Reducing Risk of Relevant Transfusion-Transmitted Infection

Recommendations to Reduce the
Possible Risk of Transmission of
Creutzfeldt-Jakob Disease and
Variant Creutzfeldt-Jakob Disease
by Blood and Blood Components
Guidance for Industry

Additional copies of this guidance are available from the Office of Communication, Outreach
and Development (OCOD), 10903 New Hampshire Ave., Bldg. 71, Rm. 3128, Silver Spring,
MD 20993-0002, or by calling 1-800-835-4709 or 240-402-8010, or email [email protected], or
from the Internet at
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-informationbiologics/biologics-guidances.
For questions on the content of this guidance, contact OCOD at the phone numbers or email
address listed above.

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
April 2020

Contains Nonbinding Recommendations

Table of Contents

I.

INTRODUCTION............................................................................................................. 1

II.

BACKGROUND ............................................................................................................... 2
A.
B.
C.

III.

CJD and vCJD....................................................................................................... 2
TSE Agents and Blood .......................................................................................... 3
FDA Regulatory History on CJD and vCJD and Blood Donation ................... 4

DISCUSSION .................................................................................................................... 5
A.
1.
2.
3.
B.
1.
2.
3.

IV.

Rationale for Revised CJD Recommendations .................................................. 5
Donor Deferral for Receipt of Human Growth Hormone (hGH) ..................... 5
Donor Deferral for Having a Blood Relative with CJD ................................... 5
Donor Deferral for Receipt of a Dura Mater Transplant .................................. 6
Rationale for Revised vCJD Recommendations ................................................ 6
Donor Deferral for Geographic Risk of BSE Exposure.................................... 6
Donor Deferral for Potential Exposure to U.K.-Sourced Beef on U.S. Military
Bases ................................................................................................................. 7
Donor Deferral for Injection of Bovine Insulin Since 1980 ........................... 7

RECOMMENDATIONS.................................................................................................. 8
A.

Blood Donor Screening and Management .......................................................... 8
Donor History Questionnaire ............................................................................ 8
Donor Deferral .................................................................................................. 8
Donor Requalification ....................................................................................... 9
B.
Product Retrieval and Quarantine; Notification of Consignees of Blood and
Blood Components ................................................................................................ 9
1.
Blood and Blood Components Collected from Donors with CJD, Risk Factors
Related to CJD or Geographic Risk Factors for vCJD ..................................... 9
2.
Blood and Blood Components Collected from Donors with vCJD, Donors
Suspected of Having vCJD or Under Investigation for vCJD ........................ 10
C.
Circular of Information ...................................................................................... 11
1.
2.
3.

V.

IMPLEMENTATION .................................................................................................... 11

VI.

REFERENCES ................................................................................................................ 13

APPENDIX .................................................................................................................................. 15

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Recommendations to Reduce the Possible Risk of Transmission of
Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease
by Blood and Blood Components
Guidance for Industry
This guidance represents the current thinking of the Food and Drug Administration (FDA or
Agency) on this topic. It does not establish any rights for any person and is not binding on FDA
or the public. You can use an alternative approach if it satisfies the requirements of the
applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff
responsible for this guidance as listed on the title page.

I.

INTRODUCTION

We, FDA, are issuing this guidance document to provide you, blood establishments that collect
blood and blood components, with revised recommendations intended to reduce the possible risk
of transmission of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD)
by blood and blood components. The recommendations in this guidance apply to the collection
of Whole Blood and blood components intended for transfusion or for use in further
manufacturing, including Source Plasma. We are revising or removing our prior
recommendations to screen blood donors for: 1) geographic risk of possible exposure to bovine
spongiform encephalopathy, including time spent on United States (U.S.) military bases in
Europe; 2) receipt of a blood transfusion in certain vCJD risk countries; 3) risk factors for
iatrogenic CJD (i.e., a history of taking human cadaveric pituitary-derived growth hormone
(hGH)); 4) having blood relatives with CJD; and 5) a history of injecting bovine insulin. These
changes are summarized in the Appendix of this guidance.
This guidance finalizes the draft guidance of the same title dated January 2020, and supersedes
the document entitled “Revised Preventive Measures to Reduce the Possible Risk of
Transmission of Creutzfeldt-Jakob Disease and Variant Creutzfeldt-Jakob Disease by Blood and
Blood Products, Guidance for Industry” dated May 2010 and updated January 2016 (2016
guidance).
In general, FDA’s guidance documents, including this guidance, do not establish legally
enforceable responsibilities. Instead, guidances describe the FDA’s current thinking on a topic
and should be viewed only as recommendations, unless specific regulatory or statutory
requirements are cited. The use of the word should in FDA’s guidances means that something is
suggested or recommended, but not required.

