6578 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 

I. Background 

FDA is announcing the availability of 

a revised draft guidance for industry 

entitled ‘‘Assessment of Pressor Effects 

of Drugs.’’ This draft guidance is 

intended to advise sponsors on the 

premarketing assessment of a drug’s 

effect on blood pressure. Elevated blood 

pressure is known to increase the risk of 

stroke, heart attack, and death. The 

effect of a drug on blood pressure is, 

therefore, an important consideration in 

risk assessment and product labeling. 

This draft guidance revises the draft 

guidance entitled ‘‘Assessment of 

Pressor Effects of Drugs’’ issued on May 

31, 2018 (83 FR 25013). Based on 

comments received to the docket, the 

draft guidance was updated to include 

recommendations on the design of an 

ambulatory blood pressure monitoring 

study; recommendations on the types of 

drugs that need an ambulatory blood 

pressure monitoring study; modification 

of Figure 1 in the draft guidance to show 

the relationship between the increase in 

10-year atherosclerotic cardiovascular 

disease event risk with chronic 

increases in systolic blood pressure; 

inclusion in the guidance of Table 1, 

which summarizes landmark clinical 

trials showing the reduction of major 

adverse cardiac events with decreases in 

blood pressure with antihypertensives; 

and considerations for product labeling. 

In addition, editorial changes were 

made to improve clarity. 

This draft guidance is being issued 

consistent with FDA’s good guidance 

practices regulation (21 CFR 10.115). 

The draft guidance, when finalized, will 

represent the current thinking of FDA 

on ‘‘Assessment of Pressor Effects of 

Drugs.’’ It does not establish any rights 

for any person and is not binding on 

FDA or the public. You can use an 

alternative approach if it satisfies the 

requirements of the applicable statutes 

and regulations. 

II. Paperwork Reduction Act of 1995 

While this draft guidance contains no 

collection of information, it does refer to 

previously approved FDA collections of 

information. Therefore, clearance by the 

Office of Management and Budget 

(OMB) under the Paperwork Reduction 

Act of 1995 (PRA) (44 U.S.C. 3501– 

3521) is not required for this guidance. 

The previously approved collections of 

information are subject to review by 

OMB under the PRA. The collections of 

information in 21 CFR part 312 

addressing investigational new drug 

applications have been approved under 

OMB control number 0910–0014 and 

the collections of information in 21 CFR 

part 314 addressing new drug 

applications have been approved under 

OMB control number 0910–0001. 

III. Electronic Access 

Persons with access to the internet 

may obtain the draft guidance at https:// 

www.fda.gov/drugs/guidancecompliance-regulatory-information/ 

guidances-drugs, https://www.fda.gov/ 

regulatory-information/search-fdaguidance-documents, or https://

www.regulations.gov. 

Dated: January 31, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–02371 Filed 2–3–22; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. FDA–2021–N–0335] 

Authorizations of Emergency Use of 

Certain Drugs and 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 three Emergency Use 

Authorizations (EUAs) (the 

Authorizations) 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 

AstraZeneca Pharmaceuticals LP (AZ), 

one Authorization for a drug product as 

requested by Pfizer, Inc. (Pfizer), and 

one Authorization for a drug product as 

requested by Merck Sharp & Dohme 

Corp. (Merck). 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 AZ is 

effective as of December 8, 2021, the 

Authorization for Pfizer is effective as of 

December 22, 2021, and the 

Authorization for Merck is effective as 

of December 23, 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 


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Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6579 

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. 

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 

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 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 

three authorizations for the emergency 

use of drugs and biological products 

during the COVID–19 pandemic. On 

December 8, 2021, FDA issued an EUA 

to AZ for the biological product 

EVUSHELD (tixagevimab co-packaged 

with cilgavimab), subject to the terms of 

the Authorization. On December 22, 

2021, FDA issued an EUA to Pfizer for 

the drug PAXLOVID (nirmatrelvir copackaged with ritonavir), subject to the 

terms of the Authorization. On 

December 23, 2021, FDA issued an EUA 

to Merck for the drug molnupiravir, 

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 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 

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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6580 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 


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Astra.Zen-eca Pharmaceuticals LP 

Attention; Stacey Cromer Ben:nai\ PhD 

SeniorRe:gulatory Affairs Director and team Lead 

OneMedlmmune W11,y 

Gaithersburg, MD 20878 

RE: Em.etgency Use Authorization 104 

Dear Dr: Cromer Berman: 

Decemher8, 2021 

'Ihl.s letter is in response to Astra.ZenecaPharm~euticals L:P's (AstraZeneca) request thatthe 

Food iil:ld Drug Adminisirafion (FDA or Agency) issue iil1 Emergency Use Autho'li,-,iliion (EUA) 

fortheemergency use ofEVUSHELDTM (tixagevimah co.-packagedwith cilgavimab) for the 

pre-exposure prophylaxis of coromvirus disease 2019 (CO\TlD-l 9)in certain adults and 

pediatric individuals (I 2 years of age and olderweighing at least 40 kg), as described in the 

Scope of Authorization (Section.JI)of this letter, pμtsuantto Section 564 Qftbe Federal Food, 

Drug, and Cosmetic Act(the Act) (21 U. S.C. §360hhlr3). 

On February 4, 2020, pursuant to Section 564(b)(I )(CJ of the Act; the Secretary of the 

Department of Health a1tdHuman Setvices (FIBS) determined thatthereis a public health 

emergency that has a significantpptential to affectnationals:ecutity or the health an.dsecμruy.of 

United States citi7ens livingabroad, and thatinvolves the virus that causes corona,1rus disease 

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

202b, declared that circumstances exist justifying the authorization of emergency :use ofdrugs 

and biological producis during.the COVID-19 pandemic, pursuant to Sec.tion 564 of the Act (21 

U.S.C; 360hbb-3),subjectto terms of any authorization issued under that section. 2 

tixagevimab and cilgavimab, the active components ofEVtJSHELD, are neutralizinglgGl 

monoclonal aniibodies that bind to distinct, non-overlappingepilopes within the receptor binding 

domain of the spike protein ofSARS--Co V-2. EVUSHELD tiian investigational drug and is not 

approved.for any μses,includinguse a;&pre-e.xposureprophylaxis ofCOVID'-J 9, 

Based on theteview of the data from the PROVENT elm.foal ttia.1. (NCT04G25725),a PhaselII 

randomize4, double-blind, placehq-controlled clinic-al trial, itis reaspnable to believe that 

EVUSHELD may he effective foruse !LS pre-exposure prophylaxis of COVID-19i:n certain 

adults and pediatric :individuals ( 12 years of age and older weighrni atleast40 kg), .as described 

r tJ$.JJep.artm(lf)t qfffeiilth: !ind HUl'.liafl Sm.ices; tJete.rminatianofaPublir:Ff eμJth Emergency and ~r:lamtiO/i 

lhal Circ,umstam:esExist.Justi;/yingAuJhorizciiiansPr(l'SUtUJJ to&CtiM 564(q) oftheFederalFomt Drug, mid 

CasmeticAc:!, 21 U.S.C .. § 36Ql,bb-3 •. Fcbmll.y4.,W20. 2 U.R Department ofH¢alth and HU!llan Setv.ic~Declwaaottih@Crrcittnstaiices Ex4't.J~sti.fyiiigAuthorizd/toti$ 

Pursuant to Seoiion J64(:b) ofiheFederalFood, Drug. andCoS111eticAct,21 U.S.-C § 360bb/{.3, 85I'R 18250 

(April L,2020). 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6581 


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Page 2 ---AstraZeneca Pharmaceuticals LP 

in the Scope of Authorization (Section II), and when used underthe conditions described in this 

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

potential risks of such product. 

Having concluded thatthe criteriaforissuance of this authorization under Section 564(c) ofthe 

Act are met,I am authorizing the emergency use.ofEVUSHELD for use as pre-exposure 

prophylaxis of COVID-19, as described in the Scope of Authorization section of this letter 

(Section II) a:nd subjectto the terms of this authorization. 

I. Criteria for .Issuance of Authorization 

I have concludedthatthe emergency use ofEVUSHELD for pre-exposure prophylaxis of 

COVID-19 when administered as described in the Scope of Authorization (Section II) meet$ the 

criteria for issuance of an authorization underSection 564( c) of the Act; because: 

L SARS-C-0V-2 can cause a serious or life-threatening disease or condition; including 

severe respiratory illness, to humans infected bythis vims; 

2. Based on ihe totality of scientific evidence available to FDA, itis reasonable to believe 

that EVUSHELD may be- effective foruse as pre-exposure prophylaxis of COVID-19 

in certain adults and pediatric individuals (12 years of age and older weighingat least 

40kg), as described in the Scope of Authorization(sectionII), a:nd that, when¥sed 

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

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

:( TI1ere is no adequate. approved; and available alternative to the emergency use of 

EVUSHELD as pre-exposure prophylaxis ofCOVID-19 as further described in.the 

Scope of Authorization (section II), 3 

II. Scope of Authorization 

I have concluded, pursuant to Sect10n 564(d){ i) oft.he Act, thatthe scope of this authorization is 

limited as follows: 

• Distribution oft11e authorized EVUSHELDwill be controlled by the United States 

(U.S.) Government for use consistent with the tenns and conditions of this. EU A. 

AstraZeneca willsupplyEVUSHELDto authorized distributor(s)4,who will 

distribute to healthcare facilities or healthcare providers as directed by the U.S.. 

Government, in c-0llabor.atio11 witll state and local government authorities as needed; 

• EVDSHELD may only be used in adults and pedian-ic individuals (12 years ofage 

and o Ider weighing at least 40 kg): 

3 No other criteria ofissuancehavebeenprescribedbytegulationundcr ~ction564(cX4)oftheAct. 

4 ".AuthorizedDistributor{s)" are identified by AstraZeneca asanentity or entities allowed to distribute authorized 

EVUSHELD. 
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Page 3 - AstraZeneca Pharmaceuticals LP 

• Who are not curren1ly infected with SARS-Co V-2 and who have not had a 

known recent exposure to an individual infected with SARS-Co V-2 and 

o Who have moderate to severe immune compromise due to a medical 

condition or receipt of immunosuppressive medica1ions or treatments 

and may not mount an adequate immune response to COVID-19 

vaccinations or 

o For whom vaccination wi1h any available COVID-19 vaccine, 

accordingto the approved or authorized schedule, is notrecotmnended 

due to a history of severe adverse reaction ( e.g., severe allergic re.action) 

to a COVID-19 vaccine(s)and/or COVII).19 vaccine component(s). 

Limitations on Authorized Use 

• Evusheld is not authorized for the following uses in individuals: 

• FortreatmentofCOVID-19,or 

• For post-eJq)()sure prophylaxis of COVID-19 in individuals who have been 

exposed to someone infected with SARS-Co V-2. 

• Pre-exposure prophylaxis with EVUSHELD i'l not a substitute for vaccination .in 

individuals for whom COVID-19 vaccination is recommended. Individuals for whom 

COVID-19 vaccination is recommended, including individuals with moderate to 

severe immune compromise who may derive benefit from COVID-19 vaccination, 

should receive COVID-19 vaccination. 

• For individuals who have received a CO VID-19 vaccine, EVUSHELD should be 

administered at least two weeks after vaccination. 

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

authorized Fact Sheets. 

Product Description 

EVUSHELD is supplied as a single carton (NDC 0310-7442-02) containing 1 single-dose vial of 

tixagevimab injection and 1 single-dose vial of cilgavimab injection. 

