceuticals, are invited to participate in the development of these new guidelines.

Click Here to Access – ICHM3 Exper Services - Click here

If you would like more detail in this area please get in touch with Damien Bové damien.bove@idaconsultants.com

Damien Bové works as a drug development consultant (pharmaceutical or biotechnology) and regulatory consultant, we work with our clients to define a drug development target, define a drug development strategy, define a regulatory strategy or define a commercial strategy. Our clients are generally raising funds or looking to license out their technology and we help them achieve it. If you want to know more don’t hesitate to get in touch.

Grow your Expertise for Free

As you know this website is a great resource for keeping up to date with developments and regulations, why not get our FREE monthly regulatory and market round up. You can un-subscribe at any time and we do not share your details with anybody.