Tox News: Issue 13, March 2023

Monday 17 April 2023, 14.00 – 15.30 (GMT), online via Zoom

To support registration of monoclonal antibodies (mAbs) for chronic indications, six-month toxicity studies have historically been conducted, as per ICH S6(R1) guidance. Experience with mAb development has shown a relatively benign and well-understood safety profile for this class, with most toxicity findings anticipated based on pharmacology. Under an EPAA supported and funded project, a consortium of 14 pharmaceutical companies, the Medicines Evaluation Board (MEB) and the NC3Rs conducted a study to evaluate whether a six-month toxicity study is still necessary to assess the long-term safety of mAbs.

Two recent publications from the project will be discussed during the webinar:

• Re-evaluating the need for chronic toxicity studies with therapeutic monoclonal antibodies, using a weight of evidence approach
  Peter van Meer, Medicines Evaluation Board, The Netherlands

• The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain
  Helen Prior, NC3Rs, UK

This webinar is relevant for regulatory and industry scientists working with mAbs and other drug modalities interested in exploring new approaches for chronic toxicity studies and opportunities to apply the 3Rs. There will be a panel discussion at the end of the webinar, when audience members will be able to ask questions.

Use of non-human primates (NHPs) continues to be necessary as part of the drug development process for various reasons, including current regulatory requirements and scientific justifications of human relevance, to ensure the safety of new pharmaceuticals in humans. With the increase in the development of biotherapeutics within the pharmaceutical industry in recent years, the number of NHPs used for testing has also increased. However, due to the COVID-19 pandemic and the concomitant export ban from China, there is a current NHP shortage.

The NC3Rs hosted a webinar in December 2022 to to provide an overview of the opportunities that are currently available or being considered to minimise NHP use in drug development, highlighting the work of various industry consortia.

The webinar consists of five presentations from Helen Prior (NC3Rs), Joanne Birkebak (Gilead Sciences), Charles Mattis (AbbVie), Hongbin Yu (Boehringer-Ingelheim) & Karelle Menochet (UCB) and Fred Brouta (UCB), and is relevant for regulatory and industry scientists interested in minimising the use of NHP in drug development.

*Presentation recordings are hosted on a password-protected web page. If you previously registered for the webinar and have not yet received the password, or if you were not registered but would like to view the recordings, please email enquiries@nc3rs.org.uk to request access.

A recent article in the New York Times provides an overview of the alternatives to animal testing available for drug development, showcasing recent examples of in vitro and in silico methodologies. Elisa Passini and Cathy Vickers are among the experts interviewed in the article.

Our Acting Head of Toxicology Natalie Burden has recently been accepted to join the European Register of Toxicologists - a list of toxicologists who excel by high standards of education, skills, experience, and professional standing.

Natalie has also been invited to join the newly convened steering team for the HESI Next Generation ERA Committee. Formed in 2022 by merging of the former HESI Committees on Animal Alternatives in Environmental Risk Assessment (ERA) and Bioaccumulation, their mission is to develop, refine, and communicate the scientific tools and approaches needed to support ecological risk assessment around the globe, with a focus on alternative, non-animal testing methods. Natalie will join other experts to help lead the committee, ensure progress of the projects, and assist with outreach.

The NC3Rs Tox Team representatives were recently invited to join a HESI DART working group on “Minimizing use of sexually mature NHPs for developmental and reproductive toxicology (DART) testing for pharmaceuticals”. This industry consortium aims to provide a white paper reviewing NHP use in DART packages, availability of alternative approaches and case-studies of when NHPs were or were not used.  

7 – 8 June, central London

The NC3Rs is pleased to be co-hosting the 2023 HESI annual meeting on the theme of Not just another NAMs meeting: NAMs for Safety Assessment, From Aspiration to Implementation. Through discussion across among various experts, we will tackle core questions relating to the practical application of NAMs across different sectors, elements of safety evaluation, and different value paradigms. If you are interested in navigating the often-complex intersection between innovation, health protection, implementation, and the 3Rs – this is the event for you. 

In February we hosted a brainstorming meeting in collaboration with the ABPI (Association of the British Pharmaceutical Industry), to strategically review the current landscape and identify novel opportunities to apply the 3Rs in drug development. We brought together 36 experts from the pharma industry and regulatory agencies and identified priority areas for future high impact programmes of work. Look out for further information later in 2023!

This year's International 3Rs Prize is now open to applications from anyone in the world who has published an outstanding and original paper with demonstrable 3Rs impacts in the past three years. This prestigious annual award, sponsored by GSK, consists of a £2k personal award and a £28k prize grant to further the 3Rs impact of the winning research. Researchers in any field of academia or industry are eligible to apply.

• Chien H, Prior H, Andrews L, van Aerts L, Cauvin A, Clarke D, Datta K, Dempster M, Dybdal N, Freebern W, de Haan L, Herzyk D, Hey A, Kissner T, Kronenberg S, Leach M, Lee D, Schutte K, Sewell F, Trouba K, Ulrich P, Weir L, van Meer P (2023). Re-evaluating the need for chronic toxicity studies with therapeutic monoclonal antibodies, using a weight of evidence approach. Regulatory Toxicology and Pharmacology 138:105329. https://doi.org/10.1016/j.yrtph.2022.105329

• Langan L, Paparella M, Burden N, Constantine L, Margiotta-Casaluci L, Miller T, Jannicke Moe S, Owen S, Schaffer A, Sikanen T (2023). Big Question to Developing Solutions: A Decade of Progress in the Development of Aquatic New Approach Methodologies from 2012 to 2022. Environmental Toxicology and Chemistry https://doi.org/10.1002/etc.5578

• Mitchell C, Burden N, Bonnell M, Hecker M, Hutchinson T, Jagla M, LaLone C, Lagadic L, Lynn S, Shore B, Song Y, Vliet S, Wheeler J, Embry M (2023). New Approach Methodologies for the Endocrine Activity Toolbox: Environmental Assessment for Fish and Amphibians. Environmental Toxicology and Chemistry https://doi.org/10.1002/etc.5584

• Prior H, Andrews L, Cauvin A, Chien H, Clarke D, Datta K, Dempster M, Dybdal N, Freebern W, de Haan L, Herzyk D, Hey A, Kissner T, Kronenberg S, Leach M, Lee D, Reid K, Schutte K, Sewell F, Trouba K, Ulrich P, van Aerts L, van Meer P, Weir L (2023). The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain. Regulatory Toxicology and Pharmacology 138:105339. https://doi.org/10.1016/j.yrtph.2023.105339