The U.S. Blood Supply and the COVID-19 Response: In Brief

Changes from May 28, 2020 to August 26, 2020

This page shows textual changes in the document between the two versions indicated in the dates above. Textual matter removed in the later version is indicated with ~~red strikethrough~~ and textual matter added in the later version is indicated with blue.

The U.S. Blood Supply and the COVID-19
~~May 28~~August 26, 2020 , 2020
Response: In Brief
Jared S. Sussman
The nation’s blood supply is largely managed by a network of independent blood centers and the The nation’s blood supply is largely managed by a network of independent blood centers and the
Analyst in Health Policy Analyst in Health Policy
American Red Cross, with some oversight from the Department of Health and Human Services American Red Cross, with some oversight from the Department of Health and Human Services

(HHS) and the Food and Drug Administration (FDA). These private organizations collect blood (HHS) and the Food and Drug Administration (FDA). These private organizations collect blood
Agata Dabrowska
product donations (e.g., whole blood, plasma, and platelets) from individual volunteers through product donations (e.g., whole blood, plasma, and platelets) from individual volunteers through
Analyst in Health Policy Analyst in Health Policy
scheduled appointments, walk-in appointments, and blood drives. Independent blood centers and scheduled appointments, walk-in appointments, and blood drives. Independent blood centers and

the American Red Cross each collect nearly half of blood products nationwide, with the the American Red Cross each collect nearly half of blood products nationwide, with the
remainder collected in hospital settings. remainder collected in hospital settings.

The response to the Coronavirus Disease 2019 (COVID-19) pandemic has posed significant challenges for maintenance of The response to the Coronavirus Disease 2019 (COVID-19) pandemic has posed significant challenges for maintenance of
the U.S. blood supply. Mitigation strategies to prevent the spread of COVID-19, such as closures of schools and workplaces, the U.S. blood supply. Mitigation strategies to prevent the spread of COVID-19, such as closures of schools and workplaces,
have led to blood drive cancellations at the places where such events are often held. In addition to blood drive cancellations, have led to blood drive cancellations at the places where such events are often held. In addition to blood drive cancellations,
individual state stay-at-home orders and general fear of contracting the COVID-19 virus might dissuade individuals from individual state stay-at-home orders and general fear of contracting the COVID-19 virus might dissuade individuals from
scheduling appointments to donate blood. scheduling appointments to donate blood.
Both FDA and Congress have taken action to address some of these issues. For example, FDA—the agency that regulates the Both FDA and Congress have taken action to address some of these issues. For example, FDA—the agency that regulates the
blood supply and blood products—issued guidance in April 2020 to broaden the pool of eligible blood donors and create blood supply and blood products—issued guidance in April 2020 to broaden the pool of eligible blood donors and create
alternative procedures for blood establishments during the COVID-19 pandemic. In addition, the Coronavirus Aid, Relief, alternative procedures for blood establishments during the COVID-19 pandemic. In addition, the Coronavirus Aid, Relief,
and Economic Security Act (CARES Act; P.L. 116-136), enacted on March 27, 2020, included a provision requiring the and Economic Security Act (CARES Act; P.L. 116-136), enacted on March 27, 2020, included a provision requiring the
Secretary of HHS to create a nationwide awareness campaign regarding the importance of donations to maintain the blood Secretary of HHS to create a nationwide awareness campaign regarding the importance of donations to maintain the blood
supply. supply.
Various drugs and biologics, including blood-derived therapies, are under investigation for treating and preventing COVID- Various drugs and biologics, including blood-derived therapies, are under investigation for treating and preventing COVID-
19. FDA has issued treatment and research guidance regarding two blood-derived treatments: convalescent plasma and 19. FDA has issued treatment and research guidance regarding two blood-derived treatments: convalescent plasma and
hyperimmune globulin. However, data regarding the safety and effectiveness of such treatments are still being generated. hyperimmune globulin. However, data regarding the safety and effectiveness of such treatments are still being generated.
~~Given the therapeutic potential of blood-derived therapies, and as part of its efforts to respond to the COVID-19 pandemic,~~
In the absence of any approved drugs or biologics for COVID-19, FDA has used its existing authorities to increase access to unapproved products through mechanisms such as expanded access and emergency use authorization (EUA). On August 23, 2020, FDA issued an EUA for COVID-19 Convalescent Plasma (CCP)—blood plasma that is collected from an individual who has recovered (i.e., “convalesced”) from COVID-19 and is then administered to a patient actively sick with COVID-19 for treatment. Some concern has been raised regarding FDA’s issuance of an EUA for CCP in the absence of evidence from randomized controlled trials (RCTs), which are the gold standard for evaluating the effectiveness of therapies. It is not clear the extent to which an EUA will increase access to convalescent plasma, as its availability is limited by donations. If patients are more readily able to access CCP through the EUA, participation in clinical trials may be hindered, making it more difficult to generate data regarding the effectiveness of convalescent plasma for COVID-19. Given the therapeutic potential of blood-derived therapies and that availability is limited based on donations, Congress may wish to consider further action regarding the maintenance of the U.S. blood supplyCongress may wish to consider further action regarding the maintenance of the U.S. blood supply as part of its efforts to respond to the COVID-19 pandemic. .
Congressional Research Service Congressional Research Service

The U.S. Blood Supply and the COVID-19 Response

Introduction
The nation’s blood supply is largely managed by a network of independent blood centers and the The nation’s blood supply is largely managed by a network of independent blood centers and the
American Red Cross, with some oversight from the Department of Health and Human Services American Red Cross, with some oversight from the Department of Health and Human Services
(HHS) and the Food and Drug Administration (FDA), an agency within HHS.1 These (HHS) and the Food and Drug Administration (FDA), an agency within HHS.1 These
organizations collect donated blood and its components (e.g., plasma, red blood cells, and organizations collect donated blood and its components (e.g., plasma, red blood cells, and
platelets) from individuals through scheduled appointments, walk-in appointments, and blood platelets) from individuals through scheduled appointments, walk-in appointments, and blood
drives. Independent blood centers and the American Red Cross each collect nearly half of blood drives. Independent blood centers and the American Red Cross each collect nearly half of blood
products nationwide, and the remainder is collected in hospital settings.2 Because blood products products nationwide, and the remainder is collected in hospital settings.2 Because blood products
have a limited shelf-life, ongoing donations are necessary.3 have a limited shelf-life, ongoing donations are necessary.3
Blood is used for transfusions—one of the most common medical procedures in which healthy Blood is used for transfusions—one of the most common medical procedures in which healthy
blood is given to an individual.4 Transfusions are generally considered safe. However, there is a blood is given to an individual.4 Transfusions are generally considered safe. However, there is a
small risk of complications. Certain infectious diseases can be transmitted through contact with small risk of complications. Certain infectious diseases can be transmitted through contact with
an infected individual’s blood, which is mitigated through FDA guidance and implementation of an infected individual’s blood, which is mitigated through FDA guidance and implementation of
safety protocols by blood establishments, such as deferral requirements for certain potential blood safety protocols by blood establishments, such as deferral requirements for certain potential blood
donors who may be at higher risk of transmitting an infectious disease. donors who may be at higher risk of transmitting an infectious disease.
In addition to its use in transfusions, blood and blood components can also be used in the In addition to its use in transfusions, blood and blood components can also be used in the
manufacture of blood-derived pharmaceutical products. The manufacture of blood products is manufacture of blood-derived pharmaceutical products. The manufacture of blood products is
also regulated by FDA. also regulated by FDA.
The response to the COVID-19 pandemic has posed significant challenges for the U.S. blood The response to the COVID-19 pandemic has posed significant challenges for the U.S. blood
supply. Mitigation strategies to prevent the spread of COVID-19, such as closures of schools and supply. Mitigation strategies to prevent the spread of COVID-19, such as closures of schools and
workplaces, have led to blood drive cancellations. In addition to blood drive cancellations, workplaces, have led to blood drive cancellations. In addition to blood drive cancellations,
individual state stay-at-home orders and general fear of contracting the COVID-19 virus might individual state stay-at-home orders and general fear of contracting the COVID-19 virus might
dissuade individuals from scheduling appointments to donate blood. dissuade individuals from scheduling appointments to donate blood.
This issue first emerged in early March 2020, when a critical blood supply shortage was This issue first emerged in early March 2020, when a critical blood supply shortage was
identified in the Pacific Northwest as Washington State was responding to localized COVID-19 identified in the Pacific Northwest as Washington State was responding to localized COVID-19
outbreaks.5 Around that same time, other blood establishments across the country began to issue outbreaks.5 Around that same time, other blood establishments across the country began to issue
press releases indicating an urgent need for donated blood.6 Some evidence showed that a large press releases indicating an urgent need for donated blood.6 Some evidence showed that a large

1 For more information on independent blood centers, see https://americasblood.org/about/. For more information on 1 For more information on independent blood centers, see https://americasblood.org/about/. For more information on
the American Red Cross, see https://www.redcross.org/give-blood.html. the American Red Cross, see https://www.redcross.org/give-blood.html.
2 FDA Center for Biologics Evaluation and Research, Office of Blood Research and Review, “FDA Regulation of 2 FDA Center for Biologics Evaluation and Research, Office of Blood Research and Review, “FDA Regulation of
Blood and Blood Components in the United States,” seminar, August 20, 2019, p. Slide 15, http://fda.yorkcast.com/Blood and Blood Components in the United States,” seminar, August 20, 2019, p. Slide 15, http://fda.yorkcast.com/
webcast/Play/7febcdc6189646e5b6f1a18e392815fb1d. webcast/Play/7febcdc6189646e5b6f1a18e392815fb1d.
3 Whole blood expires 21-35 days from donation. The shelf-life of other blood products ranges in length from five days 3 Whole blood expires 21-35 days from donation. The shelf-life of other blood products ranges in length from five days
(platelets) to one year (plasma); see https://www.redcrossblood.org/donate-blood/how-to-donate/types-of-blood-(platelets) to one year (plasma); see https://www.redcrossblood.org/donate-blood/how-to-donate/types-of-blood-
donations/blood-components.html. donations/blood-components.html.
4 https://www.nhlbi.nih.gov/health-topics/blood-transfusion. 4 https://www.nhlbi.nih.gov/health-topics/blood-transfusion.
5 On March 9, 2020, one blood center, Bloodworks Northwest, headquartered in Seattle, WA, issued a press release 5 On March 9, 2020, one blood center, Bloodworks Northwest, headquartered in Seattle, WA, issued a press release
warning that the Pacific Northwest blood supply was at the risk of collapse in coming days due to COVID-19 concerns. warning that the Pacific Northwest blood supply was at the risk of collapse in coming days due to COVID-19 concerns.
The release notes that the closure of schools, businesses, and events had led to the cancellation of blood drives in the The release notes that the closure of schools, businesses, and events had led to the cancellation of blood drives in the
area. For the press release, see https://www.bloodworksnw.org/wp-content/uploads/2020/03/coronavirus-press-release-area. For the press release, see https://www.bloodworksnw.org/wp-content/uploads/2020/03/coronavirus-press-release-
march-9-2020.pdf. march-9-2020.pdf.
6 In early March, blood establishments were acting independently to issue press releases raising concern and calling for 6 In early March, blood establishments were acting independently to issue press releases raising concern and calling for
individuals to donate. For an example, see New York Blood Center’s March 4, 2020, press release: individuals to donate. For an example, see New York Blood Center’s March 4, 2020, press release:
https://nybloodcenter.org/news/articles/new-york-blood-center-announces-urgent-need-blood-and-platelet-donors-https://nybloodcenter.org/news/articles/new-york-blood-center-announces-urgent-need-blood-and-platelet-donors-
fears-coronavirus-keep-healthy-donors-away/. fears-coronavirus-keep-healthy-donors-away/.
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link to page 7 link to page 7 ~~link to page 7~~ The U.S. Blood Supply and the COVID-19 Response

