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Plasma Fractionation Today and in the Future
2013 Plasma Product Biotechnology Meeting
1
What we do matters…
“When donors give plasma, it is pooled with others, and their antibodies to diseases are infused into my
children, replacing the part of the immune system they are missing……This was the answer we were
looking for, the hope for the future we once lost was restored.
Plasma donations across the country allow our children to do the things that typical kids can do. They
have fished in the Lakes of Wisconsin, stood on the sand beaches of Florida and been to museums in
Chicago! They attend school, have friends and hopes and dreams! Charlie would like to be President of
the United States one day, Tommy would like to be a firefighter, and Kate wants to own a horse ranch!
Impressive dreams for children who once had little future ahead of them.”
Dayna and her husband, Brian, are
the parents of four wonderful,
amazing children, Charlie, Kate,
Tommy, and Grace…
2
Families like Dayna’s live around the world and Global demand for
plasma products is increasing in established AND emerging markets
Global Plasma Product Sales
of nearly $14B in 2011
Key Considerations for Demand of Global Plasma Products:
• The last 5 years have seen growth across global regions, specifically in Asia and South America
• Global supply of products, regional regulations, and local access dynamics have created pockets
of strong growth…with others not yet growing
• Growth drivers include increasing diagnosis and utilization as well as expanded indications
Source: 2011 Marketing Research Bureau
$-
$1,000
$2,000
$3,000
$4,000
$5,000
$6,000
1998 2000 2003 2005 2008 2011
Glo
bal
Sal
es (
$M
) North America
Europe
South America
Asia & Pacific
Middle East
Africa
3
Global demand is expected to continue to increase with
growth drivers in a few key areas
Drivers of Global Demand
• Increasing utilization across
global regions (in both
existing and expanded
indications)
• Expanded indications for
plasma products
• Increasing diagnosis of
diseases treated with
plasma products
• Improving access to
therapies across global
regions
Source: 2010 Marketing Research Bureau
4
4
7.8
9.4
12.5
26.5
41.5
56.5
58.3
69.6
97.4
120.7
137.5
140.1
Russia
China
Brazil
Turkey
Japan
Germany
Italy
UK
Spain
France
Australia
USA
Canada
IVIG/SCIG Consumption per Capita(grams per thousand population)
2010
2005
Increasing demand for IgG is a key driver of increased
demand for fractionation technology
0
10
20
30
40
50
60
0
20
40
60
80
100
120
140
160
180
1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020
Frac
tio
nat
ion
Cap
acit
y R
eq
uir
ed
(M
L)
Un
it D
em
and
(m
etr
ic t
on
s)
Nearly 50 million Liters of plasma and fractionation
capacity will be required to support ongoing demand
for IgG…advanced technologies and processing
capabilities will be critical
• Estimates based on 2008-2012 CAGR
• Yield assumption of 3.5 g/L
Source: Adapted from Marketing Research Bureau; www.marketingresearchbureau.com
Unit demand for IgG
Estimated capacity required
5
74% of plasma product
sales in 2011 were from
North America and
Europe
There are large segments of the
world yet to experience
significant growth…and others
still without access to plasma
based therapies
Scaling of plasma production is very different from small
molecule manufacturing
Source: http://marketingresearchbureau.com/plasma-industry/current-uses-affecting-the-plasma-industry/
The high level of raw material and manufacturing costs demands advancements such as:
• Increases in production efficiency (such as yield, utilization, etc)
• Adoption of technologies to reduce cost
• Advancements in process development for improved formulations
All supporting the ultimate goal of serving our patients
6
Innovation and growth will come from product and
process development, but also from clinical development
Ongoing growth in the plasma
industry will come from
increasing production and
use of major plasma
products…
…but also from new plasma
derived products
• Several new products are
currently in clinical trials
• Multiple are in development at all
of the major plasma products
companies
7
Born from necessity, the plasma products industry has
come a very long way in 70 years…
8
The industry started with plasma fractionation (Cohn Method)
Edwin Joseph Cohn 1892 – 1953
• Developed protein chemistry (with partners
Edsall, Scatchard, et al)
• Invented plasma fractionation
• Saved thousands of lives
• Never took a patent
• Insisted on right of free publication
Scottish National Blood Transfusion Service website. Foster PR. The origin and development of plasma fractionation.
