Despite the wide application in cell culture, using serum in a medium has a few disadvantages:

• Physiological variability: Although the major constituents of serum, such as albumin and transferrin, are known, serum also contains a wide variety of minor components (e.g. nutrients, growth factors, hormones, minerals, etc.) that are not fully determined but have a considerable effect on cell growth.
• Shelf life and consistency: Serum varies from batch to batch, and at best can last one year.
• Quality control: Extensive testing is required to ensure the quality, especially when changing to a new batch.
• Specificity: Several batches of serum may be needed when more than one cell type is used.
• Downstream processing: Product purification can be complicated because of the presence of undefined substances in serum.
• Contamination: Serum is frequently contaminated with viruses, which represents an additional unknown factor to cell culture and may be harmful to cells.