percentage of blood establishments were facing critical shortages, which typically means that the percentage of blood establishments were facing critical shortages, which typically means that the
establishment has a day or less of supply.7 establishment has a day or less of supply.7
~~Recently~~Following the initial blood supply shortage, far fewer blood establishments , far fewer blood establishments ~~have reported~~were reporting critical or low supplies,8 and this critical or low supplies,8 and this is
was attributed to outreach efforts and the ability to share blood and blood components through a attributed to outreach efforts and the ability to share blood and blood components through a
national resource-sharing program, the National Blood Exchange (NBE).9 (See the national resource-sharing program, the National Blood Exchange (NBE).9 (See the “Oversight of
the U.S. Blood Supply” section below for information on the NBE.) In addition, widespread section below for information on the NBE.) In addition, widespread
deferral of elective and non-emergent medical procedures during the initial response to COVID-deferral of elective and non-emergent medical procedures during the initial response to COVID-
19 decreased the demand for transfusions.1019 decreased the demand for transfusions.10 ~~Blood supplies may be strained, as those medical~~
~~procedures resume.~~
In May 2020, as elective and nonemergent medical procedures resumed, blood centers reported inventories falling to their lowest levels since the early stages of the pandemic. This shortage prompted industry groups to issue a joint statement urging individuals to donate.11 More recently, industry groups have issued statements regarding an ongoing critical need for COVID-19 convalescent plasma donors, in particular.12 FDA issued guidance relaxing restrictions on blood donation, which did not mitigate the FDA issued guidance relaxing restrictions on blood donation, which did not mitigate the
immediate need for blood in March 2020, but may have the effect of increasing the donor pool for immediate need for blood in March 2020, but may have the effect of increasing the donor pool for
supply shortages in the future as the country continues to respond to the COVID-19 pandemic. supply shortages in the future as the country continues to respond to the COVID-19 pandemic.
Now, the industry is implementing recommended changes to expand the size of the donor pool Now, the industry is implementing recommended changes to expand the size of the donor pool
and creating blood banks of donations from donors who may have already contracted and and creating blood banks of donations from donors who may have already contracted and
recovered from COVID-19, whose blood may be used for a potential treatment. recovered from COVID-19, whose blood may be used for a potential treatment.
This report provides a brief background of the regulatory framework for the U.S. blood supply, This report provides a brief background of the regulatory framework for the U.S. blood supply,
explains the federal response to the current crisis, and discusses potential treatment of COVID-19 explains the federal response to the current crisis, and discusses potential treatment of COVID-19
using blood-derived products. using blood-derived products.
Regulation and Oversight of U.S. Blood Supply
The U.S. blood supply is largely regulated by FDA, which includes, among other things, The U.S. blood supply is largely regulated by FDA, which includes, among other things,
oversight through licensing of organizations and products. Oversight regarding emergency oversight through licensing of organizations and products. Oversight regarding emergency
response preparedness and the monitoring of local and national blood supply is a collaborative response preparedness and the monitoring of local and national blood supply is a collaborative
~~effort between HHS and industry groups, which includes professional organizations representing~~
~~blood establishments.11~~
~~FDA Regulation of the Blood Supply~~
~~FDA oversees the collection of blood and its components (e.g., plasma, red blood cells, and~~
~~platelets) intended for transfusion or for the manufacture of pharmaceutical products. FDA~~
~~regulates blood and blood products (“blood products”) as biologics under two statutes: the~~

7 America’s Blood Centers, a network of non-Red Cross blood centers representing about half of the nation’s blood 7 America’s Blood Centers, a network of non-Red Cross blood centers representing about half of the nation’s blood
supply, maintains a stoplight report with publicly available real-time data on regional blood supply availability. On any supply, maintains a stoplight report with publicly available real-time data on regional blood supply availability. On any
day in the first two weeks of March 2020, the stoplight report shows that at least 40% of blood centers had a critical or day in the first two weeks of March 2020, the stoplight report shows that at least 40% of blood centers had a critical or
low supply of blood; see https://americasblood.org/for-donors/americas-blood-supply/. low supply of blood; see https://americasblood.org/for-donors/americas-blood-supply/.
8 The America’s Blood Centers stoplight report shows that, as of May 6, 2020, a far lower percentage of blood centers 8 The America’s Blood Centers stoplight report shows that, as of May 6, 2020, a far lower percentage of blood centers
were experiencing shortages of blood. In addition, as of that date, industry groups had not issued urgent calls for blood were experiencing shortages of blood. In addition, as of that date, industry groups had not issued urgent calls for blood
donations in several weeks. donations in several weeks.
9 Monica B. Pagano, John R. Hess, and Hamilton C. Tsang, et al., “The blood supply management amid the COVID-19 9 Monica B. Pagano, John R. Hess, and Hamilton C. Tsang, et al., “The blood supply management amid the COVID-19
outbreak,” outbreak,” Transfusion, vol. 60, no. 5 (March 21, 2020), pp. 908-911. , vol. 60, no. 5 (March 21, 2020), pp. 908-911.
~~10 Ibid.~~
~~11 21 C.F.R. §607.3. The term establishment refers to “a place of business under one management at one general~~
~~physical location and includes, among others, human blood and plasma donor centers, blood banks, transfusion~~
~~services, other blood product manufacturers and independent laboratories that engage in quality control and testing for~~
~~registered blood product establishments.”~~
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~~Federal Food, Drug and Cosmetic Act (FFDCA) and the Public Health Service Act (PHSA).12~~10 Ibid. 11 AABB, America's Blood Centers, and American Red Cross, “Joint Statement on the Blood Supply,” press release, May 28, 2020, https://mk0americasbloogf2jd.kinstacdn.com/wp-content/uploads/2020/05/Joint-Statement-on-Blood-Supply.pdf. 12 America’s Blood Centers, “ABC Statement on Ongoing Critical Need for COVID-19 Convalescent Plasma Donors,” press release, August 21, 2020, https://americasblood.org/news/abc-statement-on-ongoing-critical-need-for-covid-19-convalescent-plasma-donors/. Congressional Research Service 2 link to page 14 link to page 14 link to page 14 link to page 14 The U.S. Blood Supply and the COVID-19 Response effort between HHS and industry groups, which includes professional organizations representing blood establishments.13 FDA Regulation of the Blood Supply FDA oversees the collection of blood and its components (e.g., plasma, red blood cells, and platelets) intended for transfusion or for the manufacture of pharmaceutical products. FDA regulates blood and blood products (“blood products”) as biologics under two statutes: the Federal Food, Drug and Cosmetic Act (FFDCA) and the Public Health Service Act (PHSA).14
The FDA Center for Biologics Evaluation and Research (CBER) Office of Blood Research and The FDA Center for Biologics Evaluation and Research (CBER) Office of Blood Research and
Review (OBRR) establishes regulatory policies and standards; reviews regulatory applications Review (OBRR) establishes regulatory policies and standards; reviews regulatory applications
and grants licenses for blood products; performs mission-related research; and conducts and grants licenses for blood products; performs mission-related research; and conducts
emergency preparedness and outreach.emergency preparedness and outreach.1315
Establishments that manufacture blood products must register with FDA and are subject to Establishments that manufacture blood products must register with FDA and are subject to
inspection by the agency.inspection by the agency.1416 Certain establishments—those manufacturing blood-derived Certain establishments—those manufacturing blood-derived
pharmaceutical products or intending to ship blood products across state lines—also must be pharmaceutical products or intending to ship blood products across state lines—also must be
licensed by FDA under a biologics license application (BLA).licensed by FDA under a biologics license application (BLA).1517 For example, the American Red For example, the American Red
Cross and other blood centers are licensed for blood collection because they supply blood Cross and other blood centers are licensed for blood collection because they supply blood
products to multiple hospitals, often across state lines.products to multiple hospitals, often across state lines.1618 In contrast, hospitals typically do not ship In contrast, hospitals typically do not ship
blood products across state lines and thus do not require a license, although they must register blood products across state lines and thus do not require a license, although they must register
with FDA for blood collection. with FDA for blood collection.
Blood establishments must comply with FDA regulations governing blood collection, storage, Blood establishments must comply with FDA regulations governing blood collection, storage,
testing, and processing, among other things. FDA regulations also describe eligibility criteria to testing, and processing, among other things. FDA regulations also describe eligibility criteria to
donate blood that both protect the health of the donor and ensure the safety, purity, and potency of donate blood that both protect the health of the donor and ensure the safety, purity, and potency of
the blood product.the blood product.1719 Current FDA guidance recognizes an industry-prepared standardized donor Current FDA guidance recognizes an industry-prepared standardized donor
~~history questionnaire as an acceptable mechanism for determining eligibility.18 The donor history~~
~~questionnaire incorporates all FDA guidance and regulations pertaining to donor eligibility.19~~
~~FDA often issues guidance documents that recommend how to comply with statutes and~~
~~regulations in general, as well as in specific scenarios, such as when there is stress on the blood~~

12 13 21 C.F.R. §607.3. The term establishment refers to “a place of business under one management at one general physical location and includes, among others, human blood and plasma donor centers, blood banks, transfusion services, other blood product manufacturers and independent laboratories that engage in quality control and testing for registered blood product establishments.” 14 42 U.S.C. §262, §264 and 21 U.S.C. §§301 et seq. FDA regulations pertaining to blood products are set forth at 21 42 U.S.C. §262, §264 and 21 U.S.C. §§301 et seq. FDA regulations pertaining to blood products are set forth at 21
C.F.R. Parts 600 (Biological products; general); 601 (Licensing); 606 (Current good manufacturing practice for blood C.F.R. Parts 600 (Biological products; general); 601 (Licensing); 606 (Current good manufacturing practice for blood
and blood components); 607 (Establishment registration and product listing for manufacturers of human blood and and blood components); 607 (Establishment registration and product listing for manufacturers of human blood and
blood products and licensed devices); 610 (General biological products standards); 630 (Requirements for blood and blood products and licensed devices); 610 (General biological products standards); 630 (Requirements for blood and
blood components intended for transfusion or for further manufacturing use); and 640 (Additional standards for human blood components intended for transfusion or for further manufacturing use); and 640 (Additional standards for human
blood and blood products). The regulation of blood products is described in further detail in the blood and blood products). The regulation of blood products is described in further detail in the “FDA Regulation of
Biologics” section of this report. section of this report.
1315 For CBER product jurisdiction by office, see FDA, “CBER Product Jurisdiction,” March 26, 2018, For CBER product jurisdiction by office, see FDA, “CBER Product Jurisdiction,” March 26, 2018,
https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/cber-product-jurisdiction. For more https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/cber-product-jurisdiction. For more
information on FDA regulation of biologics and drugs, see CRS In Focus IF11083, information on FDA regulation of biologics and drugs, see CRS In Focus IF11083, Medical Product Regulation:
Drugs, Biologics, and Devices. .
1416 21 C.F.R. §607.3. The term 21 C.F.R. §607.3. The term manufacture refers to “the collection, preparation, processing or compatibility testing by refers to “the collection, preparation, processing or compatibility testing by
chemical, physical, biological, or other procedures of any blood product which meets the [FFDCA] definition of a chemical, physical, biological, or other procedures of any blood product which meets the [FFDCA] definition of a
drug.” drug.”
1517 42 U.S.C. §262. FDA, “FDA Regulation of Blood and Blood Components in the United States,” 42 U.S.C. §262. FDA, “FDA Regulation of Blood and Blood Components in the United States,”
https://www.fda.gov/media/81654/download. Biologics licensure is described in further detail in the https://www.fda.gov/media/81654/download. Biologics licensure is described in further detail in the “FDA Regulation
of Biologics” section of this report. section of this report.
1618 For additional information, see “FDA Regulation of Blood and Blood Components in the United States” at For additional information, see “FDA Regulation of Blood and Blood Components in the United States” at
https://www.fda.gov/media/81654/download. https://www.fda.gov/media/81654/download.
1719 21 C.F.R. §630.10(a). Congressional Research Service 3 The U.S. Blood Supply and the COVID-19 Response history questionnaire as an acceptable mechanism for determining eligibility.20 The donor history questionnaire incorporates all FDA guidance and regulations pertaining to donor eligibility.21 FDA often issues guidance documents that recommend how to comply with statutes and regulations in general, as well as in specific scenarios, such as when there is stress on the blood supply due to the COVID-19 response.22 These guidance documents are not legally binding.23 ~~21 C.F.R. §630.10(a).~~
~~18 FDA, “Implementation of Acceptable Full-Length and Abbreviated Donor History Questionnaires and~~
~~Accompanying Materials for Use in Screening Donors of Blood and Blood Components,” May 15, 2015,~~
~~https://www.fda.gov/media/124193/download.~~
~~19 The donor history questionnaire is available at http://www.aabb.org/tm/questionnaires/Documents/dhq/v2/~~
~~DHQ%20v2.0.pdf.~~
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~~The U.S. Blood Supply and the COVID-19 Response~~

