Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 16201 

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. 

We have decreased our estimated 

burden associated with disclosures to 

reflect a decrease in related submissions 

over the past 3 years. 

Dated: March 14, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–06034 Filed 3–21–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0335] 

Authorization of Emergency Use of a 

Biological Product 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) 

under the Federal Food, Drug, and 

Cosmetic Act (FD&C Act) for use during 

the COVID–19 pandemic. FDA has 

issued one Authorization for a 

biological product as requested by Eli 

Lilly and Company (Lilly). The 

Authorization contains, among other 

things, conditions on the emergency use 

of the authorized product. The 

Authorization follows the February 4, 

2020, determination by the Secretary of 

Health and Human Services (HHS) that 

there is a public health emergency that 

has a significant potential to affect 

national security or the health and 

security of U.S. citizens living abroad 

and that involves a novel (new) 

coronavirus. The virus, now named 

SARS–CoV–2, 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. 

The Authorization, which includes an 

explanation of the reasons for issuance, 

is reprinted in this document. 

DATES: The Authorization is effective as 

of February 11, 2022. 

ADDRESSES: Submit written requests for 

a single copy of the EUA 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 Authorization may be sent. 

See the SUPPLEMENTARY INFORMATION

section for electronic access to the 

Authorization. 

FOR FURTHER INFORMATION CONTACT: 

Michael Mair, Office of 

Counterterrorism and Emerging Threats, 

Food and Drug Administration, 10903 

New Hampshire Ave., Bldg. 1, Rm. 

4340, 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 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. With this 

EUA authority, FDA can help ensure 

that medical countermeasures may be 

used in emergencies to diagnose, treat, 

or prevent serious or life-threatening 

diseases or conditions caused by 

biological, chemical, nuclear, or 

radiological agents when there are no 

adequate, approved, and available 

alternatives (among other criteria). 

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 U.S. military forces, 

including personnel operating under the 

authority of title 10 or title 50, U.S. 

Code, of attack with (A) a biological, 

chemical, radiological, or nuclear agent 

or agents; or (B) 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 

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. Under section 

564(h)(1) of the FD&C Act, revisions to 

an authorization shall be made available 

on the internet website of FDA. 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 in 

an actual or potential emergency 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), 


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16202 Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 

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. 

FDA 2 concludes: (1) That an agent 

referred to in a declaration of emergency 

or threat can cause a serious or lifethreatening 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 lifethreatening 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) of the FD&C 

Act, 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 U.S. citizens 

living abroad and that involves a novel 

(new) coronavirus. The virus, now 

named SARS–CoV–2, 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 

Authorization under section 564(c) of 

the FD&C Act are met, FDA has issued 

the authorization for the emergency use 

of a biological product during the 

COVID–19 pandemic. On February 11, 

2022, FDA issued an EUA to Lilly for 

the biological product bebtelovimab, 

subject to the terms of the 

Authorization. The initial 

Authorization, which is included below 

in its entirety after section IV of this 

document (not including the authorized 

versions of the fact sheets and other 

written materials), provides an 

explanation of the reasons for issuance, 

as required by section 564(h)(1) of the 

FD&C Act. Any subsequent reissuance 

of the Authorization can be found on 

FDA’s web page at: https://

www.fda.gov/emergency-preparednessand-response/mcm-legal-regulatoryand-policy-framework/emergency-useauthorization. 

IV. Electronic Access 

An electronic version of this 

document and the full text of the 

Authorization is available on the 

internet at: https://www.fda.gov/ 

emergency-preparedness-and-response/ 

mcm-legal-regulatory-and-policyframework/emergency-useauthorization. 

BILLING CODE 4164–01–P 


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Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 16203 


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Eli tllly attd Company 

Attet1-tion: Cbris:tfue Ph.illi,p.$', PhD, RAC 

A4vis:or G.fobalRegulatory Affail'.S: • US 

Lilly Corporate Center 

D.te>p Code 2543 

Illdianapulis, IN462J1⁄25 

RE; Emergency Use A;uthori1:atiorr 111 

Oear Ms. Phillips: 

February 11, 2Q::Z2 

'th.is letter is in response t◊ Eli LIily an.d Company's etilly") requestthatthe Food and Drug 

Administration (FDA or Agency) issue an EmergencyUseAuthorization(EUA)forthe 

emergency use or bebtelovimabforthe rreatrt1ent ofmild~to-moderate coronavirus disease2019 

