Authorization and Revocation of Emergency Use of Drugs During the COVID-19 Pandemic; Availability, 32938-32950 [2021-13183]
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Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
3. The date the application was
approved: November 20, 2019. FDA has
verified the applicant’s claim that NDA
212194 was approved on November 20,
2019.
This determination of the regulatory
review period establishes the maximum
potential length of a patent extension.
However, the USPTO applies several
statutory limitations in its calculations
of the actual period for patent extension.
In its application for patent extension,
this applicant seeks 190 days of patent
term extension.
III. Petitions
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comments and, under 21 CFR 60.24, ask
for a redetermination (see DATES).
Furthermore, as specified in § 60.30 (21
CFR 60.30), any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
during the regulatory review period. To
meet its burden, the petition must
comply with all the requirements of
§ 60.30, including but not limited to:
must be timely (see DATES), must be
filed in accordance with § 10.20, must
contain sufficient facts to merit an FDA
investigation, and must certify that a
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Petitions should be in the format
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Submit petitions electronically to
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20852.
Dated: June 16, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for
Policy.
[FR Doc. 2021–13176 Filed 6–22–21; 8:45 am]
BILLING CODE 4164–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
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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.
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ACTION:
Notice.
SUPPLEMENTARY INFORMATION:
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).
SUMMARY:
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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
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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Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
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
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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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 PropofolLipuro 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
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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.
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Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
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-preparednessand-response/mcm-legal-regulatoryand-policy-framework/emergency-useauthorization.
BILLING CODE 4164–01–P
March 12, 2021
B. Bta:un Melsungen AG
Attention: Rebecca Stola:rick
Registered Agent
901 Marcon Boulevard
Allentown., PA 18109
RE: Emergency Use Authorization ()96
Dear Ms: Stolarlck:
This letter is in response ti) your request that the Food and I>rug: Administration (FDA) issue an
Emergency Use Authorization (EUA) for em.ergency .use of Propofol-Lipuro l %: injectable
emulsion for infusion to nmintllin sedation via continuous infµsion in patien.ts greater than 16
years old who require mechanical ventilation in an Intensive Care Unit (I CU) setting during the
2019 corona'.\-irus disease (COVIl)--19) pandemic, as described in the Scope of Authoriza:tion
(Section ll)of this letter; pursuanno Section 564 ofthe Federal Food, Drug and Cosrnetio Act
(the Act) (21 U s.c. 360bbb-3}
On February 4, 2020, pursuant to Section 564(b)(l)(C) of the Act, the Secretary of the
Department of Health and Human Services (HI-lS) determined that there is a public health
emergency that.has a significant potential to :affect national security or the.health and security .of
Unittid States. cttizens Jiving abroad, and that involves the virus tha( causes COVID--19. 1 Ort tb.e
basis of such determination, the Secretaiy ofllHS on March 27, 2020, declared that
clrcumstances e.xist justifying the authorization of emergency use of drugs and biological
products during the COVII)~l9 pandemic, pursuantto Section 564 of the Act, subject totenns of
any authorization issued under that section. 2
Propofol--Lipuro 1% injectable emulsion fot infusion is an intravenous (IV) seda,tive hypnotic
drug that can be utilized to maintain sedation via continuous infusion in patients greater than 16
years old with suspected or confirmed COVI0-19 who require mechanical ventila:tionin an ICU
setting.
The Agency Jms .noted that Severe Acute Respiratozy Syndrome Corqn:avirus 2 (SARS°CoV--2),
the vims that caus.es COVI0-19, has led to an increased population with critical illness,
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that. Clirm1msfaneesBxiit ·. ..
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Cosmetic Act, 21 T.J.S..C.§ 3
. Febraary 4, 2020,
• U.S. Deparunent ofIIealfu and lltitilan Setvices,Deelarati® thatCiretlf1Jstcmces1ZxistJustify1ngAuthoritalions
PifrsuanitoSeeHon. :564(b} Pfth11 FederalFood,.IlrUJ;,.andC<1sml!fieAct, 21 US:C.. § 3~QMb"3, 85 FR 18250
(April. L 2020).
