Establishing a Method Based on an Existing Human Cell Line

If a cell line-based assay for the tests to be undertaken is already available, then it is important to assess the level of validation that has been achieved in line with international requirements [6]. If proceeding with the selected method it is important that the cell line should be obtained from the original or otherwise qualified source of cells, as a cell line transferred through different laboratories may undergo significant changes [7]. Preferably, the source of cells will be a bona fide biological resource center or culture collection which has performed basic tests to help assure authenticity and an absence of microbiological contamination (e.g., ATCC,; Coriell Institute,; ECACC, www.; DSMZ,; ICLC,; JCRB, http://www.jhsf. However, whilst such organizations operate professionally, they cannot be expected to perform qualification of the cells for all applications of each cell line, and this should therefore be an important part of the testing work-program. If an original and quality-controlled source of the cell line is not available, it is wise to obtain cells from more than one source in order to compare their performance and authenticity (see below), as cross-contamination of cell lines is all too common [7-9]. Likewise, cells with different histories of laboratory use have been shown to display different characteristics.

In addition to considering the cells it is also important to establish critical control materials. These may include preparations of particular drugs or chemicals of known activity, or standardized biological reagents used for the culture of cells (see below). Where these are chemically defined they may be available as commercial preparations which meet Pharmacopoeia standards. The European Centre for the Validation ofAlternative Methods recently held a workshop on reference standards in the context of test standardization and validation ( Aspects of stability, availability, homogeneity, purity, adequate potency within the response range of the test and scientific soundness of choice must all be considered (in addition to cost, safety and practicability) when choosing positive/negative controls and calibrants of test systems. Where the control materials are of biological origin (e.g., antibodies, growth factors, cytokines, interleukins), a local in-house control may be very difficult to standardize with outside groups. However, the World Health Organization manages a program generating biological reference materials of medical value, which are available as International References Materials (see

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