3Rs Quarterly

Drug-induced kidney injury (DIKI) is poorly predicted in animal studies. RIVM contributed to a systematic review on in vitro models to study DIKI. Early integration of regulatory and clinical perspectives can enhance standardization of in vitro modeling. Study quality was assessed with a validation score based on published regulatory guidance and industrial perspectives. Kidney regions mostly modeled are the proximal tubule, followed by glomerulus and Bowman's capsule. More complex models showed higher validation scores, reflecting the value of advanced in vitro models. 

Next Generation Risk Assessment (NGRA) is an exposure-led, hypothesis-driven approach with potential to support animal-free safety decision-making. An international workshop on application of NGRA for safety assessment of cosmetic ingredients was held in 2019. RIVM contributed to this workshop and report. It was concluded that NGRA is a promising approach, but it is still in its infancy. More in vitro and in silico methods as well as further case studies need to be developed to determine whether safety decisions are sufficiently protective for the consumer.

RIVM published a review with the Dutch Medicines Evaluation Board (MEB-CBG) and the German Bundesinstitut für Risikobewertung (BfR) on the application of organ-on-chips (OoC) in toxicology and pharmacology. The broader biological domain of OoC may enhance their predictive value, while their complexity presents issues with throughput, standardization and transferability. Open technology platforms and collaboration between developers and risk assessors may provide a strategy to build confidence in OoC application in safety and efficacy assessment.

WC11 was held online form 23 August till 2 September. The main topic of the conference was 3R in transition, acknowledging that in the past years animal-free innovations have evolved tremendously, but are yet sparsely applied. RIVM was actively involved in the organisation of the conference, as well as in ten sessions and poster presentations as organisers, chairs and presenters.

ZonMw invites industry, research institutions and legislative bodies to formulate a challenge for better prediction of clinical efficacy and/or risk and safety assessments without the use of animals. With this approach, ZonMw encourages the development of animal-free innovations with impact that must lead to marketable methods, models and/or services. Challengers can submit their proposal until 6 January 2022.

How can we encourage the acceptance and implementation of existing animal-free models? This is the key question in the new call published by the Dutch Research Agenda (NWA), with specific focus on the safety assessment of chemicals. Almost 2.9 million euros is being made available in this call for research by broad consortia of researchers and society partners. The Dutch Research Council (NWO) is realising this call in collaboration with ZonMw.

Every two years the Willy van Heumen prize is awarded to scientists whose research can replace or greatly reduce the use of laboratory animals. This year LUMC researcher dr. Ferenc Scheeren won the prize for his work on improved antibody production by specialised cells (hybridomas). By using CRISPR-Cas, the genetic code of hybridomas can be edited very precisely, which allows to generate the right antibody isotype in an efficient manner. This greatly reduces the use of animals for antibody production.

Working towards animal-free research strategies is an effort crossing international and interdisciplinary borders. TPI.tv is designed to facilitate this transition through connecting people and ideas via video messages. On TPI.tv, short video messages (‘pitches’) provide the medium for researchers to display their findings and request input if needed. New videos on TPI.tv:

Why we need this transition