1. Plasma for fractionation and PBM: which are the links?
Albert Farrugia
Senior scientific and regulatory advisor
Kedrion
Adjunct Professor
School of Surgery
University of Western Australia
10th International Seminar Blood donation and Patient Blood Management
an alliance for the sake of patients
27th – 28th October Castelbrando Cison di Valmarino (Treviso) Italy

2. Theses for this presentation
The conventional view
The convergence of evidence based medicine (EBM) with patient blood management (PBM) is decreasing the demand for red cell transfusion.
This is decreasing the need for whole blood collection and the recovery of plasma for fractionation.
Concurrently, the demand for plasma-derived therapies, particularly immunoglobulin, continues to increase.
Requirements for plasma for fractionation to meet this demand can only be met by plasmapheresis.
Does the not-for-profit sector have the capacity to generate the required plasma volumes and manufacture the products?
Is compensating individuals who undergo plasmapheresis necessary to ensure adequate plasma, and product, supply.?

3. I will address these theses and draw on what data is publicly available.

4. The convergence of evidence based medicine (EBM) with patient blood management (PBM) is decreasing the demand for red cell transfusion.

5. Blood components issued to patients at Stanford Health Centre USA
Blood components issued to patients at Stanford Health Centre USA. Effect of Best Practice Implementation
Transfusion of RBCs per 100 days at risk, decreased by 42% from 2009 through 2015
---- BPA (best practice alert) for RBC: July 2010
BPA for plasma: September 2014
Med Clin N Am 101 (2017) 431–447

6. USA hospitalizations with a red blood cell transfusion for adults, 2000-2013

7. Red Cells issued by the Australian Red Cross Blood Service

8. BUT……..

9. Estimating blood demand and supply as the baby boomers age Changes in the age‐specific US population and projected RBC collections and transfusions
(▵) units collected (projected);
(×) units transfused (projected
(▪ ) Less than 16 years old;
(◆) 16 to 64 years old;
(* ) 65 years and older
Changes in the age‐specific US population based on the 2000 census2and projected RBC collections and transfusions extrapolated from 2008 collection and transfusion data10(assuming that 55% of RBCs are utilized by patients ≥65 years old). (▪) Less than 16 years old; (◆) 16 to 64 years old; () 65 years and older; (▵) units collected (projected); (×) units transfused (projected).
Transfusion Volume 51, Issue 4, pages , 15 APR 2011

10. This is decreasing the need for whole blood collection and the recovery of plasma for fractionation

11. Blood and plasma collection in Australia 2010 -

12. Australian collection of plasma for fractionation Whole blood to apheresis plasma
601 tonnes – 25 L/103 population

13. How is plasma collection to be increased? The Australian experience
Conversion of whole blood donors to apheresis donors
Iron deficient donors
Geographically deferred from fresh component donation
Conversion of blood service to a pharmaceutical (GMP) culture
Massive public investment

15. Given the increasing demand for plasma products in Australia, the current strategy of restricting donors returning from select infectious disease outbreak areas to source plasma collection provides a simple and effective risk management approach.

16. Concurrently, the demand for plasma-derived therapies, particularly immunoglobulin, continues to increase.

17. Annual consumption growth rate in grams from 2005 to 2014: 9.2%

18. Use of IG in Australia

19. Issue of IG in Australia
Acquired hypogammaglobulinaemia secondary to haematological malignancies
Primary immunodeficiency diseases with antibody deficiency
Chronic inflammatory demyelinating polyneuropathy
Guillain–Barré syndrome
Idiopathic (autoimmune) thrombocytopenic purpura (ITP) in adults
Inflammatory myopathies (polymyositis, dermatomyositis, inclusion body myositis)
Kawasaki disease
Lambert–Eaton myasthenic syndrome
Multifocal motor neuropathy
Myasthenia gravis
Neonatal haemochromatosis
Stiff person syndrome
2010
2011
2012
2013
Established therapeutic role
2,212,914
2,505,332
2,724,809
3,025,452
84%
Emerging
therapeutic role
371,832
397,231
444,605
453,352
12%
Exceptional circumstances
61,924
76,033
101,287
120,979 3%
Not indicated
2,550
2,574
1,909 39
Other
Total
2,649,219
2,981,170
3,272,609
3,599,822
100%

20. Ig demand for PIDs Country consumption
“The average potential usage of Ig for the treatment of CVID and XLA was estimated at 72 g/ 1,000 population, which is higher than the estimated Ig usage in CVID and XLA of 27–41 g per 1,000 population in the US.”
Stonebraker et al J Clin Immunol (2014) 34:233–244

21. BUT……..

22. Competing concepts USA vs Italy
IgG levels in PID Risk of pneumonia
USA – the more, the better (guideline approach)
Orange – MA 2010
Quinti – 5 year prospective study 2011
Italy – personalised treatment, dosage increases has no benefit after a certain level

23. Requirements for plasma for fractionation to meet this demand can only be met by plasmapheresis.

24. Arithmetic
Assuming a target of 120 g/IG .per 103 population (probably inadequate)
Current best yields are 5 g/L plasma (probably optimisitc)
Hence ca 42 L/ 103 population are needed
Current blood bank practice yields ca 250 mL/blood donation
Hence 168 blood donations would have to be collected per would have to be collected, and at least 2/3 of the red cells would be discarded.
Clearly, it is not possible to use whole blood donation as the route to plasma for fractionation

25. Does the not-for-profit sector have the capacity to generate the required plasma volumes and manufacture the products?

26. The annual growth rate of source plasma collections was 8
The annual growth rate of source plasma collections was 8.3% over ten years ( ), and of recovered plasma, 0.7%.
Over 24 years ( ), source plasma collections grew by 5.6% per year, and recovered plasma, 1.2%.

27. BUT……..

28. An estimated 70% of the world's supply of plasma derivatives is generated from the plasma of around one million compensated source plasma donors in the USA.
This dependence poses a grave treat to the provision of therapies for patients.
Asia’s generates 17% to the world’s plasma for fractionation and has 61% of the world population.

29. Is compensating individuals who undergo plasmapheresis necessary to ensure adequate plasma, and product, supply?

30. Plasma Production The Top Ten
Country
Plasma production L/1000 population
Donor status
United Stated 66
Uncompensated and compensated
Austria
56.6
Czech Republic 33
Germany
31.6
Australia
21.5
Uncompensated
Netherlands
18.8
Denmark 17
France
16.3
Sweden
16.1
Belgium
15.5

31. Final reflections
Better practice of transfusion therapy is decreasing the need for red cell transfusion, although the effect of changing donor and patient demographics is uncertain.
This is continuing to increase the dependance of the manufacture of evidence-based plasma therapies on apheresis plasma, although a growing awareness of personalised medicine may affect continued demand growth.
The commercial sector sector dominates plasma supply and manufacture, although the continued dependance on the US source donor population is a concern.
The compensation of source plasma donors currently appears to be necessary in assuring supply.