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II.

BACKGROUND
A.

CJD and vCJD

CJD is a rare, but invariably fatal degenerative disease of the central nervous system,
belonging to a group of diseases called transmissible spongiform encephalopathies
(TSEs) or prion diseases (Refs. 1-8). TSEs are believed to be caused by an abnormal
isoform of a cellular glycoprotein known as the prion protein (Refs. 1-4). The general
term CJD comprises sporadic (classic) CJD (sCJD), iatrogenic CJD (iCJD), and genetic
CJD. The most common form, sCJD, accounts for about 85-95% of CJD cases, with an
estimated annual incidence of one case per million population worldwide (Ref. 1).
Genetic forms of CJD account for about 5-15% of CJD cases inherited as mutations in
the prion protein gene (PRNP), including familial CJD (fCJD), Gerstmann-SträusslerScheinker (GSS), and fatal familial insomnia (FFI) (Ref. 5). There are an estimated 56
GSS families and 27 FFI families worldwide (Ref. 2). Finally, a small percentage (less
than 1%) of CJD cases are iatrogenic (iCJD) and are acquired through transplantation of
dura mater from donors with CJD or through injections of human cadaveric pituitaryderived growth hormone (hGH) from contaminated preparations (Refs. 6-8). Thirty-three
cases of iCJD were reported among the nearly 7,700 people in the U.S. who received
hGH prior to 1977 (Ref. 7). Clinical latency for iCJD following exposure to infectious
material is typically 5-15 years, but it has also exceeded 30 years in case reports (Ref. 8).
CJD is rapidly progressive, with a median duration of illness of 4-5 months from onset of
symptoms (Ref. 1). Clinically, CJD is usually suspected on the basis of rapidly
progressive dementia, neuropsychiatric signs, and death usually within a year of
symptom onset; however, definitive diagnosis requires neuropathologic examination of
brain tissue (Ref. 1).
In 1996, the United Kingdom (U.K.) reported a previously unrecognized TSE, now
designated as vCJD (Refs. 9-11). Distinct from CJD, vCJD is a prion disease related to
bovine spongiform encephalophy (BSE, sometimes referred to as “mad cow disease”)
that is likely acquired from consuming contaminated beef products (Ref. 10). BSE was
first recognized in the U.K. in 1985 and subsequently spread to many European countries
and worldwide. Cases of BSE in the U.K. peaked in 1992, but subsequently fell to low
levels by 1996 as a result of control measures.
vCJD is distinguished from CJD by differences in clinical presentation, cerebral imaging,
and neuropathological changes (Refs. 1 and 12). Although definitive diagnosis requires
neuropathologic examination of brain tissue, the following notable features distinguish
vCJD from CJD and form the basis of a clinical diagnosis of suspected vCJD
(https://www.cdc.gov/prions/vcjd/diagnostic-criteria.html):
1. Current age or age at death <55 years.
2. Psychiatric symptoms at illness onset and/or persistent painful sensory
symptoms (frank pain and/or dysesthesia).

