Gene expression by large-scale transfection of mammalian and animal cells is becoming an established technology for the fast production of therapeutic biotech products. However, efforts are still needed to optimize production parameters in order to maximize volumetric productivity while maintaining product quality.Generally, in cell culture 5% to 15% serum is used as supplement in the standard basal media in addition to salts and amino acids for healthy cell growth. To overcome the serum related problems, serum derived and animal derived substances are being used. The serum, serum derived or animal derived substances have some advantages and disadvantages which we have summarized in this review. This article mainly focuses on the replacement of serum, serum derived or animal derived substance with plant derived peptones to fulfill the regulatory requirements.In addition, this article also highlights the methods of peptone selection, peptone screening and some issues related to peptone utilization and their solutions.On the basis of review, we found that the usage of ultrafiltered plant peptone in combination with polyamine could be the best composition for cells growth and reproducible expression of the therapeutic Bio-products. The source or type of peptone (soy peptone, wheat and rice peptone) and polyamines ( cadaverine, putrescine, spermidine, spermine, agmatine and ornithine etc) are cell dependent and can be selected on the basis of their performance with respect to cell growth, expression of protein of interest with consistency in the production process.