42850 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 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. 

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. 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0335] 

Authorizations of Emergency Use of 

Certain Biological Products 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 two Emergency Use 

Authorizations (EUAs) (the 

Authorizations) under the Federal Food, 

Drug, and Cosmetic Act (FD&C Act) for 

biological products for use during the 

COVID–19 pandemic. FDA has issued 

one Authorization for a biological 

product as requested by 

GlaxoSmithKline LLC and one 

Authorization for a biological product as 

requested by Genentech, Inc. The 

Authorizations contain, among other 

things, conditions on the emergency use 

of the authorized products. The 

Authorizations follow 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 Authorizations, which include an 

explanation of the reasons for issuance, 

are reprinted in this document. 

DATES: The Authorization for 

GlaxoSmithKline LLC is effective as of 

May 26, 2021, and the Authorization for 

Genentech, Inc. is effective as of June 

24, 2021. 

ADDRESSES: Submit written requests for 

single copies of the EUAs 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. 

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), 

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 


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Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42851 

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), 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 Authorizations 

The Authorizations follow 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 

Authorizations under section 564(c) of 

the FD&C Act are met, FDA has issued 

two authorizations for the emergency 

use of biological products during the 

COVID–19 pandemic. On May 26, 2021, 

FDA issued an EUA to GlaxoSmithKline 

LLC for sotrovimab, subject to the terms 

of the Authorization. On June 24, 2021, 

FDA issued an EUA to Genentech, Inc. 

for ACTEMRA (tocilizumab), subject to 

the terms of the Authorization. The 

initial Authorizations, which are 

included below in their entirety after 

section IV of this document (not 

including the authorized versions of the 

fact sheets and other written materials), 

provide an explanation of the reasons 

for issuance, as required by section 

564(h)(1) of the FD&C Act. Any 

subsequent reissuances of these 

Authorizations can be found on FDA’s 

web page: https://www.fda.gov/ 

emergency-preparedness-and-response/ 

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

IV. Electronic Access 

An electronic version of this 

document and the full text of the 

Authorizations and are 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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42852 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 


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GlaxoSmithKline LLC 

Attention: .Debra H. Lake; M~S. 

SenJor Dir®tor, Olol>al Regulatory All'iilits 

Five Moore Drive · 

POl3oxB398 

i)urham. North Carolina 21109-

RE: Emergency TJseAut;hQnzath:m IO.ff 

Mey 26,2021 

nits letterJs in resppnse fo Qla.xoStnithKline LLC's (GS!<,,) reque-st that the Food and Dmg 

Adrnini~tfon (FDA) issue an Emergency IJse Authorization (BUA) 19r the emergency use 9f 

sotrovimab for the treatment of mild-to-moderate coronavirus dlsease 2019 (COVID-19), as 

described in :t:he Scope of Authorization: (Section II) or this letter,. pursuanno Section 564 of the 

Fecleral Food1 I)mg; and Cos:i;neuc Act (the Act) (21 IJ.S~C. §$60bb:l>~$), 

On February 4, 1.020, pursuant to Section 564(b)(l)(C) oiihe Act;_ the Secretary of the 

Department of Health andB:uman Services. (AAS) determined that there is a public health 

emergency that.has a signifi:can:t potential to affect national security <lt the health and :security of 

United Sta:t¢.s citi1,e1i:s Jiving• ~Wad; and 1ha,t itrvo:lves the· vints that Gas1.JS!:lS cornnavi~ diseMe 

2019 .(COVID-19)..1 On the basis of such determination, the Secretary of HHS on March 27, 

2020, declared thatcircumstances exist justifying the authorization of emergency use old.rugs 

and bfologfoal ptoducts during tbe COVlI>• 19 pandemic, putsuant to: Section 564 of the Federal 

Food; Pru,g, :and CQstnetic Act (the Act) (21 U.S,C, J6Qbbb·3); :subject to terms ofany 

authorization i(;sμed. μnder that $ectkm/ 

Sottovimab is a recombinant huii1ai1 IgG'itc monoclonal .antibody that binds to a COllSetved 

epiippe on: the spike· protein r®ept<ltbindin:g domain or SAllS·CoV-2, Sottovi:tnab does not 

cornpete with lluinan ACE2 l'.eceptor bin.ding, Sotro,i:ma,b Js an inve$tig21tio.n.al drug :and Js nQt 

currently 4ppnxved for any indication, 

Based on review· ofthe interim analysis ofphase 1/2/3 data from the COMET ~ICE,clinical trial 

(NCT #0454$060), a rand<li;nizecl; doubte--blind, placeba-contr<illed clirrical trial evaluating the 

saf~ an4 e:fficacy o:fsotrovi:tnaP 500 mgIV in outpatient (l1Qn-h.osp~talizedJ ad'lllts with SAASCo V'-'2 infection, it is reasonable .to beliew that sotmvimah may be effective for the treatment of 

1 U.S. I)eparlment.ofR~ !j!liJ Ruman Service.$;D¢terminatfpn.·of'a l':t-1.hltc Hea#k EmergNIC:Y at!iJDecJ:aration 

that CirclJU!stanr;e:s Exist J~stJJJ,iris Afffelorizati0f!$Pur:rnarit to}ieqtiot'l-564(b) ofi!heFede,:1;1lFoptJ, Dr11g, arid 

CO$itll!ticA.¢t; 21 U.S.C.§ 360bblF5 .. Febrtlaly,4,2020, - 1 US, :OcpanmcntofHClllth !l!1!1. Rmnm:i: Sciyiccs,D«efi.!r(itir.m tkq.lC./'rC1im~iaru;Ysl3xi$i.JriS/'ijJing,~tfmri1.(J(i<1~ 

Pur.rtlant ta Se:ctian 564(h} of the .PederatFood,.Drug; tmdCcsmetic.Act, 2I tf:S.'C. J 360bbh0 5; 85 FR 18250 

(April 1, 2020), 
Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42853 


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Page 2 --- GlaxoSmithKline 

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 progression to severe COVID-19, including hospitalization or death, and when used under 

the conditions describedjn this authorization, the known and potential benefits of sotrovimab 

outweigh theknow11 and potential risks ofsuchproduct. 

