Investigational COVID-19 
Convalescent Plasma  
Guidance for Industry 
 
Document issued on October 13, 2023. 
 
This document supersedes the guidance of the same title issued on  
January 7, 2022.     
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Biologics Evaluation and Research 
October 2023  Contains Nonbinding Recommendations 
Preface 
 
Public Comment 
 
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 FDA-2020-D-1825 and complete 
title of the guidance in the request. 
 
Additional Copies 
 
Additional copies are available from the FDA webpage titled COVID-19-Related Guidance 
Documents for Industry, FDA Staff, and Other Stakeholder, available at 
https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-related-
guidance-documents-industry-fda-staff-and-other-stakeholders, and from the FDA webpage 
titled Search for FDA Guidance Documents available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents.  
 
Additional copies of this guidance are also 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. 
 
Questions 
 
For questions on the content of this guidance, contact OCOD at the phone numbers or email 
address listed above. 
 
  Contains Nonbinding Recommendations 
Table of Contents 
I.  INTRODUCTION..................................................................................................................... 1 
II.  BACKGROUND ....................................................................................................................... 2 
III.  RECOMMENDATIONS .......................................................................................................... 4 
A.  Pathways for Use of Investigational Convalescent Plasma ...................................... 4 
B.  Collection of COVID-19 Convalescent Plasma under the EUA .............................. 6 
C.  Collection of Convalescent Plasma Under an IND ................................................... 9 
D.  Recordkeeping ........................................................................................................... 12 
IV.  REFERENCES ........................................................................................................................ 13 
 
i 
  Contains Nonbinding Recommendations 
Investigational COVID-19 
Convalescent Plasma  
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 
 
FDA plays a critical role in protecting the United States (U.S.) from threats such as emerging 
infectious diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic.  FDA is 
committed to providing timely guidance to support response efforts to emerging threats.  
 
On August 23, 2020, FDA issued an Emergency Use Authorization (EUA)1 for COVID-19 
convalescent plasma for the treatment of hospitalized patients with COVID-19.  FDA 
subsequently reissued this EUA with revisions.  Most recently, FDA revised the EUA to limit 
authorization to the use of COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 
antibodies for the treatment of COVID-19 in patients with immunosuppressive disease or 
receiving immunosuppressive treatment in either the outpatient or inpatient setting.2  FDA 
recognizes that while COVID-19 convalescent plasma may be used under an EUA consistent 
 
1 On February 4, 2020, pursuant to section 564(b)(1)(C) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) 
(21 U.S.C. 360bbb-3) (85 FR 7316, February 7, 2020), and amended March 15, 2023 (88 FR 16644, March 20, 
2023), the Secretary of Health and Human Services (HHS) determined that there is a public health emergency, or 
significant potential for a public health emergency, that affects, or has a significant potential to affect, national 
security or the health and security of U.S. citizens living abroad, and that involves the virus that causes COVID-19.  
On the basis of such determination, the Secretary then declared, on March 27, 2020, that circumstances exist 
justifying the authorization of emergency use of drugs and biological products during the COVID-19 pandemic, 
pursuant to section 564 of the FD&C Act.  Under section 564 of the FD&C Act, the Commissioner of Food and 
Drugs may authorize unapproved medical products or unapproved uses of approved medical products to be used in 
an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions caused by chemical, 
biological, radiological, and nuclear agents, including emerging infectious disease threats when the product may be 
effective for its intended use, the known and potential benefits of the product outweigh the known and potential 
risks, and there are no adequate, approved, and available alternatives to the product.  Additional information on 
Emergency Use Authorization and a list of all current EUAs are available at https://www.fda.gov/emergency-
preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.  
2 U.S. Food & Drug Admin., U.S. Dept of Health & Human Servs., Emergency Use Authorization for COVID-19 
Convalescent Plasma (originally issued Aug. 23, 2020, and subsequently reissued with revisions) available at 
https://www.fda.gov/media/141477/download.  
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with the authorization, COVID-19 convalescent plasma may also be used under an 
investigational new drug application (IND).  For the purposes of this guidance, the term 
COVID-19 convalescent plasma refers to the convalescent plasma authorized under the EUA, 
while the term investigational convalescent plasma refers to convalescent plasma that does not 
meet all the conditions of the EUA and/or is being used under an IND. 
 