(CCiVID-19) lft certain adults ruid pediatric patients who are athigh-tisk forptogressionto 

severe COVJD-19, irichrdiug.hospitali:di:<tn or death, putst1a.i:1Jt◊ Section 564 of.1he FedeQll 

food, Dru& and.Coi.metic Act(the Act)(2l l1S,C. §36Obllb-3t 

Orr February 4, 2020, pursuantto Section 564(b)(i )(<:;) ot'the:Act; the Secretary ot'tfre 

Departmertt ofllealth attdliw:i:umServices (HFtS) determined tluttthete is a l,)ublic health 

eme:rgency thathas ai;igniftc-antp◊tentlal to ~fect11;;ttiQllai security ortheheal1b.andsecurity of 

United States citizens:livmgabroad, and thatinvolves the virus that-causes coronavirus disease 

2DT9 (CCiVID-19). l On the basis of such detemnnation, the Secretazy ofHHS onMarch 27, 

2020:, declared lhatcirc:umstances exiiajuslifyingtbe authorization o:femergency use ol'dtugs 

artd bjologi_caI ptodu:cis duting:the COVU>-19 part4emic, p.urs:uartno Se:ctio:ttSM nfihe: Act (21 

U.S.C. 360bbb-3),subjectto terms of any authorization issued underthatsection.2 

Bebtelovinmh fa a neutralizfogtgd-j monoclonal antibody that.hinds to an epltopewithln the• 

receptor binding domain ofthespike protein of SARS.:CoW2, :8ebtelovonab is nolfDAapp:rovedfor anyμses, lncludingttSe as tnmtmentfor COVID-19, 

Based on the re,,iew of the data from the BLAZE-4 clinical trial(NCT04634409); a Phase l/2 

randomized, single-doae: clinic-al trial studying bebtefovonabfot !he tteatmerttof non~ 

bospi~liied patiet1-ts \il-.iih nrild~to-moder$ CQVID-19; .. as. well ·as .availabJephirf!11a®kinetic 

data and nonclinical viral neutralization: data for Omicron and· oUla: v:ariants of concern, itis 

reasonable to beHeve that bebtelovimab may be etrective f orthe treatment of mild~to-rnoderate 

1 tis, t)epilJifiiimtvt"rtea:J'.1h ;ind IJum;an $&v1ci::$;l)ekrminr:Jtfo11pf(IPitMiP1ff!althEmerger,cya,ui~l.gl'(lti.qn 

ihatCfrcumstancesExistJustlfyingAuthorizaiionsPU/'$Ullnt toSecti.011564(Nofihe.Fedi!n:dFood, Drug, a.nd 

Cosmeiic:Act 2.1 U,S;C .. §360bbb-3.Februaty4.2;020\ .·. . · i LL.$;•1,kpartmcnto:fl:lcalth lllid Bummt $crv.iccs,.lk/qtlfatt0!1.th@Ctr¢.1i®1aii&tEir;ist,JiiStf/jiingAi:i#iiiniiiltdris 

Pursu,rmNt>Sedirm 564(b) (Jfi_heFitderalFood,.l>n!g,andC()srneticAc1(, 21 TJ.S.:C.§360:/Jb/;.3, 85 FR 18250 

(April 1,2020), 
16204 Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 


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Page 2 - Eli Lilly and Company 

COVID-19 in adults and pediatric patients ( 12 years of age and older weighing at least 40 kg) 

who are at high-risk for progression to severe COVID-19, including hospitalization or death, and 

for whom alternative COVID-19 treatment options approved or authorized by FDA arc not 

accessible or clinically appropriate, as described in the Scope ofAuthorization(Section II), and 

when used under the conditions described in this authorization, the known and potential benefits 

ofbebtclovimab outweigh the known and potential risks of such product. 

Having concluded that the criteria for issuance of this authorization under Section 564(c) of the 

Act are met, I am authorizing the emergency use ofbebtelovimab forthc treatment of mild-tomoderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 

40 kg) who are at high-risk forprogression to severe COVID-19, including hospitalization or 

death, as described in the Scope of Authorization section of this letter (Section II) and subject to 

the terms of this authorization. 

