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 is for immediate implementation. 
 
This guidance is being implemented in accordance with 21 CFR 10.115(g)(2) without prior 
public comment because the Food and Drug Administration has determined that prior public 
participation for this guidance is not feasible or appropriate.  This guidance document is being 
implemented immediately, but it remains subject to comment in accordance with the Agencys 
good guidance practices. 
 
Comments may be submitted at any time for Agency consideration.  Submit written comments to 
the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, 
Rm. 1061, Rockville, MD 20852.  Submit electronic comments to https://www.regulations.gov.  
All comments should be identified with the docket number listed in the notice of availability that 
publishes in the Federal Register. 
 
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 ocod@fda.hhs.gov, or 
from the Internet at 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-
biologics/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 
May 2022  Contains Nonbinding Recommendations 
 
Table of Contents 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
A.  CJD and vCJD....................................................................................................... 2 
B.  TSE Agents and Blood .......................................................................................... 3 
C.  FDA Regulatory History on CJD and vCJD and Blood Donation ................... 4 
III.  DISCUSSION .................................................................................................................... 5 
A.  Rationale for CJD Recommendations ................................................................. 5 
1.  Donor Deferral for Receipt of Human Growth Hormone (hGH) ..................... 5 
2.  Donor Deferral for Having a Blood Relative with CJD ................................... 6 
3.  Donor Deferral for Receipt of a Dura Mater Transplant .................................. 6 
B.  Rationale for Revised vCJD Recommendations ................................................ 6 
1.  Removal of Donor Deferral for Geographic Risk of BSE Exposure ................ 6 
IV.  RECOMMENDATIONS .................................................................................................. 8 
A.  Blood Donor Screening and Management .......................................................... 8 
1.  Donor History Questionnaire ............................................................................ 8 
2.  Donor Deferral .................................................................................................. 8 
3.  Donor Requalification ....................................................................................... 8 
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 .................................................................................................. 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 
V.  IMPLEMENTATION .................................................................................................... 11 
VI.  REFERENCES ................................................................................................................ 12 
 
i  Contains Nonbinding Recommendations 
 
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 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.   
 
This guidance supersedes the guidance of the same title dated April 2020 and updated August 
2020 (2020 guidance).  We removed the recommendations to defer indefinitely blood donors for: 
1) geographic risk of possible exposure to bovine spongiform encephalopathy for time spent in 
the United Kingdom (U.K.) from 1980-1996 and for time spent in France and Ireland from 1980-
2001, and 2) receipt of a blood transfusion in the U.K., France, and Ireland from 1980-present.  
We also provide recommendations for requalification of individuals previously deferred for these 
geographic risk factors, provided they meet all other eligibility requirements.  
 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract.  This document is 
intended only to provide clarity to the public regarding existing requirements under the law. 
FDA guidance documents, including this guidance, should be viewed only as recommendations, 
unless specific regulatory or statutory requirements are cited.  The use of the word should in 
FDA guidances means that something is suggested or recommended, but not required. 
 
 
 
 
 
 
1  Contains Nonbinding Recommendations 
 
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).  Most authorities believe TSEs are caused by an 
abnormal isoform of a cellular glycoprotein known as the prion protein (Refs. 1-4).  The 
general term CJD comprises sporadic CJD (sCJD), iatrogenic CJD (iCJD), and familial 
CJD (fCJD).  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).  Familial prion diseases account for about 5-15% of CJD cases associated with 
mutations in the prion protein gene (PRNP), including fCJD; and other, even rarer, 
familial prion diseases include Gerstmann-Straussler-Scheinker syndrome (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 cadaveric pituitary human growth hormone (hGH) 
from contaminated preparations (Refs. 6-8).  Among the nearly 7,700 people exposed to 
cadaveric pituitary hGH in the National Hormone and Pituitary Program (NHPP) in the 
United States (U.S.), 33 cases of iCJD have been reported (Ref. 7).  All the NHPP iCJD 
cases to date have occurred among about 2,600 people who began cadaveric pituitary 
hGH treatment prior to 1977, with an average treatment duration of 8.2 years (Ref. 7).  
The average incubation period between the start of NHPP cadaveric pituitary hGH 
exposure and onset of CJD symptoms is 28 years and the time between the start of NHPP 
cadaveric pituitary hGH treatment and the first sign of CJD symptoms ranges from 14 to 
45 years (Ref. 7).  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 U.K. reported a previously unrecognized TSE, now designated as vCJD 
(Refs. 9-11).  Distinct from CJD, vCJD is a prion disease attributed to human infection 
with the agent of bovine spongiform encephalopathy (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, 12).  Definitive diagnosis requires 
neuropathologic examination of brain tissue; however, several 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).  In contrast to CJD, vCJD 
typically affects younger individuals (i.e., onset or death in individuals younger than 55 
2  Contains Nonbinding Recommendations 
 