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

Act are met, I am: authorizing the emergency use of sotrovimab for trea1ment of COV~19, as 

described in the Scope of Authorization section_ of this letter (Se;;tion II)and subject to the terms 

of this authorization. · 

t Criteria for Issuance of Authorization 

I have concluded that the emerget1cy use ofs-0trovin1ab for the treatment of COVID-19 when 

administered as described in the Scope of Authorization (Section II)meets the criteria for 

issuance ofan authorization under Section 564(c) of the Act, because: 

L SARS-CoV-2 can cause a .serious or life-threatening disease or condition, including 

severe respiratory illness, to humans infected by this virus; 

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

that sotrovirnab may be effective in treating 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 viraltesting, and who are at high risk for progression to 

severe COVID-19,.including.hospitalization or death; and that, when used under the 

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

sotrovintab outweigh the known and potential risks of such products; and 

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

sotrovimabfor the trea1ment 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 viraLtesting, and who are at high risk for progression to severe 

COVID- 19, including hospitalization or death, l 

II. Scope of Authorization 

I have concluded, pursuant to Section 564(dXi) of the Act; that tbe scope of this authodzation is 

limited as follows: 

• Sotrovimab will be used onl)'by healthcare providers to treat mildato•moderate 

COVID-19 in adults and pediatric patients (12 years ofage and older weighing at 

least 40 kg) with positive t'esnlts ofditect SARS-CoV-2 viral testing, and who are at 

high.riskfor progression to severe COVID-19, including hospitalization ordeath; 

3 No other criteria of issuance have been prescribed by regulatlohunder Secti_ori 564(cX 4) of the Act. 
42854 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 


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Page 3 -- GlaxoSmithKline 

• Sotrovimab is not authorized for use in the following patient populations 4: 

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

• Adults or pediatric patients who require oxygen therapy due to Cov1D19, or 

• Adults or pediatric patients who recquire an in.crease i:n baseline oxygen 

flow rate dueto COVID-l9inthose patients on chronic mqrgenilierapy 

due to underlying no1r-COVID• 19-related comorbidity. 

• Sotrovimab may only be administered in settings in which health care pi:oviders have 

immediate access to medications to freat a. severe infusion reaction, such as 

anaphylaxis, and the ability to activate the emei:gency medical system (EMS), as 

necessary. 

• The use ofsotrovimab covered by this authorization must bein accordance with the 

authorized fact Sheets. 

Product Description 

Sotrovnnab is supplied 111 individual single dose vials. Individual vials and carton container labeling for 

sotr<>vimabare clearly marked "For use um:fer Emergency Use Authorization." Sotrovimab is a 

recombinant humanigG h: monoclonal antibody that binds to a consei:ved epitope on the spike 

protein receptor binding domain of SARS-Co V-2, Sotrovimab does not compete with. human 

ACE2 receptor bindirtg. 

Sotrovimabis available as a 500 mg/8mL (625 mg/mL) sterile, preservative-free, clear; 

colorless or yellow to brown solution tobe diluted prior to infusion. Unopened vials of sotrovimab 

should be stored under refrigerated temperature at 2°C to 8°C (36°F to 46°F). The vials should be 

kept in theirtdividual original cartons to protect from light. The diluted infusiort. solution of 

sottovimab should be adm.inisteted int1I1ediately. If immediate administration is not possible, 

store the diluted infusion solution for up to 24 hours at refrigerated temperature (2°C to &°C 

[36"F to 46°F]) or up fo 4 hours at room temperature (20°C to 250C [68°F to 77°F]) including 

transportation and infusion time. 

Each carton containing a single treatment courSe of the authorized sotrovimab will include a 

single copy each of the following product~specific doctnnents detailing information pertaining to 

its emergency use (referred to as "authorized labeling)5: 

• Fact Sheet for Healthcare Provide!'.$: Emergency Use Authorization (EUA) ofsotroviinab 

• Fact Sheet for Patients, Patents and Caregivers: Emei:gency Use Autb()rization (EUA) of 

sotrovimab for the treatmertt Coronavitu.'! Disease 2019 (COVID-19) 

4 Benefit of treatmentwith.sotrnvimab has not.been observed 1h patients hospitalized due to COVID-19. SARS~ 

Co V-2 monoclonal antibodies may be associated with worse clinical outcomes.when. administered to hospifuliz:ed 

patients with COVID 19 requiring high flow oxygen ormechm:iicalventilation. 5 The authorized labcling for EUA 100 will also be available on GSK' s website at www.sotrovimlih.com 
Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42855 


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Page 4 -GlaxoSmithKline 

I have concluded, pursuanttoSection 564( d)(2) ofthe Act, that it is reasonable to believe that 

theknovvn and potential benefits ofsotrovimab, when. used.for the treatrnentofCOVID-19 and 

~din accordance with this Scope of Authorization (Section 11), outweigh: the known and. 

pQtentialris~, 

l have concluded; pursuantto Section 564(d)(3) ofthe Act, based on the totality. ofscientific 

evidence available to FDA, that it is reasonable to believe that sotrovimab may be effective forthe 

treatment ofCOV:ID-19whenused in 11.ccorclance with lhjs Scope of Authorization (Section U), 

pursuant to Section564(c)(2XA) oftheAct 

Having reviewed the scientific informationavailabletoFDA,. including the information 

supp0rtingthe conclusions described in Section! above, lhaveconcludedthat sotrovimab.(as 

described in this Scope of Author:ization (Section Il))meet& the criteria set forth in Section 564(c) 

ofthe Act concemingsafety and potential effecliyeness. 

The erri~ency use ofy~lll' product underan EUAmust be consistenfwith, and Ulay notexceed, the 

terms of the Allthorization, including the Scope ofAuthorization(Section 11) and.the Conditions of 

Authorization (S~ion. UI). Sl;lbject to the tenns. of.this EUAand tind.rr the circumstances. setforth in 

tlte Secretary of lffiS's detennination unde.r Section $64(b )(lXG) described <lbo.ve anc,l ihe Secretary 

ofHHS's corresponding declaration.tmder Section 564(bXl), sotrovimab is authorized to trealmildto-moderate COVID-19 illness in adults and pediatric patients (l2 years ofage .and oldetweighing 

at least 4o kg) with.positive results of direct. SARS-CoV-2 vintlte$ting, who:are at high: risk for 

progression to severe COVI0-19;. including hospitalization or death, as described in the Scbpe of 

Authorization (Section ll) under this EUA; deSpite thefactthatitdoes not meetcertain requirements 

otherwise required by applicable federal law, 

nt Conditions of .Authorization 

Pursuant to Section 564. ofihe Act, lam establishing the following conditions: on this authorization: 

GSK and Authorized Distcibutors:!i 

A GSK and autliorized !liiitribufor(s) will ensure th;ii tile authorizedlabeling (i.e.; f actSbeets) 

will accompany the authorized sotrovimab as.de&.-ribed in Section II of this Letter of 

Authorization, 

R GS:t(and authorized distributor(s)will ensure that appropriate storage and cold chain is 

maintained until the product is delivered to healtlttare facihties and/or healthcare providers. 

C. GSKand authorized distributot(s) wtll ensure that the terins oftlns EU A are made 

available to all relevant stakeholders (e.g., tJ.S. iovemment agencies, state andJocal 

go-vernmentauthorities, authorized di.stcibutorS, healthcare facilities, heal1hcare providers) 

involved in distributing or receiving authorized sottQyimab, GSK will provide to all 

relevant stakeholders a copy of this letter of authorization and. connnunicate any 

6 «Authorized Distribut-0r(s)" are identified by <1SK as. an entity or entities allowed to di;;tribute authorized. 

sottovim.ab. 
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Page S - GlaxoSmithKline 

subsequent amendments that might be.made to this letter. of authorization.and its authorized 

accompanyit1g materials (Le,, Fact Sheets). 

