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The times, they are a changin’ in the biopharma market
February 2013
SHARING OPTIONS:
The
biopharmaceutical development community has successfully
developed a broad range of highly effective therapies for a wide variety of
serious and
debilitating diseases. However, developing biopharmaceuticals is
inherently an extremely challenging and commercially risky undertaking, often
working
to tight timelines and typically resource-constrained. For many, this
means adopting a pragmatic approach to development, where the goal is to get
the
product to a point where its clinical performance and analytical
characterization are "good enough" to satisfy the regulatory authorities and
get to
market.
Very often, we do not have the time, resources, or indeed, the motivation, to work toward an optimum "best-it-can-possibly-be" position. Typically, the "good-enough" approach may be adopted during selection of candidates, development of formulations and manufacturing processes and in the degree of analytical characterization performed. Although this approach has successfully delivered safe and efficacious drugs to the market, we are now moving into a new era for biopharmaceuticals, characterized by increased competition in the marketplace. Good enough to satisfy the regulators may no longer be good enough to compete effectively in the marketplace. As a result, healthcare refunders, practitioners and
patients will have an ever-increasing choice about which drug to buy and can
increasingly
be expected to base their purchasing decisions on factors such as
relative price, convenience and cost of administration, effectiveness and
degrees of
adverse reactions. Both innovator and biosimilar developers will
need to adapt in order to compete effectively in this new environment. A number
of
aspects of the development process, although already very important, will
become increasingly critical to the commercial success of the resulting
products.
A key potential cause of slow and expensive development can
be early selection of a candidate molecule that, while efficacious and
specific, is fundamentally unstable and consequently difficult to develop,
manufacture and achieve adequate storage stability in a convenient dosage form.
Picking the right candidate is, however, easier said than done. Early
in
development, both time and protein material are typically in short supply,
limiting the number of candidates that can be investigated and the extent
of
analytical characterization that is possible for each.
To overcome these issues, analytical
screening technologies
are needed which are rapid and automated (high-throughput), consume very little
material and also make analytical measurements
that are in some way predictive
of how the protein will behave during manufacture and subsequent storage. Such
technologies allow candidate protein
molecules to be screened for
"developability"—or, in the context of this article, "competitiveness"—in addition
to basic therapeutic function. If
the measurements made have some predictive
power, the risk of progressing too far with a molecule which is ultimately
incompatible with modern, cost-
effective platform manufacturing processes, or
which can't be made suitably stable for long-term storage in a convenient
dosage form, is reduced. The
same small-volume, high-throughput approach also
offers the potential to rapidly and cost-effectively test the efficacy of
protein engineering efforts
to improve stability earlier in development, and to
identify optimum solution conditions for processing and storage.
A tough, stable molecule, selected from the outset to be
inherently compatible with modern platform manufacturing processes
and for
which the successful results of long-term storage stability studies can be
(almost) assured, has a better chance of progressing through
development more
rapidly, costing less to develop and reaching the market sooner. Once at
market, the selected and/or engineered-in attributes should
result in lower
manufacturing costs, longer shelf life and potentially other benefits to the
customer, increasing the molecule's chances of commercial
success.
Instrumentation suitable for this type of stability screening is readily
available from a wide range of vendors at comparatively modest cost,
and a
number of the largest biopharmaceutical developers are already embracing this
approach.
Analysis as a route
to market … and as a roadblock
U.S. and European regulators have indicated
that the scope
and extent of expensive and time-consuming clinical testing they will require
will depend on the apparent similarity, based on initial
physiochemical
characterization. The authorities recognize the current limitations of the
analysis of proteins and recommend the use of a wide range of
analytical
measurements, each of which may have limitations, but which, when combined,
build as complete a picture—or "fingerprint"—of the molecule
as possible.
This is sometimes described as a "totality-of-the-evidence"
approach. It is
therefore potentially highly advantageous for biosimilar
developers to present as comprehensive a physiochemical analytical comparison
of their new
proposed product and the reference material, rather than taking a
more limited, "play-it-safe, bare-minimum" approach.
New technologies to
meet new challenges
Two related areas where innovation may potentially improve
the competitiveness of a product are the way it is administered to
the patient
(delivery) and the use of stabilizing additives to improve stability and shelf
life (formulation). However, for many time- and cash-pressed
developers, the concept
of thoroughly optimizing the protein formulation or adopting new formulation
technologies for improved long-term storage
stability or delivery properties
may be seen as a luxury. Additionally, biosimilar developers may consider any
deviation from the originator
formulation as a risk that will need explaining
to the regulatory authorities.
A host
of innovative approaches and technologies exist that
have the potential to improve almost every stage of the process of developing
and manufacturing
biopharmaceuticals. Embracing them, however, is not without
risk to developers, and in an environment where the status quo is considered
good enough,
they struggle to gain acceptance. A change in the market dynamics
for biopharmaceuticals may, however, mean this attitude will have to change and
opportunities for innovation will increase. In the meantime, for all the small
companies with the innovative analytical, formulation, delivery and
manufacturing technologies—hang in there!
Simon Webster is chief
scientific
officer and co-founder of Avacta Analytical, a specialist contract
research organization providing biophysical characterization services and
innovative instrumentation to the biopharmaceutical market.
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