years), presents with psychiatric symptoms at illness onset and/or persistent painful 
sensory symptoms, and has a duration of illness lasting more than 6 months.   
 
The incidence of vCJD in the U.K. peaked at 28 cases in 2000 and has decreased each 
year since (Refs. 13, 14).  The last two reported deaths from vCJD in the U.K. were in 
2013 and 2016 (Refs. 13, 14).  To date, there is no evidence of a second wave of vCJD 
cases in the U.K. (Ref. 15).  As of April 2021, 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 United States 
(U.S.), and 18 cases in eight other countries (Refs. 13, 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 infections in this cohort that were likely transfusion transmitted (Refs. 
16-19).  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, blood 
and blood components and plasma derivatives have not been implicated in vCJD 
transmission in any country other than the U.K.  The last reported case of transfusion-
transmitted vCJD in the U.K. occurred in 2006 and implicated a non-leukocyte reduced 
red cell unit.   
 
To date, no U.S.-licensed plasma-derived products have been manufactured from blood 
collected from a donor known to have developed vCJD and no cases of vCJD have been 
reported in persons treated with U.S.-licensed plasma derivative. 
 
In contrast to the 4 reported cases of vCJD transmitted by blood transfusion in the U.K., 
there have been no transfusion-transmitted cases of CJD described to date worldwide, 
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 
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 
3  Contains Nonbinding Recommendations 
 
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 concluded that there have been no cases of any type of CJD identified 
among the transfusion recipients to date. 
 
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 transfusion-
transmitted vCJD.  As the number of issues requiring Committee advice declined, the 
Committee meetings occurred infrequently and, in 2016, FDA terminated TSEAC.  
 
FDA updated the 1999 guidance several times.  Most recently, in 2020, we revised or 
removed our prior recommendations to screen blood donors for:  1) geographic risk of 
possible exposure to bovine spongiform encephalopathy in most European countries, 
including time spent on 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.  FDA did not change the 
recommendation for deferral based on time spent or transfusion in the UK, France, or 
Ireland at that time.   
 
FDAs decision in 2020 to remove certain geographic-based deferrals was based on the 
risk-ranking model that estimated the country-specific, relative risk of possible exposure 
to vCJD (Ref. 30).  The model determined that the U.K., Ireland, and France had the most 
attributed cases and thereby accounted for most of the potential risk of exposure to vCJD.  
The model also considered the extent of leukocyte reduction of the U.S. blood supply at 
the time and the associated risk reduction contributed by leukocyte reduction.  Notably, 
leukocyte reduction of blood and blood products is almost universally implemented in the 
U.S. today.  In the U.S., most whole blood/red blood cell units (97%) and platelet units 
(97%) are leukocyte reduced, which further reduces the risk of transfusion transmission 
of vCJD (Ref. 31).  
 
However, FDAs risk-ranking model did not estimate the absolute risk of transmitting 
vCJD through blood transfusion, in terms of the expected number of transfusion-
transmitted vCJD cases in the U.S. and the contribution of the deferral policy as a risk 
4  Contains Nonbinding Recommendations 
 
reduction measure.  Since publication of FDAs risk-ranking model, U.K.s Advisory 
Committee on the Safety of Blood, Tissues and Organs (SaBTO) (Ref. 32) and Medicines 
and Healthcare Products Regulatory Agency (MHRA) (Ref. 33) have conducted risk 
assessments that mathematically model the risk of vCJD infection through blood 
transfusion or immunoglobulin administration in the U.K., the country with the highest 
number of vCJD cases worldwide.)  In light of the new information, FDA has evaluated 
these new data and mathematical models, to assess the relevance of donor deferral for 
geographic risk in the UK, France, and Ireland to blood safety.  As described further 
below, based on this evaluation, FDA has determined that it is appropriate to update this 
guidance.  
 
