Using default methodologies to derive an acceptable daily exposure (ADE).

Autor: Faria EC; Janssen Pharmaceutical Company, an Affiliate of Johnson & Johnson, United States. Electronic address: efaria1@its.jnj.com., Bercu JP; Gilead Sciences, Inc., United States., Dolan DG; Amgen Inc., United States., Morinello EJ; Genentech, Inc., United States., Pecquet AM; University of Cincinnati, United States., Seaman C; GlaxoSmithKline, United Kingdom., Sehner C; Boehringer Ingelheim Pharma GmbH & Co. KG, Germany., Weideman PA; Genentech, Inc., United States.
Jazyk: angličtina
Zdroj: Regulatory toxicology and pharmacology : RTP [Regul Toxicol Pharmacol] 2016 Aug; Vol. 79 Suppl 1, pp. S28-38. Date of Electronic Publication: 2016 May 24.
DOI: 10.1016/j.yrtph.2016.05.026
Abstrakt: This manuscript discusses the different historical and more recent default approaches that have been used to derive an acceptable daily exposure (ADE). While it is preferable to derive a health-based ADE based on a complete nonclinical and clinical data package, this is not always possible. For instance, for drug candidates in early development there may be no or limited nonclinical or clinical trial data. Alternative approaches that can support decision making with less complete data packages represent a variety of methods that rely on default assumptions or data inputs where chemical-specific data on health effects are lacking. A variety of default approaches are used including those based on certain toxicity estimates, a fraction of the therapeutic dose, cleaning-based limits, the threshold of toxicological concern (TTC), and application of hazard banding tools such as occupational exposure banding (OEB). Each of these default approaches is discussed in this manuscript, including their derivation, application, strengths, and limitations. In order to ensure patient safety when faced with toxicological and clinical data-gaps, default ADE methods should be purposefully as or more protective than ADEs derived from full data packages. Reliance on the subset of default approaches (e.g., TTC or OEB) that are based on toxicological data is preferred over other methods for establishing ADEs in early development while toxicology and clinical data are still being collected.
(Copyright © 2016. Published by Elsevier Inc.)
Databáze: MEDLINE
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