OpenTox Virtual Conference 2021 Session 1

Models and Methods: the reality check by the regulatory science  community in a world of change  

Sandra Coecke1, Sonja Beken2 and Patience Browne3 

1European Commission Joint Research Centre, Ispra, Italy, 2Federal Agency for Medicines and Health Products  (FAMHP), Brussels Belgium, 3Organisation for Economic Co-operation and Development (OECD), Paris, France  

The first guidance on Good Cell Culture Practice (GCCP) dates back to 2005 (Coecke et al. 2005). With the availability of human-induced pluripotent (2006) stem cells, the potential applications of human cell culture models have been greatly broadened. When using stem cells and stem-cell-derived models in research, product development, testing, and manufacture of biotechnology products and cell-based medicines, it remains critical to include aspects of quality assurance. As such, the original set of GCCP principles of best practice can be used as a basis to assure good cell and tissue practices and conditions when working with stem cell-derived test systems in simple set-ups or in very technologically advanced formats (Pamies et al.,  2017). GCCP and its next-generation principles (GCCP 2.0) are intended as guidance to obtain reliable and relevant study data. Applying GCCP as part of overall Good In Vitro Method Practices (GIVIMP, OECD 2018) by the global life science community is leading to more harmonisation of in vitro method-related processes and procedures. Researchers are key players to ensure the use of such best scientific and quality practices and are ideal ambassadors to use them in the novel generation of stem cell and tissue-based methods. The European Commission Joint Research Centre’s European Union  Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) is working on developing and validating innovative,  mechanistic methods and approaches based on current harmonized scientific and quality standards complying with the GCCP  principles and the GIVIMP guidance document (OECD, 2018) and is crowd-sourcing for introducing stem cells and stem-cell-derived methods into the required regulatory test batteries for identifying thyroid disrupting chemicals. Key instruments to disseminate globally harmonized good cell, tissue, and method practices are published principles and guidance, conferences,  face-to-face meetings, training, webinars, templates (Krebs et al., 2019), reporting, and evaluation tools (e.g.  http://www.scirap.org/) and e-learning training materials.  

References  

Coecke S, Balls M, Bowe G, Davis J, Gstraunthaler G, Hartung T, Hay R, Merten OW, Price A, Schechtman L, Stacey G, Stokes  W (2005) Second ECVAM Task Force on Good Cell Culture Practice. Guidance on good cell culture practice. a report of the second ECVAM task force on good cell culture practice. Altern Lab Anim. 33:261-287.;  

OECD 2018, Guidance Document on Good In Vitro Method Practices (GIVIMP). Series on testing and assessment n° 286,  ENV/JM/MONO(2018)19. OECD, Paris.;  

Krebs A, Waldmann T, Wilks MF, Van Vugt-Lussenburg BMA, Van der Burg B, Terron A, Steger-Hartmann T, Ruegg J, Rovida  C, Pedersen E, Pallocca G, Luijten M, Leite SB, Kustermann S, Kamp H, Hoeng J, Hewitt P, Herzler M, Hengstler JG, Heinonen  T, Hartung T, Hardy B, Gantner F, Fritsche E, Fant K, Ezendam J, Exner T, Dunkern T, Dietrich DR, Coecke S, Busquet F,  Braeuning A, Bondarenko O, Bennekou SH, Beilmann M, Leist M. (2019) Template for the description of cell-based  toxicological test methods to allow evaluation and regulatory use of the data. ALTEX. 36:682-699.; Pamies D, Bal-Price A,  Simeonov A, Tagle D, Allen D, Gerhold D, Yin D, Pistollato F, Inutsuka T, Sullivan K, Stacey G, Salem H, Leist M, Daneshian M,  Vemuri MC, McFarland R, Coecke S, Fitzpatrick SC, Lakshmipathy U, Mack A, Wang WB, Yamazaki D, Sekino Y, Kanda Y,  Smirnova L, Hartung T. (2017) Good Cell Culture Practice for stem cells and stem-cell-derived models. ALTEX. 34:95-132.;  

Pamies D, Bal-Price A, Chesné C, Coecke S, Dinnyes A, Eskes C, Grillari R, Gstraunthaler G, Hartung T, Jennings P, Leist M,  Martin U, Passier R, Schwamborn JC, Stacey GN, Ellinger-Ziegelbauer H, Daneshian M. (2018) Advanced Good Cell Culture  Practice for human primary, stem cell-derived and organoid models as well as microphysiological systems. ALTEX. 35:353- 378.