Biotechnology of Human Plasma-Derived Medicines in Scope of Collaboration Perspectives within The Central European Initiative Dr Vadim Sentchouk PHARMLAND LLC Deputy General Director PLASMAPHARM LLC General Manager 26.10.2017
PHARMLAND COMPANY: brief description 1998 Belarus-Dutch joint venture Pharmland LLC was born. Investments from Netherlands (1998 2017) - near 42 million US $ 308 employees Revenue 2017 (estimated) near 30 million US $ R&D Center GMP Certificates, ISO 9001 Manufacturing facilities 13 000 sq.m. for: Tablets, Capsules, Sashes, Infusion solutions, Injections, Prefilled Syringes, Lyophilized Powders, Syrups, Suspensions, Medical Devices, Plasma-derived Products 2
HUMAN BLOOD PLASMA Human Blood Plasma is the liquid component of whole blood, and makes up approximately 55% of the total blood volume. It is composed primarily of water with small amounts of minerals, salts, ions, nutrients, and PROTEINS in solution. In whole blood, red blood cells, leukocytes, and platelets are suspended within the plasma. FRESH FROZEN PLASMA Plasma intended for the recovery of proteins that are labile in plasma is immediately frozen by cooling rapidly in conditions validated to ensure that a temperature of - 25 C or below is attained at the core of each plasma unit within 1 h of placing in the freezing apparatus. 3
FRACTIONATION OF HUMAN PLASMA The technology of plasma fractionation was first described in USA by Edwin J. Cohn in 1946. Modern technologies of plasma fractionation include technologies for the separation of biomolecules intended for the manufacture of plasma-derived products. Plasma Fractionation Plant chromatography, ultrafiltration, ultracentrifugation, nano-filtration, virus inactivation. 4
HUMAN PLASMA FOR FRACTIONATION (Monograph of European Pharmacopoeia and Belarus Pharmacopoeia) Liquid part of human blood; Intended for the manufacture of plasma-derived products. Collected from carefully selected, healthy donor free from detectable agents of transmissible infections. 5
http://pptaglobal.org/plasma/plasma-collection PLASMA COLLECTION PLASMA CENTER In more than 600 specialized donation centers located in the U.S., Europe, and Canada, individuals may donate plasma through a process called plasmapheresis. Plasmapheresis is a sterile, self-contained, automated process where plasma is separated from red blood cells and other cellular components of blood which are then returned to the donor. Source plasma collection in the U.S. is regulated by the U.S. Food and Drug Administration (FDA) and, in Europe by the European Medicines Agency (EMA) and national regulatory authorities. 6
LABORATORY TESTS ARE CARRIED OUT FOR EACH DONATION TO DETECT THE FOLLOWING VIRAL MARKERS: antibodies against human immunodeficiency virus (anti-hiv-1 and anti-hiv-2) + HIV virus RNA hepatitis B surface antigen (HBsAg) + hepatitis B virus DNA antibodies against hepatitis C virus (anti-hcv) + hepatitis C virus RNA 7
https://www.researchandmarkets.com/research/lht6ct/plasma THE PLASMA FRACTIONATION INDUSTRY is a sector of the Biopharmaceutical industry in which the plasma component of human blood is processed to produce therapeutic products. Europe and North America, with 77% of the plants, accounted for a combined 88% of global fractionation capacity. The Global Plasma Fractionation Market is estimated to grow to reach 26.07 USD billion by 2021 from 18.84 USD billion in 2016. The Europe Plasma Fractionation Market is estimated to grow to reach 7.04 USD billion by 2021 from 5.24 USD billion in 2016. Europe holds the second position of global market. Growth in this market is mainly attributed to growing aging population, rising incidences of bleeding and immune disorders, and growing use of immunoglobulin and alpha-1-antitrypsin. 8
