Published by NNE Pharmaplan April 2012
Biopharmaceuticals:
entering a new world
2 · Angle · April 2012
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How much is health worth?
Since the first biopharmaceutical medicine was launched several
decades ago, biopharmaceuticals have grown in importance as
they offer hope for people with debilitating and life-threatening
conditions for which there was previously no treatment or cure.
However, the success of biopharmaceuticals also presents a ­challenge
– the much higher development and production costs mean that
biopharmaceuticals can be much more expensive than conventional
chemical drugs.
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This high price tag places extra pressure on healthcare budgets and
forces payers to prioritise diseases and treatments – and define how
much a life is worth. To many countries and regions the possibilities
offered by biopharmaceuticals are simply out of reach. But biosimilar
products may provide an opportunity to improve treatment options.
As many companies face the patent expiry cliff for some of their
blockbuster products, other types of products, perhaps even
biosimilars, will become more important for their future product
portfolio.
Going forward, biosimilars will make some treatments affordable
for more patients. And biosimilars will encourage innovative
pharmaceutical companies to invest in the development of new and
improved treatments as well as more cost-effective manufacturing
solutions for existing products – including biosimilars.
In this issue of Angle, we will take you through some of these
interesting challenges and opportunities.
Please take the time to be inspired with us.
Best wishes
Morten Nielsen
CEO NNE Pharmaplan
NNE Pharmaplan is the world’s leading
engineering and consulting company
dedicated to pharma and biotech.
April 2012 · Angle · 3
Biosimilars provide competition for off-patent biopharmaceuticals.
But a number of challenges must be overcome for successful
market penetration.
Get in the game, page 10
The biopharmaceutical production facility of the future is
already here.
Biotech on demand, page 29
5Saving lives, saving
money
15Medicines for those
in need?
19Innovation for good
health
23Joining forces to
change lives
38Treatment at any cost?
46NNE Pharmaplan News
Saving lives,
saving money
As the global population grows and life expectancy rises,
biopharmaceuticals are in ever greater demand for the
treatment of life-threatening and chronic diseases.
But this class of medicine often comes with a high price tag.
6 · Angle · April 2012
Biopharmaceuticals are one of the fastest
growing segments of the pharmaceutical
industry, with more than 200 products on
the market and over 500 estimated to be in
development. Representing approximately
16% of total pharmaceutical sales, bio­
pharmaceuticals had a market value of USD
138 billion in 2010, according to IMS Health.
Often there is no other
available treatment for the
condition, which means that
biopharmaceuticals can be
truly life-saving.
Furthermore, EvaluatePharma predicts that
by 2016 seven of the top ten pharmaceuticals worldwide will be biopharmaceuticals
including five monoclonal antibodies.
Biopharmaceuticals are used to treat a wide
range of complex and devastating diseases,
some of which are life-threatening while
others drastically reduce quality of life.
Often there is no other available treatment
for the condition, which means that bio­
pharmaceuticals can be truly life-saving.
But with aging populations worldwide
treatment of chronic conditions comes with
a significant financial cost. In 2010 the
Swiss Federal Supreme Court ruled that the
maximum cost to a health insurer that could
be considered reasonable per human life
year saved was 100,000 Swiss francs (about
USD 100,000). However, this is less than the
annual cost of some biopharmaceuticals.
Until recently biopharmaceuticals have
­experienced little competition. But with
patents now expiring for many of the first
generation compounds, this is changing.
April 2012 · Angle · 7
There is a significant difference between
the traditional “small molecules” pharmaceuticals and “large molecules biopharmaceuticals”: while the manufac­turing of small
molecules can be copied and verified as
exactly the same product, large molecules
are difficult to copy because production is
based on or derived from a living organism.
Frost & Sullivan have estimated that USD 100 billion
worth of biopharmaceuticals will have lost patent
­protection by 2020.
Instead a biopharmaceutical “copy” is
called a “biosimilar”. Such a product must
be ­verified as similar in terms of quality,
safety and efficacy to the reference bio­
pharmaceutcial medicine with which it has
been compared. The first biosimilar products
were approved for the European market in
2006 and today 14 biosimilars have been
­approved in Europe and very few in the US.
But there are many products in the pipeline.
Frost & Sullivan have estimated that USD
100 billion worth of biopharmaceuticals
will have lost patent protection by 2020.
Biosimilars therefore represent one of the
most exciting and rapidly evolving areas
of product development in the pharma­
ceutical industry.
Biosimilars are making
treatment for chronic
diseases more affordable.
While not as discounted as generics for
small molecule medicines – which can
achieve price reductions of 70-80% – the
cost of a biosimilar is currently around
20-30% lower than that of the original bio­
pharmaceutical. According to the European
Generic Medicines Association, just a 20%
price reduction on five off-patent biopharmaceuticals could save the EU over EUR
1.6 ­billion per year.
Biosimilars are making treatment of chronic
diseases more affordable – which is good
news for patients in developing countries,
where healthcare costs are often paid outof-pocket, and also for developed markets
where healthcare budgets are already
overstretched. With more competition in the
coming years these costs could drop even
lower, making treatment more ­affordable
– and therefore more attainable – for the
millions of people around the world in
desperate need of these essential medicines.
Biopharmaceuticals AND
monoclonal antibodies
First used commercially several decades
ago, biopharmaceuticals are medicines
whose active substance is made by or
derived from a living organism using
biotechnology. They can consist of
relatively small molecules such as human
insulin or erythropoietin (EPO) (a
hormone that regulates the red blood cell
production), or more complex molecules
such as monoclonal antibodies.
Monoclonal antibodies (MAbs) are
antibodies produced in pure form by a
single clone of cells. They can be made
in large quantities and have a specific
affinity for certain target molecules called
antigens. These are found on the surface
of cells including those that are malignant
such as cancer cells. See page 43 for more
details.
Scan with your smartphone to watch
an interview with Judy Orem from
Oregon Health & Science University
Judy Orem was 51 years old when diagnosed with chronic myeloid
leukemia (CML), a cancer of the white blood cells. Three years later, her CML
was no longer responding to therapy and Judy was told she had very little
time left to live.
Then a friend told her about a clinical trial of a new drug called Gleevec®
and Judy was able to join the trial. Scientists had identified the specific
genetic alteration that causes the white blood cells in CML to grow out of
control and Gleevec® was the first approved drug to directly turn off the
signal of a ­protein known to cause a cancer. CML used to be considered a
death sentence, but today 95% of patients who take Gleevec® are alive after
5 years. Judy has now been taking the drug for over 12 years and is one of
the longest-living Gleevec® patients in the world.