D. GSKmayreques.t changes to this atrlhorization, ittQludittgtothe authorizedF!lcl Sheets for 

sotrovimab, Any requestforchanges.totluf:l EUA 111ustbe submitted to the OffiCl:l of 

Infectious Diseases/Office ofNew Drugs/Center for Drug Evaluation and Research, Such 

changes t'llqtlire appropriate authorization prior to implementation. 7 

E. GSKm.aydevelop &id diss.em.inate itt~clional and ~ucalional materials(e:g,, materials 

providing infonnation on product administratibmmd/orpatientmonitoring} that are 

consistent with the authorized emergency use.ofsotrovimab.as described in thisletter of 

authorization and authoozed labeling, without FDA 's review and concmtence, when 

necessary to me¢t pu'!,Jichtlalth needs. Any ~clional 1111d educational mllteriahitl:ud: are 

inconsistent. \Vi.th the atrlhorlzed labelittgfor sotrovimab are prohibited. If the Agency 

notifiesGSKthat any instructional andeducationalmaterials are inconsistent with.the 

atrthorized labelittg, GSKmust cease distribution.ofsuch.inst:ructional and educational 

materials in accordattce with the Agency•s.notification. Forih:ermore, as part of its 

notification, the Agency may also ri:,quire OSK. to issue corrective communication(s). 

R GSKwillreporl to FDA serious adverse events.and all medication errors associated with 

the use. of the authorized sotrovimab that are reported to GSK using.either of the following 

options. 

Option l: Submit reports through the Safety Reporting :Portaj(SRP)asdes.cribed on the~ 

SRPwebpage. 

Option 2: Submit reports directly thiwgli the Ele¢tronk: $qbnussions Gateway (ESGj as 

descnoeil on the FAER.S electronic submissions web page. · 

Submitted reports under both options should state: "Sotrovimab useforCOVI1).19under 

Emergency Use Authorization. (EUA);'' For reports submitted under Option 11 include this 

language at tht:1 be~g of the question "Describe Event''T<>rfurther analysis. For: reports 

submitted :under Option Z include th.is langμage at the beg]jttiing of the ''()lllle "Nattittjve" 

field. 

1 The foHowingt~s of~visions may be authorized\viiliouUeissuirig thls letter: (l) changes to the mitlforized 

lab<iling; (2) tton-substantiye edi~oriatct1n:e¢ti0Mto this leμer; (3}new ty:pes ()fa,'Utlilirized labelirtf induding new factsheets; (4) new CB.l'tort/container label$; (5) t:itpiratibn,ting e~tensio~; (6) · ch:anges to ·manufacturing 

prbcesses, inc!udil% tests ot oilier authorized Cort1pommts o( manufacturing; (7) ne~ c,oriditions of auth()ritatiort to 

requite d(lta bollection <>(study; ($) new sttertgth,s of tl'.te authorized prodi;ict, neyrprqduct squrce~(e.g., ofacti.ve 

pMt:maceutibal. ingte.die11t)or ofwoouc[9())rtponimts.ftit chart~WS' to the ll.utllorization;. insluclmg the ~~orited 

labeling, ofthe type listed in(3), (6); (7); or(8), review and c;<m¢urrenceif\reqt1ired from the Counter-Ten:oru;rrt and 

Emergency CootdinatiQll $tllff}()ffice of the Center pirector/@ER !liid the Office of C-Ountertettorism and 

En1 erging Thl:ea~/Off1® tiftlie Qhief Scientist. 
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!>age 6 -GlaxoSmithKline 

Gs AUmamifacturing, packaging, and testing sites for both drug substance.and drug product 

willcomplywithcutrent gomfn1anuf'actutingpl"licticerequitements ofthe FD&C Act 

section 50l(a)(2)(B). 

ff: G.S.K wilts11bnutinfQQ11ation fo the Ageu.cywil:hii:t threewQn011g days 'Qf~ipfofatiy 

information concerning significant quality problems with distributed drug product of 

so1rovimabthat•includ¢s.the .. folloWing: 

· • llif onnatioo c9ncetitrng any mcidentthat causes the drug product otits Iahelfu:g 

· fu be mistilken t«, ()tapplied to, another artide; or 

•· lnfonnatioo ciJfi'Cettiinganymicrobfofogfoal contammation, otany$igtillicaril: 

chet'niqaJ; pbysi~ m: other cluQ1ge or 4eterl.oni,ti◊11in:the dis.tribul.l4 drug 

product, orltt'lif failure of one ormoredistributedbatches ofilte producttomeet 

· the.establishedspecifi41atiom. 

Ifa si~crurt.qualityproolem;affects tmteleased produclandn1ayalso itnpacfJ?fOducl(~) 

preyi~lyreleasedan4 dis.tribul.ld; th~ infonni.tti,011 should besubm~d fQI'all potentially 

itnpactedlots. 

oSRWill: iru.;fod~iti its fiOttlic:ation.to the Ag¢rtcywhethetthehatcfi; otbatehe$; tit 

qμe$tion \\'iU beii:icalled. If FPA:req11~tbatthelie~ or attYother batches; atmiyfune,~ 

iecallecl, G$K must-recall them, 

IfnoHncluded in its initial notification, GSKmusf submit information confinliingfhat 

GSKhasidentifiedthe root cause ofthe· Significant quality problems, taken :corrective 

aetio; and provide aJustificati9n coliflnning thatthe con:ectlve actiQil is llpptopriate 

and effecti:ve. GSKmust submit this infonnation as soon as possible hut rtCi later.than 

4Scal~ndar days ffom the initiitl notifi<:atiQ11, 

L GSKWtlf mmufaciin'e shtroVihihli to meetan quality stantla.fds mdperthe.mmufacti.J.riiig 

processandconttolsttat¢zy,is detail~foGSl<:sEUAreq11¢$t. OSK will not implert1ent 

any changes to ibe de$Cription of the proituct..manuf~~process, ~ilities and 

equipment.and elemerits ·of the associatedcontrolstrategy that assure ~perfonnance 

and quality of the authorized product, wi1hout notificafionto and concurrence by the 

Agency a$ describedurtdetconditionD, 

1 0$:r<\\'ill lis1;sotf9yimabw:ith a iJ.Ui.<1.tte :Nt>t;: w4ertbe rnark:etmgllateg'<>ty oftJuapprttved 

Drug-Other. Ftll'.ther;•thelistingwillinclude each establishment ~heremanlifacluringis· 

perfonnedforfhe drug andfhe type ofoperation perfonnedatsuchestliblislnnent; 

R. lln'.ougha p~.ess of inventory control, GSKand attth<>tized distributot(s)will.maintatn 

n,,cQI'ds niga,rdin:g~blltion oftl.le~orized s<>irqvimab Q . .:., lc)t:μumbers, qllatltj1;y., 

receivingsite,receipt date} . . 

t. ·GSK and amhorized diS1ributot(s}witlmake available to EDAuponre@est anyreconls 

maintained in com1ectionwitb:this EDA · · 
42858 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 


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Page 7 - GlaxoSmithKline 

M. GSK will establish-a process for monitoring genomic database(s) for the emergence of 

global 'Viralvmants of SARS-CoV,2,.Astimnlacy of GSK'sprocess should be.submitted 

to the Agency as soon as practicable, but no latetthan 30.calendat days of the issuance of 

this letter, and within 30 calet1dat days ofany mat.malchanges to suchprocess. G$Kwill 

provide reports to the Agency on amontlily biisissUiillllllrizing any findings as a result of 

its monitoring acti\rities and,. as needed,. any follow-up assessments planned or conducted.. 

