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NVT Risk Assessment Section

Spring Symposium

‘How to fit an organ-on-a-chip in risk assessment’

On Tuesday April 10th, the NVT Risk Assessment Section organized its yearly spring symposium. The symposium was hosted by TNO in Zeist and entitled ‘How to fit an organ-on-a-chip in risk assessment’. With over 30 participants (risk assessors/toxicologist as well as developers of organ-on-a-chip) the symposium was a great success.

The symposium started with three introductory presentations. First, Andries van der Meer (University of Twente/hDMT) explained the basic principles of organ-on-a-chip (OC) and showed that there are many OCs available (e.g. alveolus, small airway, proximal tubule, glomerulus and small intestine). Andries also presented an example of the use of OC in drug related toxicity and indicated that it is possible to detect side effects of medicines in an earlier stage during development. Second, Minne Heringa (RIVM) addressed the question “What is needed from a risk assessment perspective?”. Risk assessors need OC models for assessment of toxicokinetics, repeated dose toxicity, acute toxicity, reproduction toxicity and non-mutagenic carcinogenicity. As risk assessors need different types of data for different cases, different demands on OC test systems are made. Third, Remko van Vught (Mimetas) presented some practical applications of OC models. For example, a case study on cisplatin induced toxicity. OC is ready for the use for safety assessment. Long-term, repeated dosing and even high throughput screening is possible.

After a coffee break the symposium continued with a workshop. The workshop consisted of four ‘corners’ with a question up for discussion. The participants divided themselves into four groups (with at least one developer of OC) and travelled past the corners. Several topics were discussed and a summary is provided below.

  1. Which answers do you expect from OC to be used in risk assessment?
    How reliable are OC systems (sensitivity, specificity, reproducibility)? How is metabolism taken into account? Hazard assessment. Predictability of long term toxicity (preferably life time toxicity).
  2. What is the technical development needed before we can use OC in risk assessment?
    Standardization and robustness. Simulation of metabolism of test compounds. The translation of in vitro findings to in vivo.
  3. What should be the priorities in OC (i.r.t. risk assessment)?
    The development from 2D models to 3D models. Mode of action to demonstrate human relevance. Quantitative translation to NOAEL. Distinction between simple and complex organs?
  4. Do you have questions/suggestions for the developers of OC?
    Provide an overview of the benefits of OC models compared to simpler/conventional in vitro models. Discuss developments with authorities/regulators to facilitate acceptance.

Below, you can find the presentations of this meeting.

1 Andries van der Meer: Organs-on-chips. Advanced in vitro models for human physiology and disease

2 Minne Heringa: Organ-on-a-Chip: What is needed from a risk assessment perspective?

3 Remko van Vught: Organ-on-a-chip: Practical applications & challenges