10 · Angle · April 2012
Get in the game
With the introduction of biosimilars into the market,
blockbuster biopharmaceuticals are facing significant competition.
Biosimilars are helping to make treatment
more affordable for chronic and life-threat­
ening diseases by competing with biopharmaceuticals that have lost patent protection.
This competition lowers the cost of treatment and challenges the manufacturers of
the original biopharmaceutical to discover
new innovative medicines.
There are a number of
barriers to overcome for
a company to successfully
launch a biosimilar.
While Europe and emerging pharmaceutical,
socalled pharmerging, markets are leading
the way, the US is expected to be the ­largest
market for biosimilars in the future. IMS
Institute for Healthcare Informatics predicts
global spending on biosimilars will exceed
USD 2 billion annually by 2015, against USD
311 million in 2011, and that by 2020 the
overall penetration of biosimilars within
the off-patent biopharmaceuticals market
will reach 50%. Furthermore, Decision
Resources anticipates that in 2020, biosimilar versions of monoclonal antibodies for
oncology indications alone will reach more
than USD 4 billion in sales in the US, France,
Germany, Italy, Spain, the United Kingdom
and Japan.
There are a number of barriers to overcome
for a company to successfully launch a
biosimilar. While producing a biosimilar
carries less risk than producing an original
biopharmaceutical, it must be proven to be
sufficiently similar to the originator in terms
of mechanism of action and have comparable efficacy, safety and quality. Production
is highly sophisticated, requiring specialist
training and dedicated production lines. It
can take approximately 8 years to develop a
biosimilar at a cost of up to USD 250 million.
Compare this to the development of a
generic small molecule medicine, which can
take just 2 years at a cost of USD 2 million,
and it is easy to understand why only a few
manufacturers have so far ventured into the
production of biosimilars.
It can take approximately
8 years to develop a
biosimilar at a cost of up
to USD 250 million.
The approval process for biosimilars has also
been a major barrier. While China and India
have had follow-on biopharmaceuticals for
some years, it wasn’t until March 2004 that
the European Medicines Agency introduced
a new abbreviated approval pathway and
guidelines for biosimilars. Other countries,
including Canada and Japan, have now implemented or proposed biosimilar approval
guidelines. The US, however, has so far not
embraced biosimillars with open arms.
April 2012 · Angle · 11
The US Food and Drug Administration (FDA)
has only recently in 2012 introduced guidelines for approval.
Convincing doctors to prescribe a biosimilar
rather than the original drug is another barrier to success. Companies must be able to
effectively brand and market the biosimilar
and have specialised sales forces – which
are not necessarily key competences of all
biotech companies.
Given all these barriers to entry, it is not
­surprising that penetration of the market­
place has been slow. But the market is
predicted to develop as more regulatory
authorities and healthcare professionals gain
experience and confidence with biosimilars.
Currently, Europe has the largest market,
accounting for 80% of global spending on
biosimilars according to IMS Health – but
only covering three originator products
(erythropoietin – EPO, human growth hormone and granulocyte colony-stimulating
factor), and just six manufacturers are
responsible for these biosimilars.
However, with many more biopharmaceu­
ti­cals facing patent expiration and several
bio­similars at various stages of development,
the number of therapeutic areas covered
by bio­similars will increase. Companies in
Europe, the US, Canada, India and Israel
are all set to compete in this market and
originator bio­pharmaceutical companies are
investing in this area, with the giants Merck
& Co, AstraZeneca and Eli Lilly all showing
signs of entering the bio­similars market in
the next few years.
Biosimilars present
a significant market
opportunity and more
choice for prescribers.
Whatever the future holds for biopharmaceuticals, everybody agrees that biosimilars
present a significant market opportunity and
more choice for prescribers – which should
ultimately lead to a better quality of life for
patients suffering from chronic diseases
around the world.
Brain cancer 8
Sarcoma 4
Head/neck cancer 3
Skin cancer 3
Leukemia 17
Lymphoma 22
Lung cancer 15
Breast cancer 10
Solid tumors 12
Liver cancer 4
Pancreatic cancer 9
Kidney cancer 5
Ovarian cancer 7
Stomach Cancer 4
Bladder cancer 1
Colorectal cancer 10
Multiple myeloma 7
Prostate cancer 5
Cancer-related conditions 2
Other cancers 10
Unspecified cancers 5
Number of MONOCLONAL ANTIBODIES IN DEVELOPMENT AGAINST
CANCER. MAbs give hope in the fight against cancer. According to the World
Health Organization, 7.6 million people died of cancer in 2008, accounting for
13% of deaths worldwide. About 70% of all deaths from cancer occur in low
and middle-income countries but more than 30% of cancers could be cured
if detected early and treated adequately. There are over 100 different types
of cancer and by the end of 2011 almost 200 monoclonal antibodies were in
development for cancer treatments.
Medicines for
those in need?
Innovative biopharmaceuticals have made it possible to treat
diseases that were fatal or severely reduced quality of life a
decade ago. But the reality is that these innovative medicines
are still not accessible to all.
16 · Angle · April 2012
A major barrier to health is
the affordability of drugs.
huge costs associated with research and
development (R&D) and that drugs for rare
conditions have such small markets.
Pharmaceutical companies must balance
their responsibility to shareholders with
their social responsibility to make innovative
medicine generally accessible.
But even with these high prices, some
are concerned that the pharmaceutical
industry as a whole is not generating a
return on R&D investment. A report by
EvaluatePharma estimates that the net
present value of new products between
2008 and 2010 averaged USD 70 billion per
year, while R&D investment was USD 127
A major barrier to health is the ­affordability
of drugs – and the price tag on some
bio­pharmaceuticals is high. Take for example
Shire Pharmaceuticals’ Elaprase for Hunter’s
syndrome, which according to Forbes
costs USD 375,000 per patient per year in
2010. Pharmaceutical companies are under
increasing pressure to reduce prices, but
in their defence they claim that there are
Some may suggest that the
industry is exacerbating the
access-to-health problem.
April 2012 · Angle · 17
billion per year.
Added to the pharmaceutical industry’s woes
is the poor R&D productivity of recent years,
with the number of new drugs ­approved in
the US declining by 24% in 2010. Pfizer’s
response to this has been to announce the
removal of USD 1.5 billion from its 2012 R&D
budget. GSK began a radical shake up of its
R&D department three years ago in an effort
to increase productivity and reduce inefficiency – but in 2010 still fell out of the world’s top
5 biggest sellers of prescription medicines.
And over the last five years AstraZeneca has
significantly reduced their manning several
times, including a very recent job cut, in
order to release more funding for R&D.
