PROTECTING THE BLOOD SUPPLY
FROM EMERGING PATHOGENS:
THE ROLE OF PATHOGEN
INACTIVATION (PI)
M.A. Blajchman, MD, FRCP(C)
McMaster University
Canadian Blood Services
WHAT IS PATHOGEN
INACTIVATION?
● A process of killing micro-organisms in biological
fluids including:
- Viruses
- Bacteria
- Parasites
● PI is a well-established approach to treat fractionated
blood products (proteins) during manufacture.
● PI is thus currently being explored to increase the
safety of plasma, platelets and blood components
including RBCs.
REDUCING THE RISK OF TRANSFUSIONTRANSMITTED INFECTIONS
•
•
•
•
•
•
•
•
Donor history
Donor examination
Donor testing
Diversion of initial aliquot
Leukoreduction
Post donation information
Donor deferral registries
Limit donor exposure
NEW TEST IMPLEMENTATION AND DECLINING
RISK OF TA-VIRAL INFECTIONS IN THE U.S.
C
u
l
t
u
r
e
+
Vamvakas EC, Blajchman MA. Blood 2009; 113: 3406-3417
Vamvakas EC, Blajchman MA. Blood 2009; 113: 3406-3417
CURRENT DONOR TESTING
FOR INFECTIOUS DISEASE
•
•
•
•
•
•
Syphilis (1938)
Anti-HIV
Anti-HTLV
HIV p24 Antigen
WNV NAT
Anti-HBc
● HBsAg
● Anti-CMV
● Anti-HCV
● HIV and HCV NAT
● Bacteria (2004)
● Chagas Disease (2009)
Chagas
DONOR TESTING FOR
HBV NAT
INFECTIOUS DISEASE
WNV
IN THE U.S.
HIV HCV NAT
HIV Ag
Anti-HCV
Anti-HTLV
ALT
Malaria
Anti-HBc
HHV8
Babesia
Anti-CMV
Leishmania
Anti-HIV
Foamy viruses
HBsAg
Syphilis
HEV
1938
1970 1975 1980
1985
1990 1995 2000 2005 2010
ONGOING AND UNTESTED
RISKS TO THE BLOOD SUPPLY
 Any agent known to cause disease in man and that has a
viremic or bacteremic phase during its clinical course.
 Agents for which there are no routine screening tests in place
include (partial list):
vCJD
HAV
Malaria
HPV
HHV-8
Dengue
Leishmania
Parvovirus
Rickettsia
SARS
Chikungunya
etc.
Babesia
Foamy viruses
HEV
RISKS OF TRANSFUSION-TRANSMITTED INFECTIONS
IN THE UNITED STATES
(1984-2005)
Blajchman MA, Vamvakas EC. NEJM 2006; 355: 1303-1305.
RISK OF TA-BACTERIAL
SEPSIS
•
•
•
•
•
Data from 2001
Canadian data published in 2007
ARC data published in 2007
Passport data reported in 2008
Murphy W et al. data published in 2008
Bacterial-Related Septic Transfusion Reactions*
(reported rates per million platelet units transfused)
Study
AP
Perez (2001)
Kuehnert (2001)
Ness (2001)
31.8
9.8
74.5
WB Platelets
71.8
10.6
67.0
RBCs
5.8
0.2
ND
AP = apheresis platelets
“It is likely that only the most severe forms of transfusion
reactions are reported and under-reporting undoubtedly occurs”.
*From McDonald CP and Blajchman MA Transfusion Microbiology 2008.
Bacterial Testing
Apheresis Platelets at CBS & HQ*
• 82,004 units tested, BacT/alert, aerobic only
• 70 units initially positive
– 6 confirmed positive
• 2 false negative PC resulted in TA-bacterial sepsis
– Salmonella sepsis in 61 yr. old man, with AML and
neutropenia.
– Serratia marcesens cultured at autopsy in a 3 year
old girl with leukemia who died of multisystem organ
failure 21 hours after transfusion with contaminated
apheresis platelets.
*Ramirez-Arcos et al, Transfusion 2007
American Red Cross
Bacterial Screening of Apheresis Platelets*
Single bottle culture of 1,004,206 AP donations (2004-06)
• 186 True Positives (1:5,399)
• False negative cultures resulted in 20 reported septic
reactions, including 3 fatalities (passive reporting)
● Partially associated with the use of 2-arm AP
procedures
●
13 of 20 reactions occurred with day 5 APs
*Eder AF et al. Transfusion 2007; 47: 1134-42.
