European perspective on plasma
collection for medicinal products
NBV-TRIP symposium 2018 05 17
Dutch Blood Transfusion Society
Norda Rut, MD PhD
NVB-TRIP symposium
NVB-TRIP symposium
European perspective on plasma
collection for medicinal products
Issues to be covered:
• Introduction
• Work in the CoE on medical use of plasma-
derived medicinal products (PDMP)
• Surveys on plasma for fractionation (PfF) in the
CoE
• Ad hoc WG TS093 Plasma supply management
• Continued work
• Conclusions
SOHO, PfF and PDMP (1)
• Substances of human origin (SOHO) are
blood and blood components, cells,
tissues and organs
• SOHO includes plasma for fractionation
(PfF)
• Plasma derived medicinal products
(PDMP) are manufactured from PfF
SOHO, PfF and PDMP (2)
• EU- blood directives and the CoE
blood guide are valid for selection of
donors, collection and preparation
of components irrespective of their
intended use
• PfF requirements are prescribed in
the European Pharmacopoeia 0853
Data on plasma supply management in
Europe (1)
• Preparation of PfF on blood establishment (BE) level
• Production of PDMP on national, regional or
international level
• Procurement of PDMP by national or hospital /
special clinic organisation
• PDMP prescribed to patients in hospital /specialised
clinics level according to national or other program
• Request of data collection on PfF
and PDMP on national level
• Demand- supply vs use – supply vs
need-supply vs self-sufficiency of
PfF for PDMP may be very difficult
to accquire and analyse
Data on plasma supply management
in Europe (2)
Main indication categories
Human albumin
• Hypovolemia, hypoalbuminea, other
applications
Human normal immunoglobulins
• Primary and secondary
immunodeficiencies, immunomodulation,
other indications
Clotting factors
• Replacement therapy in primary and
acquired deficiencies, inhibitors
Cross-sectional guidelines for therapy with blood components and plasma derivatives
4th ed 2014 (German Medical Association)
http://www.bundesaerztekammer.de/weitere-
sprachen/english/german-medical-association/
European perspective on plasma
collection for medicinal products
Issues to be covered:
• Introduction
• Work in the CoE on medical use of plasma-
derived medicinal products (PDMP)
• Surveys on PfF in the CoE
• Ad hoc WG TS093Plasma supply management
• Continued work
• Conclusions
• Report from Kreuth initiatives III-IV
• Resolution CM/Res(2015)2 on principles
concerning human normal immunoglobulin
therapies for immune deficiencies and other
diseases (Adopted on 15 April 2015)
• Resolution CM/Res(2015)3 on principles
concerning haemophilia therapies (Adopted 15 April
2015)
Medical use of PDMP and work in CoE
W Schramm, Kreuth IV
W Schramm, Kreuth IV
Surveys to 43 participating countries
Clotting factors Immunoglobulins
Response 35 MS 34 MS
National data 91% 85%
National /European
registry
71% 81%
European or inter-
national guidelines
91% 86%
National tender 54% 36%
Other aspects
surveyed
Is comprehensive
clinical care and
home care available?
Is comprehensive
clinical care and
home care available?
On demand vs
prophylaxis?
On- and off label for
immunomodulation?
Plasma – and
recombinant factors?
Reimbursement for
off-label use?
W Schramm, Kreuth IV
M Wierer, EDQM, Kreuth IV
B O’Mahoney Kreuth III
IV
II
III
Recommendations
from Kreuth
B O’Mahoney Kreuth IV
HH Peter Kreuth III
H Chapel Kreuth III
H Chapel Kreuth III
I von Schaik Kreuth III
I von Schaik Kreuth III
I von Schaik Kreuth III
I von Schaik Kreuth III
I von Schaik Kreuth III
I von Schaik Kreuth III
European perspective on plasma
collection for medicinal products
Issues to be covered:
• Introduction
• Work in the CoE on medical use of plasma-
derived medicinal products (PDMP)
• Surveys on plasma for fractionation (PfF) in the
CoE
• Ad hoc WG TS093Plasma supply management
• Continued work
• Conclusions
Collection, testing and use of blood components in
Europe
• Trend analysis 2001-2011
• Annual reports 2012, 2013, 2014, 2015
Surveys on PfF in CoE
Data on PfF 2001-2015 from 25 MS MS Population x
1000 (2013 or 2014)
MS Population x
1000 (2013 or 2014)
Austria 8 585 Latvia 1 986
Belgien 11 209 Lithuania 2 968
Bulgaria 7 246 Luxembourg 538
Croatia 4 285 Moldova 3 414
Czech Republic 10 530 Netherlands 16 865
Denmark 5 668 Norway 5 166
Estonia 1 320 Poland 38 479
Finland
5 472
Russian federation
145 164
France 66 074 Slovak Republic 5 430
Germany 81 195 Slovenia 2 060
Greece 10 500 Spain 46 296
Hungary 9 877 Sweden 9 747
Italy 60 783 Switzerland 8 200
PfF 2001-2015 in CoE and L/1000 inh
Table 3.14 Trends in Blood Transfusion in Europe (2001-2011), table 4.1
Collection, testing and use of blood components in Europe 2012 - 2015. Each year
2-6 datapoints of 25 are missing. One MS reported 0.0 L the latest year.