To overcome the product innovation gap,
many pharmaceutical companies are looking
at mergers, acquisitions and collaborations
with smaller biotech companies to help
them find the next big product. Selling
drugs for rare or orphan diseases is immensely profitable – and therefore in the
interests of shareholders – although not so
The Universal Declaration
of Human Rights states that
every person has a right to
medical care.
much for payers.
Some may suggest that the industry is
exacerbating the access-to-health problem
and that it should instead focus on reducing
the cost of existing drugs to make treatment
more affordable – particularly people who
have to pay for treatment out of their own
pockets. However, industry experts claim that
without innovative research, fatal diseases
will not be overcome and medical science will
not progress. It should also be remembered
that several drugs developed for rare conditions have subsequently been found to work
in other indications with a larger market.
Creating greater efficiency in ­manufacturing
and production processes will surely help
to lower the cost of both existing and
innovative drugs. And if prices were lower,
the market should naturally expand as more
patients and payers could afford treatment
– which is good news for shareholders,
payers and patients alike.
The Universal Declaration of Human Rights
states that every person has a right to
­medical care and that all individuals and
organs of society have a responsibility to
promote respect for this. This includes
the pharmaceutical industry. When a new
treatment has been made possible through
research and innovative thinking, it should
be made accessible to everyone including
the most vulnerable members of global
society. If it can be done, it should be done.
Innovation
for good health
A biopharmaceutical company is aiming to bring high
quality biosimilar monoclonal antibodies to the Chinese
market within the next 4 years.
Interview with Scott Liu, Co-founder of Henlius Biopharmaceuticals, Inc.
20 · Angle · April 2012
Scott Liu founded Henlius Biopharma­
ceu­ticals, Inc. together with Paul Liu and
Weidong Jiang: “We started Henlius
­because we feel there is a huge unmet
medical need in China and other parts
of the world for therapeutic monoclonal
antibodies. Usually only the regulated
markets have these therapies as they are
very expensive. For example, an entire
course of treatment with Herceptin against
breast cancer in China costs RNB 350,000
[about USD 55,600], which is more expensive than in the US because of the import
tax. The treatment is not covered by health
insurance in China – patients have to pay
for imported drugs themselves. And with
an average annual income of USD 3000,
most people can’t afford this treatment. We
decided to develop and manufacture high
quality monoclonal antibodies in China at a
reduced price to increase their affordability,
so that these drugs would not only be for
those living in rich countries.”
Drug sales are expected to
increase by USD 40 billion
over the next five years.
China has a huge home market and IMS
Health predicts that it will be the second
largest pharmaceutical market in the world
by 2016. Drug sales are expected to increase
by USD 40 billion over the next five years,
driven by demographic changes such as
the rising affluent middle class and the
increased prevalence of non-communicable
(lifestyle) diseases for which biopharmaceutical drugs offer treatment. It therefore
seems that the three founders chose a good
time to form Henlius in 2009. “We started
our company with USD 200,000 borrowed
from family and friends and just two or
three people working in California; now we
are 50 people and still hiring!” says Scott
Liu.
Today, Henlius has an R&D facility in
Fremont, California, primarily for cell line
development and another in Cao-He-Jing
High-Tech Park in Shanghai for development
and clinical research. “When we started
Henlius, we licensed technology from the
US to generate cell lines, which we then
transfer to China. We also acquire equipment in the US and ship it over as tax rates
are high in China, so this saves time and
money. But to get approval for our drugs in
China we must file clinical trials here, and
as the government of Shanghai reimburses
domestically produced biosimilars, we
have development and manufacturing in
“In China we are very
different – our focus is
on quality”.
Shanghai,” Scott Liu explains.
NNE Pharmaplan is currently project man­
aging the development of a manufacturing
plant for Henlius in Shanghai, which will
be ready at the end of 2013. “In China we
are very different – our focus is on quality,”
says Scott Liu. “With my background I have
an in-depth knowledge and understanding
of quality and our products will stand out
because of their quality. Our manufacturing
plant will adhere to US FDA and EU GMP
standards as well as to the new Chinese
SFDA regulatory requirements. Henlius
has adopted global product standards but
most Chinese companies don’t do this.
This makes us unique.”
Scott Liu continues: “We are installing single
use technology as it decreases the cost of
building the plant significantly and we have
adopted the most advanced technology to
increase manufacturing efficiency. Our hightitre manufacturing expression tech­nology
April 2012 · Angle · 21
will increase productivity and capacity.
So while most other manufactures here may
produce 1g/litre or lower, we will produce
2-3g/litre. This means savings that allow
us to put money into the quality systems.
I believe we will be the first company in
China with a single use 2000 litre bioreactor, so we will also stand out in terms of our
Manufacturers will have to
adopt new technology to
reduce costs.
state-of-the-art technology.”
Henlius is developing the biosimilar version
of several complex biopharmaceuticals as
its lead products and aims to have its first
biosimilar monoclonal antibody therapy, for
non-Hodgkin’s lymphoma, on the market
in China by 2016. “In China there are many
regulations and price controls – it is a totally
different system from the US or Europe and
it is very complicated. So we teamed up
with our major shareholder – FosunPharma
– as they have experience of drug distribution in China,” explains Scott Liu. “We
also want to bring our products to other
countries outside China, so a ­collaboration
with another ­pharmaceutical company will
absolutely be of benefit and we hope to
achieve this in the next few years.”
Looking to the future, Scott Liu concludes:
“I believe that the prices for biopharmaceuticals will be lowered as the current prices
can’t be sustained. Manufacturers will have
to adopt new technology to reduce costs.
I think big pharmaceutical companies will
establish R&D and manufacturing in China
and other emerging countries to lower
the costs of generic as well as innovative
drugs. And in this I believe Henlius is leading
the way!”
Henlius staff, from left to right: Dr. Weidong Jiang, Henlius co-founder Scott Liu, and Dr. Paul Liu
April 2012 · Angle · 23
Joining forces
to change lives
By working together, an innovative biotechnology company and
a global biopharmaceutical giant have given hope to patients
with lupus, launching the first new drug for this incurable
autoimmune disease in more than 50 years.
Interview with Jerry Parrott, Vice President of Corporate Communications and Public Policy,
Human Genome Sciences
On 9 March 2011 the US Food and
Drug Administration approved Benlysta
(­belimumab) for the treatment of adults
with active systemic lupus erythematosus
(SLE or lupus) who are receiving other
lupus medicines. While ground-breaking
for patients and doctors as there has been
no significant advance in this area for over
half a decade, it was also a major milestone
for Human Genome Sciences (HGS) and
GlaxoSmithKline (GSK), collaborators on
the drug’s development.
