Non-clinical animal toxicity studies continue to be used routinely to evaluate the safety of pharmaceuticals, and are mandated by regulatory guidelines, but they have important limitations. Their use in early drug discovery, when there is abundant chemical choice, is not practical, and they are unable to detect many clinically significant human toxicities (most notably, idiosyncratic human adverse drug reactions). In vitro methods that use human cells, and assess mechanistically relevant endpoints, have the potential to address these limitations. Useful in vitro assays for genotoxicity, skin sensitisation and eye irritancy have already been developed, and have been incorporated into regulatory guidelines. Exciting progress has also been made in the development of useful in vitro human cardiotoxicity and drug-induced liver injury (DILI) assays. It will now be important to ensure that the utility of these assays, for the prediction of human cardiotoxicity and DILI, is accepted by the scientific community and that they gain regulatory acceptance.

Safety Assessment of Pharmaceuticals

Animal toxicity studies used to assess the safety of new candidate pharmaceuticals prior to their progression into human clinical trials are unable to assess the risk of non-pharmacologically mediated idiosyncratic adverse drug reactions (ADRs), the most frequent of which are drug-induced liver injury and cardiotoxicity. Idiosyncratic ADRs occur only infrequently and in certain susceptible humans, but are caused by many hundreds of different drugs and may lead to serious illness. Areas covered: Idiosyncratic ADRs are initiated by drug-related chemical insults, which cause toxicity due to susceptibility factors that manifest only in certain patients. The chemical insults can be detected using in vitro assays. These enable useful discrimination between drugs that cause high versus low levels of idiosyncratic ADR concern. Especially promising assays, which have been described recently in peer-reviewed scientific literature, are highlighted. Expert opinion: Effective interpretation of in vitro toxicity data requires integration of endpoints from multiple assays, which each address different mechanisms, and must also take account of human systemic and tissue drug exposure in vivo. Widespread acceptance and use of such assays has been hampered by the lack of correlation between idiosyncratic human ADR risk and toxicities observed in vivo in animals.

Human biology-based drug safety evaluation: scientific rationale, current status and future challenges

/pdf/reducing-attrition-through-early-assessment-of-drug-safety-5drjme4yen.pdf

Reducing attrition through early assessment of drug safety

Reducing attrition through early assessment of drug safety: Highlights from the Society of Medicines Research Symposium, held on March 13th, 2014 - National Heart & Lung Institute, Kensington, London, U.K.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

R. Lock

Author Tools

Chat about Author

Papers

Reducing attrition through early assessment of drug safety

Reducing attrition through early assessment of drug safety: Highlights from the Society of Medicines Research Symposium, held on March 13th, 2014 - National Heart & Lung Institute, Kensington, London, U.K.