Federal Register / Vol. 86, No. 145 / Monday, August 2, 2021 / Rules and Regulations 41383 

2We last revised the expiration date for the 

Neurological Disorders body system listings when 

we updated the body system on July 1, 2016 (81 FR 

43038, 43052). 

3See the first sentence of appendix 1 to subpart 

P of part 404 of 20 CFR. 

Body system listings Current expiration date Extended expiration date 

Neurological Disorders (11.00 and 111.00) ............................ September 29, 2021 .............................. September 29, 2025. 

We continue to revise and update the 

listings on a regular basis, including 

those body systems not affected by this 

final rule.2 We intend to update the 

listings affected by this final rule as 

necessary based on medical advances as 

quickly as possible, but may not be able 

to publish final rules revising these 

listings by the current expiration date. 

Therefore, we are extending the 

expiration date listed above. 

Regulatory Procedures 

Justification for Final Rule 

We follow the Administrative 

Procedure Act (APA) rulemaking 

procedures specified in 5 U.S.C. 553 in 

promulgating regulations. Section 

702(a)(5) of the Social Security Act, 42 

U.S.C. 902(a)(5). Generally, the APA 

requires that an agency provides prior 

notice and opportunity for public 

comment before issuing a final 

regulation. The APA provides 

exceptions to the notice-and-comment 

requirements when an agency finds 

there is good cause for dispensing with 

such procedures because they are 

impracticable, unnecessary, or contrary 

to the public interest. 

We determined that good cause exists 

for dispensing with the notice and 

public comment procedures. 5 U.S.C. 

553(b)(B). This final rule only extends 

the date on which the Neurological 

Disorders body system listings will no 

longer be effective. It makes no 

substantive changes to our rules. Our 

current regulations 3 provide that we 

may extend, revise, or promulgate the 

body system listings again. Therefore, 

we determined that opportunity for 

prior comment is unnecessary, and we 

are issuing this regulation as a final rule. 

In addition, for the reasons cited 

above, we find good cause for 

dispensing with the 30-day delay in the 

effective date of this final rule. 5 U.S.C. 

553(d)(3). We are not making any 

substantive changes to the Neurological 

Disorders body system listing. Without 

an extension of the expiration date for 

this listing, we will not have the criteria 

we need to assess medical impairments 

in the body system at step three of the 

sequential evaluation processes. We 

therefore find it is unnecessary to delay 

the effective date of this final rule. 

Executive Order 12866, as 

Supplemented by Executive Order 

13563 

We consulted with the Office of 

Management and Budget (OMB) and 

determined that this final rule does not 

meet the requirements for a significant 

regulatory action under Executive Order 

12866, as supplemented by Executive 

Order 13563. Therefore, OMB did not 

review it. We also determined that this 

final rule meets the plain language 

requirement of Executive Order 12866. 

Regulatory Flexibility Act 

We certify that this final rule does not 

have a significant economic impact on 

a substantial number of small entities 

because it affects only individuals. 

Therefore, a regulatory flexibility 

analysis is not required under the 

Regulatory Flexibility Act, as amended. 

Paperwork Reduction Act 

These rules do not create any new or 

affect any existing collections and, 

therefore, do not require Office of 

Management and Budget approval 

under the Paperwork Reduction Act. 

(Catalog of Federal Domestic Assistance 

Program Nos. 96.001, Social Security— 

Disability Insurance; 96.002, Social 

Security—Retirement Insurance; 96.004, 

Social Security—Survivors Insurance; 

96.006, Supplemental Security Income) 

List of Subjects in 20 CFR Part 404 

Administrative practice and 

procedure, Blind, Disability benefits, 

Old-Age, Survivors and Disability 

Insurance, Reporting and recordkeeping 

requirements, Social Security. 

The Acting Commissioner of the 

Social Security Administration, Kilolo 

Kijakazi, having reviewed and approved 

this document, is delegating the 

authority to electronically sign this 

document to Faye I. Lipsky, who is the 

primary Federal Register Liaison for 

SSA, for purposes of publication in the 

Federal Register. 

Faye I. Lipsky, 

Federal Register Liaison, Office of Legislative 

and Congressional Affairs, Social Security 

Administration. 

For the reasons set out in the 

preamble, we are amending subpart P of 

part 404 of chapter III of title 20 of the 

Code of Federal Regulations as set forth 

below. 

PART 404—FEDERAL OLD-AGE, 

SURVIVORS AND DISABILITY 

INSURANCE (1950– ) 

Subpart P—[Amended] 

■ 1. The authority citation for subpart P 

of part 404 continues to read as follows: 

Authority: Secs. 202, 205(a)–(b) and (d)– 

(h), 216(i), 221(a) and (h)–(j), 222(c), 223, 

225, and 702(a)(5) of the Social Security Act 

(42 U.S.C. 402, 405(a)–(b) and (d)–(h), 416(i), 

421(a) and (h)–(j), 422(c), 423, 425, and 

902(a)(5)); sec. 211(b), Pub. L. 104–193, 110 

Stat. 2105, 2189; sec. 202, Pub. L. 108–203, 

118 Stat. 509 (42 U.S.C. 902 note). 

■ 2. Amend appendix 1 to subpart P of 

part 404 by revising item 12 of the 

introductory text before Part A to read 

as follows: 

Appendix 1 to Subpart P of Part 404— 

Listing of Impairments 

* * * * * 

12. Neurological Disorders (11.00 and 

111.00): September 29, 2025. 

* * * * * 

[FR Doc. 2021–16417 Filed 7–30–21; 8:45 am] 

BILLING CODE 4191–02–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

21 CFR Parts 201 and 801 

[Docket No. FDA–2015–N–2002] 

RIN 0910–AI47 

Regulations Regarding ‘‘Intended 

Uses’’ 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Final rule. 

SUMMARY: The Food and Drug 

Administration (FDA, the Agency, or 

we) is issuing a final rule to amend its 

medical product ‘‘intended use’’ 

regulations. This final rule amends 

FDA’s regulations describing the types 

of evidence relevant to determining 

whether a product is intended for use as 

a drug or device under the Federal 

Food, Drug, and Cosmetic Act (FD&C 

Act), the Public Health Service Act (PHS 

Act), and FDA’s implementing 

regulations, including whether a 

medical product that is approved, 

cleared, granted marketing 

authorization, or exempted from 


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41384 Federal Register / Vol. 86, No. 145 / Monday, August 2, 2021 / Rules and Regulations 

premarket notification is intended for a 

new use. This action also withdraws 

and replaces the portions of a final rule 

issued on January 9, 2017, that never 

became effective. 

DATES: This rule is effective September 

1, 2021. 

ADDRESSES: For access to the docket to 

read background documents or 

comments received, go to https://

www.regulations.gov and insert the 

docket number found in brackets in the 

heading of this final rule into the 

‘‘Search’’ box and follow the prompts, 

and/or go to the Dockets Management 

Staff, 5630 Fishers Lane, Rm. 1061, 

Rockville, MD 20852, 240–402–7500. 

FOR FURTHER INFORMATION CONTACT: 

Kelley Nduom, Center for Drug 

Evaluation and Research, Food and 

Drug Administration, 10903 New 

Hampshire Ave., Silver Spring, MD 

20993–0002, 301–796–5400, 

kelley.nduom@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

Table of Contents 

I. Executive Summary 

A. Purpose of the Final Rule 

B. Summary of the Major Provisions of the 

Final Rule 

C. Legal Authority 

D. Costs and Benefits 

II. Meaning of Certain Terms in This 

Preamble 

III. Background 

A. Introduction and History of This 

Rulemaking 

B. Summary of Comments to the Proposed 

Rule 

IV. Legal Authority 

V. Comments on the Proposed Rule and FDA 

Responses 

A. Introduction 

B. Comments and Responses Regarding 

Statutory and Regulatory Authority 

C. Comments and Responses Regarding the 

Design or Composition of an Article 

D. Comments and Responses Regarding the 

First Amendment 

E. Comments and Responses Regarding the 

Fifth Amendment 

F. Comments and Responses Regarding 

Definitions 

G. Comments and Responses Regarding 

‘‘Safe Harbors’’ 

H. Comments and Responses Regarding 

Examples 

I. Comments on Codified Text and FDA 

Responses 

J. Comments Recommending That FDA 

Expand the Scope of This Rulemaking 

VI. Effective Date 

VII. Economic Analysis of Impacts 

A. Introduction and Summary 

B. Final Economic Analysis of Impacts 

C. Final Small Entity Analysis 

VIII. Analysis of Environmental Impact 

IX. Paperwork Reduction Act of 1995 

X. Federalism 

XI. Consultation and Coordination With 

Indian Tribal Governments 

XII. References 

I. Executive Summary 

A. Purpose of the Final Rule 

FDA is taking this action to amend its 

existing regulations (§§ 201.128 and 

801.4 (21 CFR 201.128 and 801.4)) 

describing the types of evidence 

relevant to determining a product’s 

intended uses under the FD&C Act, the 

PHS Act, and FDA’s implementing 

regulations. The amended regulations 

better reflect the Agency’s current 

practices in evaluating whether a 

product is intended for use as a drug or 

device, including whether a medical 

product that is approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification is 

intended for a new use. This action 

withdraws the portions of the final rule 

issued on January 9, 2017 (82 FR 2193), 

that never became effective, and it 

finalizes amendments to the intended 

use regulations for medical products 

that provide more clarity and direction 

to regulated industry and other 

stakeholders regarding the types of 

evidence relevant to determining a 

product’s intended uses. 

B. Summary of the Major Provisions of 

the Final Rule 

FDA is finalizing amendments to its 

intended use regulations for medical 

products (§§ 201.128 and 801.4) to 

better reflect the Agency’s current 

practices in evaluating whether a 

product is intended for use as a drug or 

device, including whether a medical 

product that is approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification is 

intended for a new use. 

Several comments on the proposed 

rule raised legal concerns. Some 

commenters argued that FDA should 

construe its statutory and regulatory 

authorities more narrowly, and some 

asserted that the proposed rule violates 

the First and Fifth Amendments. These 

and similar arguments have been raised 

in comments received during earlier 

stages of this rulemaking as well as in 

other rulemaking proceedings, petitions, 

and litigation involving intended use 

issues. A number of other comments 

raised questions about the rule’s 

applicability to certain medical devices, 

such as devices that are exempt from 

premarket notification (510(k)) 

requirements. These comments also 

criticized the inclusion of language in 

the regulation clarifying that the design 

or composition of an article may be 

relevant to determining its intended use. 

The final rule remains largely 

unchanged from the proposed rule. In 

response to comments received, we 

have modified the codified language of 

the intended use regulation for medical 

devices to clarify its applicability to 

devices that are approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification. 

That is the only change from the 

codified language in the proposed rule. 

C. Legal Authority 

Among the provisions that provide 

authority for this final rule are sections 

201, 403(r), 503(g), and 701(a) of the 

FD&C Act (21 U.S.C. 321, 343(r), 353(g), 

371(a)); section 5(b)(3) of the Orphan 

Drug Act (21 U.S.C. 360ee(b)(3)); and 

sections 215, 301, 351(i) and (j), and 361 

of the PHS Act (42 U.S.C. 216, 241, 

262(i) and (j), and 264). 

D. Costs and Benefits 

The benefit of this final rule is the 

added clarity and certainty for firms and 

stakeholders regarding the evidence 

relevant to establishing whether a 

product is intended for use as a drug or 

device, including whether a medical 

product that is approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification is 

intended for a new use. We do not have 

evidence that the final rule will impose 

costs on currently marketed products. 

II. Meaning of Certain Terms in This 

Preamble 

As used in this rulemaking, the 

following terms have the meanings 

noted below. 