“The reality is that the
biggest challenge for a
biotech company focused
on new therapies is the
huge need for capital.”
“We started out in 1992 as a very small
biotech company with just 4 people,”
explains Jerry Parrott, VP of Corporate
Communications and Public Policy at HGS.
“The early idea for the HGS business
model was to discover and understand
genes and proteins, and use that knowledge
to develop biopharmaceutical therapies
for patients.”
“I think we were unusual in the way we
developed as a company. In 1993 we began
a relationship with GSK and now they are
our longest-standing partner. Essentially,
GSK acquired access to our technology and
intellectual property for use in developing
small-molecule drugs along with certain
opt-in rights to large-molecule drugs that
HGS would develop, and HGS received USD
125 million. In 1993, this was quite a large
amount – I believe it was the largest deal of
its kind in the biotech industry at the time.”
“The reality is that the biggest challenge for
a biotech company focused on new therapies is the huge need for capital. The risks
at the outset, the ever-increasing expense
of clinical development, and the timelines
of perhaps 12-15 years to develop a product
24 · Angle · April 2012
require a lot of investment. Without GSK
we would have needed other capital. Would
we have found it so early? Who knows, but
unquestionably we were able more quickly
to develop an infrastructure, preclinical and
clinical capabilities, manufacturing and process capabilities, and get to the next level
– thanks to the expression of confidence by
GSK in our science, our early business model
and the people who founded HGS.”
“There are about 325,000
SLE patients under the
care of rheumatologists
in the US”.
In 1996, researchers at HGS identified a
naturally occurring protein in the ­human
body called BLyS, or B-lymphocyte
April 2012 · Angle · 25
s­ timulator. Research eventually showed
there was an association between higher
levels of BLyS and disease activity in certain
autoimmune diseases, including lupus.
HGS went on to develop Benlysta, a human
monoclonal antibody drug, which is the
first in a new class of drugs called BLySspecific inhibitors that recognise and inhibit
the biological activity of BLyS.
“GSK wasn’t involved in the early development of Benlysta, but our deal with them
meant that they had the right to opt in to
co-develop and commercialise this product
after Phase 2. So in 2006 we entered into
an operating agreement with them on a
50/50 global basis, under which we would
share Phase 3 and 4 expenses and all profits
for Benlysta. The GSK alliance made it possible for us to bring Benlysta more quickly
through late-stage development and to the
market, where it can be available to patients
who may need it.”
The collaboration between
HGS and GSK has certainly
been a great success.
The Benlysta programme success has
continued with the European Commission
granting marketing authorisation for the
drug in July 2011. With a cost in the US of
approximately USD 35,000 per patient per
year, Benlysta has been predicted to reach
blockbuster status.
“There are about 325,000 SLE patients
under the care of rheumatologists in the
US and about 250,000 patients in Europe.
Under our co-development and commercialisation agreement with GSK, we have
responsibility for global supply of Benlysta.
Our company is unusual in that we focused
on building world class manufacturing and
process development capabilities at an early
stage. Today, we regard these capabilities
as an important strategic advantage. In
fact, our large-scale manufacturing facility
is now devoted entirely to the production
of Benlysta – so you can certainly say the
investment paid off.”
The collaboration between HGS and GSK has
certainly been a great success, with Benlysta
already being used to treat ­thousands of
people suffering from lupus in the US and
Europe. The Benlysta programme is a working example of how collaboration between a
small biotech and a much larger biopharmaceutical company can ensure that innovative
drugs make it successfully to the marketplace.
Systemic lupus erythematosus is an
incurable autoimmune disease where the
immune system produces autoantibodies
which attack the body’s own healthy
tissues. It is non-communicable (lifestylerelated), probably genetic and mainly
affects women.
Lupus can cause painful and swollen
joints, extreme fatigue, unexplained fever
and skin rash, kidney failure, hair loss,
weight gain and depression. The name
lupus stems from the Latin word for wolf
– Lupus vulgaris – as the severe facial rash
was thought to resemble a wolf’s bite.
Unfortunately lupus often goes undiagnosed, sometimes resulting in irreversible
damage to major organs including the
kidneys, skin, heart, lungs and brain.
It fluctuates over time, and treatment
for lupus therefore varies depending on
whether a patient is experiencing a severe
disease flare. Treatment can include antiinflammatory drugs, anti-malarial compounds, high-dose or low-dose steroids,
immunosuppressant drugs such as those
used to treat cancer drugs and now, for
appropriate patients, the new human
monoclonal antibody drug Benlysta.
How much is a human life worth? This is the challenging question which
governments must answer in order to set a threshold for healthcare ­coverage
decisions. One popular approach is to use the quality-adjusted life year
(QALY) measure, which combines the length of time that life is extended by a
medical treatment and the quality of that life. Using this measure, the price of
one year of quality life has previously been set at USD 50,000 but research in
2008 suggested the value should be closer to USD 130,000.
Biotech
on demand
China’s pioneering biopharmaceutical companies – free from
traditional constraints – are reinventing biotech manufacturing.
Interview with Frank Nygaard, Process Specialist, Monoclonal Antibody Manufacturing, and
Niels Guldager, Senior Technology Partner, Biopharmaceuticals, both from NNE Pharmaplan.
30 · Angle · April 2012
Integrated system for cell culture media preparation. Sartorius Stedim FlexAct.
By 2016, five of the top ten biopharmaceuticals are expected to be monoclonal
antibodies (MAbs). Follow-on (biosimilar)
versions of these blockbusters will most
likely become available in the coming years
due to patent expiry and the introduction
of legislation for biosimilars. Personalised
therapies will further drive the fractionation
of the biopharmaceuticals market, thus
increasing the need for smaller batch sizes
and campaign-based production schemes.
A growing need for flexible, multipurpose
and more cost-effective manufacturing will
have a significant impact on the design
of the production facilities in the future.
Demographic and market forces place China
in a position to lead the way in the transformation of biopharmaceutical manufacturing.
Maybe it is now time to exit
the stainless steel temples?
“Compared with other biopharmaceutical
products, MAbs are large proteins that
require relatively high doses – and therefore
traditionally necessitate high-volume manufacturing facilities,” explains Niels Guldager.
“Many biopharmaceutical facilities are
still designed as traditional stainless steel
­facilities with fixed piping and tank layout
and large bioreactor volumes. But such
facilities require a significant financial
investment with total installation costs in
the range of USD 100-300 million.”
