The changing landscape of mammalian cell culture manufacturing ...
The changing landscape of mammalian cell culture manufacturing ...
The changing landscape of mammalian cell culture manufacturing ...
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<strong>The</strong> Changing Landscape <strong>of</strong><br />
Mammalian Cell Culture<br />
Manufacturing Capacity<br />
Howard L. Levine, Ph.D.<br />
Eighth Annual bioProcessUK Conference<br />
Nov 30-Dec 1 2011<br />
Glasgow, Scotland<br />
BioProcess Technology Consultants<br />
www.bptc.com
Increasing Sales <strong>of</strong> Biopharmaceutical Products<br />
From Clone to Commercial®
US Approval <strong>of</strong> Monoclonal Antibody Products by Year<br />
6<br />
5<br />
No. Products Approved<br />
4<br />
3<br />
2<br />
1<br />
0<br />
Similar approval rates<br />
for the UK and Europe<br />
From Clone to Commercial®
Monoclonal Antibodies Drive Biopharmaceutical Revenue<br />
Average Revenue, US$ million<br />
Ref: Datamonitor, company‐related information<br />
From Clone to Commercial®
Top Ten Selling Biopharmaceutical Products<br />
US<br />
Product Name<br />
Company<br />
2010 Sales<br />
(Billions USD)<br />
Remicade J&J/Merck 7.324<br />
Enbrel Amgen/Pfizer 6.808<br />
Humira Abbott 6.500<br />
Avastin Roche 6.201<br />
‣ Sales <strong>of</strong> almost $50 billion<br />
‣ 8 out <strong>of</strong> 10 are produced in<br />
<strong>mammalian</strong> <strong>cell</strong> <strong>culture</strong><br />
‣ 7 out <strong>of</strong> 10 are monoclonal<br />
antibody‐related products<br />
‣ CAGR for monoclonal antibodyrelated<br />
products from 2001‐2010<br />
was >40%<br />
Rituxan Roche 6.100<br />
Lantus San<strong>of</strong>i‐Aventis 5.699<br />
Herceptin Roche 5.211<br />
Neulasta Amgen 3.558<br />
Novolog Novo Nordisk 3.512<br />
Lucentis Roche/Novartis 2.899<br />
From Clone to Commercial®
Product Demand Greatest for Monoclonal Antibodies<br />
Demand for existing commercial antibody<br />
products will nearly double by 2016<br />
‣ ~8.3 metric ton ~13.4 metric tons<br />
(2010) (2016)<br />
Product Demand for<br />
Commercial Antibody Products<br />
‣ 2010 requirements for each <strong>of</strong> the top five<br />
monoclonal antibody products ranged from<br />
1.0 –2.3 metric ton<br />
All others<br />
(27)<br />
26%<br />
Remicade<br />
17%<br />
‣ 2010 demand for all other monoclonal<br />
antibody products combined was<br />
approximately 2.5 metric tons<br />
‣ Anticipated demand for new monoclonal<br />
antibody products approved between now<br />
and 2016 is expected to be
Demand for Bio<strong>manufacturing</strong> Capacity Growing<br />
‣ Driven by growing market for approved products, large number <strong>of</strong> products in<br />
clinical development, and growing interest in biosimilars<br />
‣ Volumetric requirements will almost double by 2016, leaving companies and<br />
markets without capacity scrambling for resources<br />
From Clone to Commercial®
Distribution <strong>of</strong> Mammalian Cell Culture Capacity<br />
Greatest increase<br />
in number <strong>of</strong><br />
companies with<br />
clinical capacity<br />
From Clone to Commercial®
Geographic Distribution <strong>of</strong> Cell Culture Capacity<br />
Region<br />
North<br />
America<br />
2010 2016<br />
Volume in<br />
‘000s L<br />
1,661 2,181<br />
UK/Ireland 183 281<br />
Europe 712 1,125<br />
Korea 51 213<br />
Japan 100 125<br />
China
Balance <strong>of</strong> Supply and Demand<br />
Assumes no<br />
increase in<br />
current titers<br />
Capacity utilization to increase from 43% to 64% in next five years<br />
Perfusion capacity adjusted to equivalent<br />
fed‐batch capacity where appropriate<br />
From Clone to Commercial®
Product Companies Control ~70% <strong>of</strong> Capacity<br />
4,500<br />
3,600<br />
Installed Capacity<br />
2,700<br />
1,800<br />
900<br />
0<br />
2010 2011 2012 2013 2014 2015 2016<br />
CMO XS Product Co.<br />
Perfusion capacity adjusted to equivalent<br />
fed‐batch capacity where appropriate<br />
From Clone to Commercial®
Ten Companies Control >75% <strong>of</strong> Capacity<br />
2010<br />
Rank<br />
2016<br />
Rank<br />
Company<br />
2010 Volume<br />
(1,000s L)<br />
2016 Volume<br />
(1,000s L)<br />
1 1 Roche 525 600<br />
2 4 J&J 230 230<br />
3 5 Boehringer Ingelheim 216 216<br />
4 6 Amgen 198 198<br />
5 3 Lonza 150 232<br />
6 8 Pfizer 139 149<br />
7 2 San<strong>of</strong>i‐Aventis 133 263<br />
8 ‐ Novartis 125 ‐<br />
9 10 Lilly 122 137<br />
10 7 Biogen Idec 106 196<br />
‐ 9 Celltrion ‐ 140<br />
All Others 614 1,070<br />
TOTAL 2,558 3,431<br />
Perfusion capacity adjusted to equivalent<br />
fed‐batch capacity where appropriate<br />
From Clone to Commercial®
Utilization at Top 5 Product Companies ~50%<br />
Includes Roche,<br />
J&J, Amgen, Pfizer,<br />
San<strong>of</strong>i‐Aventis<br />
Perfusion capacity adjusted to equivalent<br />
fed‐batch capacity where appropriate<br />
From Clone to Commercial®
Utilization Pushes 75% for the Rest <strong>of</strong> the Industry<br />
