Current trends in in silico, in vitro toxicology, and safety biomarkers in early drug development.
Drug Chem Toxicol
; 42(2): 113-121, 2019 Mar.
Article
in En
| MEDLINE
| ID: mdl-29161932
ABSTRACT
The development of new medicines is a long and expensive process. Despite growing efforts in R&D over the last decades, attrition rate due to safety issues (especially cardiac and hepatic toxicity) remains a major challenge for the pharmaceutical industry. This may lead to market withdrawal or late stage halting of a drug development program. Consequently, early detection of toxicity issues is critical to avoid late-stage failures. To this end, development of predictive toxicology assays and models have become a strategic matter for drug makers. An integrated approach confronting knowledge-based data sources with in vitro and in vivo experimental data should be performed. A well-defined balance between in vivo and in vitro assays should guide the safety assessment process and include a rationale taking into account ethical considerations as well as associated resourcing involved with animal use. Innovation in de-risking strategies may support refinement of regulatory testing and contribute to (i) improve drug safety evaluation alleviating assessment of the risk-benefit ratio and (ii) promote the access to safe drugs for patients. In this review, promising innovative approaches aiming at facilitating early detection of toxicity during drug development are described.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Toxicology
/
In Vitro Techniques
/
Computer Simulation
/
Drug Development
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Aspects:
Ethics
Limits:
Animals
/
Humans
Language:
En
Journal:
Drug Chem Toxicol
Year:
2019
Document type:
Article
Affiliation country:
Belgium