title: Preclinical safety testing for cell-based products using animals.
abstract: The objectives of preclinical testing include to show why there might be therapeutic benefit in patients and to provide information on the product's toxicity. For cell-based products, given even once, there may be long term exposure and this could imply, unlike for conventional drugs, that all preclinical studies may be needed prior to first human use. The duration of exposure to cells should be studied in animals to guide toxicity assessments. Distribution of cells after administration by a route resembling that intended in humans should be studied to understand potential risks. Risk of tumour formation with the product may also need to be characterised. To the extent that this information can be generated by in vitro testing, studies in animals may not be needed and limitations on the capability of preclinical data to predict human toxicity are recognised: species-specificity make some cell products act only in humans and a human cell-product might be expected to be rejected by immunocompetent animals. Does this suggest testing in immunosuppressed animals or of development of an animal-cell product supposedly similar to the human cell product? No single answer seems to fit every situation.
authors.affiliation: Medicines & Healthcare Products Regulatory Agency, 151 Buckingham Palace Road, London SW1W 9SZ, UK. Electronic address: jw.mcblane@mhra.gsi.gov.uk.
authors.forename: James W
authors.initials: JW
authors.lastname: McBlane
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects; D006801:Humans; D061214:Patient Safety
keywords: Advanced therapy medicinal products; Cell therapy; Clinical trials; Marketing authorisation; Preclinical testing; Tumourigenicity