title: Beta-glucan contamination of pharmaceutical products: How much should we accept?
abstract: 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.
authors.affiliation: Cancer Research UK Centre for Drug Development, Cancer Research UK, Angel Building, 407 St John Street, London, EC1V 4AD, UK. claire.barton@cancer.org.uk.
authors.forename: Claire
authors.identifier: 0000-0002-6407-1479
authors.initials: C
authors.lastname: Barton
authors.affiliation: Biotherapeutics Development Unit, Cancer Research UK, South Mimms, Hertfordshire, EN6 3LD, UK.
authors.forename: Kim
authors.initials: K
authors.lastname: Vigor
authors.affiliation: Biotherapeutics Development Unit, Cancer Research UK, South Mimms, Hertfordshire, EN6 3LD, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Scott
authors.affiliation: Cancer Research UK Centre for Drug Development, Cancer Research UK, Angel Building, 407 St John Street, London, EC1V 4AD, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Jones
authors.affiliation: Biotherapeutics Development Unit, Cancer Research UK, South Mimms, Hertfordshire, EN6 3LD, UK.
authors.forename: Heike
authors.initials: H
authors.lastname: Lentfer
authors.affiliation: Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, St. John's Institute of Dermatology, King's College London, 9th Floor, Guy's Tower Wing, Guy's Hospital, London, SE1 9RT, UK.|NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals, King's College London, 9th Floor, Guy's Tower Wing, Guy's Hospital, London, SE1 9RT, UK.|Division of Cancer Studies, Department of Research Oncology, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Bax
authors.affiliation: Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, St. John's Institute of Dermatology, King's College London, 9th Floor, Guy's Tower Wing, Guy's Hospital, London, SE1 9RT, UK.|NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals, King's College London, 9th Floor, Guy's Tower Wing, Guy's Hospital, London, SE1 9RT, UK.|Division of Cancer Studies, Department of Research Oncology, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
authors.forename: Debra H
authors.initials: DH
authors.lastname: Josephs
authors.affiliation: Division of Genetics and Molecular Medicine, Faculty of Life Sciences and Medicine, St. John's Institute of Dermatology, King's College London, 9th Floor, Guy's Tower Wing, Guy's Hospital, London, SE1 9RT, UK.|NIHR Biomedical Research Centre at Guy's and St. Thomas's Hospitals, King's College London, 9th Floor, Guy's Tower Wing, Guy's Hospital, London, SE1 9RT, UK.
authors.forename: Sophia N
authors.initials: SN
authors.lastname: Karagiannis
authors.affiliation: Division of Cancer Studies, Department of Research Oncology, Faculty of Life Sciences and Medicine, King's College London, 3rd Floor Bermondsey Wing, Guy's Hospital, Great Maze Pond, London, SE1 9RT, UK.
authors.forename: James F
authors.initials: JF
authors.lastname: Spicer
mesh_terms: D000818:Animals; D059451:Biosimilar Pharmaceuticals / Q000378:metabolism*; D002986:Clinical Trials as Topic; D006801:Humans; D056747:Immunomodulation; D009369:Neoplasms / Q000628:therapy*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D018570:Risk Assessment; D013678:Technology, Pharmaceutical; D047071:beta-Glucans / Q000378:metabolism*
chemical_list: D059451:Biosimilar Pharmaceuticals; D004364:Pharmaceutical Preparations; D047071:beta-Glucans
keywords: Antibodies; Beta-glucan; Biotherapeutics; Cancer; Immunostimulation; Lentinan