Dawn O’Connell 

Assistant Secretary for Preparedness and Response

Office of the Assistant Secretary for Preparedness and Response 

Office of the Secretary

U.S. Department of Health and Human Services 

200 Independence Avenue, SW 

Washington, DC 20201 

Dear Ms. O'Connell: 

On February 4, 2020, pursuant to Section 564(b)(1)(C) of the Federal Food, Drug, and Cosmetic 

Act (the Act) (21 U.S.C. 360bbb-3), the Secretary of the Department of Health and Human 

Services (HHS) determined that there is a public health emergency that has a significant potential 

to affect national security or the health and security of United States citizens living abroad, and 

that involves the virus that causes Coronavirus Disease 2019 (COVID-19) (the virus was later 

named SARS-CoV-2).1 On March 27, 2020, on the basis of such determination, the Secretary of 

HHS declared 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 Act (21 

U.S.C. 360bbb-3), subject to the terms of any authorization issued under that section.2

On August 23, 2020, the Food and Drug Administration (FDA) issued an Emergency Use 

Authorization (EUA) for the emergency use of COVID-19 convalescent plasma for the treatment 

of hospitalized patients with COVID-19 pursuant to Section 564 of the Act.3 FDA has since

reissued the letter of authorization to revise the indication4 and to revise or add tests acceptable 

for use in the manufacture of COVID-19 convalescent plasma.5

1 U.S. Department of Health and Human Services (HHS). Determination of a Public Health Emergency and 

Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, 

Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3. February 4, 2020. 2 HHS. Emergency Use Authorization Declaration. 85 FR 18250 (April 1, 2020).

https://www.govinfo.gov/content/pkg/FR-2020-04-01/pdf/2020-06905.pdf. 3 Additional information about this EUA can be found on the FDA website at https://www.fda.gov/emergencypreparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#coviddrugs. 4 In the February 4, 2021 revision to the EUA, FDA limited the authorization for COVID-19 convalescent plasma to 

the use of COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies only for the treatment of

hospitalized patients with COVID-19 early in the course of disease and those hospitalized with impaired humoral 

immunity. Additionally, this revision to the EUA revised the cutoff of the Ortho VITROS Anti-SARS-CoV-2 IgG 

test for qualification of COVID-19 convalescent plasma as high titer. 5 In the November 30, 2020, February 4, 2021, February 23, 2021, and March 9, 2021 reauthorizations, the tests 

acceptable for use in the manufacture of COVID-19 convalescent plasma were revised. Appendix A was updated 

with each revision to maintain a current list of authorized tests. 

December 28, 2021
Page 2 – Ms. O'Connell, ASPR

On December 28, 2021, having concluded that revising this EUA is appropriate to protect the 

public health or safety under Section 564(g)(2)(C) of the Act (21 U.S.C. § 360bbb-3(g)(2)(C)), 

FDA is again reissuing the March 9, 2021 letter of authorization in its entirety with revisions to:

limit the authorization to the use of COVID-19 convalescent plasma with high titers of antiSARS-CoV-2 antibodies for the treatment of COVID-19 in patients with immunosuppressive 

disease or receiving immunosuppressive treatment; revise acceptable tests and increase 

qualifying result cutoffs (listed in Appendix A) to be used for manufacturing COVID-19 

convalescent plasma with high titers of anti-SARS-CoV-2 antibodies; and make corresponding 

changes to the authorized Fact Sheets. 

COVID-19 convalescent plasma is human plasma collected from individuals whose plasma 

contains high titers of anti-SARS-CoV-2 antibodies (as described in Appendix A), and who meet 

all donor eligibility requirements (21 CFR 630.10 and 21 CFR 630.15) and qualifications. It is 

an investigational product and is not currently approved or licensed for any indication.

The August 23, 2020 issuance of this EUA for COVID-19 convalescent plasma was based on 

review of historical evidence using convalescent plasma in prior outbreaks of respiratory viruses, 

certain preclinical evidence, results from small clinical trials of convalescent plasma conducted 

during the outbreak, and data obtained from the National Convalescent Plasma Expanded Access 

Protocol (EAP) sponsored by the Mayo Clinic.