Term Meaning 

A medical product that is approved, cleared, granted marketing authorization, or exempted from premarket notification.This term refers to a medical product that may be legally introduced 

into interstate commerce for at least one use under the FD&C Act or 

the PHS Act as a result of having satisfied applicable premarket statutory and regulatory requirements. 


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Term Meaning 

A medical use that is approved, cleared, granted marketing authorization, or exempted from premarket notification.This term refers to an intended use included in the required labeling for 

an FDA-approved medical product, an intended use included in the 

indications for use statement for a device cleared or granted marketing authorization by FDA, or an intended use of a device that falls 

within an exemption from premarket notification. 

Firms ......................................................................................................... This term refers to manufacturers, packers, and distributors of FDAregulated products and all their representatives, including both individuals and corporate entities. 

Healthcare providers ................................................................................ This term refers to individuals such as physicians, veterinarians, dentists, physician assistants, nurse practitioners, pharmacists, or registered nurses who are licensed or otherwise authorized by the State 

to prescribe, order, administer, or use medical products in a professional capacity. 

Medical products ...................................................................................... This term refers to drugs and devices, including human biological products. 

Products unapproved for any medical use .............................................. This term refers to medical products that are not approved, cleared, 

granted marketing authorization, or exempted from premarket notification (as that phrase is described above) by FDA for any medical 

use, and which must be approved, cleared, granted marketing authorization, or exempted from premarket notification to be legally 

marketed for such use. This term also includes products that are 

marketed for non-medical uses, such as dietary supplements, conventional foods, and cosmetics. 

Unapproved use of a medical product that is approved, cleared, granted marketing authorization, or exempted from premarket notification.This term refers to an intended use that is not included in the required 

labeling of an FDA-approved medical product, an intended use that 

is not included in the indications for use statement for a device 

cleared or granted marketing authorization by FDA, or an intended 

use of a device that does not fall within an exemption from premarket notification. 

III. Background 

A. Introduction and History of This 

Rulemaking 

The Agency issued a proposed rule in 

2015 and a final rule in 2017 revising 

the language of its medical product 

intended use regulations, with the 

intent to conform them to the Agency’s 

current practice in applying the 

regulations (see final rule, ‘‘Clarification 

of When Products Made or Derived 

From Tobacco Are Regulated as Drugs, 

Devices, or Combination Products; 

Amendments to Regulations Regarding 

‘Intended Uses’’’ (82 FR 2193, January 9, 

2017)). These amendments did not 

reflect a change in FDA’s approach 

regarding types of evidence of intended 

use for drugs and devices. However, 

after receiving a petition that requested 

the Agency reconsider these 

amendments, FDA delayed the effective 

date of the 2017 final rule and reopened 

the docket to invite public comment. A 

number of comments submitted during 

the reopening raised questions and, on 

March 16, 2018 (83 FR 11639), FDA 

delayed the effective date of the 

intended use amendments until further 

notice to allow further consideration of 

the substantive issues raised in the 

comments received. After considering 

the issues raised in the petition and 

comments submitted during the 

reopening, FDA issued a notice of 

proposed rulemaking in September 2020 

(85 FR 59718, September 23, 2020, the 

‘‘NPRM’’) to withdraw the portions of 

the final rule issued on January 9, 2017, 

that never became effective and to 

propose a new rule to provide more 

clarity regarding the types of evidence 

that are relevant in determining a 

product’s intended uses. 

B. Summary of Comments to the 

Proposed Rule 

Approximately 15 comments on the 

proposed rule were submitted to the 

docket. These comments were 

submitted by various industry trade 

organizations, consumer advocacy 

groups, and individuals. Several 

comments raised legal concerns with 

the proposed rule, including arguments 

to the effect that the rule violates the 

First and Fifth Amendments. Other 

comments raised questions and 

concerns about the rule’s applicability 

to certain medical devices, such as 

devices that are 510(k)-exempt. These 

comments also generally objected to the 

inclusion of language in the regulation 

clarifying that the design or composition 

of an article may be relevant to 

determining its intended use. 

IV. Legal Authority 

Among the statutory provisions that 

provide authority for this final rule are 

sections 201, 403(r), 503(g), and 701(a) 

of the FD&C Act, section 5(b)(3) of the 

Orphan Drug Act, and section 351(i) of 

the PHS Act. Section 201 of the FD&C 

Act defines ‘‘drug’’ (subsection (g)(1)), 

‘‘device’’ (subsection (h)), ‘‘food’’ 

(subsection (f)), ‘‘dietary supplement’’ 

(subsection (ff)), ‘‘cosmetic’’ (subsection 

(i)), and ‘‘tobacco product’’ (subsection 

(rr)(1)); section 5(b)(3) of the Orphan 

Drug Act defines ‘‘medical food’’; and 

section 503(g)(1) of the FD&C Act 

provides that combination products are 

those ‘‘that constitute a combination of 

a drug, device, or biological product.’’ 

Section 351(i) of the PHS Act defines 

‘‘biological products’’, and section 351(j) 

of the PHS Act provides that the 

requirements of the FD&C Act apply to 

biological products. Section 403(r) of 

the FD&C Act establishes the 

requirements under which certain 

labeling claims about uses of 

conventional foods and dietary 

supplements to reduce the risk of a 

disease or affect the structure or 

function of the human body are not 

evidence of intended use as a drug. 

Under section 701(a) of the FD&C Act, 

FDA has authority to issue regulations 

for the efficient enforcement of the 

FD&C Act. FDA regulates the 

manufacture, sale, and distribution of 

drugs, devices, combination products, 

tobacco products, foods (including 

dietary supplements), and cosmetics 

under the authority of the FD&C Act. 


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V. Comments on the Proposed Rule and 

FDA Responses 

A. Introduction 

We received approximately 

15 comment submissions on the 

proposed rule by the close of the 

comment period, each containing one or 

more comments on one or more issues. 

We describe and respond to the 

comments in sections 

B through J of this section. We have 

numbered each comment to help 

distinguish between different 

comments. We have grouped similar 

comments together under the same 

number, and, in some cases, we have 

separated different issues discussed in 

the same comment and designated them 

as distinct comments for purposes of 

our responses. The number assigned to 

each comment or comment topic is 

purely for organizational purposes and 

does not signify the comment’s value or 

importance or the order in which 

comments were received. 

In addition to the comments specific 

to this rulemaking that we address in 

the following paragraphs, we received 

several general comments expressing 

support for or opposition to the rule. 

These comments express broad policy 

views and do not address specific points 

related to this rulemaking. Therefore, 

these general comments do not require 

a response. To the extent that comments 

expressing opposition to the rule 

requested that we refrain from finalizing 

the rule, we decline to do so. In general, 

comments outside the scope of this 

rulemaking have not been addressed 

here. Summaries of the remaining 

comments, as well as FDA’s responses, 

are included in this document. 

B. Comments and Responses Regarding 

Statutory and Regulatory Authority 

(Comment 1) One comment asserted 

that under the relevant statutes, 

legislative history, and case law, 

evidence of intended use is limited to 

promotional claims that have been made 

in the marketplace. The comment 

argued that the NPRM was wrong in 

stating that evidence of intended use 

can be derived from ‘‘any relevant 

source,’’ including ‘‘circumstances 

surrounding distribution.’’ Other 

comments also encouraged the Agency 

to focus primarily or only on 

promotional claims. 

(Response) We disagree. Nothing in 

the statute requires the narrow scope 

that the comment suggested. Although 

the first comment mentioned above 

loosely refers to the statutory and 

regulatory regime as support for its 

preferred interpretation, it does not cite 

any statutory language that dictates an 

exclusively claims-based approach to 

intended use. As four justices of the 

Supreme Court recognized in rejecting 

the argument that the statute limits 

evidence of intended use to promotional 

claims: ‘‘The [FD&C Act] . . . does not 

use the word ‘claimed’; it uses the word 

‘intended’ ’’ (FDA v. Brown & 

Williamson Tobacco Corp., 529 U.S. 

120, 170 (2000) (dissenting opinion) (the 

majority declined to resolve the issue, 

id. at 131–32)). The fact that intended 

use can be established through 

promotional claims does not preclude 

the possibility that other evidence may 

be relevant as well. 

Nor does the comment cite any 

legislative history that supports an 

exclusively claims-based approach to 

intended use. Indeed, the legislative 

history supports reliance on evidence of 

use by healthcare practitioners and 

consumers as relevant to intended use. 

The House Report on the Medical 

Device Amendments of 1976 states that 

‘‘[t]he Secretary may consider . . . use 

of a product in determining whether or 

not it is a device’’ (see H.R. Rep. 853, 

94th Cong., 2d Sess. 14 (1976), reprinted 

in An Analytical Legislative History of 

the Medical Device Amendments of 

1976, Appendix III (Daniel F. O’Keefe, 

Jr. and Robert A. Spiegel, eds. 1976)). 

Similarly, the legislative history of the 

1938 Act states expressly that ‘‘the use 

to which the product is to be put will 

determine the category into which it 

will fall’’ (see S. Rep. No. 361, 74th 

Cong., 1st Sess. 4 (1935), reprinted in 

3 Legislative History 660, 663). 

Nor does the language of the existing 

regulation support the commenter’s 

position. ‘‘[N]owhere does the 

regulation state that’’ evidence of 

intended use is limited to statements or 

claims ‘‘published to the marketplace’’ 

(see United States v. Vascular Solutions, 

Inc., 181 F. Supp. 3d 342, 347 (W.D. 

Tex. 2016)). Indeed, the existing 

regulations specifically state that 

evidence of intended use includes 

‘‘circumstances surrounding the 

distribution of the article’’ and 

‘‘circumstances that the article . . . is 

offered or used for a purpose for which 

it is neither labeled or advertised.’’ This 

language was included when the 

regulation was first codified in 1952 (see 

17 FR 6818, 6820 (1952) (Ref. 1)). 

Furthermore, the case law does not 

resolve the matter in favor of the 

position advanced by the commenter. 

Courts have repeatedly held that 

intended use is determined by looking 

to any relevant evidence, including 

statements and circumstances 

surrounding the manufacture and 

distribution of a medical product (see, 

e.g., United States v. Article of 216 

Cartoned Bottles, ‘‘Sudden Change,’’ 

409 F.2d 734, 739 (2d Cir. 1969) (‘‘It is 

well settled that the intended use of a 

product may be determined from its 

label, accompanying labeling, 

promotional material, advertising and 

any other relevant source.’’) (citations 

omitted); V.E. Irons, Inc. v. United 

States, 244 F.2d 34, 44 (1st Cir. 1957) 

(observing that a court is ‘‘free to look 

to all relevant sources in order to 

ascertain what is the ‘intended use’ of 

a drug’’)). As explained by one court: 

‘‘Whether a product’s intended use 

makes it a device depends, in part, on 

the manufacturer’s objective intent in 

promoting and selling the product. All 

of the circumstances surrounding the 

promotion and sale of the product 

constitute the ‘intent’. It is not enough 

for the manufacturer to merely say that 

he or she did not ‘intend’ to sell a 

particular product as a device. Rather, 

the actual circumstances surrounding 

the product’s sale, such as the identi[t]y 

of actual customers and their use of the 

product and labeling claims, determine 

the ’intended’ use of the product as a 

device under the Act’’ (United States v. 

789 Cases, More or Less, of Latex 

Surgeons’ Gloves, 799 F. Supp. 1275, 

1285 (D. Puerto Rico 1992) (internal 

citations omitted)). 

Courts have rejected the commenter’s 

proposition that evidence of intended 

use is limited to a manufacturer’s public 

claims concerning a device or drug (see 

Nat’l Nutritional Foods Ass’n v. 

Matthews, 557 F.2d 325, 334 (2d Cir. 

