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
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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.

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 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.

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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.

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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.

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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

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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.

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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)
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 Kedrion S.P.A, Italy
 LFB S.A., France
 Sanquin, Netherlands

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PLASMA PROTEINS FOR CLINICAL USE
Plasma Protein Indications for Clinical Use
Albumin restoring of blood volume in trauma, burns and surgery patients,
hypoalbuminemia
Immunoglobulins: passive prophylaxis, primary immunodeficiency disease, secondary
immune deficiency diseases, Kawasaki's disease,
chronic lymphocytic leukemia or HIV infection during childhood to
Intravenous, prevent bacterial infections, bone marrow transplantation to prevent graft
Subcutaneous, versus host disease and bacterial infections,
Specific immune thrombocytopenic purpura, Guillain–Barré syndrome,
polyneuropathies and other neurological disorders
Coagulation factor VIII hemophilia A, genetic deficiency
Von Willebrand Factor genetic deficiency
Coagulation factor IX hemophilia B, genetic deficiency
Coagulation Factor X genetic deficiency
Coagulation factor XIII genetic deficiency
Prothrombin Complex hemophilia B, anticoagulant overdose
Concentrate
C1 inhibitor hereditary angioedema
Antithrombin III congenital deficiency, disseminated intravascular coagulation
Fibrinogen congenital deficiency, massive haemorrhage
Alpha-I-Antitrypsin hereditary deficiencies, emphysema and COPD cirrhosis
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Country Population Potential Plasma for National state owned Private Plasma Fractionation Open markets to products fulfilling Self-sufficiency In Human
01.01.2017 Fractionation Collection fractionator owned fractionator Capacilty relevant regulatory requirements Plasma and Products

Austria 8 772 865 900 000 L No Octapharma, 1 700 000 L Yes

Austria

Albania 2 876 591 300 000 L No No 0 Yes No

Belarus 9 504 704 950 000 L «RNPC Transfusiology and Pharmland JV LLC 650 000 L Yes
medbiotechnology» +
50 000 L

Bulgaria 7 101 859 700 000 L No No 0 Yes No

Bosnia and 3 509 728 350 000 L No No 0 Yes No

Herzegovina

Hungary 9 797 561 1 000 000 L No Kedrion, Italy 300 000 L

Italy 60 589 445 6 000 000 L No Kedrion, Italy 1 500 000 L
Macedonia 2 073 702 200 000 L No No 0 Yes No
Моldova 3 553 100 350 000 L No No 0 Yes No
Poland 37 972 964 3 750 000 L No No 0 Yes No

Romania 19 638 309 1 950 000 L No No 0 Yes No

Serbia 7 040 272 700 000 L No No 0 Yes No
Slovakia 5 435 343 550 000 L No No 0 Yes No
Slovenia 2 065 895 200 000 L No No 0 Yes No
Ukraine 42 482 000 4 250 000 L Blood Centers Biofarma 90 000 L Yes
Croatia 4 154 213 400 000 L No No 0 Yes No
Montenegro 622 218 50 000 L No No 0 Yes No
Czech Republic 10 578 820 1 000 000 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)

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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)

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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.

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 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.

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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

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 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 ……..

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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
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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

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“We be of one blood, ye and I”
― from "The Jungle Book" by Rudyard Kipling (1894)

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