A focus on increased process and facility productivity is therefore both inevitable and necessary. There are a whole range
of technical objectives that are part of the development process. Measures such as antibody titre, process yield, the number
of stages of purification and capital investment are but a few of the typical targets for any development program. However,
there is perhaps a less well recognized effect of the listed demands above that should influence strategic process research.
That is the likely growth of personalized medicines. This is now starting to emerge because:
- Gene discovery will also help identify target populations for specific drugs.
Whilst we should not overestimate the timescale by which this will start to impact — simply because of the very long timescale
associated with drug development — it does seem reasonable to assume that our targeting of new drugs to populations where
they have an effect will increasingly become a reality. The consequence of such a trend may well be a demand for smaller volumes
of more customized biologic medicines — an effect that would erode much of the benefit that large-scale manufacture brings
in ultimate production cost.
Thus the pressures on technology not only relate to improved manufacturing productivity and development time, but also to
the need to create smarter manufacturing operations able to switch more easily between products and processes — and doing
so without compromising on efficacy or patient safety. Speed of response, small-scale manufacturing and process flexibility
will become increasingly important. Clearly, this would also place even greater demands and dependency on the skills of the
workforce.
Despite these big issues faced by the biotech industry, it is worth reviewing the key global numbers for biologic products
in 2004, since these help to illustrate the likely future scale of changing manufacturing needs. Today there are about 60
biologics with licensed status. Assuming only a modest survival rate through trials, another 50 could join them by 2010. The
new arrivals would come from a combination of the nearly 400 biopharmaceuticals currently in trials and further 600 in pre-clinical
development. There also remain at least 200 diseases (unmet needs) to be challenged so the growth in need is hardly an issue.
And while there are clear differences in mood, emphasis and financial attitudes characterising healthcare biotech in the US
and Europe, the overall picture is one of growth and returning confidence after two very difficult years for the industry's
self-esteem.
As Ernst & Young recently reported to a New York meeting, 2003 saw an increase in pharma biotech revenues of more than 22
percent; FDA approvals up by 25 percent and product sales of US $28 billion, marking the biggest revenue increase in the industry's
history. Its 2004 Global Biotech Report put it like this: "... the stage is set for a tremendous increase in new products...the
focus is on the end game, new drugs for patients. This recovery is about real products."
Accordingly, we can reasonably expect many more drugs in terms of absolute numbers, but probably within a gradually changing
product mix, with quite possibly relatively fewer blockbusters.
Arguably, the rapid growth in monoclonal antibodies in development has tended to overshadow many of the other changes and
needs that are relevant to biomanufacturing. This rather unique sector of the market offers substantial treatment options
and with successful products such as Enbrel and Herceptin it has attracted continued major investment.
Purification strategies for antibodies tend to be straightforward and similar but cell growth and volumetric productivity
remain rather limiting, thus technology advance has tended to address gene expression and process titre which now regularly
achieves over 1 gram per liter. With mainstream diseases such as cancer and arthritis the target, manufacturing operations
even early in the product lifecycle are normally based on multiple 10,000 to 20,000 liter batch vessels, underpinning 100s
kilos per annum scale production. But away from the antibody sector there are some rather different needs.
ORPHAN DRUGS
There is now a clear trend in the industry towards a strategy of seeking early licensing of biologics targeted to small-volume
orphan indications. Around 160 submissions have received Orphan Medical Product designation over the last three years with
90 percent of them from small bioscience companies. This strategy should help biotech companies achieve the milestone of an
early biologics license in a cash-constrained environment. Simultaneously though, it also has a major impact on biomanufacturing
by reducing many of the benefits and efficiencies of scale. Thus all of the costs of manufacture, facility compliance and
product licensing are loaded onto relatively small volumes of product - will this compound the global concerns about biologic
pricing?
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