6 

Following the August 23, 2020, authorization, additional studies, including randomized, 

controlled trials, have provided data to further inform the safety and efficacy of COVID-19 

convalescent plasma, and further characterize product attributes and patient populations for its 

use. For the December 28, 2021 authorization, FDA reviewed additional studies including 

several randomized controlled trials and observational studies, which reported on the use of 

COVID-19 convalescent plasma in both the inpatient and outpatient settings. Based on 

assessment of these data, transfusion of COVID-19 convalescent plasma in hospitalized 

immunocompetent patients is unlikely to be associated with clinical benefit and the known and 

potential benefits do not outweigh the known and potential risks in this population. However, 

evidence supports a potential clinical benefit of transfusion of COVID-19 convalescent plasma

with high titers of anti-SARS-CoV-2 antibodies to treat COVID-19 in patients with 

immunosuppressive disease or receiving immunosuppressive treatment. Based on the totality of 

the scientific evidence available, it is reasonable to believe that the known and potential benefits 

of COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies, when used 

under the conditions described in this authorization, outweigh its known and potential risks for

6 A national expanded access protocol (EAP) sponsored by the Mayo Clinic was established in April 2020 and 

enrolled >100,000 subjects. The EAP discontinued enrollment in August 2020, following the issuance of the EUA 

for the emergency use of COVID-19 convalescent plasma for the treatment of hospitalized patients with COVID-19. 

The goal of this uncontrolled, single-arm study was to provide access to COVID-19 convalescent plasma in 

hospitalized subjects with severe or life-threatening COVID-19 or judged by the treating provider to be at high risk 

of progression to severe or life-threatening disease.
Page 3 – Ms. O'Connell, ASPR

the treatment of COVID-19 in patients with immunosuppressive disease or receiving 

immunosuppressive treatment.

7

 

Given that the clinical evidence in patients with immunosuppressive disease or receiving 

immunosuppressive treatment supporting this EUA remains limited, data from additional 

randomized, controlled trials are needed. 

Having concluded that the criteria for issuance of this authorization under 564(c) of the Act are 

met, I am authorizing the emergency use of COVID-19 convalescent plasma with high titers of 

anti-SARS-CoV-2 antibodies for treatment of COVID-19 in patients with immunosuppressive 

disease or receiving immunosuppressive treatment, in either the outpatient or inpatient setting, as 

described in the Scope of Authorization section of this letter (Section II) and subject to the terms 

of this authorization. 

I. Criteria for Issuance of Authorization 

I have concluded that the emergency 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 when administered as 

described in the Scope of Authorization (Section II) meets the criteria for issuance of an 

authorization under Section 564(c) of the Act, because: 

1. SARS-CoV-2 can cause COVID-19, a serious or life-threatening disease or condition, 

including severe respiratory illness, in humans infected by this virus; 

2. Based on the totality of scientific evidence available to FDA, it is reasonable to 

believe that COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 

antibodies may be effective in treating COVID-19 in patients with 

immunosuppressive disease or receiving immunosuppressive treatment, and that, 

when used under the conditions described in this authorization, the known and 

potential benefits of COVID-19 convalescent plasma with high titers of anti-SARSCoV-2 antibodies when used to treat COVID-19 outweigh the known and potential 

risks of the product; and 

3. There is no adequate, approved, and available alternative to the emergency use of 

COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies for 

7 Information derived from ongoing clinical trials of COVID-19 convalescent plasma (particularly randomized 

controlled trials), as well as clinical trial results from studies of other investigational medical products to treat 

COVID-19, will continue to inform the risk-benefit assessment for this EUA. 
Page 4 – Ms. O'Connell, ASPR

the treatment of COVID-19 in patients with immunosuppressive disease or receiving 

immunosuppressive treatment.

8, 9

II. Scope of Authorization 

I have concluded, pursuant to Section 564(d)(1) of the Act, that the scope of this authorization is 

limited to the use of the authorized COVID-19 convalescent plasma with high titers of antiSARS-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.