Tixagevimab injection (NDC 0310-8895-01) is a sterile, preservative-free, clear to opalescent 

and colorless to sligl1tly yellow solution supplied in a single-dose vial for intramuscular use. TI1e 

vial stoppers are not made with natural rubber latex. Each 1. 5 mL contains 150 mg tixagevimab, 

L- histidine (2.4 mg), L- histidine hydrochloride monohydrate (3. 0 mg), polysorbate 80 (0.6 mg), 

sucrose (123.2 mg), and Water for Injection, USP. 

5 For additional information please see https:/ /www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-

vaccines-us.httnl Healthcare providers should considerthe benefit-risk for an individual patient. 
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Cilgavimab injection (NDC 0310-1061-01) is a sterile, preservative-free, clear to opalescent and 

colorless to slightly yellow solution supplied in a single-dose vial for intramuscular use. The vial 

stoppers are not made with natural mbber latex. Each 1.5 mL contains 150 mg cilgavimab, Lhistidine (2.4 mg), L- histidine hydrochloride monohydrate (3.0mg), polysorbate 80 (0.6 mg), 

sucrose (123.2 mg), and Water for Injection, USP. 

Unopened vials oftixagevimab and cilgavimab must be stored in a refrigerator at 2°C to 8°C 

(36°F to 46°F) in the original carton to protect from light. Vials must not be frozen or shaken. 

Unused portions must be discarded. 

EVUSHELD 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 AstraZeneca's website www.EVUSHELD.com (referred to as the 

"authorized labeling"): 

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

EVUSHELD 

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

EVUSHELD forCoronavims 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 ofEVUSHELD, when used for pre-exposure prophylaxis of 

COVID-19 in certain adults and pediatric individuals (12 years of age and older weighing at 

least 40 kg) 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) of the Act, based on the totality of scientific 

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

pre-exl)osure prophylaxis of COVID-19 in certain adults and pediatric individuals ( 12 years of age 

and o lderweiglring at least 40 kg)when used in accordance with this Scope of Authorization 

(Section II), pursuantto Section 564( cX2)(A) of the Act. 

Having reviewed the scientific information available to FDA, including the infommtion 

supporting the conclusions described in Section I above, I have concluded that EVUSHELD (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. 

The emergency use of your product under an EU A must be consistent with, and may not exceed, the 

terms of the Authorization, including the Scope of Authorization (Section II) and the Conditions of 

Authorization (Section III) Subject to the terms of this EUA and underthe circumstances set fot1h in 

the Secretaiy ofHHS's detennination under Section 564(b)(1XC)described above and the Secretaiy 

of HHS' s corresponding declaration under Section 564(b X 1 ), EVUSHELD is authorized for use as 

pre-exposure prophylaxis of COVID-19 as described in tins Scope of Authorization (Section II) 

under this EUA, despite the fact that it does not meet certain requirements otherwise required by 

applicable federallaw. 
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III. Conditions of Authorization 

Pursuant to Section 564 of the Act, I am establishingthe following conditions on this authorization: 

AstraZeneca and Authorized Dist:ributors6 

A. AstraZeneca and authorized distributor(s) will ensure that EVUSHELD is distributed with 

the authorized labeling (i.e., Fact Sheets )will be made available to healthcare facilities 

and/or heal1hcare providers as described in Section II of this Letter of Aulhorization. 

B. AstraZeneca and authorized distributor(s)will enstu:e thatappropriatl:l storage and cold 

chain is maintained until the product. is delivered to healthcare facilities and/or heal1hcare 

providers. 

C. AstraZeneca and airthorized distributor(s) will ensure that the tem1s of this EUA are made 

available to all relevant stakeholders (e.g., U.S. go.vemment agencies, state and .local 

government authorities, authorized.distributors, heal1hcare facilities, healthcare providers) 

involved in distributing or receiving EVUSHELD. AstraZeneca will provide to all relevant 

stakeholders a copy of this Letter of Authorization and commU11icate any subsequent 

amendments that might be made to this Letter of Authorization and its authorized 

accompanying materials (i.e., Fa"'t Sheets). 

D. AstraZeneca may request changes to this authorization, including to the authorized Fact 

Sheets for EVU SHELD. Any reque,.'t for changes to this EU A must be. submitted to the 

Office oflnfectious Diseases/Office ofN ew Drugs/Center for Drug Evaluation and 

Research. Such changes reqtrire appropriate authorization priorto implementation. 7 

E. AstraZeneca may develop and disseminate instructional and educational materials ( e.g., 

materials providing information on product administration ru1d/orpatientmonitoring) that 

· are consistent with the authorized emergency use ofEVUSHELD as described in this 

Letter of Authorization and authorized labeling, without FDA 's review and concurrence, 

when necessary to meet public health needs. Any instructional and educational materials 

that are inconsistent with the authorized labeling for EVUSHELD are prohibited. Ifthe 

Agency notifies AstraZeneca that any instructional and educational materials are 

6 "AuthorizedDistributor(s)" are identified by Astraieneca as ah entity or entities allowed to distribute EVUSHFLD 

for the use authorized in this letter. 7 The followingtypesofrevisions may be authorized withoutreissuing this letter: (1) changes to.the authorized. 

labeling; (2) non-substantive editorialcorrec.tions to this letter; (3) new types of authorized labeling, including new fact sheets; (4 )new carton/container label~; (5)expira tiondating extensions; (6)changes to manufacturing 

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

require data collNtion or study; (8 )new strengths of the authorized product, new product sources (e.g., of active 

pharmaceuticalingredient)or of product components. For changes to the authorization, including the authorized 

labeling, of the type listed in (3 ), ( 6), (7), or (8 ), review and concurrence is required from the Counter.Terrorism and 

Emergency Coordination StaIDOffice ofthe CenterDirector/CDER. andtheOffice ofCounterterrorism and 

Emerging Threats/Office of theChiefScientist. 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6585 


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faconsisteritwithfli.e auihorizedfabeling,AstraZenecamustcease,distributionof such 

,-insttuciioruilande:db.<iatfonal rrtaterials._'F'ut1hennore,.11$J>.ut{)f'itS.notffi¢ation.:the•Agency 

•ma}t alsqre~.A.sttl!Ze~io:fasue:-c~i::t'ive!!Qifittiqlμ¢!ITTP.11{S): 

R. ,AstraZenecawillrepoitto FDA.serious adverseevenisandallmedicatfonerrorsassociated 

•withthe use,;ttEVUSHELDfor;its~dusetlurt:arereportedto AstraZeneca.using eithet·ofth¢.f'QlloWing~ptionsi · ·--

•~~e1t~=~l'.eP9tP:th:rou.~me $:¢'etyRel!Orim~J>o,W(SlU>)'liSd~gi~.®Ji.e:J\DA, 

·~!~~-==~~~f:!1~1:!hf$~~=~~ufmtissions GaumraytFSct)·$ 

Submittedreports-underboth-optionsshould.sfute:-'!EVUSHELD,use for:COVIO-l9°\111der 

Emergency,Use Authorization.(EUA)/1 Forrep.ortuubmitted-umlerl)ption 1. include.this •:~:t:i~~=i:t::a\~:~:::::.~~=th~:.;~, 

fiel& -

H; -AstraZenecaWillsubniitinfonnafionto the.Agency•within'threewotkihgdaysofreceiptof 

-:l;=:g:=!r!::i=:~~~!:l:!:!;::1 ,.. llif'(')nrtlitioncqooei:1iihganyinddentthatc:iWsesihe:dtugprodl)ct()t·it& illbe:iiig 

to he niistakenfor,orappliedto,.anotherarlicle, or · · 

•• Inf ol11lafion conc~g llDymi~objologica1 cQrttlimll)afj(m -tit aey $igtufi;ci.urt 

cherrtical;.physical~or<>i:herchangeordeteriorationinthe distributeddrug 

prod~ or any failure-ofone onnore-disuibutedbatches of the productto meet 

the esciblishedspeciticatioos. 

lf:{l:slgn_ifi®tq~-pr9&lem:Ji.tf¢cl$11i1tele~ed-prodμcl-anil•-•~YalsQ'tro:p®tprodμci($) 

•previouslyreleased.and•distributed;then-informationshouldhe·subniittedfor•all:potentially 

,impacted fots. 

Ifnot included in its initialnotification, AstraZeneca must-submit information 

c9ntinningthat &tra:Zenecahas i4en:tifie4the·roQt cause-of the: i;ign;ificant qμi!iity 

pf!>:bl~s,Wcen c◊ttectiv:e ai>ti()ll, and,pro.yid'e: ajusiiffoation-coni1m1ingthafthe · 

correctiveaclion is appropriate and ·effceciive. Astrazenecamustsubmi1this 
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Page 7 -AstraZeneca PhannaceuticalsLP 

information as.soonaspossible.butno laterthan 45 calendar daysfromthe initial 

notification~ 

l. .~~rtecawiUmlitfii:(®ture.:EVDSfi£11)Jorttei!fal1.qi.Ul1itysfundar~and·perthe 

··manu:facturingprocess,and·contrcil:straiegy.as detailed.inAstraZ.eneca~sEUArequest. 

·:S!~=:;::.;::;a:::::::.:::1:':::~f!e:~:~control 

;:;~~~::;;::;e!':1'~8!~:!;:t!::~==·wi~ut. 

t ~~~=~-==~ 

K. .. Asfr.aZenecawillestablish·aprocess:foi:monitoring;genomicdatabase(s)forthee~ce 

of.global viral variants of SARS--CoV~2.A summaryofAstraZeneca'sprocessshould be 

}!!:!:!fth1:i:::::~:l=::~~utoi::;::~~:~~!!:!:ess .

.. AstraZeneca:willprovide.reporlstotheAgency·ona:·monlhlybasis·suminariiing:an:y·· 

•findingsas·.aresult.:of•its monitoring.activities·•and..·asneeded,any.follow-up assessments 

·p.lannedorconducted. 

:L .FDAlllay·reqμir<1.ASfr.aZenecatoassess the aciivityofthea:μthorizeifEVUS:HELJJagli~ 

.lltly glol:>al$AM~CoV~2:yariati.t(s}oflllWf~t(i:);g_ Viμilltlisthatareprev:menfofbecotning 

;preva:lentthathatborsubstiftitions.in.thetatgetproteinor:inprotein(s)thatinteractWiththe. 

~=£~~=~ adetailedstudyreportwithin30calendardaysofstudy·completion, AstraZenecawill · 

.$1:ibmit•an:y:re.levan:tptoposal(s}torevise theatrlhorizedlabelingl>~edontheresultsot'its 

.assessment;..a:srt1aybe ne·ces·sa.ry•or•4pPtopriatebagedonthe·foregomgassllSSrttent 

fyl. AsitaZene~i;!JaU ptovi~ 1I1iitipl~sa~ r~qe~ o.f:ii1!'.ll~al:l ~IJ(>f()ilgt!:vittlm,joth:e 

·us. DepartmentofHealth.and.HumanServices(HHS)forevaJuationofactivityaga:inst 

:;:ut:~~irt~:;:~ ~!!1:~::1;:::::~=h~;:substituticms 

===~==~== a:ssays,celt culture va:riantassa:ys (pseudotyped·V1tUS.Jike·particfosand/or.a:uthentic mus), 

-1111d ifl wweff':icacy:as$8cY& · 

N: AstraZenecamustprovidirthe folfowiitginformationfo the Agency: 

•• All anti-drug antibody (ADA). assessments that have nofbeen colllpleted at 

the time of this authotiiationfor subjects fromthe)'.!RQVENTclm.ie4lttial 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6587 


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Page 8 AstraZeneca Pharmaceuticals LP 

for days 1, 29, 5 8, and 183 by April 22, 2022. 

• Interim analysis results through Day 28 for the first 50 subjects to receive a 

second dose from the PROVENT repeat-dose sub-study by April 22, 2022. 