Six MS reported 0.0 L throughout the period.
0
10
20
30
40
50
60
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Austria Belgien Bulgaria Croatia Czech Republic
Denmark Estonia Finland France Germany
Greece Hungary Italy Latvia Lithuania
Moldova Norway Netherlands Poland Russian federation
Slovak Republic Slovenia Spain Sweden Switzerland
Apheresis PfF L/1000 inhabitants in
Sweden
0
2
4
6
8
10
12
14
16
18
In 1996: 6,53 SEK/USD and evaluation of
production of apheresis plasma in BE
Large differences in costs in 19 BE
Improved exchange rate 1996-2001- no
measures taken
Apheresis PfF L/1000 inhabitants in
Sweden
0
2
4
6
8
10
12
14
16
18
Sustained fall of the exchange rate SEK vs USD OR €
preparation cost vs offered price = decline of
plasmapheresis activities
IE FVIII per capita in Sweden
0
1
2
3
4
5
6
7
8
9
10
1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014
rVIII pVIII
L plasma per 1000 inhab in Sweden
0,0
5,0
10,0
15,0
20,0
25,0
30,0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
aferes komponent
European perspective on plasma
collection for medicinal products
Issues to be covered:
• Introduction
• Work in the CoE on medical use of plasma-derived
medicinal products (PDMP)
• Surveys on plasma for fractionation (PfF) in the
CoE
• Ad hoc WG TS093 Plasma supply management
• Continued work
• Conclusions
TS 093 Plasma supply management
An ad hoc working group (WG) under the European
transfusion committee (CD-P-TS).
Working plan in Nov 2014, rev April 2018
• Demand, use and need vs supply
• Tools for evaluation of IgG use- vs plasma supply
• Surveys on plasma supply management
• Tools for safe and sustainable plasmapheresis
• Meeting with the extended group
Progress reports to the plenary CD-P-TS
Activities of the TS093 reported to the
CD-P-TS
Background, target and activities PA/PH/TS (14) 28 2R
Demand, use and need vs supply PA/PH/TS (16) 25 2R
Survey 1 PA/PH/TS (16) 21
Survey 2 PA/PH/TS (16) 38
Safe and sustainable apheresis PA/PH/TS (16) 37 R
Extended group meeting PA/PH/TS (17) 32 R
Please follow the project on:
https://www.edqm.eu/en/blood-transfusion-projects-1449.html
Survey 1: PfF in CoE delivered to
• Contract fractionation and national use of
PDMPs
• Contract fractionation and also international
marketing authorization* of some PDMPs
• Commercial fractionation and international
marketing authorization* of all PDMP’s (like
Sweden)
* Plasma Master file, yearly evaluation of epidemiological
data by EMA and inspection/licensing according to GPG
46
Survey 1 outcomes: 15 MS and 2 OS
47
Survey 1 outcomes: data from 2013, 17 MS and 2 OS
Survey 1
Range liter of plasma collected per 1000 population:
1.03 L to 77.53 L
- Higher volume = more apheresis
- Higher volume = more likely to pay or compensate
Variation in Ig use: range 5.41 – 187.97 g/1000 pop
- One OS highest use per capita, highest plasma
supply
- For all other countries weak correlation Ig use and
plasma collection
- Unevenness of Ig usage and plasma collection
reflects trade in plasma/PDMP’s 49
Survey 1 Recommendations (1)
1. Conduct follow-up survey to:
• Evaluate obstacles for collection of PfF
• Identify measures to improve cost efficiency
• Identify collection and cost targets
• Identify how EDQM can assist to optimise
• Inform the development of recources for collection of
PfF
01/10/12©2012 EDQM, Council of Europe. All rights reserved. 50
Survey 1 Recommendations (2)
2. Include data on wastage of plasma in the CoE
annual survey so strategies and tools can be
developed to minimise wastage
3. Develop a tool to assess use – vs supply using
data on IgG use, IgG yield and PfF volume
available.