The Authorized COVID-19 Convalescent Plasma (Product Description): 

COVID-19 convalescent plasma is human plasma collected from individuals whose plasma 

contains SARS-CoV-2 antibodies and who meet all donor eligibility requirements (21 CFR 

630.10 and 21 CFR 630.15) and qualifications.

10 Under this EUA, authorized COVID-19 

convalescent plasma will be obtained from registered or licensed blood establishments from 

donors in the United States 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).

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 listed in Appendix A.

If a blood establishment is considering using a different test in manufacturing in order to qualify 

COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies, they should 

contact the FDA Center for Biologics Evaluation and Research (CBER) to determine 

acceptability of the proposed test, which if accepted, would require an amendment to this EUA

(see Appendix A).

To be labeled as COVID-19 convalescent plasma under this EUA, units containing anti-SARSCoV-2 antibodies must be labeled as high titer according to the results of the tests listed in 

Appendix A. 

Health care providers will administer the authorized COVID-19 convalescent plasma with high 

titers of anti-SARS-CoV-2 antibodies according to standard hospital procedures and institutional 

medical and nursing practices. Clinical dosing may first consider starting with one high titer 

8 At the time of reissuance of this letter of authorization, one drug had been approved by FDA for the treatment of 

certain hospitalized patients with COVID-19 and was available. However, this drug is not considered an adequate 

alternative because, among other things (1) its approved indication is limited to hospitalized patients; (2) in patients 

with immunosuppressive disease or on immunosuppressive therapy, treatment with this drug may be inadequate to 

clear the virus; and (3) CCP has a different mechanism of action which can facilitate viral clearance in patients with 

immunosuppressive disease or on immunosuppressive therapy.

9 No other criteria of issuance have been prescribed by regulation under Section 564(c)(4) of the Act. 10 For more information see FDA’s guidance for industry, entitled “Investigational COVID-19 Convalescent 

Plasma,” available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigationalcovid-19-convalescent-plasma. 
Page 5 – Ms. O'Connell, ASPR

COVID-19 convalescent plasma unit (about 200 mL), with administration of additional high titer 

COVID-19 convalescent plasma units based on the prescribing physician’s medical judgment 

and the patient’s clinical response. The authorized storage and handling information is included 

in the authorized Fact Sheet for Healthcare Providers.

COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies is authorized to 

be accompanied by the following product-specific information pertaining to emergency use, 

which is required to be made available to health care providers and patients respectively:

• Fact Sheet for Health Care Providers: Emergency Use Authorization (EUA) of COVID19 Convalescent Plasma for Treatment of Coronavirus Disease 2019 (COVID-19).

• Fact Sheet for Patients and Parents/Caregivers: Emergency Use Authorization (EUA) of 

COVID-19 Convalescent Plasma for Treatment of Coronavirus Disease 2019 (COVID19).

I have concluded, pursuant to Section 564(d)(2) of the Act, that it is reasonable to believe that 

the known and potential benefits of COVID-19 convalescent plasma with high titers of antiSARS-CoV-2 antibodies, when used for the treatment of COVID-19 in patients with 

immunosuppressive disease or receiving immunosuppressive treatment, in either the outpatient 

or inpatient setting, and used in accordance with this Scope of Authorization (Section II), 

outweigh its known and potential risks. 

I have concluded, pursuant to Section 564(d)(3) of the Act, based on the totality of scientific 

evidence available to FDA, that it is reasonable to believe that COVID-19 convalescent plasma

with high titers of anti-SARS-CoV-2 antibodies may be effective for the treatment of COVID-19

in patients with immunosuppressive disease or receiving immunosuppressive treatment, when 

used in accordance with this Scope of Authorization (Section II), pursuant to Section 

564(c)(2)(A) of the Act. 

Having reviewed the scientific information available to FDA, including the information 

supporting the conclusions described in Section I above, I have concluded that COVID-19 

convalescent plasma (as described in this Scope of Authorization (Section II)) meets the criteria 

set forth in Section 564(c) of the Act concerning safety and potential effectiveness.