1977) (‘‘In determining whether an 

article is a ‘drug’ because of an intended 

therapeutic use, the FDA is not bound 

by the manufacturer’s subjective claims 

of intent but can find actual therapeutic 

intent on the basis of objective evidence. 

Such intent also may be derived or 

inferred from labeling, promotional 

material, advertising, and any other 

relevant source.’’) (internal citation and 

quotations omitted); United States v. 

Travia, 180 F. Supp. 2d 115, 119 (D.D.C. 

2001) (‘‘Labeling is not exclusive 

evidence of the sellers’ intent. Rather, 

. . . ‘it is well established that the 

intended use of a product, within the 

meaning of the [FD&C Act], is 

determined from its label, 

accompanying labeling, promotional 

claims, advertising, and any other 

relevant source’ . . . even consumer 

intent could be relevant, so long as it 

was pertinent to demonstrating the 

seller’s intent . . . [I]f the government’s 

allegations are true, the sellers did not 

need to label or advertise their product, 

as the environment provided the 

necessary information between buyer 

and seller. In this context, therefore, the 


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fact that there was no labeling may 

actually bolster the evidence of an 

intent to sell a mind-altering article 

without a prescription-that is, a 

misbranded drug.’’) (citations omitted); 

United States v. Vascular Solutions, 

Inc., 181 F. Supp. 3d at 347 (the 

position that evidence of objective 

intent is limited to statements 

‘‘published to the marketplace’’ is 

‘‘absurd[]’’)); see also United States v. 

Storage Spaces Designated Nos. 8 and 

49, 777 F.2d 1363, 1366 n.5 (9th Cir. 

1985) (concluding that products 

innocuously labeled as ‘‘incense’’ and 

‘‘not for drug use’’ were in fact drugs 

where the ‘‘overall circumstances’’ 

demonstrated vendor’s intent that 

products be used as cocaine substitutes); 

United States v. An Article of Device 

Toftness Radiation Detector, 731 F.2d 

1253, 1257 (7th Cir. 1984) (intended use 

established in part by witness testimony 

that device had been used to treat 

patients, together with other evidence 

regarding a training program and 

financial arrangements offered by the 

defendant); United States v. 

Undetermined Quantities of an Article 

of Drug Labeled as ‘‘Exachol’’, 716 F. 

Supp. 787, 791 (S.D.N.Y. 1989) 

(explaining that ‘‘FDA is not bound by 

the vendor’s subjective claims of intent’’ 

and that ‘‘[a]n article intended to be 

used as a drug will be regulated as a 

drug . . . even if the product[’]s 

labelling states that it is not a drug’’); 

United States v. 22 Rectangular or 

Cylindrical Finished Devices, 714 F. 

Supp. 1159, 1165 (D. Utah 1989) (‘‘The 

objective intent referred to in the 

regulation may be shown not only by a 

product’s labeling claims, advertising or 

written statements relating to the 

circumstances of a product’s 

distribution, . . . but also by a product’s 

actual use. See H.R. Rep. No. 853, 94th 

Cong., 14 (1976). . . . There also can be 

no dispute that the sterilizer, in its 

actual use, plays an integral role in the 

surgical treatment of patients.’’); Hanson 

v. United States, 417 F. Supp. 30, 35 (D. 

Minn. 1976) (finding plaintiffs’ beliefs 

that many people will die if they are 

deprived of the tablets and vials at issue 

relevant to establishing intended use), 

aff’d, 540 F.2d 947 (8th Cir. 1976); 

United States v. Device Labeled 

‘‘Cameron Spitler Amblyo-Syntonizer’’, 

261 F. Supp. 243, 245 (D. Neb. 1966) 

(‘‘While claimant contends that the 

machines have not been represented as 

a cure for any particular eye 

malfunction, he admits the use of them 

in the treatment of certain eye maladies. 

Clearly, the seized machines are each a 

device within the meaning of 

§ 321(h).’’)). 

Although one comment cited to 

several cases that relied only on 

promotional claims as evidence of 

intended use, only a very few, if any, 

cases have actually excluded non-claims 

evidence from consideration as 

evidence of intended use on the ground 

that the evidence was not promotional. 

The presence of claims may be 

particularly significant in determining 

intended use where a product, such as 

honey, does not have a therapeutic 

benefit or physiological effect (see, e.g., 

United States v. An Article . . . ‘‘U.S. 

Fancy Pure Honey’’, 218 F. Supp. 208, 

211 (E.D. Mich. 1963) (claim that honey 

is a panacea for various diseases and 

ailments established the intended use as 

a drug), aff’d, 344 F.2d 288 (6th Cir. 

1965). But the converse is not true—the 

absence of claims on a product that does 

have a physiological effect will not 

automatically render the product 

immune from FDA jurisdiction (see, 

e.g., United States v. Carlson, 810 F.3d 

544 (8th Cir. 2016) (synthetic drugs, 

such as synthetic marijuana, labeled as 

incense, herbal incense, herbal 

potpourri, bath salts, etc., and that also 

bore the statement ‘‘not for human 

consumption,’’ found to be subject to 

FDA’s jurisdiction as drugs)). 

As FDA has explained, limiting 

evidence of intended use to only 

promotional claims would allow 

manufacturers to circumvent FDA 

regulation by masking their true intent, 

either by simply omitting explicit 

promotional claims or by making claims 

that are not true (for example, ‘‘not for 

human use’’). See 82 FR 14319 at 14321 

through 14322 (March 20, 2017); 82 FR 

2193 at 2196 (January 9, 2017); 80 FR 

57756 at 57757 (September 25, 2015). 

As courts have recognized, ‘‘[s]elfserving labels cannot be allowed to 

mask the vendor’s true intent as 

indicated by the overall circumstances.’’ 

United States v. Storage Spaces 

Designated Nos. 8 and 49, 777 F.2d 

1363, 1366 n.5 (9th Cir. 1985)). This is 

an issue that comes up frequently with 

respect to products in domestic 

commerce as well as imported goods 

and has resulted in FDA-issued warning 

letters, import refusals, civil injunction 

actions, and criminal prosecutions. FDA 

believes it is worth repeating the 

following previously cited examples, 

see 82 FR 14319 at 14321 through 14322 

(March 20, 2017), of the types of 

situations in which evidence of 

intended use has been derived from 

sources other than explicit promotional 

claims: 

• Persons distributing substances that 

are known to be used recreationally to 

achieve a mind-altering effect, such as 

dextromethorphan (the active ingredient 

in some cough suppressants) and 

nitrous oxide (which is a prescription 

drug) (see, e.g., United States v. 

Johnson, 471 F.3d 764, 765 (7th Cir. 

2006); United States v. Schraud, 2007 

U.S. Dist. LEXIS 89231, 3–6 (E.D. Mo. 

December 4, 2007); United States v. 

Travia, 180 F. Supp. 2d 115, 119 (D.D.C. 

2001); United States v. LA Rush, 

2:13–cr–00249, First Superseding 

Information (C.D. Cal. April 3, 2014)). 

• Persons distributing synthetic 

drugs, such as synthetic marijuana, 

labeled as incense, potpourri, bath salts, 

and/or bearing the statement ‘‘not for 

human consumption’’ (see, e.g., United 

States v. Carlson, 810 F.3d 544 (8th Cir. 

2016); United States v. Carlson, 12–cr– 

00305–DSD–LIB, Amended Superseding 

Indictment (D. Minn. Sept. 11, 2013) 

and Court’s Instructions to the Jury, (D. 

Minn. October 8, 2013); United States v. 

Bowen, 14–cr00169–PAB, Indictment 

(D. Colo. May 5, 2014) and Rule 

11(c)(1)(A) and (B) Plea Agreement and 

Statement of Facts Relevant to 

Sentencing (D. Colo. January 29, 2015). 

• Persons distributing imitation drugs 

claimed to be incense or dietary 

supplements, such as imitation cocaine 

or imitation Ecstasy (see, e.g., United 

States v. Storage Spaces Designated 

Nos. ‘‘8’’ & ‘‘49’’, 777 F.2d 1363, 1366 

(9th Cir. 1985); United States v. 

Undetermined Quantities of . . . Street 

Drug Alternatives, 145 F. Supp. 2d 692 

(D. Md. 2001)). 

• Persons distributing products 

containing the active ingredients in 

prescription drugs, such as VIAGRA, 

CIALIS, LEVITRA, or BOTOX, as less 

expensive alternatives to the approved 

products, with labeling that states that 

they are ‘‘all natural’’ or ‘‘herbal’’ 

supplements or ‘‘for research only’’ (see, 

e.g., United States v. Dessart, 823 F.3d 

395 (7th Cir. 2016); United States v. 

Zeyid, 1:14–cr–0197, First Superseding 

Indictment (N.D. Ga. June 24, 2014) (see 

also Ref. 2); United States v. Livdahl, 

459 F. Supp. 2d 1255, 1260 (S.D. Fla. 

2005)). 

Other instances where a person’s 

claims about the intended use of a 

product are belied by the person’s 

activities or non-promotional statements 

or by circumstantial evidence (see, e.g., 

United States v. An Article of Device 

Toftness Radiation Detector, 731 F.2d 

1253, 1257 (7th Cir. 1984); United States 

v. 789 Cases of Latex Surgeons’ Gloves, 

799 F. Supp. 1275, 1294–1295 (D.P.R. 

1992)). 

In these situations, the evidence 

relied on to establish intended use has 

included general knowledge of actual 

use by customers to achieve a mindaltering effect; the known effects of a 

product or substance; implied claims 


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1The comment erroneously asserts that FDA’s 

reliance on evidence other than promotional claims 

to assert jurisdiction over cigarettes in a 1996 final 

rule was ‘‘roundly rejected by the courts.’’ In fact, 

the Supreme Court’s majority opinion declined to 

address the issue, and the dissent endorsed FDA’s 

analysis (see FDA v. Brown & Williamson Tobacco 

Corp., 529 U.S. 120, 131–32 (2000); id. at 170 

(dissenting opinion). 

from using names that sound similar to 

the names of controlled substances; the 

circumstances surrounding the sale 

(e.g., a rock concert venue; receiving the 

product in bulk and repackaging into 

smaller plastic bags; the use of private 

email addresses; the absence of 

labeling); shipping orders, other 

correspondence, and memoranda 

relating to marketing and distribution; 

statements made in training sessions; 

and admissions. 

Evidence other than promotional 

claims has also been used to establish 

that products offered for import into the 

United States without labeling or other 

claims that identify them as a drug or 

device are in fact intended for use as a 

drug or device and are therefore subject 

to refusal if it appears that they fail to 

meet certain requirements for importing 

medical products (see 21 U.S.C. 

381(a)(3)). For example, the defendants 

in United States v. Zeyid, 1:14-cr-0197, 

First Superseding Indictment (N.D. Ga. 

June 24, 2014) (see Ref. 2), imported 

products containing active ingredients 

that were the same as those used in 

prescription drugs but that were labeled 

as ‘‘tea,’’ ‘‘coffee,’’ and ‘‘beauty 

products.’’ 

(Comment 2) One comment asserted 

that the position on intended use 

described by FDA in the NPRM was an 

‘‘alternative, novel interpretation [] with 

which FDA has flirted from time to time 

in the past.’’ 

(Response) We disagree. This is not 

the first time FDA has responded to 

arguments that its interpretation of the 

scope of evidence relevant to ‘‘intended 

use’’ is too broad—those arguments 

have been raised in comments in earlier 

stages of this and other rulemaking 

proceedings, petitions, and litigation 

involving intended use issues. Contrary 

to the comment’s assertion that the 

NPRM presented a novel interpretation 

of intended use, FDA has steadfastly 

maintained for decades that, in 

determining a product’s intended use, 

the Agency may look to any relevant 

source of evidence, including a variety 

of direct and circumstantial evidence. 

