Plasma Fractionation Today and in the Future 2013 Plasma Product Biotechnology Meeting 1
What we do matters Dayna and her husband, Brian, are the parents of four wonderful, amazing children, Charlie, Kate, Tommy, and Grace 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. 2
Global Sales ($M) Families like Dayna s live around the world and Global demand for plasma products is increasing in established AND emerging markets $6,000 $5,000 $4,000 $3,000 $2,000 $1,000 North America Europe South America Asia & Pacific Middle East Africa $- 1998 2000 2003 2005 2008 2011 Key Considerations for Demand of Global Plasma Products: Global Plasma Product Sales of nearly $14B in 2011 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 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) Canada USA Australia France IVIG/SCIG Consumption per Capita (grams per thousand population) 97.4 120.7 140.1 137.5 Expanded indications for plasma products Spain UK 58.3 69.6 Increasing diagnosis of diseases treated with plasma products Improving access to therapies across global regions Italy Germany Japan Turkey Brazil 12.5 9.4 26.5 41.5 56.5 2010 2005 China 7.8 Russia 4 Source: 2010 Marketing Research Bureau 4
Unit Demand (metric tons) Fractionation Capacity Required (ML) Increasing demand for IgG is a key driver of increased demand for fractionation technology 180 60 160 140 120 100 80 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 50 40 30 60 40 20 Unit demand for IgG Estimated capacity required 20 10 0 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 Estimates based on 2008-2012 CAGR Yield assumption of 3.5 g/l 0 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 Source: Adapted from Marketing Research Bureau; www.marketingresearchbureau.com 5
Scaling of plasma production is very different from small molecule manufacturing 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 Source: http://marketingresearchbureau.com/plasma-industry/current-uses-affecting-the-plasma-industry/ 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 Photo: http://www.springerlink.com/content/v5385816700m4020/fulltext.pdf?page=1 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 9
Key points in the history of fractionation development along with important Baxter contributions Intramuscular immunoglobulin (IMIG) was developed and introduced as replacement therapy for patients with congenital antibody deficiencies. The Cohn fractionation process originally developed with Albumin as the first product Fractionation process improved to generate higher yields in the production Methods were developed to purify factor VIII and factor IX for hemophilia patients Alpha-1 protease inhibitor (A1PI) was developed for a congenital form of emphysema Purification methods had improved enough to enable the production the first commercial preparations of intravenous immunoglobulin (IVIG). Dynamic periods of growth and changes across the industry 1940 s 1950 s 1960 s 1970 s 1980 s 1990 s 2000 s 1941 Baxter developed the first plasma collection and storage unit 1952 - Baxter acquired Hyland Laboratories, the first U.S. company to make human plasma commercially available 1968 Baxter released the first commercially produced Factor VIII 1979 Baxter introduced the first automated blood-cell separator 1983 - Baxter introduced the first heat-treated factor VIII concentrate for hemophilia, reducing risk of viral transmission 1992 Baxter launched the first recombinant Factor VIII 2005 Baxter released the first albumin in a flexible container Source: marketingresearchbureau.com; www.baxter.com 10
Plasma fractionation has improved over the years, but is still the same basic process 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 Immune globulin 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 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 Samsung BioLogics is located in Incheon, Korea, where a state-of-the-art, multi-product biologics facility (69,000m 2 / 740,000ft 2 ) is currently being constructed on a large parcel (274,000m 2 / 2,950,000ft 2 ), 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 12
Samsung BioLogics manufacturing plant timeline and schedule to begin production this quarter "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 May 2011 April 2012 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 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 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 13
Example: Samsung BioLogics Cell Culture 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 Source: Samsung BiolLgics Website, www.samsungbiologics.com Fill & Finish 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 Purification 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 14
New Technology concepts for plasma manufacturing are out there and our role is to leverage them to benefit patients Mario Duller and his mother, Gabriele Gründl, are grateful for the treatment options available to Duller for his primary immunodeficiency. 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 Duller, 24, is training to become a farmer, and enjoys outdoor activities Source: Baxter website and internal Baxter analysis; PPBM website 15
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 What we do matters 16