Recent increases in cell culture yields have
led to significantly reduced bioreactor
volume requirements, which again has
opened the door for single-use manufacturing technologies such as pre-sterilised
assemblies of plastic bags, tubing and filters
that are only used once and then disposed
of. With a concomitant financial investment
reduction and simplified installation, singleuse technology can be more appealing than
stainless steel technology.
“Combining single-use technology and
high-yield processes can further reduce
the price tag for comparable facilities by
April 2012 · Angle · 31
70 to 90 percent. This combination is being
pursued in a number of biopharma facilities
in China today – the full effect is truly a
new biopharma manufacturing paradigm.
Maybe the time has come to exit the stainless temples? China is reinventing biotech
manufacturing because the future is now in
this market”, says Niels Guldager.
There is a need for speed in
securing market shares.
Frank Nygaard elaborates on the subject:
“Additionally, as products contacting surface
are used only once, single use technology
runs a much lower risk of batch-to-batch
contamination, which is of particular importance in multipurpose facilities. A ­facility
based on single use technology is easy to
reconfigure and can therefore be ready for
a new product in a matter of days”. This
flexibility translates to reduced development
timelines and thus accelerated time-tomarket peak. In an increasingly fractionated
market the need for speed to secure market
shares is more important than initial minimal
cost of manufacturing. And with markedly increased cell culture yields, the cost
contribution from the manufacturing facility
is limited compared with development costs.
This is where the facility lifecycle enters
the picture – with single use technology
it becomes possible to optimise facility
­installations based on anticipated life cycle
stages. For instance, the strategy could be
to start with just one single use bio­reactor
to get material for clinical trials and then
upgrade the facility with additional bio­
reactors later in anticipation of market supply production while clinical trials are taking
place. As the next pipeline product must
be developed, the facility can change the
lifecycle stage back to clinical ­production
and the extra bioreactors can be moved to
a market supply expansion facility. Such a
strategy becomes possible because single
use technology is so decoupled from the
facility building itself.”
Going green by going
single use.
“As an interesting side effect, our
­environmental impact studies show that
single use technology is perhaps 50%
Lipitor
Plavix
Advair
Remicade
Enbrel
Humira
Avastin
Rituxan
Diovan
Crestor
2010
2011
2012
2013
2014
2015
2016
Top ten pharmaceuticals 2011 and years of patent expiry. Biopharmaceuticals
2017
2018
32 · Angle · April 2012
less energy intensive than stainless steel
­manufacturing”, Niels Guldager points out
and continues: “It may appear counterintuitive, but the emissions from disposing
plastics are more than offset by elimination
of the cleaning and sterilisation processes
required for reusable technology, basically
because heating up many tons of water is
extremely energy intensive”. Full implementation of high yield processes and single
use technology results in facilities with a
markedly reduced carbon footprint per kg
product compared to the stainless steel
facilities of the 1990ies. “So to that end
you will most likely be going green by going
single use, but the high yield process itself is
the most important factor”, Niels Guldager
concludes. The local aspect should also be
factored in. Most facilities are designed
for local supply, and a further reduction of
carbon footprint by energy optimisation for
local climate conditions and using locally
available building materials will appear as
new facility features.
It’s not about low cost
manufacturing hubs.
The need for local biopharma manufacturing
capacity is increasing in the fast growing
emerging markets as the customer base
expands and national initiatives manage
the markets. The trend is being amplified
by blockbuster patent expiry and the
implementation of regulatory legislation for
accelerated pathways for biosimilars. Frank
Nygaard says: “For biopharmaceuticals,
emerging markets are not about low cost
manufacturing hubs, but about being on
location to get access to the local market.
Consequently, many big pharmaceutical
companies as well as local ­manufacturers
are investing in new facilities in these
countries.” Because of the local focus, it’s
a matter of several local facilities instead of
one central facility for global supply. Such
facilities must clearly meet local manufacturing regulations but also increasingly adhere
to global Good Manufacturing Practice
(GMP) standards. So here we see two new
features of the biopharma facilities of the future. They are adaptable to local conditions
and yet comply with global regulations as
quality requirements are being harmonised.
“A blueprint facility concept that can be
established as interesting markets develop
will become an important strategic asset for
biopharma players with global aspirations”,
predicts Frank Nygaard.
China is moving ahead of
mature markets.
Niels Guldager continues: “You can talk
of innovative production techniques in the
sense that our emerging markets customers
are highly innovative and open-minded and
therefore capable of leveraging technologies
and market dynamics radically. Obviously,
the traditional stainless steel production
concept may not be the right solution going
forward; but while single-use facilities are
still regarded as the plants of the future in
mature markets, they are fast appearing as a
preferred solution to the blooming biopharmaceutical industry in emerging markets.”
In China, new technologies and quality
systems are being taken up at a rapid pace,
so this emerging market is moving ahead
of mature markets. China does not have a
specific biosimilar regulatory path today, and
any new therapy will need to go through all
clinical development phases. This situation
favours the development of biobetters or
biosuperiors (products that promise additional advantages as opposed to just being
similar). The patient population allows for
extremely fast clinical trials and therefore
fast and cost-effective product development.
April 2012 · Angle · 33
“Since full clinical data will be produced, we
see the emergence of new business models
based on relatively fast initial product registration in China, followed by a strategy to
leapfrog back to mature markets and obtain
market approval, and perhaps based on a limited additional data set. When that happens,
the blueprint facility concept will again be a
strategic asset in order to expand capacity
for global supply”, says Niels Guldager.
Biotech on demand
will become an
important capability.
In reality, the important issue is not stainless steel or single-use technology, but
rather how technologies can be combined
to provide the most productive and costeffective process in a fast and predictable
way. “Choosing one or the other technology
concept or a hybrid of the two depends on
both strategic considerations and feasibility
studies of each individual case. The future
will change biopharmaceutical manufacturing paradigms from stainless steel to hybrid
combinations of single-use and stainless
steel and complete single-use facilities.
That is clear by now – and we see these
opportunities being aggressively explored
in China,” states Frank Nygaard. Today new
biopharma manufacturing facilities have to
be smaller and more flexible, efficient and
cost-effective, and able to adapt quickly
to changes in market demand. In the end
it is not really about technology, but more
about product and process know-how to
get to the market. “In this respect, single
use technology is a magnificent enabler.
For instance, we can now place an entire
small-scale clinical production line inside
a 100 m2 environment with these tech­
nologies. Biotech on demand – the ability
to rapidly establish local manufacturing
capacity based on new market opportunities – will become an important capability
for successful companies in the future. And
single use technology combined with next
generation facility design will do just that”,
concludes Niels Guldager.