FDA’s position is reflected in the 

notices issued in this rulemaking over 

the past 5 years (see, e.g., 85 FR 59718 

at 59721 (September 23, 2020); 82 FR 

14319 at 14320 (March 20, 2017); 82 FR 

2193 at 2206 (January 9, 2017); 80 FR 

57756 at 57757 (September 25, 2015)), 

and has been noted in court decisions 

(see, e.g., Spectrum Pharma. v. Burwell, 

824 F.3d 1062, 1069 (D.C. Cir. 2016) 

(‘‘To be sure, FDA recognizes that there 

may be situations in which it will look 

beyond just the manufacturer’s 

statements [to determine intended 

use].’’); United States v. Travia, 180 F. 

Supp. 2d 115, 119 (D.D.C. 2001) (‘‘The 

government argues that the Court 

should look to the objective intent of the 

sellers in this case, which would permit 

the Court to view the totality of the 

circumstances—namely, the selling of 

balloons of laughing gas in the parking 

lot at a rock concert—surrounding the 

sale of the nitrous oxide here. See, e.g., 

21 CFR 201.128.’’)). This position has 

also been explained in numerous 

litigation briefs and other FDA 

pronouncements, such as in the 

following excerpts from examples of 

such documents issued from 2000 to 

2017: 

• In determining a product’s intended 

uses, ‘‘[l]abeling is not [the] exclusive 

evidence.’’ See United States v. Travia, 

180 F. Supp. 2d 115, 119 (D.D.C. 2001). 

Instead, ‘‘it is well established that the 

‘intended use’ of a product, within the 

meaning of the Act, is determined from 

its label, accompanying labeling, 

promotional claims, advertising, and 

any other relevant source.’’ Action on 

Smoking and Health v. Harris, 655 F.2d 

236, 239 (D.C. Cir. 1980) (quotation 

marks omitted); see also V.E. Irons, Inc. 

v. United States, 244 F.2d 34, 44 (1st 

Cir. 1957) (‘‘[W]e are free to look to all 

relevant sources in order [to] ascertain 

what is the ‘intended use’ of a drug.’’). 

Courts have considered ‘‘relevant 

sources’’ to include, for example, 

product formulation and method of 

intake, actual use of the product by 

consumers and medical practitioners, 

and circumstances of sale in 

determining intended use. See, e.g., 

United States v. Ten Cartons, More or 

Less, of an Article . . . Ener-B Vitamin 

B–12, 72 F.3d 285, 287 (2d Cir. 1995); 

United States v. Storage Spaces, 777 

F.2d 1363, 1367 (9th Cir. 1985); United 

States v. An Article of Device . . . 

Toftness Radiation Detector, 731 F.2d 

1253, 1257–58 (7th Cir. 1984) (Litigation 

brief (2011), Ref. 3). 

• Courts have recognized that 

intended use may be shown by nonspeech evidence that has included, for 

example, product formulation and 

method of intake, actual use of the 

product by consumers and medical 

practitioners, and circumstances of sale 

(Litigation brief (2010), Ref. 4 at 8–9 

n.5). 

• Courts have repeatedly held that, 

although promotional claims are one 

source of evidence of intended use, FDA 

is authorized to rely on any other 

relevant source of evidence [including] 

. . . [the product’s] method of intake, 

. . . [how any claims are] understood by 

a consumer. . ., [suggestive] product 

names, . . . [and] meta-tags (Litigation 

brief (2001), Ref. 5 at 20–26). 

• [Evidence of intended use to be 

presented at trial includes:] 

(1) Defendant intended the nitrous 

oxide he was offering for sale on his 

website bongmart.com to be used as a 

drug, despite his marking the nitrous 

oxide ‘For Food Use Only;’ (2) 

Defendant knew that the nitrous oxide 

cartridges were commonly used as a 

drug for getting high; and (3) 

Defendant’s customers actually used the 

nitrous oxide sold by Defendant as a 

drug (Litigation brief (2000), Ref. 6 at 6). 

• It has been the Agency’s 

longstanding position that in 

determining a product’s intended use, 

the Agency may look to any relevant 

source of evidence. . . . To hold 

accountable firms that attempt to evade 

FDA drug jurisdiction by avoiding 

making express claims about their 

products or disclaiming a particular 

intended use, courts have relied on a 

variety of evidence to establish intended 

use, including general knowledge of 

actual use by customers to get high or 

have some other mind-altering effect; 

the known effects of a product or 

substance; implied claims from using 

names that sound similar to controlled 

substances; the circumstances 

surrounding the sale (e.g., a rock concert 

venue; receiving the product in bulk 

and repackaging into smaller plastic 

bags; the use of private email addresses; 

the absence of labeling); shipping 

orders, other correspondence, and 

memoranda relating to marketing and 

distribution; statements made in 

training sessions; and admissions 

(Regulatory letter (2017), Ref. 7 at 9–10). 

• The manufacturer’s intent will 

necessarily be determined on a case-bycase basis, looking at the totality of the 

facts and circumstances. . . . The trier 

of fact will take into account the full 

body of evidence. If evidence of 

distribution or sponsorship activity 

forms part of the basis of FDA’s claim, 

the trier of fact will consider the context 

of that activity . . . in assessing the 

manufacturer’s objective intent 

(Regulatory letter (2002), Ref. 8 at 6).1

In addition, issues involving the 

scope of evidence relevant to 

establishing intended use frequently 

arise in FDA’s day-to-day operations in 

protecting the public health, including 

Warning Letters and import 

determinations (see, e.g., FDA Warning 


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Letter to HelloCig Electronic 

Technology Co., Ltd (Ref. 9) (relying in 

part on undeclared active 

pharmaceutical ingredient as well as 

implied claims from imagery to 

determine product’s intended use); FDA 

Warning Letter to Duy Drugs, Inc. (Ref. 

10) (relying in part on undeclared 

sildenafil to establish intended use); 

Letter from Steven B. Barber, District 

Director, Cincinnati District, FDA to 

Marc C. Sanchez, Esq., Mood and Mind, 

LLC, (Ref. 7 at 9–10) (relying in part on 

known attributes and common uses of 

product to establish use; Letter from 

Daniel Solis, Director, Import 

Operations Branch, Los Angeles District 

to Carol A. Pratt, K&L Gates LLP (Ref. 

11) (relying in part on information 

available on the internet reflecting 

general understanding by consumers of 

mind-altering properties and purported 

medical uses of product, as well as 

pattern of changes to the importer’s 

website and blog to conceal the true 

intended use of the product by deleting 

references to the amount of a 

psychoactive component in the 

product); FDA Warning Letter to 

Lifetech Resources Labs Inc. (Ref. 12) 

(relying in part on ‘‘presence of the 

prostaglandin analog, isopropyl 

cloprostenate, along with appearance 

claims’’ to establish intended use); FDA 

Warning Letter to INZ Distributors (Ref. 

13) (relying in part on presence of 

analogue of an erectile dysfunction drug 

to determine product’s intended use)). 

One of the purposes of this rulemaking 

is to put to rest any dispute about FDA’s 

interpretation of its statute and 

regulations, and its policy—as 

embodied in this rule as well as in the 

precedent cited above—regarding 

evidence that may be relevant to 

establishing intended use. 

(Comment 3) With respect to the 

many situations where manufacturers 

and distributors attempt to evade FDA 

regulatory oversight by omitting 

promotional medical product claims, 

examples of which are provided above, 

one comment suggested that the 

Government could use other regulatory 

tools rather than apply FDA’s 

authorities for premarket review of 

medical products. Specifically, the 

comment suggested that FDA employ ‘‘a 

combination of post-market risk 

mitigation techniques’’ which would 

require FDA to engage in the 

‘‘collection, review, and potential 

description in labeling’’ of the risks 

associated with the ‘‘unlabeled use’’ 

before taking enforcement action against 

the product to protect the public health. 

The same comment suggested that, 

alternatively, FDA could consider 

evidence other than promotional claims, 

but only to establish that in fact a 

promotional claim had been made. 

(Response) FDA declines this 

suggestion. The fundamental purpose of 

the FD&C Act is to help protect ‘‘the 

lives and health of people which, in the 

circumstances of modern industrialism, 

are largely beyond self-protection’’ 

(United States v. Dotterweich, 320 U.S. 

277, 280 (1943)). ‘‘[R]emedial legislation 

such as the Food, Drug, and Cosmetic 

Act is to be given a liberal construction 

consistent with the Act’s overriding 

purpose to protect the public health’’ 

(United States v. An Article of Drug . . . 

Bacto Unidisk, 394 U.S. 784, 798 

(1969)). Although FDA generally 

considers risk as part of its 

determination whether to take 

enforcement action, part of the impetus 

for Congress’ development of the 

premarket review requirements was the 

determination that exclusive reliance on 

postmarket remedies, such as 

enforcement actions for false or 

misleading labeling, is inadequate 

because it does not prevent consumers 

from experiencing harm from unsafe 

and/or ineffective treatments. 

FDA’s position regarding evidence 

relevant to establishing intended use 

helps protect the public health. To 

describe more fully one of the examples 

cited above: In United States v. Johnson, 

471 F.3d 764 (7th Cir. 2006), the 

defendant imported dextromethorphan 

hydrobromide (DXM), the active 

ingredient in some cough suppressants, 

and distributed it for recreational use. 

During the 4 months his company was 

in operation, five customers died. 

Because DXM is not a controlled 

substance, no charges were brought 

under the Controlled Substances Act, 

but the court found that FDA had 

jurisdiction under the FD&C Act (id. at 

765). Defendant pleaded guilty to three 

counts of introducing a misbranded 

drug into interstate commerce and 

received a 77-month sentence (id.). In 

upholding that sentence, the Seventh 

Circuit noted that the defendant 

‘‘knew—not merely should have 

known—that there was a substantial risk 

that more of his customers would die, 

and yet he continued to sell DXM for 

recreational use and failed to warn 

existing customers, including the two 

teenagers who died after he learned of 

the first two deaths’’ (id.). 

Because FDA’s position on intended 

use helps ensure that it can help curb 

the distribution of dangerous and 

fraudulent products, FDA declines to 

construe intended use more narrowly 

than the statute provides. 

(Comment 4) One comment objected 

to FDA’s statement in the proposed rule 

that relying exclusively on firms’ claims 

to determine intended use would 

adversely affect public health by 

opening the door to the marketing of 

products that are unapproved for any 

medical use. The comment argued that 

there is no public health need for FDA 

to rely on evidence other than express 

claims to determine intended use 

because the FD&C Act and other statutes 

provide other authorities that allow 

FDA to take action against products that 

contain an active ingredient from an 

FDA-approved drug, controlled 

substance, or other pharmacological 

ingredient. Specifically, the comment 

recommended that FDA use its dietary 

supplement and food additive 

authorities to keep products containing 

pharmacological ingredients out of 

dietary supplements and conventional 

foods, rather than using an intended use 

analysis to classify and regulate the 

products as drugs. The specific 

authorities mentioned in the comment 

were the definitions of ‘‘food’’ and 

‘‘dietary supplement’’ and the 

corresponding adulteration provisions 

of the FD&C Act; the premarket 

notification requirement for certain 

dietary ingredients not marketed in the 

United States before October 15, 1994; 

and the premarket approval requirement 

for food additives. Similarly, another 

comment argued that rather than 

continuing to take the approach to 

intended use outlined in the NPRM, the 

Government could apply other 

provisions of Federal law; and that 

where there are gaps in existing legal 

provisions, FDA could seek specific 

product-based legislative changes. 