I. Criteria for Issuance of Authorization 

I have concluded that the emergency use ofbebtelovimab for treatment of mild-to-moderate 

COVID-19, when administered as described in the Scope of Authorization (Section II), meets 1he 

criteria for issuance of an authorization under Section 564( c) of the Act, because: 

l. SARS-Co V-2 can cause a serious or life-threatening disease or condition, including 

severe respiratory illness, to humans infected bythis virus; 

2. Based on the totality of scientific evidence available to FDA, it is reasonable to believe 

that bebtelovimab maybe effective 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) who 

are at high-risk for progression to severe COVID-19, including hospitalization or 

death, as described in the Scope of Authorization (section II), and that, when used 

under the conditions described in this authorization, the known and potential benefits 

of bebtelovimab outweigh the known and potential risks of such product; and 

3. TI1ere is no adequate, approved, and available alternative 3 to the emergency use of 

bebtelovimab for the treatment of mild-to-moderate COVID-19 in adults and pediatric 

(12 years of age and older weighing at least 40 kg) patients as fut1her described in the 

Scope of Authorization (section II). 4 

II. Scope of Autbotization 

I have concluded, pursuant to Section 564( d)(l) of the Act, that the scope of this authorization is 

limited as follows: 

3 Although Veklury (remdesivir)is an approvedaltemativeto treat COVID-l 9in adults and pediatric patients\vithin 

the scope ofthisauthorization,FDAdoesnotconsiderit to be an adequate alternative for certain patients for whom 

it may not be feasible orpractical(e.g,, it requires a 3-day treatment duration} 

4 No other criteria ofissuance have been prescribed by regulation under Section 564( c X4)of the Act 
Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 16205 


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Page 3 -- Eli Lilly and Company 

• Distribution of the authorized bebtelovimab will be controlled by the United States 

(U.S.) Govemment for use consistent with the tenns and conditions of this EUA. 

Lilly will supply bebtelovimab to authorized distributor(s)5, who will distribute to 

healthcare facilities or healthcare providers as directed by the U.S. Govemment, in 

collaboration with state and local govemmentauthorities as needed; 

• Bebtelovimab may only be used for the treatment of mild-to-moderate CO VID-19 in 

adults and pediatric patients (12 years ofage and older weighing at least 40 kg): 

• With positive results of direct SARS-Co V-2 viral testing, and 

• Who are at high-risk6 for progres.<iionto severe COVID, including 

hospitalization or death, and 

• For whom altemativeCOVID-19treatmentoptions approved or authorized by 

FDA are not accessible or clinically appropriate. 

• Bebtelovimab is not authorized for use in the following patient populations 7: 

• Adults or pediatric patients who are hospitalized due to COVID-19, or 

• Adults or pediatric patients who require oirygen therapy and/or respiratory 

support due to COVID-19, or 

• Adults or pediatric patients who require an increase in baseline oxygen flow 

rate and/or respiratory support due to COVID-19 in those patients on chronic 

oxygen therapy and/or oxygen support due to underlyingnon-COVID-19-

related comorbidity; 

• Bebtelovimab is not authorized for treatment of mild-to-moderate COVID-19 in 

geographic regions where infection is likely to have been caused by a non-susceptible 

SARS-Co V -2 variant, based on available information including variant susceptibility 

to these drugs and regional variant frequency. 8 

• Bebtelovimab may only be administered in settings in which health care providers 

have immediate access to medications to treat a severe infusion reaction, such as 

5 "AuthorizedDistributor(s)" are identified by Lilly asan entity or entities allowed to distribute authorized 

bebtelovimab. 

6 For information on medical conditions andfactorsassociated\vith increased risk for progression to severeCOVID 

19, seethe Centers for DiseaseControland Prevention(COC)website: https://\vww.cdc.gov/coronavirus!'.2019-

ncov /need-extra-precautions/people-ivith-medical-conditionsh tml 7 Treatment with bebtelovimab has not been studied in pa tientshospitalizeddue to COVID-19. Monoclonal 

antibodies, such as bebtelovimab, may be associated with worse clinical outcomes when administered to 

hospitalized patients with COV1D-l 9requiringhigh flow oxygenormechanicalventilation. 8 FDA will monitor conditions to determine whetheruse in a geographic region is consistent with this scope of 

authorization, referring to available information, including information onvariantsusceptibility (see, e.g., section 

12.4 of authorized Fact Sheet for Health Care Providers), andCIX' regional variant frequency data available at: 

https://covid.cdc gov/coyid-data-tracker/#variant-proportions. FDA's determination and any updates will be 

available at: https://www.fda.gov/emergency-preparedness-and-remonse/mcm-)egal-regulatory-and-policyfra mework/emergency-use-authorization#coviddrugs. 
16206 Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 


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Page 4 - Eli Lilly and Company 

anaphylaxis, and the ability to activate the emergency medical system (EMS), as 

necessary; 

• The use ofbebtelovimab covered by this authorization must be in accordance with the 

authorized Fact Sheets. 

