Cell substrates are cells used to manufacture a biological product. It is well established that cell substrates themselves and events linked to cell growth can affect the characteristics and safety of the resultant biological products. Therefore, a thorough understanding of the characteristics of the cell substrate is essential in order to identify points of concern and to develop a quality control system that addresses those points. Recent advances in the use and quality control of new animal cell substrates, particularly continuous cell lines (CCLs) and insect cells, led to the conclusion that an update of the current WHORequirements (TRS 878) [ 1] should be prepared. In order to facilitate the resolution of regulatory /scientific issues related to the use of animal cell cultures, including human, as substrates for the production of biological products, WHO initiated this revision of its Requirements on cell substrates by establishing a Study Group (SG). Animal cells refer to cells derived from organisms classified in the animal kingdom. This document is the result of the SG effort, including wide consultations with individuals and organizations with expertise in this area. After receiving comments from this consultative process, as well as from invited reviewers, further revision of the draft recommendations was undertaken and presented to the ECBS in 2010. During the development of this document, guidances on this topic issued by other relevant organizations were considered. Effort was made to be compatible with the existing guidances, whenever possible. These recommendations provide guidance to National Regulatory Authorities (NRAs), National Control Laboratories (NCLs) and manufacturers on basic principles and, in some cases, on detailed procedures that are appropriate to consider in the characterization of animal cells that are proposed for use in the manufacture of biological products. Although the decision-making authority lies with the NRA, it is advisable that NCL experts on this topic be consulted.