• AstraZeneca must conduct an additional study attempting to select for 

SARS-Co V-2 with reduced susceptibility to tixagevimab in culture. Such 

study must employ alternative strategies as agreed upon between 

AstraZeneca and the Agency. AstraZeneca must provide the Agency with a 

proposed protocol by January 7, 2022. AstraZeneca must submit a report of 

summary findings as soon as available, but no later than June 30, 2022. 

• Report from AstraZeneca's study evaluating the potential fortixagevimab 

and cilgavimab to mediate antibody-dependent enhancen1ent of infection 

using sub-saturating concentrations of each monoclonal antibody by June 30, 

2022. 

• Final results from PROVENT and STORM CHASER by December 30, 

2022. Results, to include baseline and all subsequent study visits, of the 

following biomarkers from the PROVENT repeat-dose sub-study: d-dimer, 

P-selectin, thrombin, and Factor VIII. 

• Topline data, to include safety, phannacokinetic, ADA, and biomarker 

results for thrombotic events from the first 9 months of the PROVENT 

repeat-dose sub-study by January 31, 2023. 

• Monthly aggregate reports for serious adverse events in the Cardiac Disorder 

System Order Class (SOC) and other non-cardiac thrombotic serious adverse 

events. 

0. AstraZeneca and authorized distributor(s) will make available to FDA upon request any 

records maintained in connection with this EUA. 

Healthcare Facilities to Whom EVUSHELD Is Distributed and Healthcare Providers Administering 

EVUSHELD 

P. Healthcare facilities and healthcare providers will ensure that they are aware of the Letter 

of Authorization, and the terms herein, and thatthe authorized Fact Sheets are made 

available to healthcare providers and to patients, parents, and caregivers, respectively, 

through appropriate means, priorto administration ofEVUSHELD. 

Q. Healthcare facilities and healthcare providers receiving EVUSHELD will track all serious 

medication etTors and adverse events that are considered to be poten1ially attributable to 

E\11JSHELD use and nrnst report these to FDA in accordance with the Fact Sheet for 

Healthcare Providers. Complete and submit a MedW atch form 

(www.fda.gov/medwatch/report.htm), or complete and submit FDA Form 3500 (health 

professional) by fax (1-800-FDA-0178) (these forms can be found via link above} Calll: 

800-FDA-1088 for questions. Submitted reports should state, "EVUSHELD use for 

COVID-19 under Emergency Use Authorization" at the beginning of the question 

"Describe Event" forfurtheranalysis. A copy of the completed FDA Form 3500 should 

also be provided to AstraZeneca per the instructions in the authorized labeling. 
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Page 9 -AstraZeneca Pharmaceutical1,,LP 

R Healthcarefacilities andhealthcare.provilers·will.ensure.thatappropriate.storageandcold 

chain istnaintaineduntil:theproductis adnrinisteredconsistentwiththetertns.of'thidetter 

and.tlie anth,<»izedla.beling, 

S,. ·Torough.aprocessofinvenforycontrot.healthcare•facilitieswillma:intainrecordsre!Jllding 

1he dispensingand adtnihistrationofEVUSHELDforthe useauthorizedinthis lettet(Le., 

lotnunibers, (lWUltity, recei\7nl.!ts~ receipt date), produ¢tstor~e. an:dmaintaitipatient · 

· in:f'o~on (e . .g;, patientnam:e; age. 4iseli$e milliifestatiQii,n:uinh¢1' ofdQsesadinmisttited. 

·per patient; other drugs administered). 

t.. Heaithcarefaci11ties Will ensure.that·any:recordsassociat«l.wfrhthis•EUAa:remaititained. 

untilMtified by.AstraZene¢aand/or FDA. Sucliteoordswiltbemad¢ avaitabteto 

As:tr:aZ.e~~.J:tas •. ·:iuuI•:E1lAfQtinspection::ttpo,1 rectue$t; 

:U: .Healthcare••facilities and•providers-willreporttherapeutics•infonnafion.andutilizafiondata 

as directed. by1h.e U.S. Department ofHealth andHumanServices. 

Cc)nditions l{efatecH<>Printe:dMatter; Advertising. and Promotion 

V'. All descriptive printed matter; advertising.and promotionalma.terialsrelatingtothe use of 

EVUSHELDunderthisauthorizafionshall beconsistentwiththeauthorizedlabeling, .as 

we1Lasthe tenns setforthm this EUA.andmeetthe requitetrtents setforthfo·Section 

5Q2(1i)an,d(n)()fthe Acf; lll, applicable~ imd FDA implementing ~gulalion:s, Refer~Ctl!l to 

•"appfQVed llill<:ling'\''perajittl3dlalleiing:'orsitnilart~nnsintbes~re.quitementsshall ~. 

understoodforeferto:theauthorizedlabelingfortheuse•ofEVUSHELDunder•this 

authorizatmti Inaddi'tion;suchmaterials shall: 

• Betailt>tedtotheintt:ndec.bmdi~ce. 

• Nottake the formo:t'tetnmdetadvertisemertts; asth!lttemlis descii):,ed ffi 21 

CFR202.1(e)(2X:i), 2.1 cFR20(f2Q0ili1d 21 CFR20l. toO(f} 

·• Presentthe same·risk infotmationrelatingto the:tnaJotside effects and 

c.onttaindications concurrently in the audio and visual parts-0fthe prtl!lenta:tfon 

foradvertisingand promotionalmatetia.lsin.audio-visual fonnat 

••• Beaccompanied.bythe authorizedlabe~ ifthepromotionalmlii:enals arenot 

subjectto Section 502(n}oftheAct. 

•• Be:submittedto FDA accompanied by FonnFDA•2253 atthetime of initial 

dissemination ot:fust use, 

ttilie.Agencynotities Ali'ffllZertecathat any descriptive printed matter; advettismlfQt 

pro:ni9ticmalllla,ierialsd.on:Qtmeetthetennilsetfeilthin:~nditions V-X oftbis EU!\; 

AstraZenecamustcease.distribution ofsuchdescriptive·printedma1tei; advertising. or 

promotional materials in accordance with. the Agency>s notification. Furthennore; as part 

of its fio'tification.,. theAgenc.ymayalso requite Asmtl.enec:ato issue corrective 

communication(s);. 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6589 


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Page 10-AstraZen~ca Pharmaceuticals LP 

W. No descriptive printed matter, adveruiing., orpromotionalmaterials rela1ingto the use of 

EVUSHELD undetthis llli1horization may represent orsuggestthat EVUSHELDis safe·or 

effectivewhenw;edaspre;.expo$U.tt!prophylaxisofCO-VID-19 asnescribedinthe·Scope 

of AuthorizatiQn (Section It). 

x All descriptive pnntednfatter, advertising".aridpromotiomilniaterialt relating to.the use of 

EVUSHElDunderthis authotization clearly and conspicuously shalls1ate that: 

• EVUSHELb hasnot beenapproved,but haS been authot'izea for.emergency 

.QSe by FDAunderanEOA;forpn:'-exposureprophylaxis ofCOVID-1? in 

certaiti.adul~ ~pedi~iric indivi~ (12 y¢al'S ofage in.id olderweighingat 

1east40 kg); and 

• the .. emergertcyuseofEVUSHEtb is otuy authorizedforthe duratiOn of the 

declaration that cnt1utnslances existjustifyingthe ituthonz.ation of the 

emer:gencyuseofdrugs and biologicalproducts during the COVID019 

pand.emi,c underSection 5-64(t,)(l)()fthe {\ct 21 US,C. § 360bbb-:3(bXl); 

unlessthedeclaration.istenninated or authorization revoked sooner. 

TiiisEUA willbeeffoctiveuntilthe.declarationthat.circumstances existjustifyihgthe 

authorizationofthe emergencyuseofdrugsand biologfoalproductsduringtheCOVID-19 

pandemicistenninatedunderSection 5'64(b)(2) oftheActorthe EUAis revoked unde:rSection 

.564(g) 9fthe A.ct 

Sincerely; 

Isl 

Jacquelint: A. O'Shaughnessy. Ph.D. 

Acting Chief ·scientist 

Food and DrugAdministration 
6590 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 


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Pfizer, Inc. 

Aiten:tfon:; .Ka:renJlake:r 

Dttector; Global Regulatory Affairs: 

235 Eas:t42nd Street 

New York, NY 10017-5755 

RE: Emergency Use Authorization l05 

Dear Ms. Baker: 

December 22, 2021 

This letteris: in response to Pfiter; foci's. (Pfit.et) tequestthanhe Food and t>tugAdministration 

(FDA orAgency)issue an :Emergency Use Authorization (EUA)for the emergency use of 

PAXLOVID (ninnatrelvir co-packaged with ritonavir) for the treatmentofniild-to-moderate 

coronavirus disease.2019 (COVID-19) in certain adults.and pediatric patients pursuant to Section 

564 of the Federal Food, Drug, and.Cosmetic Act (th:e Act) (21 OAtC. §360hbb-3). 

On Februiuy 4, 2020, ptl!'$uantto Section 564(b)(1 )(C) ofthe Act, the Secretary ofthe 

Department of Health and HumanS:etvices (HHS) determined that.th.ere is a public health 

emergency that has a significant potential to affectnathmalsecuri'ly orthehealth :and security of 

United States citizens: living abroad, and that.involves the virus that causes corona:,iws disease 

2019 (COVID-19}. 1 On the basis of such determination, the Secretary of:aHS on Mat(;.lh 27, 

2020; declared thatcircumstances existjusJifying the authorization of emergency use of drugs 

and biologicalprcrducts:duringthe COVID-19 pandemic,p.ursuantto $ection564 of the Act(21 

Li.KC. 360.bbb-3),subject to cerms of any authorization issued undetihat section. 2 

PAXLOVlDis comprised. of.nirmatrelvir, a SARS°CoV •2 main protease (Mpro: also referredto 

as 3CLpro ornsp5 protease) inhibitor, co-packaged with ritqnavir, an HlV-1 proteas1dnhil:>iior 

and CYP3Ainhibitor: Ritonavir, which has no activity against SARS-CoV-2 on its own, is 

included to inhibit the CYP3A-mediatedmetabolism 6f nirmatrelvit nnd consequently increas.e 

ninruttrelvir piasma concentrations to levels anticipated to inhibit SAR:$-'Co V-2 replication.. 

PAXLOVIO is not approved for any use, includftl:g for use:for the treattnen.t of COVID~W 

Based on the .totality of scientific evidence available t◊ FDA, including data from the clinical 

trial EP{CsHR (NCT04960ZQ2), a Phase 2/3 randomized, double bhnd, placebo-ecmtrolled 

clinical trial, it is reasonable to believe that PAXLOVTD may· be eff ectiveforthe treatment of 

mild-to-moderate COVTD-l 9 in adults and pediatric patients (12 years ot'age and older weighing 

l U.Sibepa.i:Lmertt, qllleaHh ®d il(imittr Servic~;Determinatiano/ aPub/ic.Heq/t/JEmergem;y andDe.cla1rittan 

ihatCircumsJances-ExtsiJustijyingAuthortzattonsPursuant toSection564(t/)aftheFede,;al.Forxi; Drug, and 

Cosmerfo;1ct, 21 U.S;C. §360bblr3. February4.,W20. 2 US. bcp~1tmcr1t.ofHcalth anq Human Sctvicc.•,;Di(diilY//iaiithqtl"tre1i11i;slalr~s HiczytJit§ti}jlingAtithdiiiiiti6tts 

Purww:inti<~Sedum 564(b) of theF:ederafFmrd, Drug, andCr1.~metfo Ac.l,21 U:.'{G.§ 360bf!1,:.J, 85 FR 18250 

(April 1,2020); 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6591 


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Pagi) 2 -- Pfiz<)r, Inc. 

at least 40 kg) with positive results of direct SARS-Co V-2 viral testing, and 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 when used under the conditions desctibed in this 

authotization, the known and potential benefits of PAXLOVID outweigh the known and 

potential risks of such product. 