FDA is issuing this guidance to provide recommendations to health care providers and 
investigators on the use of COVID-19 convalescent plasma or investigational convalescent 
plasma.  The guidance also provides recommendations to blood establishments on collection.  
This document supersedes the guidance of the same title issued in January 2022 (previous 
versions February 2021, January 2021, November 2020, September 2020, May 2020, and April 
2020).  The recommendations in this guidance are unchanged from the January 2022 guidance.  
However, we have removed the language limiting the duration of the policy in the guidance to 
the public health emergency related to COVID-19 declared by HHS in accordance with section 
319(a)(2) of the Public Health Service Act (PHS Act) (42 U.S.C. 247d(a)(2)), which expired on 
May 11, 20233.  The revised duration of the guidance is described in the paragraph immediately 
below.   
 
This policy is intended to remain in effect only for the duration of the declaration under section 
564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) by the Secretary of Health and 
Human Services (HHS) on March 27, 2020 declaring that circumstances exist justifying the 
authorization of emergency use of drugs and biological products during the COVID-19 
pandemic,4 or until the time that FDA determines it is appropriate to revoke the EUA for 
COVID-19 convalescent plasma because the circumstances that justify its issuance no longer 
exist.  In preparation for when the EUA is no longer in effect, blood establishments interested in 
submitting an IND or biologics license application for COVID-19 convalescent plasma may 
contact the Center for Biologics Evaluation and Research (CBER), Office of Blood Research 
and Review (OBRR).  In addition, we are considering a future guidance with recommendations 
for such submissions.  
 
Given the COVID-19 public health emergency, and as discussed in the Notice published in the 
Federal Register of March 25, 2020, titled Process for Making Available Guidance Documents 
Related to Coronavirus Disease 2019, available at https://www.govinfo.gov/content/pkg/FR-
2020-03-25/pdf/2020-06222.pdf, this guidance was initially implemented without prior public 
comment because FDA determined that prior public participation for that guidance was not 
feasible or appropriate (see section 701(h)(1)(C) of the FD&C Act (21 U.S.C. 371(h)(1)(C)) and 
Title 21 of the Code of Federal Regulations (CFR) 21 CFR 10.115(g)(2)).  FDA is now reissuing 
this guidance in accordance with 21 CFR 10.115(g)(4), with minor changes as described above.   
 
In general, FDA guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
 
3 FDA announced its plans for COVID-19-related guidance documents in the Federal Register (85 FR 15417, March 
13, 2023), available at https://www.federalregister.gov/documents/2023/03/13/2023-05094/guidance-documents-
related-to-coronavirus-disease-2019-covid-19. 
4 See 85 FR 18250, available at https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-
use-authorization-declaration. 
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as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
 
II.  BACKGROUND 
 
There is currently an outbreak of respiratory disease caused by a novel coronavirus.  The virus 
has been named SARS-CoV-2 and the disease it causes has been named Coronavirus Disease 
2019 (COVID-19).  On January 31, 2020, HHS issued a declaration of a public health 
emergency related to COVID-19 and mobilized the Operating Divisions of HHS.5  In addition, 
on March 13, 2020, there was a Presidential declaration of a national emergency in response to 
COVID-19.6   
 
One investigational treatment for COVID-19 is convalescent plasma collected from individuals 
who have recovered from COVID-19, which contains antibodies to SARS-CoV-2 (Refs. 1-4).  
Use of convalescent plasma has been studied in other respiratory viral infections, including 
SARS-CoV-1, H1N1 influenza, and MERS-CoV (Refs. 5-7).  
 
On August 23, 2020, FDA issued an EUA for COVID-19 convalescent plasma for the treatment 
of hospitalized patients with COVID-19.  FDA has subsequently reissued the EUA with 
revisions.  Most recently, FDA revised the EUA to limit authorization to the use of COVID-19 
convalescent plasma with high titers of anti-SARS-CoV-2 antibodies for the treatment of 
COVID-19 in patients with immunosuppressive disease or receiving immunosuppressive 
treatment in either the outpatient or inpatient setting.  Given that the clinical evidence in patients 
with immunosuppressive disease or receiving immunosuppressive treatment remains limited, 
data from additional adequate and well-controlled randomized trials remain necessary for a 
definitive demonstration of COVID-19 convalescent plasma efficacy and to determine the 
optimal product attributes. 
 