The emergency use of the authorized product under this EUA must be consistent with, and may 

not exceed, the terms of the Authorization, including the Scope of Authorization (Section II) and 

the Conditions of Authorization (Section III). Subject to the terms of this EUA and under the 

circumstances set forth in the Secretary of HHS’s determination under Section 564(b)(1)(C) 

described above and the Secretary of HHS’s corresponding declaration under Section 564(b)(1), 

COVID-19 convalescent plasma with high titers of anti-SARS-CoV-2 antibodies is authorized for 

the treatment of COVID-19 in patients with immunosuppressive disease or receiving 

immunosuppressive treatment, as described in the Scope of Authorization (Section II) under this 

EUA, despite the fact that it does not meet certain requirements otherwise required by applicable 

federal law.
Page 6 – Ms. O'Connell, ASPR

III. Conditions of Authorization 

Pursuant to Section 564 of the Act, I am establishing the following conditions on this 

authorization: 

ASPR

A. ASPR will ensure that the terms of this EUA are made available to all relevant 

stakeholders (e.g., U.S. government agencies, state and local government authorities, 

registered or licensed blood establishments, hospitals, health care providers) involved 

in distributing or receiving authorized COVID-19 convalescent plasma. ASPR will 

provide to all relevant stakeholders a copy of this letter of authorization and 

communicate any subsequent amendments that might be made to this letter of 

authorization and its authorized accompanying materials (i.e., Fact Sheets).

B. ASPR may request changes to this authorization, including to the authorized Fact 

Sheets for COVID-19 convalescent plasma. Any request for changes to this EUA 

must be submitted to the Office of Blood Research and Review (OBRR)/CBER. Such

changes require appropriate authorization from FDA prior to implementation.11

C. ASPR will report to FDA serious adverse events and all medication errors associated 

with the use of the authorized COVID-19 convalescent plasma that are reported to 

ASPR, or of which ASPR otherwise becomes aware, during the pandemic. 

D. ASPR will make available to FDA upon request any records maintained in connection 

with this EUA.

Registered or Licensed Blood Establishments

E. Registered or licensed blood establishments will ensure that the authorized COVID-19 

convalescent plasma, accompanied with the authorized labeling (i.e., Fact Sheets), is 

distributed to hospitals consistent with the terms of this letter, and that such hospitals 

are aware of the letter of authorization.

F. Registered or licensed blood establishments will ensure that appropriate storage and 

cold chain is maintained.

11 The following types of revisions may be authorized without reissuing this letter: (1) changes to the authorized 

labeling; (2) non-substantive editorial corrections to this letter; (3) new types of authorized labeling, including new 

fact sheets; (4) new carton/container labels; (5) expiration dating extensions; (6) changes to manufacturing 

processes, including tests or other authorized components of manufacturing; (7) new conditions of authorization to 

require data collection or study. All changes to the authorization require review and concurrence from OBRR. For 

changes to the authorization, including the authorized labeling, of the type listed in (3), (6), or (7), review and 

concurrence is also required from the Preparedness and Response Team (PREP)/Office of the Center Director 

(OD)/CBER and the Office of Counterterrorism and Emerging Threats/Office of the Chief Scientist. 
Page 7 – Ms. O'Connell, ASPR

G. Through a process of inventory control, registered or licensed blood establishments

will maintain records regarding distribution of the authorized COVID-19 convalescent 

plasma (i.e., donor records, quantity, receiving site, receipt date).

H. Registered or licensed blood establishments will make available to FDA upon request 

any records maintained in connection with this EUA. 

Hospitals to Whom the Authorized COVID-19 Convalescent Plasma is Distributed, and 

Health Care Providers Administering the Authorized COVID-19 Convalescent Plasma

I. Hospitals and health care providers receiving authorized COVID-19 convalescent 

plasma will ensure that they are aware of the letter of authorization, and the terms 

herein, and that the authorized Fact Sheets are made available to health care providers 

and to patients and caregivers, respectively, through appropriate means. 

J. Healthcare facilities and healthcare providers will ensure that appropriate storage and 

cold chain is maintained until the product is administered consistent with the terms of 

this letter.