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

Act are met, I am authorizing the emergency use of P A,,"'i'.:LOVID for the treatment of mild-tomoderate COVID-19 in certain adults and pediattic patients, as described in the Scope of 

Authorization section of this letter (Section II) and subjectto the terms of this authotization. 

I. Criteiia for Issuance of Authorization 

I have concluded that the emergency use of P A,,"\'.LOVID for the treatment of COVID-19, when 

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

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

1. SAR.S-Co V-2 can cause a serious or life-threatening disease or condition, including 

severe respiratory illness, to humans infected bythis vims; 

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

that PA,,-XLOVID may be 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) with 

positive results of direct SARS-Co V-2 viral testing, and 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 underthe conditions described 

in.this authorization, the known and potential benefits of PAXLOVID outweigh the 

known and potential risks of such product; and 

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

PA.XLOVID for the treatment of mild-to-moderate. COVID-19 in adults and pediatric 

patients (12 years of age and older weighing at least 40 kg) with positive results of 

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

COVID-19, including hospitalization or death. 3 

II. Scope ofAuthorization 

I have concluded, pursua11t to Section 564( d)( 1) of the Act, that the scope of this. authorization is 

limited as follows: 

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

(U.S.) Government for use consistent with the terms and conditions of this EUA. 

Pfizer will supply PAXLOVIDto authotized distributor(s)4, who will distribute to 

3 No othercriteria ofissuance have been prescribed by regulation under Section564(cX4)oftheAct. 4 "AuthorizedDistributor(s)" are identified by Pfizer-as an entity or entities allowedto distributeauthorized 

PAl{LOVID. 
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Page 3 -- Pfizer, Inc. 

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

collaboration with state and local government authorities as needed; 

• PAXLOVID may only be used by healthcare providers to treat mild-to-moderate 

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

least 40 kg) with positive results of direct SARS-Co V-2 viral testing, and who are at 

high risk 5 for progression to severe COVID-19, including hospitalization or death; 

Limitations on Authorized Use 

• PAXLOVID is not authorizedforinitiationoftreatment in patients requiring 

hospitalization due tq severe or critical COVID-19. 6 

• PAXLOVID is not au1horizedforuse as pre-exposure or as post~exposure 

prophylaxis forprevention of COVID-19. 

• P AXLOVID is not au1horized foruse for longer than .5 consecutive days. 

• PA){LOVID may only be prescribed for an individual patient by physicians, 

advanced practice registered nurses, and physician assistants that are licensed or 

authorized under state. law to prescribe drugs in the therapeutic class to which 

PA.XLOVID belongs (i.e., anti-infectives). 7 

• The use of P AXL◊VID covered by this authorization must.be in accordance with the 

authorized Fact Sheets. 

Product Description 

PAX.LOVID consists of two 150111gtablets ofnit111atrelvirthat are co-package<! with one 

100 mg tab let ritonavir. 

Nit1natrelvir is supplied as an oval, pink, iriunediate-release, film-coated tablet de bossed with 

"PFE" on one side and "3CL" on the other side. 

Ritonavir is supplied as a white, film-coated, ovaloid tablet de bossed wi1h the "a" logo and the 

codeNK. 

The authorized storage and handling infor111ation for P AXLOVID is ii.1cluded in the authorized 

Fact Sheetfor Healthcare Providers. 

5 For information on medical conditions andfactorsassociated'With increased risk forprogression to severe COVID 

19, see the Centers forDisea seControl and Prevwtion.(CDC)website: https;//www.cdc.gov/coronavirus/2019-

ncov/need-extra-precautions/pegple-wit.h-medical-conditions.h1ml. 

6 Pa tients.requiringhospitalizationdue to severe or critical COVID• l 9afterstarting treatment with PAXLOVID 

may complete the full 5-da y treatment course per the healthcare provider's discretion. 7 The term "State" includes any State or Territory of the United States,.theDistrictofColumbia, and the 

Commonwealth of Puerto Rico. See section20l(aXl )oftheAct. 
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Page 4 - Pfizer, Inc. 

PA.c"'CT,OVID 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 Pfizer's website www.COVID19ora1RX.com (refertedto as the 

"authorized labeling''): 

• Fact SheetforHealthcare Providers: EmergencyUseAuthorization(EUA)for 

PA.cXLOVID 

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

PAXLOVIDfor Coronavirus Disease 2019 (COVID-19) 

Ihave 'Concluded, pursuantto Section 564( d )(2) of the Act, that it is reasonable to believe that 

the knownandpotential benefits of PAXLOVIT>, when u$ed forthetreatment 9fCOVID-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(dX3)ofthe Act, based on the totality of scientific 

evidence available to FDA, that it is reasonable to believe that PA.XLO VID may be e:ll'ective for 

the treatmentofCOVIl)..19 when used in accordance with this Scope of Authorization (Section 

II), pursuant to Section 564{cX2XA) of the Act 

Havingreviewedthescientific information available to FDA, including the informati01i 

supportingtheconclusions described in Section I above,lhaveconcluded thatPAXLOVID(as 

described in this Scope ofAuthorization (Section II)) meets the criteria setforth in Section 564(c) 

of the Act: concerning safety and potential effectiveness. 

1lie emergency use of PAXLOVIDunderthisEUAmust be consistentwith, and maynotexceed; 

the terms of the Autlmrizi¢i.on, including the Scope of Authorization(Section II) and the Conditions 

of Authorization (Section III} Subject to the terms of this EUAand under the circumstances set 

forth in the Secretary ofHHS's detertnit1ation under Section 564(bXl)(C) described above and the 

SecretaryofHHS's corresponding declaration under Section 564(bXl), P AXLOVIbis authorized 

for-thetreatmentofruikUo-moderate CO'Vll)..19 in.adults andpediatricpatients (12 years of age 

and o lderweighing at least 40 kg)withposi1ive results of direct SARS-Co V• 2 viral testing, and wbo 

are at high risk for progression to severeCOVlI).19, including hospitalization otdeath, as described 

in the ScopeofAuthorization(Section II) under this EUA, despitethefactthatit doesrtot meet 

certain requirements othetwise required by applicable federal law. 

III. ConditionsofAuthorlzation 

Pursuantto:Section 564 of the Act, I am establishing thef ollowing:Con<litions on thisimthorization: 

Pfizer and Authorized Distnbutors8 

A. Pfizer and authorized distributo:r(s) will ensure that P AXIDVID is distributed and the 

authorized labeling (i.e., Fact Sheets )will be made available to healthcare facilities and/or 

healthcare providers as described in Sectiot1 II of this Le.tuir of Authorization. 

8 SupraatNote4. 
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Page 5 -- Pfizer, Inc. 

B. Ffizet and authorized distributot( s) will ensure that appropriate storage is maintained .until 

the product is delivered to healthcare facilities and/or healthcare pl'OViders. 

C. Ffizer and authorizeddistributot(s) will ensure that the terms of this EUA are made 

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

government authorities, authorized distributors, healthcare facilities, healthcare providers) 

involved in distributing or receiving PAXLOVID. Pfizer will provide to all relevant 

stakeholders a copy of this_ Letter of Authorization and communicate any subsequent 

amendments that might be made to this Letter of Authorization and its authorized 

accompanying materials (i.e., Fact Sheets). 

I); pfizer may request changes to this authorization, it1cluding to the authorized Fact Sheets for 

PAXL0Vm. Anyrequestforchangesto this EUAmust be submitted to the Office of 

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

changes require appropriate authorizati011 prior to implementation. 9 

E.. Pfizer may develop and disseminate instructional and educational materials ( e.g., materials 

providing infonnation on product administration and/or patient monitoring) that are 

consistent with the authorized emergency use of P AXL0VID as described in this Letter of 

Authorizati0t1 and authorized labeling, without FD A's review and concurrence, when 

necessary to meet public health needs. Any instructional and educational materials that are 

inclmsistent withtlte au1horized labeling for P AXL0VID are prohibited. If the Agency 

notifies Pfizer that any instructional and educational materials are inconsistent with the 

authorized labeling, Pfizermust cease distribution of such instructional and educati011al 

materials. Furthermore, as part of its notificati0t1, the Agency may also require Pfizer to 

issue corrective communication(s). 

F. Ffizer willrepmt to FDA serious adverse events a:nd all medicati011 errors associated with 

the use. of P AXL0VID for its authorized use that are reported to. Pfizer using either of the 

following opti011s. 

Option 1: Submit reports through the Safety ReportingPortal(SRP) as del3Cribedon the FDA 

SRPweb page. 

Option 2: Submit reports directly through the Electronic Submissions Gateway (ESG) as 

described on the F AERS electronic submissions web page. 

9 The following types ofrevisionsmaybe authorized withoutreissuing this letter: (l) changes fo the authorized 

labeling; (2)non-substantive editorial corrections to this letter; (3)newtypes of authorized labeling, including new fact sheets; (4)new carton/cootainer labels; (5)expirationdating extensions:, (6)changes to manufacturing 

processes, including tests or other a u1horized components of manufacturing; (7) new conditions of authorization to 

require data collection or study; (8 )new strengt~ of the authorized J.'lroduct, new product sources (e.g., of active 

phannaceutical ingredient) or ofproduct components. Forchanges to the authorization, including the authorized 

labeling, of the type listed in (3), (6), (7), or(8), review and concurrence is required from the Counter-Terrorism and 

Emergency Coordination Staff/O±lice of the Center Director/CDER: and theOffice ofCounterterrorism and 

Emerging Threats/Office of the Chief Scientist. 
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Submitted reports under both options must state: '"P A,XLOVID use forCOVID-19 under 

Emergency Use Authorization(EUA)." For reports submitted underOption 1, includelhis 

language at the beginning of the question"Describe Event" forfurther anaJysis. Forreporls 

submitted under Option 2, include this language at the beginning of the "Case Narralive" 

field. 

n All manufacturing, packaging, and tes1ingsites for both drug substance and drug product 

will comply with current good manufacturing practice requirements ofSection 

50 I ( a X2)(B) of the Act. 

H. Pfizer will submit information to the Agency within three working days of receipt ofany 

inf onnation concerning significant qualify problems with dru_g product distributed under 

this emergency useatithorization for P AXLOVID that in dudes the following: 

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

to be mistaken for, or applie.dto,anotherarticle; or 

• lnfonnation concerning any microbiological contamination, or any significant 

chemical,physical, orotherchange or deterioration in the distnbuteddrug 

product, or any failure of one or more distributed batches of the productto meet 

the established specifications. 

If a significantqualityprobiem affects unreleased product and may aJso impact product(s) 

previously released and distributed, then information must be submitted for all potentially 

impacted lots. 

Pfizer will include in its notification tothe Agency whether the batch, or batches, in 

·question will be recalled 

If not included in its initial notification, Pfizer must submit infonnation conflflllingthat 

f'fizer has identified the root cause of the significant quality problems,taken corrective 

action, and provide a justification confmningthat the corrective action is appropriate 

.and effective. Pfizer must submit this information as soon as possible but no lateithan 

45 calendardaysfromthe initial notification. 

I. Pfizer will manufacture PA.XLOVIThomeet all quality standards and perthe 

manufacturing process and control strategy as detailed inPfizer'sEUArequest Pfizer will 

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

facilities and.equipment, and elements of the associated control strategy that assure process 

performance and quality of the au1horized product, without notification to and concurrence 

by the Agency as described under condition D. 

