Beta-glucan contamination of pharmaceutical products: How much should we accept?

• Published in: Cancer Immunology, Immunotherapy Vol. 65; no. 11; pp. 1289 - 1301
• Main Authors: Barton, Claire, Vigor, Kim, Scott, Robert, Jones, Paul, Lentfer, Heike, Bax, Heather J., Josephs, Debra H., Karagiannis, Sophia N., Spicer, James F.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2016; Springer Nature B.V
• Subjects: Animals; beta-Glucans - metabolism; Biosimilar Pharmaceuticals - metabolism; Cancer Research; Clinical trials; Clinical Trials as Topic; Contaminants; Glucans; Humans; Immunology; Immunomodulation; Immunostimulation; Medicine; Medicine & Public Health; Neoplasms - therapy; Oncology; Pharmaceutical Preparations - metabolism; Pharmaceuticals; Polysaccharides; Review; Risk Assessment; Technology, Pharmaceutical; β-Glucan; Antibodies; Biotherapeutics; Immunostimulation; Beta-glucan; Lentinan; Cancer
• ISSN: 0340-7004; 1432-0851; 1432-0851
• DOI: 10.1007/s00262-016-1875-9

Beta-glucans are large polysaccharides produced by a range of prokaryotic and eukaryotic organisms. They have potential immunostimulatory properties and have been used with therapeutic intent as anti-microbial and anti-tumour agents. A range of other potentially beneficial effects have been described, and oral forms of beta-glucans are widely available over-the-counter and online. Parenteral formulations are popular in parts of Asia and are the subject of ongoing trials, worldwide. Beta-glucans are also potential contaminants of pharmaceutical products, and high levels have been described in some blood products. However, little is known about the clinical effects of such contamination, considerable uncertainty exists over the level at which immunostimulation may occur, and there are no guidelines available on acceptable levels. We encountered beta-glucan contamination of one of our products, and we suspect that others may encounter similar issues since the origin of beta-glucan contamination includes commonly used filters and solutions applied in the manufacture of biotherapeutic agents. It is likely that regulators will increasingly enquire about beta-glucan levels in pharmaceutical products, especially those with an immunomodulatory mechanism of action. Here, we review the literature on beta-glucans in pharmaceutical products and propose an acceptable level for therapeutic agents for parenteral use.