1. XXXth International congress of ISBT, June 7-12, 2008, Macao In the name of Allah

2. XXXth International congress of ISBT, June 7-12, 2008, Macao Dr. H. Abolghasemi Managing Director Iranian Blood Transfusion Organization Plasma for Fractionation IRAN Experience

3. XXXth International congress of ISBT, June 7-12, 2008, Macao Product demand Annual need for blood products is increasing Marketing research Bureau 2006-2007 Clotting factors IVIg Albumin Average annual growth rate of factor VIII, factor IX, AAT, fibrin sealant, IVIg, and albumin being 3%,1.9%,13%,3.4%,6-8%, 2% respectively.

4. 24.03.2006Dr. M. KloftXXXth International congress of ISBT, June 7-12, 2008, Macao Worldwide plasma market including recombinant products MRB-Report: Feb 2005 Figures 2005 estimated US$ bn. Others 1

5. 24.03.2006Dr. M. KloftXXXth International congress of ISBT, June 7-12, 2008, Macao Worldwide need of immunoglobulins MRB-Report: Feb 2005 IVIG (tons) CAGR 2004/10 = 6,5 % 2

6. XXXth International congress of ISBT, June 7-12, 2008, Macao Why contract fractionation? National blood services play crucial role in providing safe and adequate plasma to be fractionated to the very important medicine including clotting factors,albumin and immunoglobulines.Although importing these medicines might be a prompt aproach to furnish national market with these medicines, worldwide shortage of these medicines and limited resources available in countries health care system make this approach far from ideal

7. XXXth International congress of ISBT, June 7-12, 2008, Macao Why contract fractionation? An alternative would be either to produce these medicines locally or use contract fractionation approach in order to meet needs of local market Due to its financial and technical requirements and considerations establishing a facility for local production at least in developing countries has not been fruitfful

8. XXXth International congress of ISBT, June 7-12, 2008, Macao Why Contract Fractionation in IRAN? Cost-effectiveness because of Rich resource of blood donors in our country The number of plasma units in our blood centers being higher than the hospital demand rate. Decrease in import demand of blood products including IVIg and factor VIII.

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10. Iranian Blood Transfusion Organization Integral part of the national health system Blood donation being voluntary and non- remunerated (100%) Centralized. All blood centers throughout the country are under supervision of IBTO headquarters. All procedures, kits, and equipment are the same and follow a similar standard in all blood centers. All organizational policies mandated by the headquarters are issued to all centers.

11. XXXth International congress of ISBT, June 7-12, 2008, Macao IBTO HEADQUARTERS BTC BCC Ministry of Health A Provincial Transfusion Center BTC: Blood Transfusion Center BCC: Blood Collection Center

12. XXXth International congress of ISBT, June 7-12, 2008, Macao Trend of Blood Donation in Iran (1974-2007) Units

13. XXXth International congress of ISBT, June 7-12, 2008, Macao Trend of Yearly Donation Index in Iran(1974-2007) Per 1000

14. XXXth International congress of ISBT, June 7-12, 2008, Macao Percent Trend of Transition to 100% Voluntary Blood Donation in Iran (1996-2007)

15. XXXth International congress of ISBT, June 7-12, 2008, Macao National Blood Program Donor ScreeningBlood TestingQ.C Blood Donor Recruitment Program Blood CentersNational 1) Follow the program of recruitment, retention, and recognition of blood donors 2) Build effective communication between staff and blood donors 3) Embark on establishing blood drives in safe places and make efforts for their being improved so that demands are met 4) Provide training to volunteers and exert management to maximize impact of the public awareness-raising program 1) Develop and implement a continuous national awareness- raising program to highlight the importance of regular blood donation 2) Oversee the recruitment, retention, and recognition of blood donors to ensure an adequate supply of safe blood for use by all hospitals in Iran 3) Have accessibility to more than 185 fixed blood donation centers throughout the country 4) Work in partnership with mass media to encourage voluntary blood donation 5) Provide training to blood centers’ staff in the field of donor recruitment

16. XXXth International congress of ISBT, June 7-12, 2008, Macao IBTO started to send the recovered plasma for fractionation to two fractionation facilities in Europe following the contract concluded in 2005. End products are returned to our country. Our goal is to have a safe and sufficient plasma derivatives to meet the majority of needs of our population in the country

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19. Flow work for plasma shipment to fractionation center Assessment of the shipment volume agreement of medicines regulatory Authority Audit of the selected centers by an appointed official auditor from Europe Audit of the fractionation center by an Iranian auditor (appointed by supplier party and Health Minister) Licensing Approval of plasma contract for fractionation

20. XXXth International congress of ISBT, June 7-12, 2008, Macao Quantity shipment of plasma can still raise because just 16 out of 30 blood transfusion centers across Iran have already been active contributing to contract fractionation. We have formulated and started to implement the program to increase the total number of blood centers eligible to send plasma Increase Quantity of Plasma Increase Total Number of Donations

21. XXXth International congress of ISBT, June 7-12, 2008, Macao 3 kinds of products: 1) Haemoctin 2) Intratect 3) Human Albumin

22. XXXth International congress of ISBT, June 7-12, 2008, Macao Improvements in IBTO system Plasma fractionation caused improvement in the system specially Documentation,take PCR sample and cold chain. More strict standards for plasma fractionation. Several external audits from certified body of Europe. pushing toward implimentation of automation in our system.