(Response) We decline the comments’ 

suggestions. Although it is true that the 

authorities mentioned in the comment 

enable FDA to keep some products 

containing pharmacological ingredients 

out of the food supply and dietary 

supplement marketplace, the comment 

overstates the reach of FDA’s other 

authorities and overlooks the fact that 

simply being outside the dietary 

supplement or food definition does not 

make a product unlawful and subject to 

enforcement action. To establish 

jurisdiction over a product as a drug and 

remove it from the marketplace, or 

require the manufacturer to obtain FDA 

approval for the product before 

marketing it, FDA must be able to 

establish that the product is a drug 

based on evidence of its intended use 

Thus, the regulatory tools the comment 

recommends are not a substitute for 

FDA’s medical product authorities that 

include an intended use determination. 

As the previous comment response 

explained, suggestions that FDA use 

other regulatory tools in place of 


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intended use would have a significant 

negative impact on public health. To 

protect consumers from dangerous 

products containing pharmacological 

ingredients like the cough suppressant 

in United States v. Johnson that caused 

several deaths, FDA intends to continue 

considering the full range of evidence 

relevant to determining intended use. 

(Comment 5) One comment agreed 

with the NPRM that evidence of 

intended use could include conduct 

other than claims, but suggested that the 

rule clarify that the conduct must be 

promotional. 

(Response) FDA declines this 

suggestion. FDA believes that the key 

issue in the intended use analysis is 

whether the evidence is ‘‘relevant,’’ 

which does not necessarily depend on 

whether there is evidence of 

‘‘promotional’’ activity. The NPRM 

provided several examples to help 

inform the assessment of relevance. As 

the preamble explained, where a firm 

disseminates additional specific safety 

and warning information to healthcare 

providers to minimize the risk to 

patients receiving the drug for the 

unapproved use—an example of nonpromotional speech—FDA would not 

consider such evidence to be relevant to 

intended use (see 85 FR 59718 at 

59726). But the preamble provided other 

examples of evidence that would not 

necessarily be considered promotional 

that would still be relevant to intended 

use—such as designing a stent to be 

specifically sized for a use that is 

different from the purported use (see 85 

FR 59718 at 59725). As another 

example, a factfinder might consider, as 

evidence of a new intended use, a 

spacer that the manufacturer claims can 

be used to elute one liquid, but is in fact 

designed with holes that are sized to 

elute a more viscous substance that 

contains a different active ingredient. 

Accordingly, FDA declines the 

suggestion to include ‘‘promotional’’ as 

a limiting principle for non-claimsbased evidence that may be relevant to 

intended use. 

This conclusion is consistent with 

recent case law. The case law describes 

the standard for determining intended 

use as ‘‘all relevant evidence.’’ This 

allows the fact finder to evaluate the 

facts of the specific case, which may 

involve a variety of situations and 

circumstances. For example, in United 

States v. Carlson, 810 F.3d 544 (8th Cir. 

2016), defendants owned and/or worked 

at the Last Place on Earth, a head shop 

in Duluth, Minnesota, which sold 

synthetic drugs, such as synthetic 

marijuana. The products were labeled as 

incense, herbal incense, herbal 

potpourri, bath salts, etc., and also bore 

the label statement ‘‘not for human 

consumption,’’ but defendants knew 

that customers purchased them to 

consume as drugs (see id. at 549; see 

also Amended Superseding Indictment, 

12–cr–00305–DSD–LIB ¶ 9 (D. Minn. 

September 11, 2013)). The trial court 

instructed the jury that the product’s 

intended use ‘‘is what a reasonable 

person would conclude the 

manufacturer, seller or dispenser of the 

product intended the product to be used 

for, based on all of the relevant 

information’’ (see The Court’s 

Instructions to the Jury, 12–cr–00305– 

DSD–LIB at 58 (D. Minn. October 8, 

2013)). The court explained that the jury 

could consider ‘‘any and all testimony 

and evidence,’’ whether or not the 

manufacturer, seller, or dispenser made 

contrary claims or no claims (see id. at 

58–59). All of the defendants were 

convicted of distributing misbranded 

drugs in violation of the FD&C Act (see 

Carlson, 810 F.3d at 550). 

In United States v. Dessart, 823 F.3d 

395 (7th Cir. 2016), the defendant used 

a website to sell products containing 

human growth hormone (‘‘HGH’’), 

steroids, and the active ingredients in 

the prescription drugs VIAGRA 

(sildenafil), CIALIS (tadalafil), and 

LEVITRA (vardenafil). Id. at 398. The 

website said that the products were ‘‘for 

research only.’’ Id. The defendant was 

indicted on 23 counts of violating the 

FD&C Act. Id. at 399. The court 

instructed the jury: ‘‘[Y]ou should 

consider what a reasonable person 

would conclude the manufacturer or 

seller of the product intended the 

product to be used for, based on all of 

the relevant information. . . . You are 

not bound by any claims or statements 

made by the manufacturer or seller if 

there is other evidence concerning the 

use intended by the manufacturer or 

seller that conflicts with those claims or 

statements.’’ Jury Instructions, Case No. 

12–CR–85 at 4–5 (E.D. Wis. June 19, 

2014). The jury convicted on all counts. 

Dessart, 823 F.3d at 400. 

In United States v. 789 Cases of Latex 

Surgeons’ Gloves, 799 F. Supp. 1275, 

1294–1295 (D.P.R. 1992), the 

Government sought condemnation of 

surgeon’s gloves and their components, 

including cornstarch, stored in a rodentinfested facility. Although the product 

manufacturer argued that it did not 

intend for the gloves to be used in 

medical procedures, the court found 

that ‘‘[t]he circumstances surrounding 

the manufacture, distribution, and 

actual use of Plastic Material’s gloves 

present overwhelming evidence that 

claimant’s gloves are intended for use 

as—and therefore are—devices within 

the meaning of the Act’’: e.g., the sole 

customer, the United States, purchased 

gloves only for medical use; and the 

cornstarch used to store the gloves was 

of a type used only with gloves intended 

for medical procedures. 

In each of these cases, restricting 

relevant evidence to promotional claims 

and conduct could have led the 

factfinder to conclude that the products 

were outside of FDA’s jurisdiction. 

(Comment 6) One comment asserted 

that the phrase ‘‘any relevant evidence’’ 

as used in the case law should be 

understood, under the statutory 

interpretation principle ejusdem 

generis, to refer only to evidence of 

promotional claims. 

(Response) FDA disagrees. First, most 

obviously, principles of statutory 

construction are not typically applied to 

language in court decisions. Second, 

throughout this preamble, we have cited 

numerous examples where courts and 

FDA have considered evidence other 

than promotional claims to be relevant 

to establishing intended use. 

C. Comments and Responses Regarding 

the Design or Composition of an Article 

(Comment 7) Several comments stated 

that FDA should reconsider the 

proposed regulatory text identifying 

evidence about the ‘‘design or 

composition’’ of an article as a type of 

evidence relevant to establishing 

intended use. Some comments also 

asserted that the characteristics and 

design of a medical product that is 

approved, cleared, granted marketing 

authorization, or exempted from 

premarket notification do not determine 

intended use and that intended use does 

not depend on the design of the 

product. Some comments requested that 

FDA remove this phrase from the 

codified language describing the types 

of evidence relevant to determining a 

product’s intended uses. 

(Response) We disagree with the 

comments and decline to remove 

‘‘design or composition’’ from the 

codified language. As explained in the 

preamble, the revisions to the intended 

use regulations do not reflect a change 

in FDA’s policies and practices. Rather, 

the amendments to the intended use 

regulations are intended to describe the 

types of evidence relevant to 

determining a product’s intended use 

based on FDA’s current practices. The 

design and composition of an article are 

examples of the types of evidence that 

may be relevant when determining the 

article’s intended use. For example, 

FDA may consider the design or 

composition of a product, which 

includes product characteristics, when 

determining whether the product is 

‘‘intended to affect the structure or any 


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function of the body’’ and therefore 

meets the device definition in section 

201(h) of the FD&C Act (21 U.S.C. 

321(h)). The addition of the phrase 

‘‘design or composition’’ to the codified 

reflects FDA’s longstanding and current 

policy that these are relevant to 

intended use. 

As discussed in the preamble to the 

NPRM, an example of a situation where 

design features have been found 

relevant to intended use include the 

design of a stent to be specifically sized 

for a use that is different from the 

purported use (see 85 FR 59718 at 

59725). Another example can be found 

in United States v. Caputo, 517 F.3d 935 

(7th Cir. 2008), where the Seventh 

Circuit upheld a conviction for 

misbranding under the FD&C Act where 

design features were part of the 

evidence of intended use. There, the 

district court recited evidence of the 

differences in design between two 

versions of the device that necessitated 

separate premarket review applications: 

‘‘The larger sterilizer had different 

design and engineering characteristics: a 

six cubic foot chamber; a 5% peracetic 

acid mixture; different temperature, 

pressure, and gas flow rate; and a single, 

as opposed to multiple, use of the 

sterilant’’ (United States v. Caputo, 456 

F. Supp. 2d 970, 973 (N.D. Ill. 2006), 

aff’d in relevant part, 517 F.3d 935 (7th 

Cir. 2008)). As another example, a 

factfinder might consider, as evidence of 

a new intended use, a spacer that the 

manufacturer claims can be used to 

elute one liquid, but is in fact designed 

with holes that are sized to elute a more 

viscous substance that contains a 

different active ingredient. 

Another example where composition 

has been found relevant to intended use 

is United States v. Undetermined 

Quantities . . .‘‘Pets Smellfree,’’ 22 F.3d 

235 (10th Cir. 1994). In that case, the 

Government had seized and sought to 

condemn ‘‘Pets Smellfree’’ as an 

adulterated and misbranded drug. The 

product was promoted as an animal 

food additive to reduce pet odor when 

ingested. In determining that the 

product was a drug, the Tenth Circuit 

relied heavily on expert testimony about 

the physiological effects of a 

pharmacologically active ingredient, 

chlortetracycline, in reducing the level 

of bacteria in the animals’ digestive 

systems and oral cavities (see id. at 240). 

Other examples include United States v. 

Zeyid, 1:14-cr-0197, First Superseding 

Indictment (N.D. Ga. June 24, 2014) (see 

Ref. 2), where imported products 

labeled as ‘‘tea,’’ ‘‘coffee,’’ and ‘‘beauty 

products’’ contained active ingredients 

that were the same as those used in 

prescription drugs; FDA Warning Letter 

to HelloCig Electronic Technology Co., 

Ltd. (Ref. 9), where undeclared active 

pharmaceutical ingredient was 

considered relevant to intended use; 

and FDA Warning Letter to INZ 

Distributors (Ref. 13), where presence of 

analogue of an erectile dysfunction drug 

was considered relevant to intended 

use. 

(Comment 8) Some comments 

suggested that consideration of ‘‘design 

or composition of the article’’ as a type 

of evidence of intended use may inhibit 

technological advancements and 

discourage manufacturers from 

developing products that, based on their 

design, may be used for multiple uses. 

(Response) FDA disagrees with these 

comments. We do not believe that 

considering a product’s design or 

composition to be relevant to the 

intended use of a product impedes 

technological advancements or 

discourages product development. As 

stated above, the relevance of a 

product’s design and composition to 

intended use is a part of FDA’s 

longstanding policy and has not 

hindered such improvements. For 

example, during premarket review of 

software, FDA may not always review a 

software device function that is 

included in the design but has been 

locked out, because it is not part of that 

specific premarket submission by the 

firm. If, however, the firm wants to 

unlock the software device function in 

the future, it must first obtain any 

necessary premarket clearance, 

marketing authorization or approval for 

the product with that function. 

(Comment 9) One comment suggested 

that FDA should not seek enforcement 

after a product is approved, cleared, or 

granted marketing authorization solely 

based on that product’s design or 

characteristics, and another comment 

suggested that FDA should not assert a 

new intended use based solely on such 

features. 

