Cell line issues: historical and future perspectives.

The initial decision to use only primary cell cultures for the production of human biological products was challenged in the late 1960s by the introduction of human diploid cells (HDCs), and again in the 1980s by continuous cell lines (CCLs). The history of the HDC controversy is reviewed and lessons from that era that are relevant to the use of CCLs are pointed out. With the introduction of recombinant DNA technology in the 1980s, and the potential usefulness of CCLs in product development, the issue of cell acceptability became more urgent, and several attempts were made to reach a consensus on regulatory issues. In 1986, the World Health Organization convened a Study Group to review the safety issues related to products derived from CCLs. The Study Group made a clear recommendation to pursue CCLs in product development because of the demonstrated capability of modern manufacturing processes to cope with contaminants. Issues such as acceptable levels of cellular DNA in products, the relationship of purity to safety, and the relevance of the genetic stability of recombinant cells to product consistency are current examples of areas in need of discussion and agreement. A system in which regulatory authorities, industry, and the general biomedical community cooperate in finding solutions is ultimately in everyone's best interest.