[Federal Register Volume 86, Number 118 (Wednesday, June 23, 2021)]
[Notices]
[Pages 32938-32950]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2021-13183]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2020-N-1729]


Authorization and Revocation of Emergency Use of Drugs During the 
COVID-19 Pandemic; Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
issuance of an Emergency Use Authorization (EUA) (the Authorization) 
for a drug for use during the COVID-19 pandemic. FDA issued the 
Authorization under the Federal Food, Drug, and Cosmetic Act (FD&C 
Act), as requested by B. Braun Melsungen AG. The Authorization 
contains, among other things, conditions on the emergency use of the 
authorized drug. The Authorization follows the February 4, 2020, 
determination by the Secretary of HHS that there is a public health 
emergency that has a significant potential to affect national security 
or the health and security of United States citizens living abroad and 
that involves a novel (new) coronavirus. The virus is now named SARS-
CoV-2, which causes the illness COVID-19. On the basis of such 
determination, the Secretary of HHS declared on March 27, 2020, that 
circumstances exist justifying the authorization of emergency use of 
drugs and biological products during the COVID-19 pandemic, pursuant to 
the FD&C Act, subject to the terms of any authorization issued under 
that section. FDA is also announcing the revocation of the 
Authorization issued to Eli Lilly and Company for bamlanivimab alone. 
FDA revoked this authorization on April 16, 2021. Reprinted in this 
document is the issuance of the Authorization and the revocation, which 
include an explanation of the reasons for issuance or revocation.

DATES: The Authorization for B. Braun Melsungen AG was effective as of 
March 12, 2021 and the revocation for Eli Lilly and Company was 
effective as of April 16, 2021.

ADDRESSES: Submit written requests for single copies of the 
Authorization and/or revocation to the Office of Counterterrorism and 
Emerging Threats, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 1, Rm. 4338, Silver Spring, MD 20993-0002. Send one self-
addressed adhesive label to assist that office in processing your 
request or include a fax number to which the Authorizations may be 
sent. See the SUPPLEMENTARY INFORMATION section for electronic access 
to the Authorizations.

FOR FURTHER INFORMATION CONTACT: Michael Mair, Office of 
Counterterrorism and Emerging Threats, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 1, Rm. 4332, Silver Spring, MD 20993-
0002, 301-796-8510 (this is not a toll free number).

SUPPLEMENTARY INFORMATION:

I. Background

    Section 564 of the FD&C Act (21 U.S.C. 360bbb-3) allows FDA to 
strengthen the public health protections against biological, chemical, 
nuclear, and radiological agents. Among other things, section 564 of 
the FD&C Act allows FDA to authorize the use of an unapproved medical 
product or an unapproved use of an approved medical product in certain 
situations.

II. Criteria for EUA Authorization

    Section 564(b)(1) of the FD&C Act provides that, before an EUA may 
be issued, the Secretary of HHS must declare that circumstances exist 
justifying the authorization based on one of the following grounds: (1) 
A determination by the Secretary of Homeland Security that there is a 
domestic emergency, or a significant potential for a domestic 
emergency, involving a heightened risk of attack with a biological, 
chemical, radiological, or nuclear agent or agents; (2) a determination 
by the Secretary of Defense that there is a military emergency, or a 
significant potential for a military emergency, involving a heightened 
risk to United States (U.S.) military forces, including personnel 
operating under the authority of title 10 or title 50, United States 
Code, of attack with (i) a biological, chemical, radiological, or 
nuclear agent or agents; or (ii) an agent or agents that may cause, or 
are otherwise associated with, an imminently life-threatening and 
specific risk to U.S. military forces; \1\ (3) a determination by the 
Secretary of HHS that there is a public health emergency, or a 
significant potential for a public health emergency, that affects, or 
has a significant potential to affect, national security or the health 
and security of U.S. citizens living abroad, and that involves a 
biological, chemical, radiological, or nuclear agent or agents, or a 
disease or condition that may be attributable to such agent or agents; 
or (4) the identification of a material threat by the Secretary of 
Homeland Security pursuant to section 319F-2 of the Public Health 
Service (PHS) Act (42 U.S.C. 247d-6b) sufficient to affect national 
security or the health and security of U.S. citizens living abroad.
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    \1\ In the case of a determination by the Secretary of Defense, 
the Secretary of HHS shall determine within 45 calendar days of such 
determination, whether to make a declaration under section 564(b)(1) 
of the FD&C Act, and, if appropriate, shall promptly make such a 
declaration.
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    Once the Secretary of HHS has declared that circumstances exist 
justifying an authorization under