Frank Nygaard (left) and Niels Guldager (right) are some of NNE Pharmaplan’s experts on
biopharmaceuticals.
Within information technology, Moore’s Law states that the number
of transistors which can be placed on an integrated circuit doubles every two
years.
Biotechnology now has its own version of Moore’s Law with the exponentially
falling time and cost of sequencing the human genome for the purpose of
identifying possible genetic diseases: It took 13 years at a cost of USD 3 billion
to sequence the first human genome, but in a couple of years the cost could
drop to USD 1000 and in 5 years further still to USD 100, with the results
ready in a matter of weeks – making it possible for the total sequencing of an
individual’s DNA to be a routine medical test.
The global status of approval pathways. While the European
Medicines Agency launched an abbreviated approval pathway for biosimilars
in 2004, the US – which has the potential to be the largest ­market for biosimilars – has significantly lagged behind. In a report in 2008, the Congressional
Budget Office predicted that creating a pathway for biosimilars could save
the US about USD 25 billion over 10 years from 2009.
However, it wasn’t until March 2010 that President Obama signed The Patient
Protection and Affordable Care Act (PPACA), which allowed the creation of a
shorter approval pathway for biosimilars. But still it took until 9 February 2012
for the US Food and Drug Administration (FDA) to release its draft guidance
to assist in the development and approval of biosimilars. The guidance could
however be in danger if the lawsuit currently before the US Supreme Court,
which aims to overturn the PPACA, is successful in voiding the health reform
law in its entirety – as it would also nullify the biosimilars pathway provision.
April 2012 · Angle · 37
Biosimilar pathways
Law in place
Biosimilar pathways under development
No laws or pathways
“We are pleased that the FDA has developed these important guidances,
marking another important step forward on the pathway to biosimilars.”
Jim Greenwood
President and CEO of Biotechnology Industry Organization
“These draft documents are designed to help industry develop biosimilar versions
of currently approved biological products, which can enhance competition and
may lead to better patient access and lower cost to consumers.”
Janet Woodcock
M.D., director of FDA’s Center for Drug Evaluation and Research.
Treatment
at any cost?
The prices of biopharmaceutical drugs support
the creation of a two-tier society: those who can
afford to survive and those who can’t.
April 2012 · Angle · 39
Global spending on healthcare is declining,
from USD 251 billion in 2005 to an estimated USD 210-240 billion in 2015, according to
the IMS Institute for Healthcare Informatics.
At the same time, the cost of innovative
biopharmaceuticals is rising – pricing a drug
at USD 100,000 used to be unusual, but
now this price level has become routine.
Unsurprisingly, old and
elderly people are the
biggest consumers of drugs.
Publicly funded healthcare systems, such
as the National Health Service (NHS) in the
UK, must evaluate the benefit of a treatment
against its cost. To do so, they must assign a
monetary value to a human life. Apparently
one year of quality life is worth USD 50,000
– so states the international standard used
to determine whether a treatment should be
provided. But many biopharmaceuticals cost
more than this and the strain on healthcare
budgets to treat a patient with a chronic,
life-long condition is therefore significant
– particularly as people are living longer.
So where should publicly
funded healthcare systems
draw the line?
Unsurprisingly, old and elderly people are
the biggest consumers of drugs and it is
estimated that worldwide the number of
people aged over 65 will double by 2030
to more than 1 billion. Emerging countries
such as China are experiencing huge
growth, with an increasing middle-class
that demands innovative treatments. In the
US the government health programme for
the elderly – Medicare Part B – is barred
from considering price when it decides
whether to cover injected drugs.
So where should publicly funded healthcare
systems draw the line? Some have the
controversial opinion that public funds
should not be used to treat people with
an unhealthy lifestyle – such as smokers,
heavy drinkers and the obese – for medical
conditions which they argue are selfinflicted. Should a smoker receive expensive
monoclonal antibody lung cancer therapy
for a year when the same funds could be
used to perform cataract operations on 12
people, for example? A survey conducted by
Doctor magazine among family and hospital
doctors in the UK sparked outrage in 2008
as 94% of respondents said an alcoholic
who refused to stop drinking should not
be allowed a liver transplant, 50% said
smokers should be denied a heart bypass
and 25% believed that the obese should
be denied hip replacements.
However others argue that doctors – and
indeed governments – should not “play
God” by making judgements on lifestyle
and that it is morally wrong to deny treatment on financial grounds. But the reality
is that with many countries battling the
economic recession, healthcare budgets are
not inexhaustible and tough decisions need
to be made.
What is clear is that in this ethical dilemma
there are no easy solutions. But can survival
of only the richest and those with health
insurance be the answer?
Patients with Paroxysmal Nocturnal Hemoglo-binuria (PNH)
suffer from a rare genetic, life-threatening disease that causes the breakdown
of red blood cells, which can lead to various medical complications and
premature death.
In 2007 the FDA approved the first product for the treatment of PNH
– a monoclonal antibody called Soliris®.
Today Soliris® is the world’s most expensive drug at a price of USD 500,000
per patient per year, reflecting the USD 800 million and 15-year investment it
took to develop this orphan drug.
April 2012 · Angle · 43
Trojan horses
and bugs
What will be the next big thing in the biopharmaceutical industry?
Interview with Juan Harrison, Vice President, Business Innovations, New Frontier Sciences,
Takeda Pharmaceuticals International
According to Juan Harrison, Vice President
for Business Innovations, New Frontier
Sciences at Takeda, one of the fastest
­growing areas of interest in the pharmaceutical industry is monoclonal antibodies,
and many pharmaceutical companies
with a traditional focus on small molecule
­chemical products are now investing in
this field of research.
“So whereas small
molecule drugs may need
to be taken a few times
a day or week, monoclonal
antibody therapy may only
have to be administered
once a month.”
Monoclonal antibodies are able to specifically target proteins on cells – unlike small
molecule drugs which may also bind with
peripheral targets so causing side effects.
Evolved from biological systems, human
monoclonal antibodies are able to circulate
and remain active in the blood stream for
up to one month.
“So whereas small molecule drugs may
need to be taken a few times a day or
week, monoclonal antibody therapy may
only have to be administered once a month.
Added to this is the high variety of ways
in which monoclonal antibodies can be
used – ­such as neutralising specific proteins,
turning a receptor on or off, or recruiting an
immune response against disease-causing
cells – and it is easy to understand the
excitement about possible future therapies
and ­indications for monoclonal antibodies,”
explains Juan Harrison.