~~supply due to the COVID-19 response.20 These guidance documents are not legally binding.21~~
However, blood establishments use FDA guidance to create standard operating procedures. However, blood establishments use FDA guidance to create standard operating procedures.
Oversight of the U.S. Blood Supply
Coordination of blood availability and emergency preparedness is a collaborative effort between Coordination of blood availability and emergency preparedness is a collaborative effort between
many stakeholders, with input from HHS, FDA, and other federal entities, as well as from many stakeholders, with input from HHS, FDA, and other federal entities, as well as from
nonfederal partners. The HHS Office of Infectious Disease and HIV/AIDS Policy (OIDP) nonfederal partners. The HHS Office of Infectious Disease and HIV/AIDS Policy (OIDP)
supports the coordination of blood safety and emergency preparedness and response activities. supports the coordination of blood safety and emergency preparedness and response activities.
OIDP staff serve as liaisons on a number of councils, task forces, advisory committees, and OIDP staff serve as liaisons on a number of councils, task forces, advisory committees, and
programs.programs.2224
Of particular interest for the COVID-19 pandemic response is the Inter-organizational Task Force Of particular interest for the COVID-19 pandemic response is the Inter-organizational Task Force
on Domestic Disasters and Acts of Terrorism (the task force), which is led by the American on Domestic Disasters and Acts of Terrorism (the task force), which is led by the American
Association of Blood Banks (AABB).Association of Blood Banks (AABB).2325 When an event affects the local blood supply (e.g., When an event affects the local blood supply (e.g.,
disaster, terrorism), the affected blood center contacts AABB. After this initial contact, AABB disaster, terrorism), the affected blood center contacts AABB. After this initial contact, AABB
convenes a conference call with task force members, which typically results in issuance of convenes a conference call with task force members, which typically results in issuance of
coordinated recommendations and messages to the blood community, donors, and the public. coordinated recommendations and messages to the blood community, donors, and the public.
Concurrently, AABB assists the affected blood center(s) to increase the local blood supply Concurrently, AABB assists the affected blood center(s) to increase the local blood supply
through a resource-sharing program, the National Blood Exchange. NBE is the primary resource-through a resource-sharing program, the National Blood Exchange. NBE is the primary resource-
sharing program for blood centers in the United States.sharing program for blood centers in the United States.2426 NBE facilitates sharing of blood NBE facilitates sharing of blood
products, in general, and in response to an emergency. NBE can move blood from blood centers products, in general, and in response to an emergency. NBE can move blood from blood centers
with surpluses to those that cannot meet anticipated need. This program, administered by AABB, with surpluses to those that cannot meet anticipated need. This program, administered by AABB,
allows for the transfer of surplus blood products at any time of the day to areas in need. NBE allows for the transfer of surplus blood products at any time of the day to areas in need. NBE
monitors the blood supply across blood centers and across regions for potential shortages. monitors the blood supply across blood centers and across regions for potential shortages.
In general, HHS does not monitor in real time the U.S. blood supply. Licensed blood In general, HHS does not monitor in real time the U.S. blood supply. Licensed blood
establishments are required to report significant interruptions in manufacturing to FDA.establishments are required to report significant interruptions in manufacturing to FDA.25
~~However, real time monitoring is only available through the NBE system and only registered~~
~~AABB members can access information on blood supply availability through NBE.~~
~~Industry and Federal Response to COVID-19~~
~~FDA, HHS, and the blood industry have responded to a potential critical shortage of blood due to~~
~~the COVID-19 pandemic. In addition, Congress included a provision in the Coronavirus Aid,~~
~~Relief, and Economic Security Act (CARES Act; P.L. 116-136), enacted on March 27, 2020 that~~

2027 20 FDA, “Implementation of Acceptable Full-Length and Abbreviated Donor History Questionnaires and Accompanying Materials for Use in Screening Donors of Blood and Blood Components,” May 15, 2015, https://www.fda.gov/media/124193/download. 21 The donor history questionnaire is available at http://www.aabb.org/tm/questionnaires/Documents/dhq/v2/DHQ%20v2.0.pdf. 22 21 C.F.R. §10.115. For FDA blood guidance, see https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/ 21 C.F.R. §10.115. For FDA blood guidance, see https://www.fda.gov/vaccines-blood-biologics/biologics-guidances/
blood-guidances. blood-guidances.
2123 21 C.F.R. §10.115(d). 21 C.F.R. §10.115(d).
2224 OIDP maintain a list of its roles and responsibilities for the various entities; see https://www.hhs.gov/oidp/topics/ OIDP maintain a list of its roles and responsibilities for the various entities; see https://www.hhs.gov/oidp/topics/
blood-tissue-safety/roles/index.html. blood-tissue-safety/roles/index.html.
2325 Membership on the task force includes federal agencies (HHS, FDA, and CDC) and nonfederal entities such as the Membership on the task force includes federal agencies (HHS, FDA, and CDC) and nonfederal entities such as the
AABB and the American Red Cross. For more information, see http://www.aabb.org/programs/disasterresponse/Pages/AABB and the American Red Cross. For more information, see http://www.aabb.org/programs/disasterresponse/Pages/
default.aspx#1. default.aspx#1.
2426 For more information on the NBE, see NBE, “System at Work,” http://www.aabb.org/programs/nbe/Pages/ For more information on the NBE, see NBE, “System at Work,” http://www.aabb.org/programs/nbe/Pages/
default.aspx#2. default.aspx#2.
2527 21 C.F.R. §600.82 21 C.F.R. §600.82
Congressional Research Service Congressional Research Service
4 4

The U.S. Blood Supply and the COVID-19 Response

However, real time monitoring is only available through the NBE system and only registered AABB members can access information on blood supply availability through NBE. Industry and Federal Response to COVID-19 FDA, HHS, and the blood industry have responded to a potential critical shortage of blood due to the COVID-19 pandemic. In addition, Congress included a provision in the Coronavirus Aid, Relief, and Economic Security Act (CARES Act; P.L. 116-136), enacted on March 27, 2020 that directed the Secretary of HHS to carry out a national awareness campaign regarding the nation’s directed the Secretary of HHS to carry out a national awareness campaign regarding the nation’s
blood supply. blood supply.
FDA first issued information for blood establishments on February 4, 2020, including FDA first issued information for blood establishments on February 4, 2020, including
considerations for altering blood donation practices in response to COVID-19.considerations for altering blood donation practices in response to COVID-19.2628 This information This information
was updated on March 11, 2020, and again on May 11, 2020.was updated on March 11, 2020, and again on May 11, 2020.2729
The May 11 release suggests that some blood establishments may want to consider donor The May 11 release suggests that some blood establishments may want to consider donor
education, encourage self-deferral, and manage post-donation information about COVID-19. The education, encourage self-deferral, and manage post-donation information about COVID-19. The
May 11 release recommends that individuals self-defer from donating blood for 14 days after May 11 release recommends that individuals self-defer from donating blood for 14 days after
either (1) resolution of symptoms after a diagnosis of COVID-19 or (2) the last positive either (1) resolution of symptoms after a diagnosis of COVID-19 or (2) the last positive
diagnostic test if no symptoms developed. Donors are also directed to report a subsequent diagnostic test if no symptoms developed. Donors are also directed to report a subsequent
diagnosis after donation. The May 11 release does not recommend using laboratory tests to screen diagnosis after donation. The May 11 release does not recommend using laboratory tests to screen
asymptomatic donors or deferral for recent travel to specific areas with COVID-19 cases.asymptomatic donors or deferral for recent travel to specific areas with COVID-19 cases.2830
Historically, FDA has recommended donor deferrals that vary from short periods of time after a Historically, FDA has recommended donor deferrals that vary from short periods of time after a
specific event to indefinite, lifetime deferrals for individuals that are at risk of transmitting specific event to indefinite, lifetime deferrals for individuals that are at risk of transmitting
infectious diseases. infectious diseases.
To date, there is no reported transfusion-transmitted case of COVID-19. To date, there is no reported transfusion-transmitted case of COVID-19.2931 However, there exists a However, there exists a
theoretical risk of transmission through blood transfusion, and there are still many unknowns theoretical risk of transmission through blood transfusion, and there are still many unknowns
regarding the virus that causes COVID-19.regarding the virus that causes COVID-19.3032 Transmission primarily occurs through respiratory Transmission primarily occurs through respiratory
body fluids, but the virus that causes COVID-19 has been detected in blood samples from body fluids, but the virus that causes COVID-19 has been detected in blood samples from
infected individuals, thereby raising questions about the possibility of transmission through blood infected individuals, thereby raising questions about the possibility of transmission through blood
transfusion from blood collected from an infected donor.transfusion from blood collected from an infected donor.3133 The potential of transmission through The potential of transmission through
blood transfusion, although theoretical, necessitates some precautionary measures. blood transfusion, although theoretical, necessitates some precautionary measures.
Blood centers and the American Red Cross issued specific guidance to potential blood donors Blood centers and the American Red Cross issued specific guidance to potential blood donors
regarding COVID-19, which was largely based on the FDA notices. Organizations representingregarding COVID-19, which was largely based on the FDA notices. Organizations representing
~~the industry also issued press releases calling for individuals to schedule appointments for~~
~~donation and reassuring them about the safety of donating blood.32~~
~~The task force urged blood centers to contact state and local emergency management and public~~
~~health agencies to request inclusion in emergency planning and response activities.33 The task~~
~~force recommended that blood centers share draft letters from HHS and the Federal Emergency~~
~~Management Agency (FEMA) that highlight the importance of working with the blood centers~~
~~during an emergency response.34 The HHS letter was drafted prior to the COVID-19 pandemic.~~