THE PASSPORT STUDY
• FDA mandated post-marketing surveillance of 7day apheresis platelets (AP)
• Participation of 51 US Blood Centers
• Assessed the risk of bacterial contamination in
7-day AP compared to 5-day AP
• Cultures (BacT/ALERT, 2 bottles, 5 ml each)
• Release: 100% at 24-36 h post-collection
• Surveillance: PC inventory on day 7
• Passive reporting of clinical outcomes
PASSPORT Surveillance Cultures
• 4369 PC initially culture negative
– Re-tested after day 7
– 3 true positives: S. aureus , S. epidermidis,
S. veridans
• Residual risk: 686 per million PC (1 in ~1500)
L. Dumont, BPAC, May 2008
Release and Surveillance Confirmed Positive
10000
7 / 8282
1000
329
445
121
119
100
932
865
312
231
200
185
6 / 6438
845
662
ARC
1-Bottle Test
388,903
PASSPORT
12,823
Irish
30,407
8,995
Welsh
26,579
150,284
Diversion Diversion
4mL
8mL
388,903
ARC
386,611
10
1,004,206
Positive per million
4 / 6039
PsPrt
PsPrt
Surv.
Irish Aph
Surv.
Irish BC
Welsh
Aph
Surv.
Welsh
BC
2-Bottle Test
Contaminated Platelet Units Often
Escape Bacterial Culture Detection*
• 100% bacterial screening of platelet concentrates (PC)
introduced by Irish Blood Transfusion Service in 2005
• Overall Sensitivity of Screening: 29.2% (CI: 19.4-39.1%)
– All PCs tested prior to release on day after
manufacture
• 0.08% (35/43,220) positive
– PCs false negative at release
• Expired PCs retested, 0.22% (18/8282) positive
• Repeat test of PCs in stock on day 4 of storage to re-qualify,
0.12% (4/3320) positive
*W.G. Murphy et al, Vox Sanguinis 2008 (e-pub)
● “It is unthinkable that a manufacturer of other
intravenous medications could eschew reasonable
methods to eradicate possible contamination on the
basis that only organisms of questionable clinical
significance persisted in the preparations infused.”
● “It is also unthinkable that end users of
intravenous agents would be asked to check sterility
before use, …….”
● “It is apparent to us that bacterial testing, whether
early or late, lacks sufficient robustness …… as the
method of choice once a method of eradication of
adequate proven safety and utility is available.”
W.G. Murphy et al Vox Sanguinis 2008 95:13-19
TAS RISK - SUMMARY
• Current methods for the bacterial
screening of platelets are clearly
inadequate.
• Considerable
TAS
risk
remains,
particularly for recipients of platelets, as
~1 in 1500 PC units may not be
identified as containing bacteria.
• PI has shown efficacy in killing bacteria
that may be present in PCs.
FRACTIONATED PLASMA
PROTEINS
It is particularly relevant that there has been
no reported transmissions of HIV, HBV or
HCV by a pathogen inactivated plasma
derivative since 1987.
Should we not apply PI technology to all
blood products, including platelets, RBCs
and plasma?
BIOPHARMACEUTICAL PATHOGEN
REDUCTION/CLEARANCE
Product
NAT
Product
NAT
TECHNOLOGY
Nanofiltration
Affinity Purification
Solvent-Detergent
AHF Heat
Low pH
UV/Propiolactone
Fractionation
Pasteurization
1985
2000
LESSONS LEARNED FROM PI
OF PLASMA PROTEINS
• Efficacy of biological products is
maintained.
• Toxicity not usually encountered.
• Immunogenicity seldom encountered.
• Viral safety clearly can be achieved.
PATHOGEN-INACTIVATED BLOOD
COMPONENTS
• Goal: Eliminate transmission of viruses, bacteria
and parasites (known and unknown)
• Secondary Specific Drivers:
- Bacteria
- Parasites
- CMV
- GvHD
ADDITIONAL CONSIDERATIONS APPLICABLE
TO BLOOD COMPONENTS
• Eliminating infectivity from components is more difficult
than eliminating infectivity from derivatives:
–
–
–
–
Higher viral concentration
More proteins to consider
Cells (platelets, RBCs) more fragile
Some microbes not sensitive to PI (i.e. prions).
• Validation studies need to examine a wider range of
variables than encountered in the protein setting.
• GMP requirements are yet to be enunciated.