In 2016 the top 5 players possessed 78% of total global fractionation capacity: Baxalta Inc. / Shire, USA / Ireland CSL Ltd., Australia Grifols S.A., Spain Octapharma AG, Switzerland Creat Group, China (RAAS Group, China / Bio Product Laboratory Ltd., UK / Biotest AG, Germany) -------------------------------- Kedrion S.P.A, Italy LFB S.A., France Sanquin, Netherlands 9
PLASMA PROTEINS FOR CLINICAL USE Plasma Protein Albumin Immunoglobulins: Intravenous, Subcutaneous, Specific Coagulation factor VIII Von Willebrand Factor Coagulation factor IX Coagulation Factor X Coagulation factor XIII Prothrombin Complex Concentrate C1 inhibitor Antithrombin III Fibrinogen Alpha-I-Antitrypsin Indications for Clinical Use restoring of blood volume in trauma, burns and surgery patients, hypoalbuminemia passive prophylaxis, primary immunodeficiency disease, secondary immune deficiency diseases, Kawasaki's disease, chronic lymphocytic leukemia or HIV infection during childhood to prevent bacterial infections, bone marrow transplantation to prevent graft versus host disease and bacterial infections, immune thrombocytopenic purpura, Guillain Barré syndrome, polyneuropathies and other neurological disorders hemophilia A, genetic deficiency genetic deficiency hemophilia B, genetic deficiency genetic deficiency genetic deficiency hemophilia B, anticoagulant overdose hereditary angioedema congenital deficiency, disseminated intravascular coagulation congenital deficiency, massive haemorrhage hereditary deficiencies, emphysema and COPD cirrhosis 10
Country Population 01.01.2017 Potential Plasma for Fractionation Collection National state owned fractionator Private owned fractionator Plasma Fractionation Capacilty Open markets to products fulfilling relevant regulatory requirements Self-sufficiency In Human Plasma and Products Austria 8 772 865 900 000 L No Octapharma, Austria 1 700 000 L Yes Albania 2 876591 300 000 L No No 0 Yes No Belarus 9 504 704 950 000 L «RNPC Transfusiology and medbiotechnology» Pharmland JV LLC 650 000 L + 50 000 L Yes Bulgaria 7 101859 700 000 L No No 0 Yes No Bosnia and Herzegovina 3 509 728 350 000 L No No 0 Yes No Hungary 9 797561 1 000000 L No Kedrion, Italy 300 000 L Italy 60589445 6 000000 L No Kedrion, Italy 1 500000 L Macedonia 2 073702 200 000 L No No 0 Yes No Моldova 3 553100 350 000 L No No 0 Yes No Poland 37 972 964 3 750000 L No No 0 Yes No Romania 19638309 1 950000 L No No 0 Yes No Serbia 7 040 272 700 000 L No No 0 Yes No Slovakia 5 435343 550 000 L No No 0 Yes No Slovenia 2 065895 200 000 L No No 0 Yes No Ukraine 42 482 000 4 250000 L Blood Centers Biofarma 90 000 L Yes Croatia 4 154213 400 000 L No No 0 Yes No Montenegro 622218 50000 L No No 0 Yes No Czech Republic 10578820 1 000000 L No No 0 Yes No Total (CEI) 237 800 000 23 600 000 L Total (USA) 325 700 000 38 298 234 L (2016) 15 326 821 L (2007) 11
Country Population 01.01.2017 Potential Plasma for Fractionation Collection Austria 8 772 865 900 000 L Albania 2 876 591 300 000 L Belarus 9 504 704 950 000 L Bulgaria 7 101 859 700 000 L Bosnia and Herzegovina 3 509 728 350 000 L Hungary 9 797 561 1 000 000 L Italy 60 589 445 6 000 000 L Macedonia 2 073 702 200 000 L Моldova 3 553 100 350 000 L Poland 37 972 964 3 750 000 L Romania 19 638 309 1 950 000 L Serbia 7 040 272 700 000 L Slovakia 5 435 343 550 000 L Slovenia 2 065 895 200 000 L Ukraine 42 482 000 4 250 000 L Croatia 4 154 213 400 000 L Montenegro 622 218 50 000 L Czech Republic 10 578 820 1 000 000 L Total (CEI) 237 800 000 23 600 000 L Total (USA) 325 700 000 38 298 234 L (2016) 15 326 821 L (2007) 12