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3. Dementia and development ≥4 months after illness onset of at least two of the
following five neurologic signs: poor coordination, myoclonus, chorea,
hyperreflexia, or visual signs.
4. A normal or an abnormal EEG, but not the diagnostic EEG changes often seen
in classic CJD.
5. Duration of illness of over 6 months.
6. Routine investigations of the patient do not suggest an alternative, non-CJD
diagnosis.
7. No history of iatrogenic exposure to CJD, such as receipt of cadaveric human
pituitary growth hormone or an allogeneic dura mater graft.
8. No history of CJD in a first degree relative or prion protein gene mutation in
the patient.
The incidence of vCJD in the U.K. peaked at 29 cases in 1999 and has decreased each
year since (Refs. 13 and 14). The last two reported deaths from vCJD in the U.K. were in
2013 and 2016 (Refs. 13 and 14). To date, there is no evidence of a second wave of
vCJD cases in the U.K. (Ref. 15). As of October 8, 2019, there has been a total of 232
cases of vCJD worldwide, with 178 in the U.K., 28 in France, four in Ireland, four in the
U.S., and 18 cases in eight other countries (Refs. 13 and 14).
Of the four cases of vCJD in the U.S., two were reported in former residents of the U.K.;
one in a former resident of Saudi Arabia; and one in a former resident of Kuwait, Russia
and Lebanon (Ref. 12). None of these patients had donated blood in the U.S.
B.

TSE Agents and Blood

Among the 178 vCJD cases in the U.K., 18 were individuals who donated blood
components that were traced to 67 transfusion recipients (Ref. 16). There have been four
documented vCJD cases in this cohort that were likely transfusion transmitted. Of these
cases, three deaths from vCJD were linked to blood transfusions between 1996-1999 of
non-leukocyte reduced red blood cells (RBC) collected from two blood donors who died
from vCJD within 1-3 years of their donations (Refs. 16-19). The fourth possible case
was a latent transmission to a patient who died five years after the implicated transfusion
without symptoms of vCJD, but who had abnormal prion accumulation in the spleen at
autopsy (Ref. 18). The U.K. has also reported one possible latent transmission of vCJD
by plasma-derived Factor VIII to an asymptomatic 73-year-old patient with hemophilia,
based on postmortem findings (Ref. 20). At this time, plasma derivatives have not been
implicated in vCJD transmission in any country other than the U.K. To date, no U.S.licensed plasma-derived products have been manufactured from a donor known to have
developed vCJD and no cases of vCJD have been reported from use of a U.S.-licensed
plasma derivative.
In contrast to vCJD, no transfusion-transmitted cases of CJD have been described to date,
and the risk remains theoretical (Refs. 16, 21-29). The evidence base supporting the
improbability of transfusion transmission includes five case-control studies of over 600
CJD cases, two autopsy studies of patients with hemophilia, a large binational cohort

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study, and two ongoing lookback studies tracing recipients of components collected from
donors later found to have CJD (Refs. 16, 21-29). The U.K. lookback study includes 29
sCJD blood donors with transfusions to 211 recipients, and four fCJD blood donors with
transfusions to 15 recipients (Ref. 16). The U.S. lookback study includes 63 sCJD blood
donors with transfusions to 817 recipients; one iCJD donor linked to eight recipients; and
one fCJD donor linked to one recipient (Ref. 28). These studies have investigated the
reported causes of death and have continued the surveillance of surviving transfusion
recipients. Many recipients lived five or more years after transfusion (76 recipients in the
U.K. study; 264 recipients in the U.S. study), which likely would allow sufficient time to
recognize cases should they occur (Refs. 16, 28). The U.S. study also describes 414
recipients who received transfusion within five years of the donors’ CJD diagnosis or
symptom onset, of which, 105 of those recipients survived more than five years (Ref. 28).
Both studies have concluded that there have been no cases of any type of CJD identified
among the transfusion recipients to date.
Differences between CJD and vCJD are also apparent in experimental studies with
respect to prion protein detection in blood, the extent of replication in lymphoid tissues
and infectivity through blood exposure in animal studies (Refs. 30 and 31). Abnormal
prion protein accumulates in lymphoid tissues in persons with vCJD, but generally not in
persons with sCJD or genetic CJD, possibly reflecting the different propensity for
detection of the agent in blood and transmission of vCJD by blood transfusion (Ref. 16).
Correspondingly, a recent study demonstrated that the prion protein was detected in the
blood of all 14 patients with vCJD tested, but not in any of the 16 patients with sCJD or
in 137 controls who were either healthy or had other neurological diseases (Ref. 31).
C.

