Relevant marketing elements and intelligence for the understanding of the biopharmaceutical and single-use technology.

1. Single Use Technology in
the Pharmaceutical
industry
Paris, February 2014

2. The single-use technology (SUT) market is estimated to more than quadruple in the
coming years, which will pull the need for compatible bioreactors of volume lower
than 2000L
Evolution of Biotechnology & Equipments Markets – 2011 to 2016, est., $ Billions -
2011
2016 est.
300,0
12,5
+107%
+136%
145,0
5,3
2,8
0,6
Biotherapeutics overall
Upstream (bioproduction)
+367%
Total SUT market
0,5
1,3
+160%
R&D-support
single-use systems
Disposables and related market estimates; the good manufacturing practice (GmP) market for single-use technology (SUT) today is estimated at
us $150 million (for plastic tubing, manifolds, and connectors used with stainless steel systems).
For bioreactors, the market is almost equally divided between SIP and SUT. Most of the bioreactors in place have a volume inferior than 2000L.
“There’s been a shift from blockbuster drugs produced in massive quantities to niche-busters, so we’re moving toward smaller volumes at the
same time that titers in bioreactors are getting higher”.
Sources : contractpharma.com
2

3. Disposable Bioreactors have seen a peak of interest in late 2011, as well as a
few months ago
Disposable bioreactors online queries – 2004-2013, % of maximum search volume -
Sources : Google Trends
3

4. The SUT still have many limitations which limit their implementation in the
pharmaceutical industries
Manufacturing disposable equipment having high-quality/high-tech control systems at the same time is a big
challenge, since these manufacturing processes need different core competencies.
Single-use sensors still have a lack of performance and, therefore, sometimes do not meet the needs for highperformance process control. Also finding materials free from leachables/extractables is still a challenge.
Manufacture single-use bioreactors that encompass microbial culture with, for example, high oxygen demand or a
larger pH range is a challenge. The limits here are clearly the higher requirements for material stability and higher
performance sensors, similar to nondisposable solutions.
Customers need to be open to redeveloping and optimizing their processes to the technology, which will result in
an increased overall yield.
Single-use bioreactors are relatively expensive and have to be handled correctly to avoid damage. Construction of
the bags requires mechanical welding of the seams and this needs to be of the highest quality in order to ensure
that welds do not come apart and result in lost sterility and consequently loss of the entire run.
The complete lack of standardization renders the implementation of SUT, or any change in the production process
more complex than necessary.
Customers are asking for more detailed characterization of films, raw materials, and other plastic components with
the goal of better assessing the patient risk associated with production single-use bioreactors.
Sources : genengnews.com
4

5. Substituting products are rare, however new competitors could emerge
Risks for GPC activity:
“Virtual R&D”.
Mutualization of R&D by CMOs growing larger.
Integration of bioreactor design and production in pharmaceutial companies / CMOs.
Low required investment to enter the market
5

6. The pharmaceutical market undergoes a financial transition which renders
the development of new therapeutics even riskier than in the past
„The cost of developing an asset has remained relatively static while the likely revenues have declined. The
cost of developing an aset, from discovery to launch, has increades slightly by four per cent from $1,089
milion to $1,137 in 2012. Average inflow per asset is forcast to decline by 14% relative to 2010 to reach a
figure of $2,166 million in 2012.“
Sources : Deloitte Life Science innovation Report
6

7. Only 5 out of the 12 biggest pharmaceutical companies have enough
molecules in the pipeline to stay financially healthy in 2017
Drug pipeline & associated estimated revenues– 2012-2017est, # of drugs, Bn€ Number of drugs in development
Incremental revenues from new pipeline 2012-2017
EU companies
EU companies
EU
comp.
7,5 Bn€
7,3 Bn€
12,0 Bn€
7,4 Bn€
6,5 Bn€
5,3 Bn€
4,1 Bn€
8
21
Johnson Novo
&
Nordisk
Johnson
3,2 Bn€
53
56
65
3,0 Bn€
28
35
37
3,0 Bn€
Bayer
Novartis
Merk
Eli Lilly
Sources : Businessweek
60
Astra- Bristolzeneca Meyers
67
80
90
5,3 Bn€
3,0 Bn€
Pfizer
Sanofi
Roche GlaxoSmithKline
7