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
32941
Page 2 -- B. Braun Melsungen
necessitating sedation drug products for mechanically ventilated patients. As a result, there is an
insufficient supply of the FDA-approved propofol available for use in mechanically ventilated
critically ill patients. 3 Based on the totality of scientific evidence available, FDA has concluded
that it is reasonable to believe that the Propofol-Lipuro 1% injectable emulsiott for infusion may
be effective to maintain sedation via continuous infusion in patients greater than 16 years old
with suspected or confinned COVID-19 who require mechanical ventilation in an ICU setting.
Having concluded that the ctiteria for issuance ofthis authorization under Section 564(c}ofthe
Act are met, I run authorizing the emergency use of your Propofol-Lipuro 1% injectable
emulsion for infusion, as described in the Scope of Authorization (Section II) of this letter,
subject to the terms of this authorization.
I.
Criteria for lssuance of Authorization
I have conclude.cl that the e1'nergency use of Propofol-Lipuro 1% injectable emulsion for
infusion, as described in the Scope of Authorization (Section II) of this letter, meets the criteria
for issuance of an auth_orization under Section 564(c) of the Act, because I have concluded that:
L SARS•CoV~2 can cause a serious or life-threatening disease or condition, including
severe respiratory illness requiring mechanical ventilation, to humans infected by this
vims;
2. Based on the totality of scientific evidence available to FDA, it is reasonable to believe
that Propofol-Lipuro 1% injectable emulsion for infusion may be. effective to maintain
sedation via continuous infusion in patients greater than 16 years old with suspected or
confirmed COVID-1.9 4 who require mechanical ventilation in an IC,U setting, and that,
when. administered as described in the Scope of Authorization (Section II) atld used
under the conditions described in this authorization, the known and potential benefits
of Propofol-Lipuro 1% injectable emulsion for infusion outweigh the known and
potential risks of such product; and
3. There is no adequate, approved, at1d available alternative to the emerge11cy use of
Propofol-Lipuro 1% injectable emulsion.for infusion due to insufficient supplies of
FDA-approved alternatives to fully meet the emergency need during the COVID-19
pandemic. 5
FDA also assessed the supply of FDA-approved alternatives, which includes dexinedetoi:nidine a:l\d midazolanL At
the time of this authorization, FDA has detehninedthat there is insufficient supply of the FDA-approved alternatives
to fully meet the emergency need for Ptopofol-Lipuro 1% injectable emulsion_ for infusion in 100 mL vials,
4 In the circumstances of this_ public health emergency, it would not be feasible to require healthcare providers to
seek to limit Propofol-Liputo 1% injectable emulsion for infusion only to be used for patients with suspected or
confirmed COVID-19; therefore, this authorization di:ies not Jim it u,1e to such patients.
3 No other criteria of issuance have been prescribed by regulation under Section 564(c)(4)ofthe Act.
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Page 3 - B. Braun Melsungen
IL
Scope of Authorization
I have conch.ided, pursuant to Section 564(dX1) of the Act, that the scope ofthis authorization is
limited as follows:
•
Propofol-Lipuro 1% ittjectable emulsion for infusion will be used only to maintain
sedation via continuous infusion in patients greater than 16 years old who require
mechanical ventilation. 6
•
Propofol-Lipttro 1%injectable emulsion for infusion will be administered only bya
licensed healthcare provider in fill ICU 1,etting.
•
Propofol-Lipuro 1% irtjectable emulsion for infusiM will t1ot be admirtistered to pregnant
women; unless there are no FDA-approved products available to maintain sedation for
these patients should they require mechanical ventilation in an ICU setting.
•
Propofol~Lipt1to 1% injectable emulsion for infusion will be used only in accordance
dosmg.regitnens as detailed in the authorized Facts Sheets.
\>,:ith the
Product Description
Propofoi-Lipuro 1% injectable emulsion fodnfusion is classified as a sedative hypnotic drug.