N. FDAmayrequireGSl{t{)assessthe activity of the authorized sottovinrab againstany 

global SARS-CoV~:2 variant(s) of interest (e;g,, variants thatare prevalent or becoming 

prevalent that harbor substitutions inthe target protein or in protein(!t) thatinteractwith the 

target protein), GSK will perform the required assessment in a manner andtimeframe 

•~.upon by GSK and the Agency. GSK will submit to FDA a preliminary summary 

report inimediatelyupon completi'on.-0f its li$sessment followed by a detailed study report 

within30calendardays ofstudycompletiolli GSKwill submitanyrelevant proposal(s)to 

revise the authorized labeling based on the results of its assessment,. as may be necessary.or 

appropriate based on the foregoingasse$sment 

n GSK..shall provide $1llllples as requested of the authorized sottovimab tQ the U.S. 

Deparlmeut of Health and Human Services (HHS)fonvaluation of activity .against 

emerging.global·viral. variant, of SARS.:CoW2, including specific amino acid 

substitution(s) ofinterest (e.g., variants that are highly prevalentorthat harbor substitutfons 

in the target protein) within 5 business days. ofany request made by HHS. Analyses 

performed with the supplied quantity of authorizedsottovimab may include, but are not 

limited to, cell culture potency assays, protein binding assays, cellcuffure variant assays 

(pseudotyped virus-like particles and!or:authentic virus1 and in vivo efficacy assays. 

P. GSKwill submitto'FDA all sequencing 4ata assessing sotrovunab, including sequencing 

of any participruitsamples from the :full analysis population from<JOMET-JCE that.have 

not yet been completed no later than September 30,·2021, GSK will provide the Agency 

with aftequency table reporting all substitutions detected for.all participants at all available 

timepoints at af'tequency.>1 %. 

Q; OSK.: will suhmjtto FDA allSA'R:S;;Co V~2 viraj.shedding and viral. load data; including 

quantitation.ofviral shedding and viral load for any participant samples fromthe full 

analysis population from COMET-ICE that have not yet been completed, noJaterthan 

June 30,2021. 

Healthcare Facilities to Whom the Authorized Sotrovimab Is Distrib:uted and Healthcare J>roviders 

Administering the Authorized Sotrovimab 

R Healthcare facilities and healthcare pr9videts will ensure that they are aware ofthe lett~ Qf 

authorization, Md thetenns herein; and that the authorized FacfSheets are made available 

to healthcare providers and to patients and. caregivers, respecti.vely;.through appropnirte 

means~ prior to administration of sotrovimab, 
Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42859 


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Page 8 --Glaxo$mithKlin:e 

S; Healthcare.facilities andhealthoare providers receivingsotrovimabwill1rackserious 

-adverse events that are consi'detedtobe pot¢ntililltattrlbutab1e 10 sotrovima(;use and must 

repott1hesi:!10 FDAinaccordan.~ wi1hthe FactSheetfot llealtbcare ~\iidets. C6mplet¢ 

~ct,s_μJ!tμit-aMedWllfch::t'<mtt{W:WW;filaJtov/ittedwatchlt@m:t;htm,lor Cc»:t1plete~i;t :$Ul>lJ!lt,:F:Pi\-F<>mi~sQO tlwmttrprof~,icm{ll}l>yfl,llfi(l,,~OP-Jtr>4"0f'.!$,) (~f~.:im 

'.befoundvia]ink:above). Call 1-..800,:FDA.-'108&.for-questions. Submtltedreporls·should 

state, •'Sotrovimab ®fot00VJ:]).l9ooder Etnetg!fflcy Use Authorization" at the 

.he~#f ili'¢ tprestimt "Pe$crlbe E:v!int"f orfurihet apaiy$i:$; 

T, Heal1hcare·facilities and healthcare providers will ensure1hatapproprfate storage andoold 

chain.ismaintained.untiL1he.produotis administeredconsistentwifu thetennsof1his.tetter. 

u: ').lm)μgha pmc_esi; of inventory cQltl:tot healthcarefaciliti~ \¥ill mlliil:taitf ®ords regmfuig 

1hedispensed aμthorize4sob;ovirnab(i.e.,fotnumbets; quantity; receiv:i/1gsite, receipt · 

date),produclstorage;and.maintainpatientinfonnation{e.g.,.patientname; age;.disease 

mariffestation, tlill'l1her-of doses ildministered per patient, oilier drugs adlninisteied). 

v: 1:tea11hclitefaciiities will ensurirffiatlliiy rec'OttJil asi;ocia:ted with this; EQA.c are. m~ed_ 

ut1tilμqfifi.ed by 0$:K lllldlqrf:'DA, Siwh recordi;willbemade availlμ>Je-toGSl\. lUIS, imd 

FDA;forinspeclion.uponrequestComlitions. Relatedto,Prirtted Matter, Adveft®t)g and Promotion 

w. Alldescriptiy~ prurted rn~er, adv~ing; anci promoti()tlalmateriaTu relatirtgfo the~ of 

1he,sotrovimab under1his authorization shall be consistent witlt.1he authorized labeling; as 

wellasthe terms setfortli.inthisEt:rA, andmeettherequiiements setforthin section 

S02(;1) and (n)ofthe Act atid FPA:implementin:gregulations. lh addition, such.material~ 

shall:. 

• Be tailored to the inten4ed llUdil,U,l"Ce, 

• Nqftaketliefonn oft¢mfudet'adv:ettisements. asiliatJenni~ describe4in.J1 

CFR202,l(eX2Xi). 21 CFR20MOOand21 CFR201.100(f); 

•• ~etlfril<kfufoftl11lfiottCOI1currenfurinthe iμi(.lioa:iid•.\iisnat·parls-ofthe 

presentationforadvertisementsdisseminated.through•mediasuch•asradio, 

television, ottelephone communications. 

.. Beaccotrtpariiedbyffie authorizedl:abeling, 

•; Besubmittedto FDAaccompaniedby FonnFDA-2253 atthe.timeofinitial 

dissemittation or-tii"Stuse. 

lfffie Ag.;ncyrt()tifi~ G$K that a:ny'd~scr:ipti,ve printe4 t®tter; adv:ert;isi~otptQUl()tionat 

•materials do nofmeef1he-terms setforth inoonditions W,-,Yof1hisEUA, GSKmust cease 

distribution of such descriptive printed matter. advertising; or promotionalmaterials in . 