8. The number of clinical trials is still growing, but might reach a peak despite
efforts made by goverments to facilitate drug devlopment
Evolution of number of clinical trials – Thousands of clinical trials, 2000-2012 Registered studies (thousands)
Y-to-Y Growth
138,8
+52%
119,4
101,3
+30%
+27%
+19%
+19%
+16%
+26%
83,5
66,4
+15%
+18%
+21%
+15%
+14%
2011
2012
49,3
35,9
25,0
5,6
7,0
8,6
10,3
12,1
2000
2001
2002
2003
2004
Sources : clinicaltrials.gov
2005
2006
2007
2008
2009
2010
8

9. The market share of biopharmaceuticals is growing but is controlled by only
a few key companies
Evolution of the Pharmaceutical Market
– Billion USD, 2001-2011 -
Biopharmaceutical Global Production Capacity
– Share of production capacity, 2011 -
Biopharmaceuticals
Rest of Pharma
855
812
770
727
684
641
489
38
(8%)
451
523
46
(9%)
477
560
51
(9%)
509
599
59
(10%)
69
(11%)
82
(12%)
95
(13%)
106
(14%)
117
(14%)
128
(15%)
889
139
(16%)
Others
Roche
21%
25%
Novartis 5%
540
572
602
632
664
695
727
750
Eli Lilly 5%
Sanofi
9% Johnson
& Johnson
6%
9%
6%
Pfizer
7%
Lonza
8%
Boehringer
Ingelheim
Amgen
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
Sources : GiResearch
9

10. The top CMOs are based in Germany, Switzerland and the USA, and have
made a growth of 9,9 % between 2011 and 2012
Top 10 CMO ranking– Million USD, # of Employees, 2012-
10

11. Of the top 27 european companies by R&D investment, 6 are Pharmaceutical
companies, and account for 23% of the total investment in 2010.
Top 27 European Investors in R&D– Billion Euros, 2011 Volkswagen
Nokia
Daimler
Sanofi-Aventis
GlaxoSmithKline
Siemens
Robert Bosch
Bayer
AstraZeneca
EADS
Ericsson
BMW
Alcatel-Lucent
Boehringer Ingelheim
Peugeot (PSA)
Finmeccanica
Fiat
Volvo
SAP
Renault
Philips Electronics
STMicroelectronics
Continental
BASF
Merck DE
Banco Santander
Novo Nordisk
3,21
3,20
3,08
3,02
2,77
2,56
2,45
2,40
1,97
1,94
1,80
1,73
1,73
1,70
1,63
1,53
1,41
1,40
1,34
1,27
4,94
4,85
4,39
4,38
4,24
3,82
Sources : The 2011 EU Industrial R&D Investment Scoreboard
6,26
In the pharmaceutical sector, the top
3 countries investing in R&D are :
United Kingdom
France
Germany
11

12. Although the number of approvals is similar in Europe and in the U.S.A.,
France is less and less involved in new drug development
The Food and Drug Administration (FDA) approved the same number of new drugs in 2010 and 2011 as the
Medecines Agency (EMA), +/-1. However, France is less and less chosen by the EMA as reviewer in
centralized procedures.
Also, only 7% of AMM filing belonged to France in 2010 vs. 14% in 2009.
Sources : LEEM
12

13. There is a cyclical tendency that might reflect the intensive financial needs of
the pharmaceutical industry
Filings of NME/NBE and approvals by the FDA– # of filings & approals, 1993-2012 NME/NBE filings
NME/NBE approvals by the FDA
53
50
45
41
43
39
36 35
28
29
25 26
36
30
21
35
24
30
26
22
26
21
17
36
34
32
30
26 27
39
38
20
24
22
26
22 21
18
1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Sources : FDA Filling and approval file Allyprime
13