FDA Regulatory History on CJD and vCJD and Blood Donation

In 1987, FDA first issued recommendations in a memorandum to blood establishments
for deferral of individuals who received human cadaveric pituitary growth hormone
injections to reduce the possible risk of transmission of CJD by blood and blood
products. In 1999, FDA issued the first guidance with recommendations for CJD and
vCJD. FDA held several Transmissible Spongiform Encephalopathies Advisory
Committee (TSEAC) meetings between 1995 and 2015 to review the available scientific
evidence and the risk assessment of geographic donor deferrals and transfusiontransmitted vCJD. As the number of issues requiring Committee advice declined, the
Committee meetings occurred infrequently and, in 2016, FDA terminated TSEAC.

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III.

DISCUSSION
A.

Rationale for Revised CJD Recommendations

Based on the available scientific data and on public comments, FDA is revising its
recommendations on reducing the possible risk of transmission of CJD and vCJD by
blood and blood components.
There is currently no donor screening measure that can identify individuals who will later
develop CJD. Exposure of transfusion recipients to blood from asymptomatic CJD
donors has been demonstrated; however, no transfusion-transmitted cases of CJD have
been reported, and the risk of such transmission remains theoretical. Standard procedures
are already in place to assure that donors are healthy at the time of donation and serve as
an effective safeguard against collecting blood or blood components from a donor after
the onset of clinical symptoms of CJD. As a precaution, we recommend that any donor
suspected of having CJD or any other TSE is permanently deferred. In addition, we
recommend that establishments quarantine and retrieve blood and blood components
collected from donors with CJD based on post-donation information.
1.

Donor Deferral for Receipt of Human Growth Hormone (hGH)

In the 2016 guidance, we recommended that individuals who report having
received hGH should be permanently deferred from blood donation. Human
cadaveric pituitary-derived hGH was available in the U.S. from 1958 to 1985. All
associated cases of iCJD in the U.S. resulted from exposure to hGH prior to 1977
(Ref. 7). The national program to communicate annually with hGH recipients
ended in June 1999, although surveillance activities continue (Ref. 7). The
average incubation period for iCJD from hGH treatment is 15 years, although
there have been case reports of incubation periods longer than 30 years (Ref. 6).
Because the risk exposures to hGH occurred prior to 1977, it is unlikely that any
additional cases of iCJD will occur in this cohort. Therefore, we recommend that
establishments may remove hGH from their medication deferral lists used in
donor screening.
We recommend that donors previously deferred for receiving hGH are not eligible
for reentry as a precaution, because of the remote possibility of long incubation
periods. (Ref. 6).
2.

Donor Deferral for Having a Blood Relative with CJD

In the 2016 guidance, we recommended that prospective blood donors should be
indefinitely deferred if they report having a blood relative with CJD. However,
almost all cases reported are sCJD, not a genetic form of CJD. Blood relatives of
individuals with sCJD are not at increased risk of developing the disease. The
rare genetic forms of CJD (e.g., fCJD, GSS, or FFI) share pathophysiological
features with sCJD, and the transmission risk by blood components remains

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theoretical. Consequently, we recommend that establishments may stop asking
prospective donors about having blood relatives with CJD.
As a precaution, however, individuals who volunteer that they have blood
relatives known to have a genetic form of CJD (e.g., fCJD, GSS, or FFI) should
be deferred. Establishments should also quarantine and retrieve in-date blood and
blood components upon receipt of post-donation information about blood
relatives with CJD.
We recommend that donors who volunteer that they have one or more blood
relatives with genetic CJD (e.g., fCJD, GSS, or FFI) are not eligible for reentry.
3.