. ~cordance•withtheAgency;snoti.fication.·Furthermore,_aspart-of·itsnotification.the 

_ Agency may also require OSK to issue -cotte~~ comtt1.urticatitm(s). 
42860 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 


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Page 9 ... GlaxoSmithKline 

X. No desc-'t'iptive printed matter, advertising, or promotional materials relating to the use of 

sotrov:imabunder thi.s aulhorization may represent or suggest that sottovimab is safe or 

effective when used forthe treatment ofmild-t.o-moderate C0Vll).19in. adults and 

pediatric patients ( 12 years of age a11d older weighing at least 40 kg) with positive resu.hs of 

direct SARS-Co v~2 viral testing, and who are at high risk. for progression to severe 

COVID-19,includinghospitalization or death. 

Y. All descriptive printed matter, advertising, .and promotion.al materiai, relating to the use of 

the sottovimab clearly and conspicuously shalls:tate that: 

• Sotrovin1ab has not been approved, but has been aulhorized for emergency use 

by FDA under an EU A, to treat mild-to-moderate COVID-19 in adults and 

pediatric patients ( 12 years of age a11d older weighing at least 40 kg) with 

positive results of direct SAAS-Co V•2 viral testing, .and who are at high risk for 

progressi<>n to severe COVID-19; including h<>spitalizatio11 or death; and 

• 111e em.ergency use ofsotrovimab is oruy authorized for the duration of the 

declaration that circumstances exist justifying the authorization of the 

einergencyu.<ie of dl'tlgs and biological prodi1cts doring the COVID-19 

pandemic under Sectioi1 S64(b)(l) ofthe Act, 21 U.S.C. § 360bbb•3(b)(l), 

unless the declaration its terminated or authorization revoked sooner. · 

IV. .Duration of Authorization 

This EUA will be effective until the declaration that circumstances exist justifying the 

authorization of the emef8e11cy use of dmi'!! and biological products during tbe COVID-19 

pandemic is tem1inated under Section 564(bX2) of the Act or the EUA is revoked under S.ection 

.564(g) of the Act. 

Sincerely, 

RADM Denise M. Hinton 

Chief Scientist 

Food and Drug Adininistratioo. 
Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42861 


khammond on DSKJM1Z7X2PROD with NOTICESEN05AU21.029</GPH>

r2i~:~t~•Ltt1. ... . Attention: :q~y J;'hanibipillai Regtilatbfy: Project•Matiiigeftient 

I DN.A:Way,.Bldg45-l 

S§'!ltl:t S~JJ~i~(@ 9494~Q 

lUtt Bmergem:;rt.Jse.Authoiizat:ion.Q~9 

June:M, 2021 

bear•·Ms;. l'harribtpillah 

Tfilslettedsinrespoiiseto'·C'kn:entec};fuc,+s.(Gimente6h).requestthattheFoodand·0rug 

Admini:stration(EDA)issueanEmerg-encyUse Authorization(EUA)fortheeme1¥ency·use of 

.Ac:teμit:a1(tqc~b) .• f¢i'fb¥··tteattrieyij:~f¢:otQiliivirosdi:~~¢2Ql9(CO\ffD~19) ·uJ§~ 

hospitalized patients;. aS describedfothe Scope of.Authorization (Sectirn .ti) of this letter~ 

pu:rsuantto.Section·5~4ofthe:Federal.•Food,Qrug, •. andQosmeticAc:t•(the·Act)(2l.U;S,Q .• . §36Ubbl);;3)2 . . 

iqti .. Il~btwify4,202Q,•ptiisplltjtto ~e¢tioii~6~(1:>)(I)(Q)<>ftheJ\cit, ... tlte $eqr¢tatypfthe DepartmentofHealthand.Jlitrnan.Setvices(HH$)detetmined:tbatthereis•li:publichealth 

E:itl.erget:icY thaj:.11l'lsJt $ig~i.fi¢lt:irt.pot¢ii,tiaJ:tQ a+f ectlli!.1i◊miJ. ~cμtify ◊,ttlie .. h.~tl:tJri14 $¢cuiifyof United•Stlitescit:izenslivingabroacl,•and•thatinvohresthe.V1Ii.:is·ihat•causes corbtlav.imstlisease 

1619•·(dOVIb.0 rn)?Orr·the•basis·ofsuch.·deterrnination,.the SecrefuryofHHS onMarch21; 

· 2020,.4ec1a.redtlfut:~cmrista.ndes ~stj~lifyirtgthe ailthori,zati611. 6fertt~gency~~◊fdftig~· 

•andbiologicalproduds duringthecoVID~l9.pandemit;pursuantto Seclion564◊ftheAct:01 

·u. ~;C\ 3:Ql>ol1~1), .. sul:>jec:t totermsofariyauthorizati@issuedlm4erthatsecti@?·• 

Actemraisarecombinanthuma:nizecl.monodooal0antlbmlythat:se1ec1iveiybinds·•.fo·ooth·•sohible. 

·•aridfuerriptarte~Qoil.¢hurtiiinIL-~fecept~•(~L-6R,andiflIL•6R):and.siibs:e4uentlymhipi~.IL6'-Jtiedi~t~p$j"g't1aljitgtht®gh·tl:t~se t.eceptot$. Ac~isgpA-wov-@f'otseVe@,μtdi¢~ti®s4'; itowever; Acterm:a is notapprovedfor theJreatment ofCOV1D-i9. · · · · 

i1•Fortheptitposesofthis:Letttt.·ofAtith&izlitio:n,·lheuseofthetraderiameiActernra;iiiiiiteridedfo:refei'fo1:he 

·cotninerdally11vailable:Actemrathat is. in-United·Stiites•dii!tribiitiort under the apPtoved Biologjcs•·License 

Appliclitiori 125276; otil.y:.Asdistus!ied•filrth«·in.SectioliIIofthiS·letter,Acteirirathafis·ci:itnmetcially available 

•imderthis·licensure:ii.•authorizedforeritergfflcy:·•USeCoosistentwiththetc:nns·andconditions .. ofthis.letter,. 

·

2U;lJ;.DtjiattmenfofHeiilth•andHi.itrninSeivices,.Deteritiini:itiiinqfahiblii:.Hei,JthEiiiei'gencycitid1Jecliiriiti<in 

tJtarctriimlsti:iik:es.ExistJurtfhmgAJliJtoi:fziiliri!J.J>ursuanfto.Seiioon·sM(bJ<Jftbe.FeciiriilFood.•Dtug; and· 

CatmtticAct, .21 U£C. §36Qbb/j;J;:FebrullryA,:.t020. . . lm11~~~~%t,7Je•~es~~~lfi~~~~~-~~£&k>,~ 

.•• ;Ig:1;:~:::::r~~==~~:s1t~;J;~ff~~ns~lbLpcft 
42862 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 


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Page 2 - Genentech, Inc. 