J. Through a process of inventory control, Pfizer and authorizeddistribirtor(s) willmaintaiii 

records regarding distnbution of PAXLOVID (i.e., lot numbers, quantity, receiving site, 

receipt date). 
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K .Pfizerwill establish a process,formoni1Dringgenomicdatabase(s}forthe.emergence of 

glohalvital\latia.trtS.QfSARS-Cov~::bmd willprt>,vide~repot1S to the Age:ncyonamonthly 

basis stifillilariiinganyfmdingitas a resriftof:iis moriitoringactivities and,.as nee4ed, any. 

fijlfow-up il$Sess:tn¢ilts planntid or conl.bzjed Updated da1aJistin~ summariziiig;aniino · 

. acidvariabilityshotildbe:providedatleastmomhlYfor Mpro-ammo acld·sequences; and at 

~~?.:?'SSf:;t==r 

L. FDAmay·require:Pfizerfo assesstheaclivityoftheauthorizedPAXLOVIUagainstany· 

gfobalsARS~Co:Y~2Vmant(:s)-0fitttetest(e,g;,viiriant$thatareptevalentorheoomihg:. •=:==~s~~::i::::~1:s0:!::1&:~:::::in:the 

agreed upon by Pfizer and the.Agency, ffizer:will submitt<>'FDAa prelii:niharysummar:y 

·.report immediatelyuponcomplettonofits,assessmentfollowed. bya de1ailed study.report 

· withih30calendar days of study completion. Pftzerwillsubmit anyrelevantproposal(s)to 

tev'isetheJ1uth:orizedlab¢Iln:gbased 01i:-theresults ofitsi assessme.rtt;.asmaybenecesS$)''6r . approprj$ ~d.QnihefqregofugllS~ssmen{ · · ·· 

XL Pfizer shallprovidesamples asrequestedoftheautho:rizednmnatretvirfo the U.S. 

DepartmerrtofHealth andHumattServic:es(HHS)forevahiation•of-activityagamst 

·emerginggloblil.vii'alva:riants ofSA,:RSaCoy;;z.mcludingspecinc:•~o.•acid 

:substitution(s) llfinterest (e,lh variants that.are 1iigblyprew:le~llortha(ham·Ol'.su1l!!tittitio11S 

··iu0thetal;get-prote~s}ortargeh:il~vagesit~!i)·withinSb11Sitiess'days··Qfanyreqi;iest·tt1a(fe 

··by HHS. Analysesperfonned•with.thesuppliedquantityofauthorizedniimatrelvir·may·· 

•.~~:~:::n◊t limitedt(I, cel.J.ctil1ilieJlotehc):'assays,biQChelllicalassays,andin.vi'vo 

.N: •Pfizermust:providethe:foBQwmginfonn:ation:fothe·Agency:• 

L :Pfizermust c6tiductcell culture phenotypic::anaiyses-ofrec6111binarttSARSQoV~2:vim-ses•orteplicons;c:lltJ.'Ying·spec·ifi¢amirt.o acid·changes.potentially 

lt!IS◊c:iated with~duc~nintr~Jyjr~ptipiJityin n:9ru,:(~cal ot¢linwlil: 

studies,,orpolymotphismsemerging.in,novel,SARS-CoV-,2variarits, Specific 

amino acid changes thatsfuutd'be c;hatac~rized includethefoUowing: 

o f::O°c:!~~J::;:Soci~withtediicedniimattel\iirsuscf!Ptibilliy 

: ==1:===::=ll,o, 

;::::~:~cr::::::rorprolongedvir<>logicshe~ot 

o· .·ammo ·acidpolymorphismsideritifiedii1resi:stance:su1Veillance·• 

analyses. 

Ammo acid changes ili bothMpto andMpto cleaVage.sitessfouldbe 

consit.leredmthese_an.ilY$es. $p.ecffic ~o acidci@.ges:ofinterestfor 
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phenotypic characterization in cell culture assays currently include Mpro 

substitutions Y54A,E55L, Fl40A,S144A,E166A, H172Y,Q189K, and 

A260V. When warrnnted due to technical challenges, alter11ative approaches to 

the requested cell culture assays will be co11Sidered 011 a case-by-case basis. 

Pfizer must submit a preliminary summary report no laterthan February 28, 

2022 for any currently ongoing studies, and at least every 6 months thereafter as 

additional data accumulate. 

2. Pfizer must evaluate the cell culture antiviral activity ofoirmatrelvit against an 

a.uthenticSARS-CoV~2 isolate representative of the Omicron variant Pfizer 

must submit a summary report no later than February 28, 2022. 

3. Pfizer must cooduct studies characterizing potential nirtnatrelvirresistimce 

mechan.iS!lls in SARS-Co V-2 in cell culture, including selection and genotypic 

and phenotypic characterization ofllim1atrelvir-resista11t virus. Pfizer must 

submit a briefmoothly progress report on these studies; a preliminary summary 

report no laterthanApril 30, 2022, and a final reportwithin30 days of study 

completion. 

4. Pfizer must complete analyses ofSARS-CoV-2 shedding and nucleotide 

sequencing from the EPIC-HRclinical trial. Viral sequencing analyses 

should be conducted for all clinical samples with sufficient viral RNA levels, 

including samples collected at baseline, on-treatment and post-treatment, to 

identify and characterize the pote.ntial emergence or persistence of amino 

acid changes associated with P AXLOVID treatment. Pfizer must submit a 

summary of available data (including analysis-ready datasets) no later than 

February 28, 2022, and a final report and associated datasets (including 

analysis-ready datasets and raw fastq NGS data) no later than April 30, 2022. 

5. Pfizer will submit the clinical study report containing data from all enrolled 

subjects in the EPIC-HR clinical trial no later than January 15, 2022. 

6. Pfizer will provide results from a safety and pharmacokinetic study 

evaluating P AXLOVID as treatment of mild-to-moderate COVID-19 in 

patients with severe renal impairment (for both patients requiring and not 

requfringhemodialysis), withthe studyprotocol submitted 110 late.tthru1. 

March 31, 2022. 

7. Pfizer will provide the audited final report of the rat PPND study, An Oral 

(Gavage) Study of the l{tfects of PF~0732 J 33 2on Pre- and Postnatal 

De1,elopment1 Including Maternal Function in Rats, 110 later tha11 April 30, 

2022. . 

0. Pfizer and authorized distributor(s) will make available to FDA upon request any records 

maintained in c01111ection with this EU A 

Healthcare Facilities to Whom P AXLOVID Is Distributed artd Ilealthcare Providers Administering 

PAXLOVID 

P. Healthcare facilities and healthcare providers will ensure that they are aware of the Letter 

of Authorization, and the terms herein, a11d that the authorized Fact Sheets are.made 
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P,age 9 - P,fizer,Jnc. 

• availabletohealthcare providers. andtopatients,parents, and.oaregivera,.respectively, 

tht◊1:t$h·.amiropda~means, priortoadtttiriisW1t)fuof:PA:XLOV1b: · 

Q, Uea1th~facilrues @dh:el3lthcai'eptQVi\etSt¢'c¢i\fihgPJ\XLQV10willitc®k:all serious 

medicalion .. errorsand adverse evettfsthatare considered to bepotetiti:a.lly:attributaole to 

·PAXLOVID tlse•an:dtnustreporttheset() FDAin.·atcotdance·withtheFact•Sheetfor 

llelllth¢attJ>mvi~ts.·G~leye~d stibniita M:edWat!)hfott:r) 

. cwww~fda:go:v!med\\laWbite@ft.111lnl or cW'fiJilete~ sJJbmitFOA Fotn:t 35do @~1th 

·prof:essiqn!tl.)l>yfax(l~8®'-F:PA-Ol~}(tlteSt1 fonnscanllef:QU11d'1ialirik1:1.bove); C:all.b 

·soO•FDA-10S:8'forquesfionKStibmittedreportsmuststat~f!PAXLOVIDuseforCOVID:-

. 19 undetEmerge~tlseA:tltn<>.nzation"atthe beginmn~<>f'theguestion''Descnoe E'venf' 

forfuriher aniU)'Sis, A copy of'ih.¢ c~l~edFDAFotm3500 must also.lter,rovidedto 

l>f'.izetp~theirt~QnSlll.t®llutb:orizedl~l~; . 

R. .Healthcare•facilities andhealthcareprovii:lerswill ensurethat:appropriatestorageis 

·maintained.untiUhe productisadministeredconsistentwith.thetenns,ofthis:letterandthe 

authorized labeling. 

S. Through.ap::rocessofinventorycontrot:.:heaithcarefacilities·willmaintainrecordsrefJl!ding 

the di!!pensiilgandadministrationof PAX I.OVID for theuse.authorized inthis. le'lter(ie.,, 

101.numl>ers,q)iantityj receivingsit~ receipt datelproductstorage, andmaintainpati'ent 

infotmatiot1(e.,g;,.patientnatt1e;age,•disease mllnifestatio~.rtUtlil:!~·ofdoses;1dmifiistered 

Ptlf Pati~t; giherdrugs ll~bni~d). 

T. Healthcarefacilities willensurethatanyrecordi!:associatedwiththis.EUAaremairitained 

·untilrtotified by Pf"izerand/otFDA Si:it:hrecotdswill be madeavailablet0:l>.tizer,HHS, 

and fDAJqrin!!f!ecti,on upot1request · 

U: Healthcarefacilities andproviderswillreporttherapeuticsinfonnationandutilizationd'ata 

as dfre¢ted.byHHS; 

. c:Ondnfons Refatedt-0 Printed.Matter., Advertising, artd Promotion 

V'. All descriptive printed matter; advertising, and promotionaJmaterialsrelatingtotheuse of 

PAXLOVID underth:isauthorizationshall be consisten.twiththe auth:ori&edlitbeli11g. as 

wen as the terms setforth.inthis EDA. andmeetthe teqwrerru:rtts setfottli.irt:Sectiim 

5()2(a)and(rt)-0fthe Aci,as ~pplicabfo; ~ IDA iinplementingregulatiorts: R.efetenc\es to 

••a,pproved la!Jellng'1,/'pen:nitted·Iallel41:g''9r·similwteilJl$in·theserequirerrrents~lillll be 

understoodtorefertotheauthorized.labelingfortheuse-0fPAXLOVIDunderthis 

authorization Inaddition, such materials shall:. 

•• l3etailoredtQtheintertdedaudience. 

•• Not take.the fonnofreminderadvertisements, asthattermis descrioedin2l 

CFR.202. l(e)(ZXQ, Zl CFR200,200and2i CFR20i.lQ()(f} 
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Page 10 - }>fizer, Inc. 

• Presentthe same risk. information relating to the major side-effect!:! and 

contraindications concurrently in the audio and visual parts ofthepresenta1ion 

foradvertisingandpromotionalmaterialsinaudio-visualformat 

•• Beaccornplllliedbythe authorizedlabeling; ifthepromotioruilmaterials-arenot 

subject to Section 502(n}oftheAct 

• Besubmi:ttedtQFDA a®mpaniedhyFottnFDA•2253.att:hetime.ofmitla1 

dissemination ()f fttst\i!le. 

Ifihe·.Agencynotifies Prizerihatany descriptiveprintedmatteriadveriisingorpromotional 

mateiialsdon:otmeetthetermssetforthin.ooru:litionsV~XofthisEUA, Pfizermustcease 

distributimofstichtlesctiptivepririredfuattet,.advertising,.orpromotiotlilmaterlals in 

accotdat'lcewith.theAgency'snotiftcation. Furthermore,.aspattofitS ttotification,. the 

A,gel)cyw.aya.tso·.teqμke·l:'flzertQ•is~e.cQttectiYec:omm:lllU<:atiQi1@, 

W: •No de.scriptiveprintedmafter1 advertising;or·promotionalmaterials.relatingtotheuseof 

PAXLOVtt> underthis.auth~on•rnat~reserttor·suggestthat:PA.XLO'\III)issafeor 

effective whenu~dfotthe :treatment ofCOVID0 19. 