K. Hospitals and health care providers administering COVID-19 convalescent plasma

will track serious adverse events that are considered to be potentially attributable to 

COVID-19 convalescent plasma use and must report these to FDA in accordance with 

the Fact Sheet for Health Care Providers. Health care providers must maintain records 

and conduct a thorough investigation of adverse reactions after transfusion of 

convalescent plasma, and must report fatalities related to transfusion, as required 

under 21 CFR 606.170.

L. Through a process of inventory control, hospitals will maintain records regarding the 

administered authorized COVID-19 convalescent plasma (e.g., donation identification

number, quantity, receiving site, receipt date), product storage, and maintain patient 

information (e.g., patient name, age, disease manifestation, number of doses 

administered per patient, other drugs administered). 

M. Hospitals will ensure that any records associated with this EUA are maintained until 

notified by ASPR and/or FDA. Such records will be made available to ASPR, HHS, 

and FDA for inspection upon request. 

Conditions Related to Printed Matter, Advertising, and Promotion 

N. All descriptive printed matter, advertising, and promotional materials relating to the 

use of the authorized COVID-19 convalescent plasma shall be consistent with the 

authorized labeling, as well as the terms set forth in this EUA, and meet the 

requirements set forth in Section 502(a) and (n) of the Act and FDA implementing 

regulations. 
Page 8 – Ms. O'Connell, ASPR

O. No descriptive printed matter, advertising, or promotional material relating to the use 

of COVID-19 convalescent plasma may represent or suggest that such product is safe 

or effective. 

P. All descriptive printed matter, advertising, and promotional materials relating to the 

use of COVID-19 convalescent plasma clearly and conspicuously shall state that: 

• COVID-19 convalescent plasma has not been approved or licensed by FDA but

has been authorized for emergency use by FDA under an EUA for the treatment 

of COVID-19 in patients with immunosuppressive disease or receiving 

immunosuppressive treatment; and

• The emergency use of COVID-19 convalescent plasma is only authorized for the 

duration of the declaration that circumstances exist justifying the authorization of 

the emergency use of drugs and biological products during the COVID-19

pandemic under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless 

the declaration is terminated, or authorization revoked sooner. 

IV. Duration of Authorization 

This EUA will be effective until the declaration that circumstances exist justifying the 

authorization of the emergency use of drugs and biological products during the COVID-19 

pandemic is terminated under Section 564(b)(2) of the Act or the EUA is revoked under Section 

564(g) of the Act. 

Sincerely,

--/S/--

Jacqueline A. O'Shaughnessy, Ph.D.

Acting Chief Scientist 

Food and Drug Administration 

Enclosures
Page 91 – Ms. O'Connell,

Appendix A: Table of Tests Acceptable for Use in the Manufacture of COVID-19 Convalescent

Plasma with High Titers of Anti-SARS-CoV-2 Antibodies

Tests Acceptable for Use in the Manufacture of 

COVID-19 Convalescent Plasma with High Titers of Anti-SARS-CoV-2 Antibodies

Manufacturer

(listed 

alphabetically)

Assay Qualifying 

Result

Date of Listing 

under this EUA

Abbott AdviseDx SARSCoV-2 IgG II

(ARCHITECT and Alinity i) ≥ 1280 AU/mL December 28, 2021

Diasorin LIAISON SARS-CoV-2 

TrimericS IgG ≥ 87 AU/mL December 28, 2021

EUROIMMUN Anti-SARS-CoV-2 S1 Curve ELISA 

(IgG) >55 RU/mL February 9, 2022

GenScript cPass SARS-CoV-2 Neutralization 

Antibody Detection Kit Inhibition ≥ 80%

December 28, 

2021

Kantaro

COVID-SeroKlir, Kantaro SemiQuantitative SARS-CoV-2 IgG 

Antibody Kit

Spike ELISA 

> 69 AU/mL

December 28, 

2021

Ortho VITROS Anti-SARS-CoV-2 IgG 

Quantitative Reagent Pack >200 BAU/mL

December 28, 

2021

Roche Elecsys Anti-SARS-CoV-2 S > 210 U/mL

December 28, 

2021