http://www.scotblood.co.uk/site/pubdocs/PRESENTATION%20THE%20ORIGIN%20AND%20DEVELOPMENT%20OF%20PLASMA%20FRACTIONATION.pdf
Photo: http://www.springerlink.com/content/v5385816700m4020/fulltext.pdf?page=1
9
Key points in the history of fractionation development
along with important Baxter contributions
1940’s 1950’s 1960’s 1970’s 1980’s 1990’s 2000’s …
The Cohn
fractionation process
originally developed
with Albumin as the
first product
Methods were
developed to purify
factor VIII and
factor IX for
hemophilia
patients
Intramuscular
immunoglobulin
(IMIG) was developed
and introduced as
replacement therapy
for patients with
congenital antibody
deficiencies. Purification methods had
improved enough to enable the
production the first commercial
preparations of intravenous
immunoglobulin (IVIG).
Alpha-1 protease inhibitor (A1PI) was
developed for a congenital form of emphysema
Fractionation process
improved to generate higher
yields in the production
1941 – Baxter
developed the
first plasma
collection and
storage unit
2005 – Baxter
released the
first albumin in
a flexible
container
1992 – Baxter
launched the
first
recombinant
Factor VIII
1968 – Baxter
released the
first
commercially
produced
Factor VIII
1952 - Baxter
acquired Hyland
Laboratories, the
first U.S. company
to make human
plasma
commercially
available
1983 - Baxter
introduced the first
heat-treated factor
VIII concentrate for
hemophilia,
reducing risk of
viral transmission
Dynamic periods of
growth and
changes across the
industry
1979 –Baxter
introduced the
first
automated
blood-cell
separator
10
Source: marketingresearchbureau.com; www.baxter.com
Plasma fractionation has improved over the years, but is
still the same basic process
• Immune globulin
• Over the last 70 years, the same basic process has advanced in scope and
scale…benefiting hundreds of thousands of patients around the world
• Technologies have advanced…processes and products have improved…the
industry has grown…and it is all expected to continue
Where will the next generation
of innovation come from?
• Current industry players R&D?
• New plasma companies from
emerging markets?
• Continued improvement of existing
products/processes?
• New entrants with different views of
the industry?
Source: Transfusion Medicine Reviews, Vol 21, No 2 (April), 2007: pp101-117
11
Example: Samsung BioLogics
Samsung BioLogics is located in Incheon, Korea, where a state-of-the-art, multi-product
biologics facility (69,000m2 / 740,000ft2) is currently being constructed on a large parcel
(274,000m2 / 2,950,000ft2), allowing for potential expansion
• The new production facility contains stainless steel bioreactors (total capacity of 30,000L), and is being
designed and built with the capacity to support rapid high protein production
• The facility will also contain the Samsung BioLogics Research and Development Center, an
administration building, an Upstream Suite, a Downstream Suite, a Fill & Finish Suite, and a warehouse
with long term cold storage capacity
Source: Samsung BiolLgics Website, www.samsungbiologics.com
Samsung BioLogics aims to be a world leader in biologics development and
manufacturing and to dedicate itself to improving global healthcare
Samsung BioLogics’ cluster of research centers will
offer a full range of biologics development and
manufacturing solutions for full-scale manufacturing of
therapeutic proteins:
• Process Development and Optimization
• cGMP Production and Manufacturing Scale-up
• Quality Assurance/Quality Control
• Regulatory Compliance Functions
12
Samsung BioLogics manufacturing plant timeline and
schedule to begin production this quarter
13
"Concurrent processing" is a building method Samsung boasts its
expertise in that allows undertaking construction, process design,
validation and production preparations all at the same time, rather than
taking each step separately and in sequence. This significantly reduces
time needed for developing a pharmaceutical plant, thus contributing to
reducing costs and ultimately helping alleviate the burden on patients.