Product Description 

Bebtelovimab injection (NDC 0002-7589~01) is a sterile, preservative-free clear to opalescent 

and colorless to slightly yellow to slightly brown solution supplied in a single-dose vial. Each 

carton contains a single vial ofbebtelovimab, which is labeled "For Use Under Emergency Use 

Authorization (EUA)". 

TI1e authorized storage and handling information is included in the authorized Fact Sheet for 

Healthcare Providers. 

Bebtelovimab is authorized for emergency use with the following product-specific information 

required to be made available to healthcare providers and to patients, parents, and caregivers, 

respectively, through Lilly's website www.LillyAntibody.com/bebtelovimab(referredto as the 

"authorized labeling"): 

• Fact Sheet for Healthcare Providers: Emergency Use Authorization (EU A) for 

bebtelovimab 

• Fact Sheet for Patients, Parents, and Caregivers: Emergency Use Authorization(EUA) of 

bebtelovimab for Coronavirns Disease 2019 (COVID-19) 

I have concluded, pursuant to Section 564( d)(2) of the Act, that it is reasonable to believe that 

the known and potential benefits ofbebtelovimab, when used for the treatment ofCOVID-19 

and used in accordance with this Scope of Authorization (Section II), outweigh the known and 

potential risks. 

I have concluded, pursuant to Section 564(d)(3) ofthe Act, based on the totality of scientific 

evidence available to FDA, that it is reasonable to believe that bebtelovimab may be effective for 

the treatment ofCOVID-19when used in accordance with this Scope of Authorization (Section 

II), pursuantto Section 564(c)(2)(A) ofthe Act. 

Having reviewed the scientific infonnation available to FDA, including the infonnation 

st1pportingthe conclusions described in Section I above, I have concluded that bebteloviinab (as 

described in this Scope of Authorization (Section II)) meets the criteria set forth in Section 564(c) 

of the Act concerning safety and potential effectiveness. 

TI1e emergency use ofbebte!ovin1ab under this EUA must be consiste11t with, and may not exceed, 

the tenns of the Authorization, including the Scope of Authorization (Section II) and the Cot1ditio11s 

of Autlmrization (Section III). Subject to the terms of this EU A and under the circumstances set 

forth in the Secretary ofHHS's determination under Section 564(b XI )(C) described above and the 

Secretary ofHHS's con-espondingdeclaration under Section 564(bX1), bebtelovimab is authorized 
Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 16207 


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Page 5 Eli Lilly and Company 

for the treatment of COVID-19 as described in this Scope of Authorizati.on (Section II) under thi~ 

EUA, despite the fact that it does not meet certain requirements otherwise required by.applicable 

federal law. 

Ill. Conditions of Authorization 

Pi.lrsuantto Sec1ion 564 of the Act, lam.establishing the following conditions on this authorization: 

Lilly and Authorized Distributots 9 

A. Lilly and authorized distributor( s) will ensure that the authorized bebtelovimab is 

distributed,.as directed by the U.S. government, and the au1horized labeling (i.e., Fact 

Sheets) will be made available to hea11hcare facilities and/or healthcare providers consistent 

with the terms ofthis letter. 

B. Lilly and authorized distributor( s) will ensure that the terms of this EU A are made available 

to all relevant stakeholders (e.g., U.S. government agencies., state and local government 

authorities, authorized distributors, healthcare facilities, healthcare providers) involved in 

distributing or receiving bebtelovimab. Lilly will provide to all relevant stakeholders a copy 

of this Letter of Au1horization and communicate any subsequent amendm.ents that might be 

made to this Letter of Authorization and its authorized accompanying materials (i.e., Fact 

Sheets). 