 
III.  DISCUSSION  
 
A.  Rationale for CJD Recommendations 
 
The recommendations on reducing the possible risk of transmission of CJD are 
unchanged from the 2020 guidance.  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 
(Refs. 16, 21-29).  Standard procedures are 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) 
 
Human cadaveric pituitary hGH was available in the U.S. from 1958 to 1985 
(starting in 1986, all U.S.-produced hGH was recombinant).  Thirty-five cases of 
iCJD in the U.S. occurred among about 2,600 patients who began NHPP 
cadaveric pituitary hGH treatment prior to 1977 (Ref. 7).  The average incubation 
period for iCJD from the start of NHPP hGH treatment to the onset of CJD 
symptoms is 28 years, and the time between the start of NHPP hGH treatment and 
the first sign of CJD symptoms ranges from 14 to 45 years (Refs. 6, 7).  The 
prevalence of individuals who might have been treated with cadaveric pituitary 
hGH prior to 1977 is very low among blood donors, and the transmission risk of 
CJD by blood components remains theoretical (Ref. 28).  Consequently, we do 
not recommend inclusion of hGH in medication deferral lists used in donor 
screening educational materials.   
 
As a precaution, however, we recommend that individuals who volunteer that 
they received cadaveric pituitary hGH should be permanently deferred.  
 
5  Contains Nonbinding Recommendations 
 
Donors previously deferred for receiving cadaveric pituitary hGH are not eligible 
for requalification under 21 CFR 630.35(b) (Refs. 6, 7).  
 
2.  Donor Deferral for Having a Blood Relative with CJD 
 
Familial prion disease is extremely uncommon, and most cases reported by 
donors are sCJD, and not familial prion disease.  Blood relatives of individuals 
with sCJD are not at increased risk of developing the disease.  Familial CJD 
shares pathophysiological features with sCJD, and the transmission risk by blood 
components remains theoretical for both types.   
 
As a precaution, we recommend that individuals who volunteer that they have 
blood relatives known to have a familial prion disease (e.g., fCJD, GSS, or FFI) 
should be permanently deferred.  Establishments should also quarantine and 
retrieve in-date blood and blood components upon receipt of post-donation 
information about blood relatives with CJD.   
 
Donors who volunteer that they have one or more blood relatives with familial 
prion disease (e.g., fCJD, GSS, or FFI) are not eligible for requalification under 
21 CFR 630.35(b).   
 
3.  Donor Deferral for Receipt of a Dura Mater Transplant 
 
We recommend that blood establishments defer donors who receive human 
cadaveric dura mater allografts 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 new 
information in the risk assessments published by U.K.s SaBTO (Ref. 32) and MHRA 
(Ref. 33).  These risk assessment models, which FDA has independently evaluated, 
demonstrate that, in the UK, the current risk of vCJD transmission by blood and blood 
components would expose transfusion recipients to no or minimal additional risk of vCJD 
in the future, and, for blood components that are leukocyte reduced, the possible risk is 
even further reduced (Refs. 32, 33).   
 
We have determined that our recommendations will simplify the donor screening process 
and increase the number of eligible donors while maintaining the safety of blood and 
blood components.  
 
1.  Removal of Donor Deferral for Geographic Risk of BSE Exposure 
 
The U.K. SaBTO recently updated their risk assessment for transfusion of plasma 
collected in the U.K.  Since 2004, plasma has been imported from outside the 
U.K., for transfusion to individuals born after 1995 or with thrombotic 
6  Contains Nonbinding Recommendations 
 
thrombocytopenic purpura.  The model predicted that if the risk reduction 
measures were not in place, an additional 1 or 2 clinical cases of vCJD from 
plasma transfusion may occur in the U.K. over the next 50 years.  Based on this 
risk assessment, the U.K. eliminated their risk reduction measures in 2021, and 
stopped importing plasma from outside the U.K. for transfusion (Ref. 32).  
Further, the MHRA risk assessment demonstrated that the risk from the use of 
U.K.-sourced plasma for the manufacture of immunoglobulin products was 
negligible and led to the conclusion that U.K.-sourced plasma is now acceptable 
for the manufacture of immunoglobulins in the U.K. (Ref. 33).  As noted above, 
FDA has reviewed the methods and modeling data in these U.K assessments and 
believes they are valid estimates of risk.  Thus, FDA has concluded that these new 
data support removing the recommendation for deferral of individuals for 
geographic risk for time spent in the U.K.  
 
