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###### Department of Health and Human Services

###### Food and Drug Administration

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

# AGENCY:

Food and Drug Administration, HHS.

# ACTION:

Notice.

# 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.

Once the Secretary of HHS has declared that circumstances exist justifying an authorization under       ( print page 32939)    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.

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:
    - 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.
    - 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.
    - 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.
    - 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.       ( print page 32940)    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.*
      ( print page 32941)          ( print page 32942)          ( print page 32943)          ( print page 32944)          ( print page 32945)          ( print page 32946)          ( print page 32947)          ( print page 32948)          ( print page 32949)          ( print page 32950)    

Dated: June 17, 2021.

Lauren K. Roth,

Acting Principal Associate Commissioner for Policy.

# Footnotes

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.
        Back to Citation      

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.
        Back to Citation      

BILLING CODE 4164-01-P

[FR Doc. 2021-13183 Filed 6-22-21; 8:45 am]

BILLING CODE 4164-01-C