Lhasa Limited shared knowledge shared progress
  • Highlighted Item:
  • Webinar:
  • Publisher:
  • Publication Date:
    Apr 2006
  • Reference:
    Regulatory Toxicology and Pharmacology, 2006, 44(3), pp282-293
  • DOI:
  • PMID:
  • Publication Type:
  • Related Products:
  • Scientific Area:
  • Endpoint:
  • Industry Type:
  • Related event:

The application of structure-based assessment to support safety and chemistry diligence to manage genotoxic impurities in active pharmaceutical ingredients during drug development

Caron S; Cyr MO; Dobo KL; Greene N; Ku WW;

Starting materials and intermediates used to synthesize pharmaceuticals are reactive in nature and may be present as impurities in the active pharmaceutical ingredient (API) used for preclinical safety studies and clinical trials. Furthermore, starting materials and intermediates may be known or suspected mutagens and/or carcinogens. Therefore, during drug development due diligence need be applied from two perspectives (1) to understand potential mutagenic and carcinogenic risks associated with compounds used for synthesis and (2) to understand the capability of synthetic processes to control genotoxic impurities in the API. Recently, a task force comprised of experts from pharmaceutical industry proposed guidance, with recommendations for classification, testing, qualification and assessing risk of genotoxic impurities. In our experience the proposed structure-based classification, has differentiated 75% of starting materials and intermediates as mutagenic and non-mutagenic with high concordance (92%) when compared with Ames results. Structure-based assessment has been used to identify genotoxic hazards, and prompted evaluation of fate of genotoxic impurities in API. These two assessments (safety and chemistry) culminate in identification of genotoxic impurities known or suspected to exceed acceptable levels in API, thereby triggering actions needed to assure appropriate control and measurement methods are in place. Hypothetical case studies are presented demonstrating this multi-disciplinary approach.

Visit site

Additional Documents

    © 2021 Lhasa Limited | Registered office: Granary Wharf House, 2 Canal Wharf, Leeds, LS11 5PS, UK Tel: +44 (0)113 394 6020
    VAT number 396 8737 77 | Lhasa Limited is registered as a charity (290866)| Company Registration Number 01765239 (England and Wales).

    Apart from the free survey software, we also have access to QuestionPro's free survey templates . We've found many of them useful and powerful to collect insights from various stakeholders of our organization.