(Response) FDA applies applicable 

premarket and postmarket statutory and 

regulatory requirements to determine 

whether a product is legally marketed. 

FDA examines all relevant evidence in 

assessing compliance with such 

requirements. As previously noted, FDA 

may consider a product’s design or 

composition as one type of evidence 

relevant to the product’s intended use. 

D. Comments and Responses Regarding 

the First Amendment 

(Comment 10) One comment stated 

that because the rule identifies speech 

as potentially relevant to establishing 

intended use, and such speech may be 

truthful, the rule is ‘‘suspect’’ under the 

First Amendment. The comment 

requested that FDA add specific 

statements to the codified language to 

address these concerns. Other 

comments similarly stated that the 

proposal does not adequately take into 

account the limitations on FDA’s 

authority to regulate truthful and nonmisleading speech. 

(Response) We disagree that the rule 

is vulnerable under the First 

Amendment. First, as noted in the 

preamble to the NPRM, we do not 

believe this rulemaking implicates the 

First Amendment. The intended use 

regulations describe evidence that may 

be relevant to establishing intended use; 

they do not in themselves directly 

regulate speech (85 FR 59718 at 59723). 

Indeed, the changes to the codified 

language proposed and finalized in this 

rulemaking do not directly involve 

speech: Whether, and to what extent, a 

factfinder may rely on product design, 

product composition, and knowledge as 

evidence of intended use, is not itself a 

First Amendment question, because 

speech will not typically be involved in 

such evidence. See 82 FR 2193 at 2207. 

Second, in the regulatory regime 

under the FD&C Act and the PHS Act, 

intended use helps determine the 

marketing status for products that are 

potentially subject to those Acts, which 

products Congress has directed FDA to 

regulate in the interest of the public 

health. Part of the regulatory regime for 

medical products involves, for example, 

the review of appropriate labeling in the 

context of premarket review and 

postmarket regulatory surveillance. The 

categorical exclusion of all truthful 

speech from regulatory review would 

undermine FDA’s ability to promote and 

protect the public health through 

premarket review of medical products, 

including review of proposed labeling, 

and postmarket regulatory surveillance 

and actions. 

For example, the Government 

prosecuted a clinic operator under the 

FD&C Act for injecting liquid silicone 

into the body to augment tissues such as 

the buttocks or breasts (Refs. 14 and 15). 

Silicone when used for industrial 

purposes would not fall within FDA’s 

jurisdiction. However, in this case, 

evidence that helped establish the 

intended use of the products included 

testimony of victims about the claims 

made to them by the defendant that the 

product would enhance the size of their 

buttocks. Those claims may have been 

truthful in the sense that they revealed 

one effect of the product. However, the 

injection of liquid silicone into the body 

for tissue augmentation can result in 

serious adverse health consequences, 

including hardening of tissue at the 

injection site, embolization, and even 


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2See Reference 16 (‘‘This pattern in the law— 

using intent as the predicate for regulation and then 

using speech as evidence of intent—is quite 

common, and not peculiar to pharmaceutical 

regulation. As early as 1888, the Supreme Court 

affirmed a state court criminal conviction for 

someone who manufactured an ‘oleaginous 

substance’ otherwise perfectly legal, except that he 

intended for it to be used as food, and thereby his 

manufacture of it fell under the purview of a state 

regulator. Similarly, a hollow piece of glass with a 

bowl on the end is illegal drug paraphernalia only 

if intended for such illicit uses. An automobile is 

not subject to regulation by the Federal Aviation 

Administration, unless it is ‘intended to be used for 

flight in the air.’ ’’) (citations omitted). 

death. FDA has not approved any liquid 

silicone products for injection to 

augment tissues anywhere in the body. 

Therefore, it was in the interest of 

public health for FDA to take action 

against the person responsible for the 

administration of these products, and 

such action was well within FDA’s 

jurisdiction and permissible under the 

First Amendment. 

There are many industries whose 

operations involve some amount of 

communication with the public. The 

fact that those communications may be 

truthful does not shield those 

industries’ operations from Government 

regulation. ‘‘[I]t has never been deemed 

an abridgment of freedom of speech . . . 

to make a course of conduct illegal 

merely because the conduct was in part 

initiated, evidenced, or carried out by 

means of language, either spoken, 

written, or printed’’ (Rumsfeld v. Forum 

for Academic and Institutional Rights, 

Inc., 547 U.S. 47, 62 (2006) (citation 

omitted)). And, as the Court recently 

confirmed, ‘‘ ‘the First Amendment does 

not prevent restrictions directed at 

commerce or conduct from imposing 

incidental burdens on speech’ ’’ (Barr v. 

Am. Ass’n of Political Consultants, 140 

S. Ct. 2335, 2347 (2020) (quoting Sorrell 

v. IMS Health Inc., 564 U.S. 552, 567 

(2011))). 

Thus, as we explained in the NPRM, 

courts have long upheld the premarket 

review requirements of the FD&C Act 

and the PHS Act, and the role of 

intended use within that framework, as 

necessary to promote and protect the 

public health and as fully consistent 

with the First Amendment (see 85 FR 

59718 at 59723). More specifically, 

courts have held that, under the holding 

of Wisconsin v. Mitchell, 508 U.S. 476, 

489 (1993), the Government’s reliance 

on speech as evidence of intended use 

under the FD&C Act does not infringe 

the right of free speech under the First 

Amendment (see, e.g., Whitaker v. 

Thompson, 353 F.3d 947, 953 (D.C. Cir. 

2004); Nicopure Labs, LLC v. FDA, 944 

F.3d 267, 283 (D.C. Cir. 2019); United 

States v. Cole, 84 F. Supp. 3d 1159, 

1166 (D. Or. 2015); United States v. 

Regenerative Sciences, LLC, 878 F. 

Supp. 2d 248, 255–56 (D.D.C. 2012), 

aff’d, 741 F.3d 1314 (D.C. Cir. 2014); 

United States v. Livdahl, 459 F. Supp. 

2d 1255, 1268 (S.D. Fla. 2005); United 

States v. Lane Labs-USA, Inc., 324 F. 

Supp. 2d 547, 579–80 (D.N.J. 2004); see 

also United States v. Article of Drug 

Designated B-Complex Cholinos 

Capsules, 362 F.2d 923, 927 (3d Cir. 

1966); United States v. General 

Nutrition, Inc., 638 F. Supp. 556, 562 

(W.D.N.Y. 1986)). Indeed, reliance on 

speech as evidence of intent is common 

in the law.2

Third, as also explained in the NPRM, 

even if this rulemaking or regulatory 

regime were appropriately subject to 

First Amendment review, FDA’s 

consideration of speech as one type of 

evidence of intended use under its 

statutory and regulatory framework 

easily satisfies any applicable test. 

Under the Central Hudson framework, 

the threshold question is whether the 

speech is false or inherently or actually 

misleading or concerns unlawful 

activity—such speech may be 

prohibited (see Central Hudson Gas & 

Elec. Corp. v. Pub. Serv. Comm’n, 447 

U.S. 557 (1980); In re R.M.J., 455 U.S. 

191, 203 (1982); 44 Liquormart, Inc. v. 

Rhode Island, 517 U.S. 484, 497 n.7 

(1996); 1–800–411–Pain Referral Serv., 

LLC v. Otto, 744 F.3d 1045, 1056 (8th 

Cir. 2014)). When commercial speech 

relates to an illegal activity, there is no 

First Amendment interest to weigh 

against the governmental interest 

supporting the regulation of commercial 

activity (Pittsburgh Press Co. v. Human 

Relations Comm’n, 413 U.S. 376, 389 

(1973)). Regulated parties cannot be 

allowed to escape reasonable 

Government regulations by 

‘‘bootstrap[ping] themselves into the 

heightened scrutiny of the First 

Amendment simply by infusing the 

prohibited conduct with some element 

of speech’’ (Ford Motor Co. v. Tex. DOT, 

264 F.3d 493, 506–507 (5th Cir. Tex. 

2001)). 

For example, in United States v. 

Caputo, 517 F.3d 935 (7th Cir. 2008), 

the court found that it did not need to 

resolve the question of whether 

promotional claims for an approved 

medical device were protected by the 

First Amendment because defendants’ 

product was not approved: ‘‘[t]here was 

no lawful activity for speech to 

promote’’ (id. at 941). In United States 

v. Cole, 84 F. Supp. 3d 1159 (D. Or. 

2015), defendants distributed 

unapproved products with claims that 

they treated diseases, including 

Alzheimer’s and HIV infection. The 

court rejected defendants’ First 

Amendment defense, explaining that, 

because ‘‘[d]efendants’ speech concerns 

an illegal activity—the introduction into 

interstate commerce of unapproved new 

drugs[,] . . . the First Amendment is not 

violated’’ (id. at 1166–67). In United 

States v. LeBeau, 2016 U.S. Dist. LEXIS 

13612 (E.D. Wisc. February 3, 2016), the 

court similarly rejected defendant’s First 

Amendment defense to a charge of 

distributing an unapproved new drug 

and explained that, because defendant’s 

speech occurred while promoting and 

distributing a product that was intended 

for treatment of diseases and had not 

been approved by the FDA, his 

commercial speech did not concern 

lawful activity and did not pass step (1) 

of Central Hudson (see id. at 29). The 

Seventh Circuit affirmed, explaining 

that ‘‘[b]ecause LeBeau’s statements 

promoted the unlawful sale of an 

unapproved drug, they were not entitled 

to protection’’ (United States v. LeBeau, 

654 Fed. App’x 826, 831 (7th Cir. 

2016)). 

Even where the threshold step of 

Central Hudson does not apply, FDA’s 

reliance on speech as evidence of 

intended use in the context of premarket 

review directly advances, and is 

appropriately tailored to achieve, 

substantial public health interests and 

therefore satisfies the remaining steps of 

the Central Hudson analysis. The 

medical products FDA regulates have 

the potential to adversely impact public 

health and safety. The premarket review 

requirements of the FD&C Act and the 

PHS Act require companies to conduct 

scientific research to determine the 

safety and effectiveness of medical 

products before they are marketed and 

provide mechanisms to help ensure that 

protections are in place that will allow 

the public to obtain the benefits of these 

products while mitigating the risks. 

Accordingly, these premarket review 

provisions ‘‘do not ban manufacturers 

from making accurate claims’’ but 

instead ‘‘require them to substantiate 

such claims.’’ Nicopure Labs, LLC v. 

FDA, 944 F.3d 267, 285 (D.C. Cir. 2019). 

(Comment 11) One comment asserted 

that the NPRM failed to provide a 

meaningful explanation of how its 

consideration of speech as evidence of 

intended use comports with the Central 

Hudson test, particularly whether there 

are any less speech-restrictive 

alternatives with respect to speech 

regarding unapproved uses of approved 

products. The comment cites United 

States v. Caronia, 703 F.3d 149 (2d Cir. 

2012) and criticizes the Government for 

not providing a sufficient explanation of 

its consideration of less-restrictive 

alternatives in the context of that 

lawsuit. Another commenter similarly 


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asserted that the NPRM did not 

adequately justify under Central 

Hudson the Government’s policy 

regarding off-label use/promotion. 

(Response) Again, as noted above and 

in the NPRM, we do not believe this 

rulemaking implicates the First 

Amendment, particularly given that the 

changes to the codified language 

proposed and finalized in this 

rulemaking do not directly involve 

speech. As further explained in the 

NPRM, ‘‘[b]ecause ‘intended use’ is only 

one element of an alleged violation of 

the FD&C Act, this rule does not itself 

implicate the First Amendment and 

does not attempt to resolve all First 

Amendment arguments that might be 

made by a firm in defending against an 

enforcement action under the FD&C 

Act.’’ 85 FR 59798 at 59723 n.5. 