- Mr. Kim
Feb 2011
Samsung BioLogics
established
Samsung Electronics Co. Ltd.,
Samsung Everland, Samsung
C&T Corp. partnered with
Quintiles of the United States
to set up Samsung BioLogics
May 2011
Groundbreaking
Samsung BioLogics held a
groundbreaking ceremony
in the free economic zone
at the port city of Incheon
for the state-of-the-art
manufacturing plant
April 2012
CEO Update
Mr. Tae-Han Kim, president
and CEO of Samsung
BioLogics announced plant is
60% complete and on
schedule to begin production
in first half of 2013
May 2013
Plan of 18-24 months
from groundbreaking
to production
Source: Samsung BiolLgics Website and Press Releases
Example: Samsung BioLogics
• Mammalian cell based cGMP
biologics manufacturing services for
clinical and commercial supply
• Facilities include six 5,000L
production bioreactors, two individual
inoculation suites, and dedicated
media preparation and hold tanks
Core Competencies
• State-of-the-art bioreactors (3X40L/
3X200L/ 3X1,000L/ 6X5,000L)
• Wave bioreactors
• Sterilization-in-place (SIP) capacity
with multiple clean-in-place (CIP)
skids
• Dedicated automated glass washers
and autoclaves
• Capacity for centrifugation and depth
filtration
• Cell banking and storage with liquid
nitrogen freezers
• Dedicated media preparation suite
(Grade C) with down flow booth
• The downstream process cGMP purification
area offers four physically independent suites
• Classified Grade C or higher
Core Competencies
• Chromatography columns up to 1.4m in
diameter
• Individual chromatography skids
• Ultrafiltration / Diafiltration and viral reduction
systems (tangential flow filtration)
• Virus inactivation / Virus filtration
• Pre- and post-viral segregated design
• Dedicated bulk fill suite
• Dedicated automated glass washers and
autoclaves
• cGMP filling facility is being furnished
with equipment including formulation,
aseptic liquid filling, pre-filled syringe
lyophilization, and packaging apparatus
• Can provide packaging, labeling, and
management logistics support for clinical
trial products, plus all of the required
documentation needed for market
authorization
Core Competencies • Grade B based design
• Aseptic liquid filling of vials
• Aseptic lyophilization filling of vials
• Aseptic preparation of pre-filled syringes
• Capacity for an automated labeling,
packaging and shipping area
• Dedicated wash room and media fill
room
• Flexible and modular construction, with
capacity for future expansion
Cell Culture
Fill & Finish
Purification
14
Source: Samsung BiolLgics Website, www.samsungbiologics.com
New Technology concepts for plasma manufacturing are out
there and our role is to leverage them to benefit patients
• Examples of technology concepts that may be applied to advance fractionation:
– Protein separation technology that can replace the ethanol fractionation
• Steric exclusion chromatography that behaves likes a rapid high-capacity
alternative to size exclusion chromatography
• Fluidized bed chromatography as an alternative for packed bed column to prevent
the column clogging
– Continuous centrifugation to reduce maintenance and cycle time and increase the
manufacturing capacity
• Most importantly for this audience are key topics that will be presented in across all of the
sessions of this conference…to just name a few:
– 102 - Ensuring Raw Material Integrity for the manufacture of Plasma Products
– 206 - Strategies for Nanofiltration of Therapeutic Plasma Proteins
– 305 - Prion Removal from Human Plasma Using Surface-Modified Membranes
– 402 - Does Sialylation Change IVIG Therapy in the Future?
– 506 - Entering into Technology Transfer from the Process Supplier: Give Aways from Experience
– 603 - Short Monolithic Columns – Novel Technology Platform for the Analytics and
Isolation/Purification of Human Plasma Proteins701 Immunoglobulin Purification: Overcoming
Yield Increase and High Concentration Challenges
– 702 - Continuous Improvement in Downstream Processing of Plasma Proteins
15
Mario Duller and his mother, Gabriele
Gründl, are grateful for the treatment
options available to Duller for his primary
immunodeficiency.
Duller, 24, is training to
become a farmer, and
enjoys outdoor activities Source: Baxter website and internal Baxter analysis; PPBM website
The plasma industry is facing many challenges from the lab to
the clinic
Key Challenges…
• Emerging human pathogens and extending the ability to continuously supply
safe products through the detection and effective removal or inactivation
• Maintaining strong global supply and manufacturing networks with increasing
complexity to get the right product to the right patient at the right time
• Building and managing key alliances and partnerships including tech transfer
• Engaging the role of biosimilars
16
What we do matters…
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