CSL Limited is an Australian multinational specialty biotechnology company that researches, develops, manufactures, and markets products to treat and prevent serious human medical conditions.CSL's product areas include blood plasma derivatives, vaccines, antivenom, and cell culture reagents used in various medical and genetic research and manufacturing applications.[3] The company was established in 1916 as Commonwealth Serum Laboratories and was wholly owned by the Australian federal government until its privatisation in 1994.
History
Origin and Penfold directorship
CSL was founded in 1916 as Commonwealth Serum Laboratories, an Australian government body focused on vaccine manufacture.[4] Under the first director, William Penfold,[5] CSL commenced operation in the vacant
32,000 (2024)‡R2R‡
divisions
CSL Behring
CSL Plasma
CSL Seqirus
CSL Vifor
homepage
https://www.csl.com/
Walter and Eliza Hall Institute
building at the
Royal Melbourne Hospital
in 1918 before moving to its purpose-built Parkville premises in the following year.
Morgan directorship
After ongoing disputes with the Department of Health and its director-general John Cumpston, Penfold resigned in 1927 and was replaced by Frederic Morgan.[6] Soon after Morgan's appointment, CSL was drawn into a serious public health disaster when a batch of its diphtheria toxin-antitoxin was implicated in the deaths of twelve children in what became known as the Bundaberg tragedy of 1928.Although CSL's manufacturing processes were absolved, its labelling procedures were seen to be in error, leading to an enduring focus on the highest standards across the facility's production.[7]
Antivenene research and production
In 1928, CSL also became involved in antivenene (antivenom) manufacture in conjunction with the snake venom research undertaken by Charles Kellaway at the Hall Institute.[8] This led to the successful clinical testing of antivenene against tiger snake Notechis scutatus bite in 1930 and its commercial release in 1931.
In 1934, the research on snake venoms was transferred from the Hall Institute to CSL under the direction of former snake showman and herpetologist Tom "Pambo" Eades. This represented the initiation of research at the laboratories – an outcome its directors had been seeking for over a decade. The relationship with the Hall Institute continued until World War II, particularly via joint projects on viral diseases including polio and influenza coordinated by Frank Macfarlane Burnet and Esmond "Bill" Keogh.Keogh played an important role in the establishment of penicillin production at CSL in 1944 – a critical wartime achievement.[9]
Plasma fractionation and Wiener directorship
In 1952, operation commenced plasma fractionation.[10] Thereafter the range of antivenoms increased, including those against other snake species such as death adder (Acanthophis antarcticus) and the taipan (Oxyuranus scutellatus), plus spiders including the redback (Latrodectus hasselti) and – after much difficulty – the Sydney funnel-web (Atrax robustus).Much of this work, including the introduction in 1962 of a polyvalent antivenom against all of the major terrestrial Australian snakes, occurred under the direction of Saul Wiener, while from 1966 until the mid-1990s, venom research was coordinated by the eccentric but dedicated Struan Sutherland, who in 1979 released new guidelines for snakebite first aid,[11] and a new test for snakebites that would identify which snake had envenomated the victim.[12]
early production of insulin for treatment of Australian diabetics (1923)
development of a tetanus vaccine (1938)
development of a combined vaccine for diphtheria, tetanus and whooping cough (1953)
rapid adoption and production of a polio vaccine (1956)
development of a multi-purpose animal vaccine covering pulpy kidney (enterotoxemia), tetanus, black disease, malignant oedema and blackleg (1961)
production of Rhesus (D) immunoglobulin to prevent haemolytic disease in newborns due to Rh factor incompatibility (1966–67)
pioneering heat treatment to protect blood and plasma products from infection with HIV (1983)
collaboration on development of the world's first human papillomavirus vaccine, Gardasil, building on the pioneering work by Professor Ian Frazer (1994–2005).[14]
Privatisation
In 1994, the Commonwealth facility was privatised by the Keating government as CSL Ltd. and was publicly listed and traded on the Australian Securities Exchange.The company completed an initial public offering in June 1994 at A$2.30 per share (76.7c adjusted for split).CSL stock is part of the S&P/ASX 20 Index.[15]
Acquisition of ZLB Bioplasma AG and Aventis Behring