 
   
 
5 Secretary of Health and Human Services, Determination that a Public Health Emergency Exists (originally issued 
Jan. 31, 2020, and subsequently renewed).  The COVID-19 PHE ended on May 11, 2023.  See the HHS COVID-19 
Public Health Emergency (PHE) web page at https://www.hhs.gov/coronavirus/covid-19-public-health-
emergency/index.html#:~:text=Based%20on%20current%20COVID%2D19,day%20on%20May%2011%2C%2020
23  
6 Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19) (Mar. 
13, 2020), available at https://trumpwhitehouse.archives.gov/presidential-actions/proclamation-declaring-national-
emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/.  On February 24, 2021, there was a 
Presidential Declaration continuing the national emergency concerning the COVID-19 pandemic beyond March 1, 
2021.  See Continuation of the National Emergency Concerning the Coronavirus Disease 2019 (COVID-19) 
Pandemic (February 24, 2021), available at https://www.federalregister.gov/documents/2021/02/26/2021-
04173/continuation-of-the-national-emergency-concerning-the-coronavirus-disease-2019-covid-19-pandemic.  The 
national emergency related to the COVID-19 pandemic ended on April 10, 2023.  See Joint Resolution terminating 
a National Emergency, available at https://www.congress.gov/118/plaws/publ3/PLAW-118publ3.pdf.    
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III.  RECOMMENDATIONS 
 
A.  Pathways for Use of Investigational Convalescent Plasma 
 
Because convalescent plasma for the treatment of COVID-19 has not yet been approved 
for use by FDA,7 it is an investigational product.  As such its administration must be 
under the EUA or an IND.  The emergency use of COVID-19 convalescent plasma is not 
authorized under the EUA unless it is consistent with, and does not exceed, the terms of 
the Letter of Authorization, including the Scope of Authorization and Conditions of 
Authorization.8  Alternatively, investigational convalescent plasma may be administered 
under the traditional IND regulatory pathway, a single-patient IND for emergency use, or 
an intermediate-size population expanded access IND (section 351(a)(3) of the PHS Act 
(42 U.S.C. 262(a)(3)); section 505(i) of the FD&C Act (21 U.S.C. 355(i)); 21 CFR 
601.21; and 21 CFR Part 312).   
 
FDA does not collect convalescent plasma or provide convalescent plasma.  Health care 
providers or acute care facilities should obtain convalescent plasma from an FDA-
registered or licensed blood establishment. 
 
The following pathways are available for administering or studying the use of 
convalescent plasma: 
 
1.  Emergency Use Authorization 
 
On August 23, 2020, FDA issued an EUA for COVID-19 convalescent plasma for the 
treatment of hospitalized patients with COVID-19.  FDA has subsequently reissued 
the EUA with revisions.  Most recently, FDA revised the EUA to limit authorization 
to the use COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 
antibodies for the treatment of COVID-19 in patients with immunosuppressive 
disease or receiving immunosuppressive treatment in either the outpatient or inpatient 
setting. 
 
Health care providers intending to administer COVID-19 convalescent plasma under 
the EUA are not required to report its use to FDA.  Providers should refer to the Fact 
Sheet for Health Care Providers9 for information on the intended use and known and 
potential risks and benefits of COVID-19 convalescent plasma.  The Fact Sheet also 
provides a description of the product, information on the dosage, administration and 
storage of COVID-19 convalescent plasma, use in specific populations, and 
instructions for communicating with recipients.  
 
As described in the Fact Sheet, health care providers must maintain records and 
conduct a thorough investigation of adverse reactions after transfusion of COVID-19 
 
7 Convalescent plasma is a biological product subject to the licensure requirement under section 351 of the PHS Act. 
42 U.S.C. 262(a).    
8 See https://www.fda.gov/media/141477/download. 
9 See https://www.fda.gov/media/141478/download. 
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convalescent plasma and must report fatalities to FDA as required in 21 CFR 
606.170.  Refer to FDAs guidance entitled Notifying FDA of Fatalities Related to 
Blood Collection or Transfusion for recommendations on reporting fatalities related 
to blood transfusion to FDA (Ref. 8). 
 
2.  Clinical Trials 
 
The EUA is not intended to replace clinical trials that are critically important for the 
definitive demonstration of safety and efficacy of investigational convalescent 
plasma.  Ongoing clinical trials of investigational convalescent plasma should not be 
amended based on the issuance of the EUA.  Healthcare providers are encouraged to 
enroll patients in those trials and complete clinical trials to fully answer the questions 
about the effectiveness of convalescent plasma for the treatment of COVID-19.  
 
