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

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.
Competing Interests: Compliance with ethical standardsConflict of interestClaire Barton is a freelance pharmaceutical physician/medical advisor with Barton Oncology Ltd and in the last 5 years has undertaken consultancy work with Roche Products Ltd, Cancer Research UK Centre for Drug Development, Wellcome Trust Ltd, SFL Services GmBH, Mosaic Biomedicals SL, Alacrita LLP, Astex Therapeutics Ltd, BerGen Bio A/S, EngMab AG, Inbiomotion SL, Michelangelo Foundation, Norgine Pharmaceuticals Ltd, Ono Pharma UK Ltd, Piqur Therapeutics AG, and Shionogi Ltd. Claire Barton is on the advisory board for SFL Services GmBH and owns shares in GlaxoSmithKline. All other authors declare they have no conflict of interest.