FDA Workshop on

“Emerging Infectious Diseases:

Evaluation to Implementation for Transfusion
and Transplantation Safety”

Day 1: “Evaluating Emerging Infectious

Diseases (EIDs) for Transfusion Safety”
May 11, 2010

Paul A. Mied, Ph.D.

Update for the Blood Products Advisory Committee
July 26, 2010
Goal of the EID Workshop

To explore strategies for EID

threat detection, intervention,
and the prioritization of effort
 Key Questions
1. How do we and should we characterize the
risk to blood safety from an EID?
2. What are the criteria to prioritize EIDs
that pose a threat to blood safety?
3. How should regulators, blood
organizations, manufacturers, and other
stakeholders develop a response to the
threat from EIDs?
 Emerging Infectious Diseases
 New infections
 Re-emerging infections
 Drug-resistant infections
whose incidence in humans has
increased within the past 20 years or
whose incidence threatens to increase
in the near future.
Factors that Contribute to the Emergence
and Spread of Infectious Diseases
 Physical Environmental Factors
 Genetic and Biological Factors
 Ecological Factors
 Social, Political, and Economic Factors

- human demographics, behavior, and sanitation

- closer human contact with wildlife and its habitat
- failure of control measures
- international travel and commerce
- microbial adaptation and change
- human susceptibility to infection
- climate and weather
 Surveillance

 the ongoing systematic collection,

analysis, and interpretation of
outcome-specific data
↓
needs to be disseminated
in a timely fashion
 Some Thoughts about EIDs
 About 70% of our 68 or so EIDs have been
zoonotic
 New threats will emerge; many will be zoonotic
 Key will be:
- “to unite human and veterinary medicine
- to anticipate potential threats to blood safety
- to be vigilant for early detection
↓
Improve predictive capability, coordination
and communication through strong national and
international partnerships”
 Horizon Scanning
 the systematic examination of
potential threats, opportunities,
and likely developments
 the ability to detect novel and
unexpected issues, persistent
problems, or trends
 Repositories of Specimens
 Specific purpose for each
 TTVS, RADAR, and TRIPS linked donor-
recipient Repositories
 Contributions of each Repository
- evaluation of transfusion-transmission of
known agents
- may be very useful for that purpose for
new and future EID agents
Critical Information about an EID
 Is the agent blood-borne?
 Is there an asymptomatic blood-borne phase?
 Have transfusion transmissions been observed?
 Does the agent survive component mfg and storage?
 Does the agent cause disease? What is the disease attack
rate, severity, mortality, treatability of the disease?
 What is the prevalence and incidence in donors? Is it
significant?
 Is there professional, regulatory, and public concern?
 Are interventions available?
 What would be the impact of those interventions on
resources?
AABB TTD EID 4-Year Project
Goals:
1. To describe known and potential EID
agents for which transfusion
transmission is documented or its
potential exists, and no effective
intervention exists;
2. To create fact sheets for the agents;
3. To prioritize agents as to their blood
safety threat.
 Perspectives on Prioritization
 “Prioritization is not the main function. We get a
feel for which ones have significant risk that
requires us to take action.”
 “If you can develop a multi-pathogen (detection)
chip or pathogen reduction, the question of
prioritization becomes moot”
 “It’s more difficult to factor in public perception
and the societal concerns”
 “We acted because a test was available; but the
paradigm has changed for test manufacturers”
 “We acted in the face of a disease:
SFV: No TTD XMRV: No TTD?”
Key Questions on Prioritization

 “What is acceptable risk?”

 “When do we act with an
intervention? And, when an
intervention is introduced, can it be
removed if it is no longer needed?”
 “How do we know when a trigger
for action is reached?”
 Two EID Case Studies
 1. Babesia
- expanding geographically
- regional testing is conceivable

 2. XMRV
- no transfusion transmission observed
- no known causative relationship to disease
- donor prevalence is unknown
- test methods have not been standardized
- literature is controversial: inconsistent findings
for viral markers
 The Precautionary Principle

“ Action should be taken even if its

value cannot be proven; that is,
even if there is only a theoretical
risk of harm.
If risk is possible, then we must err
on the side of caution.”
 How do we Prioritize Our
Response to an EID Threat?

 “We could develop a scoring

system or a formula for
prioritizing”

 We could develop an “EID Agent

Priority Matrix”
 EID Agent Priority Matrix
high

vCJD
Plasmodia

Influenza virus subtype H5N1

moderate

Leishmania
HIV variants
SLE virus

T. cruzi
Chikungunya virus
Public Perception

Dengue viruses
B. burgdorferi

Babesia
CWD

low

HHV-8
HAV
B19 virus

very low

SFV
absent

theoretical very low low moderate high

Science/Epidemiology
Stramer et. al. 2009 Transfusion 49: Suppl.
“ XMRV is an excellent model”

 Deliberate action plan

 Does it cause disease?
 Is it transfusion transmitted?
 A model for the future
“WNV was a very good model”

 Developed a Model: Likely to

be transfusion transmitted
 Infection; disease;
epidemiology; a test in place
 “What’s the appropriate
action now?”

 Babesia: “Implementing blood

donor testing is an option that
could be considered”
 XMRV: “Continue research and
perhaps consider implementing an
interim blood safety intervention”
 Decision-making Framework of
Health Canada
3 phases:
1. Issue Identification: identify a
possible risk to blood safety;
2. Risk Assessment by surveillance and
hemovigilance; Benefit Assessment;
3. Risk Management: identify and
analyze options, select and implement
strategy, monitor results; surveillance
 Risk Assessment
 Hazard Identification
 Dose Response Assessment for the
infectious agent
 Exposure Assessment:
distributions, not point estimates
 Risk Characterization
 Risk Management: Risks vs
Benefits, compare “what-ifs”
What do we Need to Manage EID Risks?

 “Stronger links with other governments,

regulatory authorities and public health.”
 “Increased networking of researchers; global
coordination of responses to EIDs.”
 “Collaboration and communication with our
domestic and international stakeholders.”
 “A forum to describe how the decisions that were
made were made.”
Question: “What is the appropriate vehicle or
process to put this forum into action?”
 Tools to Address EIDs
 TessArae High Multiplicity Resequencing
Pathogen Microarrays (RPM)
 Technologies for prion protein assays and blood
filters that are under development
 Pathogen Reduction Technology (PRT)
- Expectations vs realities
- Perceived costs vs potential benefits of lower infection
rates and eliminating some current tests.
- “Combining methods may offer advantages:
Orthogonal process approach was suggested – combines
NAT and PRT to cover the Window Period.
Could Testing + Inactivation or Removal = Reduced
Deferrals?”
 Final Questions
 What do we do about lack of
interest and participation from the
manufacturers due to the small
market and margins?
 Where will the funding come from
as threats emerge or current
technology becomes antiquated?