Additionally, based on the smaller number of vCJD cases in France and Ireland, 
FDA expects the risk of vCJD transmission by blood and blood components in 
France and Ireland would be even lower than what was modeled in the risk 
assessments for the U.K. (Refs. 32, 33).  Consequently, we are removing the 
recommendation for deferral of individuals who spent time in the U.K. (from 
1980-1996) and Ireland and France (from 1980-2001).  
 
Finally, the U.K. assessment of the risk of transfusion-transmitted vCJD in the 
U.K. predicted a small number of cases might be associated with plasma or 
platelet transfusion over the next 50 years (Ref. 32).  By extrapolation, we believe 
there would be an even lower risk of transfusion-transmitted vCJD in France and 
Ireland.  Consequently, we are removing the recommendation for indefinite 
deferral of individuals who have received a blood transfusion in the U.K., France 
or Ireland from 1980-present.   
 
Donors previously deferred for geographic risk for time spent in the U.K., France, 
and Ireland - or for receipt of a blood transfusion in the U.K., France, or Ireland - 
can be assessed for requalification under 21 CFR 630.35(b) and may be eligible 
for reentry, provided they meet all other eligibility requirements.   
 
In the 2020 guidance, we removed the recommendation for indefinite deferrals for 
time spent in other European countries, time spent on U.S. military bases, and 
receipt of bovine insulin since 1980.  Donors previously deferred for these 
reasons can be assessed for requalification under 21 CFR 630.35(b), provided 
they meet all other eligibility requirements. 
 
 
 
 
 
 
7  Contains Nonbinding Recommendations 
 
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:  
 
a.  Assess donors for a history of ever receiving a human cadaveric 
(allogeneic) dura mater transplant.  
 
2.  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 
familial prion disease (e.g., fCJD, GSS, or FFI) or who received 
cadaveric pituitary hGH treatment.1   
 
b.  Defer permanently a donor who has received a human cadaveric 
(allogeneic) dura mater transplant.  
 
3.  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).  
 
 
1 We do not recommend asking donors about a history of vCJD, CJD or any TSE, or about blood relatives with 
familial prion disease (e.g., fCJD, GSS, FFI) or about receipt of cadaveric pituitary hGH because of the inability to 
identify asymptomatic individuals harboring TSEs and the rarity of the conditions.  However, donors that volunteer 
such information should be permanently deferred.   
 
8  Contains Nonbinding Recommendations 
 
Accordingly, donors who were previously deferred for geographic risk factors for 
vCJD or receipt of a blood transfusion in the U.K., France or Ireland, may now be 
eligible provided they meet all other eligibility requirements. 
 
The following are not eligible for requalification and the recommendation for 
deferral remains in place: 
 
  Donors previously deferred for receiving cadaveric pituitary hGH.  
 
  Donors that have one or more blood relatives with familial prion disease 
(e.g., fCJD, GSS, or FFI).   
 
Donors previously deferred for having a blood relative with CJD can be reentered 
if the blood relative was not diagnosed with familial prion disease (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 
 
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 familial prion disease (e.g., fCJD, GSS, or FFI), or who 
should have been deferred for risk factors for CJD (i.e., receipt of cadaveric 
pituitary hGH treatment or human cadaveric (allogeneic) dura mater transplant) 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.   
 
9  Contains Nonbinding Recommendations 
 
Quarantined blood components from donors with CJD, who have a blood relative 
diagnosed with familial prion disease (e.g., fCJD, GSS, or FFI), or with risk 
factors for CJD (i.e., receipt of cadaveric pituitary hGH treatment or human 
cadaveric (allogeneic) dura mater transplant) may be used in laboratory research.  
You should relabel these products with the following statements:  
 
  Biohazard; 
  Collected from a donor determined to be at risk for CJD; or 
Collected from a donor diagnosed with CJD; and 
  Caution:  For laboratory research use only. 
 
