We recently invited our scientific community to vote for their favourite Lhasa 2024 publication across 3 categories: Toxicology (excluding nitrosamines), Toxicology (specifically nitrosamines) and Chemistry. These awards not only recognise exceptional contributions by Lhasa scientists, but also highlight impactful research that drives progress in our fields and informs the direction of future publications.
The winners were revealed during our annual Lhasa Christmas party — did your favourite scientific paper make the list?
Toxicology excluding nitrosamines
Published in Computational Toxicology, this publication details an alternative approach to animal testing, which can be used to screen for developmental and reproductive toxicity (DART) hazards at the early stages of compound development. This work highlights a step forward in animal-free safety assessments, with the potential to aid regulatory DART-based safety assessments.
Key highlights include:
- The creation of a vast DART adverse outcome pathway (AOP) network with 340 key events (including 68 molecular initiating events). AOPs are a formalised approach to documenting the mechanisms of DART.
- An evaluation of the performance of the AOP framework as a DART hazard screening tool, enhancing the development and application of new approach methodologies (NAMs) for hazard identification.
- Contributions to integrated approaches to testing and assessment (IATAs) for regulatory purposes.
- A case study exploring how the DART AOP framework could support NAM based ICH S5 submissions.
This publication was not only the winner in its category but also received the most votes overall. To celebrate this achievement, we’ve made it open access for all to enjoy. Read the full publication here.
Toxicology specifically nitrosamines
As nitrosamine safety assessments in drugs and medicines continue to be a critical area of focus, this publication provides invaluable insights into the mechanisms of nitrosamine mutagenicity and their correlation with carcinogenic potency. Understanding these mechanisms is essential for identifying high-potency nitrosamines and mitigating associated risks.
Key insights include:
- Detailed analysis of potential metabolic activation and deactivation pathways, such as α-carbon hydroxylation, oxidative N-dealkylation and denitrosation.
- Confirmation that the mechanism that leads to high carcinogenic potency for nitrosamines is α-carbon hydroxylation.
- Evaluation of the mutagenic and carcinogenic risks of nitrosamines, including nitrosamine drug substance-related impurities (NDSRIs).
This paper equips researchers and regulators with the knowledge needed to better assess and control nitrosamine-related risks in pharmaceuticals, access it here.
Chemistry
This collaborative effort, involving industry leaders from GSK, Pfizer, Hoffmann-La Roche, AstraZeneca, and Amgen, presents a series of real-world case studies demonstrating how ICH M7 Control Options 3 and 4 can still be effectively leveraged with low a purge ratio. By utilising analytical data related to a key control point in the process, in conjunction with the original purge rationale, control of mutagenic impurities can be sufficiently demonstrated.
Key highlights include:
- Practical approaches to purge control strategy decisions.
- Demonstrations of mutagenic impurity control through industrial case studies.
- Valuable insights for regulatory compliance and the development of robust impurity management strategies.
This paper serves as a practical guide for pharmaceutical scientists navigating the complexities of ICH M7 compliance, read it here.
Looking ahead
The Lhasa 2024 Publication Awards celebrate hard work, innovation and collaboration with our members, and we’re excited to see how this year’s achievements will inspire future research. Congratulations to all our winners and thank you to everyone who voted and contributed to this year’s successes. Together, we’re shaping the future of toxicology and chemistry to inform decision making on chemical safety and reduce the need for animal testing.
Last Updated on January 2, 2025 by lhasalimited
