Evolving improvements in diagnostic tools are expected to lead to disease prevention, as well as earlier treatment, with less
need for medication. One aspect of this evolution is the earlier identification of patients who are not likely to respond
to treatment, and of patients who may experience severe side effects. Thus, such individuals would not be treated at all with
the drug in question.
LOWER-SCALE PRODUCTION APPROACHES ARE NEEDED
For MAbs specifically, the current spectrum of marketed protein drugs (shown in Figure 1) indicates that production scales
for a few of these have already reached ton levels. One example is Rituximab, a MAb used for treating B-cell non-Hodgkin's
lymphoma, B-cell leukemias, and some autoimmune disorders. Rituximab is marketed as Rituxan by Genentech and as MabThera by
Roche. For most MAbs, the scale of production ranges from 50 and 100 kgs to several hundred kilograms. An example of this
would be Adalimumab, a drug marketed by Abbott under the name Humira for treating rheumatoid, psoriatic, and juvenile idiopathic
arthritis, as well as Crohn's disease and chronic psoriasis. In addition, most recombinant proteins other than antibodies
are manufactured at relatively small scales—as low as a few hundred grams per year, and rarely more than 10 kgs per year.
The exception to this would be the various insulins, which are individually manufactured at lower-ton scales but which, as
a group, may reach 10 tons of production annually.
Figure 1. Production volume and revenue map, 2006 data
The spectrum of marketed protein drugs includes the plasma proteins human albumin and intravenous immunoglobulin. Interestingly,
these first-generation biopharmaceutical proteins are, as a group, manufactured at multiton scales—up to 500 tons per year
for global albumin. Chromatographic purification has been used to manufacture some of these proteins since the 1970s,
and it is expanding in this sector as a means of improving the manufacturing, purity, and safety of these drugs.3 This approach is feasible and economical because members of the plasma fractionation industry are among the most mature
and financially pressured players. These companies are probably on a level with insulin manufacturers because insulins are
typically manufactured using multiple chromatographic purification steps. Together, these two categories of biopharmaceuticals
provide additional proof that today's technology can provide for patients' needs.
In the future, successful antibody manufacturing companies will have fewer ton-scale proteins (perhaps five to seven brands
at the most), and will find economical ways to produce their much lower-scale antibody products (those of between 50 and 500
kgs per year, and rarely approaching 1,000 kgs per year). Although there will probably be few technical hindrances, a number
of practical matters will require attention. One of these matters will be using existing facilities for product manufacture.
Most of the first generation and many of the second generation facilities have been built with little flexibility to accommodate
additional processes with different design or at different scale. Another will be much greater economic pressure resulting
from two factors: pressure from healthcare systems to reduce reimbursement levels, and competition with biosimilars that reduce
the margins of the most profitable protein drugs.