The critical role transgenic animals could play in the future of biopharmaceutical production has been tackled by a task force in a new report out this week.
The potential such animals could have in the manufacture of biopharmaceutical proteins has been one of the major incentives driving investigation and creation of transgenic animals, and with therapeutic products derived from these genetically modified creatures now beginning to gain regulatory approval, commercial interest is in the technique is hotting up.
The significant cost savings to be had through using transgenic livestock instead of traditional methods of protein production have been well documented, and comparisons make for stark reading.
To illustrate, experts have estimated that producing a single gram of therapeutic protein using traditional cell lines such as Chinese Hamster Ovary (CHO) cells can cost anywhere from $300 to $3,000 (€221 to €2210).
In contrast, using a transgenic goat to produce the protein in milk drops the cost to $20-$105 per gram, and transgenic hen eggs are even cheaper, working out at around $0.1-$0.25 per gram of protein
The initial capital expenditure is also somewhat less intensive using transgenic livestock, with the cost of constructing a new facility based on traditional cell-based techniques hitting $150m - $400m, compared with the cost of a transgenic goat or cow at $10,000 - $50,000, or a transgenic chicken coming in at $1,000.
"With moderate alterations in production practices, it is possible to take advantage of the tremendous protein-producing capabilities of domestic livestock," states the report, published this week by the Council for Agricultural Science and Technology (CAST).
"Biopharming, the production of biopharmaceuticals using domestic livestock, can have significant advantages compared with other production methods in terms of safety, biological activity, and production costs."
Back in June 2006 the European Medicines Agency (EMEA) gave the very first European approval of a transgenically produced protein product. ATryn, produced by US firm GTC Biotherapeutics, is produced in the milk of goats that have a transgene for human antithrombin, and is used as an anticoagulant to treat a rare congenital disease.
This first step to move trangenically produced protein products out onto the market could prove to be the just the tip of the ice-berg, with all eyes on ATryn to see how it fares out in the cold reality of the marketplace.
According to the chairperson of the CAST task force, Carol Keefer, wide-scale commercial adoption of protein production using transgenic animals is getting closer and closer, with GTC's product cutting a path for other biotech companies.
"I think as soon as ATryn goes to market and proves acceptable and profitable, more pharma companies will explore the use of transgenic animals for protein production," she told in-PharmaTechnologist.com.
Already there are many companies investing in research into producing bioproducts through transgenic livestock. The majority are still in research stages, but US company Avigenics and Netherlands-based firm Pharming currently both have products in clinical trials.
Aside from the economic cost benefits biopharming appears to promise, the procedure can also offer other distinct advantages over current cell-based production methods.
For example, using transgenic animals to produce biopharmaceuticals currently harvested from human tissues represents a safer technique in terms of preventing transmission of human diseases such as HIV/AIDS or Creuzfeldt-Jakob disease, say the report authors.
In some cases, using transgenic animals can also lead to production of a better protein, said Keefer, i.e. a protein more similar to the version naturally produced in humans.
"Proteins are modified during production in the cell, and transgenic animals can do these modifications in a manner more similar to the human-produced protein than other production systems such as yeast or bacteria."
Despite the apparent attractions of biopharming, the report acknowledges that it is critical to establish economic feasibility of the process before it will be adopted by drug firms. For example, issues surrounding protein purification can seriously affect the ultimate economics and commercialisation of a final product.
Feasibility concerns or lack of funding have caused some commercial pharma projects applying these new technologies to be scrapped or delayed on a purely economic basis.
"These are business issues caused not necessarily by technical challenges but by unknown factors that arise as new technologies develop without an established track record or sufficient guidelines for completing the necessary regulatory steps," states the report.
"In fact, regulatory guidelines are being developed concurrently with the establishment of the new technology, creating uncertainty within the business community as to the costs and timelines associated with recombinant protein production."
While transgenic livestock are likely to play an increasingly significant role in the production of therapeutic proteins, Keefer was by no means suggesting that it would to do away with other production methods altogether.
"Each production method has its advantages and disadvantages," she said.
"Depending on the protein, the amount of protein needed (based on market demand and dosage required), and the activity of the protein, a company would choose the best suited system. [For example] if the therapeutic protein could have an effect on the physiology of the transgenic animal, then you would either modify the protein so it was inactive during production, or perhaps choose another system."
Despite this, the authors of the report clearly have very high expectations of biopharming and the part it will play in the production of new medications to treat human diseases. The unique possibilities that transgenic livestock present in this area are too big a prospect to be ignored, and the authors call for "continued support of research by both government and commercial entities...such that additional promising biotherapies can be developed."
Further information and the CAST report can be found here .