32938 Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices 

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. 

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 

Anyone with knowledge that any of 

the dates as published are incorrect may 

submit either electronic or written 

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 

true and complete copy of the petition 

has been served upon the patent 

applicant. (See H. Rept. 857, part 1, 98th 

Cong., 2d sess., pp. 41–42, 1984.) 

Petitions should be in the format 

specified in 21 CFR 10.30. 

Submit petitions electronically to 

https://www.regulations.gov at Docket 

No. FDA–2013–S–0610. Submit written 

petitions (two copies are required) to the 

Dockets Management Staff (HFA–305), 

Food and Drug Administration, 5630 

Fishers Lane, Rm. 1061, Rockville, MD 

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 

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. 

Once the Secretary of HHS has 

declared that circumstances exist 

justifying an authorization under 


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Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices 32939 

2The 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. 

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 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 

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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32940 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 


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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: 

March 12, 2021 

This letter is in response ti) your request that the Food and I>rug: Administration (FDA) issue an 

Emergency Use Authorization (EUA) for em.erg ency .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°Co V--2), 

the vims that caus.es COVI0-19, has led to an increased population with critical illness, 

1 U.R. Dt;partmerti.ofHeaitli and Human Setvices:,DeteniiifkilwnofaFubllc HeaiihEmergenty andDl!:ckifati(Jli 

that. Clirm1msfaneesBxiit ·. .. AY(hfJrizat/onsP1ll'Sl/1Wt. (QSeetioo.:564(liJ ofthr..Fer:kmW(J(Jd, Drug, Clrtd 

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 


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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-1.94 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 

3 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. 
32942 Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices 


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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 

\>,:ith the dosmg.regitnens as detailed in the authorized Facts Sheets. 

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) of the 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(dX3Jof the Act, based on the total'ity of scientific 

eviden:ce available to FDA, that it is reasonable to believe that Propofol-Lipuro 1% injectable 

6 See foolnote 4. 
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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 .of the 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 EU A 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 

product. 
32944 Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices 


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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 PropofoI0Lipuro 1% injectable emulsion for infusion. Any 

request for changes to this EU A 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 

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. · 

& The following 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 of product 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 of the Chief Scientist. 
Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices 32945 


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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 

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 


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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 

potentially itttributtb1e.t<>the :use ofPropofol-Lipuro •1% 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 

regardingthe dispensed authorizedPropofol-Lipuro. 1% injectable emulsion forin:fus1on 

(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). 

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 material1 relatingto 

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: 

• 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 


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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--

RADM Denise M. Hinton 

Chief Scientist 

Food and Drug Administration 
32948 Federal Register / Vol. 86, No. 118 / Wednesday, June 23, 2021 / Notices 


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{ ✓-'\. U.S. FOOD & DRUG ,J 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~Co V-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 EU A 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[.,,]." 

Since the initial authorization of bamlanivimab for emergency use, there has been a sustained 

increase in SARS-Co V-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 


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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 E484 K substiMion are circulating 

at rates exceeding 1 0o/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. 

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 

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: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: 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. 

DATES: 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. 

ADDRESSES: 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. 

Electronic Submissions 

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’’). 

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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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 

rQod•·•a.tld••nrugAdminl:$.1:tatiort