2.  Blood and Blood Components Collected from Donors with vCJD, Donors 
Suspected of Having vCJD, or Under Investigation for vCJD   
 
We recommend that you contact FDA2 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 
consignees to retrieve and quarantine all in-date components from 
that donor. 
 
If such blood components were transfused, you should consider 
identifying the transfusion recipients 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 donors 
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:  
 
   
 
2 Contact CBERs 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. 
10  Contains Nonbinding Recommendations 
 
  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 full-
length and abbreviated DHQ, and accompanying materials to reflect the new donor deferral 
recommendations.   
 
Licensed blood establishments must report changes to their approved Biologics License 
Application (BLA) to FDA in accordance with 21 CFR 601.12.  
 
1.  Licensed blood establishments that revise their DHQs and accompanying 
material or 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) must report the change to FDA 
in an annual report under 21 CFR 601.12(d), noting the date the process 
was implemented.  
 
2.  Unlicensed establishments are not required to report this change to FDA. 
   
11  Contains Nonbinding Recommendations 
 
VI.  REFERENCES  
 
1.  Centers for Disease Control and Prevention (CDC), Variant Creutzfeldt-Jakob Disease 
(vCJD), https://www.cdc.gov/prions/cjd/index.html. 
2.  Creutzfeldt-Jakob Disease Foundation Inc, About CJD and Prion Disease, 
https://cjdfoundation.org/about-cjd. 
3.  Asher, DM, 2016, Transmissible Spongiform Encephalopathies.  In: RM Kliegman, BF 
Stanton, St Geme JW III, NF Schor, editors, Nelson Textbook of Pediatrics, Elsevier: 
Philadelphia, PA.  
4.  Seed, CR, PE Hewitt, RY Dodd, F Houston, and L Cervenakova, 2018, Creutzfeldt-Jakob 
disease and blood transfusion safety, Vox Sanguinis, 113: 220231.  
5.  Mastrianni, JA, 2003, Genetic Prion Diseases.  In:  MP Adam, HH Ardinger, RA Pagon, 
et al., editors. GeneReviews [Internet], Seattle (WA):  University of Washington, 
Seattle; 19932019, https://www.ncbi.nlm.nih.gov/books/NBK1229/. 
6.  Fradkin, JE, LB Schonberger, JL Mills, WJ Gunn, et al., 1991, Creutzfeldt-Jakob disease 
in pituitary growth hormone recipients in the United States. JAMA, 265: 880884. 
7.  National Institute of Diabetes and Digestive and Kidney Diseases, National Hormone and 
Pituitary Program (NHPP):  Public Health Service Interagency Coordinating Committee 
on Human Growth Hormone and Creutzfeldt-Jakob Disease:  Meeting Summary for 
November 18, 2020, https://www.niddk.nih.gov/about-niddk/advisory-coordinating-
committees/interagency-coordinating-committee-human-growth-hormone-creutzfeldt-
jacob. 
8.  Croes, EA, G Roks, et al., 2002, Creutzfeldt-Jakob disease 38 years after diagnostic use 
of human growth hormone, J Neurol Neurosurg Psychiatry, 72(6): 792793. 
9.  Will, RG., JW Ironside, et al., 1996, A new variant of Creutzfeldt-Jakob disease in the 
UK, Lancet, 347(9006): 921925. 
10.  Bruce, ME, RG Will, et al., 1997, Transmissions to mice indicate that new variant CJD 
is caused by the BSE agent, Nature, 389: 498501. 
11.  Hewitt, P and R Will, 2019, vCJD Case Studies, In: Blood Safety, H Shan, RY Dodd, 
editors, Springer Cham, 143155, https://doi.org/10.1007/978-3-319-94436-4_7  
12.  CDC, About Variant CJD, https://www.cdc.gov/prions/vcjd/index.html.  
13.  The National CJD Research and Surveillance Unit (NCJDRSU), The University of 
Edinburgh, http://www.cjd.ed.ac.uk/surveillance. 
14.  Creutzfeldt-Jakob Disease International Surveillance Network (formerly EuroCJD), CJD 
Surveillance Data 1993-2021, https://www.eurocjd.ed.ac.uk/data.   
15.  Garske T and AC Ghani, 2010, Uncertainty in the tail of the variant Creutzfeldt-Jakob 
Disease epidemic in the U.K., PLoS One, 5(12): e15626.  
16.  Urwin PJM, JM Mackenzie, CA Llewelyn, RG Will, and PE Hewitt, 2016, Creutzfeldt-
Jakob disease and blood transfusion:  updated results of the UK Transfusion Medicine 
Epidemiology Review Study, Vox Sanguinis,110: 310316.  
17.  Llewelyn, CA, PE Hewitt, et al., 2004, Possible transmission of variant Creutzfeldt-Jakob 
disease by blood transfusion, Lancet, 363(9407): 417421. 
18.  Peden, AH, MW Head, et al., 2004, Preclinical vCJD after blood transfusion in a PRNP 
codon 129 heterozygous patient, Lancet 364(9433): 527529. 
19.  U.K. Health Protection Agency, 2006, New case of transfusion-associated vCJD, 
Commun Dis Resp CDR Wkly, 16: serial online. 
12  Contains Nonbinding Recommendations 
 