Donor Deferral for Receipt of a Dura Mater Transplant

The recommendation to defer donors who receive human (cadaveric) dura mater
allografts remains unchanged because such transplantation is still performed in
the U.S. and presents a remote risk of iCJD.
B.

Rationale for Revised vCJD Recommendations

We are changing the geographic deferral recommendations for vCJD risk based on the
findings of our risk assessment that the revised recommendations will achieve a similar
reduction of vCJD risk exposure while simplifying the donor screening process and
potentially allowing more donors to donate.
1.

Donor Deferral for Geographic Risk of BSE Exposure

FDA developed a quantitative risk assessment based on a global geographic riskranking model (Ref. 32) that estimated the contributions of donors potentially
exposed to BSE in various countries. The model evaluated both risk reduction
and donor loss resulting from the current geographic donor deferral policy
compared with alternative deferral options. The model also evaluated the
potential additional risk reduction afforded by leukocyte reduction of RBC. The
model indicated that U.K., Ireland, and France, the three countries with the most
attributed vCJD cases and BSE-related risk, contributed 95% of the total risk
exposure in the U.S. Estimating that about 95% of RBC currently transfused in
the U.S. are leukocyte reduced, the model predicted that deferring donors only for
time spent in the U.K., Ireland, and France would maintain a predicted level of
blood safety similar to that achieved with the current policy (Ref. 32). Based on
these results, we recommend indefinite deferral only of donors who spent time in
the U.K., Ireland, and France.
We maintain the recommendation in the 2016 guidance to defer prospective
donors who report receiving a blood transfusion in France or the U.K. We also
recommend deferral for transfusion in Ireland from 1980-present to align the

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deferrals for blood transfusion with the geographic deferrals for time spent in the
U.K., France, and Ireland (Ref. 32).
We recommend that donors previously deferred for geographic risk for time spent
in other European countries can be assessed for requalification using the revised
recommendations for vCJD geographic deferrals and may be eligible for reentry.
2.

Donor Deferral for Potential Exposure to U.K.-Sourced Beef on U.S.
Military Bases

In the 2016 guidance, we recommended that prospective donors should be
deferred based on cumulative time spent on U.S. military bases in Europe from
1980-1996. The deferrals were first recommended in 2001 because some U.S.
military bases in Northern Europe sourced beef from the U.K. between 1980 and
1990 and military bases elsewhere in Europe between 1980 to 1996 (Ref. 33).
During this time, over 4.4 million military personnel and civilians might have
ingested beef obtained from the U.K. on military bases in Europe; however, there
have been no reported cases of vCJD in the intervening 20 years. This
observation supports that the risk associated with time spent on U.S. military
bases in Europe is different from the country-based risk calculations for time
spent in the U.K., France, and Ireland that was based on the number of BSErelated vCJD cases in those countries. Therefore, we no longer recommend
deferral of individuals for time spent on U.S. military bases in Europe.
We recommend that donors previously deferred for time spent on military bases
in Europe can be assessed for requalification and may be eligible for reentry.
3.

Donor Deferral for Injection of Bovine Insulin Since 1980

In the 2016 guidance, we recommended that prospective donors should be
deferred if they report injecting bovine insulin, which may have been
manufactured after 1980 from cattle in the U.K. However, no cases of
transmission of vCJD have been reported in recipients of bovine insulin
manufactured in BSE-affected countries. Therefore, establishments may remove
bovine insulin from their medication deferral lists used in donor screening.
We recommend that donors previously deferred for injecting bovine insulin can
be assessed for requalification and may be eligible for reentry.

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IV.

RECOMMENDATIONS
A.

Blood Donor Screening and Management

The following recommendations apply to the collection of Whole Blood and blood
components intended for transfusion or for use in further manufacturing, including
Source Plasma.
1.

Donor History Questionnaire

We recommend that blood collection establishments update their donor history
questionnaires (DHQ), including full-length and abbreviated DHQ and
accompanying materials (e.g., flow chart, medication deferral list), and processes
to incorporate the revised recommendations provided in this guidance.
We recommend that the updated DHQ and accompanying materials include the
following elements:

2.

a.

