European perspective on plasma collection for medicinal...

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

http://nvbtransfusie.nl/nvb-trip-symposium-2018/








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/




• Introduction



• 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

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

I von Schaik Kreuth III




• Introduction




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




• Introduction

• Work in the CoE on medical use of plasma-derived

medicinal products (PDMP)


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.


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.


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


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


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

European perspective on plasma collection for medicinal...

Documents

Transcript of European perspective on plasma collection for medicinal...