PATHOGEN INACTIVATION
METHODOLOGY
•
•
•
•
•
•
•
Solvent-detergent (SD plasma)
Methylene blue (MB, for plasma)
Psoralens (S-59, Amotosalen)
Riboflavin (vitamin B2)
S-303 (for RBCs, Amustaline)
Other dyes
UVC (under investigation for platelets)
Disrupting Nucleic Acid
REASONS FOR SLOW
ACCEPTANCE OF PI
• Perceived current safety of the volunteer
blood supply.
• No single method to treat all components.
• Success of surveillance and screening in
dealing with emerging pathogens, even if
delayed.
• Inability of current technologies to inactivate
all agents (small, non-encapsulated viruses,
spores, high-titer viremia, and prions).
• Risks from the residual unknown agents?
• Cost/Benefit ratio acceptable?
CAUTIONS REGARDING PATHOGEN
INACTIVATION TECHNOLOGY
• Each technology is different:
– Chemical/biological characteristics;
– Spectrum of pathogen reduction;
– Activity for specific pathogens -“log reduction;”
– Activity in specific components;
– Adducts and metabolites;
– Lack of knowledge of the profile of adverse
reactions (toxicity).
FUTURE SCREENING TEST
DEVELOPMENT
•
•
•
•
•
•
Babesia testing?
Chagas’ disease testing ?
Dengue (DFV) virus testing?
Malaria testing?
Point-of-use bacterial testing?
Chikungunya virus?
U.S.TRANSFUSION-ASSOCIATED
BABESIA MORTALITY
• Human babesiosis is a protozoal zoonotic illness
that is transmitted by Ixodes scapularis ticks.
• Various babesia species can infect vertebrate
hosts.
• 70 Babesia TTIs have been reported in North
America since 1979, most in the last decade.
• Ten TTI babesia deaths since 1997, nine within
the last 3 years.
• Babesia would be readily killed by PI.
Gubernot DM et al. Clin Infect Dis 2009; 48: 25-30.
MALARIA RISK MANAGEMENT
•
•
•
•
The parasites are readily killed by PI.
Would avoid malaria donor deferrals.
Travel deferrals for malaria avoided.
Testing strategy implementation will
be avoided altogether.
AVOIDANCE OF BACTERIAL
TESTING
• Current PI strategy would do nothing to
prevent TAS due to contaminated RBCs.
• PI impact on platelet viability is minimal.
• Could result in significant cost savings.
• Increased safety of platelets.
• Platelet inventory could be released
earlier.
AVOIDANCE OF NEW
MICROBIOLOGICAL THREATS
•
•
•
•
•
Good likelihood of killing most emerging agents.
Fewer donor deferrals will be required.
Test avoidance (WNV, Syphilis, anti-HBc).
No impact on prions!
Would eliminate the need for Chagas’ Disease
testing.
• N.B. This would apply only if RBC or whole
blood PI also becomes available.
IMPACT ON CONTINUED NEED FOR
UNIVERSAL LEUKOREDUCTION
• With implementation of PI, there would be
no need to γ-irradiate blood components.
• Thus there would be no need for blood
irradiators in Blood Centres.
• May however not address the HLAalloimmunization risk of non-LR platelets.
IMPACT OF PI ON CMV TESTING
• Current CMV TTI risk ~2%.
• Reduced risk of CMV transmission to
susceptible patients.
• When PI becomes universal, CMV testing
would no longer be required.
• Avoids a special inventory for “CMV-safe”
products.
IMPACT ON DONOR TESTING
• Simplified donor questionnaire.
• MSM would no longer be an issue.
• Less time would be needed to screen
donors.
WHAT PI WILL PROBABLY NOT
DO
• Will not reduce TRALI risk.*
• Will not reduce prion risk or
associated vCJD travel deferrals.
• Will not prevent the occurrence of
transfusion errors.
*The use of SD-plasma will likely reduce the TRALI risk with its use
(Prowse C. Transfus Med Rev 2009; 23: 124-133).
__________Pathogen
Inactivation
Making Decisions About New Technologies
CONSENSUS CONFERENCE ON
PATHOGEN INACTIVATION
Sponsors: Canadian Blood Services
Héma Québec
(BEST Collaborative)
March 29-30, 2007
STEERING COMMITTEE
Morris Blajchman, MD, FRCPC (Chair)
Canadian Blood Services
Gilles Delage MD
Héma-Québec
Jaroslav Vostal, MD, PhD
CBER, FDA
Dana Devine, PhD
Canadian Blood Services
Stephen Wagner, PhD
American Red Cross
Sunny (Walter) Dzik, MD
Massachusetts General Hospital
Kathryn Webert, MD, FRCPC
McMaster University
Heather Hume, MD
Canadian Blood Services
Lorna Williamson, MD, FRCP
University of Cambridge
NHS UK Blood and Transplant
BEST Collaborative, Chair
Harvey G. Klein, MD
NIH (Panel Chair)
CONSENSUS CONFERENCE PROCESS
March 29 – 30, 2007
• Topic Identified.