Based on review ofthe d.ata from the RECOVERY clinical trial (NCT #04381936), a 

randomized, open-label, controlled, platform trial; the COV ACTA trial (NCT 

#04320615), a randomized, double-blind, placebo-controlled clinical trial; the EMPACTA 

clinical trial (NCT #04372186), a randomized, double-blind, placebo-controlled clinical trial; 

and the 1"1..:,Jcv1u•nv clinical trial (NCT #04409262), .. a randomized, double-blind, pla.cebocoutrolled clinical trial, it is reasonable to believe that. Acternra may he effective for the 

treatment of COVID-19 in. hospitalized adults and pediatric patients (2 years and older) 

who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or 

invasive mechanical ventilation, or ex1racorporeal.membrane oxygenation (ECMO), and when 

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

Actetnta outweigh the know11 a11d potential risks ofsuch product. 

Having concluded that the criteria for issuance ofthls. authorization under Section 564(c) ofthe 

Act are met, I am authorizing the emergency use of Actemra for the treatment of COVID-19, as 

described in the Scope of Authorization section of this letter (Section 1I) a11d subject to theterms 

ofthis authorization. 

I. Criteria for Issuance of Authorization 

l have concluded that the emergency use of Actemra for the treatment ofCOVID-19 when 

administered as described in the Scope of Authorizati0l1 (Section lI) meets .the criteria for 

issuance ofan 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 te.spiratory iltness, to humans inf'ected by this. virus; 

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

that Actemra may be effective for the treatment ofCOVID-19. in hospitalized adults 

and pediatric patients (2 years of age and older)who are receiving systemic 

corticosteroids and require supplemental oxygen, non°lnvasive or invasive mechanical 

ventilation, or ECMO, an.cl that, when used under the conditions described in this 

authorization, the known and potential benefits of Actemra outweigh the known and 

potential risks of such product; and 

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

Actemra for the treatment ofCOVID-19 in hospitalized adults a11d pediatric patients (2 
Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42863 


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Page 3 - Genentech, Inc. 

yeiirs of age and older) who are receiving systemic corticosteroids and require. 

supplemental oxygen, non-invasive or invasive mechanical ventilation, or ECM0.5•6 

II. Scope ofAnthorization 

Ihave concluded, pursUartt to Section 564(dX1) of the Act, that the scope Qfthis authorization is 

limited as fQllQWs: 

• Actemra will be used only by heatthca:te providers to treat COVID-19 in hospitalized 

adults and pediatric patients(2 years of age and older) who are receiving systemic 

.corticosteroids and require supplemental oxygen, non-invasive or invasive 

mechanical ventilation, or-ECMO. 

• Actemramay ®ly be administered ViafottaVetrous infusion; 

• The use of Actemra covered by this authorization must be in accordance withihe 

authorized Fact Sheets; 

Product Description 

Actemra is supplied in individual single dose vials. Actemra is a recotnbinilnt htltl'l.anized monoclonal 

antibody that selectively binds to both soluble and membrane-bound human IL-6 receptors (slL6R and mIL-6R)and subsequently inhibits IL-6-mediated signaling through these receptors. 

Actemra injection is a preservative-free, !lierile clear; colorless to pale yellow solution, The 

authorized product includes commercially available 7Actemra, which is supplied as SO mg/4 mL 

(NDC 50242-135-01 ), 200 mg/10 mL (NDC 50242• 136-01). and.400 mg/20 mL (NDC 50242-

137-01) individually packaged 20 mg/mLsingle-dose vials for further dilution prior to 

intravenous infusion. Do not use beyond the expiration date on the container or package. 

Actemra must be refrigerated at 36"F to 466 F {2°C to 8°C). Do not freeze. Prote~t the vials from 

light by storage in the original package until tiine ofuse. 

5 On October 22, 2020, Veklury (remdesivir) was approved to treat COVID-Hfin adults and pediatric patients (12 

yean, of age and older and weighing at least 40 kg)requiri:ng hospitalization, Vek;lury is a nucleoside nbonucleic 

acid polymerase inhibitor lhathas dem.onstrated antiviral activity against SARS-COV-2. Actemraisarecombinant 

humanized monoclonal ®tlbody that selectively binds to both soluble andmembrane0boundhuman IL·6 receptors 

(sIL"6R and mlL•6R) and subsequently inhibits IL-6-mediated signaling through these receptors. Severe COVID-19 

infection has been associated with hyperinflammation. In this context, high.levels of IL~6, as well as other proinflammatary cytokines and inflammatory.markers, have been. observed in some patients.with severe COVID019 

infection, ThllS, a product inhibiting IL-6, such as Acremra, may potentially act on tlw COVID-19-associated 

inflammatory response. This.is distinct from Veklury,. which acts as an.antiviral agent We also note thatVekiury''s 

FDA-approved indication is for a narrower population than the use authorized forActemra under this EUA 6Noother criteria .of i$:.~ance have ~n prescribed by regulation under Section 564(c )(4}of the Act 7 Supm at Note 1. · 
42864 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 


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Rage 4-Qenentech, Inc. 

Act¢mrai~ authijriz'edfo,r,emergency use with the followitlgproduct~st>e¢itlc information 

requireijt!:l be m~de ayailabletohealthoil,l'epr!:!'\'iqetshrtd Jiatietlts, parents, Attd oaregivei:s, 

resp~tivefy', througll.G®.ente9'h 's wel!site irtwww.;aotemrahcp.99m/covid~19(referi-edto as~the 

••authorizedlabeling"}: · · 

• Fact Sheet fur Healthcare Providers: Emergency UseAuthorizatfon (EUA) forAcfemra 

• FMt Sheet fur Patients, Parents and.care~!e~LEm~gertqy Use Authorization(EUA) of 

,A.ctemrafor>ebron'a\'ifus.l)iseasti:2019(CPVJD;.19) 

lhave conclud¢; pur~uantto Sec:tionS64(4)(2)ofthe,A.ct;.that it is rell$o,nabletobelieve th~t 

the known and potentfalhenefits ofActemra,when usedforthetreatmentofCOVID~19 and 

used in accordance with this Scope of Authorizatioo (S~tion.lI),.outweighthe kn◊wtt and 

pi)tentfalrisks. 

lhave concluded;. pursuanft.o Section 564(d)(3)ofthe A:ct, based ollthefotality ofscientific 

evidence available to FDA, thatitisreasonableto believe that Actemramay be.effective.for the 

treatmertto£CQVID-i9whenused macoordancewith this. Soope.ofAttth<>rization(Seotfontl), 

pursuantto:Seotion S,64(c)(2)(A)ofthe.Act. 

Havingreviewed the sdentificinfonnatfun available to FDA,;·.includingtheinfonnation 

sup~ortmgthe .eonclusions descdbe?in Section I. ab<>v~,Ihave concluded th4:1.Actentra(~ 

de!iertbedirt.this S.:ope of AUth<>rization(Sectlon Il)) meets the criteriasetfotfuin.$ectioo 564{d) 

ofthe Act oonoeming sawty and potential effectiveness. 

ill. Conditions ofAuthorization 

~tt<> Section SM ofthe Act.I am estabiishlngth.eJo1lowntgcontfitions onthisatitb.QriZatfon: 

Genentech and AuthorizedDistribtitorss: 

A. Genentech and atitht>rized distti'butor(s rwiilensure that Actemra is distributed. with the 

FDA·llJ>PfOVe4 paokagemsertandtheattthorizedlabeling (i.e., FactSheets)willbemade 

aVllil@le ~ healthcare :faoilitiesa:n:<V◊rhealthca.t"¢ pt◊viders as des:,:rt"bed iRSectionJl <>f 

this Letter.ofAuthorization .. 

