Putting Science into Standards workshop on standards for organ-on-chip

Abstract

The European Commission Joint Research Centre and the European Standardization Organizations CEN and CENELEC organized the “Putting Science into Standards” workshop, focusing on organ-on-chip technologies. The workshop, held online on 28–29 April, 2021, aimed at identifying needs and priorities for standards development and suggesting possible ways forward.

Highlights

• •A 2-days workshop on standards for organ-on-chip, from engineering to life science.
• •The workshop was organised by the European Commission JRC and CEN-CENELEC.
• •Expected performances of off-the-shelf devices and banked cells to be a priority.
• •The panellists proposed the creation of a CEN-CENELEC Focus Group.

The European Commission Joint Research Centre and the European Standardization Organizations CEN and CENELEC organized the “Putting Science into Standards” workshop, focusing on organ-on-chip technologies. The workshop, held online on 28–29 April, 2021, aimed at identifying needs and priorities for standards development and suggesting possible ways forward.

Main text

Introduction

Standards are documents that provide requirements, specifications, guidelines, or characteristics that can be used to ensure that materials, products, processes, and services are consistently fit for purpose. Standards are established by consensus and formally approved by Standards Developing Organizations (SDOs), although many informal standards developed by professional association or consortia are also widely adopted. Policy-makers and regulators rely on standards to design and enforce legislation since they address a wide range of needs, including ensuring product functionality, compatibility and interoperability, and safeguarding human health.

Several recent position papers have described the vision of stakeholders on the role of standards in the organ-on-chip (OoC) field (Fabre et al., 2020; Mastrangeli 2019a, Mastrangeli et al., 2019b; Marx et al., 2020; Piergiovanni et al., 2021). There is widespread agreement that standardization is an important enabler for innovation, supporting the development and application of OoC devices in several ways. These include performance assessment and benchmarking, interoperability, and qualification for different contexts of use. Standards can also improve communication among stakeholders, for example, by providing agreed terminology and reporting methods.

To further advance in this direction, there is a need to bring together SDOs, OoC developers, and end users with a view to identifying priorities for standards development and to set the wheels in motion.

Putting Science into Standards for OoC

The European Commission’s Joint Research Centre and the European Standardization Organizations CEN and CENELEC (CEN-CNLC) carry out a yearly foresight on standardization action called “Putting Science into Standards” (PSIS), which seeks to feed the European standardization system with scientific input. This initiative is a unique opportunity to gather stakeholders to identify issues and priorities, to share views on future developments, and to provide recommendations to CEN-CNLC on possible next steps. OoC has been selected as topic of the 2021 edition of PSIS workshop, which took place online on 28–29 April, 2021.

The first half-day was dedicated to creating a common ground for the multi-disciplinary participants, with presentations from OoC and standardization experts to summarize the state-of-the-art and the motivation to develop standards. During the second day, workshop participants chose from one of three parallel thematic tracks: life science, engineering, and regulatory and data management. The discussion in each track was led by a panel of selected experts and complemented by input from workshop participants.

Life science

The life science track was divided into the sub-sessions: “Cells and Tissues,” “Biomaterials and 3D printing,” and “Assays and Biomarkers.” Standardizing biology per se is, of course, not possible due to the nature of biology itself. It is, however, possible to standardize the procedures that we use to model it to ensure relevance, reproducibility, and robustness. One main recommendation from the sessions was to make better use of guidance documents, such as Good In Vitro Method Practices and Good Cell Culture Practices, and to properly document experimental methods using Standard Operating Procedures. For an OoC model to be fit for its intended purpose, its ability to capture key aspects of (patho)physiology and to reproduce specific organ functions is essential. This can be achieved by using cell models with proper functionality. With the advent of (human) stem cells, new tissue specific cell sources have arisen, in addition to primary cells from donors and cancer cell lines. Standardization for stem cells will need to consider requirements for genetic stability and reproducibility that are necessary not only for in vitro methods, but also in clinical translation for regenerative medicine.

Engineering

The engineering track was divided into the sub-sessions: “Sensing and Integration,” “Interoperability and Control Systems,” and “Microfluidics.” Participants felt that ready-to-use devices and components would greatly facilitate the adoption of OoC if these were suitably characterized to facilitate their proper use. A standard catalog of components, as well as standardized dimensions and geometries, could help interoperability, at the same time allowing enough design choice for developing novel devices. Metrology standards, which serve measurement purposes, were seen as being fundamentally important to support the development of a common strategy for testing and calibration. Moreover, a general standard protocol for materials characterization could help tackle a number of associated issues, such as unwanted or uncontrolled adsorption of molecules onto OoC materials. This has often been a bottleneck for interpreting dosage responses of cells to compound libraries or medicines.

Regulatory and data management

The regulatory and data management track was divided into the sub-sessions: “Good Experimental Practices,” “Data acquisition and Management,” and “Characterisation and Reporting.” Regulators are looking favorably to the use of OoC and propose that the community focuses initially on data-rich contexts of use, such as liver metabolism and cardiotoxicity. The choice of suitable reference compounds should be considered, for example, by using commercially available molecules in relevant doses. There are several initiatives to define lists of reference chemicals for specific contexts of use. By using appropriate negative and positive controls with unambiguous effects in humans, it is possible to define the predictive capacity of a test method. Adherence to established reporting standards is crucial to encourage regulatory uptake, including descriptions of a minimum set of operational parameters that demonstrate reliability. Enabling data-sharing across different repositories for multiple usage was highlighted as an important topic, with many community standards already existing. High-priority actions to be put forward included the use of a common vocabulary, uniform data formats, and minimum information checklists for metadata.

Next steps

A plenary panel discussion brought together senior representatives from different fields to collect views on ways forward. Some believed that end users are primarily attracted by off-the-shelf devices and banked cells that should be thoroughly characterized. Standards can then guarantee that the performance is as expected. On a more practical note, the panel proposed the creation of a CEN-CNLC focus group on OoC with the specific task to identify a roadmap and agree on priorities that would guide the development of standards via existing or newly created CEN-CNLC Technical Boards. This focus groups should interact closely with the European Society of Organ-on-Chip and the International Society for Stem Cell Research that could readily provide access to a large network of experts and resources to support standardization activities.