16 Feature

Filtration+Separation March/April 2011

Pharmaceuticals:

Filtration plays
key role in
pharmaceuticals
and biotechnology
en Sutherland reviews the present state of the pharmaceutical and
K biotechnology component of the chemicals production sector and
looks at the range of applications for filtration and other separation
equipment, at a fairly critical time in the history of the industry.

The whole chemicals industry is huge, being what are essentially chemical routes to these largely chemical, that for the biotechnological
the largest user of mechanical separation drugs, as well as the bulk fermentation routes segment is almost entirely biological, and
processes, with about one sixth of the global to antibiotics. hence clearly sustainable.
market for filtration and sedimentation
The biotechnological industry on the other In the present context, there is an obvious
equipment (and over one fifth of the filter
hand is not at all well understood, partly problem in trying to draw boundaries. For
media market). It is also in a state of flux
because of the wide range of names being example, a great deal of effort is being put into
– technically, economically, corporately
used in it. The main difference is that while the biotechnological development of drugs,
and even geographically – and was so
the basis for pharmaceutical processing is which should be considered as part of the
even before the impact of the 2008/2009
recession. The same is equally true in its ‘life
sciences’ component, the pharmaceutical and
biotechnology industries.
This component is made up of two quite
different segments: the pharmaceutical
industry, which contains many large and
mainly profitable companies, in a well
established sector, quite well distributed
around the world; and the biotechnological
industry, made up of a few sizeable companies
and many small ones, in a rapidly developing
business, mainly based in the USA and
western Europe, spending large sums of their
investors’ capital, but without, as yet, making
very much profit.

Definitions
The pharmaceutical industry is quite well
understood: it concerns the development and
manufacture of drugs for human and animal
welfare. It is known for a wide range of drugs
for use against human afflictions, and employs The pharmaceutical industry concerns the development and manufacture of drugs for human and animal welfare.

Filtration+Separation March/April 2011
Biochemical separation follows a particular cell growth process.
pharmaceutical industry. On the other hand, a
significant amount of drug manufacture starts
with fermentation of natural products, and so
could be counted as biotechnological.
Other problematic class boundaries are those
between this whole sector and ‘household
goods’, and ‘medical and health’. A group
of special foods designed to be particularly
beneficial to human health are now being
referred to as ‘nutraceuticals’, and there are
even ‘cosmeceuticals’ with proven benefits to
the skin.
Biotechnology has three main aims (which
could be said to be those of all of humanity):
• to heal the world’s sick and ailing;
• to produce better crops, and so improve the
provision of food; and
• to produce alternatives to fossil fuels as a
source of energy or as chemical feedstocks.
Accordingly, biotechnology can be classified
by its fields of application:
• human and animal health (also called red
biotechnology);
• crop production and agricultural
process improvement (also called green
biotechnology, with blue biotechnology
to describe the less-common marine
applications); and
• non-food uses of crops and other products,
such as biodegradable plastics and
biofuels (also called industrial or white
biotechnology).
The potential for industrial biotechnology is
enormous, as it can, in principle, replace the
whole of the petrochemical industry, both for
liquid fuels and chemicals. It will be able to
do this at three levels: the specific production
of one chemical by fermentation or enzyme
processing, production of a range of organic
chemicals in a biorefinery as by-products from
biofuel production, or production of a specific
chemical in genetically modified plants or algae.
Pharmaceutical and
biotechnological processing
characteristics
The whole sector, therefore, covers all of those
processes that are concerned with human and
animal health and well-being, as well as those
that use living organisms to produce useful
materials. The majority of these operations
are carried out in the liquid phase, with solid
suspensions being very common, so that
the use of filtration and centrifugation is
widely found, as a solid recovery step, or in
purifying ingredients, intermediates or final
products, in the recycling or treatment of
waste streams and in protective systems for the
manufacturing processes.
An important characteristic of this whole sector
is that of scale: the size of the operation. Whilst
several of its processes are large (bioethanol,
Laboratory research and development is a vital element in the pharmaceutical and biotechnology sector.
Feature 17
antibiotics), the majority of biotechnical
applications are small, verging sometimes on the
microscopic. Not only does this usually call for
batch operation, but also the equipment must be
extremely precisely designed.
Some of these products (or by-products) can
be very toxic. Operating systems then need to
be very secure, with all entry and exit points
well protected against leakage of process
materials into the surrounding environment
– a vital example of a need for thorough
vent filtration. The reverse situation is also
true that most biotechnical processes are
very delicate and so easily contaminated by
impurities in ambient air – from which they
must be adequately protected. The required
protection may just be against dust particles,
but may also need combination filters to
remove gaseous impurities as well.
Standards for design and operation are strict,
imposed both by national and international
institutions, at least as severe as those of, for
example, the US Food and Drug Administration.
The codes embodied in Good Manufacturing
Practice are essential in this sector. The
separation equipment used in it must be able to
operate in a state of scrupulous cleanliness, with
an essential need to avoid cross-contamination.
The equipment should thus be easily cleaned,
preferably by some kind of clean-in-place
process, which may involve steam sterilisation
or an aggressive cleaning solution. The cleansing
processes must allow sufficient residence time for
the cleaning solutions to do their job.
It is as important to keep the process fluids free
of unwanted contaminant as it is the equipment
in which they are to be processed. Heat
sterilisation is often sufficient for this purpose,
but there are many situations where the resultant
heat damage could not be tolerated. In this case
the ability of microfilters to remove bacteria, and
ultrafilters to remove viruses, is used to sterilise
liquids by filtration.
Biochemical separations
The key biochemical separation follows a
particular cell growth process, in which a
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Filtration+Separation March/April 2011

