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Analysis of US Source Plasma

Infectious Disease Residual

Risk compared to Recovered

Plasma Residual RiskIPFA/BCA Global Symposium on the Future

for Blood and Plasma Donations

George Schreiber, ScD, PPTA Director, Epidemiology

September 11-12, 2017

Atlanta, Georgia

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U.S. Plasma Collection

September 2017 IPFA/BCA Global Symposium

Source: MRB


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Trends in RBC collections, rejects,

transfusion, blood center outdates

Source: Centers for Disease Control and Prevention



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39

7

40

6

40

7

34

2

29

5

29

9

315 34

9 38

9

39

9

40

1

40

4

411

42

7

47

8

53

0

0

100

200

300

400

500

600

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

# C

en

ters

Number of US Source Plasma Centers 601



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40

30

20

10

0

13

.23

3.7

73

13

.82

4.5

45

12

.64

4.4

62

10

.31

7.6

74

10

.36

8.4

80

12

.44

2.2

14

15

.32

6.8

21

18

.81

7.8

69

22

.02

8.8

60

19

.80

7.4

73

23

.57

3.4

88

26

.21

4.0

19

29

.39

1.0

97

32

.55

0.2

93

35

.46

4.6

12

38

.29

6.2

34

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

2016

Do

na

tio

ns (

10

6)U.S. Source Plasma Donations,

2001-2016



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Plasma Quality Steps

• Medical history and physical examination (protects donor health and reduces recipient risk)

Donor Screening

Laboratory Testing

Qualified Donors (Source Plasma)

60 Day Inventory Hold (Source Plasma)

Residual Risk Assessments

Epidemiological [viral marker] standards (Source Plasma)

Important Plasma Quality Steps



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Source Plasma Steps

Viral Marker

Standard

•Center’s viral marker rates compared to industry average

•Centers repeatedly exceeding Alert Limits subject to lose IQPP certification

Qualified Donor

Standard

•New donors must pass 2 medical screenings and testing

•Reactivated donors (Qualified with > 6 month lapse) must requalify

•One time donor infectious disease unites discarded

Standards = Lowered

Risk



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Inventory Hold

Standard

•Plasma held in inventory for at least 60 days after donation

•Allows for interdetection and destruction of plasma based on post-donation disqualifiers

NAT Testing

Standard

•Requires NAT for HIV, HBV and HCV at minipool and at First Homogeneous Pool level

•Requires in-process testing for HAV and Parvovirus B19

Standards Lowered

Risk



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Viral Marker Standard

A statistically reliable system to ensure collection

from quality Source Plasma collection centers, based

on viral marker rates.

• In place for over a decade

• Serves as a guide for quality improvement

• Marker specific for HIV, HCV, and HBV

• Academic peer-reviewed

• Approach endorsed by FDA



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Viral Marker Alert Limits

• Alert Levels allow for identification of centers

with higher than expected viral positivity rates.

• Allows for continuous epidemiological

evaluation at individual plasma collection

centers together with an annual update of the

assessment.

• Reference rates based on overall industry

averages for donors contributing to the pool,

measured in a defined time period with the

most appropriate testing technology.



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Qualified Donor Positivity Rates


Rate

Pe

r 1

00

,000 D

on

atio

ns


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Residual Risk

Estimates of a potentially

infectious unit being

released for fractionation

or transfusion



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Residual Risk

Residual Risk of Viral Agent Entering

the Manufacturing Pool

• The presence of certain viruses in asymptomatic donors who

are negative on the screening tests (window period donations)

constitutes the major risk of viruses entering the fractionation

process.

• The Residual Risk is the estimated probability of a potentially

infectious plasma unit entering the manufacturing pool.

Accounts for Source Industry inventory hold.

• Used to assess the impact of Industry safety initiatives.

• Can be used to estimate pool viral load.

• The viruses of concern are: HCV, HIV, and HBV.



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Key Points to Remember

• Residual Risk is risk of a POTENTIALLY

contaminated unit entering manufacturing pool

(applicable to both source and recovered plasma).

• Potentially contaminated units have detection

levels below that of the NAT test.

• All manufactured plasma derived products have

virus removed or inactivated.

• Residual risk of transmission is then reduced to

zero.



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1,51 1,520,83

1,470,96 1,37 1,35 0,98 0,78 0,87 0,85 0,97 0,89 0,92 0,97

4,63,87

1,95 2,22 2,08 2,66 2,06 1,74 1,58 1,56 1,58 1,96 2,0 1,97 1,9

30,95

28,78

13,57 14,01

9,77

12,7413,92 13,9

11,9812,91

10,419,29

7,42

8,978,15

0

5

10

15

20

25

30

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

HIV

HCV

HBV

Resid

ua

l R

isk/1

06 D

on

atio

ns


Source Plasma Residual Risk


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HIV, HCV and HBV Residual Risks (per 106

donations) for Source

Qualified Donations and Recovered Repeat and All Donations

* Zou, et al., Transfusion 2010;50:1495-1504.

Virus

Source Plasma

(2008)

Qualified

Donations

Recovered

(2007-2008)

Repeat

Donations

Recovered

(2007-2008)

All

Donations

Source

Plasma

Qualified

Recovered

HIV * 0.98 0.54 0.68 1.4

HCV * 1.74 0.60 0.87 2.0

* * Stramer, et al., Transfusion 2013; 53:2449-2458.

Virus

PPTA

(2009-2011)

Qualified

Donations

Recovered

(2009-2011) Repeat

Donations

Recovered

(2009-2011)

All

Donations

PPTA

Qualified

Recovered

All

HBV **12.0 0.83

1.19

1.22

1.74

9.84 WP 18.5

6.90 WP 26.5



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Estimated Percentage of 6000 Liter – Plasma Pools

Containing at Least One Potential WP Donation


Source

7,500

Donations

Recovered

24,000

Donations

HCV 1.3% 2.1%

HIV 0.7% 1.6%

HBV 9.0%2.9% 18.5 WP

4.2% 26.5 WP


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Recovered Source

Plasma Safety Profile


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Viral Load

Viral Load in Manufacturing Pool

Detection limit

(96 minipool)

2015

Residual

Risk

Chance

of WP

donation

in pool

Maximum

Viral Load

1 WP/pool

(6000 donations)

Maximum

Viral Load of

WP

donations

HCV 675 IU/mL 1.9 0.01 0.11 IU/mL 675 IU/mL

HIV 4420 IU/mL 0.97 0.005 0.74 IU/mL 4420 IU/mL

HBV 220 IU/mL 8.15 0.05 0.04 IU/mL 220 IU/mlL



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Effects on Viral Load

Effect of Viral Inactivation / Removal on Viral Load

Viral Load (IU/mL)

1 WP donation in pool

9 logs reduction 12 logs reduction

HCV 1.1 / 1010 1.1 / 1013

HIV 7.4 / 1010 7.4 / 1013

HBV 4.0 / 1011 4.0 / 1014

• Assuming one WP donation in the manufacturing pool, viral load

reduction is complete.



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Inherent Truths

Demographic variations in infectious disease prevalence and incidence exist.

Viral removal and inactivation are key to ensuring the safety of fractionated plasma products.

Risk of a potentially infectious unit entering the plasma manufacturing pool is small. Viral inactivation and removal significantly reduces viral risk in finished plasma products.



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Inherent Truths


Plasma derived products have never been safer as a result of the rigorous efforts of the industry to ensure quality donors, sensitive testing, and virus inactivation/removal technologies.

There has been no confirmed case of transmission of viral infection in more than two decades, attesting to the safety of plasma derived products.


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