Investigators wishing to study the use of convalescent plasma in a clinical trial should 
submit requests to FDA for investigational use under the traditional IND regulatory 
pathway (21 CFR Part 312).  (CBER) (OBRR) is committed to engaging with 
sponsors and reviewing such requests expeditiously.  During the COVID-19 
pandemic, INDs may be submitted via email to CBERDCC_eMailSub@fda.hhs.gov.   
 
3.  Expanded Access 
 
An IND application for expanded access is an alternative for use of investigational 
convalescent plasma for patients with serious or immediately life-threatening 
COVID-19 disease who are not eligible or who are unable to participate in 
randomized clinical trials (21 CFR 312.305).  During the COVID-19 pandemic, INDs 
for expanded access, that are not single patient INDs, may be submitted via email to 
CBERDCC_eMailSub@fda.hhs.gov.   
 
a.  Single Patient IND for Emergency Use 
 
Given the public health emergency that the COVID-19 pandemic presents, 
FDA is continuing to facilitate access to investigational convalescent plasma 
through the process of a physician requesting a single patient IND for an 
individual patient with serious or life-threatening COVID-19 under 21 CFR 
312.310.  This process allows the use of an investigational drug for the 
treatment of an individual patient by a licensed physician upon FDA 
authorization, if the applicable regulatory criteria are met.  Note, in such 
cases, a licensed physician seeking to administer investigational convalescent 
plasma to an individual patient must request the IND (21 CFR 312.310(b)).   
 
Note:  Given that the intended use of COVID-19 convalescent plasma under 
the EUA is for treatment of COVID-19 in patients with immunosuppressive 
disease or receiving immunosuppressive treatment in either the outpatient or 
inpatient setting, and COVID-19 convalescent plasma is not authorized for the 
treatment of COVID-19 in immunocompetent patients, FDA expects few 
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requests for single patient INDs.  FDA recommends that physicians seeking to 
use convalescent plasma for treatment of COVID-19 in patients with 
immunosuppressive disease or receiving immunosuppressive treatment should 
do so under the EUA and not under single patient INDs.  Other options for the 
use of investigational convalescent plasma are listed above. 
 
To obtain a single patient IND for emergency use, the requesting physician 
may contact FDA by completing Form FDA 3926 
(https://www.fda.gov/media/98616/download) and submitting the form by 
email to CBER_eIND_Covid-19@FDA.HHS.gov.  CBER requests that all 
forms be filled out electronically to facilitate rapid review.  Handwritten 
forms are often hard to read and may delay the processing of the request.  For 
more detailed instructions see the Form FDA 3926 Instructions 
(https://www.fda.gov/media/98627/download).  
 
For requests when the provider is unable to complete and submit Form FDA 
3926 due to extenuating circumstances, or in the case of a medical emergency 
between the hours of 8pm and 8am Eastern Time (ET), i.e., when 
authorization and issuance of an IND number is needed before 8am ET the 
next morning, the provider should contact FDAs Office of Emergency 
Operations at 1-866-300-4374 to be routed to the appropriate clinical review 
staff for assistance with submitting the request and issuance of an IND 
number.   
 
B.  Collection of COVID-19 Convalescent Plasma under the EUA 
 
Blood establishments collecting authorized COVID-19 convalescent plasma must 
comply with the Conditions for Authorization in the EUA.  Please refer to the Letter of 
Authorization for the Conditions of Authorization for registered and licensed blood 
establishments.10   
 
Note:  Registered and licensed blood establishments do not need to contact FDA or 
request a supplement to their license, respectively, to collect and manufacture COVID-19 
convalescent plasma for the authorized use under the EUA provided they 1) follow their 
standard operating procedures for plasma collection and all applicable regulations, and 2) 
collect plasma from individuals who meet the donor qualifications specified below.  
Once manufactured, COVID-19 convalescent plasma may be distributed for use under 
the EUA.  Blood establishments do not need to request an alternative procedure or 
exception under 21 CFR 640.120(a) to collect and distribute COVID-19 convalescent 
plasma. 
 