Assess donors for a history of ever receiving a human cadaveric
(allogeneic) dura mater transplant.

b.

Assess donors for cumulative time spent in the U.K. (i.e., England,
Northern Ireland, Scotland, Wales, the Isle of Man, the Channel
Islands, Gibraltar, or the Falkland Islands) between 1980 to 1996.

c.

Assess donors for cumulative time spent in France 1 or Ireland from
1980 to 2001. Note that this assessment does not include time
spent in the U.K, which is evaluated separately in section IV.A.1.b.
of this guidance.

d.

Assess donors for a history of ever receiving a blood transfusion in
the U.K. (i.e., England, Northern Ireland, Scotland, Wales, the Isle
of Man, the Channel Islands, Gibraltar, or the Falkland Islands),
France1, or Ireland from 1980 to the present.

Donor Deferral
a.

Defer permanently a donor who has been diagnosed with vCJD,
CJD or any other TSE or who has a blood relative diagnosed with
genetic CJD (e.g., fCJD, GSS, or FFI). 2

1

This assessment does not include time spent in French overseas departments (e.g., Martinique, French Guiana,
Guadeloupe, Mayotte, and Réunion).
2
We do not recommend asking donors for a history of vCJD, CJD or any TSE or for family history of genetic CJD
(e.g., fCJD, GSS, FFI). However, donors that volunteer such information should be permanently deferred.

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3.

b.

Defer permanently a donor who has received a human cadaveric
(allogeneic) dura mater transplant.

c.

Defer indefinitely a donor who has spent three months or more
cumulatively in the U.K. (i.e., England, Northern Ireland, Scotland,
Wales, the Isle of Man, the Channel Islands, Gibraltar, or the
Falkland Islands) from 1980 to 1996.

d.

Defer indefinitely a donor who has spent five years or more
cumulatively in France1 or Ireland from 1980 to 2001. Note that
this assessment does not include time spent in the U.K, which is
evaluated separately in section IV.A.1.b. of this guidance.

e.

Defer indefinitely a donor with a history of blood transfusion in the
U.K. (i.e., England, Northern Ireland, Scotland, Wales, the Isle of
Man, the Channel Islands, Gibraltar, or the Falkland Islands),
France1, or Ireland from 1980 to the present.

Donor Requalification

Under 21 CFR 630.35, you may determine a deferred donor to be eligible if, at the
time of the current collection, the criteria that were the basis for the previous
deferral are no longer applicable. For donors deferred for reasons other than
reactive screening test results for relevant transfusion-transmitted infections under
21 CFR 610.41(a), you must determine that the donor has met the criteria for
requalification by a method or process found acceptable for such purposes by
FDA under 21 CFR 630.35(b).
Accordingly, donors who were previously deferred for certain risk factors for
vCJD and CJD may now be eligible based on the revised recommendations in
section IV of this guidance, except as follows:
•

Donors previously deferred for receiving hGH are not eligible for reentry.

•

Donors that have one or more blood relatives with genetic CJD (e.g.,
fCJD, GSS, or FFI) are not eligible for reentry.

Donors previously deferred for having a blood relative with CJD can be reentered
if the blood relative was not diagnosed with genetic CJD (e.g., fCJD, GSS, or
FFI). If the donor does not know these terms, the donor is eligible for reentry.
B.

Product Retrieval and Quarantine; Notification of Consignees of Blood and
Blood Components
1.

Blood and Blood Components Collected from Donors with CJD, Risk
Factors Related to CJD, or Geographic Risk Factors for vCJD

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If you collected blood or blood components intended for transfusion or further
manufacture from a donor who has been diagnosed with CJD, who has a blood
relative diagnosed with genetic CJD (e.g., fCJD, GSS, or FFI), or who should
have been deferred for risk factors for CJD or geographic risk factors for vCJD as
described in section IV.A.2. of this guidance, we recommend the following:
a.

