Representatives from the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA) recently drafted a commentary that addressed the Center’s outlook on the challenges and opportunities of using alternatives in drug development, especially for regulatory purposes.
As you know, drugs are tested preclinically to assess their safety before they enter human clinical trials. Federal regulations and guidances from the FDA and the International Council for Harmonization are generally flexible about the specific number and type of studies to be performed for these preclinical safety tests. CDER’s commentary points out that these guidances are “nonbinding and typically note that alternative approaches can be used if they satisfy the applicable statutes and regulations.” Despite this, whole animal testing approaches combined with cell-based tests are traditionally used for this purpose.
The ability of this “standard” testing strategy to predict human risk has come increasingly into question, however, and CDER believes that human-relevant alternative approaches could improve the predictivity of preclinical tests. Based on information gleaned from the Office of New Drugs, CDER identified the following areas as being in need of developing more predictive, human-relevant alternatives:
- safety pharmacology
- general toxicology
- prediction of human cancer risk
- prediction of human pregnancy/reproductive risk
- special toxicity (commonly defined as ocular, dermal and phototoxicity studies)
The commentary goes on to discuss some alternatives that are already being used in preclinical tests in these areas, as well as known shortcomings of those models or gaps that remain. It is important that such assessments are made, so that alternative methods can be actively developed to address any unmet needs in the current preclinical drug development approach.
We are pleased that the FDA/CDER are taking steps to identify specific preclinical testing areas that would benefit from the use of alternatives and that they are committed to continued participation in the development and regulatory use of alternatives.
As NAVS/IFER begin to review pre-proposal applications for the current cycle of Graduate Student Fellowships, we will keep these subject areas in mind to see if, and how, we can play a role in supporting the development of these much-needed alternatives.
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