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PHARMLAND HUMAN PLASMA PLANT: brief history The new Plasma plant was constructed according to the Investment Agreement between Pharmland JV LLC and Government / Ministry of Health of the Republic of Belarus from 3 August, 2013, and in force till 2023. Investments 23 million US$. The construction of Plasma Plant was finished in 2015. During 2015-2016 analytical equipment, technological skids and systems were installed, Plasma Plant validations finished. The first fractionation trials with plasma batches, albumin and immunoglobulin purification started from October 2016. Marketing Authorization, GMP certification, regular fractionation of plasma, plasma-derived products manufacturing and sales from December 2017 March 2018. 14
PHARMLAND PHARMACEUTICAL PLASMA-DERIVED PRODUCTS: ALBUPHARM - Albumin solutions (Eur./Belarus Pharm.): 5% solution 20% solution 25% solution IMMUNOPHARM - Intravenous Immunoglobulin (IVIG) solutions (Eur./Belarus Pharm.): 5% solution 10% solution 16,5% solution PHARMACLOT - Coagulation Factor VIII (Eur./BelarusPharm.): Lyophilized powder 500 I.U., 1000 I.U. per vial. PHARMAFIX - Coagulation Factor IX (Eur./Belarus Pharm.): Lyophilized powder 500 I.U., 1000 I.U. per vial. 15
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PHARMLAND PLASMA PLANT CAPACITY: 650 000 L of plasma per year for fractionation and manufacturing of finished products for Belarus and other markets 150 000 L of plasma for Belarus market 2017 (100%): Albumin near 1250 kg (from 50 000 L of plasma), IVIG near 120 kg (from 35 000 L of plasma), CF VIII near 35 mln IU (from 150 000 L of plasma), CF IX near 5 mln IU (from 20 000 L of plasma), Up to 500 000 L of plasma per year for fractionation and manufacturing of intermediates (cryopaste, prothrombin complex, fraction II+III (or II), fraction V) and finished products for other markets 17
PLASMA SOURCES FOR PHARMLAND PLASMA PLANT : 50 000 L now available, collected by the government plasma centers; Ministry of Health of the Republic of Belarus shall be obliged to supply plasma for fractionation according to the Investment Agreement with Pharmland; 100 000 L will be available in 2018-2019, collected by the government plasma centers according to the Investment Agreement with Pharmland; 150 000 450 000 L will be available within 2018-2021, collected by Pharmland owned plasma centers; Pharmland started its own investment project at the end of 2016; up to 650 000 L Pharmland is now in negotiations to buy additional plasma from Georgia, Latvia, Poland, and.. 18
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Matteo Renzi Prime Minister, Italy Maria Linna Marcucci Co-owner of Kedrion Biopharma s.p.a, Italy Vadim Sentchouk Pharmland LLC 40 Deputy General Director
Perspectives of Collaboration in Biotechnology of Human Plasma- Derived Medicines on the strategic objectives of the Central European Initiative Pharmland Plasma Fractionation Plant with 650 000 L Plasma Fractionation capacity: Albumin products for 84 million people Immunoglobulin products for 45 million people Coagulation Factors products for 45 million people Support CEI Member States on their path towards regional and European integration and cooperation in: Plasma Collection, Plasma Fractionation, Manufacturing of Plasma-Derived Medicinal Products, Investigation of NEW Plasma-Derived Medicinal Products, Support CEI Member States on their path to reach self-sufficiency in Human Plasma and Plasma-derived Products 41
We be of one blood, ye and I from "The Jungle Book" by Rudyard Kipling (1894) 42