Plasma Fractionation Today and in the Future

2013 Plasma Product Biotechnology Meeting

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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…

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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

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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

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Cap

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y R

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(M

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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

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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

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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

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Born from necessity, the plasma products industry has

come a very long way in 70 years…

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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

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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

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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

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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

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Samsung BioLogics manufacturing plant timeline and

schedule to begin production this quarter

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"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

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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

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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

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What we do matters…