The authorized product is fill injectable emulsion in 100 mL vials containing 10 mg!mL of
propofol for continuous IV administration to maintain sedation in patients greater than 16 years
old who require mechanical ventilation in a:nICU setting.
Propo:fol-tipuro 1% injectable emulsion for infusJ.on is authoriiedfor emergency use as
described in the Scope of Authorization (Section II) with the following ptoduct~specific
information to be made available to healthcare proViders and patients, parent$ iltld caregivers,;
respectively, through B. Braun Metsungen 's website at:
https:11www:bbraunusamrnten/cornpany/newsroorn/covid1'9,htmW;
•
Fact Sheet for Health Care Providers: Em¢rgency lJse Authorization (EtJA) of PropofolLipuro 1%injectablecemulsion for infusion
•
Fact Sheet for Patients, Parents, and Caregivers: Emergency UseAuthorization(EUA) of
Propofol,Lipuro 1%injectableemulsion for infusion
I have cc)llcluded, putsuantto Section.564(dX2) ofthe Act, that it is reasonable to believe that the
known and potential benefits of Propofol-Lipuro 1% injectable emulsion fodnfusion, when used
in accordance with this Scope of Authorization (Section Il); outweigh its kuown and potential
risks.
Ihave concluded, pursuant to.Section 564(dX3Jofthe Act, based on the total'ity ofscientific
eviden:ce available to FDA, that it is reasonable to believe that Propofol-Lipuro 1% injectable
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Page 4 - B. Braun Melsungen
emulsion for infusionmay be effective when used in accordance wi:th thi:s Scope ofAuthorization
(Section II), pursuant to Section 564(c)(2)(A) of the Act.
Having reviewed the scientific information available to FDA; including the infom)ati:on
supportingthe conclusions described in Section I above; I have concluded that Propofol0 Llpuro 1%
injectable emulsion for infusion (as described in this Scope ofAuthorization (Section II))meetsthe
criteria set forth in Section 564(c) of the Act concerning safety and potential effectiveness.
The emer:gency use of your product under an EUA must. be consistent with, and mzy not exceed,
the terms of the Authorization, ipcluding the Scope of Authorization (Sectio11 II) and the
Conditions of Authorization (Section IV), Subject to the term<: of an EUA and .under the
circumstances set forth in the Secretary ofHHS's determination under Section 564(b)(l)(C)
described above and the Secretary ofFIHS's corresponding dedatation under Section 564:{b)(1),
Propofol-Lipuro 1% injectable emulsion for infusion is authorized to main1ain sedation via
continuous infusion in patients greaterthan 16years old with suspected or confirmed COVID-19
who re.quire mechanical ventilation in an ICU setting as described in the Scope of Authorization
(Section II) under this BUA, despite the factthat it does notmeetcertainrequitements otherwise
required by applicable federal law.
III.
Conditions ofAuthorization
Pursuant to Section 564 .ofthe Act; I am establishing the folfowing conditions on this
authorization:
B. Braun Melsungen and Authorized Distributors1
A B. BraunMelsungen and authorized distribtitor(s)will ensure thatthe authorized
Propofol-Lipuro 1% injectable.emulsion is distributed ilnd the authorized labeling (Le.,
Fact Sheets} will be made· available. fo healthcare facilities. and healthcare providers
consistent with.the tenns of this letter.
B. B. Brm111Melsungen and authorized distributor(s)will ensure appropriate storage is
maintained until the. producfis delivered to healthcare facilities andior healthcare
providers.