26 28 FDA, “Important Information for Blood Establishments Regarding the Novel Coronavirus Outbreak,” press release, FDA, “Important Information for Blood Establishments Regarding the Novel Coronavirus Outbreak,” press release,
February 4, 2020, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-information-February 4, 2020, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/important-information-
blood-establishments-regarding-novel-coronavirus-outbreak. blood-establishments-regarding-novel-coronavirus-outbreak.
2729 FDA, “Updated Information for Blood Establishments Regarding the Novel Coronavirus Outbreak,” press release, FDA, “Updated Information for Blood Establishments Regarding the Novel Coronavirus Outbreak,” press release,
May 11, 2020, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/updated-information-blood-May 11, 2020, https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/updated-information-blood-
establishments-regarding-novel-coronavirus-covid-19-outbreak. establishments-regarding-novel-coronavirus-covid-19-outbreak.
2830 Ibid. Ibid.
2931 Ibid. Ibid.
3032 Le Chang, Ying Yan, and Lunan Wang, “Coronavirus Disease 2019: Coronaviruses and Blood Safety,” Le Chang, Ying Yan, and Lunan Wang, “Coronavirus Disease 2019: Coronaviruses and Blood Safety,” Transfusion
Medicine Reviews, [Epub ahead of print] February 21, 2020. , [Epub ahead of print] February 21, 2020.
3133 Wenling Wang, Yanli Xu, and Ruqin Gao, et al., “Detection of SARS-CoV-2 in Different Types of Clinical Wenling Wang, Yanli Xu, and Ruqin Gao, et al., “Detection of SARS-CoV-2 in Different Types of Clinical
Specimens,” Specimens,” JAMA, vol. 323, no. 18 (March 11, 2020), pp. 1843-1844. , vol. 323, no. 18 (March 11, 2020), pp. 1843-1844.
~~32 For an example of a call to donate, see http://www.aabb.org/press/Pages/pr200312.aspx.~~
~~33 For more information, see http://www.aabb.org/programs/disasterresponse/Pages/default.aspx#4.~~
~~34 HHS, “Raising Priority Status of Blood with State/Local~~Congressional Research Service 5 The U.S. Blood Supply and the COVID-19 Response the industry also issued press releases calling for individuals to schedule appointments for donation and reassuring them about the safety of donating blood.34 The task force urged blood centers to contact state and local emergency management and public health agencies to request inclusion in emergency planning and response activities.35 The task force recommended that blood centers share draft letters from HHS and the Federal Emergency Emergency Management Agency (FEMA) that highlight the importance of working with the blood centers during an emergency response.36 The HHS letter was drafted prior to the COVID-19 pandemic. ~~Management Agencies,” April 10, 2019,~~
~~Congressional Research Service~~
5

~~The U.S. Blood Supply and the COVID-19 Response~~

The FEMA letter was published on March 19, 2020, to specifically address the COVID-19 The FEMA letter was published on March 19, 2020, to specifically address the COVID-19
response.response.3537
FDA Guidance to Address COVID-19-Related Supply Issues
FDA issued four guidance documents on April 2, 2020, to address COVID-19-related blood FDA issued four guidance documents on April 2, 2020, to address COVID-19-related blood
supply issues. This new guidance did not mitigate the immediate need for blood in March 2020, supply issues. This new guidance did not mitigate the immediate need for blood in March 2020,
but may increase the donor pool for supply shortages in the future as the country continues to but may increase the donor pool for supply shortages in the future as the country continues to
respond to the COVID-19 pandemic. One document creates alternative procedures for blood respond to the COVID-19 pandemic. One document creates alternative procedures for blood
collection, while the other three relax restrictions on donor eligibility intended to protect the collection, while the other three relax restrictions on donor eligibility intended to protect the
blood supply.blood supply.3638 FDA has traditionally issued guidance on reducing potential risks associated with FDA has traditionally issued guidance on reducing potential risks associated with
blood donations. The new guidance documents alter donor deferral recommendations for blood donations. The new guidance documents alter donor deferral recommendations for
potential donors regarding three areas of blood supply safety: potential donors regarding three areas of blood supply safety:
 Human Immunodeficiency Virus (HIV) transmission by blood and blood  Human Immunodeficiency Virus (HIV) transmission by blood and blood
products (HIV guidance); products (HIV guidance);3739
 transfusion-transmitted Malaria (Malaria guidance);  transfusion-transmitted Malaria (Malaria guidance);3840 and and
 transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob  transmission of Creutzfeldt-Jakob Disease (CJD) and Variant Creutzfeldt-Jakob
Disease by blood and blood components (CJD guidance). Disease by blood and blood components (CJD guidance).3941
These recommendations are intended to broaden the pool of potential donors while maintaining These recommendations are intended to broaden the pool of potential donors while maintaining
the safety of the blood supply. the safety of the blood supply.
The FDA guidance documents are expected to remain in effect for the duration of the public The FDA guidance documents are expected to remain in effect for the duration of the public
health emergency.health emergency.4042 Unlike the typical process for issuing new guidance, these guidance 34 For an example of a call to donate, see http://www.aabb.org/press/Pages/pr200312.aspx. 35 For more information, see http://www.aabb.org/programs/disasterresponse/Pages/default.aspx#4. 36 HHS, “Raising Priority Status of Blood with State/Local Emergency Management Agencies,” April 10, 2019, http://www.aabb.org/programs/disasterresponse/Documents/letterhhs.pdf. 37 ~~Unlike the typical process for issuing new guidance, these guidance~~
~~documents were issued without a public comment period, in accordance with a notice published~~
~~in the Federal Register that outlined a process for making available guidance documents related~~
~~to COVID-19.41 Under this process, FDA is accepting comments for the published guidance and~~
~~is to consider the comments and potentially update the guidance to incorporate them. The only~~
~~exception is the guidance related to CJD, which finalizes draft guidance from January 2020. FDA~~
~~indicated that the HIV and Malaria guidance will continue to apply outside the context of the~~
~~current public health emergency, subject to comments received on the interim final guidance.~~

~~http://www.aabb.org/programs/disasterresponse/Documents/letterhhs.pdf.~~
35 FEMA, “Raising Priority Status of Blood with State/Local Emergency Management Agencies,” March 19, 2020, FEMA, “Raising Priority Status of Blood with State/Local Emergency Management Agencies,” March 19, 2020,
http://www.aabb.org/programs/disasterresponse/Documents/FEMA-Letter.pdf. http://www.aabb.org/programs/disasterresponse/Documents/FEMA-Letter.pdf.
3638 FDA, “Coronavirus (COVID-19) Update: FDA Provides Updated Guidance to Address the Urgent Need for Blood FDA, “Coronavirus (COVID-19) Update: FDA Provides Updated Guidance to Address the Urgent Need for Blood
During the Pandemic,” press release, April 2, 2020, https://www.fda.gov/news-events/press-announcements/During the Pandemic,” press release, April 2, 2020, https://www.fda.gov/news-events/press-announcements/
coronavirus-covid-19-update-fda-provides-updated-guidance-address-urgent-need-blood-during-pandemic. coronavirus-covid-19-update-fda-provides-updated-guidance-address-urgent-need-blood-during-pandemic.
3739 FDA, FDA, “Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by
Blood and Blood Products,” Guidance for Industry, April 2, 2020, https://www.fda.gov/media/92490/download. Blood and Blood Products,” Guidance for Industry, April 2, 2020, https://www.fda.gov/media/92490/download.
3840 FDA, “Revised Recommendations to Reduce the Risk of Transfusion-Transmitted Malaria,” FDA, “Revised Recommendations to Reduce the Risk of Transfusion-Transmitted Malaria,” Guidance for Industry,Guidance for Industry,
April 2, 2020, https://www.fda.gov/media/72243/download.April 2, 2020, https://www.fda.gov/media/72243/download.
3941 FDA, “Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant FDA, “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, April 2, 2020, Creutzfeldt-Jakob Disease by Blood and Blood Components,” Guidance for Industry, April 2, 2020,
https://www.fda.gov/media/124156/download. https://www.fda.gov/media/124156/download.
4042 A public health emergency was first declared on January 27, 2020. It was renewed on April 26, 2020. HHS, A public health emergency was first declared on January 27, 2020. It was renewed on April 26, 2020. HHS,
“Renewal of Determination That a Public Health Emergency Exists,” press release, April 21, 2020, “Renewal of Determination That a Public Health Emergency Exists,” press release, April 21, 2020,
~~https://www.phe.gov/emergency/news/healthactions/phe/Pages/covid19-21apr2020.aspx.~~
~~41 FDA, “Process for Making Available Guidance Documents Related to Coronavirus Disease 2019,” 85~~ ~~Federal~~
~~Register~~ ~~16949, March 5, 2020.~~
~~Congressional Research Service~~
6

~~The U.S. Blood Supply and the COVID-19 Response~~

Congressional Research Service 6 The U.S. Blood Supply and the COVID-19 Response documents were issued without a public comment period, in accordance with a notice published in the Federal Register that outlined a process for making available guidance documents related to COVID-19.43 Under this process, FDA is accepting comments for the published guidance and is to consider the comments and potentially update the guidance to incorporate them. The only exception is the guidance related to CJD, which finalizes draft guidance from January 2020. FDA indicated that the HIV and Malaria guidance will continue to apply outside the context of the current public health emergency, subject to comments received on the interim final guidance. However, the alternative procedure guidance is to terminate when the public health emergency is However, the alternative procedure guidance is to terminate when the public health emergency is
terminated. terminated.
Alternative Procedure Guidance
FDA issued guidance titled “Alternative Procedures for Blood and Blood Components During the FDA issued guidance titled “Alternative Procedures for Blood and Blood Components During the
COVID-19 Public Health Emergency; Guidance for Industry” (Alternative Procedure Guidance) COVID-19 Public Health Emergency; Guidance for Industry” (Alternative Procedure Guidance)
on April 2, 2020, that creates exceptions to procedures included in the regulatory framework for on April 2, 2020, that creates exceptions to procedures included in the regulatory framework for
determining donor eligibility and for storage of certain blood products during the COVID-19 determining donor eligibility and for storage of certain blood products during the COVID-19
emergency.emergency.4244 The changes are intended to expand the availability of blood products. Under typical The changes are intended to expand the availability of blood products. Under typical
circumstances, certain blood donations may be considered unsuitable because of a failure to circumstances, certain blood donations may be considered unsuitable because of a failure to
follow procedures put in place to protect the health of the donor (e.g., a physical assessment to follow procedures put in place to protect the health of the donor (e.g., a physical assessment to
determine the potential donor’s blood pressure, pulse, weight, and donation frequency).determine the potential donor’s blood pressure, pulse, weight, and donation frequency).4345 The The
guidance recommends using such blood donations, which would have previously been considered guidance recommends using such blood donations, which would have previously been considered
unsuitable because they might have adversely affected the health of the donor. This guidance does unsuitable because they might have adversely affected the health of the donor. This guidance does
not eliminate the physical assessment requirement, but it allows collected blood to be used in the not eliminate the physical assessment requirement, but it allows collected blood to be used in the
event that there was an error. event that there was an error.
In addition, the emergency guidance increases the time in which blood centers must obtain In addition, the emergency guidance increases the time in which blood centers must obtain
omitted donor information—from within 24 hours of omitted donor information—from within 24 hours of ~~donation44~~donation46 to within 72 hours. to within 72 hours.4547 Lastly, the Lastly, the
guidance decreases the recommended amount of time, from 60 to 45 calendar days that certain guidance decreases the recommended amount of time, from 60 to 45 calendar days that certain
plasma donations must be quarantined prior to use.plasma donations must be quarantined prior to use.4648 Plasma from paid donors is quarantined Plasma from paid donors is quarantined
before use to ensure that the donor meets all eligibility requirements.before use to ensure that the donor meets all eligibility requirements.4749
HIV Transmission by Blood and Blood Products
Long-standing FDA guidance, first established in 1985, deferred men who have sex with men Long-standing FDA guidance, first established in 1985, deferred men who have sex with men
(MSM) from donating blood for life. This lifetime deferral applied to men who had sex with men (MSM) from donating blood for life. This lifetime deferral applied to men who had sex with men
even one time. The intent of the deferral was to reduce the risk of HIV transmission by blood and even one time. The intent of the deferral was to reduce the risk of HIV transmission by blood and
~~blood products. In 1992, FDA issued a memo that reiterated the lifetime deferral for MSM. FDA~~
~~revised its recommendations in 2015 to apply the deferral for 12 months rather than a lifetime.48~~
~~The 12-month deferral period also applied to women who had sex with MSM, as well as to~~
~~individuals who were tattooed or pierced, had sex in exchange for money or drugs, had engaged~~
~~in nonprescription injection drug use, had received a blood transfusion, had come into contact~~
~~with another individual’s blood, and/or had a history of syphilis or gonorrhea. The new guidance,~~
~~issued in response to the COVID-19 pandemic, revises the recommended deferral period from 12~~
~~months to 3 months for each of these groups.49~~