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section 564 of the FD&C Act, FDA may authorize the emergency use of a 
drug, device, or biological product if the Agency concludes that the 
statutory criteria are satisfied. Under section 564(h)(1) of the FD&C 
Act, FDA is required to publish in the Federal Register a notice of 
each authorization, and each termination or revocation of an 
authorization, and an explanation of the reasons for the action. 
Section 564 of the FD&C Act permits FDA to authorize the introduction 
into interstate commerce of a drug, device, or biological product 
intended for use when the Secretary of HHS has declared that 
circumstances exist justifying the authorization of emergency use. 
Products appropriate for emergency use may include products and uses 
that are not approved, cleared, or licensed under sections 505, 510(k), 
512 or 515 of the FD&C Act (21 U.S.C. 355, 360(k), 360b and 360e) or 
section 351 of the PHS Act (42 U.S.C. 262), or conditionally approved 
under section 571 of the FD&C Act (21 U.S.C. 360ccc). FDA may issue an 
EUA only if, after consultation with the HHS Assistant Secretary for 
Preparedness and Response, the Director of the National Institutes of 
Health, and the Director of the Centers for Disease Control and 
Prevention (to the extent feasible and appropriate given the applicable 
circumstances), FDA \2\ concludes: (1) That an agent referred to in a 
declaration of emergency or threat can cause a serious or life-
threatening disease or condition; (2) that, based on the totality of 
scientific evidence available to FDA, including data from adequate and 
well-controlled clinical trials, if available, it is reasonable to 
believe that: (A) The product may be effective in diagnosing, treating, 
or preventing (i) such disease or condition; or (ii) a serious or life-
threatening disease or condition caused by a product authorized under 
section 564, approved or cleared under the FD&C Act, or licensed under 
section 351 of the PHS Act, for diagnosing, treating, or preventing 
such a disease or condition caused by such an agent; and (B) the known 
and potential benefits of the product, when used to diagnose, prevent, 
or treat such disease or condition, outweigh the known and potential 
risks of the product, taking into consideration the material threat 
posed by the agent or agents identified in a declaration under section 
564(b)(1)(D) of the FD&C Act, if applicable; (3) that there is no 
adequate, approved, and available alternative to the product for 
diagnosing, preventing, or treating such disease or condition; (4) in 
the case of a determination described in section 564(b)(1)(B)(ii), that 
the request for emergency use is made by the Secretary of Defense; and 
(5) that such other criteria as may be prescribed by regulation are 
satisfied.
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    \2\ The Secretary of HHS has delegated the authority to issue an 
EUA under section 564 of the FD&C Act to the Commissioner of Food 
and Drugs.
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    No other criteria for issuance have been prescribed by regulation 
under section 564(c)(4) of the FD&C Act.