R denentecliand.authortzeddistributor(s)\¥illensurethat~riatesto~atidcotd.chairt 

is maintau:ied until the product is delivered to healthC8.1"¢facilities and/or healthc11te 

providers, 

c. -Oenentecli andautboriZed dtstributor(s)wiif ensure thatthetetiris oftfilsEUA are made 

availableto.allrelevantstakeholders{e;g., U.S. go.vet:nmentag¢ncies,state andlocal 

govemm.entauthorities, authorized distribut<>rs,. healthcarefacilities; healthoareipr:ovidets) 

irtvtilvednt:distri~titμlg•OJ.'.TCCeiyiμgAct.imra.•Ge11.en:techwiU·provideto•allrelev~t 

8"Atithorized0istributor(s)" are.identifiedbyGenentechas. an.entity or·entities.allowedfo.·disb:ibuteActemrn for 

the useauthorized.inthisJetter. 
Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42865 


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Page 5 - Genentech, fuc. 

:stakeholder$ a copy of this LetterofAuthoriza1ionand coi:mnunicate any subsequent 

ameniJments·that•rhightbe1nadetothistetfer•ofAuthorizaiion: md·its:autborized 

acc;ompan¥iug.materials (i;e,, FllCt Sheets), 

a Genentechmaytequest dumgesto this authorization. mdudihgto the authorized Fact 

Sheets for Act¢111ta. Any requestfor changes to this E:UA must be submitted t◊ :the 

Diyision of Pulmonology; Allergy and Critical Care/Office of Immunology and 

fuflammation/Office ofNew Drugs/Centerfor DrugEvafuationand Research (CDER). 

Such ch~··requireappropriateauthorization·priortoiinplementation,9 

E. dertentecfrmaydevelop and di$seminate.msttuctfortalan:d eilucational material.if(e.g., 

material$ provirungf1rl'otmitti()il Oil. pmdiJ'1t•~isfrati?ilM4/orpati~t.monitotitigjthl¢ 

areco11$istentwi1Jithe authorizedemergencyuseofAc;t¢mraas describedin this Letterof 

Authorization•and authorized labeling; ·withoutFDA's·•review•.and concurrence,when 

rtecessacyto meet public health11eeds. Any inslructiortal iiiid educatio11almaterial.sth~tate 

in.con:sistentwiththe autho1:1Zed labeling·forActenitalltepte>hibited. .. IftheAgertcynotifo~!i 

G:enentechtha.tany i.rtstructi()QaI Md edμcatiortaI mat¢riaisare inc;(}tl$istentwiththe 

authorized labeling, Genent¢chmust ceasedistributionofsuch inslructionaland 

educatiortal materials. Furthermore, as pmt ofi.tsrtotiffoatiort,the Agertcymity alsorequire 

Oenentechtoissue·c~ve.COtnill:Ui1ication(s). 

Fi Genentechwillteporlto FDA serious adv~e events and.all medication errors associat,ed 

with the use ofActemra:for·furauthorized. use that are reporledto Genentech. using either of 

the follo'wirtg options. 

Optic>nl: Subtriitreporlathroughthe SafetyReporlm:glforfuJ. ($RP)ll$ de$Crl.bed onthefJjA ,mwebpage, · · · 

Option 2, stlbihlt.teports dt:ectiythrou@tthe Electrotiic subtriissions:0atewaJ(ESG)as 

desenbed on theFAERS el@@i¢subrtiissrons.webpage, 

$'llbmitte4 repo).1ll 11t1d~ both. options shoi.ild state: "A:cjenira 11se for COVll).;19 under 

Emergency Use Authorization. (EUA)/' For reports sUbrhitted under Option], include this 

langwtge at the ~~ of the ~estlon ''Des'Cribe Event"forfu.rthei:anal.)'Sis. Forreportis 

submitted .. nndet Option 2, inclμde .this 1~ a,t the begin.tiiugofthe ''Case Natrativ:e" 

fie1& . 

~ The followipg:types. ofrevisions.ma:y birauthorizedwithout.reissuing this lefter, (1) changes to the 11Uthorized 

labeling; (2) non.substantive editorial couectionsto this letter; (3Jnew types of authorized labeling; includipg: new 

factsheets;(4)new carton/container labels;(5)expiration·dating.extensions; {('i)changes•tomanufacturing 

processes; inclu~ tests or other authoriz.ed components of manufacturing; (7Jnew conditions ofauthoriz.litionfo 

require data collection orstudy; (8) new strengths of the authorizedproduct,newproduct sources(e,g.; of active 

pharmaceutical ingredient)or ofproduc.t.components. For changes to the11Uthoriz.ation; includipg: the authorized 

labeling; of the type.listed in(3), (6), (7), or.(8}, review andconcurrenceisrequired.ftom the Couriter .. Te1Torism and 

Emergency Coordination S!afli'Officeofthe Genter Pirector/cPERand the OfficeofCounterterrorism and 

Emergipg: ThreaWOffice ofthe•Chief Scientist. 
42866 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 


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G; A1fmahilfacturing, pack;igin~.and:testing $hes.for both drug substance and drug product 

\\'ill comply With c-atrent good manufacturing practice requitem:enti; of Section 

5Ql(a)(2)(B) ofthe.Act 

H. .Genentecliwi.Ilsuhmitmfonnation tothe:Agency withlri.threeworkirig days <>ftece1.pto:t' 

anyinfonnationconcerningsigriifi¢ahtqualitypfoblems with dtugproductdistributed. 

un.derthis em:ergency•us.e ®thotitatio11·.forAcletnfathatinclud¢$thefollo~: 

• lmormati.011. ~ncemfu:ganyin!:idetttthatcauses·thedrug product or ib:•·tabeling 

to be mistaken for; orapph'ed to, another article; or 

• Information concerningmiymicrobiologicalcontamin.atio~ or any sigriificant 

chenucal, physica1, or. other. change or deterioration in the dismbuted dt:ug 

produ~ oranyfail~ of one ormoredi$1tt"buted batches of the ptoduiJtto m~t 

the esta:blishedspeci:fications, 

Ifa sigriificantqualityproblem affects unreleasedproductandmay atsoinipactproduct(s) 

pr¢viomlyreleaseda:11d distributed, then .infortnati6n should be submittedfor a1lp()te11tially 

iillpacted Jots. · 

Genentech will include inits notification to the Agency whether the batch. or batches, in 

question will berecalled. 

lfnotit1cluded in its ihitial n◊ti:fication, Qenentech must submit i11formation cottfirming 

that Genen~;;:h hi.tS ide1:itifie<fth.erQOt Clluseofthe ~ignificantqualityprobiems,taken 

corrective action, and provide ajustification confttming thatthe corrective action is 

appropriate and effective. Gene11tech mustsubmitthis information as soon as possible 

butn() httetthan 45 calen.dat daysfrorn the Initial notific4tion. · 

L GenentecllwillmanufactureA-1'temra to meet all qualify sta:ndards and per the 

lllllllilf~ processandconlrolstrategy as detailedfo Genentech~s EUArequest. 