C. Lilly may request changes to this authorization, irtcludingto the authorized Fact Sheets for 

bebtelovimab. Any request for changes to this EU A must be submitted to the Office of 

Infectious Diseases/Office ofN ew Drugs/Center for Drug Evaluation and Research. Such 

changes require appropriate authorization priorto implementation. 10 

D. Lilly may develop and disseminate instructional a1,d educational materials (e.g., materials 

providing infonnation on product administration amVor patient monitoring) that are 

co11siste11t with the authorized emergency use ofbebtelovimab as described in this Letter of 

Authorization and authorized labeling, without FD A's review a11d co11currertce, when 

11ecessaiy to meet public health needs. Any instrw.,i:ional and educational materials that are 

i11consistent with the autho,ized labeli11g for bebtelovitnab are prohibited. If the Agency 

notifies Lilly that. any instructional and educational materials are inconsistent with the 

autholized labeling, Lilly mrn'lt cease distribution of such instructional and educational 

9 Supra a.tNote5. 10 The following types ofrevisions maybeauthorizedwithoutreissuingthis letter: (1) changes to the authorized 

labeling; (2)non-substantive editorialcorrections to this letter; (3)newtypes of authorized labeling, including new 

fact sheets; (4)new carton/container labels; (5 )expira tiondating extensions; (6)changes to manufacturing 

processes, including tests or other authorized components of manufacturing; (7) new conditions of authorization to 

require data collection or study; (8)new strength5 of the authorized product, new product sourc.es (e.g., of active 

phannaceuticalingredient)or of product. components. For changes to the authorization, includingthe authorized 

labeling, of the type listed in (3), (6), (7), or(S), review and concurrence is required from the Counter-Terrorism and 

Emergency Coordination Staff/Office of the CenterDirector/CDER. and the Office ofCounterterrorism and 

Emerging Threats/Office of the Chief Scientist. 
16208 Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 


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Page t3-Eli Lilly and Company 

materials. FurthfflllOre, asp art of its notification,theAgency may also.requite Lilly to 

.issue corrective communication(s). 

E. Ltlly wiilreporttoFDAallsetious adverse events andmedication errorspotenuallytelated 

tobebtelovimab usethatarerepQttedio LillyU$ingeithert>fthefollowingoptions; 

Optfon'l:Submitreportsllitoughthe SafetyRepoftingPortal(SRP) as described on the IDA 

SRP web page. 

Option 2: $ut>m:lt repurts di/.lclly through th.e Eleciroriic $ubUll$si-OnS Qil.tewaY (~) l!S• 

describedontheFAERS eleclroriicsubmissionswebpage. 

Submi:ttedrep0rts under both optionsmuststate:"Bebtelqviniab useforCOVID,191.111det 

Emergency Use Autlroriz.ation (EtJAr Forreports submitted under Option 1, include. this 

1l!llguage at 'the beginningofthe quemion "Describe Event''forfuttheramtlysis. For~orls 

.subμii,ttett under Option 2,. include this lil,llgtu.ige atthe beginningo:fthe •~cruie Nanati:ve" 

field. 

R AA manufactuting; packaging, and.testlngsites tor both diugsubstmce and drug product 

usedfot EtJAsupplywill comply with currentgood manufaj:Uringpractice re~.nts 

ofSection 501(~)(2X]3Jofthe Act. · 

G: Ulfywill subrn:itinfotntlltionto~Agencywithinthtee·wod{mgdaysof'receipt..of~ 

inf onmition cuncerniftgsjgt1ifiCil.nt (}Ulllifyptub1ems with distributed drug productof 

bebtelovimab that includes the foUowing: 

• Information concerning any incident that causes the drug product or its labeling 

to be mistaken for,, or applied to,anotherarticle; or 

• Information concerning anymicrobiologkal contamination, or any significant 

chemiCil.l,physical, or.other.change or·detem>ration in the distnbuteddrug 

product, or anyfailure.oforte ormore·.distributed batchesofthedrugprotluctto 

meet.the·estab1ished.specifteatioos. 

If a significantquality problem .affects tm.ieleasedprocfucl and may almi111pactprodrict(s) 

previooslyreleased.and<listributed,then.informationmustbesubinittedforallpotentially 

impacted lots. 

Lilly will include in its notification to the Agency whether the batch, or batches, in question 

will be recalled.IfFDArequeststhatthese,oranyotherbatches, atanytime, berecalled, 

Lilly must recall them. 

Ifnot included in its initialnotification, Lil1y:mustsubmitinformatfon confttnringthat 

Liily has identifi~d the root cause ofthe significaniquality problems, taken corrective 

action, and provide ajustificafion confirming that the corrective action is appropriate 

and effective. Lilly mustsubmit this informationas soon as possible but no later than 

45 calendan:i~ysfromthe initiil.l ttotificatfrm, 
Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 16209 


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Page 7 - Eli Lilly and Company 

H. Lil]y will manufacture bebtelovimab to meet all quality s1andards and per the 

manufacturing process and control strategy as detailed in Lilly's EU A request. Lilly will 

not implement any changes to the description of the product,manufacturing process, 

facilities and equipment, and elements of the associated control strategythatassure process 

perf onnanceand quality of the authorized product, without notification to and concurrence 

by the Agency as described under coodition D. 

