The effective use of vaccines over the last few decades has resulted in reduction in the incidence of many infectious diseases in developed countries and especially in the prevention and control of major infections like Poliomyelitis, Diphtheria, Pertussis, Tetanus, Measles, Mumps, Rubella and Hepatitis - B. yet vaccines are not valued sufficiently and millions of children still die each year from vaccine preventable diseases. The production of vaccines using a variety of cell substrate has been an enormous success and in the last five decades of vaccine production there has been series of landmarks. The landmark was in 1950s, the use of primary cells was accepted for the production of Polio virus vaccine.

Subsequently two decades later in 1970s the diploid cells were accepted for vaccine production. Then in 1980s certain continuous cell lines (CCL) were accepted for the production of vaccines.

Biologicals produced in CCL have found applications in wide ranging fields, which includes hormone replacement, vaccines, immunosuppression and immunotherapy and control of homeostasis. Therapies are being developed for wide variety of conditions including thrombo hemorrhagic syndromes, inborn errors of metabolism, cataracts and arthritis.

Primary Cell Substrates
They are easy to prepare and obtained directly from the trypsinised tissues of normal animals. These cells have played a prominent role in the development of virology as a science and of immunology in particular. For more than forty years these substrates have been used in production of live and inactivated vaccines namely Poliomyelitis, Measles, Mumps and rubella. These cells have disadvantages like having a finite life span and each batch can''t be characterized like diploid and CCLs.

Cell population have a finite life span, do not produce tumors when inoculated into experimental animals and can be characterized more exhaustively. These cell lines are with an infinite life span and can be characterized exhaustively. They are anchorage independent.

The first cell line used for the preparation of human virus vaccine was made in 1950s for the experimental Adeno virus vaccine. It was only in 1980 the first cell line was licensed for the production of human biologicals. Tissue plasminogen activator was produced using Chinese hamster ovary (CHO) cell lines in USA and inactivated Poliomyelitis vaccine using Vero cell line in France. Presently Vero cell line is being used to produce human vaccines like Poliomyelitis and Rabies and the safety has been established.

The main potential risks associated with the use of cell substrates for the production of biologicals has been considered to be present in three types of contaminants; namely contaminating virus, residual host cell DNA and growth promoting proteins. The WHO acceptance in 1987 of interferons and monoclonal antibodies produced by tumor cells for use in humans, the issues regarding the use of neoplastic cells for the production of purified biological products were resolved. But the use of neoplastic cells as substrate for viral vaccines, especially live virus vaccines, continues to be controversial The continuous cell lines may not express tumorigenic properties below certain passage level but subsequently may display increasing evidence of tumori-genic phenotype with increasing passage. Therefore it is important to establish an age limit for in-vitro cultures.