C. B. Braun Melsungen authorized distributor(s) will ensure thatthe terms of this EUA are
111ade. available to all relevant stakeholders(e'.g., U.S. governmentagencie,;, state and
localgovernmetrtauthqrities, authorized distributorS; healthcare facilities,hea!thcare
providers) involved in distributing or receiving authorized Propofol-Lipuro 1% injectable
emulsion for infusion. B. Braun. Melsungen willprovide to all relevant stakeholders a
copy ofthis letter of authorization atid.communicate llll:Y subsequent amendments.that
m1ght be made to this letter of authorization and its authorized accornpanyit1g.materials
(i.e., Fact Sheets),
7 "1\uthQtiZ<Jd Distributor(s)"
are identified by the sponsor.in EU.A.requests as an entity iiifowed to ;;ilstribute the
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Page 5 -- B. Braun Melsungen
D. B. Braun Melsungen may request changes to this authorization, including to the
authorized Fact Sheets for PropofoI Lipuro 1% injectable emulsion for infusion. Any
request for changes to this EUA n1t1st be submitted to the Division of Anesthesiology,
Addiction Medicine, and Pain Medicine (DAAP)/Office ofNeurosciem;e/Office of New
Drugs/Center for Drug Evaluation and Research (CDER), Such changes require
appropriate authorization from FDA prior to implementation. 8
0
E. B. Braun Melsungen may develop and disseminate instructional and educational
materials (e. g;, materials providing information on product atlministration and/or patient
monitoring) that are consistent with the authorized emergency use of Propofol-Lipuro 1%
injectable emulsion for infusion as described in this letter of authorization and authorized
labeling, without FDA's review and concurrence, wheil necessary to meet public health
needs. Any instructional and. educational materials that are inconsistent with.the
authorized labeling of I?ropofol0 Lipuro 1% injectable emulsioil for infusion are
prohibited. Should the Agency become aware of any instructional oreducatiomtl
materials that are inconsistent with the authorized labeling of Propofol-Lipuro injectable
emulsion for inrusion, the Agency will require B. Melsungen to cease distribution ofsuch
instructioilal or educational materials.
F. B. Braun .Melsungen will report to FDA serious adverse events and all medication errors
associated with the use of the Propofol-Lipuro 1% injectable emulsion for infosion that
are reported to B. Braun Melsungen using either of the following optioilS.
Option 1: Submitreports through the Safety Reporting Portal (SRP)as described <mthe
FDA SRPweb page.
Option 2: Submit reports directly through the Electronic Submissions Gateway (ESG) as
described on the FAERS electroilic submissions web page.
Submitted reports under both options should state: "Propofol-Lipuro 1%use for COVID,
19 under Emergency Use Authorization (EDA)". For reports submitted under Option 1,
include this language at the beginning of the question "Describe Event" for further
analysis, For reports submitted under Option 2, include. this language at the beginning of
the<'Case Narrative:' field.
·
types ofrevisions may .be authorized without teissuirtg this letter: (l). changes to the· authorized
labeling; (2) non-substantive editorial 'correctio!'!S to this letter; (3) new.types of: authorized labeling, including new
fact sll:eets; (4) new carton/container labels; (5} expiration dating extensions; (0) changes to manufacturiiig
processes; including test5 or other m.rthorized components ofmariufru;turing; (7) new conditions ofauthoriziltioli to
require data. coliection or study; (&) nll.w strengths of the authorized ptoduct, new protluct sources (e.g,, of active
pharmaceutical ingredient) or ofproduct component:t All changes to the authorizationreqrnre review and
cortcurtence from DAAP/CJJEg,· Fot changes to the authorization,, including the authorized labeling, of.the type
listedin (3), (6),.(7), or (8), review and concurrence alsoisre.quitedfrom the Counter-Te(forism and Eniergency
Coordination Staff/Offi~ of the CenterDirector!CDERanii the Office of CoU!'lteitett.oriSJ:11 andErn,;,rging
ThreaWbffii;e ofthe Chief Scientist.
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& The following
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
32945
Page 6 -- B. Braun Melsungen
G. All manufacturing, packaging, and testing sites for both drug substance and. drug product
will comply with cu1Tet1t good manufacturing practice requirements of Section
501(a)(2)(B) of the Act.