Nevertheless, in another proceeding, 

FDA has addressed in detail the issues 

raised by these comments (see 

Memorandum: Public Health Interests 

and First Amendment Considerations 

Related to Manufacturer 

Communications Regarding 

Unapproved Uses of Approved or 

Cleared Medical Products (January 

2017) (Ref. 17)). Rather than repeat that 

analysis here, we summarize it briefly 

and incorporate the relevant portions of 

the document. The memorandum 

describes in detail the public health 

interests underlying and advanced by 

FDA’s consideration of communications 

regarding unapproved uses of medical 

products that are approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification 

as relevant to the premarket review 

requirements of the FD&C Act and PHS 

Act (see Ref. 17 at 3–16). As the 

memorandum explains, those 

requirements, among other things, 

motivate the development of scientific 

evidence that enables the reliable, 

population-level determination of the 

safety and efficacy of medical products 

for each intended use; require that the 

evidence be developed and 

independently reviewed before the 

products are marketed to the general 

public for each intended use; and 

require that the product bear labeling 

that identifies each medical use of the 

product that is approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification 

and provides information for healthcare 

providers and patients on using the 

product safely and effectively for those 

uses that are approved, cleared, granted 

marketing authorization, or exempted 

from premarket notification. In the 

memorandum, FDA also examined 

alternative approaches suggested by the 

court in United States v. Caronia, as 

well as by commentators (see id. at 26– 

34). FDA explained that, although many 

of these proposed approaches addressed 

one or more of the interests served by 

the premarket review requirements, 

FDA found that none of them integrated 

the complex mix of numerous interests 

at play and thus none of the proposed 

approaches best advanced those 

multiple interests (see id.). 

(Comment 12) One comment asserted 

that the right of a manufacturer to 

convey truthful and non-misleading 

information is protected under 

Thompson v. Western States Medical 

Center, 535 U.S. 357 (2002). 

(Response) We disagree with the 

suggestion that Western States shields 

truthful and non-misleading speech 

from Government regulation. In that 

case, the Court applied the Central 

Hudson test to evaluate the regulation of 

the speech at issue, 535 U.S. at 368–77. 

In an analysis that broke no ‘‘new 

ground’’ (id. at 368), the Court 

explained that, in general, the 

Government should not restrict the 

communication of truthful and nonmisleading information for the sole 

purpose of preventing members of the 

public from making bad decisions with 

the information (see id. at 374). 

However, that rationale is not applicable 

to this rulemaking because the 

premarket review requirements of the 

FD&C Act and PHS Act advance several 

different Government interests in 

protecting public health, as discussed 

above (see also Ref. 17). 

(Comment 13) One comment asserted 

that the First Amendment protects not 

only the right to speak freely but also 

the right to hear and receive valuable 

information, and that this interest is 

particularly acute for the audience of 

physicians. 

(Response) FDA has recognized that, 

under certain circumstances, both 

healthcare providers and patients may 

be interested in information about 

unapproved uses of products (see Ref. 

17 at 17). In part because of this 

consideration, FDA has issued guidance 

documents describing circumstances in 

which the Agency does not intend to 

object to a firm’s product 

communications or to view such 

communications as evidence of a new 

intended use (see 85 FR 59718 at 59723 

& n.7). Nothing in this final rule reflects 

a change in FDA’s policies and 

practices, as articulated in various 

guidance documents, regarding the 

types of firm communications that 

ordinarily would not, on their own, 

establish the firm’s intent that a medical 

product that is approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification 

be used for an unapproved use. As 

discussed elsewhere in this preamble, 

FDA declines the suggestion to expand 

the scope of this rulemaking to 

additional subjects. 

(Comment 14) One comment 

referenced for support a 1999 district 

court decision in a case brought by 

Washington Legal Foundation. Another 

comment referenced the same litigation 

and asserted that FDA is subject to a 

permanent injunction curtailing the 

Agency’s authority to bar manufacturers 

from sharing peer-reviewed medical 

texts and journal articles about off-label 

uses of their FDA-approved products. 

(Response) We believe these 

comments have little bearing on the 

current rulemaking. First, as explained 

in the NPRM, the proposed revisions to 

the intended use regulations do not 

reflect any change in FDA’s policies and 

practices, as articulated in various 

guidance documents, regarding the 

types of firm communications to which 

the Agency does not intend to object or 

to view as evidence of a new intended 

use. Among the guidance documents 

describing these existing policies are 

several that relate to the distribution of 

peer-reviewed medical texts and journal 

articles (see 85 FR 59718 at 59723 & 

n.7). Second, with respect to the district 

court decision referenced in the 

comments, the D.C. Circuit ‘‘vacate[d] 

the district court’s decisions and 

injunctions insofar as they declare the 

FDAMA and the CME Guidance 

unconstitutional’’ (see Washington Legal 

Found. v. Henney, 202 F.3d 331, 337 

(D.C. Cir. 2000); see also Washington 

Legal Found. v. Henney, 128 F. Supp. 

2d 11, 15 (D.D.C. 2000) (holding that 

‘‘injunction has been wholly vacated by 

the Court of Appeals’’); id. (holding that 

Court of Appeals ‘‘vacated all of this 

Court’s previous constitutional rulings 

on the matter’’); 65 FR 14286 (2000) 

(describing FDA’s understanding of the 

outcome of the Washington Legal 

Found. litigation); Letter from Margaret 

M. Dotzel, Assoc. Commissioner for 

Policy, FDA to Daniel J. Popeo & 

Richard A. Samp, Wash. Legal Found., 

Docket No. 01P–0250 (January 28, 2002) 

(same)). 

(Comment 15) Some comments 

asserted that content-based restrictions 

on commercial speech are subject to 

strict scrutiny or heightened scrutiny. 

One comment argued that Sorrell v. IMS 

Health Inc., 564 U.S. 552 (2011), Reed 

v. Town of Gilbert, 135 S. Ct. 2218 

(2015), Matal v. Tam, 137 S. Ct. 1744 

(2017), and Barr v. Am. Ass’n of 

Political Consultants, 140 S. Ct. 2335 

(2020) support the proposition that all 

content-based speech restrictions, even 


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those involving commercial speech, are 

subject to strict scrutiny, effectively 

overruling the Central Hudson and 

Wisconsin v. Mitchell lines of cases. 

Relying primarily on Sorrell and 

mentioning Barr, another comment 

asserted that FDA understated the 

constitutional limits on its authority in 

the NPRM. Another comment suggested 

that heightened scrutiny is warranted 

under Sorrell in the fields of medicine 

and public health. 

(Response) We disagree. As we 

discussed in the NPRM, the Supreme 

Court in Sorrell suggested that contentand speaker-based restrictions would be 

subject to ‘‘heightened scrutiny,’’ but 

nevertheless continued to apply the 

‘‘commercial speech inquiry’’ as 

outlined in Central Hudson (85 FR 

59718 at 59724 n.11). Several courts of 

appeals have subsequently concluded 

that Sorrell did not overrule or 

fundamentally alter the Central Hudson 

analysis (see Retail Digital Network, LLC 

v. Prieto, 861 F.3d 839, 846 (9th Cir. 

2017) (en banc) (Sorrell ‘‘did not mark 

a fundamental departure from Central 

Hudson’s four factor test, and Central 

Hudson continues to apply’’ to 

regulations of commercial speech, 

regardless of whether they are content 

based); Missouri Broad. Ass’n v. Lacy, 

846 F.3d 295, 300 n.5 (8th Cir. 2017) 

(‘‘The upshot [of Sorrell] is that when a 

court determines commercial speech 

restrictions are content- or speakerbased, it should then assess their 

constitutionality under Central 

Hudson.’’) (quotation marks omitted; 

alteration in original); see also Vugo, 

Inc. v. City of New York, 931 F.3d 42, 

50 (2d Cir. 2019) (‘‘No Court of Appeals 

has concluded that Sorrell overturned 

Central Hudson. We agree with our 

sister circuits that have held that Sorrell 

leaves the Central Hudson regime in 

place, and accordingly we assess the 

constitutionality of the City’s ban under 

the Central Hudson standard.’’), cert. 

denied, 140 S. Ct. 2717 (2020)). 

In Reed v. Town of Gilbert, the Court 

applied strict scrutiny to content-based 

restrictions on non-commercial speech 

in sign ordinances. Although some of 

the language in the majority opinion in 

that case is broad, most lower courts 

have subsequently rejected arguments 

that Reed applies to the regulation of 

commercial speech (see, e.g., Vugo, Inc. 

v. City of New York, 931 F.3d 42, 49– 

50 & n.6 (2d Cir. 2019) (holding that 

Central Hudson still applies to 

commercial speech after Reed and 

Sorrell), cert. denied, 140 S. Ct. 2717 

(2020); Nationwide Biweekly Admin., 

Inc. v. Owen, 873 F.3d 716, 732 (9th Cir. 

2017) (‘‘Reed did not relate to 

commercial speech . . . and therefore 

did not have occasion to consider th[at] 

doctrine[.]’’)). Indeed, as one comment 

noted, in Matal v. Tam, a decision 

regarding content-based commercial 

speech issued after Reed, only one 

Justice advocated overruling Central 

Hudson in favor of strict scrutiny (137 

S. Ct. 1744, 1769 (2017) (Thomas, J., 

concurring in part and concurring in the 

judgment)). No other Justice joined that 

opinion. While no First Amendment 

analysis garnered five votes in Matal, 

one four-Justice opinion applied Central 

Hudson (id. at 1764); the other fourJustice opinion stated that heightened 

scrutiny should be applied to viewpoint 

discrimination, but explained that 

viewpoint discrimination is an 

‘‘egregious’’ subcategory of contentbased regulation, and further noted that 

regulations regarding product labeling 

or consumer protection may be 

evaluated differently from the trademark 

matter at issue in that case (id. at 1766, 

1768). 

There was similarly no majority First 

Amendment analysis in Barr v. Am. 

Ass’n of Political Consultants, 140 S. Ct. 

2335 (2020). There, the plurality 

opinion explained that strict scrutiny 

should be applied to a law that singled 

out a specific subject matter for 

differential treatment—permitting 

robocalls for collecting money owed to 

the Government while prohibiting 

robocalls for all other purposes (see id. 

at 2346). Similarly, Justice Gorsuch’s 

opinion emphasized that the statute 

under review favored certain voices 

while punishing others (see id. at 2364) 

(Gorsuch, concurring in the judgment in 

part and dissenting in part). In addition, 

the plurality opinion further 

circumscribed the scope of its holding: 

‘‘The issue before us concerns only 

robocalls to cell phones. . . . Our 

decision is not intended to expand 

existing First Amendment doctrine or to 

otherwise affect traditional or ordinary 

economic regulation of commercial 

activity’’ (see id. at 2347; see also Am. 

Hosp. Ass’n v. Azar, 983 F.3d 528, 542 

(D.C. Cir. 2020) (in upholding an HHS 

rule challenged in part on First 

Amendment grounds, the court 

distinguished Barr on the grounds that 

the restrictions in Barr involved 

political speech and the regulation at 

issue in Am. Hosp. Ass’n involved 

ordinary regulation of commercial 

activity)). 

Accordingly, given that the Supreme 

Court has not overruled Central Hudson 

or Wisconsin v. Mitchell and given that 

the laws being reviewed in the cited 

cases were quite different from the 

premarket review provisions of the 

FD&C Act, we believe it would be wrong 

to conclude that the Supreme Court has 

implicitly but sweepingly reversed these 

long-standing precedents to invalidate 

the regulatory regime under the FD&C 

Act. And even if some form of 

heightened scrutiny were applicable to 

reliance on speech as evidence of 

intended use, FDA believes that the 

public health necessity of the premarket 

review provisions discussed in this 

preamble, including its references, 

justifies and necessitates this regime 

under any standard. 