I. Lilly wiii listbebtelovimab with a unique produi.,--t:NDCunderthemarketing category of 

Emergency Use Authorization. Further, the listing will include each establishment where 

manufacturing is perfonnedforthe drug and the type of operation performed at each such 

establishment 

J. Through a process of inventory control, Lilly and authorized dishibutor( s) will maintain 

records regarding distribution ofbebtelovimab (i.e., lot numbers, quantity, receiving sire, 

receipt dare). 

K. Lilly will establish a processforniorutoring genomic database(s) for the eniergence of 

global viral variants of SARS-Co V-2. A summary of Lilly's process should be submitted 1o 

the Agency as soon as practicable, butnolaterthan30calendardaysoftheissuanceofthis 

letter, and within 30 calendar days of any.material changes to such process. Lilly will 

provide reports to the Agency on a monthly basis summarizing any fmdings as a result of 

its monitoring activities and, as needed, any folow-up assessments planned or conducted 

L. FDA may require Lilly to assess the activity oftheauthoriz:edbebrelovimabagainstany 

global SARS-CoV-2 variant(s)ofinterest(e:g,, variants that are prevalent or becoming 

prevalent that hatborsubstitutions in the target protein or in protein(s) thatinteractwith the 

target protein). Lilly will petfonn the required assessment in. a manner and timefranie 

agreed upon by Lilly and the Agency. Lilly will submit to FD A a preliminary summary 

report immediately upon comp Ietion of its assessment followed by a detailed study report 

within. 30 calendar days of study .completion. Lilly will submit any relevant proposal(s)to 

revise the authorized labeling based on theresults of its assessment,asmay be necessary or 

appropriate based on the foregoing assessment 

M. Lilly shall provide samples as requested of the. authorized bebtelovimab to the HHS for 

evaluation of activity against emergmgglobal viral variants of SARS-Co V-2, mcludmg 

specific amino acid substitution(s )of mterest ( e.g., variants that are higluyprevalent or that 

harborsubstitutions in the target protein) within. 5 business days of any request made by 

HHS. Analyses performed with the supplied quantity of authorized bebtelovimab may 

mdude,but are not limited to, cell culture potency assays, protein bmdingassays, cell 

culture variantassays(pseudotyped virus-like particles and/or authentic virus), and in viw 

efficacy assays. 

N. Lilly must provide the following information to the Agency: 
16210 Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 


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Page 8 - Eli Lilly antJ Company 

1 Lilly will:sul:mih.study i:ep<>tt.to 11DAcharacterizingthe developmentQf~ARSCo Y::2 resis1ancetobebtelovimab in cell culture passage experiments noJaterthan 

30dil:ys of'the com:pteri:on oftheseexperunems.. 

2. ti11y wi1lsubmitttiFDAall:sequencmgdata assessirtg;hebtefo\ilma:h; ilicluduig 

sequencingofanyparticjpantsarnplesfmmthefullanalyi,~•.·populationfrom 

PYAH arms 9;.14that havenotyetbeencompfoted no laterth'llll.March3 l, 20-22. 

3, Lilly wmsubmita proposed clinical trial protocolto further evaluate bebtelovimab 

fotthette atm.ent of 111ild4:o,;1110detate COVID-l9m rton~hospitali.zed palierits rtti 

laterthan.MatchJ, 2()22. 

0, Lilly and authorized.distributor(s) will make available to FDA uponrequesfany records 

.maintained inconnectionwiththis EU:A. 

He'afthcare Facilitiest0Whoo1Bebfulovimah·1:s Disiribut:edandltealthcare Providers.Adinii:listering 

bebtelovimab 

P. Healthcare.facilities and healthcare. providers will ensurethatthey are.aware of the. letter of 

authoiization, an<lthe·te~•.heiem.and;thatthe .• aUlhorized:Faqt·$eetsaremide available 

tq healthcareproyiders'andto patien!sa.11.d, -ca:regivers;respectiyely, through appropriate 

meansi priorto administrationofbebteloyimab as <les<:ribedm.the :Scope of Authoru:ation 

(Sectionll)_underthis BUA · 

Q: ltea:1th¢i!Je facjlities andl1:ealthcate1,r1.>vklerst¢¢¢1"uigbebtelo'1ntuihWilHtllCkall Sef'j:()IJ$ 

. ad\!eI':se ey@ts arid ~ili.cation. ettOI'Sthat are c~msidtlt¢d w be poten1ialty: related to 

bebtelovitnabuseand musfrepotttheseioFI)A.inaccordancewiththe Fac(Sheetfor 

·ttealthcare.Providers .. Complete.andsubmitaMedWatchform. 