}(: . All descriptiveptjtttedmafter; ~dve~mg.Mcl promotiQmi!lllliteri1U,r¢laungtotlleuse of 

PAXLOVlD underthisauthorizafionclearly andconspicuouslyshall state that: 

• PAXLOVUlhas notbeet11tpP!OVedtbuthas1'een lllithonzedf<>r: 

emersency use by Fl>A under lii1 EUJ\, forthetreatm.eot Qftnild-tomQderate .CO\TIQ-l?inadults andvediatricpatients(l2years of age: 

and older weighing af Ieast40 kg)withposi1iveresul1s of direct SARS~ 

Cov .. 2 viraltestitlg,andwho are athigh0riskforprogression to.severe 

COVID-19,inclUdinghospitalization<>fdeath;and 

• The emer~cyuseof RAXit()Vl'fiisonlyiu,1t11Qtized.f«thedurati9n 

Qfthedecllitat:t'Qnthat.citctJmStancesexistjustifyingtheauthorizajionQf 

the emergency use of drugs andbiohgical products during the COVID19 pandemic under Section$64(bXl)oftheAct, 21URC. § 360bbtr. 

3{b)(1),urt~$the decfatiltionis terminated otauthorizatiortrevoked 

SMn.et. 

IV. Durationof.Authorizd.on 

ThisEUA wiltbeeffectiveun1ilthededaratfon thatcircumstances e-xistjustifyfu~llfo 

authorization of the emetgenqyuse.ofd~ andbiologicalproductsiduringtheCOVID~t9 

PMdemic isJerminatedunclerSecti.Qn 564(b)(2) Qfthei\.ctQtthe EtJAi!:! revoked μni,ler.Sec.tion 

564(g)ofthe Act 

!.'age Tl -.I>fizer, Inc. 

Sincerely. 

Isl 

hcq11elμ1e A O'Sha11ghness5', Ph.D. 

Acting Chief .Scientist 

Food and DrugAdminisfratiou 
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Merck Sharp & Oofrme Corp. 

AttennQll: Sushma Xumar, PhD; Pl\11? 

December23, 2021 

Senior Director, Global Regulatory Affai.rs andClirticl'\lSafety 1 MerckDriye · · · · 

POBoxlOO 

Whit¢b:(ruse Stati◊n,NJ 0&&&9"0100 

RE; Emergency Use All.ihoriz-1:ttim:r mi 

near iJ1-: Kumar: 

This letteris in respo1,1s.etoMerck:Sharp & Oohme C◊rp, 's(Mecrck) reqμE$tthatfh.e.l'ood and 

Drug Administration (FDAor Agency )issue: an Emergency Use AU1horization (EUA)f orthe 

emergency use of moJnupiravirf or the tteatmerttofmild,to--mo:derate corortavirus, disease 2019 

(COVlD•l9) in c.ertaiintdults who ate athigh--risk forp:togressiMto severe COVlD•l9. 

irrcludingho.spitalization ordeatll, p.ursuantto Sec:tiofl $64 ofthe: Federal food, Dxug. afld 

Cosmetic Act (the Act) (2 l lJ;RC. §3601,l,h-3). 

On February 4, 2020, pursuantto Section 56.4(b)(l )(C) ot'the Act the Secretary of the 

Department offlealth afltUlumaflServ:ices (lU{S) determined .thattherefs atrublic health 

emergenpy thatJ.uisasigoificafltpotel'.),tial to affectnationalsecurity orthehealih afldsecurityof 

United St11tes citizens living abroad, and thatinvolves the virus th:atcauses coronavirus disease 

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

2020, declared i.lHlLcircumstances existjustifyingthe authorization ofemetgency us:e ofd:tu~ 

afld biOlogicalprodu<:1$ d4rirtg.(he COVID..J '1 pal'l(l.~c. pursuan.tto Section564 ofthe !\ct (21 

U.S. C. 36:0bbb-3),.subjectio terms of any authorizaaon issued underthatsection.:i 

Moinupiravids a nucleoside analogue that inhibits SARS~CoV -2 repli:cati011by viral 

mutagen.esis. M◊lnUpiravitis notFDa~app.t-0Yed fOtaflY uses, ihcludinguse. as trea11nentfot 

COVID-19, . 

Based onthe review of the dataftomtlre MOYe0 0UT cllirlcaitrfai (NCT04575597)~ a Phase 1ll 

rafldo:mized, double-blind, placebo-controlled clihical trial studyihgmohtupiravirfot the 

:treatmwt ofnon-h◊spitatized patients \'\'ith rnild-to-moderate: COVlD-19whu are athigh ris:kfor 

progression to severe COVID•l9; ihclu4in8 hospitalization or dea~ it is: reasonable .to believe 

tlratmolnupiravirmay be effective for the treatment ofmild-to~moderate COVID~l 9 in adults 

1 t1,S,Depi\iim¢!ito1'.1Ieahh ®d 1lt®;m $erv,~t:s,De.termi11auonofaPu6l1p'/1ealth'll,,w:rgenqyam.i.beclamiion 

ihaiCircumstancesExtstJ11siijyingAulhorlzat1011JPursuani toSectianS64'(q)oftheFedera1Forxi, Drug, and 

Cosmettc;fo( 21 U:S:C.§360bblr3.Februmy4,2020, 

i 1J. S, Department ot'Bciilth at\4 H::utni!!i Smiccs; JJec.iartiJirmJhiilCtftiifns)i:!li&s Ettst.h{St.tjy/ng ,4iirhotfiti1fijf!S. 

Pu.r.mantf(JSeptkm 564(b) oft~FederatFood;Drtrg,andCo.t1t11:ltcAet,2l fZS.C:§360hhh-3, 85 FR 18250 

(April 1,2020); 
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Page 2 -- Merck Sharp & Dohme Corp. 

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

for whom attemative COVID-19treatment options authorized by FDA are not accessible.or 

clinically appropriate, as described in the Scope of Authorization (Section II), and when used 

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

molnupiravir outweigh the known and potential risks of such product. 

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

Act are met, I am authorizing the emergency use of molnupiravir for the treatment of mild-tomoderate COVID-19 in adults who are athigh-riskforprogressionto severe COVID-19, 

including hospitalization or death, as described in the Scope of Authorization section of this 

letter (Section II) and subject to the tenns of this authorization. 

I. Criteria for Issuance of Authorization 

I have concluded that the emergency use of molnupiravir 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: 

1. 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 molnupiravir may be effective for the treatment of mild-to-moderate COVID-19 in 

adults 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 molnupiravir outweigh the known and potential risks of such 

product and 

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

molllllpiravir for the treat1nent of mild-to-moderate COVID-19 in adults as further 

described in the Scope of Authorization (section II). 3 

II. Scope of Authorization 

I have concluded, pursuant to Section 564(d)( 1) of the Act, that the scope of this authorization is 

limited as follows: 

• Distribution of the authorized molnupiravit will be contro lied by the United States 

(U.S.) Govemment foruse consistent with the terms and conditions of this EU A. 

Merck will supply molnupiravirto authorized distributor(s)4, who will distribute to 

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

collaboration with state and local government authorities as needed; 

3 No other criteria ofissuance have been prescriboo by regulation under Section564( c X4)of the Act. 4 "Authorized Distribu 1m( s )" a re identified by Merck as an entity or entities a llo woo to distribute au 1horized 

molnupiravir. 
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Page 3 -- Merck Sharp & Dohme Corp. 

• Molnupiravir may only be usedf or the treatment of mild-to-moderate C0VID-19 in 

adults: 

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

• Who are at high-risk5 for progression to severe C0VID, including 

hospitalization or death, and 

• For whom alternative C0VID-19treatment options authorized by FDA are not 

accessible ot clinically appropriate. 

Limitations on Authorized Use 

• Molnupiravir is not authorized foruse in patients who are less than 18 years of 

age. 

• Molnupiraviris not authorized for initiation of treatment in patients requiring 

hospitalization due to CO VID-19. 6 Benefit of treatment with moln upiravir has 

not been observed in subjects whe11 treatment was initiated after hospitalization 

due to COVID-19. 

• Molirnpiraviris rtot authorizedforuse for1ongetthan 5 cortsecutivedays. 

• Molnupiravir is not authorized for use as pre-exposure or as post-exposure 

prophylaxisforpreventionofC0VID-19. 

• Molnupiravir may only be prescribed for an individual patient by physicians, 

advanced prac.,1ice registered nurses, and physician assistants that are licensed or 

authorized under state 7 Jaw to prescribe drugs in the therapeutic class to which 

molnupiravir belongs (i.e., anti-infectives). 

• 'The use of molnupiravii: covered by this authorization must be i11 accordance with the 

authorized Fact Sheets. 

Product Description 

The authorized molnupfravir is supplied as a bottle (NDC~0006-505S-06, NDC-0006-5055-07) 

cot1taining a.sufficient quantity ofmolnupiravir 200 mg capsules to complete a fulltreatmetlt 

course (i.e., 40 capsules). Molnupiravir is manufactured as a Swedish Orange, opaque capsule 

co11tai11ingthe Merck corporate logo at1d "82" print.ed in white ink. 

s For information on medical conditions and factors associated with .increased ri.<ik forprogression to severe COVID 

19, seethe Centers for Disease Control and Preverition(CDC)website: https://www.gdc.gov/corgnayirus/2019-

. ncov/need-extr<H;n;ecautigns/pegple-with,medical-cgndition5,html 

~ Patients requiring hospitalizationafter starting treatment with molnupiravirmay completethefull 5 day treatment 

course per the healthcare provider's discretion. 7 The term "State"includes any State or Territory of the United States, theDistrictofCo!umbia, and the 

Commonwealth of Puerto Rico. See section201 (aXl) oftheAct. 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6603 


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Page 4 -- Merck Sharp & Dohme Corp. 

Tue authorized sto~ and handling infonnation is included in the authorized Fact Sheet for Healthcare 

Providers. 

Mohmpiravir is authorizedfor emergency use with the following product-specific information 

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

through Merck's website www.molnupiravir.com (referred to as the. "authorized labeling"): 

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

molnupiravir 

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

molnupiravir for Coronavin1s 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 of molnupiravir, when used for the treatment of COVID-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) of the Act, based on the totality ofscientific 

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

the treatment ofCOV1D-19 when used in accordance with this Scope of Authorization (Section 

II), pursuant to Section 564(c)(2)(A) of the Act. 

Having reviewed the scientific information available to FbA, including the information 

supportingthe conclusions described in Section I above, I have concluded that molnupiravir(as 

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

of the Act conceming safety and potential effectiveness. 

The emergency use of mo lmtpiravir product under this. EUA mu<;t be consistent v.ith, and may not 

exceed, thetem1s of the Authorization, including the Scope of Authorization (Section II) and the 

Conditions of Authoriza1ion (Section III). Subjectto. the terms of this EUA and under the 

circumstances set forth in the Secretary of HHS's determination under Section 564(b )(1 XC) 

described above and the Secretary of HHS ·s cottesponding declaration mider Section 564(b XI), 

molnupiravir is authorized for the treatment of CO VID-19 as described in this Scope of 

Authorization (Section II) under this EUA, despite the fact that it does not meet certain requirements 

otherwise required by applicable federal law. 

III. Conditions of Authorization 

Pursuant to Section 564 of the Act, I am establishing the following conditions on this authorization: 

Merck and Authorized Distributors 8 

A. Merck and authorized distributor( s) will ensure that mo lnupiravir is distributed and the 

authorized labeling (i.e., Fact Sheets )will be made available to healthcare facilities and/or 

healthc,u·e providers as described in Section II of this Letter of Authorization. 