   
 
10 See https://www.fda.gov/media/141477/download. 
 
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1.  Donor Eligibility 
 
As described in the authorization letter, COVID-19 convalescent plasma is human 
plasma collected from individuals whose plasma contains high titers of anti-SARS-
CoV-2 antibodies and who meet all donor eligibility requirements (21 CFR 630.10 
and 21 CFR 630.15) and qualifications.  Under the EUA, authorized COVID-19 
convalescent plasma must be collected by registered or licensed blood establishments 
from donors in the U.S. or its territories in accordance with applicable regulations, 
policies, and procedures.  Testing for relevant transfusion-transmitted infections (21 
CFR 610.40) must be performed and the donation must be found suitable (21 CFR 
630.30). 
 
COVID-19 convalescent plasma is collected from individuals who meet the 
following qualifications:   
 
a.  Evidence of COVID-19 documented by laboratory testing in either: 
 
1.  Individuals who had symptoms of COVID-19 and a positive test result 
from a diagnostic test approved, cleared, or authorized by FDA.   
 
OR 
 
2.  Individuals who did not have a prior positive diagnostic test and/or never 
had symptoms of COVID-19 may be qualified to donate if they have had 
reactive (positive) results in two different tests approved, cleared, or 
authorized by FDA to detect SARS-CoV-2 antibodies.  
 
A list of all current EUA COVID-19 in vitro diagnostics is available at:  
https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-
regulatory-and-policy-framework/emergency-use-
authorization#covidinvitrodev. 
 
b.  Complete resolution of symptoms at least 10 days before the donation.  A 
negative result for COVID-19 by a diagnostic test is not necessary to qualify 
the donor.  
 
c.  Male donors, female donors who have never been pregnant, or female donors 
who have been tested since their most recent pregnancy and results interpreted 
as negative for HLA antibodies.   
 
d.  To ensure that COVID-19 convalescent plasma collected from donors 
contains antibodies directly related to their immune responses to SARS-CoV-
2 infection, you should not collect COVID-19 convalescent plasma from: 
 
   
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i.  Individuals who have received an investigational COVID-19 vaccine as a 
participant in a clinical trial, or received an authorized or licensed 
COVID-19 vaccine, unless they: 
 
1)  had symptoms of COVID-19 and a positive test result from a 
diagnostic test approved, cleared, or authorized by FDA (i.e., 
individuals who meet the qualification for evidence of COVID-19 
described in section III.B.1.a.1 of this guidance),  
 
AND 
 
2)  are within 6 months after complete resolution of COVID-19 
symptoms. 
 
Administration of COVID-19 vaccines for the purpose of boosting immunity of 
convalescent plasma donors would need to be conducted within a clinical trial 
under IND (21 CFR Part 312).   
 
OR 
 
ii.  Individuals who received an investigational COVID-19 monoclonal 
antibody therapy as a participant in a clinical trial or received an 
authorized or licensed COVID-19 monoclonal antibody therapy, until at 
least three months after receipt of the therapy.    
 
2.  Testing for anti-SARS-CoV2 Antibodies 
 
a.  Under the EUA, all plasma donations must be tested by registered or licensed 
blood establishments for high titers of anti-SARS-CoV-2 antibodies as a 
manufacturing step to determine suitability before release, using one of the 
tests and qualifying results referenced in the EUA Letter of Authorization.11  
 
b.  Plasma units that meet the specific testing requirements for SARS-CoV-2 
antibodies described in the EUA qualify as COVID-19 convalescent plasma 
with high titers of anti-SARS-CoV-2 antibodies.12  (See section III.B.3 of this 
guidance for labeling requirements.) 
 
c.  Blood establishments considering the use of a test not referenced in the EUA 
to qualify COVID-19 convalescent plasma should have the test developer 
contact CBER OBRR to determine acceptability of the proposed test, which if 
accepted, would require an amendment to the EUA.  FDA will consider data 
submitted to support such use in assessing the acceptability of other tests.   
 
11 See https://www.fda.gov/media/141477/download. 
12 Plasma units that do not qualify as COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 
antibodies under the EUA may qualify for investigational use under an applicable IND or may be relabeled as Fresh 
Frozen Plasma or other plasma type, as applicable, depending on the manufacturing process.   
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  Contains Nonbinding Recommendations 
 
Requests should be submitted to CBER-EUA-CCP-Assays@fda.hhs.gov. 
 
3.  Labeling 
 
COVID-19 convalescent plasma must be appropriately labeled.   
 
a.  The requirements in 21 CFR 606.121 for the container label apply, including 
the requirement to include a reference to the circular of information. 
 