Most recently, antibody-drug conjugates
have been in the news and in August 2011,
Adcetris, the first treatment for Hodgkin
lymphoma in more than 30 years, was
approved by the FDA. While Adcetris
was discovered and is marketed in North
America by Seattle Genetics, Takeda holds
the rights outside North America.
44 · Angle · April 2012
One problem with
monoclonal antibodies is
their sheer size.
“Often lots of nasty toxic drugs are given
to cancer patients with the hope that the
cancer cells react faster to the toxin than the
healthy cells,” says Juan Harrison. “But with
antibody-drug conjugates we can target
the cancer cells more specifically. A drug
is attached to the antibody which hones
in on the cancer cell. This cell ‘swallows’
the construct and digests the protein part,
releasing the drug which is now toxic and
kills the cancer cell.”
“Personalised therapy will
further enhance the success
of monoclonal antibody
therapy in the future.”
One problem with monoclonal antibodies
is their sheer size. These big molecules do
not easily cross blood vessels, meaning
that their use is limited. Developers are
therefore looking at reducing their size by
getting rid of unnecessary parts, leaving just
protein skeletons or scaffolds. The resulting
fragments retain the targeting specificity of
whole monoclonal antibodies but can be
produced more economically and possess
other unique and superior properties for
a range of diagnostic and therapeutic
applications.
“Personalised therapy will further enhance
the success of monoclonal antibody therapy
in the future – as it is already doing today
with Herceptin,” says Juan Harrison.
Herceptin, a monoclonal antibody drug
for some forms of breast cancer, works
best on patients who are positive for
Human Epidermal growth factor Receptor 2
(HER2+). Another breakthrough in personalised therapy came in January 2012, with
the first ever drug to treat the underlying
cause of cystic fibrosis, rather than just the
symptoms. Vertex’s Kalydeco, which will
cost USD 294,000 a year per patient, has
been approved by the FDA for a rare form of
cystic fibrosis in patients who have a specific
gene mutation. “Kalydeco is an excellent
example of the promise of personalised
medicine – targeted drugs that treat patients
with a specific genetic makeup,” said FDA
Commissioner Margaret A Hamburg, MD
in the approval announcement.
Juan Harrison explains: “Personalised
therapy is absolutely critical. Everyone is
looking at finding the appropriate drug for
the patient. Without personalised therapy,
diagnosis is based on imperfect knowledge
and only a portion of patients will be good
candidates for the drug. This means that
a lot of people who don’t respond receive
the drugs, which creates a burden on
healthcare budgets.
Now personalised medicine will mean that
therapy can be given with a higher degree
of predictability, so improving treatment of
patients while lowering overall healthcare
costs.”
“I believe we only
understand about 1%
or less of biology”
According to Juan Harrison, other exciting
areas of research to watch for in the future
include regenerative therapeutics and
the use of stem cell therapies. But while
much of the research into synthetic tissueengineered organs grown in the lab is still
in its infancy, the first ever Phase 1 clinical
use of human embryonic stem cells (hESCs)
was published in the Lancet in January 2012.
April 2012 · Angle · 45
Therapy in the future: A monoclonal antibody.
Steven Schwartz et al reported functional
visual improvements in patients with macular
degeneration who were injected with hESCs.
“I believe we only understand about 1%
or less of biology and so it’s an enormous
field, still ripe for discovery,” says Juan
Harrison. “For example, we now know the
human genome, but it is wrong to think
that this is enough. If you count the number
of microbes living on a human’s skin – the
bacteria, fungus, mites, etc – the number
of non-human cells on the surface alone
will outnumber human cells manifold”. In
fact, the total number of genes associated
with the human microbiome could exceed
the total number of human genes by a
factor of 100 to 1. “We’ve evolved over
millions of years and so have the bugs which
live on and in us – they produce genetic
products but nobody knows what these
do or how they affect our health. Little has
happened in this area so far because we
simply did not have the tools to sequence
the genomes of the thousands of microbes
in our bodies, nor the computational tools
to analyse the associations of microbial gene
products and human health – until now. I
predict a huge explosion in this space in the
future,” concludes Juan Harrison.
46 · Angle · April 2012
NNE Pharmaplan news
New CVP of Sales and Business
Development
Effective 1 November 2011, Morten Holm Christiansen
assumed the position as Chief Sales Officer and CVP of
Sales and Business Development at NNE Pharmaplan.
Mr Christiansen has previously served as Chief
Financial Officer (CFO) of NNE Pharmaplan from
2003 to 2005. Morten Holm Christiansen joined the
Novo Group in 1994, where he has held a number
of executive positions, latest as Vice President of
Global IT operations. Prior to that, he worked as
senior consultant in the Danish consulting company
Accenture.
Morten Holm Christiansen is 46 years old and holds
an MSc in Economics and MBA from IMD.
“I am convinced that with his past NNE Pharmaplan
experience, combined with an impressive track
record, Morten Holm Christiansen can boost our
development of Sales and Business Development
and at the same time strengthen the NNE Pharmaplan
management team”, states Morten Nielsen, CEO of
NNE Pharmaplan.
New biotech concept
The dynamic development of the biotech sector has
resulted in an increased number of biotech projects
and customers worldwide during the last few years, in
particular in the emerging markets. NNE Pharmaplan
is seeing many smaller, more flexible biotech facilities
based on single-use technology, especially in China.
To address these requirements, NNE Pharmaplan has
established a standard biotech facility concept called
Biotech on Demand™, which can be built on site in
the traditional way or off site as a modular facility.
Standardised process and utility modules are combined
in various ways to accommodate all the different
functions in a modern biotech facility and the need
for flexibility and adaption to local building and GMP
regulations and practices. The Biotech on Demand™
concept includes the engineering and supply of a
facility as well as related quality systems, Standard
Operation Procedures (SOPs) and the organisation of
necessary quality tests.
NNE Pharmaplan is currently applying the standard
Biotech on Demand™ concepts in the design of a
number of new biotech facilities.
April 2012 · Angle · 47
been on our wish list of countries where we would
like to expand our business. The Emerging Markets
region was set up to be the main contributor of our
growth, and Brazil is an important market as well as an
entrance door to the rest of South America.”
Brazil is the world’s ninth-largest market for pharmaceuticals and drugs. The office is already engaged
in projects and several of NNE Pharmaplan’s global
accounts have production facilities in the country.
The project office started out with five employees,
including the Brazilian resident manager Isabel Gomez
Alvarez and her husband Gustavo Vivacqua (JGVI),
who have been part of the NNE Pharmaplan family for
several years.