In 2000, CSL doubled its size through the purchase of a Swiss plasma company, the Bern-based ZLB Bioplasma AG.[16] In 2004, during a period of plasma oversupply, the company expanded again with the purchase of the German medical company Aventis Behring.[17] The company was the second Australian public company to have reached a share price of over $100 per share.[18]
Acquisition and merging of Novartis' vaccine business
In October 2014, Novartis announced its intention to sell its influenza vaccine business, including its development pipeline, to CSL for $275 million.CSL merged it into its BioCSL operation.[19]
In November 2015, BioCSL rebranded the combined business with Novartis Influenza Vaccines as Seqirus [Sek-eer-us], creating the world's second-largest influenza vaccine company.[20]
In August 2017, the business announced it would acquire Calimmune and its stem cell therapy platform.[21]
Completed in 2018, Seqirus's Holly Spring, NC, the plant was funded with $59 million from the U.S. government.[22]
in June 2020, CSL announced it would exercise its right to acquire Vitaeris.[23]
In December 2021, the business announced it would acquire Swiss drugmaker, Vifor Pharma AG, for $11.7 billion.[24]
In August 2022, CSL rebranded all of its divisions to start with the CSL name. Therefore, the divisions became CSL Behring, CSL Plasma, CSL Seqirus, and CSL Vifor.[25]
Acquisition history
CSL Limited (Founded 1916 as Commonwealth Serum Laboratories)
The company's headquarters remain in Parkville, Victoria, an inner suburb of Melbourne, and has offices and laboratory space in Sydney.
CSL Behring is headquartered in King of Prussia, USA and it has manufacturing operations and R&D laboratories in Broadmeadows, Victoria, the Swiss city of Bern, in Marburg in Germany, and Kankakee, USA.
Seqirus has its headquarters in Maidenhead and has production facilities in Holly Springs, US, Liverpool, UK, and Parkville, Victoria
Vaccines
A/H1N1 2009 pandemic
CSL's vaccine for swine flu, the world's first, was approved in September 2009 for use by people over age 10.[26] The federal government ordered 21million doses of vaccine for Australians.[27]CSL also provided vaccines for customers in Singapore and the US.
On 28 September 2010, the Australian Therapeutic Goods Administration (TGA) conducted an analysis of febrile convulsions following immunisation in children following monovalent pandemic H1N1 vaccine (Panvax/Panvax Junior, CSL).[28]
A paper published in the Medical Journal of Australia provides a possible reason for CSL's 2010 flu vaccine causing febrile convulsions in children. The authors hypothesise that suboptimal use of the detergent called deoxycholate – used in the manufacturing process by CSL (one of the few vaccine manufacturers that use it) – to split the flu virus from its membrane may be at fault.[29]
COVID-19 pandemic
On 7 September 2020, CSL signed agreements with the Australian government to supply the University of Queensland vaccine (V451) and to manufacture (with AstraZeneca) the Oxford University vaccine (AZD1222), which would yield nearly 85 million doses for Australians. The agreement was contingent on the future success of clinical trials of these vaccines. Most of the manufacture would occur in Melbourne, Australia.[30][31]
On 11 December 2020, after a high percentage of the University of Queensland vaccine trial participants returned "false positive" results for HIV, it was decided that vaccine development will not proceed to Phase 2/3 trials.[32]
On 23 March 2021, the Therapeutic Goods Administration provisionally approved the first batches, numbering 832,000 doses, of the Oxford–AstraZeneca COVID-19 vaccine manufactured by CSL in its plant in Broadmeadows, Victoria.The Australian Government has contracted CSL to produce 50 million doses of the vaccine.
Divisions
CSL Limited's products can be separated by company division. Some of the key products produced by each division, have included:
Product availability varies from country to country, depending on registration status.
Beriglobin P, human hepatitis Aimmunoglobulin, liquid 16% solution for intramuscular injection
Berirab P, human rabiesimmunoglobulin, liquid 16% solution for intramuscular injection
Carimune NF, Sandoglobulin, Sanglopor human normal immunoglobulin, freeze-dried formulations for intravenous administration
Cytogam, human cytomegalovirusimmunoglobulin. Liquid immunoglobulin
Honours
In 2011, the company received the Minister's Award for Outstanding Equal Employment Opportunities Initiative for their Thinking Kids Children's Centre.[38]
See also
Australian Red Cross Blood Service
Sources
AH Brogan, Committed to Saving Lives: a History of the Commonwealth Serum Laboratories (Melbourne: Hyland House, 1990).
