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Our recombinant proteins are beta-lactam free. Here’s why.

While critical for human health, Beta-Lactam antibiotics such as penicillin and cephalosporin can also have adverse effects on some people. Allergic reactions can range from relatively minor skin rashes to life-threatening anaphylaxis and decreases in blood pressure. While effective in treating infections caused by gram-positive and gram-negative bacteria, up to 10% of adults in the United States have had an allergic response to penicillin.

Given the health risks presented by this broad class of antibiotic compounds, the U.S. Food and Drug Administration (FDA) requires detection of penicillin G and ampicillin residues in non- Beta-Lactam pharmaceuticals at the level of 0.03 ppm. Because of the cross-reactivity (cross-sensitivity) of Beta-Lactams, FDA also recommends that manufacturers establish appropriate separation and control systems to prevent two types of contamination:

  • Contamination of a non-penicillin Beta-Lactam by any other non-penicillin beta-lactam
  • Contamination of any other type of product by a non-penicillin Beta-Lactam

Beta-Lactams are commonly used as selection markers in the production of recombinant proteins. Plasmids containing the gene encoding the protein to be produced also carry the gene for beta-lactamase. Bacteria which take up the plasmid will not die in the presence of a Beta-Lactam antibiotic, which is added to the fermentation process. Despite efforts to remove the antibiotic in subsequent downstream steps used to purify the recombinant protein, a residual amount may remain. If the recombinant protein is then used in culture protocols for cell therapy applications and those cells are infused into a patient, a hypersensitivity reaction may occur.

In the best interest of your research, drug development, and patient safety, Shenandoah Biotechnology converted away from Beta-Lactams and now use kanamycin or another non- Beta-Lactam antibiotic as a selectable marker. The use of penicillin and streptomycin – commonly referred to as “pen-strep” – has also been eliminated in favor of gentamycin in our cell culture suite.

As you consider sources for recombinant proteins to be used in your culture processes, be sure there is no risk of Beta-Lactam antibiotics being present. Ask your supplier of recombinant proteins whether they are Beta-Lactam free, so you have increased confidence that you’ve made the right choice.

[1] Romano, A., Torres, M. J., Namour, F., Mayorga, C., Artesani, M. C., Venuti, A., Guéant, J. L., & Blanca, M. (2002), Immediate

hypersensitivity to cephalosporins. Allergy, 57, 52-57. https://doi.org/10.1034/j.1398-9995.57.s72.18.x

[2] Centers for Disease Control and Prevention (CDC). (2006). Sexually transmitted diseases treatment guidelines 2006.

Available at: www.cdc.gov/std/treatment/2006/penicillinallergy.htm.

[3] FDA Guidance for Industry. (2013). Non-penicillin Beta-Lactam Drugs: A CGMP Framework for Preventing Cross Contamination. Available at: www.fda.gov/files/drugs/published/Non-Penicillin-Beta-Lactam-Drugs–A-CGMP-Framework-for-Preventing-Cross-Contamination.pdf