R B. Braun Melsungen will submit infonnation to the Agency within three working days of
receipt concerning significant quality problems with distributed drug product of PropofolLipuro 1%), that includes the following: (i) Information concerning any illcident that
causes the drug product or its labeling to be mistaken for, or applied to, another article; or
(ii) Infonnation concerning any microbiological contamination, or any significant
chemical, physical, or other change or deterioration in the distributed dmg product, or
any failure of one or more distributed batches of the drug product to meet established
specifications. If a quality problem affects unreleased product and may also implicate
product(s) previously released and distributed, then the quality alert should be submitted
for all impacted lots. B. Braun Melsungen will include in its notification to the Agency
whether the batch, or batches, in question will be recalled. If FDA requests that these, or
any other batches, at any time, be recalled, B. Braun Melsungen must recall them.
I.
Braun Melsungen will manufacture Propofol-Lipuro 1%, injectable emulsion for infusion
to meet all quality standards, and per the manufacturing process and control strategy as
detailed in B. Braun Melsungen's EUA request. B. Braun Melsrn1gen will not implement
any changes to the description of the product, manufacturing process, facilities and
equipment, and elements of the associated control strategy that assure process
performance and quality of the authorized product, without prior notification to and
conctmence by the Agency as described in condition D.
J. B Braun Melsungen will list Propofol-Lipuro 1% injectable emulsion for infusion with a
unique product NDC under the marketing category of Unapproved Drug- Other. Further,
the listing will include each establishment where manufacturing is perfonned for the drug
and the type of operation perfonned at each such establishment.
K. Through a process of inventory control, B . Braun Melsungen and authorized
distributor(s) will maintain records distribution of the authorized product (i.e., lot
numbers, quantity, receiving site, receipt date).
L. B. Braun Melsungen and authorized distributor(s) will make available to FDA upon
request any records maintained in connection with this EUA.
Hospitals and Other Healthcare Facilities to Whom The Authorized Product Is Distributed and
Healthcare Providers Administering the Authorized Product
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M. Healthcare facilities and healthcare providers will ensure that they are aware of the letter
of authorization, and the terms herein, and that the authorized Fact Sheets are made
available to healthcare providers and to patients and caregivers, respectively, through
appropriate means, prior to administration of Propofol-Lipuro 1% injectable emulsion for
infusion as described in the Scope of Authorization (Section II) under this EUA.
32946
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
Pa~ 7 - B. Braun Melsungen
N; Healtticatefaci.lities futd healthcare providers receivingPropofol-Llpuro 1% injectable
emulsion:Jortnfusi<>n will trackserious adverstl\ events• tlii1t are 0011.sl.dered to be
•1%
potentially itttributtb1e.t<>the :use ofPropofol-Lipuro
inje~ble emwsirm foritrlµsio~1
tmtlerthis ll1,lthoriza:tiot1 Mel m:ustreporttheseto l!J:):Aj11 accortllll,lcewiththe FaqtSlieet
for Healthcare Providers, Complete and submit aMedWafohform
twww.fda.i0Y1~tc~@.htt1,1), or•Completeand submit.FDA Fonn3SOO (health
professional). brf~ (l-$00-FPA•Ol't~) (these fotms c~ be fou11d via: Urik ab.ow), Call
l-800-FDA-Hj88for questions. Submitted reports shoukt st11te, ''Propofol-Lipl!fQ
1% injectable emulsion for infusion use forCOVID•l9under Emergency Use
Authorization(EUA)" at the beginning of the question "Describe Event1'for :further
analysis.
o.
Hi::althcl[itefacilities and healthcare providers willensute·thafappropri11testorage,i:s
maintained m1tilthe products nre administered consistentwith the tenns of this letter,
R. Throu~1 a process of inventory c?ntroI,. hea:lthcareiacilities will maintaintecords
injectable emulsion forin:fus1on
regardingthe dispensed authorizedPropofol-Lipuro.
(i.e.,, lotnuml,ei,:s:; quantity, receivmg site, receipt date), prodµct StQragei artd1Uamtai11
patient information(e.g., patientname;agei disease manifestation; days of infusion per
patient, other drugs administered).