Table 1: Top 20 pharmaceutical and biotechnology companies

Company Base $ bn Company Base $ bn
Johnson & Johnson USA 61.9 Eli Lilly USA 21.8
Pfizer USA 50.0 Bristol-Myers Squibb USA 18.8
Roche Switzerland 47.4 Boehringer Ingelheim Germany 16.5
Novartis Switzerland 46.3 Takeda Pharmaceutical Japan 15.8
Glaxo SmithKline UK 45.8 Amgen USA 14.6
Sanofi-Aventis France 42.0 Teva Pharmaceutical Israel 14.4
AstraZeneca UK 33.7 Merck KGaA Germany 11.6
Abbott Laboratories USA 30.8 DSM Netherlands 10.4
Merk & Co USA 27.4 Astellas Pharmaceutical Japan 9.9
Bayer Germany 24.6 Novo Nordisk Denmark 9.8

Table 2: Corporate acquisitions Table 3: Pharmaceutical and

Company Activity biotechnology market, 2010
Pfizer expands further by buying Pharmacia (2002), Wyeth (2009) Market category 2010 market, $m
and King Pharmaceutical (2010) Total filtration & 1846
Sanofi-Syntholabo buys Aventis, to form Sanofi-Aventis (2004) sedimentation
Bayer buys Schering (of Germany) (2006) Sedimentation 384
Merck KGaA buys Serono and sells generics division to Mylan (2007), and Filtration 1462
buys Millipore (2010)
Total filter media 1118
Novartis sells Gerber Products to Nestlé (2007) and buys Alcon from
Nestlé (2010)
Schering-Plough buys Organon Biosciences, the biotech division of AkzoNobel (2008) Some idea of the consolidation that has
Takeda Pharma buys Millennium Pharma (2008) already taken place is shown by the leading
Teva Pharma buys Barr Pharma (2008) and Ratiopharm (2010) company changes in Table 2, which lists
AstraZeneca buys MedImmune (2008) mainly pharmaceutical company mergers
Roche buys a large stake in Genentech (2009) and then the balance (2010) since 2000 up to the Genzyme acquisition
Merck & Co buys Schering-Plough (2009) completed as this article was being written.
Abbott Labs buys Solvay Pharma (2009) Before the events listed in Table 2, there
Warner Chilcott buys the pharmaceuticals business of Procter & Gamble (2009) were some major changes in the late 1990s,
Daiichi Sankyo buys Ranbaxy (2010) including:
GSK buys Stiefel Laboratories (2010) • the acquisition of Ciba-Geigy by Sandoz
Johnson & Johnson buys Crucell (2010) to form Novartis, in 1996;
Sanofi-Aventis buys Genzyme (2011)
• the acquisition of Astra by Zeneca (once
the pharmaceutical division of ICI) to
mass of cells is caused to grow and multiply, • in test laboratories and in the production form AstraZeneca, in 1998;
at the same time making a specific valuable of test kits; • the acquisition of Hoechst (once the
product, usually a protein. This material may
• in the filtration of medical gases and third largest chemicals company in
be produced in several ways, inside or outside
the protection of breathing equipment, the world) by Rhône-Poulenc, to form
the cell, and has to be liberated by breaking
especially inhalers; Aventis, in 1999;
the cell walls. Whatever its origins, it must
then be separated from the cell material, and • in diagnostic kits for hospital, medical and • the more-than-doubling in size of Pfizer
the surrounding liquor. This is almost always domestic use, such as tests for pregnancy or by its acquisition of Warner-Lambert,
done by means of a high speed disc separator diabetes; and also in 1999; and
centrifuge, probably followed by a polishing
• in detection kits, and bioassays and for • the acquisition of SmithKline Beecham
filter, employing microfiltration, and possibly a
other analytical techniques. by Glaxo Wellcome to form GSK, in
cross-flow ultrafilter as well.
January 2000.
It is, thus, easily seen what an important part The corporate structure of the
filtration and centrifugal sedimentation play in sector The equipment market
the main production process of the biochemical
sector, requiring very careful separations by The pharmaceutical industry contains some The filtration and sedimentation equipment
particle size. Other separation systems are also very well known companies. The largest market size estimates for the pharmaceutical
of increasing value in life science application: in the sector are listed in Table 1, which and biotechnology sector are given in Table
dialysis for blood purification, chromatography shows, for each company, the country in 3, as a total equipment figure, and then split
for separations as well as analysis, pervaporation which it is based, and its 2009 turnover in between sedimentation and filtration (with a
systems for the concentration of delicate billions of dollars. separate estimate for filter media sales). The
by-products, and even diafiltration, for salt estimates are quoted for 2010, in millions of
The pharmaceutical industry has US dollars at the mid-year average currency
removal in ultrafiltration. experienced quite a long period of corporate value.
A wide range of precise filtration equipment is acquisition activity, and this pattern
used in the biotechnology sector: is starting to affect the biotechnology The equipment estimates in Table 3 only
component as well, as start-up companies include that ancillary equipment (such
• in laboratory research and development for feel the need for increased capital or wider as drive motors) necessary for its safe
the discovery of new drugs; market contact. operation.