01/10/12©2012 EDQM, Council of Europe. All rights reserved. 51
IgG use reported and estimated IgG made
from available PfF estimate yield 1 L plasma = 4 g IgG
Table 4.1- 4.2 Collection, testing and use of blood components in
Europe 2013 or 2014
0
50
100
150
200
250
IgG/1000 inh used IgG available from collected plasma /1000 inh
Survey 2 65 initial and 38 complete responses - all
agreed to share data in anonymised form
BE MS/OS
Blood establishments which do not supply plasma
for
fractionation
5 5
Blood establishments which only supply
recovered plasma for fractionation
12 8
Blood establishments which only supply
apheresis plasma for fractionation
0 0
Blood establishments which supply both
recovered and apheresis plasma for fractionation
21 17
Survey 2 outcome (1)
Key take home messages:
- 87% of BE’s provide PfF
- 13% not, due to small population; immature Quality
System; no acces to fractionation plant; lack of expertise;
donor eligibility requirements
- 55% of BE’s supply both apheresis and recovered PfF.
More likely with volume target, cost target, efficiency
improvement program and guidance appropriate use of
plasma for transfusion.
01/10/12©2012 EDQM, Council of Europe. All rights reserved. 54
Survey 2 outcome (2)
Key take home messages (2)
-Majority of BE’s have identified a plasma collection
volume target
-Availability of recovered PfF reduced due to decline in
RBC usage
-Main barrier preventing investment in plasmapheresis is
financial:collection cost higher than selling price / lack of
funding
- 2 governments capped domestic collection of PfF and
prefer to purchase (cheaper) imported product
01/10/12©2012 EDQM, Council of Europe. All rights reserved. 55
Survey 2 Recommendations
Key recommendations:
1. CD-P-TS should inform their MoH/government about
current difficulties in collecting enough PfF
2. The Committee of Ministers should be engaged to meet
commitments in Resolution 2015 (2) and 2015 (3)
3. Evidence based recommendations for plasmapheresis
should be updated in the CoE Guide to support safe and
sustainable plasmapheresis
01/10/12©2012 EDQM, Council of Europe. All rights reserved. 56
L plasma from an average (male) donor (82,9 kg and 179,4 cm) average (9) or maximal
donations (26, 26, 33, 52, 104) per year
5,4
15,6
6,4
18,6
6,8
24,8
6,8
39
7,4
85,9
0
10
20
30
40
50
60
70
80
90
100
average max average max average max average max averge max
Sweden 1 Swedenh 2 CoE Germany USA
* Sweden 2: a: study by U Jansson
Safe – donor safety on short and long term
Plasma quality and safety – screening tests and protein content
Sustainability – donor availability, quality system maturity and
economic viability
Safe and sustainable plasmapheresis
issues to discuss based on PA/PH/TS (16) 37 R
Citrate and bone density
Malignancy
Iron deficiency
Vasavagal donor event rates
Maximum volume per collection – donor safety
IgG levels and long term donor safety
Annual collection volume and frequency –
impact on donor health
02/11/2016 adapted from J Pink 20160920 60
Extended WG meeting recommendations
A scientific meeting on plasma supply
management needs to be arranged by EDQM with
the goal to collect evidence based data to support
the revision of the text of the recommendations to
be published in the 20th edition of the Guide
concerning donor selection, donor protection,
donor management and plasmapheresis in order
to collect plasma for fractionation.
Please follow: https://www.edqm.eu/en/blood-transfusion-projects-1449.html
Decrease of WB collection and recovered PfF
Safe and sustainable plasmapheresis
• donation volume and frequency?
• based on QC for the individual donor?
• sustainable donor pool for both blood and plasma
supply?
• QS following Good Practice Guidelines?
• Uniform application of EU/CoE rules and
recommendations for donors and donations?
Challenges for BE’s in plasma supply
management
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