(W:WW:fdago:v/medwatch!report:htm); or com:pleteandsuhmitFOA. Fot'm 3$06(h:eaith 

professional}byfax(1-8()()..FDA·Ol'78)(these fonm:canbe.foundv.ialirikabove) Calil-

&IJl}•:FDA~rosgrorqueSti.()11:s,. Submitted.reports musts~ ''Bebtelovimabuse for . COVIIJ..19under Emergency Use Authorizatiori"'atthe beginning ofthe.question 

''.DescribeEvent"fodurtheranalysis. 

R, Hea.lthbltrefiicilities andhelllthwe providerswill ertstttethatappr<>ptiate stora.geis 

tllllinui:ihe<lm,μlthe produ~isS!ill'littjstere<lc~stetdwitl:l.the~o:(tl:l.isletterl\11dthe 

authori:zedlabeling. 

s. Thrtiughaprocessofiriventotycofili~•heait:hcarefacilltiesWill111ahtliirirecOi'dsl'e~ 

the dispensihgand admini:strafion.ofbebtefov:irnabfortheu:se authorizeclin·thisletter(i,e;, 

lotnUlll~; quaI1tify; receiving:si~ receipt ¢tte), pn>dl!Cts\Qrage; and:maintain patie1.1t 

·i:¢'011n1.WQ11(e.g;,pati~1tname,age;diiiease matUfesiatiQn..nmnberqfl:lose~adulttlist«ed 

perpatien1⁄2 otherdrugs administered) 

t ·Healthcarefacilities will ensureth;danyr¢4ords:associatedwith:this:Et)Aaremafutamed 

u1.1tllrtotified byLill'yand/01:Fl>A. Such records will l:letlllirle 11:vailable tqLilly, HHS, and 

FDAforimipechonuponrequest 
Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 16211 


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P;age 9 - Eli Lilly and Gompany 

TJ: Healthcare.facilities andprc>viders wiUnmort therapeutics infonnation an4 utilization data 

as directedbyHHS~ 

dondilions ReiatedtoPrirtted Mattet A.d.vertismg,ili:id Promotion 

V. All descriptive printedmatter, advertising, and promotioruilmafurnilsrelatingfotheuse of 

·bebtelovimabundetthisauthorizationshallbeconsistentwi1hthe.authoriz.edla:bel~·as 

wellas.the terms set.forth in thisEUA. and me et the requirements setforthirtSeclfon 

502(a)and(ri) ofthe Act,as a:pp1foabte, artd EDA implementingtegulatfon& .Rifetences to 

'1ttpproyed l~tfug'\''pmtiiff~ll!cb!:lin:g" or·siruilar t1a:rm1rin·these.r:1a:qμiri;ti;1ents1:1hi:ul bl: 

un:derstood torefertotheauthorizedlabelingforthe·use:ofbebtelovitnabunderthis 

authorization; In addition, suchmaterilil.s shlil.l: 

• 13e Wlored to the.intended audience, 

• Nottakethe fonnofremmderadverlisemerils, as:thattermis describedin21 

CFR202. i(e)(2X'.i), 21 CFR200:200 and21 dFR201. lOO(f). 

• Presefitthe sattteriskinfottnationtelatingto thema:jotside 'effects an.ii 

cQnil:aindic;m:ons cQncim:ent.1:yinth.:.1n1,diO'andviS!llilpa:rw.ofthepres@fu.1i.on 

f9tady~ifig art!! ptottioti®al t'lflrteri:al$'in.'a.ti/li(Fvisual for:rnat . • Be acconipaniedbythe authorized libeling; if the pronio:ti9natn:rntetfa1s are not 

slJbjectto Section 5Q2(n)oftheAct · · 

• BesubmiitedtoFOA accompaniedhy FonrtFfi:A~225aattheiimeofihltfai 

di~sei:nifitttimorfmit.μi:ie; · 

fi'thei\gen~n:otWKJs ti.i1ythatartydescriptiveprintedmatter,adV¢rtiliingOt prorn◊tfouaI 

material$ do not meetthetei11JS s¢tfc>tth.incot:tditi<>mtY·throughX◊fthisEUA.,LlllymU$t 

cease distribution o:fsuch descriptiye ptfuted matter; advertising, orprc>Ill()tional materials 