• Steering Committee crafts questions,
identifies speakers, and appoints panel.
• Speakers outline key issues (day 1).
• Panel deliberates and produces statement.
• Draft Statement presented (day 2).
• Panel refines Consensus Statement.
QUESTIONS POSED TO THE PANEL ─ 1
1. Implementation criteria: Is the current risk of transfusion-transmitted
diseases acceptable in relation to other risks of transfusions? a) If so, under
what new circumstances should pathogen inactivation be implemented?
b) Should the criteria be the same for RBCs, platelets, and FFP?
c) Should different criteria be used for certain patient populations?
2. Licensing requirements: What minimum acceptable safety and efficacy
criteria should be put into place for the pre-approval assessment of pathogen
inactivated products? Specifically: a) What criteria should govern acceptable
toxicology standards and how should they be assessed? b) What type of
post-marketing surveillance should be required (if any) with the
implementation of pathogen inactivated blood components.
3. Blood Service and Clinical issues: For pathogen inactivation
technologies that have been approved by the regulatory authorities, what
implications should be considered prior to their widespread adoption? Also, if
pathogen inactivated components differ in function from non-pathogen
inactivated equivalent products, how should this information be disseminated?
QUESTIONS POSED TO THE PANEL ─ 2
4. Risk management issues: If pathogen inactivation were to be
implemented for all components; in principle, what criteria would allow:
a) The relaxation of any current donor deferral/exclusion policies?
b) The cessation of any currently undertaken screening tests? c) A decision
not to implement new screening tests for agents susceptible to pathogen
inactivation? Should multiple inventories be considered for each component
and if yes how should allocation be decided?
5. Cost-benefit impact: How should the costs/benefits of pathogen
inactivation be assessed? Should these be aligned with other blood safety
interventions and/or other health care interventions?
6. Research requirements: What other information, considerations, and
research-related questions would need to be answered in order to decide
whether/when a particular pathogen inactivation procedure should be
implemented?
CONSENSUS PANEL
Harvey G. Klein - Panel Chair
National Institutes of Health
David Anderson (Hematologist)
Jeffrey S. Hoch (Health Economist)
QE II Health Sciences Centre
Halifax, NS
St. Michael’s Hospital
Toronto, ON
Marie-Josée Bernard (Ethicist)
Nancy Robitaille (Hematologist–Paeds)
CRIR
Montreal, QC
CHU St. Justine
Montreal, QC
Ritchard Cable (Transfusionist)
American Red Cross Blood Services
Farmington, CT
Marco L.A. Sivilotti (Toxicologist)
Queen’s University
Kingston, ON
William Carey (Blood Recipient)
Fiona Smaill (Infectious Disease Expert)
Owen Sound, ON
McMaster University Health Sciences
Hamilton, ON
CONSENSUS CONFERENCE SPEAKERS
TOPIC
SPEAKER
1. Microbiological reasons for considering
PI in Transfusion Medicine.
Dr. H. Alter
2. Biochemical and biological mechanisms
of PI methodology.
Dr. R. Dodd
3. Toxicology issues relating to the PI
of blood products: Impact on recipients.
Dr. J. Chapman
CONSENSUS CONFERENCE SPEAKERS
TOPIC
SPEAKER
4. Efficacy of PI FFP.
Dr. C. Prowse
5. Efficacy of PI platelets.
Dr. S. Slichter
6. Clinical experience with PI
platelets.
Dr. J-P Cazenave
7. Efficacy of PI RBCs.
Dr. J. AuBuchon
8. Immunogenic issues with the use of
PI RBCs.
Dr. G. Garratty
CONSENSUS CONFERENCE SPEAKERS
TOPIC
SPEAKER
9. The place of PI in the Transfusion Medicine
overall risk-benefit ratio.
Dr. W. Dzik
10. Regulatory issues: FDA perspective.
Dr. J. Vostal
11. Regulatory Issues:
European community perspective.
Dr. M. Heiden
12. Regulatory Issues:
Canadian perspective.