III. The Authorization

    The Authorization follows the February 4, 2020, determination by 
the Secretary of HHS that there is a public health emergency that has a 
significant potential to affect national security or the health and 
security of United States citizens living abroad and that involves a 
novel (new) coronavirus. The virus is now named SARS-CoV-2, which 
causes the illness COVID-19. Notice of the Secretary's determination 
was provided in the Federal Register on February 7, 2020 (85 FR 7316). 
On the basis of such determination, the Secretary of HHS declared on 
March 27, 2020, that circumstances exist justifying the authorization 
of emergency use of drugs and biological products during the COVID-19 
pandemic, pursuant to section 564 of the FD&C Act, subject to the terms 
of any authorization issued under that section. Notice of the 
Secretary's declaration was provided in the Federal Register on April 
1, 2020 (85 FR 18250). Having concluded that the criteria for issuance 
of the Authorizations under section 564(c) of the FD&C Act are met, FDA 
has authorized the emergency use of a drug during the COVID-19 
pandemic. On March 12, 2021, FDA issued an EUA to B. Braun Melsungen AG 
for Propofol-Lipuro 1% injectable emulsion, subject to the terms of the 
Authorization. The Authorization in its entirety (not including the 
authorized version of the fact sheets and other written materials) 
follows, below in section VI Electronic Access, and provides an 
explanation of the reasons for issuance, as required by section 
564(h)(1) of the FD&C Act.

IV. EUA Criteria for Issuance No Longer Met

    On November 9, 2020, FDA issued an Authorization to Eli Lilly and 
Company for bamlanivimab alone and reissued the Authorization on 
February 9, 2021 and March 2, 2021. Notice of the issuance of the 
Authorization was published in the Federal Register on February 19, 
2021 (86 FR 10290), as required by section 564(h)(1) of the FD&C Act. 
FDA authorized bamlanivimab alone for emergency use for the treatment 
of mild to moderate COVID-19 in adults and pediatric patients (12 years 
of age and older weighing at least 40 kg) with positive results of 
direct SARS-CoV-2 viral testing, and who are at high risk for 
progressing to severe Coronavirus Disease 2019 (COVID-19) and/or 
hospitalization. Subsequent to the issuance of the Authorization, as 
described in the revocation letter reprinted in this notice, FDA 
considered new data and new information that became available. Under 
section 564(g)(2) of the FD&C Act, the Secretary of HHS may revoke an 
EUA if, among other things, the criteria for issuance are no longer 
met. On April 16, 2021, FDA revoked the EUA for Eli Lilly and Company 
for bamlanivimab alone because the criteria for issuance were no longer 
met. Based on a review of the new data and new information, FDA 
concluded it is no longer reasonable to believe that the known and 
potential benefits of bamlanivimab alone outweigh the known and 
potential risks for the product. A summary of these new data and new 
information includes the following:
    <bullet> Vesicular stomatitis virus-based pseudovirus expressing 
spike protein with variant substitutions, specifically E484K and L452R, 
exhibit large reductions (>1,000 fold) in susceptibility to 
bamlanivimab alone in neutralization assays.
    <bullet> The Centers for Disease Control and Prevention (CDC) 
national genomic surveillance program has reported an increasing 
frequency of SARS-CoV-2 variants that are expected to be resistant to 
bamlanivimab alone.
    <bullet> Testing technologies that enable health care providers to 
test individual patients for SARS-CoV-2 viral variants prior to 
initiation of treatment with monoclonal antibodies are not available 
and frequencies are changing rapidly. Therefore, empiric treatment with 
monoclonal antibody therapies that are expected to retain activity 
broadly across the U.S. is needed to reduce the likelihood of treatment 
failure.
    <bullet> On April 8, 2021, the National Institutes of Health 
updated its treatment guidelines for COVID-19 recommending against the 
use of bamlanivimab alone.
    Accordingly, FDA revoked the EUA for emergency use of bamlanivimab 
alone to treat COVID-19, pursuant to section 564(g)(2) of the FD&C Act.

V. The Revocation

    Having concluded that the criteria for revocation of the 
Authorization under section 564(g) of the FD&C Act are met, FDA has 
revoked the EUA for Eli Lilly and Company for bamlanivimab alone.

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The revocation in its entirety follows, below in section VI Electronic 
Access, and provides an explanation of the reasons for revocation, as 
required by section 564(h)(1) of the FD&C Act.

VI. Electronic Access

    An electronic version of this document and the full text of the 
Authorization and revocation are available on the internet from https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization.
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    Dated: June 17, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for Policy.
[FR Doc. 2021-13183 Filed 6-22-21; 8:45 am]
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