FDA recognizes that the current circular of information does not contain 
specific information about COVID-19 convalescent plasma regarding 
indications for use, dosage information, contraindications, or cautions, but it 
provides information on the use of plasma. 
 
b.  COVID-19 convalescent plasma is not an approved product.  The container 
label must not indicate a license number. 
 
c.  COVID-19 convalescent plasma units must be clearly labeled as high titer 
COVID-19 convalescent plasma based on the results of the SARS-CoV-2 
antibody test used as part of manufacturing.  This information may be placed 
on the container label or on a tie tag. 
 
d.  We recommend the use of a uniform container label for COVID-19 
convalescent plasma.  In particular, we recommend the use of the 
International Society of Blood Transfusion (ISBT) format specified in the 
U.S. Industry Consensus Standard for the Uniform Labeling of Blood and 
Blood Components Using ISBT 128. 
 
e.  The manufacturing process used and the expiration date on the label for 
COVID-19 convalescent plasma should be the same as for other plasma 
products that are of the same type.  For example, COVID-19 Convalescent 
Plasma, Fresh Frozen, should be frozen within 8 hours after collection, stored 
at -18oC or colder and have an expiration date of one year from the date of 
collection.   
 
C.  Collection of Convalescent Plasma Under an IND 
 
Under FDAs IND regulations, an IND (including an intermediate-size population 
expanded access or single patient IND) must provide information with respect to the 
investigational drug, chemistry, manufacturing, and controls adequate to ensure the 
proper identification, quality, purity, and strength of the investigational drug (21 CFR 
312.23(a)(7) and 21 CFR 312.305(b)(2)(vi)).  For INDs for use of investigational 
convalescent plasma, the IND should contain, among other things, adequate information 
to demonstrate that the plasma will contain SARS-CoV-2 neutralizing antibody titers, if 
available.  Accordingly, health care providers or acute care facilities should include 
information in the IND submission that the investigational convalescent plasma will be 
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obtained from an FDA-registered blood establishment that follows the donor eligibility 
criteria and donor qualifications described in section III.C.1 of this guidance in collecting 
plasma from donors.   
 
1.  Donor Eligibility 
 
a.  Investigational convalescent plasma must only be collected from individuals 
who meet all donor eligibility requirements (21 CFR 630.10 and 21 CFR 
630.15).  Donation testing for relevant transfusion-transmitted infections must 
be performed (21 CFR 610.40) and the donation must be found suitable (21 
CFR 630.30). 
 
b.  We recommend investigational convalescent plasma is collected from 
individuals who meet the following qualifications: 
 
i.  Evidence of COVID-19 documented by laboratory testing in either: 
  
1.  Individuals who had symptoms of COVID-19 and a positive test result 
from a diagnostic test approved, cleared, or authorized by FDA.  
 
OR  
 
2.  Individuals who did not have a prior positive diagnostic test and/or 
never had symptoms of COVID-19 may be qualified to donate if they 
have had reactive (positive) results in two different tests approved, 
cleared, or authorized by FDA to detect SARS-CoV-2 antibodies.   
 
A list of all current EUA COVID-19 in vitro diagnostics is available at:  
https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-
regulatory-and-policy-framework/emergency-use-
authorization#covidinvitrodev. 
 
ii.  Complete resolution of symptoms at least 10 days before the donation.  A 
negative result for COVID-19 by a diagnostic test is not necessary to 
qualify the donor.  
 
iii. Male donors, female donors who have never been pregnant, or female 
donors who have been tested since their most recent pregnancy and results 
interpreted as negative for HLA antibodies.   
 
2.  Testing for anti-SARS-CoV2 Antibodies   
 
Plasma donations should be tested for anti-SARS-CoV-2 antibodies to determine 
suitability before release in accordance with an applicable IND.    
 
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  Contains Nonbinding Recommendations 
Note:  Plasma units that do not qualify as COVID-19 convalescent plasma under the 
EUA may qualify for investigational use under an applicable IND.  The units should 
be labeled as described in section III.C.3 of this guidance.  
 
Registered and licensed blood establishments that collect plasma intended for 
transfusion do not need to contact FDA or request a supplement to their license, 
respectively, or obtain their own IND to collect and manufacture convalescent plasma 
for investigational use provided they 1) follow their standard operating procedures for 
plasma collection and all applicable regulations, and 2) collect plasma from 
individuals who meet the donor qualifications specified in this guidance, which 
would be included in the applicable IND(s) held by a health care provider or other 
sponsor.  
 