45% 45% 45% 45% 45% 45%<br />
Perfusion capacity adjusted to equivalent<br />
fed‐batch capacity where appropriate<br />
From Clone to Commercial®
Bio<strong>manufacturing</strong> Capacity Adequate but Tightening<br />
Increase in number <strong>of</strong> products and expanding markets<br />
will increase demand by ~1 million liters by 2016<br />
• Current and anticipated supply <strong>of</strong> capacity is<br />
sufficient to meet the market needs for the<br />
foreseeable future<br />
Existing capacity may not be available or appropriate<br />
• Product companies control >70% <strong>of</strong> total capacity<br />
• Utilization rates for the majority <strong>of</strong> the industry will<br />
reach almost 75% by 2016<br />
Companies without <strong>manufacturing</strong> capacity or secure<br />
<strong>manufacturing</strong> contracts may experience difficulties in<br />
accessing capacity in the coming years<br />
From Clone to Commercial®
Trends Influencing Future Capacity Requirements<br />
Higher yielding<br />
processes<br />
Biosimilars<br />
New Product Types<br />
‣ Today’s bioreactors will<br />
produce more product<br />
per batch<br />
‣ Existing markets –<br />
spread capacity<br />
demand among more<br />
players<br />
‣ New markets –<br />
potential increase in<br />
demand<br />
‣ Shift away from full<br />
length, naked<br />
monoclonal antibodies<br />
to other scaffolds or<br />
more potent products<br />
may alter demand<br />
From Clone to Commercial®
Modern, State-<strong>of</strong>-the art Processes<br />
‣ Cell <strong>culture</strong> titers <strong>of</strong> titer >5 g/L imply smaller bioreactors producing similar<br />
quantities to today’s “six pack” facilities<br />
‣ Multi‐product capabilities and flexibility will become increasingly important<br />
‣ Disposable technologies will become increasingly prevalent<br />
‣ Continuous processing, PAT and other modern <strong>manufacturing</strong> methods will be<br />
incorporated into bioprocessing<br />
Photos courtesy <strong>of</strong> Pall Life Sciences and Sartorius Stedim<br />
From Clone to Commercial®
Biologic Products – Current and Future<br />
‣ New MAbs, F c ‐fusion proteins, F ab ,<br />
Antibody‐Drug Conjugates, alternate<br />
scaffolds<br />
‣ Smaller niche markets that current<br />
products<br />
‣ Biosimilar products currently approved in<br />
Europe<br />
‣ Many Mabs will be <strong>of</strong>f patent in next few years<br />
• Some already available in India and China<br />
Adapted from Stout, J. BPI Conference 2011<br />
From Clone to Commercial®
Many Biosimilars in Development Worldwide<br />
Already Approved<br />
Abseamed<br />
Binocrit<br />
Epoetin alfa Hexal<br />
Biograstim<br />
Filgrastim Hexal<br />
Filgrastim Ratiopharm<br />
Nivestim<br />
Ratiograstim<br />
Tevagrastim<br />
Zarzio<br />
Omnitrope<br />
Valtropin<br />
Retacrit<br />
Silapo<br />
MAbs Soon To Be Off Patent<br />
Avastin<br />
Enbrel<br />
Erbitux<br />
Herceptin<br />
Humira<br />
Lucentis<br />
Remicade<br />
Rituxan<br />
Ref:<br />
http://www.gabionline.net/Biosimilars/General/Biosimilars‐approvedin‐Europe<br />
and http://www.gabionline.net/Reports/Top‐25‐biotechdrugs‐the‐next‐biosimilars‐targets<br />
From Clone to Commercial®
Interest in Antibody-Drug Conjugates is Growing<br />
Are more ADCs entering and<br />
moving through the pipeline<br />
compared to 5 years ago<br />
How important a class <strong>of</strong><br />
compounds do you expect<br />
ADCs to become<br />
bioPULSE<br />
From Clone to Commercial®
Impact <strong>of</strong> Antibody-Drug Conjugates on Demand<br />
What impact will ADCs<br />
have on the demand for<br />
<strong>cell</strong> <strong>culture</strong> capacity<br />
‣ Responses equally split between increasing demand for<br />
capacity or no impact on future capacity requirements<br />
‣ Although doses <strong>of</strong> ADCs will be lower than unconjugated<br />
monoclonal antibodies, no responses that ADCs would lower<br />
demand for <strong>cell</strong> <strong>culture</strong> capacity<br />
bioPULSE<br />
From Clone to Commercial®
Analysis <strong>of</strong> Bio<strong>manufacturing</strong> Capacity<br />
‣ Comprehensive in‐depth analysis <strong>of</strong> the<br />
biopharmaceutical market and the<br />
impact <strong>of</strong> current trends on the supply<br />
and demand for <strong>mammalian</strong> <strong>cell</strong> <strong>culture</strong><br />
<strong>manufacturing</strong> capacity through 2016<br />
‣ Provides detailed information on<br />
<strong>manufacturing</strong> capacity world‐wide<br />
• Analysis <strong>of</strong> market trends<br />
• Projections for capacity utilization<br />
• Impact <strong>of</strong> disposables, and biosimilars,<br />
and more<br />
‣ To order visit www.bptc.com/reports.php<br />
From Clone to Commercial®
Thank You!<br />
Howard L. Levine, Ph.D.<br />
hlevine@bptc.com<br />
+1.781.281.2703<br />
BioProcess Technology Consultants, Inc.<br />
12 Gill Street, Suite 5450<br />
Woburn, MA 01801
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