42 https://www.phe.gov/emergency/news/healthactions/phe/Pages/covid19-21apr2020.aspx. 43 FDA, “Process for Making Available Guidance Documents Related to Coronavirus Disease 2019,” 85 Federal Register 16949, March 5, 2020. 44 FDA, “Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency,” FDA, “Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency,”
Guidance for Industry, April 2, 2020, https://www.fda.gov/media/136603/download. Guidance for Industry, April 2, 2020, https://www.fda.gov/media/136603/download.
4345 21 C.F.R. §630.10(f). 21 C.F.R. §630.10(f).
4446 21 C.F.R. §630.10(c)(2). 21 C.F.R. §630.10(c)(2).
4547 FDA, “Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency,” FDA, “Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency,”
Guidance for Industry, April 2, 2020, p. 4, https://www.fda.gov/media/136603/download. Guidance for Industry, April 2, 2020, p. 4, https://www.fda.gov/media/136603/download.
4648 FDA, “Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency,” FDA, “Alternative Procedures for Blood and Blood Components During the COVID-19 Public Health Emergency,”
Guidance for Industry, April 2, 2020, p. 3, https://www.fda.gov/media/136603/download. [21 C.F.R. § 640.69(f)]. Guidance for Industry, April 2, 2020, p. 3, https://www.fda.gov/media/136603/download. [21 C.F.R. § 640.69(f)].
4749 21 C.F.R. §640.69(e). Congressional Research Service 7 link to page 11 The U.S. Blood Supply and the COVID-19 Response blood products. In 1992, FDA issued a memo that reiterated the lifetime deferral for MSM. FDA revised its recommendations in 2015 to apply the deferral for 12 months rather than a lifetime.50 The 12-month deferral period also applied to women who had sex with MSM, as well as to individuals who were tattooed or pierced, had sex in exchange for money or drugs, had engaged in nonprescription injection drug use, had received a blood transfusion, had come into contact with another individual’s blood, and/or had a history of syphilis or gonorrhea. The new guidance, issued in response to the COVID-19 pandemic, revises the recommended deferral period from 12 months to 3 months for each of these groups.51 ~~21 C.F.R. §640.69(e).~~
~~48 FDA, “Revised Recommendation for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood~~
~~and Blood Products; Draft Guidance for Industry; Availability,” 80 Federal Register 27973-27976, May 15, 2015.~~
~~49 FDA, “Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood~~
~~Congressional Research Service~~
7

~~link to page 11~~ ~~The U.S. Blood Supply and the COVID-19 Response~~

Transfusion-Transmitted Malaria
Since 1994, FDA has recommended deferral of blood donors who have had malaria or have had Since 1994, FDA has recommended deferral of blood donors who have had malaria or have had
possible exposure to malaria during travel to or residence in malaria-endemic countries.possible exposure to malaria during travel to or residence in malaria-endemic countries.5052 The The
occurrence of transfusion-transmitted malaria is relatively low in the United States,occurrence of transfusion-transmitted malaria is relatively low in the United States,5153 and the and the
recommendation contributes to thousands of deferrals every yearrecommendation contributes to thousands of deferrals every year. Table 1 lists recommended lists recommended
deferral periods under the new and previous guidance for different travel scenarios. deferral periods under the new and previous guidance for different travel scenarios.
Table 1. Malaria-Related Donor Deferral Recommendations Under Previous and
Current FDA Guidance
2013 Deferral
2020 Deferral
Donor History
Guidance
Guidance
Travel to a malaria-endemic area (resident of a nonendemic country) Travel to a malaria-endemic area (resident of a nonendemic country)
1 year 1 year
3 months 3 months
Resident of a malaria-endemic country Resident of a malaria-endemic country
3 years 3 years
3 years 3 years
Travel to a malaria-endemic area (resident of a malaria-endemic Travel to a malaria-endemic area (resident of a malaria-endemic
3 years 3 years
3 years 3 years
country)—less than 3 consecutive years in nonendemic country country)—less than 3 consecutive years in nonendemic country
Travel to a malaria-endemic area (resident of a malaria-endemic Travel to a malaria-endemic area (resident of a malaria-endemic
1 year 1 year
3 months 3 months
country)—3 or more consecutive years in nonendemic country country)—3 or more consecutive years in nonendemic country
Malaria diagnosis Malaria diagnosis
3 years 3 years
3 years 3 years
Source: FDA, “Revised Recommendations to Reduce the Risk of Transfusion-Transmitted Malaria,” Guidance FDA, “Revised Recommendations to Reduce the Risk of Transfusion-Transmitted Malaria,” Guidance
for Industry, April 2, 2020, p. 12. for Industry, April 2, 2020, p. 12.
Transmission of Creutzfeldt-Jakob Disease by Blood and Blood Components
Recommended deferrals for individuals who may have been exposed to Creutzfeldt-Jakob Recommended deferrals for individuals who may have been exposed to Creutzfeldt-Jakob
Disease and variant-Creutzfeldt-Jakob Disease (commonly known as “mad cow disease”) were Disease and variant-Creutzfeldt-Jakob Disease (commonly known as “mad cow disease”) were
previously broad, including indefinite deferrals for individuals who spent five or more years in previously broad, including indefinite deferrals for individuals who spent five or more years in
Europe since 1980 and certain military personnel and families that spent time on U.S. military Europe since 1980 and certain military personnel and families that spent time on U.S. military
bases in Europe.bases in Europe.5254 The new guidance eliminates those deferrals but continues to recommend The new guidance eliminates those deferrals but continues to recommend
indefinite, lifetime deferrals for specified residency in some European countries (i.e., France, the indefinite, lifetime deferrals for specified residency in some European countries (i.e., France, the
United Kingdom, and Ireland). United Kingdom, and Ireland).
~~CARES Act Section 3226~~
~~The Coronavirus Aid, Relief, and Economic Security Act (CARES Act; P.L. 116-136), enacted on~~
~~March 27, 2020, included one provision related to the blood supply. Section 3226 of the CARES~~
~~Act requires the Secretary to carry out a national campaign to improve awareness of, and support~~
~~outreach to the public and health care providers about, the importance and safety of blood~~
~~donation and the need for donations to the blood supply.~~
~~The provision requires the Secretary to consult with heads of relevant federal agencies,~~
~~accrediting bodies, and representative organizations to carry out the campaign. In addition, the~~
~~Secretary is authorized to contract with public and private nonprofit entities to carry out the~~
~~campaign.~~

50 FDA, “Revised Recommendation for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood and Blood Products; Draft Guidance for Industry; Availability,” 80 Federal Register 27973-27976, May 15, 2015. 51 FDA, “Revised Recommendations for Reducing the Risk of Human Immunodeficiency Virus Transmission by Blood and Blood Products,” Guidance for Industry, April 2, 2020, pp. 8-9, https://www.fda.gov/media/92490/download. and Blood Products,” Guidance for Industry, April 2, 2020, pp. 8-9, https://www.fda.gov/media/92490/download.
5052 FDA, “Revised Recommendations to Reduce the Risk of Transfusion-Transmitted Malaria,” Guidance for Industry, FDA, “Revised Recommendations to Reduce the Risk of Transfusion-Transmitted Malaria,” Guidance for Industry,
April 2, 2020, p. 3, https://www.fda.gov/media/72243/download. April 2, 2020, p. 3, https://www.fda.gov/media/72243/download.
5153 Ibid., p. 3. Ibid., p. 3.
5254 FDA, “Recommendations to Reduce the Possible Risk of Transmission of Creutzfeldt-Jakob Disease and Variant FDA, “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, April 2, 2020, pp. 16-17, Creutzfeldt-Jakob Disease by Blood and Blood Components,” Guidance for Industry, April 2, 2020, pp. 16-17,
https://www.fda.gov/media/124156/download. https://www.fda.gov/media/124156/download.
Congressional Research Service Congressional Research Service
8 8

The U.S. Blood Supply and the COVID-19 Response

CARES Act Section 3226 The Coronavirus Aid, Relief, and Economic Security Act (CARES Act; P.L. 116-136), enacted on March 27, 2020, included one provision related to the blood supply. Section 3226 of the CARES Act requires the Secretary to carry out a national campaign to improve awareness of, and support outreach to the public and health care providers about, the importance and safety of blood donation and the need for donations to the blood supply. The provision requires the Secretary to consult with heads of relevant federal agencies, accrediting bodies, and representative organizations to carry out the campaign. In addition, the Secretary is authorized to contract with public and private nonprofit entities to carry out the campaign. The provision requires the Secretary to submit a report to the Senate Committee on Health, The provision requires the Secretary to submit a report to the Senate Committee on Health,
Education, Labor, and Pensions and the House Committee on Energy and Commerce not later Education, Labor, and Pensions and the House Committee on Energy and Commerce not later
than two years from enactment (i.e., March 27, 2022) that (1) describes the activities carried out, than two years from enactment (i.e., March 27, 2022) that (1) describes the activities carried out,
(2) describes trends in blood supply donations, and (3) evaluates the impact of the public (2) describes trends in blood supply donations, and (3) evaluates the impact of the public
awareness campaign. awareness campaign.
Potential Use of U.S. Blood Supply to Treat
COVID-19
To date, no therapeutics—drugs or biologics—have been approved to treat COVID-19. Although To date, no therapeutics—drugs or biologics—have been approved to treat COVID-19. Although
various drugs and biologics, including blood-derived therapies, are being studied to determine various drugs and biologics, including blood-derived therapies, are being studied to determine
their capacity to treat or prevent COVID-19, the data regarding whether they can do so safely and their capacity to treat or prevent COVID-19, the data regarding whether they can do so safely and
effectively are still being generated.effectively are still being generated.
As described further below, FDA has used its existing authorities to expand access to unapproved products, including COVID-19 Convalescent Plasma (CCP). Convalescent Plasma and Hyperimmune Globulin
FDA has identified two investigational blood-derived therapies for the treatment of COVID-19: FDA has identified two investigational blood-derived therapies for the treatment of COVID-19:
convalescent plasma and hyperimmune globulin. Both are made from the blood plasma (the fluid convalescent plasma and hyperimmune globulin. Both are made from the blood plasma (the fluid
portion of human blood) of a person who has recovered from the disease.portion of human blood) of a person who has recovered from the disease.5355 Individuals who Individuals who
recover from COVID-19 typically develop antibodies to the SARS-CoV-2 virus that causes the recover from COVID-19 typically develop antibodies to the SARS-CoV-2 virus that causes the
disease. disease. ~~Limited anecdotal evidence suggests~~There is evidence to suggest that these antibodies can be administered that these antibodies can be administered safely to treat to treat
critically ill patients with COVID-19.critically ill patients with COVID-19.5456
Convalescent plasma refers to blood plasma that is collected from an individual who has refers to blood plasma that is collected from an individual who has
recovered (i.e., “convalesced”) from a disease, in this case COVID-19, and then administered to a recovered (i.e., “convalesced”) from a disease, in this case COVID-19, and then administered to a
patient actively sick with COVID-19 for treatment. Convalescent plasma therapy has been patient actively sick with COVID-19 for treatment. Convalescent plasma therapy has been
~~studied in, although not approved for, the treatment of other viral respiratory diseases, including~~
~~severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and~~
~~H1N1 influenza.55 Several steps are involved in using convalescent plasma as a treatment—~~
~~including obtaining blood from a recovered donor, testing it for safety, isolating the plasma, and~~
~~then transfusing it into a patient with COVID-19.56 Some estimates indicate that one donor could~~
~~treat two or three recipients.57 Plasma transfusions are generally safe; however, they are not~~

