The August issue of Nature Biotechnology has a very interesting snippet of news – from two points of view. From a strict virology point of view, it is interesting that commercial production of a therapeutic enzyme in an industrial plant can be shut down because of infection of their mammalian cell line with a contaminating mammalian virus.
From the second point of view…well, our lab has a very strong interest in producing recombinant proteins (and especially candidate vaccine proteins) in plants – and here is a story showing just why plants may be a really good alternative means of production for pharmaceuticals. First, the story:
Nature Biotechnology 27, 681 (2009) doi:10.1038/nbt0809-681a
Virus stalls Genzyme plant by Victor Bethencourt
Genzyme of Cambridge, Massachusetts, faces millions in lost revenue from its top-selling specialty drugs Cerezyme and Fabrazyme as result of a viral contamination at its Allston, Massachusetts plant. The company has announced that it will temporarily shut down the facility owing to a bioreactor contamination with Vesivirus 2117 [my emphasis - Ed], which does not cause human infections, but impairs growth of the biologics-producing Chinese hamster ovary (CHO) cells. It reportedly originated from tainted nutrient medium and belongs to the same strain that caused delays at the Allston site and its European biologics plant in Belgium last year. Genzyme anticipates supply constraints of Cerezyme (imiglucerase), a treatment for Gaucher disease, and Fabrazyme (agalsidase beta), used to treat Fabry disease, while the facility shuts down for 6 to 8 weeks to allow decontamination.
OK, really interesting, that: a vesivirus – genus Vesivirus, family Caliciviridae, nice link here for structure, and here for Genzyme’s press release – that is being transmitted around via cell culture media, between manufacturing plants. One of the perils of using mammalian cells to make things…!
The article goes on:
…With sales of $1.2 billion for Cerezyme and $494 million for Fabryzyme in 2008, analysts estimate the manufacturing crisis will result in $100–300 million in lost sales. The US Food and Drug Administration (FDA) has contacted rival manufacturers Shire of Basingstoke, UK, and Carmiel, Israel–based Protalix, who have enzyme replacement therapies for Gaucher disease in clinical trials, to file treatment protocols, which would allow physicians to use their drugs ahead of approval.
And of course, Protalix makes its glucocerebrocidase in cultured carrot cells, in disposable “bioreactor bags”…. In completely defined chemical media, with no risk of plant virus contamination – not that plant viruses can infect cultured plants cells, by any means short of being shot in on gold beads! Their web site Press Room page had this to say as of 25th August:
Aug. 25, 2009 (Business Wire) — Protalix BioTherapeutics, Inc. (NYSE-Amex:PLX), announced today that it has received Fast Track Designation from the U.S. Food and Drug Administration (FDA) for prGCD, the Company’s proprietary plant-cell expressed recombinant form of glucocerebrosidase (GCD) for the treatment of Gaucher disease.
I wrote the following about Protalix after attending the Plant-Based Vaccines and Antibodies Conference in Verona in June this year (September issue of Expert Rev Vaccines, 8: 1151-1155, 2009):
“Einat Almon-Brill (Protalix Biotherapeutics, Israel) described their production of recombinant human glucocerebrosidase (rGCD) as a therapy for Gaucher disease, caused by a hereditary mitochondrial defect. They used a contained disposable bioreactor system with suspension-cultured carrot or tobacco cells, and claimed there were no mammalian cell culture risk factors; they obtained uniform glycosylation, and the exposed mannose allowed rapid macrophage uptake. The rGCD half-life was twice as long as commercial product, and had been trialled in Europe, Israel, South Africa, and North and South America.”
I wish I’d bought stock…or had the money to, or knew how to! The time of plant-made pharmaceuticals – PMPs – is coming.