Ali Akbar Pourfathollah IBTO Managing Director Professor of Immunology

May, 2016 Tunisia

Plasma Fractionation: Experience of Iran

Iran Iran, a country with a population over 75

millions, is 17th largest and populous country in the world.

In past three decades, the government of Iran has

invested substantially on primary and secondary health care and the country now has a substantially advanced health system infrastructure;

History of Blood Transfusion in Iran History of Blood transfusion in Iran can be

traced back to 1940s. During 1940-70, military hospitals and Iranian Red lion & Sun Society (later called Iranian Red Crescent Society) were in charge of blood collection from volunteers and relatives of patients.

In the late 1960s, only untested whole blood preserved in glass bottles, which were washed and re-sterilized in the Pasteur Institute of Iran, were available.

Iranian Blood Transfusion Organization IBTO is a national centralized organization that was

established in 1974. 100% of IBTO’s blood establishments are community-

based and IBTO is managed administratively by Iranian government.

Blood Collection 2,071,031 of blood donations were collected in the

whole country in 2014 . The rate of blood donation per 1000 population was

26.6 in 2014.

Blood Supply Network Blood collection centers (BCCs):

109 Blood Collection & Preparation Centers:

57 Blood Transfusion centers (BTCs):

34 Mobile Team: 82 Total (in 31 provinces):

282

Caspian Sea

Persian Gulf Gulf of Oman

Blood Collection Centers: Donors registration, selection and phlebotomy Blood Collection & Preparation Centers: Donors registration, selection and phlebotomy, Processing, and distribution of blood and blood components Blood Transfusion Centers (BTC): Donors registration, selection and phlebotomy, Processing, Screening tests, Blood grouping, Quality Control Dept., Quality assurance Dept. and distribution of blood and blood components

Type of Blood Donation Iran is the first country in Eastern Mediterranean Region (EMR) which

reached 100% Voluntary Non-remunerated Blood Donation in 2007.

The rate of regular blood donation was 51.5 in 2014.

(25%Repeated Donor and 23.5%First time donors)

Blood Components More than 98% of blood units are separated into components

including RBC, FFP, Cryoppt, SDP, CPP, Platelet and WRBC.

Totally, 91 blood centers prepare blood components in Iran.

Policy Change in IBTO Financing Till 2015, all blood products were distributed free of charge

to all private and public hospitals and the government was the sole financial supporter of IBTO.

In 2015, based on the efforts made by IBTO through optimization of blood usage, most of the blood components incorporated into pricing framework.

According to the decision made by Iranian government, insurers have to reimburse the costs related to the processing.

As a result, it is planned to obtain 30% of the costs of IBTO 's operation from cost recovery system.

Iran Plasma Toll Manufacturing:

A successful model and experience

Global overview of recovered plasma

Each year 21.6 million liters of plasma are recovered from whole blood

4.2 million units are transfused 8.1 million units are sent for fractionation 9.3 million liters are discarded

Source: Improving access to safe blood products through local production and technology transfer in blood establishments, WHO, 2015

Global financial loss due to plasma wastage

WHO estimates that close to 9.3 million liters of recovered plasma is currently wasted.

This corresponds to more than 40% of the world resources in recovered plasma, and represents a market value of about US$ 650 to US$ 1020 million (based on a price range of US$ 70 to US$ 110 per liter). Source: Improving access to safe blood products through local production and technology

transfer in blood establishments, WHO, 2015

Iran plasma toll manufacturing project

In recent decades, administration of whole blood has drastically been declined and over 98% of blood donations have been converted to blood components.

Shift from administration of whole blood to component therapy has resulted in generation surplus plasma.

Based on annual number of whole blood collection, IBTO is able to produce 250,000 liters surplus plasma.

Iran toll manufacturing project In 2005, IBTO entered into a contract with

Iranian Blood Research and Fractionation Holding Co. for contract fractionation of the surplus plasma (40,000 L at that time).

With increasing quality assurance and quality systems, 165,000 L plasma was sent for fractionation to Europe in 2014.

Plasma Sent for Fractionation (2005-2014)

Savings from contract fractionation

Source: Improving access to safe blood products through local production and technology transfer in blood establishments, WHO, 2015

Savings from contract fractionation In 2010, Iran became self-sufficient in the

production of IVIg and plasma factor IX from Iranian plasma.

Considering the fact that 100% of Albumin now is being produced through contract fractionation, the rate of direct saving is estimated to be reached to 17 million US$.

Average consumption of PDMs (2014)

•*It will increasingly be replaced by recombinant products.

Plasma Derived

Medicines

Consumed Production/L Plasma for Fractionation

FVIII (MIU)* 180 160 IU 1,125,000

IVIg (Kg) 1,240 4.4-4.9 gr 281,818

Albumin (Kg) 11,278 24-24.2 gr 469,916

Safety of Iranian Recovered Plasma

No Plasma sent to CSL Behring 57.355 L Total Donations 301.888 Donations have been tested 211.528 HBV positive 0 HCV positive 0 HIV positive 0 HAV positive 4 Parvovirus B19 positive 52 total 56 or 0.02% of donors *NAT test performed by Swiss Red Cross

Plan to reach 90% regular blood donation

3 Research Plans for Regular Blood Donors 1-In Ardabil province: “Test Only” for first time donors 2-In Kurdistan province, plasma is separated from first time donors as recovered plasma and other products (RBC & Platelet) are derived from regular and repeated donors 3-In Fars province, first time donors are invited for source plasma donation. (Plasmaphersis)

Recovered plasma

Recovered plasma

Iranian Plasma Self-sufficiency program

Current situation: 200,000 liter by IBTO Recovered plasma 200,000 liter source plasma produced in 8

private centers that are under the supervision of IBTO & Iranian FDA

Future plan: Aims to add 200,000 liter source plasma within 2

Years to assure self sufficiency

Challenges in Plasma Toll Manufacturing

Fractionator selection Plasma volume Contract duration Product profile Multiple External audits Cold chain maintenance Transporting plasma across international borders NAT test