1%
Q; Healthcare facilities wilLensure that any records associated. with this. EtJAaretnain.tained
until notified byR Bra:un.Melsimge11 lll,lg/orFDA Suc~rec<>rdswiJ.LbemadeavaHable
to BBraun Medical, HHS, and FDAforinspection. upon request
Co11ditigns Related to Prl:gtedMatter,Advertisin.g4mlPromotio1i
R All descriptive pnnted matter, as well as advertising and promotional material1relatingto
the. use ofthe Propofol-Lipuro l%iajectable emulsion.for infusion shall be consistent
With the authorized fabelin~ aS well as the terms set forth in this EDA and the applicable
requirem'ents s~ forth inJhe Acl and FOA regulatfons.
·
S:. Nodescripfive prifitedmatter,as well as advertising or promotional material; relating to
the use of the Propofol-Lipuro 1% injectable emulsion.for infusiM may reptesentor
suggest thatsuch products are safe oreffective.
T, A.ll descriptive printed 111atter; as weIJ as advertisingll1,ldpromoi:fo11a.l n:i:i:terial, relatingto
.the use of Propofol4.ipuro !%injectable emulsion for infusion clearly and conspicuously
shall state that:
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• the Ptopofci1-Lip:uro 1% injectable emUisioh fofi~ioh. is notFDA-appro:ved,
but haS been authorized for emergency use by FDAto maintain setlatiotrvia
cwtinuous infusion in patient& gr~aterthan 115 y<lars old with suspect<ld or
confirmed COVID,19 who require mechanical ventilation in an ICU setting
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
32947
Page 8 -- B. Braun Melsungen
•
the Propofol-LipurQ 1% injectable emulsion for infusion is authorized only for
the duration of the declaration that circumstances exist justifying the authorization
ofthe emergency use under Section 564(b)(l) ofthe Act; 21 U.S.C. § 360bbb3(h)(l), unless the authorization is terminated or-revoked sooner.
IV. Duration of Autltorization
This EUA will be effective until the declaration that circumstances existjristifying the
authorization of the emergency use of drugs and biologics for prevention andttea-iment of
COVID-19 is terminatetl under Settion S64(b)(2) of the Act or the EUA is revoked under
Section S64(g)ofthe Act.
Sincerely,.
-4SI--
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RADM Denise M. Hinton
Chief Scientist
Food and Drug Administration
32948
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
,J
{✓-'\. U.S. FOOD & DRUG
ADMINISTRATION
April 16, 2021
SusanWarner, Pharm.D.
Advisor
Global Regulatory Affairs - US
Eli Lilly and Company
Lilly Corporate Center
Indianapolis, Indiana 46285
RE:
Emergency Use Authorization 090
DearDt. Warner'.
This letter is in response to your request, dated April 15, 2021, that the Food and Drug
Administration (FDA) revoke the Emergency Use Authorization (EUA) for emergency use of
bamlanivimab 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) andlor hospitalization. The EUA (EUA 090) was originally issued on November 9,
2020 and reissued on February 9, 2021 and Marcli 2, 2021.
The authorization of a product for emergency use under section 564 of the Federal Food, Drug,
and Cosmetic Act (the Act) (21 U.S.C. 360bbb-3) may, pursuant to section 564(g)(2) of the Act,
be revised or revoked when the criteria under section 564(b)(l) of the Act no longer exist, the
criteria undeT section 564(c) of the Act for issuance of such authorization are no longer niet, or
other dtcumstances make such revision or revocation appropriate to protect the public health or
safely.
As part of the Agency; s ongoing revie,v ofthe circumstances and appropriateness of EUA 090,
FDA has continually reviewed new data and additional new information to assess whethetthe
criteria for issuance of EUA 090 continue to be met Under section 564(c)(2) of the Act, an
EUA may be issued only if FDA concludes, among other things, "that, based on the totality of
scientific evidence available to the Secretm}', 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 prevenling-(i) such disease or condition [ .... ]; 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[.,,]."