53 55 FDA, “Coronavirus (COVID-19) Update: FDA Coordinates National Effort to Develop Blood-Related Therapies for FDA, “Coronavirus (COVID-19) Update: FDA Coordinates National Effort to Develop Blood-Related Therapies for
COVID-19,” April 3, 2020, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-COVID-19,” April 3, 2020, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-
coordinates-national-effort-develop-blood-related-therapies-covid-19. coordinates-national-effort-develop-blood-related-therapies-covid-19.
5456 Ibid. C Shen, Z Wang, F Zhao, et al., “Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Ibid. C Shen, Z Wang, F Zhao, et al., “Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent
Plasma,” Plasma,” JAMA (March 27, 2020). JD Roback and J Guarner, “Convalescent Plasma to Treat COVID-19 Possibilities (March 27, 2020). JD Roback and J Guarner, “Convalescent Plasma to Treat COVID-19 Possibilities
and Challenges,” and Challenges,” JAMA (March 27, 2020). (March 27, 2020).
~~55 FDA, “Investigational COVID-19 Convalescent Plasma,” Guidance for Industry, April 2020~~FDA, Clinical Memorandum Regarding EUA 26382: Emergency Use Authorization (EUA) Request (original request 8/12/20; amended request 8/23/20) for COVID-19 Convalescent Plasma (CCP), https://www.fda.gov/, https://www.fda.gov/
media/media/~~136798/download. Y Cheng, R Wong, YO Soo, et al., “Use of convalescent plasma therapy in SARS patients in~~
~~Hong Kong,” Eur J Clin Microbiol Infect Dis, vol. 24, no. 1 (January 2005). IF Hung, KK To, CK Lee, et al.,~~
~~“Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus~~
~~infection,” Clinical Infectious Diseases, vol. 52, no. 4 (February 2011).~~
~~56 A Joseph, “Everything we know about coronavirus immunity and antibodies—and plenty we still don’t,”~~ ~~STAT~~
~~News, April 20, 2020, https://www.statnews.com/2020/04/20/everything-we-know-about-coronavirus-immunity-and-~~
~~antibodies-and-plenty-we-still-dont/.~~
~~57 American Association of Hematology, “COVID-19 and Convalescent Plasma: Frequently Asked Questions,”~~
~~updated April 10, 2020, https://www.hematology.org/covid-19/covid-19-and-convalescent-plasma.~~
~~Congressional Research Service~~
9

~~The U.S. Blood Supply and the COVID-19 Response~~

141480/download. Congressional Research Service 9 The U.S. Blood Supply and the COVID-19 Response studied in, although not approved for, the treatment of other viral respiratory diseases, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and H1N1 influenza.57 Several steps are involved in using convalescent plasma as a treatment—including obtaining blood from a recovered donor, testing it for safety, isolating the plasma, and then transfusing it into a patient with COVID-19.58 Some estimates indicate that one donor could treat two or three recipients.59 Plasma transfusions are generally safe; however, they are not without risk and can cause allergic reactions and other side effects in some patients.without risk and can cause allergic reactions and other side effects in some patients.5860 Data are Data are
limited regarding the limited regarding the ~~safety and~~ effectiveness of convalescent plasma in treating COVID-19, but effectiveness of convalescent plasma in treating COVID-19, but
~~anecdotal~~ available evidence suggests the treatment may be safe and effective for some patients.evidence suggests the treatment may be safe and effective for some patients.59
61 A related therapy, A related therapy, hyperimmune globulin, is a manufactured biological product containing , is a manufactured biological product containing
concentrated antibodies collected from convalescent plasma. Although convalescent plasma units concentrated antibodies collected from convalescent plasma. Although convalescent plasma units
vary in antibody types (e.g., IgG, IgM) and vary in antibody types (e.g., IgG, IgM) and ~~levels~~amount (titer) based on the plasma donor, hyperimmune based on the plasma donor, hyperimmune
globulin preparations are typically standardized.globulin preparations are typically standardized.6062 FDA has approved hyperimmune globulin FDA has approved hyperimmune globulin
therapies for several non-COVID-19 indications, including exposure to Hepatitis B and treatment therapies for several non-COVID-19 indications, including exposure to Hepatitis B and treatment
of inhalational anthrax, among others.of inhalational anthrax, among others.6163 According to one drug manufacturer currently in the According to one drug manufacturer currently in the
process of developing hyperimmune globulin for COVID-19, manufacturing this product “will process of developing hyperimmune globulin for COVID-19, manufacturing this product “will
require plasma donation from many individuals who have fully recovered from COVID-19, and require plasma donation from many individuals who have fully recovered from COVID-19, and
whose blood contains antibodies that can fight the novel coronavirus. Once collected, the whose blood contains antibodies that can fight the novel coronavirus. Once collected, the
‘convalescent’ plasma would then be transported to manufacturing facilities where it undergoes ‘convalescent’ plasma would then be transported to manufacturing facilities where it undergoes
proprietary processing, including effective virus inactivation and removal processes, and then is proprietary processing, including effective virus inactivation and removal processes, and then is
purified into the [hyperimmune globulin] product.”purified into the [hyperimmune globulin] product.”6264
Serological tests that detect COVID-19 antibodies may help identify the best treatment Serological tests that detect COVID-19 antibodies may help identify the best treatment
candidates, as well as potential plasma donors. However, questions remain regarding immunity to candidates, as well as potential plasma donors. However, questions remain regarding immunity to
the SARS-CoV-2 virus, including whether antibodies confer immunity and if so, to what extent, the SARS-CoV-2 virus, including whether antibodies confer immunity and if so, to what extent,
reinfection, and the accuracy of available serological tests.reinfection, and the accuracy of available serological tests.63
~~FDA Regulation of Biologics~~
~~FDA regulates convalescent plasma and hyperimmune globulins as biological products~~
~~(biologics)—therapeutics derived from or made in a living system.64 Generally, a biologic may be~~
~~provided to patients only if FDA has licensed (i.e., approved) it for marketing under a biologics~~
~~license application, authorized its use in a clinical trial under an investigational new drug~~
~~application (IND), or authorized its use through expanded access under an IND, including an~~
~~emergency IND (eIND).~~

5865 57 FDA, “Investigational COVID-19 Convalescent Plasma,” Guidance for Industry, April 2020, https://www.fda.gov/media/136798/download. Y Cheng, R Wong, YO Soo, et al., “Use of convalescent plasma therapy in SARS patients in Hong Kong,” Eur J Clin Microbiol Infect Dis, vol. 24, no. 1 (January 2005). IF Hung, KK To, CK Lee, et al., “Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection,” Clinical Infectious Diseases, vol. 52, no. 4 (February 2011). 58 A. Joseph, “Everything we know about coronavirus immunity and antibodies—and plenty we still don’t,” STAT News, April 20, 2020, https://www.statnews.com/2020/04/20/everything-we-know-about-coronavirus-immunity-and-antibodies-and-plenty-we-still-dont/. 59 American Association of Hematology, “COVID-19 and Convalescent Plasma: Frequently Asked Questions,” updated April 10, 2020, https://www.hematology.org/covid-19/covid-19-and-convalescent-plasma. 60 FDA, “Investigational COVID-19 Convalescent Plasma - Emergency INDs Frequently Asked Questions,” April 3, FDA, “Investigational COVID-19 Convalescent Plasma - Emergency INDs Frequently Asked Questions,” April 3,
2020, https://www.fda.gov/media/136470/download. 2020, https://www.fda.gov/media/136470/download.
5961 Ibid. Ibid.
6062 JD Roback and J Guarner, “Convalescent Plasma to Treat COVID-19 Possibilities and Challenges,” JD Roback and J Guarner, “Convalescent Plasma to Treat COVID-19 Possibilities and Challenges,” JAMA (March (March
27, 2020). 27, 2020).
6163 FDA, “Immune Globulins,” August 16, 2019, https://www.fda.gov/vaccines-blood-biologics/approved-blood- FDA, “Immune Globulins,” August 16, 2019, https://www.fda.gov/vaccines-blood-biologics/approved-blood-
products/immune-globulins. products/immune-globulins.
6264 Takeda, “Global Plasma Leaders Collaborate to Accelerate Development of Potential COVID-19 Hyperimmune Takeda, “Global Plasma Leaders Collaborate to Accelerate Development of Potential COVID-19 Hyperimmune
Therapy,” Newsroom, April 6, 2020, https://www.takeda.com/newsroom/newsreleases/2020/global-plasma-leaders-Therapy,” Newsroom, April 6, 2020, https://www.takeda.com/newsroom/newsreleases/2020/global-plasma-leaders-
collaborate-to-accelerate-development-of-potential-covid-19-hyperimmune-therapy/. collaborate-to-accelerate-development-of-potential-covid-19-hyperimmune-therapy/.
6365 CRS In Focus IF11516, CRS In Focus IF11516, COVID-19 Testing: Key Issues. JD Roback and J Guarner, “Convalescent Plasma to Treat . JD Roback and J Guarner, “Convalescent Plasma to Treat
COVID-19 Possibilities and Challenges,” COVID-19 Possibilities and Challenges,” JAMA (March 27, 2020). A (March 27, 2020). A. Joseph, “Everything we know about coronavirus Joseph, “Everything we know about coronavirus
immunity and antibodies—and plenty we still don’t,” immunity and antibodies—and plenty we still don’t,” STAT News, April 20, 2020, https://www.statnews.com/2020/04/, April 20, 2020, https://www.statnews.com/2020/04/
~~20/everything-we-know-about-coronavirus-immunity-and-antibodies-and-plenty-we-still-dont/.~~
~~64 PHSA §351(i)(1) [21 U.S.C. § 262(i)(1)] defines a biologic as “a virus, therapeutic serum, toxin, antitoxin, vaccine,~~
~~blood, blood component or derivative, allergenic product, protein, or analogous product, or arsphenamine or derivative~~
~~of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a~~
~~disease or condition of human beings.” See CRS Report R44620,~~ ~~Biologics and Biosimilars: Background and Key~~
~~Issues~~.
~~Congressional Research Service~~
10

