Good cell culture practice

Last but not least there is an urgent need to "harmonize" or "standardize" all these procedures so that improved interlaboratory comparisons can be achieved. Such procedures include, cell isolation, growth substrates, cell culture media including the mode of medium application. A first initiative in this direction has been taken by ECVAM (European Center for the Validation of Alternative Methods, a section of the European Commission Institute for Health and Consumer Protection) by founding a task force dealing with the creation of guidelines for "Good Cell Culture Practice" [247, 248]. 

Gstraunthaler G. Standardisation in Cell and Tissue Culture -The Need for Specific GLP Guidelines in the Cell Culture Laboratory (Good Cell Culture Practice - GCCP). ALTEX 23 SuppI 274-277,2006. 

Balls M, Coecke S, Bowe G, Davis J, Gstraunthaler G, Flartung T, Flay R, Merten OW, Price A, Schechtman EM, Stacey G, and Stokes W.The Importance of Good Cell Culture Practice (GCCP). AETEX 23 SuppI 270-273, 2006. 

Schechtman L, Stacey G, Stokes W (2005) Guidance on good cell culture practice. Altern Lab Anim 33 261-287... 

Hartung T, Gstraunthaler G, Balls M (2000) Bologna statement on good cell culture practice (GCCP). ALTEX 17 38-39... 

It is essential that the highest scientific standards should be made, through, for example, compliance with the principles of Good Cell Culture Practice, which is analogous to Good Laboratory Practice and Good Manufacturing Practice. 

Endotoxins are found in some bacterial sources, such as E. coli. For other products they are considered a contaminant that should not be present and can be controlled by adherence to good manufacturing practices (GMPs). Nucleic acids, once considered a significant risk, are now thought of as cellular impurities, and their removal should be validated [2,3]. Proteins that pose a potential risk (e.g., immunogenicity) include host cell proteins, aberrant protein product, proteins used in cell culture, and those associated with the process (e.g., protein A affinity ligands or nucleases employed to reduce viscosity). 

In the Phase I studies it was shown that in cell cultures [NaCa(P03)3] fibers degraded and cleared as predicted. Rather than attempting to give a detailed analysis of the work here the reader is referred to the original article. There, the minute compliances with the Good Laboratory Practice Regulations dictated by the EPA are related. It will suffice for our purposes to quote the summary statement from the article. 

Trichomonad flagellates seemed to be a good first choice. The human pathogen Trichomonas vaginalis and the cattle pathogen Tritrichomonas foetus were much-studied species available in bacterium-free cultures and were thus amenable to biochemical and cell fractionation studies, approaches extensively practiced by our group. The available physiological data showed that the respiration of these species was not of mitochondrial type, because it could not be inhibited with cyanide and other mitochondrial inhibitors. Furthermore no cytochromes were detected in these trichomonads (Ryley 1955). 

Figure 9-6 A generic strategy integrating the three facets of developmental toxicity risk assessment namely (a) the risk of pharmacologic modulation of the therapeutic target during gestation, (b) in silico, SAR and (c) in vitro screening. Abbreviations The chick embryo neural retina (CENR) embryonic stem cell test (EST), whole embryo culture (WEC), Good Laboratory Practice (GLP), Embryo/Fetal Developmental Toxicity (EFD) study. "Front-loading" is the conduct of the EFD study prior to Phase lib.

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