“Biologics development is an intricate, multifaceted exercise with many potential areas for waste and opportunities for failure...”

1. June 2012
BIOLOGICS ENABLING TOOLS
PART 2
B I O L O G I C S
THIS DECADE
by Simin Zaidi
BIOSIMILAR

2. NPT | The Community of Big Thinkers
B
eing in the Biologics industry
and interacting with many
different product development
teams, I often have the pleasure
of learning about potential biological
miracle products. From Biologic drugs
that can turn back time on a DNA level
to self-administrable agents that allow
soldiers to protect themselves from bio/
chemical-warfare agents in the field, the
potential is awesome. However working
in applied science, my job involves
taking these technologies and making
them into a reality. To be of practical
consequence, brilliant ideas have to get
past the inventor’s self-gratifying “pie
in the sky” stage of “could” solve-blank,
to one not as sexy. Economics and
Regulations are obvious driving forces
at this next stage; however the correct
methodology for execution of a successful
biopharmaceutical product development
process is still largely nebulous. It must
be, as the rate of success is so low.
The three main areas of Biologics Product
Development covered in this article are
Discovery, Manufacturing and Clinical
phases. The tools used to accomplish
them define these areas. These tools can
be‘hard’or‘soft’.Soft tools include project
and operations management, scientific
method, engineering problem solving,
analytical ability, risk management, and
business strategy. Hard tools include
software, measurement and analysis
tools, raw materials, process equipment,
and communication and information
management tools.
Discovery
The majority of Biologics Discovery still
takes place primarily in North America
and Europe. This decade will see growth
of successful discovery efforts in countries
such as Singapore, India, China, Russia,
South Korea and South America. This
effort, supported by wealth and often
government policy, also relies on the
hiring of experienced personnel from
the nations currently
leading in Biologics
development. In other
words there is a need for
soft tools in the latter
group of countries.
Massive layoffs in
North America and
Europe do help supply
competing economies
with this key ingredient
of expertise and
experience. On the flip
side, often the political
and cultural differences
are still likely to be a
deterrent to individuals
considering relocation.
Despite the risk of
Intellectual Property
protection issues,
many small to mid-
size companies are
outsourcing parts of their more labor
intensive discovery efforts to countries
such as China.
Contract research organizations
(CRO) and even offshore departments
specializing in scouting, affinity
maturation of large molecules and
early animal studies, are a financially
attractive and possibly competent enough
alternative making sense to Western
companies looking to stretch their
finances. I don’t doubt that colleagues
in discovery would shake their heads at
the experimental design and methods
used at these CROs however if these
CROs can afford to perform many more
experiments, in the same amount of
time it would take an elegantly designed
study here, actual success rates among
experiments becomes less important.
The key is that a successful outcome is
reached, in the same amount of time and
at a significantly lower cost. Whether
such CROs are able to achieve an
acceptable balance of expertise at a lower
cost as a long term business model is to
be seen in the coming years.
In the meantime, in North America
and Europe the innovative flames do
remain stoked. Increasingly sophisticated
modeling and predictive discovery
techniques developed out of the
experience of scientists and engineers
and fueled by entrepreneurs are coming
to fruition. Expensive machines that
some of us would have only dreamed
of a few years ago can perform highly
complex development tasks, precisely
and rapidly. Similarly in terms of tool
innovation; animal testing concerns, non-
embryonic stem cell culture techniques
and biomarker discovery are leading
to the rise in the number of companies
offering non-animal models for aiding
and complementing discovery, analytical
and clinical efforts. It may be foreseeable
later this decade that we see reduced
Clinical Study costs as reliable models
begin to replace the need for as many
studies in animals and humans.
BIOLOGICS THIS DECADE PART II - BIOSIMILAR
“Biologics development is an intricate, multifaceted exercise with
many potential areas for waste and opportunities for failure...”