Genet1techwillnotim:pleni.entany changes to the description. of the product, manufncturifig 

process, facilities.ani.lequipment; and ele111en.~ of the llS!lOCili.ted control. str:ategythatass~ 

prgcessproonnance,aJ:1.d.qu@ty Qftheautb~d prgduct, \Vithout11otificatiot),.to and, 

concurrence T)ytheAgency as described qndercondition D. 

J. Thfough aproceS$ ()tinventory con~ol. denentectandauthorlzed.dtstributOI(s)wi.U 

maintain records regarding•dismbutionofActetnta(i.e,, iotnumbers, quantity;receiving 

site,r:eclilip~~} · 

K. Genentechmid authorizeddistributor(s)willmake available to FDA upon request any 

records maimained in connectil:>tt.With this BUA. 

Healthcare Facilities to Whom ActemralsOistriouted.andHealthcare Pt()viders.Adminisforing 

Actemra 
Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 42867 


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L Heal1hcarefacilities and.hea11hcare providers will ensure 1hatthey are aware of the Letter 

o.fAuthorization, and 1he tenns herein, and that 1he authorized Fact Sheets are made 

available to. heal1hcare providers and to patients, parents, and.caregiv~ respectively, 

through appropriate means, prior to administrati-OU of Actemra. 

M. Healthcare facilities and healthcare providers receiving Actemra will track seriousadvetse 

eventl> that are considered to be poten(ially attributable.to Actemra use and must report 

1hese to FDA in accordance wi1h 1he Fact Sheet for Heal1hcare Provid.ers. Complete and 

submit a MedWatch form (www;fda:.gov1medwatch/mporth1m). or complete and submit 

FDA Form 3500 (heal1h professional) byfax (l-800-FDA-0178) (1hese forms can befouiid 

via link above). Call l-800.:FDA-1088 for questions. Submitted reports should state, 

"Actemra usefor COVID-19 undetEmergenc:yOseAu1horization'' atthe beginnfugo.fthe 

question "Describe Event" for further analysis. A copy of1he completed FDA Form 3500 

.should also be provided to Genentech per 1he instructions in the au1horized labeling. 

N. Heal1hcare facilities and healthcate providers will ensure that appropriate storage and cold 

chain is maintained until1he product is administered consistent with 1he terms of 1his letter 

and the authorizedlabeling. 

o. Through a process of inventory control, healthcare facilities will maintain records regarding 

the. dispensing and administration of Actemra for the use authorized in 1his letter (i.e., lot 

numbers, quantity, receiving site, receipt date), producfstorage, and maintain patient 

information ( e:g.., patient name,, age; disease manifestation, number of doses administered 

per patient, other drugs administered). 

P: Heal1hcare facilities will ensure 1hat any records associated with this EU A are maintained 

until notified by Genentech and/or FDA Such records will be made available to 

Genentech, HHS~ and FDA for inspection uponrequest. 

Conditions Related to Printed Matter, Advertising, and Promotion 

Q. All descriptive printed matter, advertising, and promotional materials relating to the use of 

Actemra under1his authorization shall be consistent with 1he authorized labeling, as well as 

the terms set forth in 1his EU A, and meet 1he requirements set forth in Section 502(a) and 

(n) of the Act, as applicable, and FDA implementing regulations. References to "approved 

labeling'', "permitted labeling'' or similar terms in these requirements shall be understood 

to refer to 1he authorized labeling for 1he use of Actemra under 1his authorization. In 

addition,.such materials shall: 

• Be tailored to 1he intendedaudience. 

• Not take 1he form of reminder advertisements, as 1hat ferm is descnbed in 21 

CFR202.l(eX2Xi), 21 CFR200.200 and21 CFR201.100(t). 

• Present 1he sanie risk mfurmatioilrelatiilg to the major side effects and 

contraindications concurrently in 1he audio and visual parts ofthe presentation 

for advertising and promotional materials inaudio-visual format 
42868 Federal Register / Vol. 86, No. 148 / Thursday, August 5, 2021 / Notices 

Dated: July 30, 2021. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2021–16705 Filed 8–4–21; 8:45 am] 

BILLING CODE 4164–01–C 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Center for Advancing 

Translational Sciences; Notice of 

Closed Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended, notice is hereby given of the 

following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The cooperative agreement 

applications and the discussions could 

disclose confidential trade secrets or 

commercial property such as patentable 

material, and personal information 

concerning individuals associated with 

the cooperative agreement applications, 

the disclosure of which would 


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Page 8 - Genentech, Inc. 

• Be accompanied by the authorized labeling, if the promotional materials are not 

subject to Section 502(n) of the Act. 

• Be.submitted to FDA accompanied by Fortn FDA:2253 at the time of initial 

dissemination or fast use. 

lfthe Agency notifies Genentech that any descriptive printed matter, advertising or 

promotional materials do not meet the terms set forth in conditions Q-S of this EUA; 

Genentech must cease distribution of such descriptive printed matter, advertising,-0r 

promotional materials in accordance with the Agency's notificati-On. Furthermore, as part 

of ifs notification, the Agency may also require Genentecht-0 issue rorrective 

communication(s ). 

R No descriptive printed matter, advertising, or promotional materials relating to the use of 

Actemra underthis authorization may represent or suggest that Actemra is safe or effective 

when used for :the treatment of COVID-19 in hospitalized adults and pediatric patients (2 

years of age and older) who are receiving systemic c-0rticosteroids and require 

supplemental oxygen,non-invasiveorinvasivemechamcal ventilation, or ECMO. 

S. Ail descriptive printed matter, advertising, and promotional material, relating to the use of 

Actemra under this authorization clearly and ronspicuously shall state that: 

• Actemra.has not been approved, but has been authorized for emergency use by 

FDA under an EU A, to treat COVID-19 in hospitalized adults and pediatric 

patients (2 years of age and older) who are receiving systemic corticosteroids 

and require supplemental oxygen,non-invasive or invasive mechanical 

ventilation, or ECMO; and 

•• Theemergencyuse of Actemrais only anthorizedforthe durationofthe 

declaration that circumstances existjustifying the authorization of the 

emergency use of drugs and biological products during the COVID-19 

pandemic under Section 564(b X 1) of the Act, 2 lU.S.C. § 36dbbb-3(b Xl ), 

unless the declaration is terminated or authorization revoked sooner; 

IV. Duration ofAuthorb.ation 

This EU A will be effective until the declaration that circumstances exist justifying the 

authorization of the emergency use of drugs and biological products during the COVID-19 

pandemic is terminated under Section 564(b )(2) of the Act or the EUA is revoked under Section 

564(g) ofthe Act. 

Sincerely, 

--JS!--

RADM Denise M. Hinton 

Chief Scientist 

Food_ ancl Drug Administration