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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 by Anna Lewcock.
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."

[www.biopharma-reporter.com]