20.  Peden, A, L McCardle, Head MW, Love S, et al., 2010, Variant CJD infection in the 
spleen of a neurologically asymptomatic UK adult patient with haemophilia, Hemophilia, 
16: 296304. 
21.  Esmonde, TF and RG Will, 1993, Creutzfeldt-Jakob disease and blood transfusion, 
Lancet, 341: 205207.  
22.  Heye, NS, S Hensen, et al., 1994, Creutzfeldt-Jakob disease and blood transfusion, 
Lancet, 343: 298299.  
23.  Wientjens, DP, Z Davanipour, et al., 1996, Risk factors for Creutzfeldt-Jakob disease: a 
reanalysis of case-control studies, Amer Acad Neurol, 46: 1287-1291.  
24.  Sullivan, M, L Schonberger, et al., 1997, Creutzfeldt-Jakob disease investigational 
lookback study, Transfusion, 37 suppl: 2s.  
25.  Evatt, B, H Austin, et al., 1998, Surveillance for Creutzfeldt-Jakob disease among 
persons with hemophilia, Transfusion, 38: 817820.  
26.  Lee, C, J Ironside, et al., 1998, Retrospective neuropathological review of prion disease 
in UK haemophilic patients, Thromb Haemost, 80: 909911.  
27.  Van Duijn, CM, N Delasnerie-Laupretre, et al., 1998, Case-control study of risk factors 
of Creutzfeldt-Jakob disease in Europe during 1993-1995 European Union (EU) 
collaborative study, Lancet, 351: 1081-1085. 
28.  Crowder, LA, LB Schonberger, RY Dodd, WR Steele, 2017, Creutzfeldt-Jakob disease 
lookback study:  21 years of surveillance for transfusion transmission risk, Transfusion 
57: 18751878. 
29.  Holmqvist, J, A Wikman, OBV Pedersen, KR Nielsen, K Rostgaard, H Hjalgrim, G 
Edgren, 2020, No evidence of transfusion transmitted sporadic Creutzfeldt-Jakob disease: 
results from a bi-national cohort study, Transfusion, doi: 10.1111/trf.15751, 
https://www.ncbi.nlm.nih.gov/pubmed/32187687. 
30.  Yang, H, Y Huang, L Gregori, et al., 2017, Geographic exposure risk of variant 
Creutzfeldt-Jakob disease in US blood donors: a risk-ranking model to evaluate 
alternative donor deferral policies, Transfusion, 57: 924932.  
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and Utilization Survey, Transfusion, 61: S11S35, https://doi.org/10.1111/trf.16606. 
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platelets as risk reduction measures for variant Creutzfeldt-Jakob disease:  The SaBTO 
review. Transfusion Medicine, 2021; 1-8.  
33.  Medicines and Healthcare Products Regulatory Agency, Critical risk assessment report: 
use of UK plasma for the manufacture of immunoglobulins and vCJD risk, 2021.  Critical 
risk assessment report:  use of UK plasma for the manufacture of immunoglobulins and 
vCJD risk - GOV.UK (www.gov.uk).  
 
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