Quarantine all undistributed in-date blood and blood components
from such a donor.

b.

If you distributed blood or blood components intended for
transfusion or for further manufacture from such a donor, we
recommend that you notify consignees to retrieve and quarantine
the in-date blood and blood components.
If the blood components were transfused, we do not recommend
tracing and notification of recipients of prior donations.

c.

We do not recommend retrieval or quarantine of plasma
components that have been pooled for further manufacture or
plasma derivatives manufactured from the plasma of such a donor.

Quarantined blood components from donors with CJD, or from donors with risk
factors for CJD or geographic risk factors for vCJD may be used in laboratory
research. You should relabel these products with the following statements:
•
•
•
2.

“Biohazard;”
“Collected from a donor determined to be at risk for CJD;” or
“Collected from a donor diagnosed with CJD;” or “Collected from
a donor with potential risk of exposure to variant CJD;” and
“Caution: For laboratory research use only.”

Blood and Blood Components Collected from Donors with vCJD, Donors
Suspected of Having vCJD, or Under Investigation for vCJD

We recommend that you contact FDA 3 as soon as possible upon learning that you
collected blood or blood components from a donor later determined to have
vCJD, a donor suspected of having vCJD or under investigation for vCJD (i.e.,
CJD diagnosis and age younger than 55 years). In addition, you should consider
notifying state and local public health authorities.
a.

If you collected blood or blood components from such a donor,
you should immediately quarantine all undistributed in-date blood
and blood components held at your establishments and notify

3

Contact CBER’s Office of Communication, Outreach and Development (OCOD) by calling 1-800-835-4709 or
240-402-8010. After regular business hours and on weekends, call the FDA emergency number: 1-866-300-4374.

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consignees to retrieve and quarantine all in-date components from
that donor.
If such blood components were transfused, you should consider
identifying the transfusion recipient’s physician of record, so that
notification and counseling may be performed as appropriate.
b.

You should immediately retrieve and quarantine plasma
components that have been pooled for further manufacture and
plasma derivatives manufactured from such a donor.
We recommend that you contact FDA regarding a donor’s
diagnosis of vCJD or suspected vCJD. Our recommendations
regarding product disposition of plasma derivatives from such
donors will depend upon results of the investigation.

Quarantined blood components from donors with vCJD or suspected vCJD may be
used in laboratory research on vCJD by qualified laboratories. You should relabel
these products with the following statements:
• “Biohazard;”
• “Collected from a donor with variant CJD” or “Collected from a donor
with suspected variant CJD;” and
• “Caution: Only for laboratory research on variant CJD.”
C.

Circular of Information

For Whole Blood and blood components intended for transfusion, the circular of
information should include the following warning statement:
“Because Whole Blood and blood components are made from human blood, they may
carry a risk of transmitting infectious agents (e.g., viruses, bacteria, parasites, the variant
Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, the Creutzfeldt-Jakob disease
agent (CJD).”

V.

IMPLEMENTATION

You may implement the recommendations once you have revised your DHQ, including the fulllength and abbreviated DHQ, and accompanying materials to reflect the new donor deferral
recommendations.
Licensed blood establishments must report changes to their approved BLA to FDA in accordance
with 21 CFR 601.12.

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1.

Licensed blood establishments that revise their DHQs and accompanying
material must report the change to FDA in a Changes Being Effected
(CBE) Supplement under 21 CFR 601.12(c)(5) (see 21 CFR 601.12(a)(3)).
The blood and blood components collected using the change may be
distributed immediately upon receipt of the supplement by FDA. Include
the following information in your CBE Supplement:
a.
b.
c.

Form FDA 356h “Application to Market a New or Abbreviated
New Drug, or Biologic for Human Use.”
Cover letter describing the request and contents of the supplement.
The DHQ and accompanying document(s). Please highlight the
modifications.

2.