Dr. P. Ganz
CONSENSUS CONFERENCE SPEAKERS
TOPIC
SPEAKER
13. Public health aspect of residual risks
relating to transfusions.
Dr. M. Kuehnert
14. Economic issues. Cost benefits of
PI in relation to other aspects of
transfusion medicine.
Dr. B. Custer
15. Overview of newer PI technologies.
Dr. S. Wagner
PRIMARY PUBLICATIONS
1. Preliminary Panel Report: Klein HG et al.
Vox Sanguinis 2007; 93: 179-182.
2. Final Panel Report:
Klein HG et al.
Transfusion 2007; 47: 2338-2347.
3. Proceedings: Webert KE et al. Transfusion
Medicine Reviews 2008; 22: 1-34.
SECONDARY PUBLICATIONS
4. Editorial: McCullough J. Pathogen inactivation: A new
paradigm for blood safety. Transfusion 2007; 47: 2180-2184.
5. Editorial: Sher GD, Devine DV. The consensus development
process in transfusion medicine:
Does it add value?
Transfusion 2007; 47: 2176-2179.
6. Alter HJ. Pathogen reduction: A precautionary principle
paradigm. Transfusion Medicine Reviews 2008; 22: 97-102
Alter HJ: “I was in that packed hotel ballroom in
1994 when Dr. David Kessler urged blood banks
to develop NAT for routine donor screening. His
talk raised eyebrows and great skepticism; but
because of his position of authority, it drove the
system……, and resulted in the remarkably rapid
development of practical NAT assays that have
been an enormous addition to blood safety.”
NEW PI PARADIGM WOULD:
• Replace current paradigm which has
been mostly reactive.
• Proactive paradigm would potentially
deal with emerging microbiological
agents (probably most).
• Would prevent GvHD.
● Research should be encouraged to identify rare
and long-term consequences of the transfusion of PI
products.
Chronically
populations might serve
transfused
patient
as an ideal surveillance
population to identify long-term
pathogen inactivated products.
toxicities of
PI RESEARCH OPPORTUNITIES :
SUMMARY OF AN NHLBI WORKSHOP*
• Took place in July 2008.
• 30 invited participants and speakers.
• The focus was non-microbiological research
questions.
• The idea was to identify research opportunities
of various PI methods for platelets, RBCs,
plasma and whole blood.
• Currently available PI technologies were
reviewed.
*Klein HG et al. Transfusion 2009: On line
GENERAL RESEARCH
QUESTIONS POSTED
1. What are the appropriate methods for the clinical
evaluation of candidate PI technologies?
2. Are there potential novel and/or improved methods for
evaluating the efficacy of PI?
3. How will PI affect the risk of acute and delayed
transfusion reactions such as fever, hemolysis,
anaphylaxis, TRALI or other acute lung injury?
4. Will new technologies render blood functionally
leukoreduced and will they be equivalent to the gamma
irradiation currently being used in preventing GVHD?
5. How will PI affect recipient immune responsiveness
and/or tolerance?
6. Will certain patient populations be at particular risk, or
alternatively derive special benefit from PI treated
components?
NOVEL PI TECHNOLOGY
DEVELOPMENTS
• Methods that can be used for the PI of whole
blood.
• Alternative approaches to the inactivation of
cellular blood products using new chemicals
and/or new technologies.
• Investigations into novel methods that can be
used specifically for the PI of RBCs.
• PI technology that will have both an improved
safety profile and ability to maintain in vivo
function, recovery, and survival.
EXPLORING ADVERSE EVENTS
RELATED TO PI TECHNOLOGIES
• Mechanism(s) of the adverse side effects that have been
observed during clinical testing of PI-treated PLTs.
Particular priority should be given to investigations of
possible pulmonary toxicity.
The development of
suitable animal models is also encouraged.
• The development of a database capturing information on
adverse events detected during clinical trials.
• Further evaluation of the distribution and metabolism of
different additives and derivatives.
• Identification and use of improved models, including
animal models, for the comparative assessment of PItreated cell/protein safety and efficacy.
SAFETY AND EFFICACY
• Evaluation of the effect of PI treatment on the noninfectious
complications of transfusion.
• Exploration of study designs that will allow the evaluation of the
safety and efficacy of PI products used in trauma patients.
• Exploration of study designs that will allow the evaluation of the
safety and efficacy of PI products used in vulnerable populations.
• Evaluation of the impact of residual photoactive chemicals after
PI treatment on blood product toxicity and stability in vivo.
• Investigation of methods that will facilitate the removal and/or
inactivation of pathologic prion proteins.