·in accordance.wilhthe•Agency'snotification.Furlheimore;.aspart·ofitsnotification,ithe 

Agencymay.a:Isorequite·Lillyto issue•correciivecommumcation(s} 

w. N~ cleseriptive priqt~bnlliter, a:dvertisfug; otpi:om.o1iotialmai¢rlal$te1a.1ingto the use of 

bebtelovimabunder:this .. authorizationmayrepresentor~ggestthatbebfulovimabi$Sllfeor 

.effectivewhenusedforthetreatmentofCOVIl),19 .. 

x: Ail descriptive printedmatter; advertismi.andpr-0motio11airnaterla1~re1a:~tothe use of 

bebtelovimab•umlerthisautlmri.Z!ltionclea:dy·and conspic.uoll$ly·shall stltteth'l!I;: 

•· tJetiteloV:iinab ha:s :tRJf be~ approye4. btitba:sheert-a:uihqrized for ernetgettcy 

use·by FDA:underanEUAiforthetreabnentofmild.to•modemteCOVID-19 

inaduitsartd pediatticpatients(l2yearsofage and older:weigbirtgat1east 40 

kg)wMarea:t liig1t,;;risk fut progression tll.seveteCOV:rt)-19,includittg 

hospitalization ordeath,-atidforwhonialtetna:1iv:eCdVID-19treatmentoptions 

l!cPprovedor autl:1Qtized.by1IT:>A,ai;e11otaccessil:il~orclm.fcl!clfy·!ippiut>Jiate; and 

• The·emergencyuseofbebtelovimabis onlyauihorizedforthedurationofthe 

declarationthlitcircumsfance.sexistjustifyingthe authoriz.ationofthe 
16212 Federal Register / Vol. 87, No. 55 / Tuesday, March 22, 2022 / Notices 

Dated: March 14, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–06009 Filed 3–21–22; 8:45 am] 

BILLING CODE 4164–01–C 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2022–N–0236] 

Prioritizing the Addition of Maximum 

Daily Exposure Information and 

Removing Dosage Form Information 

From the Inactive Ingredient Database; 

Establishment of a Public Docket; 

Request for Comments 

AGENCY: Food and Drug Administration, 

Department of Health and Human 

Services (HHS). 

ACTION: Notice; establishment of a 

public docket; request for comments. 

SUMMARY: The Food and Drug 

Administration (FDA, we, or Agency) is 

announcing the establishment of a 

docket to solicit comments that will 

assist the Agency in determining how 

best to prioritize the addition of 

maximum daily exposure (MDE) 

information for inactive ingredients that 

do not currently include MDE 

information in the Center for Drug 

Evaluation and Research’s Inactive 

Ingredient Database (IID) and whether to 

restructure the IID by removing dosage 

form information. 

DATES: Submit either electronic or 

written comments on the notice by June 

21, 2022. 

ADDRESSES: You may submit comments 

as follows. Please note that late, 

untimely filed comments will not be 

considered. The https://

www.regulations.gov electronic filing 

system will accept comments until 

11:59 p.m. Eastern Time at the end of 

June 21, 2022. 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 No. FDA– 

2022–N–0236 for ‘‘Prioritizing the 

Addition of Maximum Daily Exposure 

Information and Removing Dosage Form 

Information From the Inactive 

Ingredient Database; Establishment of a 

Public Docket; Request for Comments.’’ 

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 


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Page l O - Eli Lilly and Company 

emergency use of drug; and biological products during the COVID-19 

pandemic under Section 564(b)(l )ofthe Act, 21 U.S.C. § 360bbb-3(b XI), 

unless the declaration is temiinated or au1horizatiort revoked sooner. 

IV. Duration of Authonzation 

This EUA will be effective until the declaration that circuinstances exist justifymgthe 

authorization of the emergency use of drugs and biological ptoductsdurmgthe COVID-19 

pandemic is tennmated under Section 564(b )(2) of the Actor the EDA is revoked under Section 

564(g)ofthe Act. 

Smcerely, 

Isl 

Jacquelme A. O'Shaughnessy, Ph,D. 

Acting Chief Scientist 

Food and DrugAdmmistration