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Target molecules assessment of (clinical) need
and production feasibility (WG3)
The production of complex valuable recombinant
proteins such as biopharmaceuticals, including
vaccines,
in plants can potentially address many of the challenges posed by existing
methods of production.
The combination of low capital investment, low cost of goods, coupled with
highly scalable
manufacturing capability is particularly important for many products and will
enable the development
of new applications (such as passive immunotherapy with monoclonal antibodies)
that are currently not
achievable with conventional fermenter based production technologies.
The following
principal advantages which plants can offer need to be evaluated case by case
when choosing the best
production system:
-
Scalability. No
other production system offers the potential scalability of plants. Whilst
some high-value products
could be produced in sufficient amounts in plant cell culture in the future,
contained technologies in
greenhouses or growth at agricultural levels will allow product
manufacture on a massive scale.
This in turn will enable the design of new products and
approaches
in many areas, and in the medical arena, will offer the prospect of
providing medicines
and vaccines at a scale that could finally match the global health need.
-
Costs. Plants
are cost-effective and easy to grow. The cost of raw goods will certainly be
low. However, as this
typically represents only a small percentage of the total cost of a product,
this is not
necessarily where the major financial savings are to be found. The major
cost attraction
of
plants is that the initial investment into a production line is
significantly lower compared
with
conventional fermenter facilities. Many observers have also noted that for a
plant-derived pharmaceutical
the requirement for a major capital investment can be delayed until much
later in the product
development line.
-
Adaptability.
Plant cells are higher eukaryotes, and therefore possess, like mammalian
cells, an endomembrane
system that allows them to produce extremely complex proteins such as
monoclonal antibodies that are
currently not feasible in, for example, microbial systems.
Indeed,
all the generally recognized forms of antibody and related engineered
molecules have been
successfully expressed in plants. In addition, there are examples of
proteins that, at
present,
can only be produced in plants (for example secretory IgA antibodies, and
recombinant immune complexes).
Thus plants appear to be highly amenable to the production
of
a wide range of proteins.
-
Speed. The latest advances in plant
biotechnology now allow large scale amounts of high
quality
recombinant proteins to be produced extremely rapidly. This has allowed at
least three plant-based
commercial ventures to develop technologies, which will allow them to
compete, for
example, with existing systems for the production of influenza vaccine, or
for the requirement
for rapid scalability of products to respond to bio-terrorist threats.
Of course, not all pharmaceuticals will be
appropriate, or will need to be made in plant systems.
Currently,
those application areas that are thought likely to benefit most are:
-
Medicines that are required in very large
quantities e.g. monoclonal antibodies, some sub-unit
vaccines,
HIV protein microbicides.
-
Medicines that can only be made in plants e.g.
secretory IgA antibodies - at present this major
class
of antibody that is important for mucosal prevention of disease cannot be
made efficiently
by any other means.
-
Medicines that are specifically designed
for production in plants e.g. recombinant immune
complexes
- with a growing understanding of the mechanisms of protein production in
plants, has come
the ability to engineer molecules with enhanced immunological properties.
However, it has always been the cases that as
new technologies are developed; potential
applications
also develop to capitalize on the innovative aspects of the new technologies.
This will undoubtedly
also be the case for plant biotechnology and MF, and it will be extremely
important to monitor
potential targets for MF, with the latest plant biotechnological developments
in mind. |