8 Supra at Note 4. 
6604 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 


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Page 5 -- Merck Sharp & D.ohme Corp. 

B. Merck and authorized distributor(s) will ensure that appropriate storage is maintained until 

the product is delivered to healthcare facilities and/or healthcare providers. 

C. Merck and authorized distributor(s) will ensure that the terms of this EUA 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 molnupiravir. Merck will provide to.all relevant 

stakeholders a copy of this Letter of Authorization and commtmicate any subsequent 

amendments that might be made to this Letter of Authorization and its authorized 

accompanying materials (i.e., Fact Sheets). 

D. Merck may request changes to this authotization, including to the authorized Fact Sheets 

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

Infectious Diseases/Office ofN ew Dmgs/Centerfor Drug Evaluation and Research. Such 

changes require appropriate authorizati011 prior to implementation. 9 

E. Merck may develop and dissemin.ate instn1ctional and educational. materi.als (e.g., materials 

providing infommtion on product administration and/or patient monitoring) that are 

consistent with the authorized emergency use ofmolnupiravit as described in thisLetfer of 

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

necessaryto meet public health. needs. Any instructional and educational materials that are 

inconsistent with the au1horized labeling f ormolnupiravir are prohibited. Ifthe Agency 

notifies Merci( that any instructional and educational materials are inc011siste1rt with the. 

authorized labeling, Merck must cease distribution ofsuch instructional and educational 

materials. Furthermore, as part of its notificatioo, the Agency may also require Merck to 

issue corrective communicatioo(s). 

F. Merck will report to FDA serious adverse events and.all medication errorsassociatedwith 

the use of molnupiravir for its authorized use that are reported to Merck using either of the 

following options. 

Option 1 :. Submitreportsthroughthe SafetyReportingPortal(SRP) as described on the ,IDA 

SltP web page. 

Option 2: Submit reports directly through the ElectronicSubmissions Gateway (ESG) as 

described on the F AERS electronic submissions web page. 

9 11le following types of revisions may be authorized withoutreissuing this letter: (1) changes fo the authorized 

labeling; (2)non-substantive editorialcottections to this letter;.(3)newtypes of authorized labeling, including new fact sheets:, (4 )new carton/container labels; (5 )expira tiondating extensions; (6)changesto manufacturing 

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

require data coJle.ction or study; (8 )new strengths of the authorized product, newpro<;luct sourc<"S (e.g., of active 

phannaceutical ingredient) or of product domponents. For changes to the authorization, including the authorized 

labeling, of the type listed.in (3), (6), (7), or(8), review and concurrence is required from the Counter-Terrorism and 

Emergency Coordination Staff/Otlice oftheCenterDirector/CDBR and the Office of'Counterterrorism and 

Emerging Threats/Office of the Chief Scientist. 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6605 


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!>age 6 -,MerckSharp & Pohme Corp. 

Submittedreporls underbothoptionsmuststate;''Molnupiraviruse forCOVID-19 under 

Etnetgenqt.Tse Autho~ (EUA)t Fottepotts submitted undetOption 1, inc'iude1his 

language attheheginiilitgofthe question ''Descme Event''fotfurthetanafysis, Fotreports 

suQmitte4 under Option 2, im.:lu.dethis langμage:atthe beginning of the "Case 1-l'a:mrtive'' 

field. . 

G, .Allnfantifacttirlrig,packa:gm:g,andtestirigsitesforboth.dfugsubstance.anddfugprod'.uct 

·wm complywitlicuttentgoodtttanuracturlngpractice·requifetnertt$ ofSectioo 

5Ql(a)(2}(13)-0ftheA<;t · · · 

R Merckwill submit informafionto theAgencywithinthreeworldngdays ofreceipf. of any 

·infoi:'mlltion .. concerning.sigttificant•quality pml:!lems·with dtugprod:ttct~istributedutidet 

this•.EPAf9r·t11olnupira,mtl:m:findudesthefol1oWirig: 

• • 1nf()ni1a«dn C'Oficertifug anyinciderttthai causes the di-ugprodootor ·its ~1mg 

to be mistakenfo1\ or appliedto,.anotherarticle; or 

•• In:fonnano1:rconc~gany111i'Cf<>biologiclll contan::iinafion, or anysigajfi~t 

<.hemJct,tl,.physiplll,Otothercltangeordeteriorationiti:the 4i~uted<irug 

product,oranyfailureofoneormoredistributedbatchesofthe•producttomeet 

the esta6Ji$hed ~peclficafions. 

'I(i1:significan.iquality·prohlemmfecls unreleasedprodllcl.ancl•maY•·a~oimpactproduct(s.) 

previouslyreleasedanddistributed,theninformationmustbe.submit1edfurallpoteritially 

impacted lots. 

M~t~kwill in.ch::u:hdnits. notificatioot<>athe Agen~ywhe1het the batch, or batches, in 

questi;onwill berecaUed · · · 

ttrH>tlftcluded 1n its1nitiafnotificati◊n, Merck mustsubm1tilifQtmatit>ncoriftin11ng 

thatMerckhMidentiftedthe toott:auseof:the ~ignificantquality problems, taken 

corret:tive action~ and provide aju$fificati0rt CQtifirmingJh:atthec c.on-ectiveaction is 

approp~ateandeffective, Merckmuststibmitthis infortnafionas soon as possible but 

M laterthan45 calendar days fromtheinitialnotification 

1 Mer¢kwillmllliuf'a~emohi.upltavirto.tt1e1:1ta:11 quafity stimdat~ i!iidpetthe 

manufacturingprqce~ amlconfrolsirategyas detailed.inMetck'sEUA request Mmk. 

will also•testthe.active·phannaceuficalingredient(APl)startingmalerial·foradditional 

qualityattributes agreeduponbyMerck andtheAgency.Merckwillnotimplementany 

changestothe descriptiortofilieptdduct,.manufllciilringptoce~,facilmes andequipm• 

and.elet11t1rtts..·offfi:e.as.<iociated•t:ontrolstmtegythatas.<iμrep~~sperfonnll!lce.a,ndquality 

of theauthoriz:ed product. \Yilhoutnotificaticmtd and t:oncurrence by th:e.Agency as · · 

•describedunderconditfonDi 
6606 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 


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Page 7 -.Merck.Sharp & I)ohme Corp. 

J, 'Through a processof inyentorycontrol,Merckandauthorized.distributor(s)will maintain 

records regardingdistributionofmolnupiravir(i;e., lotnumbers, quantify, receivingsite, 

receipt date). 

K. tvlerckwiIIestablishaprocessformorutoringgenomicda~se(s)fortheemergenc.,of 

globalvitalvariantsofSARS-CoV~2 .. AsummaryofMerck'sprocessshouldbe.submitted 

to the Agencyas soonaspracticab1e, butno laterthlll130 calendar days ofthe issuance of 

this letter, and within30 calendar days Qfanymaterial changes to sucfrprocess. Merck will 

provideteportstotheAgenccyonamonthlybasissummarizing11J1Yfindings.as aresultof 

itsmonitoring1tcti'vitiesand;asneeded,anyfollowaup~essn1entsplannedorcooducted; 

L. FDA may require.Merck to assess the activity of the authorizedmolnupiraviragainst any 

global SARSaCoV;.2variant(s)of:interest(e,g:, variant'i that are prevalentorhecoming 

prevalent:thathaworsubstifutions in the target protein odnpro'teih(s)that interactwiththe 

target protein) .. Merckwil1pe1fonntherequired assessment in a.manner and timeframe 

agreed upon by Merckandthe Agency; Merok.will submifto FDAapreliminazy summa:iy 

rep?rt immediately upon completion ofits assessment followed by a detailed study report 

within 30calendar days ofstudy compktion, Merck.will submit any relevant propooal(sJtO 

revise the autlwrizedla®ling based on the.results ofits ~~ment, ;is1nay b~1'eces~ or 

appropriate bllSed onilleforeg()Ulgasse!!Sment 

M. Merck·shaii provide samples as requestedofmolnupifavifto.iheU.R Department of' 

Health and Human Services (HHS) for evalua1:ion. ofacli'vityagainst emergingglobalviral 

varian1s ofSARSs0:>V~2: including specific amino ac.id.substit.Ution(s) <'!finterest (1tg., 

varianistbatlll'e.highlyprevalentorthatharllors1Jbstitutionsinthetatgetprofei11)within5 

businessdays ofanyrequestmade by HHS. Analysesperfonnedwiththesuppliedquantify 

ofmolnupiravirmayinclude, hut are notiimitedto, ceil.Ptlhure.potency assays, 

biochemical assays, and in vivo i:.ifficacyassays: 

N: Merck musfprovidethe following information to the Agency: 

L Merck will conduct a thorough investtgation info the differences ili efficacy 

observe.cl in the firstand seconclhalfofl>art2.◊ftrial MK-44&2-002. This 

assessmentsh<>1Jld inv()lve the synthesis of djttll, including, 1:mtnot limited to; 

additional. baseline serology testing, a.detailed comparison ofbaseline. 

characteristics (including demographic, clinical disease, and virologic 

characteristics), and an exploration ofpoterttialdifferences in standard of 

care byregfon and overtime. Merckwillsnbmit a report ofitsfindingstothe 

Agt:ncy. Merclcwillsub111ita prelirninlμ'Y report no laterth.tt1Mllrch 31, 

2022and afinalreportincQrporating.available serologyresultsnolaterthan 

septembet30,2022. 

2. Merck wm su!Jmitthe completevh:a1sheddingtestdtsandfu1fgenome 

SARs~CoV-2 nnc.teotide sequencingresultsfromihefuU randomized 

population:in si:udy MK-4482~()().2 ~art 2. Viral sequ.encins analysessh◊t:i.14 

include allBaseline andEnd~of•Treatinent (DaySJsamples with sufficient 

RNA levels for analysis1 as well as allPost-Tteatnrentsamples with viral 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6607 


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Page 8 Merck Sharp & Dohme Corp. 

RNA levels 2'.100,000 copies/mL. Cell culture infectivity assessments should 

be conducted for any clinical specimens in which amino acid changes were 

detected in the SARS-Co V-2 spike protein. Submissions should include 

summary report( s) and associated datasets (including analysis-ready datasets 

and raw fastq NGS data). A separate summary should be provided describing 

the results of the viral shedding and sequencing analyses specifically from 

immunocompromised patients. Merck will submit a preliminary report and 

associated datasets for the viral shedding and Baseline/Day 5 sequencing 

analyses no later than March 31, 2022,and a final report and datasets 

including the remaining analyses no later than June 30,2022. 

3. Merck will evaluate the cell culture antiviral activity ofmolnupiravir against 

an authentic SARS-Co V-2 isolate representative of the Omicron variant. 

Merck must submit a study report no later than February 28, 2022. 

4. Merck will conduct a pharmacokinetic (PK) study in wild type Fisher 344 

rats to establish if NHC or NHC-TP is detected in testes. Ib.e study should 

include plasma exposure levels that meet/exceed the human exposure for 

NHC. Merck will submitthe results of the PK study no later than March 31, 

2022. 

o If the results of the PK study demonstrate NHC or NHC-TP 

distribution to testes, Merck will also conduct a male germ cell 

mutation assay in the Big Blue rat model. Merck must submit a 

protocol for the Big Blue rat assay no later than 30 days after the PK 

results are submitted to FDA, or by April 30, 2022. Results from the 

Big Blue rat assay will be submitted no later than July 31, 2023. 

0. Merck must maintain a pregnancy surveillance program to collect information through 

telephone and online repo1ting of pregnancies and collect outcomes for individuals who are 

exposed to molnupiravirduring pregnancy. Merck must submit to the Agency reports 

detailing any available exposure information and outcome(s) data on a monthly basis 

unless othenvise notified by FDA 

P. Merck and authorized distributor(s) will make available to FDA upon request any records 

maintained in conne<.1:ion with this EUA. 