A new dot on the NNE Pharmaplan
world map
The last piece of the BRIC puzzle fell into place in
November 2011 when NNE Pharmaplan opened a new
project office in Curitiba, Brazil. NNE Pharmaplan has
been represented in Russia, India and China for many
years already. Opening of a new project office in Brazil
is an important step in NNE Pharmaplan’s growth
strategy. Regional Manager of Emerging Markets Ole
Spang-Hanssen explains: “For a long time, Brazil has
GROWING BIOTECH STRENGTH IN
NNE PHARMAPLAN IN CHINA
Several successful biotech projects continue to
enhance NNE Pharmaplan’s biotech expertise in China.
To improve services to customers, a biotech center of
excellence has been developed.
Biotech project design team.
Back row from the left: Jin Wei, Process Engineer;
Ruan Zi Jie, Architect; Kang Wei, Project Manager.
Front row from the left: Tong Ling, Senior Automation
Engineer; Liu Yi, Senior HVAC Engineer; Shu Xia
Huang, Manager Architectural Department
”The Brazilian market is really warm and we believe
this is the right time to be here. We started the office,
after we had enough projects to support the office
startup. The Brazilian office has started very promising.
We are still working on establishing the office with a
lot of focus on hiring the right people and we have
been very successful hiring the best people we can
find in the market. Customers have been knocking on
our doors already. That’s a very good start.”
48 · Angle · April 2012
You’ll never walk alone
NNE Pharmaplan is currently expanding its network
of partners in the field of modern biotech in order
to offer full-service solutions to its customers – all
the way to approval of product on the market. The
cooperation partners include modular construction
companies, single-use equipment and consumables
suppliers, contract development companies and
regulatory experts.
A sample of the Flexplant facility.
One of the partnerships is with Thalle Integrated
Systems (TIS), which has developed a proprietary
platform technology called the PlantConnex SystemTM
and the BioTypeKitTM. TIS will deliver the facility
exterior, i.e. the building blocks that form the walls
and skeleton of the facility as well as cleanrooms
and HVAC (heating, ventilation and air-conditioning)
systems, tailored to single-use biotechnology. Within
this framework NNE Pharmaplan will design and
deliver the facility interior i.e. process and utilities.
April 2012 · Angle · 49
Picture NNE Pharmaplan from the inside
The NNE Pharmaplan annual report gives you the 2011
highlights and key figures of the NNE Pharmaplan
organisation. Together with the annual report, we
publish our Communication on Progress (COP 2011)
report – a sustainability report required by NNE
Pharmaplan’s UN Global Compact membership.
Find both reports at
nnepharmaplan.com/Who-we-are/Media/Downloads/
Setting new health care packaging
standards in India
West Pharmaceutical Services is the world leader
specialising in the manufacture of systems and devices
for parenterally administered medicines. The company
is headquartered in Pennsylvania in the US.
To cater for the fast growing Indian market, they
will set up a production facility of rubber stoppers,
aluminium caps and flip-off seals near Chennai in the
southern part of India.
These products will help avoid contamination of
products and thus enhance the quality and safety of
injectable drugs produced by Indian pharmaceutical
and biotech manufacturers.
NNE Pharmaplan is providing the engineering,
procurement, construction management and
qualification services. The facility will be completed
in the fourth quarter of 2013 and is a good example
of NNE Pharmaplan’s proven track record with
international customers in India.
50 · Angle · April 2012
NNE Pharmaplan at the ACHEMA 2012
exhibition/congress
Single-use biotech reactors; design of small-scale
fill-and-finish facilities; quality audits at pharmaceutical manufacturer; Manufacturing Execution Systems
(MES) within the pharma­ceutical industry; pharmaceutical engineering in China and much more… whatever
your field of interest is, you have a good chance of
attending an exciting NNE Pharmaplan specialist
lecture at the 2012 ACHEMA event.
In addition, our experts will talk on different topics
at our booth every day. We invite you to visit NNE
Pharmaplan at booth number E4 in hall 9.1, where
we will be happy to discuss how your company can
benefit from our extensive project and practical experience in the different areas of the pharma and biotech
industries.
ACHEMA is the world forum of the process ­industry
and the trend-setting technology summit for
biotechnology, chemical engineering and environmental protection. The 30th ACHEMA, taking place on 18
to 22 June 2012 in Frankfurt, Germany, will again be
the leading international meeting point for decisionmakers and experts. Around 4,000 pharmaceutical
engineering exhibitors from 50 countries will participate, and the organisers expect more than 180,000
visitors, including 30,000 executives.
See you in Frankfurt!
Find a detailed description of
all NNE Pharmaplan lectures
under “upcoming events” at
the front page on our website
­nnepharmaplan.com. Here you
will also see all the other events
around the world where you can
meet NNE Pharmaplan.
April 2012 · Angle · 51
Calendar
Where to meet NNE Pharmaplan in the spring of 2012.
Check “Upcoming events” at the front page of our website nnepharmaplan.com for more information.
April
April
3 April
27 April
Gentofte, Denmark
Vendor of services and process equipment to the
pharmaceutical industry.
NNE Pharmaplan open course.
Gentofte, Denmark
How will the new science and risk-based approach impact cGMP regulation?
NNE Pharmaplan open course.
5-6 April
Virginia, USA
Flexible facilities and systems.
11 April
Gentofte, Denmark
ASTM E2500 – a science and risk-based approach
to achieve qualification compliance.
NNE Pharmaplan open course.
12 April
Webinar
How will the new science and risk-based
approach impact cGMP regulation?
Pre-conference introduction webinar.
16-17 April
May
2-3 May
Gentofte, Denmark
Design for Six Sigma.
NNE Pharmaplan training course.
8-11 May
Ruds Vedby, Denmark
Beyond Project Leadership (BPL).
23-24 May
Copenhagen, Denmark
Computer validation.
NNE Pharmaplan/Key2Compliance course.
Beijing, China
ISPE China conference 2012.
Connecting a world of pharmaceutical knowledge.
June
20 April
22 June
Gentofte, Denmark
How many batches are needed in process
validation? NNE Pharmaplan open course.
Frankfurt, Germany
ACHEMA 2012.
23-26 April
Shanghai, China
Vaccines China 2012. Forging successful colla­
borations and ensuring quality and compliance.
24-25 April
22 June
Düsseldorf, Germany
Pharma Congress 2012.
Production and technology.
Lyngby, Denmark
Green battle.
Conference for DTU students.
CANADA. With an average of
205 deaths every day, cancer is the
leading cause of premature death.
Shanghai Henlius Biotech is building
a new state-of-the-art facility for production
of MAb-based therapeutics for treatment
of malignant tumours.