23. XXXth International congress of ISBT, June 7-12, 2008, Macao Automation of lab tests and implementation of the new software

24. XXXth International congress of ISBT, June 7-12, 2008, Macao Automation of lab tests

25. XXXth International congress of ISBT, June 7-12, 2008, Macao Home made Blast freezers replaced mechanical freezing. The plasma core temperature reaches -30°c within less than 1 hour in blast freezer.

26. XXXth International congress of ISBT, June 7-12, 2008, Macao Improvement of the cold rooms and freezing rooms Freezer temperature shall be less than -25°C during the whole storage period. Because we already have a contract with a European country, our freezing storage standards shall comply with European Pharmacopoeia. The European Pharmacopoeia has a provision stating that if the temperature of the plasma is between -20°C and -15°C for a maximum of 72 hours, or if it is above -15°C (but colder than - 5°C) in no more than one occurrence, the plasma can still be used for fractionation.

27. XXXth International congress of ISBT, June 7-12, 2008, Macao Look back Improvement of our look back system. Every blood donor can be recalled if the follow up is necessary. System is established to immediately notify fractionation center once a test is positive. Donor Fractionation center

28. XXXth International congress of ISBT, June 7-12, 2008, Macao Responsibilities and roles of blood establishment who expert committee 2007 Collects and analyses the epidemiologic data and surveilance of donor population based on results of screening tests. Develops and implements the criteria in selection and interview of donors. Performs validated tests (or the tests maybe sub-contracted). Hemovigilance:Informs plasma fractionator (and when appropriate the regulatory authority) when relevant information is obtained. Collects blood plasma, prepares, freezes, and stores the plasma, according to good manufacturing practice (GMP). Prepares the NAT samples following fractionators' specifications Implements GMP.

29. XXXth International congress of ISBT, June 7-12, 2008, Macao Responsibilities and roles of plasma fractionators who expert committee 2007 Review the epidemiological data. Verifies donor selection criteria set by national regulatory authority are met; may provide additional selection criteria. Agrees on the tests kits used and audits the virology laboratory. Hemovigilance: Takes appropriate measures if plasma pool or product quality is compromised. Preparation of plasma : Sets the specifications and audits. Provides the standard operating procedure for NAT samples and performs (or sub-contracts) the validated testing. Applies the fractionation methods including viral inactivation following GMPs and processes described in marketing authorization. Prepares of plasma product regulatory files GMP : Audits the blood establishment. Does pharmacovigilance studies and informs regulatory authorities and blood establishment when relevant side-effects are found.

30. XXXth International congress of ISBT, June 7-12, 2008, Macao Responsibilities and roles of regulatory authorities who expert committee 2007 Review the epidemiological data. Sets the criteria and inspects the blood establishment. Approves test kits and inspects the blood establishment. Evaluates haemovigilance/post-donation reports with regards to product quality and safety. Approves and inspects the blood establishment. Approves the procedure and inspects the plasma fractionator. Evaluates the data presented in the dossiers prepared by the fractionator, and inspects fractionation facility. Reviews and evaluates regulatory files. Inspects blood establishment and enforces GMP. Grants the marketing authorization. Evaluates pharmacovigilance reports with regards to product quality and safety.

31. XXXth International congress of ISBT, June 7-12, 2008, Macao Notification obligation :  Deviation is subsequently discovered in any of screening tests performed on the plasma unites supplied  A regular donor is found to be positive for a marker although the previous donation was found negative. (starting look back procedure)  A donation is found to have transmitted an infectious disease potentialy transmissible by plasma.  We are informed that a donor previousely contributing to plasma for fractionation has developed an infectious disease potentially transmissible by plasma  Post transfusion infection following transfusion of blood components obtained from a donor who has also donated one or more unites of plasma for fractionation  A unit positive for viral markers has been sent by mistake

32. XXXth International congress of ISBT, June 7-12, 2008, Macao Conclusion : Advantages of plasma fractionation contract in IRAN Prevention of 200,000 liters of fresh frozen plasma to be wasted 35% cost reduction of plasma derivatives and a reduction in products import with foreign resources Prevention of patient exposure to foreign biological products and patient protection against unwanted infections Standardization of plasma for fractionation leading to the improvement of all the procedures in preparation of blood components Implementation of a look back system and tracing back based on the NAT results

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34. Thank you