Healthcare Facilities to Whom Molnupiravir Is Distributed and Healthcare Providers Administering 

Molnupiravir 

Q. Healthcare facilities and healthcare providers will ensure that they are aware of the Letter 

of Authorization, and the tem1s herein. Healthcare providers must provide and document 

that a copy of the authorized Fact Sheet for Patients and Caregivers has been provided, 

either through electronic means or hardcopy, to the patient or caregiver prior to prescribing 

molnupiravir. 

R. Healthcare providers must infom1 patients or caregivers of the information detailed in the 

sectionM andatory Requirements for Administration ofM olnupiravir Under Emergency 

Use Authorization in the Fact Sheet for Healthcare Providers. 
6608 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 


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P~e 9 -MerckSharp & Dohme Col:}). 

S:. MoJnupiravinnayonly-beprescribedto a pre.gnantindividualafter the prescribing 

•fidlthcate.prov:idet'has•completed·fhemandatoeyrequfrements·<>ripatie:ntass.es!lfflent, 

patierttcottn.selirtg, artd doomnentation a!/ desttibedinthe FactSheetfor Healthcare · 

·Pro-vi<l.ers. SeeMani,fatotJtRequirerrurntsfQrA.drnin:istraJidn. of}yf;olnuwravir U.n.d.et 

-Emergency UseAuthorizati'oninthe FactSheet.forHealthcareProviders,. 

T .. Healtb~pr1wl.dersntustinforrn afid-doctmtentthatpregnant individualswho:are •::=~~=~~!8;!~1::::;~a;a:::~:::i:~J:i!ai::toparticipateinthepregnancy-surveillanceprogramandallowstheprescribinghealthcare 

•providerto disclosepatientspecificinformationtoMerck,theprescribinghelilthcare.-

pro.videtrnust provide the pa1ient's ~ and.contact infonnatfon.to Merclc at 1-877-888-

4'.Z~J Qrpte8,1Wtcytepotfing:tll$d.CQQL 

U: Healthcare:faciliti1,s an.dhealthcareproyilersieceivingmohtupiqwirwill trackall 

:medication errors and serious adverse. e.ven1s thatareconsidered to bepoterrtially 

-attributable tomohiupiraviruse•andn.ru$treportthesetoFDAin accordance with the Fact --=~;J~::~::~:=l~~=t==~:~~t:rm ;!S()Q.·(h~lth professional} byfax(l~80!FFDA:.;Ol7&}(these fonns c-an·be,.found vialinkabove} Call 1• 

80~FDA-J088forquestioos.-SUbmittedrq,orts.muststate,. "MoJnupiraviruse.fotCOVID- · 19tirtdetEmergency OseAuihorizatron"•atthe beginning of the question··•oescnbe Event'' 

for further anlilysi's;.Ac.Opy of the c001pletedFPAFotm3SOOmustlilso be provided to 

Merel<: perth.e. itlsnucitiOllS il:tth.e atd;Jlorizeil J.$e ling, · · 

v: Heait:hcitreJ'acffities an,.fl:teatfhca:teptovKierswU1 erisW'e fh•at appropriate stotiige:is 

maintainedtillfilthe productisadministe:redci:lnsi'$teirtwiththetertnii0 ofthislettetand1he 

authorizedlabeling. 

W'. :r:!1!t:=::a°l~~~~t:c:::::£:::t!:ot~r:~!e 

lot n.umbel!I; quantity, rec:eivingsi~ r!aleeipt date), productst0rase, andmaintaitrpa1ient ·-

in:formati.011(e:g,,patien.tl:i~1;,i~, d.i~ase manifestatio~ n.unwet of d.osesadJ:μiniitered 

p:erpati~ otberdrugs administered}-

X: ltealthcarefacitl.iies wttt ensure.iha1:anyrec0rcJgassoclated·wltinitlsEDAaremattitaiii:ed 

-u11tiln.otified J;y:Merckand/oi:FDA Sucltr:ecorcfu.will·t,em-ade•avaihibleto:Merck, 'flliS, 

.an.d FPAfor,:i.n.specliOJ1uponre.quest 

·y; •Healthcare.facilities afidproviderswillr1,POrltherapeuticsinformationand:titilizatfond'ata_ 

as directedJ-,:yHHS. 
Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 6609 


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Page 10 - MerckSharp & Dohme Corp. 

Conditions Relatedt-0 Printed Matter; Advertising, and Promotion 

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

molnupiravitunderthis authorization shall be consistent with the authorized labeling, as 

well as the terms set forth in this EDA, and meet the requirements set forth in Section 

502(a)and(n)ofthe Act,as applicable, andFDAimplementingregulations. References to 

"approved labeling", "pennitted labeling" or similar terms in these. requirements shall be 

understood to referto the authorized labeling forthe use of molrtupiravit under this 

authorization Inaddi:t:ion, such materials shall: 

• Betailotedtotheintended audience, 

• Not take the form.of reminder advertisements, as thatterm is described in 21 

CFR202.l(e)(2Xi),2J CFR200.200and21 CFR20l.IOO(f} 

• Presentthe same risk information relating to the major side effects and 

contraindications concurrently in the audio and visual parts of the presenta1ion 

for advertising and promotional materials in. audio-visual fonnat 

• 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 FormFDA-2253 atthetiine of initial 

dissemination or first use. 

If the Agency notifies Merck that any descriptive printedm:atter, advertising or promotional 

materials do not meet the terms set forth in conditions Z through BB ofthis EDA, Merck 

mustcease distribution of such descriptive printed matter, advertising, orpromotional 

materials in accordance with the Agency's notification. Furthermore, as part of its 

notification, the Agency may also require Merck to issue. corrective communication(s) 

AA No descriptive printed matter, advertising, or promotional materialsrela1ingto the 

use of mohrupiravitunderthis authorization may represent or suggestthatmolnupiravir is 

safe or effective when used for the treatment of COVID-19. 

BB. All descriptive printed matter, advertising, andpromotional material, relatingtothe 

use.of mohrupiravirunder.this authorizationclearly and conspicuously shall state that 

• Molnupitavit has not been approved, but bas been authorized for emergency 

use by FDA under an EU A,forthe trea1ment of mild-to-moderate COVH)-19 

in adults who are at high-risk for progression to severe COVID-19, in.eluding 

hospitaliza1ioo or death, and for whom alternative CO\711). 19treafment options 

authorized by FDA are.not11ccessible or clinically appropriate; and 

• The emergencyuseofmolnupitavirisoruy authorizedforthe dura1ion of the 

declaration that circums1ances exist justifying the authorization of the 

emergencyuse of dru~ and biological products duringthe COVID-19 

pandemicunderSeciion564(b)(l)oftheAct, 21 U.S.C. §360bbb-3(bX1), 

unless the declaration is tenninated or authorization revoked sooner. 
6610 Federal Register / Vol. 87, No. 24 / Friday, February 4, 2022 / Notices 

Dated: January 28, 2022. 

Lauren K. Roth, 

Associate Commissioner for Policy. 

[FR Doc. 2022–02359 Filed 2–3–22; 8:45 am] 

BILLING CODE 4164–01–C 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Health Resources and Services 

Administration 

Agency Information Collection 

Activities: Submission to OMB for 

Review and Approval; Public Comment 

Request; The Stem Cell Therapeutic 

Outcomes Database, OMB No. 0915– 

0310—Extension 

AGENCY: Health Resources and Services 

Administration (HRSA), Department of 

Health and Human Services. 

ACTION: Notice. 

SUMMARY: In compliance with of the 

Paperwork Reduction Act of 1995, 

HRSA has submitted an Information 

Collection Request (ICR) to the Office of 

Management and Budget (OMB) for 

review and approval. Comments 

submitted during the first public review 

of this ICR will be provided to OMB. 

OMB will accept further comments from 

the public during the review and 

approval period. OMB may act on 

HRSA’s ICR only after the 30 day 

comment period for this Notice has 

closed. 

DATES: Comments on this ICR should be 

received no later than March 7, 2022. 

ADDRESSES: Written comments and 

recommendations for the proposed 

information collection should be sent 

within 30 days of publication of this 

notice to www.reginfo.gov/public/do/ 

PRAMain. Find this particular 

information collection by selecting 

‘‘Currently under Review—Open for 

Public Comments’’ or by using the 

search function. 

FOR FURTHER INFORMATION CONTACT: To 

request a copy of the clearance requests 

submitted to OMB for review, email 

Samantha Miller, the acting HRSA 

Information Collection Clearance Officer 

at paperwork@hrsa.gov or call (301) 

443–9094. 

SUPPLEMENTARY INFORMATION: 

Information Collection Request Title: 

The Stem Cell Therapeutic Outcomes 

Database OMB No. 0915–0310— 

Extension. 

Abstract: Given the rapid evolution of 

COVID–19 and its impact on those with 

compromised immune systems, it is 

imperative for the transplant 

community to continue collecting 

COVID–19 related data. Having access 

to COVID–19 vaccination status on 

blood stem cell recipients and 

understanding immune responses will 

assist with making informed decisions 

regarding direct clinical care. This will 

also inform critical policy decisions. 

The Stem Cell Therapeutic and 

Research Act of 2005, Public Law (Pub. 

L.) 109–129, as amended, provides for 

the collection and maintenance of 

human blood stem cells for the 

treatment of patients and research. It 

also maintains a scientific database of 

information relating to patients who 

have been recipients of a stem cell 

therapeutics product (e.g., bone marrow, 

cord blood, or other such product) from 

a donor. 

Given the rapid evolution of the 

COVID–19 public health emergency and 

its impact on immunocompromised 

patients, availability of new vaccines, 

and continual changes in vaccination 

recommendations, HRSA wants to 

leverage the required data collection 

platform of the Stem Cell Therapeutic 

Outcomes Database to obtain vaccine 

information for all US allogeneic 

hematopoietic stem cell transplant 

recipients. 

A 60-day notice published in the 

Federal Register, 86 FR 67478 

(November 26, 2021). There were no 

public comments. 

Need and Proposed Use of the 

Information: To collect COVID–19 

vaccine data, HRSA is requesting an 

extension of OMB’s approval of both the 

Pre-Transplant Essential Data (Pre-TED) 

Form 2400 and Post-Transplant 

Essential Data (Post-TED) Form 2450. 

Collecting these data will help 

clinicians and policymakers to 

understand the landscape of vaccination 

among immunocompromised patients 

before and after a blood stem cell 

transplant. 

This information will be used to 

analyze outcomes based on vaccine 

manufacturer/type, doses received 

(including potential boosters), timing, 

and inform future vaccination strategies. 

Information currently collected 

regarding COVID–19 infections has 

already been used in research studies. 

Data collected prior to a patient 

receiving a blood stem cell transplant 

will be used to characterize frequencies 

of vaccination, and the level of 

protection afforded during and after 

transplant based on the incidence of 

COVID infection. Post-transplant, this 

information can be used to assess 

vaccination rates and timing in blood 

stem cell recipients, characterize 

emerging vaccination strategies (which 

may include ‘‘boosters’’), describe 

possible short and long-term side effects 


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'Ibis Et)A will:be~ff ec:tive Ufitilthe 1.lec}$.tation, that circu~es existjustifyingthe 

authorization•ofthe emergencyuseofd~andbiolo:gicalproduclsduringtheCOV:IDsl9 

plWdemicmtemrinated undcetSectio:tt 564(b}(2) of the Act or the EU A is revoked under Stction 

564(g).oftheAa. 

Jacqueline A O'Shaμghnessy, J>li;D; 

i\c~gCnief ~ci¢ritist 

Food.and Drug.Administration