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Since the initial authorization of bamlanivimab for emergency use, there has been a sustained
increase in SARS-CoV-2 viral variants across the U.S. that are resistant to bamlanivirnab
administered alone. As parl of the Agency's ongoing review of the circumstances and
appropriateness ofEUA 090, we revimved emerging information and assessed whether, based on
the totality of scientific evidence available, the criteria for issuance of the EUA continue to be
rnet:
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
32949
Page 2 - Dr. Warner, Eli Lilly and Company
A summary of these ne\v data arid.new information.includes ihefollowing:
•
Vesicular stomatitis virus-based pseudovirus expressing spike protein wiih variant
substitutions, specificaily E484KaridL452R, exhibit large r.eductfons (>l,000 fold) in
~usceptibility to ban1lanivimab alone in neutralization assays.
•
The Center for Disease Control (CbC) national genomic surveillance ptogtam has
reported an increasii1g frequency ofSARS-Co V-2 variants ihat are expected to be
resistant to bamlanivin1ab alone;
o As of mid-March 2021; approximately 20% of isolates sequenced in the U.S.
were reported as lineages expected to be resistant to bamlanivimab alone,
increasing from approximately 5% in mid-Janmtry 2021.
o The CDC national genomic surveillance program bas published detailed data
regarding var1arits ofihe B.1.427 and B.1.429 lineages, first detected i:11
California, which harbor ihe L452R substifution. These variants have now been
identified at frequencies exceeding 20% in eight state1, and frequencies exceeding
10% in two additionlll states.
o There are recent reports ihat variants with the E484K substiMion are circulating
at rates exceeding 10o/oin the New York City n1etropolitan area including
northern New Jersey.
•
Testing te.:hnologies that enable health care ptov:idets to testindividuai patients for
SARS-CoV-2 viral variants prior to initiation oftreatrrtentwith n1onodotialantibodies
are11ot available and frequencies are changing rapidly. TI1erefore, empiric treatri1ent with
monoclonal antibody therapies that are expected to retain activity broadly across ihe U.S.
is needed to reduce the likelihood of treatment failure.
•
On April8, :2021, ihe Natiot1al Institutes of Health updated its tieatrrtent guidelines for
COVID-19 recommending against the use ofbamlanivi:mab alone.
Given the above, we have concfoded thattbe known and potent1al benefits of bamlariivimab
alone no longer outweigh the known and potential risks for ihe product. As such, FDA has
detertnined thatthe criteria under section $64(c) of the Act for issuance ofEllA 090 referenced
above are no l<>nger met.
In your letter requesting that FDA revoke EUA 090, you state that you do notintend to request
the return ofbamlanivimab that has. been distributed prior to this t"l;lVocation, as the distributed
product continues to be authorized for l,\se togeihei: with etesevimab under EUA 094. FDA
concurs with ihis approach toward disposition of the previously distributed bamlanivimab
authorized for emergency use under EUA 090. Stakeholders may order etesevi:mab alone topair
with existing supply of bamlaniviinab thatmay be on hand.
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Accordingly; FDA revokes the EUA for emergency use of bamlanivi:mab administered alone for
the treatrrtent of mild to moderate COVID-19, pursuant to section.564(gX2) ofthe Act.
32950
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices
Page 3-Dr.. Wamer,EliLillyandCompany
Notice ottliis'reVOcationwiUl:ie·ptil:ilished hitheFederalRegister,pursuant tosection564{h)(l)
ofiheA¢t
Sincerely~
RADM:Denise M. Hin.tori
ChiefSdentist
Dated: June 17, 2021.
Lauren K. Roth,
Acting Principal Associate Commissioner for
Policy.
[FR Doc. 2021–13183 Filed 6–22–21; 8:45 am]
BILLING CODE 4164–01–C
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Food and Drug Administration
[Docket Nos. FDA–2020–E–1256; FDA–
2020–E–1257; and FDA–2020–E–1258]
Determination of Regulatory Review
Period for Purposes of Patent
Extension; TURALIO
AGENCY:
Electronic Submissions
Food and Drug Administration,
HHS.
ACTION:
Notice.