~~The U.S. Blood Supply and the COVID-19 Response~~
Congressional Research Service 10 The U.S. Blood Supply and the COVID-19 Response FDA Regulation of Biologics FDA regulates convalescent plasma and hyperimmune globulins as biological products (biologics)—therapeutics derived from or made in a living system.66 Generally, a biologic may be provided to patients only if FDA has licensed (i.e., approved) it for marketing under a biologics license application (BLA), authorized its use in a clinical trial under an investigational new drug application (IND), or authorized its use through expanded access under an IND, including an emergency IND (eIND). Under certain emergency circumstances, FDA may issue an emergency use authorization (EUA) to allow the use of an unapproved medical product or the unapproved use of an approved product. Licensure Under a Biologics License Application (BLA)
Most biologics available to patients are licensed under a BLA for marketing and use. For Most biologics available to patients are licensed under a BLA for marketing and use. For
purposes of licensure, FDA requires data from clinical investigations—formally designed, purposes of licensure, FDA requires data from clinical investigations—formally designed,
conducted, and analyzed studies of human subjects—to provide evidence of a biologic’s safety, conducted, and analyzed studies of human subjects—to provide evidence of a biologic’s safety,
purity, and potency. Such investigations must be conducted under an IND, which is a request for purity, and potency. Such investigations must be conducted under an IND, which is a request for
FDA authorization to administer an investigational drug or biologic to humans.FDA authorization to administer an investigational drug or biologic to humans.6567 An IND must An IND must
include information about the investigational drug or biologic and its chemistry, manufacturing, include information about the investigational drug or biologic and its chemistry, manufacturing,
and controls; the proposed clinical study design; completed animal test data; and the lead and controls; the proposed clinical study design; completed animal test data; and the lead
investigator’s qualifications, among other things.investigator’s qualifications, among other things.6668 The investigator also must provide assurance The investigator also must provide assurance
that an Institutional Review Board (IRB) will provide initial and continuous review and approval that an Institutional Review Board (IRB) will provide initial and continuous review and approval
of each of the studies in the clinical investigation to ensure that participants are aware of the of each of the studies in the clinical investigation to ensure that participants are aware of the
drug’s investigative status and that any risk of harm will be necessary, explained, and drug’s investigative status and that any risk of harm will be necessary, explained, and
minimized.minimized.6769 FDA has 30 days to review an IND and, unless the agency objects, clinical testing FDA has 30 days to review an IND and, unless the agency objects, clinical testing
may commence after that review. After completing clinical testing, the manufacturer may submit may commence after that review. After completing clinical testing, the manufacturer may submit
a BLA for licensure to FDA’s Center for Biologics Evaluation and Research. A BLA must contain a BLA for licensure to FDA’s Center for Biologics Evaluation and Research. A BLA must contain
certain information—for example, data from nonclinical laboratory and clinical studies—and certain information—for example, data from nonclinical laboratory and clinical studies—and
licensure is based on a determination by FDA that the biologic and the facility in which it is licensure is based on a determination by FDA that the biologic and the facility in which it is
manufactured, processed, packed, or held, meet standards to ensure that the product is safe, pure, manufactured, processed, packed, or held, meet standards to ensure that the product is safe, pure,
and potentand potent~~.68~~
(effective).70 Investigational Use and Expanded Access Prior to or in absence of an effective BLA, a patient may access an investigational biologic under Prior to or in absence of an effective BLA, a patient may access an investigational biologic under
an IND by participating in a clinical trial. An individual who is not eligible for participation in a an IND by participating in a clinical trial. An individual who is not eligible for participation in a
clinical trial (e.g., because they do not meet the study criteria, or because the trial is not enrolling clinical trial (e.g., because they do not meet the study criteria, or because the trial is not enrolling
20/everything-we-know-about-coronavirus-immunity-and-antibodies-and-plenty-we-still-dont/. 66 PHSA §351(i)(1) [21 U.S.C. §262(i)(1)] defines a biologic as “a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.” See CRS Report R44620, Biologics and Biosimilars: Background and Key Issues. 67 FFDCA §505(i) [21 U.S.C. §355(i)]; PHSA §351(a)(3) [42 U.S.C. §262(a)(3)]; 21 C.F.R. Part 312. 68 21 C.F.R. §312.23. 69 21 C.F.R. §312.23(a)(1)(iv) and 21 C.F.R. Part 56. 70 PHSA §351(a)(2)(C) [42 U.S.C. §262(a)(2)(C)]. FDA regulations at 21 C.F.R. §601.2(a) specify the required contents of a BLA. Congressional Research Service 11 The U.S. Blood Supply and the COVID-19 Response new patients) may request access to an investigational therapy through an expanded access new patients) may request access to an investigational therapy through an expanded access
protocol, provided that an IND is in effect for the investigational therapy and protocol, provided that an IND is in effect for the investigational therapy and
 the physician determines that the patient has no comparable or satisfactory  the physician determines that the patient has no comparable or satisfactory
alternative therapy, and that the probable risk from the investigational therapy is alternative therapy, and that the probable risk from the investigational therapy is
not greater than the probable risk from the disease or condition, and not greater than the probable risk from the disease or condition, and
 FDA determines there is sufficient evidence of safety and effectiveness and that  FDA determines there is sufficient evidence of safety and effectiveness and that
provision of the investigational therapy will not interfere with “the initiation, provision of the investigational therapy will not interfere with “the initiation,
conduct, or completion of clinical investigations to support marketing conduct, or completion of clinical investigations to support marketing
approval.”approval.”6971
In cases where access to a clinical trial or the expanded access protocol is not available or In cases where access to a clinical trial or the expanded access protocol is not available or
feasible, a physician may request an eIND for an individual patient.feasible, a physician may request an eIND for an individual patient.7072
The provision of an investigational therapy in a clinical trial is intended to generate evidence of The provision of an investigational therapy in a clinical trial is intended to generate evidence of
safety and effectiveness to support marketing approval of a therapeutic. In contrast, expanded safety and effectiveness to support marketing approval of a therapeutic. In contrast, expanded
access protocols are access protocols are primarily intended to provide investigational therapies to patients who have exhausted intended to provide investigational therapies to patients who have exhausted
all other options all other options ~~and are not intended to be used~~rather than to obtain safety and effectiveness data. to obtain safety and effectiveness data.

~~65 FFDCA §505(i) [21 U.S.C. §355(i)]; PHSA §351(a)(3) [42 U.S.C. §262(a)(3)]; 21 C.F.R. Part 312.~~
~~66 21 C.F.R. §312.23.~~
~~67 21 C.F.R. §312.23(a)(1)(iv) and 21 C.F.R. Part 56.~~
~~68 PHSA §351(a)(2)(C) [42 U.S.C. § 262(a)(2)(C)]. FDA regulations at 21 C.F.R. §601.2(a) specify the required~~
~~contents of a BLA.~~
~~69 FFDCA §561(b) [21 U.S.C. §360bbb(b)].~~
~~70 21 C.F.R. §312.310.~~
~~Congressional Research Service~~
11

~~The U.S. Blood Supply and the COVID-19 Response~~

~~FDA Treatment and Research Guidance for COVID-19~~
~~FDA has not approved a BLA for convalescent plasma for treatment of COVID-19 and, as such,~~
~~considers it an investigational biologic. FDA has~~ Emergency Use Authorization (EUA) FDA also may enable access to unapproved medical products through EUA, if the HHS Secretary declares that circumstances exist to justify the emergency use of an unapproved product or an unapproved use of an approved medical product.73 Following the HHS Secretary’s declaration, FDA, in consultation with the HHS Assistant Secretary for Preparedness and Response (ASPR), the National Institutes of Health (NIH), and the Centers for Disease Control and Prevention (CDC), may issue an EUA authorizing the emergency use of a specific medical product, provided that the following criteria are met:  the agent that is the subject of the EUA can cause a serious or life-threatening disease or condition;  based on the totality of the available scientific evidence, it is reasonable to believe that the product may be effective in diagnosing, treating, or preventing such disease or condition, and that the known and potential benefits of the product outweigh its known and potential risks; and  there is no adequate, approved, or available alternative to the product.74 The standard of evidence for an EUA is different than that for approval. EUA issuance, as noted above, is based on FDA’s determination that the totality of the available scientific evidence suggests that a product may be effective in diagnosing, treating, or preventing a disease or condition and that the known and potential benefits of the product outweigh its known and potential risks. This is different from the standard required for FDA approval of a drug or 71 FFDCA §561(b) [21 U.S.C. §360bbb(b)]. 72 21 C.F.R. §312.310. 73 FFDCA §564 [21 U.S.C. §360bbb-3]. For additional information about EUA, see CRS In Focus IF10745, Emergency Use Authorization and FDA’s Related Authorities, and CRS Report R46427, Development and Regulation of Medical Countermeasures for COVID-19 (Vaccines, Diagnostics, and Treatments): Frequently Asked Questions. 74 FFDCA §564(c) [21 U.S.C. §360bbb-3(c)]. These criteria are explained in more detail in the FDA guidance Emergency Use Authorization of Medical Products and Related Authorities, January 2017, p. 7, https://www.fda.gov/media/97321/download. Congressional Research Service 12 The U.S. Blood Supply and the COVID-19 Response biologic, which is based on substantial evidence of effectiveness derived from adequate and well-controlled studies. FDA must impose certain conditions as part of an EUA to the extent practicable (e.g., distributing certain information to health care providers and patients) and may impose additional discretionary conditions where appropriate.75 On February 4, 2020, the HHS Secretary determined that there is a public health emergency that has a significant potential to affect national security or the health and security of U.S. citizens living abroad, and that involves COVID-2019.76 On the basis of this determination, the HHS Secretary declared that circumstances exist justifying the authorization of emergency use of unapproved drugs and biologics.77 Pursuant to this declaration, on August 23, 2020, FDA issued an EUA for CCP for patients hospitalized with COVID-19.78 FDA Treatment and Research Guidance for COVID-19 FDA has not approved a BLA for convalescent plasma for treatment of COVID-19 and, as such, considers it an investigational biologic. In April 2020, FDA issued guidance clarifying that administration of issued guidance clarifying that administration of
~~COVID-19 convalescent plasma~~CCP by a health care provider must occur either in a clinical trial by a health care provider must occur either in a clinical trial
under an IND, under an expanded access IND, or under a single-patient eIND.under an IND, under an expanded access IND, or under a single-patient eIND.71 79 To facilitate To facilitate
patient access to investigational convalescent plasma for treatment of COVID-19, FDA, working patient access to investigational convalescent plasma for treatment of COVID-19, FDA, working
with federal partners and academia, with federal partners and academia, ~~has opened~~initiated an expanded access protocol for patients across an expanded access protocol for patients across
the United Statesthe United States~~. Such access~~, the National Expanded Access Treatment Protocol (EAP) sponsored by the Mayo Clinic. Access is limited to individuals with severe or life-threatening COVID-19, is limited to individuals with severe or life-threatening COVID-19,
or to those who have been judged by the treating provider to be at high risk of progression to or to those who have been judged by the treating provider to be at high risk of progression to
severe or life-threatening disease.severe or life-threatening disease.~~72 More than 2,200 sites and over 5,900 physician investigators~~
~~have signed on to participate in the expanded access protocol, with the Mayo Clinic providing the~~
~~cognizant IRB.73 In cases where access to a clinical trial or the expanded access protocol is not~~
80 The EAP was designed to primarily provide patient access to CCP, with the secondary purpose of examining safety, and then efficacy within the limits of the study design (i.e., the EAP is not a randomized controlled trial [RCT]).81 In June 2020, the Mayo Clinic reported that CCP used in patients hospitalized with COVID-19 is safe, based on a diverse sample of 20,000 patients.82 The study did not establish efficacy. A pre-print paper published on August 12, 2020, using data from the EAP further reported that transfusion of CPP “with higher antibody levels to hospitalized COVID-19 patients [~35,000] significantly 75 FFDCA §564(e) [21 U.S.C. §360bbb-3(e)]. 76 HHS, “Emergency Use Declaration,” 85 Federal Register 13907, publication date March 10, 2020, effective date February 4, 2020. 77 HHS, “Emergency Use Authorization Declaration,” 85 Federal Register 18250, publication date April 1, 2020, effective date March 27, 2020. 78 FDA Letter of Authorization to Dr. Robert P. Kadlec, ASPR, August 23, 2020, https://www.fda.gov/media/141477/download. 79 FDA, “Investigational COVID-19 Convalescent Plasma,” April 2020, updated May 1, 2020, https://www.fda.gov/media/136798/download. Also see Expanded Access to Convalescent Plasma for the Treatment of Patients With COVID-19, https://www.uscovidplasma.org/. 80 Ibid. 81 US COVID Plasma, “Comparing EAP vs. EUA: What you need to know,” August 24, 2020, https://www.uscovidplasma.org/pdf/EAP%20vs%20EUA.pdf. 82 R Nellis, “Mayo finds convalescent plasma safe for diverse patients with COVID-19,” June 18, 2020, https://newsnetwork.mayoclinic.org/discussion/mayo-finds-convalescent-plasma-safe-for-diverse-patients-with-covid-19/. M Joyner, K Bruno, S Klassen, et al., “Safety Update: COVID-19 Convalescent Plasma in 20,000 Hospitalized Patients,” Mayo Clinic Proceedings, pre-proof, July 19, 2020. Congressional Research Service 13 The U.S. Blood Supply and the COVID-19 Response reduced mortality compared to transfusions with low antibody levels.”83 As of August 23, 2020, the EAP had enrolled more than 100,000 subjects.84 While the Mayo Clinic has announced that it would discontinue enrollment to the EAP, eligible patients already enrolled would receive CCP. In cases where access to a clinical trial or expanded access is not available, a physician may request an eIND for an individual patient—limited to those with available, a physician may request an eIND for an individual patient—limited to those with
severe or life-threatening COVID-19. severe or life-threatening COVID-19. ~~The~~FDA’s guidance further provides recommendations for guidance further provides recommendations for
~~collection of COVID-19 convalescent plasma~~collection and donation of CCP. To donate, an individual must be recovered, as . To donate, an individual must be recovered, as
specified; have a prior diagnosis of COVID-19 documented by a laboratory test; and meet other specified; have a prior diagnosis of COVID-19 documented by a laboratory test; and meet other
donor criteria.donor criteria.7485 For individuals who did not receive a diagnostic test at the time of illness, a For individuals who did not receive a diagnostic test at the time of illness, a
serological test can help identify individuals previously infected with SARS-CoV-2 who have serological test can help identify individuals previously infected with SARS-CoV-2 who have
developed antibodies against the virus. developed antibodies against the virus.
FDA has not approved a BLA for hyperimmune globulin for treatment of COVID-19 and FDA has not approved a BLA for hyperimmune globulin for treatment of COVID-19 and
considers it an investigational biologic. Although FDA’s convalescent plasma guidance does not considers it an investigational biologic. Although FDA’s convalescent plasma guidance does not
address hyperimmune globulin specifically, patients may access investigational hyperimmune address hyperimmune globulin specifically, patients may access investigational hyperimmune
globulin under an IND by participating in a clinical trial or through expanded access. In addition, globulin under an IND by participating in a clinical trial or through expanded access. In addition,
FDA is reportedly helping coordinate a study of hyperimmune globulin that will be conducted by FDA is reportedly helping coordinate a study of hyperimmune globulin that will be conducted by
the National Institute of Allergy and Infectious Diseases (NIAID) at the the National Institute of Allergy and Infectious Diseases (NIAID) at the ~~National Institutes of~~
~~Health (NIH).75~~NIH.86 The Biomedical Advanced Research and Development Authority (BARDA) The Biomedical Advanced Research and Development Authority (BARDA)
within HHS is also collaborating with various entities to facilitate the development of these within HHS is also collaborating with various entities to facilitate the development of these
investigational treatments. This collaboration includes working with the American Red Cross to investigational treatments. This collaboration includes working with the American Red Cross to
recruit donors and collect, store, and distribute convalescent plasma, as well as expanding recruit donors and collect, store, and distribute convalescent plasma, as well as expanding
existing private-public partnerships. For example, through a partnership with BARDA, Emergent existing private-public partnerships. For example, through a partnership with BARDA, Emergent
BioSolutions is to collect donated plasma and use its hyperimmune platform to develop and BioSolutions is to collect donated plasma and use its hyperimmune platform to develop and
manufacture COVID-19 hyperimmune globulin.manufacture COVID-19 hyperimmune globulin.76

