We have located links that may give you full text access.
JOURNAL ARTICLE
REVIEW
Management of organic impurities in small molecule medicinal products: Deriving safe limits for use in early development.
Regulatory Toxicology and Pharmacology : RTP 2017 March
Management of organic non-mutagenic impurities (NMIs) in medicinal products is regulated by the ICH Q3A, B and C guidelines that are applicable at late stages of clinical development (Phase III onwards) and as a consequence there is no guidance for the assessment and control of NMIs in early clinical trials. An analysis of several key in vivo toxicology databases supports the ICH Q3A defined concept that a lifetime dose to 1 mg/day of a NMI would not represent a safety concern to patients. In conjunction with routine (Q)SAR approaches, this 1 mg/day value could be used as a universal qualification threshold for a NMI during any stage of clinical development. This analysis also proposes that modification of this 1 mg/day dose using an established methodology (i.e. Modified Haber's Law) could support 5 mg/day or 0.7% (whichever is lower) as an acceptable limit for a NMI in a drug substance or product in early clinical studies (<6 months). Given the controlled nature of clinical development and the knowledge that most toxicities are dose and duration dependent, these proposed NMI limits provide assurance of patient safety throughout clinical development, without the requirement to commission dedicated in vivo toxicology impurity qualification studies.
Full text links
Related Resources
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app