Filtration+Separation March/April 2011
Despite being a rapidly growing sector, there are a number of issues facing the pharmaceutical industry.
It is further estimated that the biotechnology
component of the equipment market is about
5% (say, 3-7%) of the total equipment figures
in Table 3.
Growth trends
The equipment markets must correlate
strongly with the number of people that
there are in the world, and the standards
of living that those people enjoy. It
follows that the increasing population
numbers in the world, and the increasing
demands for higher standards of living and
better healthcare, especially in the larger
developing countries, will be powerful
driving forces expanding the pharmaceutical
and biotechnology markets.
On these two trends alone it is easy to predict
a golden future for the pharmaceutical and
biotechnological industries. However, both
components face some difficult problems,
which will need to be solved before this
future can be realised. The pharmaceutical
industry in particular has to deal with the
imminent loss of patent protection on a
significant number of its ‘blockbuster’ drugs,
with little sign of replacement money makers
at the moment. This is coupled with the wide
availability of generic drugs, serving the same
purpose, against which the only effective
protection is to buy the generics makers, or
produce one’s own. Most Governments with
state provided healthcare systems are pressing
heavily on the use of generics rather that
patented drugs in the interest of cost savings.
Other negative factors facing pharmaceuticals
are:
• the huge cost of developing a major drug;
• the spreading appearances of antibiotic-
resistant bacteria (such as MRSA);
• the increasing amounts of counterfeit drugs
on the market;
• the growing concern over drug safety and
the resultant greater difficulty in achieving
approval for a new drug; and
• the necessity to be scrupulously honest in
drug marketing – the recent spate of huge
fines a powerful memory.
The biotechnology industry faces many of
these problems as well, together with some of
its own:
• major production volumes of biochemicals
and biofuels will require vast areas of land
on which to grow the feedstocks, and there
is a long way to go before the proper
balance between food and bioproduct need
will be achieved;
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• most bioproducts are still being made in
relatively small quantities, and therefore at
high specific cost;
• public disenchantment with ‘scientists’ has
to be overcome, and turned into approval
of sustainable bioprocessing; and
• a more mature market has to develop,
one that is not so easily upset by a bit of
bad news (especially a drug’s failure to get
approval.
To oppose these negatives there are, of
course, a host of positives working to
promote the growth of the sector, in
particular the view of a future sustainably
supplied with chemicals and fuels produced
biochemically, and even by virus-driven
artificial photosynthesis. Biotechnical and
pharmaceutical production will be greatly
helped by a gradual change from batch to
continuous processing, and drug production
will become less wasteful.
The exciting visions of biochemicals will be
supported by the discovery of new uses for
old drugs – even thalidomide is being
rehabilitated – and by the development of
modern versions of old, familiar recipes.
Encouraging growth is certainly forecast for
the whole sector, with figures of 10 or 11%
achievable once the recession has been left
behind. In China this figure will be nearer to
15% or more (although traditional Chinese
medicine will be a tough competitor). •
Contact:
Ken Sutherland
Tel: +44 (0)1737 218868
E-mail at: ken.suth@ntlworld.com
Ken Sutherland has managed Northdoe
Limited, his process engineering and
marketing consultancy, for over 30 years.
Northdoe is largely concerned with the
marketing and technology of filtration and
related separation processes. He has written
numerous articles for this journal and for its
sister publication Filtration Industry Analyst, as
well as four books on separation processes,
most recently an A to Z of Filtration and the
fifth edition of the Filters & Filtration
Handbook, both for Elsevier.