pp 1-14 | Cite as
Manufacturing and Clinical Formulations of Botulinum Neurotoxins
Abstract
Botulinum Neurotoxins have always existed in nature, but its paralytic effect on humans due to the consumption of poorly preserved food was not recognized until 18th century. There are 8 serotypes of botulinum neurotoxins (A, B, C, D, E, F, G, H). Serotype A have been the most recognized one and was initially developed for large scale production in 1940’s. The first batch for clinical use was produced by Edward Schantz, who collaborated with Dr. Alan Scott, an ophthalmologist, evaluating botulinum neurotoxin to treat strabismus. The process Schantz used had variability and led to inconsistent batch production. However, this process is still used by various manufacturers of commercial botulinum neurotoxin products as the foundation. These manufacturers have refined the manufacturing of botulinum neurotoxins by implementing new advanced techniques, including better potency assays. Despite the improvements in the manufacturing process, botulinum neurotoxins are still one of the most potent molecules and therefore, require special handing and additional safety/security measurements during production.
Keywords
Biosafety Botox Drug product Drug substance Formulation Manufacturing Potency ProteinReferences
- Alam M, Dover JS, Arndt KA (2002) Pain associated with injection of botulinum A exotoxin reconstituted using isotonic sodium chloride with and without preservative. Arch Dermatol 138(4):510–514Google Scholar
- Allergan (2012) Allergan receives positive opinions for first-of-its-kind, fully in vitro, cell-based assay for BOTOX® and VISTABEL®; Allergan Press Release. https://www.businesswire.com/news/home/20120222006363/en/Allergan-Receives-Positive-Opinions-First-of-Its-Kind-Fully-vitro
- Allergan (2013) BOTOX® (onabotulinumtoxinA) [prescribing information]. Allergan, IrvineGoogle Scholar
- Barash JR, Arnon SSA (2014) Novel strain of Clostridium botulinum that produces type B and type H. J Infect Dis 209:183–191Google Scholar
- Brin M, James C, Matlman J (2014) Botulinum toxin type A products are not interchangeable: a review of the evidence. Biologics 2014(8):227–241Google Scholar
- Centers for Disease Control and Prevention (2009) Biosafety in microbiological and biomedical laboratories, 5th edn. US Department of Health and Human Services, WashingtonGoogle Scholar
- Erbguth FJ (2007) From poison to remedy: the chequered history of botulinum toxin. J Neural Transm 115(4):559–565Google Scholar
- Fan Y, Barash JR, Lou J, Conrad F, Marks JD, Arnon SS (2016) Immunological characterization and neutralizing ability of monoclonal antibodies directed against botulinum neurotoxin type H. J Infect Dis 213:1–9Google Scholar
- Fervert J, Ahn KY, Park MY, Sunga O (2018) Comparison of botulinum neurotoxin type A formulations in Asia. Clin Cosmet Investig Dermatol 2018(11):327–331Google Scholar
- GenomeWeb (2011) FDA approves Allergan’s cell-based assay for Botox. https://www.genomeweb.com/archive/fda-approves-allergans-cell-based-assay-botox#.XS_x0OhKhywGoogle Scholar
- Keller JE (2006) Recovery from botulinum neurotoxin poisoning in vivo. Neuroscience 139:629–637Google Scholar
- Klein AW (1998) Dilution and storage of botulinum toxin. Dermatol Surg 24(11):1179–1180Google Scholar
- Nigam PK, Nigam A (2010) Botulinum toxin. Indian J Dermatol 55(1):8–14Google Scholar
- Pickett A, Mewies M (2009) Serious issues relating to the clinical use of unlicensed botulinum toxin products. J Am Acad Dermatol 61(1):149–150Google Scholar
- Rossetto O, Pirazzini M, Montecucco C (2014) Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat Rev Microbiol 12:535–549Google Scholar
- Samizadeh S, De Boulle K (2018) Botulinum neurotoxin formulations: overcoming the confusion. Clin Cosmet Investig Dermatol 11:273–287Google Scholar
- Scaglione F (2016) Conversion ratio between Botox®, Dysport®, and Xeomin® in clinical practice. Toxins 8(3):65Google Scholar
- Schantz EJ, Johnson EA (1997) Botulinum toxin: the story of its development for the treatment of human disease. Perspect Biol Med 40(3):317–327Google Scholar
- Shenot PJ, Mark JR (2014) Intradetrusor onabotulinumtoxinA injection: how I do it. Can J Urol 20(1):6649–6655Google Scholar
- Ton J, Patel H, Bates R, Ahmad WM (2015) Process and system for obtaining botulinum neurotoxin; United State Patent US 8,932,827 B2; Patent Date 13 Jan 2015Google Scholar
- Truong D, Hallett M (2013) Manual of botulinum toxin therapy, 2nd edn. Cambridge University Press, CambridgeGoogle Scholar
- Walker TJ, Dayan SH (2014) Comparison and overview of currently available neurotoxins. J Clin Aesthet Dermatol 7(2):31–39Google Scholar
- Waters T (1992) The fine art of making poison. Discover Magazine, August 1992. discovermagazine.com/1992/aug/thefineartofmaki93