~~71 FDA, “Investigational COVID-19 Convalescent Plasma,” April 2020, updated May 1, 2020, https://www.fda.gov/~~
~~media/136798/download. Also see Expanded Access to Convalescent Plasma for the Treatment of Patients With~~
~~COVID-19, https://www.uscovidplasma.org/.~~
~~72 Ibid.~~
~~73 COVID-19 expanded access program, accessed May 18, 2020, https://www.uscovidplasma.org/. FDA, “Coronavirus~~
~~(COVID-19) Update: FDA Encourages Recovered Patients to Donate Plasma for Development of Blood-Related~~
~~Therapies,” April 16, 2020, https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-~~
~~encourages-recovered-patients-donate-plasma-development-blood.~~
7487 EUA for Convalescent Plasma for COVID-19 On August 23, 2020, FDA issued an EUA to allow for the distribution and administration of investigational CCP in the United States to treat COVID-19 in hospitalized patients. The Mayo Clinic subsequently announced that it would discontinue enrollment to the EAP, but that eligible patients already enrolled would receive convalescent plasma.88 Patients who do not qualify for access under the EUA can submit a request, through their physician, to FDA for expanded access via an IND or eIND, but not through the Mayo Clinic EAP. 83 M Joyner, J Senefeld, S Klassen, et al., “Effect of Convalescent Plasma on Mortality among Hospitalized Patients with COVID-19: Initial Three-Month Experience,” pre-print, August 12, 2020, https://www.medrxiv.org/content/10.1101/2020.08.12.20169359v1. 84 C Gallagher, “Expanded Access Program for Convalescent Plasma discontinues enrollment as FDA authorizes its emergency use,” August 23, 2020, https://newsnetwork.mayoclinic.org/discussion/expanded-access-program-for-convalescent-plasma-discontinues-enrollment-as-fda-authorizes-its-emergency-use/. 85 FDA, “Recommendations for Investigational COVID-19 Convalescent Plasma,” April 13, 2020, FDA, “Recommendations for Investigational COVID-19 Convalescent Plasma,” April 13, 2020,
https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/
recommendations-investigational-covid-19-convalescent-plasma. recommendations-investigational-covid-19-convalescent-plasma.
7586 FDA Combatting COVID-19 with Therapeutics, updated April 9, 2020, https://www.fda.gov/media/136832/ FDA Combatting COVID-19 with Therapeutics, updated April 9, 2020, https://www.fda.gov/media/136832/
download. download.
7687 HHS, “HHS facilitates development of immunotherapies for COVID-19 patients,” April 13, 2020, HHS, “HHS facilitates development of immunotherapies for COVID-19 patients,” April 13, 2020,
https://www.phe.gov/Preparedness/news/Pages/immunotherapies-COVID-13April20.aspxhttps://www.phe.gov/Preparedness/news/Pages/immunotherapies-COVID-13April20.aspx .
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~~The U.S. Blood Supply and the COVID-19 Response~~

. 88 C. Gallagher, “Expanded Access Program for Convalescent Plasma discontinues enrollment as FDA authorizes its emergency use,” August 23, 2020, https://newsnetwork.mayoclinic.org/discussion/expanded-access-program-for-convalescent-plasma-discontinues-enrollment-as-fda-authorizes-its-emergency-use/. Congressional Research Service 14 The U.S. Blood Supply and the COVID-19 Response The EUA letter to ASPR (the EUA requester) specifies that CCP must be obtained from registered or licensed blood establishments from U.S. donors in compliance with existing requirements, as well as that plasma donations be tested for relevant transfusion-transmitted infections and anti-SARS-CoV-2 antibodies. Current evidence suggests that the largest clinical benefit is associated with high titer units (i.e., those with a higher antibody content) given early in the course of disease.89 As such, with respect to anti-SARS-CoV-2 antibodies, the EUA letter specifies at what value a CCP unit would qualify as “high titer,” but also allows health care providers to use low titer units provided they are labeled appropriately. Some concern has been raised regarding FDA’s issuance of an EUA for CCP in the absence of evidence from RCTs, which are the gold standard for evaluating the effectiveness of therapies.90 Some also have criticized FDA Commissioner Hahn’s characterization of the available data, which he addressed on social media.91 As mentioned, the level of evidence required for an EUA is lower than that required for full marketing approval. 92 In the EUA letter, FDA states that it is reasonable to believe that the known and potential benefits of CCP outweigh the known and potential risks for the treatment of patients hospitalized with COVID-19. FDA further states in the letter and in a clinical memorandum that this determination was “[b]ased 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 current outbreak, and data obtained from the ongoing National Convalescent Plasma Expanded Access Protocol (EAP).”93 FDA also notes in the letter that the evidence used to support the EUA was not obtained from prospective, well-controlled RCTs, which are still needed, and that CCP “should not be considered a new standard of care for the treatment of patients with COVID-19.”94 It is not clear the extent to which an EUA will increase access to convalescent plasma, as its availability is limited by donations. However, if patients are able to more readily access CCP through the EUA, participation in clinical trials may be hindered, making it more difficult to generate data regarding the effectiveness of convalescent plasma for COVID-19. 89 FDA Letter of Authorization to Dr. Robert P. Kadlec, ASPR, https://www.fda.gov/media/141477/download. US COVID Plasma, “Comparing EAP vs. EUA: What you need to know,” August 24, 2020, https://www.uscovidplasma.org/pdf/EAP%20vs%20EUA.pdf. 90 N Florko and L Facher, “As Covid-19 pressures mount, political newcomer Stephen Hahn struggles to protect an FDA under siege,” STAT News, August 24, 2020, https://www.statnews.com/2020/08/24/newcomer-stephen-hahn-agency-seige/. L Facher, “Is convalescent plasma safe and effective? We answer the major questions about the Covid-19 treatment,” STAT News, August 23, 2020, https://www.statnews.com/2020/08/23/is-convalescent-plasma-safe-and-effective/. S LaFraniere, S Fink, K Thomas and M Haberman, “F.D.A. Allows Expanded Use of Plasma to Treat Coronavirus Patients,” New York Times, published August 23, 2020, updated August 24, 2020, https://www.nytimes.com/2020/08/23/us/politics/fda-plasma-coronavirus.html. 91 Dr. Stephen M. Hahn @SteveFDA, “I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.” August 24, 2020, 9:36 p.m., https://twitter.com/SteveFDA/status/1298071603675373569. 92 FDA, “Understanding the Regulatory Terminology of Potential Preventions and Treatments for COVID-19,” https://www.fda.gov/consumers/consumer-updates/understanding-regulatory-terminology-potential-preventions-and-treatments-covid-19. 93 FDA Letter of Authorization to Dr. Robert P. Kadlec, ASPR, https://www.fda.gov/media/141477/download. See also FDA, Clinical Memorandum Regarding EUA 26382: Emergency Use Authorization (EUA) Request (original request 8/12/20; amended request 8/23/20) for COVID-19 Convalescent Plasma (CCP), https://www.fda.gov/media/141480/download. 94 Ibid. Congressional Research Service 15 The U.S. Blood Supply and the COVID-19 Response Given the therapeutic potential of blood-derived therapies, FDA encourages eligible individuals who have recovered from COVID-19 to donate their plasma.95 To facilitate collection of CCP, more than 30 organizations have coalesced to form a national donor recruitment campaign, which aims to connect CCP donors with licensed blood and plasma donor centers.96
Author Information

Jared S. Sussman Jared S. Sussman
Agata Dabrowska Agata Dabrowska
Analyst in Health Policy Analyst in Health Policy
Analyst in Health Policy Analyst in Health Policy

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95 FDA, “Donate COVID-19 Plasma,” updated August 23, 2020, https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/donate-covid-19-plasma. 96 The Fight Is In Us, https://thefightisinus.org/en-us#about. Congressional Research Service Congressional Research Service
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