The Food and Drug
Administration (FDA or the Agency) has
determined the regulatory review period
for TURALIO and is publishing this
notice of that determination as required
by law. FDA has made the
determination because of the
submission of applications to the
Director of the U.S. Patent and
Trademark Office (USPTO), Department
of Commerce, for the extension of a
patent which claims that human drug
product.
SUMMARY:
Anyone with knowledge that any
of the dates as published (see the
SUPPLEMENTARY INFORMATION section) are
incorrect may submit either electronic
or written comments and ask for a
redetermination by August 23, 2021.
Furthermore, any interested person may
petition FDA for a determination
regarding whether the applicant for
extension acted with due diligence
during the regulatory review period by
December 20, 2021. See ‘‘Petitions’’ in
the SUPPLEMENTARY INFORMATION section
for more information.
jbell on DSKJLSW7X2PROD with NOTICES
DATES:
VerDate Sep<11>2014
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You may submit comments
as follows. Please note that late,
untimely filed comments will not be
considered. Electronic comments must
be submitted on or before August 23,
2021. The https://www.regulations.gov
electronic filing system will accept
comments until 11:59 p.m. Eastern Time
at the end of August 23, 2021.
Comments received by mail/hand
delivery/courier (for written/paper
submissions) will be considered timely
if they are postmarked or the delivery
service acceptance receipt is on or
before that date.
ADDRESSES:
Submit electronic comments in the
following way:
• Federal eRulemaking Portal:
https://www.regulations.gov. Follow the
instructions for submitting comments.
Comments submitted electronically,
including attachments, to https://
www.regulations.gov will be posted to
the docket unchanged. Because your
comment will be made public, you are
solely responsible for ensuring that your
comment does not include any
confidential information that you or a
third party may not wish to be posted,
such as medical information, your or
anyone else’s Social Security number, or
confidential business information, such
as a manufacturing process. Please note
that if you include your name, contact
information, or other information that
identifies you in the body of your
comments, that information will be
posted on https://www.regulations.gov.
• If you want to submit a comment
with confidential information that you
do not wish to be made available to the
public, submit the comment as a
written/paper submission and in the
manner detailed (see ‘‘Written/Paper
Submissions’’ and ‘‘Instructions’’).
PO 00000
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Written/Paper Submissions
Submit written/paper submissions as
follows:
• Mail/Hand Delivery/Courier (for
written/paper submissions): Dockets
Management Staff (HFA–305), Food and
Drug Administration, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.
• For written/paper comments
submitted to the Dockets Management
Staff, FDA will post your comment, as
well as any attachments, except for
information submitted, marked and
identified, as confidential, if submitted
as detailed in ‘‘Instructions.’’
Instructions: All submissions received
must include the Docket Nos. FDA–
2020–E–1256; FDA–2020–E–1257; and
FDA–2020–E–1258, for ‘‘Determination
of Regulatory Review Period for
Purposes of Patent Extension;
TURALIO.’’ Received comments, those
filed in a timely manner (see
ADDRESSES), will be placed in the docket
and, except for those submitted as
‘‘Confidential Submissions,’’ publicly
viewable at https://www.regulations.gov
or at the Dockets Management Staff
between 9 a.m. and 4 p.m., Monday
through Friday, 240–402–7500.
• Confidential Submissions—To
submit a comment with confidential
information that you do not wish to be
made publicly available, submit your
comments only as a written/paper
submission. You should submit two
copies total. One copy will include the
information you claim to be confidential
with a heading or cover note that states
‘‘THIS DOCUMENT CONTAINS
CONFIDENTIAL INFORMATION.’’ The
Agency will review this copy, including
the claimed confidential information, in
its consideration of comments. The
second copy, which will have the
claimed confidential information
redacted/blacked out, will be available
for public viewing and posted on
https://www.regulations.gov. Submit
both copies to the Dockets Management
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rQod•·•a.tld••nrugAdminl:$.1:tatiort
]]>Agencies
[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]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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.
---------------------------------------------------------------------------
\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.
---------------------------------------------------------------------------
Once the Secretary of HHS has declared that circumstances exist
justifying an authorization under
[[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.
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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:
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.
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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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