• Investigation of the effects of PI treatment on component viability
and shelf life.
• Investigations into the effects of PI on component
immunogenicity and on the immunomodulatory effects of
transfused blood products.
HEALTH ECONOMICS AND
COST-EFFECTIVENESS
• Development of analytical methods to determine what
costs can be prevented by the adoption of PI
technology and an assessment of the resources likely
to be saved by the prevention of adverse events.
• Assessing the cost utility (cost-effectiveness) of PI
technology from the societal perspective including
budget impact analysis.
• Investigate and model the impact of PI implementation
on blood availability.
• Development of cost-effective methods for PI that
would be particularly suitable and effective for use in
developing countries.
• The development of risk-benefit assessments using
simulation modeling.
PATHOGEN INACTIVATION: THE NEW
PARADIGM IN TRANSFUSION MEDICINE
PANEL RESPONSES TO
QUESTIONS*
*Klein HG et al. Vox Sanguinis 2007; 93:179-182.
Klein et al. Transfusion 2007; 47:2338-2347.
1. Is the current risk of transfusion-transmitted diseases
acceptable in relation to other risks of transfusions?
● The panel recognizes that emergent transfusion-transmitted pathogens
have been detected at an increasing rate since the HIV epidemic.
● The panel recognizes that such risks require a proactive approach in
accordance with the precautionary principle.
● The risk of bacterial contamination has been reported as high as 1 in 2,000
platelet transfusions prior to the implementation of bacterial testing of
platelets.
● Hemovigilance data suggest that these risks are in aggregate substantially
lower than the current non-infectious risks of transfusion; such as acute
hemolysis, delayed hemolysis, and TRALI.
2. What minimum acceptable safety and efficacy criteria should be put into place
for the pre-approval assessment of pathogen inactivated products?
● The Panel recognizes that the different regulatory authorities have each
established their own standard approaches to these assessments. PI
technologies that target nucleic acid should undergo careful scrutiny to
assess the potential for genotoxicity, carcinogenocity, reproductive toxicity,
and germ-line toxicity. The Panel strongly recommends the use of
adequately powered well-designed randomized clinical trials using clinically
relevant endpoints.
● The Panel encourages the harmonization of approaches and sharing of data
among the various regulatory agencies.
● The panel recommends the sharing of hemovigilance data across jurisdictions.
3. For pathogen inactivation technologies that have been approved by
the regulatory authorities, what implications should be considered
prior to their widespread adoption?
● Consultation with appropriate patient and physician stakeholder groups
as well as hospital physician and transfusion groups.
● Inventory management, particularly at the time of crossover from the
current to the new technology.
● The PI procedure should be introduced as a pilot project in one
geographic area to work out logistical, environmental and occupational
health issues before it is implemented more widely.
4. If pathogen inactivation were to be implemented for all components;
in principle, what criteria would allow changes in deferral and
screening test policies:
● Following the implementation of PI for all components existing procedures
could be modified in order to reduce donor deferrals. However, the rationale for
PI implementation should be independent of these considerations.
● The regulatory agencies and blood collectors should review the donor
screening questionnaire to eliminate or modify questions that are thought to
be of marginal value such as tattooing and certain travel deferrals.
● Cessation of screening agents that are not readily transmissible by
transfusion, e.g., T. pallidum (syphilis); agents sensitive to PI and for which
redundant safety measures are in place, such as CMV, HTLV, and anti-HBc;
and agents that are exquisitely sensitive to PI and for which the current tests
have poor specificity and sensitivity, such as bacteria.
5. How should the costs/benefits of pathogen inactivation
be assessed?
● Implementation of PI should not be based solely or even
primarily on the results of an economic analysis; as most
costs are currently unknown and the benefits are difficult to
quantify.
● Costs and benefits should
perspective, examining both
accordance with published
analysis, at a bare minimum,
price and effectiveness.
be assessed using a societal
direct and indirect costs in
recommendations. Sensitivity
should focus on variations in
6. What other information, considerations, and research-related
questions would need to be answered in order to decide whether
/when a particular pathogen inactivation procedure should be
implemented?
● Consideration be given to robust governmental support for a large scale
investment in developing an integrated PI technology for all blood
components.
● Mathematical modeling should be used to develop credible scenarios
for the unknown pathogen risk; for example, what are the “break-even”
threshold conditions and are they consistent with a worst case scenario.
This model could be used in economic analysis of candidate PI
technologies to support decisions about investment for the research
agenda