3. June 2012
Manufacturing
Yet another way of looking at Biologic
Product Development is as an exercise
with two main facets; Proof of Concept
(in terms of product safety, efficacy and
manufacturability) and production of
an actual product for proof of concept
activities. It is not unheard of that a
Biologic fails as manufacturing it is not
possible or is too costly to make economic
sense. Once the Biologic is found to be
producible the next step is producing
material for Pre-Clinical followed by
ClinicalProofofConceptwork. Thisneed
has led to the growing establishment of
Contract Manufacturing Organizations
(CMO) and CRO companies in the
West and now the East. However as we
can see with the number of United States
Food and Drug Administration 483s
being issued, Biologics production is not
as straight forward as manufacturing,
say, iPads. This is due to both
production complexity and the gravity
of intended use. In biopharmaceutical
manufacturing, my own area of focus,
many aspects are still approximated (e.g.
biologic processes) and manual, even in
a current Good Manufacturing Process
environment. It is imperative that
design space characterization, statistical
design and data analysis be added as
tools to increase processing reliability.
In addition to such tools the personnel
designing processes need to understand
the science, biological systems, scale up
complexities and regulatory requirements
to ensure proper control and repeatability.
The same applies to the operators and
quality assurance personnel involved in
manufacturing biologics. Data trending
is a quality control function as well. Such
expertise, which should be both broad
and deep, comes with relevant education,
training and years of experience with
multiple projects.So it follows that having
in-house expertise in all the necessary
product development areas for a Sponsor
company makes little sense unless they
intend to offer the services to others
as part of their business model. We are
seeing more Biologic companies retain a
smaller number employees consisting of
experts in technical and business product
development who orchestrate activities
performed by expert service companies.
Clinical
Complementary clinical studies are
carried out in countries such as India,
Mexico and Eastern Europe. The goal
in such cases may be to supplement
ongoing efforts in the intended filing
country or to provide proof of concept
data to attract investors (more so the
former as governments clamp down on
the idea of offering up their citizens as
“guinea pigs”). The advantage has been
cost savings and larger populations
with the required clinical status. This
strategy is not unique to the Biologics
industry however general understanding
of product handling (biologic molecules
and tissues are extremely sensitive to
storage conditions) and complicated
administration protocols, in addition to
“lost in translation” scenarios may add a
risky variable to the mix of developing a
Biologic. It will be key that information
exchange platforms continue to be
developed and optimized while being
available at affordable rates for this to
be successful. Many software design
companies are beginning to answer the
call for universal solutions.
Cost Control
The ultimate goal of Biologic Enabling
Tools is to control costs (by increasing
success rates and efficiencies).As a Global
Biopharmaceutical Market Report from
2010 (IMARC) points out that the high
costs of Biologics is expected to be closely
scrutinized by payers in coming years.
Coincidently a recent interview with
Fareed Zakaria on Your Money CNN,
about his upcoming special on Fixing US
Healthcare, points out analysis showing
20 countries that do Healthcare better
and less expensively than the US. Nobel
Prize Winning economist Kenneth
Arrow’s 1963 paper “Uncertainty and
the Welfare Economics of Medical
Care” points out how Healthcare does
not work as a regular market economy.
This is because one can’t predict the
need to purchase it thus leading to the
argument for an insurance system of a
sort. In addition, a universal insurance
system’s costs must be controlled. With
Healthcare being an issue that cannot
be ignored, paired with large numbers
of unemployed Biologic experts looking
for work and a growing middle class
in Eastern economies, we seem to be
approaching an inevitable truth.Biologics
represent human innovation for human
good. There are emerging markets
and there are Biologic products to be
developed and sold affordably. In other
words, the opportunity for Biologics
Product Development is ripe.
Finally
By all indications, in the coming decade,
we will see even greater international
product development efforts. In the
Biologic leader countries we should
continue to see an improvement of
product development philosophy and
methodology (that increases success rates
while decreasing costs). Materializing
shifts already apparent include a move
to smaller Biologic company workforces
consisting of technical and business
project orchestrators, the use of more
sophisticatedtechnicaltoolsandafocusof
working with contract service companies
specializing in various key areas. Due
to tightening in investment capital, it is
already a business model norm to develop
a product to a stage and then sell it to Big
Pharma. However as tools improve and
costs decrease, will we see an increase in
Biologic product success rates and move
away from this model? It is an option
worthy of consideration.
Simin Zaidi is a Bioprocess Professional in Southern California, USA, experienced in taking multiple biopharmaceutical products through Clinical and
Commercial Production. She can be reached at Stamford Bioprocess Technologies on contact@stamfordbio.com.
BIOLOGICS THIS DECADE PART II - BIOSIMILAR
“From Biologic drugs that can turn back time on a DNA
level to self-administrable agents that allow soldiers to
protect themselves from bio/chemical-warfare agents in the
field, the potential is awesome. ..”