Dando McCredie, The Fight Against Disease and CSL's Seventy Year Contribution (Richmond: Dando McCredie, c.1986).
FG Morgan, 'The Commonwealth Serum Laboratories and their work', Collected Proceedings of the Society of Chemical Industry of Victoria, XXXV (1935), 1015–31.
WJ Penfold, 'The Commonwealth Serum Laboratories', Medical Journal of Australia, 1 (14 April 1923), 396–400.
Struan K Sutherland, A Venomous Life: the Autobiography of Professor Struan Sutherland (Melbourne: Hyland House, 1998).
6.Bryan Egan. Morgan, Frederick Grantley (1891–1969) Australian Dictionary of Biography, National Centre of Biography, Australian National University, retrieved 2020-09-22^
9.Lyndsay Gardiner, Geoffrey Serle. Keogh, Esmond Venner (Bill) (1895–1970) Australian Dictionary of Biography, National Centre of Biography, Australian National University, 2000^
29.Heath A Kelly, Danuta M Skowronski, Gaston De Serres, Paul V Effler. Adverse events associated with 2010 CSL and other inactivated influenza vaccines The Medical Journal of Australia, 19 September 2011^
Vivaglobin, sub-cutaneous human immune globulin indicated for the treatment of primary immunodeficiency. This product gained FDA approval in January 2006.
Hepatitis B Immunoglobulin P Behring, human hepatitis Bimmunoglobulin, liquid 16% solution for intramuscular injection
Hizentra, Human normal immunoglobulin. Liquid 20% immunoglobulin solution, ready-to-use for subcutaneous administration
Privigen, human polyvalent immunoglobulin, liquid 10% solution for intravenous injection
Rhesogamma P, human anti-Dimmunoglobulin. Prefilled syringes of highly purified anti-Rhesus factor D IgG for intravenous administration and intramuscular injection.
Rhophylac human anti-Dimmunoglobulin. Prefilled syringes of highly purified anti-Rhesus factor D IgG for intravenous administration and intramuscular injection.
Sandoglobulin NF Liquid, Redimune, Redimune NF Liquid, human normal immunoglobulin, liquid 12% solution for intravenous administration
Tetagam P, human tetanusimmunoglobulin, liquid 16% solution for intramuscular injection
Varicellon P, human varicellaimmunoglobulin, liquid 16% solution for intramuscular injection
Vivaglobin, human normal immunoglobulin, liquid 16% solution for subcutaneous administration
Beriate, freeze-dried human coagulationfactor VIII concentrate
Berinin P, freeze-dried human coagulationfactor IX concentrate
Factor X P Behring, a freeze-dried human coagulationfactor IX and factor X concentrate
Fibrogammin P, Cluvot and Corifact, freeze-dried human coagulationfactor XIII concentrate
Helixate FS and Helixate NexGen, freeze-dried recombinantcoagulationfactor VIII
Humate-P and Haemate P, freeze-dried human coagulationfactor VIII: C and von Willebrand factor concentrate
Monoclate P, a freeze-dried monoclonal antibody purified human coagulationfactor VIII concentrate
Mononine, a freeze-dried human coagulation factor IX that has been purified using monoclonal antibodies
Stimate, a synthetic desmopressin acetate nasal spray
Octostim, a synthetic desmopressin acetate nasal spray
Zemaira, Respreeza freeze-dried Human Alpha1-proteinase inhibitor (A1-PI)
AlbuRx, Alburex, Albumeon, Human Albumin Behring, Albuminar 25, human albumin solution (5%, 20% or 25% human albumin solutions)
Berinert P, freeze-dried human C1-esterase inhibitor (C1-INH) concentrate
Beriplex P/N, freeze-dried human prothrombin complex concentrate
Haemocomplettan P, RiaSTAP, freeze-dried human fibrinogen (factor I) concentrate
Kybernin P, freeze-dried human antithrombin III concentrate
Streptase, freeze-dried streptokinase
Beriplast P Combi-Set, fibrin sealant kit, freeze-dried fibrin sealant for topical application
Fibrogammin P, freeze-dried human coagulationfactor XIII concentrate
