Some Definitions in the Childhood Vaccines Manufacturing Process. Source: European Pharmacopoeia online 8.1. 5.2.1. Terminology used in monographs on biological products. 01/2008:50201, corrected 6.0. Consulted on May 5, 2014. Manufacturing definitions:
A number of important definitions in the manufacturing process of viral and bacterial vaccines can be found in Table 14.3.
Examples of cell substrates: The following are examples of routinely used as well as novel cell substrates (Hess et al., 2012).
Primary cell culture: Primary cells are established directly from tissues of animals. Chicken embryo fibroblasts (CEFs) as well as kidney, lung, or ovary cells from dogs, monkeys, rabbits, and hamsters have been used in the manufacturing
of vaccines.
Diploid cell line: Diploid cells from human (e.g., WI-38 or MRC-5) or monkey origin (e.g., FRh1-2) have a finite capacity (i.e., a limited number of passages) for serial propagation that ends in senescence. The cells have the cytological
characteristic of a low frequency of chromosomal abnormalities.
Continuous cell line: Continuous cell lines (CCLs) have the advantages of being immortalized and easily obtained through serial subcultivations leading to spontaneous transformation of primary cells, e.g., Madin–Darby canine kidney (MDCK) cells and African green monkey continuous cell line (Vero). Targeted manipulation of primary cells by either activation of proto-oncogenes or transformation through oncogenic genes or oncogenic viruses also results in the transformed phenotype and immortalization of cells.
Novel cell substrates: Novel cell substrates are derived predominantly from human (e.g., HEK 293 and PER.C6) and avian (e.g., EB66 and CR) sources.
HEK 293: Human embryonic kidney cell 293 cell line was generated in the late 1970s by transformation of embryonic kidney cells with sheared DNA of human adenovirus type 5 (Ad5). The adenovirus-derived genes contain early transforming genes and immortalize the cell, hence resulting in continuous cell growth.
PER.C6: The PER.C6 cell line is a human retina-derived cell line that also possesses the E1A and the E1B genes of Ad5. The PER.C6 cell line is able to complement the growth of replication incompetent adenoviruses (which lack the Ad5 E1 region).
EB66: The EB66 cell line is a duck embryonic stem cellderived substrate engineered for the expression of monoclonal antibodies.
CR: The Cairina retina cell line is derived from Muscovy duck retinal tissue subsequently transfected with Ad5 E1 genes and Ad5 pIX gene, resulting in AGE1.CR.pIX. HEK 293 and PER.C6 could be considered a cell substrate for the manufacture of live attenuated viral vaccines because they produce high virus yields, which is important from a manufacturing perspective.