Once manufactured, the convalescent plasma may be distributed for investigational 
use.  
 
Blood establishments do not need to request an alternative procedure or exception 
under 21 CFR 640.120(a) to collect and distribute investigational convalescent 
plasma.  
 
3.  Labeling  
 
Investigational convalescent plasma must be appropriately labeled.   
 
a.  The container label of investigational convalescent plasma units must include 
the following statement, Caution:  New DrugLimited by Federal (or 
United States) law to investigational use (21 CFR 312.6(a)).   
 
b.  In addition, the requirements in 21 CFR 606.121 for the container label apply, 
including the requirement to include a reference to the circular of information. 
 
FDA recognizes that the current circular of information does not contain 
specific information about investigational convalescent plasma regarding 
indications for use, dosage information, contraindications or cautions, but it 
provides information on the use of plasma. 
 
c.  The investigational convalescent plasma container label must not indicate a 
license number. 
 
d.  We recommend the use of a uniform container label for investigational 
convalescent plasma.  In particular, we recommend the use of the ISBT 
format specified in the U.S. Industry Consensus Standard for the Uniform 
Labeling of Blood and Blood Components Using ISBT 128.  
 
e.  The manufacturing process used and the expiration date on the label for 
investigational convalescent plasma should be the same as for other plasma 
products that are of the same type.  For example, Convalescent Plasma, Fresh 
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Frozen, should be frozen within 8 hours after collection, stored at -18oC or 
colder and have an expiration date of one year from the date of collection.   
 
f.  Investigational convalescent plasma units may be labeled for anti-SARS-
CoV2 antibodies based on the test results as specified under the applicable 
IND.  This information may be placed on the container label or on a tie tag. 
 
 
D.  Recordkeeping   
 
A health care provider who is participating in an IND, including an expanded access IND 
or single patient IND for emergency use, must maintain records for the investigational 
convalescent plasma unit(s) administered to the COVID-19 patient (21 CFR 312.62).  
Such records should include the unique identification number(s) (e.g., the ISBT donation 
identification number(s) of the unit(s)).  
 
 
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IV.  REFERENCES 
 
1.  Roback JD and Guarner J, Convalescent Plasma to Treat COVID-19:  Possibilities and 
Challenges, JAMA 2020;323(16):15611562, https://doi:10.1001/jama.2020.4940. 
 
2.  Shen C, Wang Z, Zhao F, Yang Y, et al., Treatment of 5 Critically Ill Patients with 
COVID-19 With Convalescent Plasma, JAMA, 2020;323(16):15821589, 
https://doi:10.1001/jama.2020.4783. 
 
3.  Chen L, Xiong J, Bao L, Shi Y, Convalescent plasma as potential therapy for COVID-19, 
Lancet Infect Dis, 2020;20(4):398-400, https://doi:10.1016/S1473-3099(20)30141-9. 
4.  Duan K, Liu B, Li C, Zhang H, et al., The feasibility of convalescent plasma therapy in 
severe COVID-19 patients:  a pilot study, MedRxiv, March 23, 2020, 
https://www.medrxiv.org/content/10.1101/2020.03.16.20036145v1.full.pdf. 
5.  Cheng Y, Wong R, Soo YOY, Wong, WS, et al., 2005, Use of convalescent plasma 
therapy in SARS patients in Hong Kong, Eur J Clin Microbiol Infect Dis, 24(1):44-46, 
https://doi.org/10.1007/s10096-004-1271-9. 
6.  Leider JP, Brunker PA, Ness PM, 2010, Convalescent transfusion for pandemic 
influenza:  preparing blood banks for a new plasma product?, TRANSFUSION, 
50(6):1384-1398, https://doi.org/10.1111/j.1537-2995.2010.02590.x. 
7.  Arabi YM, Hajeer AH, Luke T, Raviprakash K, et al., 2016, Feasibility of Using 
Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia, Emerg 
Infect Dis, 22(9):1554-1561, https://doi.org/10.3201/eid2209.151164. 
 
8.  Guidance for Industry:  Notifying FDA of Fatalities Related to Blood Collection or 
Transfusion, September 2003, https://www.fda.gov/media/70676/download. 
 
 
  
 
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