<<Have to agree that plant transgenics is currently years behind animal transgenics, but will plants be able to make that up with shorter lead times to production vehicles?>>
Perhaps. But cloning may shorten the lead times for animal production systems.
<<Agree that glycosylation can be done after the fact, but expensively. Does this suggest that Cerezyme might be made more economically via pharming?>>
If we didn't already have a production plant built, we would definitely be looking into pharming for this protein. But I don't think pharming would solve the glycosylation problem for Cerezyme(R). Even the human-tissue-derived version [Ceredase(R)] has to be remodelled. The protein is produced in the macrophages and normally stays there. It needs an unnatural glycosylation pattern to get into the macrophages from the bloodstream.
I also think the next generation of treatment for Gaucher disease is more likely to be gene therapy than a cheaper form of Cerezyme.
<<I found an interesting comment from Eva Sandberg of the Danish Medicines Agency on this very subject (Nature Biotechnology, July '97 (15:7), p. 602 - sorry, no online version). According to Biotechnology, Dr. Sandberg declared that pharming is NOT from a regulatory point of view, going to be the most rapid route to the market. She added that in assessing new biological drugs, production in yeast or bacteria is preferred over production in mammalian cells, and that with transgenic animals there is "always an additional risk of failure of good manufacturing practice." Admittedly, Dr Sandberg, as head of the microbiology department at the DMA, may be a little biased, but her remarks were at the European Society of Regulatory Affairs. What do you think?>>
Some biopharmaceuticals (e.g., Cerezyme) can only be made in mammalian cells. And some candidates for future biopharmaceuticals (e.g., certain monoclonal antibodies) may be impossible to produce economically in cell culture, even in mammalian cells.
If Dr. Sandberg was quoted accurately, I'd have to conclude that the Danish regulatory system is a bit behind the times. The U.S. FDA issued a "Points to Consider" document on transgenic production more than a year ago.
With ATIII, the alternative to pharming is protein obtained form pooled human plasma. With all the scandals and hysteria in Europe about contaminated blood products and BSE, I doubt that we will have much difficulty convincing regulatory agencies in Europe that transgenic ATIII would, more a safety standpoint, be preferable to plasma-derived ATIII.
Steve Push
Genzyme Corp.
genzyme.com |