Licensed blood establishments that implement a revised version of the
DHQ and accompanying materials prepared by the AABB Donor History
Task Force or the Plasma Proteins Therapeutic Association (PPTA) found
acceptable by FDA must report the changes to FDA in an annual report
under 21 CFR 601.12(d), noting the date the process was implemented.

3.

Unlicensed establishments are not required to report this change to FDA.

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VI.

REFERENCES

1.

Centers for Disease Control and Prevention (CDC), Variant Creutzfeldt-Jakob Disease
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13

Contains Nonbinding Recommendations
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Contains Nonbinding Recommendations
APPENDIX
Table 1: Comparison of Recommendations in 2016 Guidance and 2020 Guidance
2016 Guidance
2020 Guidance
Section Recommendations
Section
Recommendations
IV.A.1. Defer permanently donors who IV.A.2.a. Defer permanently a donor who has
have been diagnosed with vCJD
been diagnosed with vCJD, CJD or
or any other form of CJD.
any other transmissible spongiform
encephalopathy or who has a blood
relative diagnosed with genetic
CJD (e.g fCJD, GSS, or FFI).
Note: We do not recommend
questioning donors for vCJD, CJD,
or any other TSE or for blood
relatives with genetic CJD (e.g.,
fCJD, GSS, or FFI) because of the
inability to identify asymptomatic
individuals harboring TSEs, the
rarity of the conditions, and the
available evidence from lookback
studies that have not identified a
case among recipients of blood from
infected donors. However,
individuals that volunteer such
information should be permanently
deferred.
IV.A.2.

Defer permanently donors if
they have received:
• A dura mater transplant.

•

IV.A.3.

an injection of human
cadaveric pituitaryderived growth hormone
(hGH).
Defer indefinitely donors with
one or more blood relatives
diagnosed with CJD.
Defer indefinitely donors who
have spent 3 months or more in
U.K. from 1980-1996.

IV.A.2.b.

N/A

Revised to clarify the source of
tissue that is a cause for deferral:
• Defer permanently a donor who
has received a human cadaveric
(allogeneic) dura mater
transplant.
Deleted

N/A

Revised (see IV.A.2.a.).

IV.A.2.c.

No change

15

Contains Nonbinding Recommendations
2016 Guidance
Section Recommendations
IV.A.4. Defer indefinitely donors who
have spent 5 years or more
cumulatively in France from
1980 – present.

IV.A.5.

Defer indefinitely former or
current U.S. military personnel,
civilian military personnel, and
their dependents, for residence
on:
• U.S. military bases in
Northern Europe (Germany,
U.K., Belgium, and the
Netherlands) for 6 months
or more from 1980 through
1990, or
• U.S. military bases
elsewhere in Europe
(Greece, Turkey, Spain,
Portugal, and Italy) for 6
months or more from 1980
through 1996.

IV.A.6.

Defer indefinitely donors with a
history of transfusion in the
U.K. or France from 1980 –
present.

2020 Guidance
Section
Recommendations
IV.A.2.d. Defer indefinitely a donor who has
spent 5 or more years cumulatively
in France or Ireland from the
beginning of 1980 to the end of
2001. Note that this assessment
does not include time spent in the
U.K., which is assessed separately in
IV.A.1.b. This assessment also does
not apply to French overseas
departments (e.g. Martinique,
French Guiana, Guadeloupe,
Mayotte, and Réunion).
N/A
Deleted

IV.A.2. e.

16

Defer indefinitely a donor with a
history of transfusion in U.K. (i.e.,
England, Northern Ireland, Scotland,
the Isle of Man, the Channel Islands,
Gibraltar, or the Falkland Islands),
France, or Ireland from the
beginning of 1980 to present.

Contains Nonbinding Recommendations
2016 Guidance
Section Recommendations
IV.A.7. Defer indefinitely donors who
have injected bovine insulin
since 1980, unless you can
confirm that the product was
not manufactured after 1980
from U.K. cattle.
IV.A.8. Defer indefinitely donors who
have spent 5 years or more in
Europe from 1980-present.

2020 Guidance
Section
Recommendations
N/A
Deleted

N/A

17

Deleted