(Comment 16) One comment asserted 

that scientific speech has been 

recognized as core speech that merits 

the highest degree of constitutional 

protection, citing Washington Legal 

Foundation v. Friedman, 13 F. Supp. 2d 

51, 62 (D.D.C. 1998). 

(Response) FDA agrees that, in certain 

contexts, scientific speech merits the 

highest degree of constitutional 

protection. However, the comment 

failed to note that the cited opinion 

determined that scientific speech will 

be evaluated under the First 

Amendment as commercial speech 

when a commercial entity seeks to 

distribute it in order to increase its sales 

of the product (see id. at 64–65). 

(Comment 17) One comment urged 

FDA to follow the Sixth Circuit’s 

decision in Int’l Outdoor, Inc. v. City of 

Troy, 974 F.3d 690 (6th Cir. 2020), 

which the comment claimed held that 

all content-based speech restrictions are 

subject to strict scrutiny, even when the 

restrictions concern commercial speech. 

(Response) FDA declines that 

suggestion for several reasons. First, 

Int’l Outdoor—like Reed—involved 

review of a sign ordinance, which does 

not raise the same complex regulatory 

and public health issues as premarket 

review under the FD&C Act and PHS 

Act. Second, a holding that strict 

scrutiny applies to all content-based 

commercial speech would run contrary 

to the weight of circuit court authority 

discussed above, including the Second 

Circuit’s recent decision in Vugo, Inc. 

confirming that Central Hudson 

continues to govern review of 

commercial speech (see 931 F.3d at 50). 

Third, the Sixth Circuit in Int’l Outdoor 

did not actually hold that strict scrutiny 

applies to all content-based commercial 

speech; the Sixth Circuit distinguished 

Vugo on the ground that the Second 

Circuit case involved only commercial 

speech, where Int’l Outdoor involved 

both core and commercial speech (see 

974 F.3d at 705). 

(Comment 18) One comment asserted 

that FDA should not continue to rely on 

Wisconsin v. Mitchell and its progeny 

because the district court in Amarin 

Pharma, Inc. v. FDA, 119 F. Supp. 3d 

196 (S.D.N.Y. 2015) construed United 


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States v. Caronia, 703 F.3d 149 (2d Cir. 

2012) to foreclose that position. Another 

comment similarly argued that the 

NPRM understated the meaning and 

impact of Caronia. 

(Response) We disagree. As we 

explained in the NPRM, the Second 

Circuit has explicitly confirmed— 

contrary to the cited conclusion in 

Amarin—that Caronia ‘‘left open the 

government’s ability to prove 

misbranding on a theory that 

promotional speech provides evidence 

that a drug is intended for a use that is 

not included on the drug’s FDAapproved label.’’ United States ex rel. 

Polansky v. Pfizer, Inc., 822 F.3d 613 

n.2 (2d Cir. 2016). And the Second 

Circuit has more generally confirmed 

the continued viability of the Wisconsin 

v. Mitchell theory after Caronia, finding 

a First Amendment challenge to reliance 

on speech to show an element of 

violation ‘‘meritless’’ because ‘‘the 

speech is not ‘itself the proscribed 

conduct.’ ’’ United States v. Pierce, 785 

F.3d 832, 841 (2d Cir. 2015) (quoting 

Caronia, 703 F.3d at 161). It is also 

noteworthy that the first comment did 

not cite any case other than Amarin, a 

district court decision on a motion for 

a preliminary injunction, in support of 

its position limiting the application of 

Wisconsin v. Mitchell. Indeed, decisions 

from other circuits issued after Caronia 

have upheld the application of 

Wisconsin v. Mitchell in the context of 

the premarket review requirements of 

the FD&C Act (see Nicopure Labs, LLC 

v. FDA, 944 F.3d 267, 283 (D.C. Cir. 

2019); United States v. Lebeau, 654 Fed. 

App’x 826, 830–31 (7th Cir. 2016); 

United States v. Facteau, 2020 U.S. Dist. 

LEXIS 167169 (D. Mass. September 14, 

2020); United States v. Cole, 84 F. Supp. 

3d 1159, 1166 (D. Or. 2015)). 

E. Comments and Responses Regarding 

the Fifth Amendment 

(Comment 19) Some comments 

questioned the constitutionality of the 

intended use regulations and asserted 

that the Fifth Amendment requires that 

the boundaries between permissible and 

impermissible communications be 

clearly drawn, particularly with respect 

to matters involving speech. One 

comment criticized FDA’s reliance on 

guidance documents to describe its 

enforcement policies in this regard. 

(Response) While FDA agrees that 

laws must give a ‘‘person of ordinary 

intelligence a reasonable opportunity to 

know what is prohibited,’’ ‘‘meticulous 

specificity’’ is not required (see Grayned 

v. City of Rockford, 408 U.S. 104, 110 

(1972)). The Supreme Court has 

recognized that laws may embody 

‘‘flexibility and reasonable breadth’’ (see 

id.) and officials implementing them 

may ‘‘exercise considerable discretion’’ 

(see Ward v. Rock Against Racism, 491 

U.S. 781, 794 (1989)), without the laws 

being declared unconstitutionally 

vague. 

More specifically, the Supreme Court 

has held that ‘‘perfect clarity and 

precise guidance have never been 

required even of regulations that restrict 

expressive activity’’ (see Ward, 491 U.S. 

at 794 (citations omitted)). It is also well 

established that the use of an intent 

standard does not render a statute 

unconstitutionally vague (see United 

States v. Williams, 553 U.S. 285, 306 

(2008); Nat’l Ass’n of Manufacturers v. 

Taylor, 582 F.3d 1, 26 (D.C. Cir. 2009) 

(‘‘an intent standard is not per se vague, 

even in a statute regulating speech’’)). 

Indeed, ‘‘absent special circumstances 

not present here, there is no reason to 

conclude that the ‘every day’ task of 

assessing intent is inherently vague 

[even] when protected speech is 

involved’’ (see Taylor, 582 F.3d at 27). 

Moreover, courts have repeatedly 

rejected due process challenges to the 

FD&C Act as unconstitutionally vague 

or ambiguous. In United States v. 

Hohensee, 243 F.2d 367 (3d Cir. 1957), 

the Third Circuit rejected an 

unconstitutional vagueness challenge to 

provisions of the FD&C Act, which 

included the determination of intended 

use. In upholding the provisions, the 

court relied in part on the Supreme 

Court determination that the FD&C Act 

should ‘‘be given a liberal interpretation 

to effectuate its high purpose of 

protecting unwary consumers in vital 

matters of health’’ (see id. at 370; see 

also United States v. Sullivan, 332 U.S. 

689, 695 (1948) (rejecting due process 

challenge to FD&C Act and finding no 

ambiguity in the misbranding language); 

United States v. Caputo, 517 F.3d 935, 

941 (7th Cir, 2008) (rejecting argument 

that line between new and modified 

devices is too vague to be enforceable); 

V.E. Irons v. United States, 244 F.2d 34, 

45 (First Cir. 1957) (rejecting as 

‘‘untenable’’ the claim that the FD&C 

Act’s misdemeanor misbranding 

provisions are unconstitutionally vague 

and upholding misbranding conviction 

for distribution of vitamin and mineral 

products shown to be intended for use 

as drugs.); United States v. General 

Nutrition, Inc., 638 F. Supp. 556, 564 

(W.D.N.Y. 1986) (‘‘The Act on numerous 

occasions has been upheld against 

vagueness challenges . . . and this 

Court is unaware of any case holding 

any provision of the Act void for 

vagueness in any circumstance.’’) 

(citations omitted)). 

The first FDA regulation describing 

how ‘‘intended use’’ is determined was 

issued in 1952 (see 17 FR 6818, 6820 

(1952) (Ref. 1)), and there have been 

only minor amendments since that time, 

including those being made through this 

rulemaking. Over nearly seven decades, 

medical product manufacturers have 

shown little difficulty in understanding 

how the regulations are applied. And, as 

noted in the NPRM, FDA has issued 

several guidance documents that 

describe circumstances in which the 

Agency does not intend to object to a 

firm’s product communications or to 

view such communications as evidence 

of a new intended use (85 FR 59718 at 

59723). FDA issues these guidance 

documents to better inform stakeholders 

regarding its policies, and feedback from 

stakeholders has generally been 

positive. The NPRM also goes further 

than previous rulemakings related to 

these regulations in providing 

illustrative examples of types of 

evidence that would and would not be 

relevant to establishing intended use. 

Accordingly, we do not believe that the 

intended use regulations are 

unconstitutionally vague. 

F. Comments and Responses Regarding 

Definitions 

(Comment 20) Some comments 

suggested clarifying and defining the 

terms ‘‘intended use’’ and ‘‘indications 

for use’’ as these terms are used for 

devices in § 801.4. One comment 

suggested defining these terms by 

adopting definitions used in other FDA 

regulations and guidance documents. 

The comment also suggested clarifying 

the definitions of ‘‘intended use’’ and 

‘‘indications for use’’ as part of a 

substantial equivalence determination 

for a device and distinguishing these 

terms from the intended use regulations 

for drugs. 

(Response) FDA disagrees with these 

comments. The intended use 

regulations, including § 801.4, describe 

the types of evidence relevant to 

determining a product’s intended uses 

under the FD&C Act, the PHS Act, and 

FDA’s implementing regulations. The 

term ‘‘indications for use’’ is not used in 

this rulemaking and as such, FDA does 

not believe there is a need to define the 

term here. Further, FDA’s substantial 

equivalence determination during its 

review of a premarket notification is 

beyond the scope of this rulemaking. 

(Comment 21) Several comments 

suggested revising § 801.4 to expressly 

include devices that are legally 

marketed without approval or clearance, 

such as devices exempt from premarket 

notification and granted marketing 

authorization. Some comments asserted 

that the terms ‘‘approved or cleared 

medical products’’ and ‘‘approved or 


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cleared medical uses’’ do not include 

such legally marketed devices and asked 

FDA to modify these terms to include 

510(k)-exempt devices. One comment 

also suggested that FDA recognize how 

its review of drug and device labeling 

differ. 

(Response) FDA agrees with adding 

language to § 801.4 to clarify that the 

regulation applies to devices that are 

exempt from premarket notification and 

devices that are granted marketing 

authorization through De Novo 

classification. We are adding the phrase 

‘‘granted marketing authorization, or 

exempt from premarket notification’’ to 

the fourth sentence of § 801.4 to make 

this clarification. 

FDA declines to compare FDA’s 

review of drug and device labeling 

because such comparison is beyond the 

scope of this rulemaking. 

(Comment 22) Some comments 

suggested defining the terms 

‘‘unapproved new use for an approved 

or cleared’’ and ‘‘unapproved use of an 

approved product’’ in the codified. 

Another comment asserted that these 

terms were not consistently used 

throughout the preamble. 

(Response) We have included related 

terms and phrases in the definitions 

section of the preamble above to help 

clarify our use of these and similar 

phrases. We do not believe that it is 

necessary to include these definitions in 

the codified language. 

(Comment 23) Some comments 

requested FDA expressly include 

laboratorians in the definition of 

‘‘healthcare providers.’’ 

(Response) The term ‘‘healthcare 

provider’’ includes a non-exhaustive list 

of individuals who are licensed or 

otherwise authorized by the State to 

prescribe, order, administer, or use 

medical products in a professional 

capacity. In some cases, this may 

include such licensed or otherwise 

State-authorized individuals with 

certain roles in a laboratory. 

G. Comments and Responses Regarding 

‘‘Safe Harbors’’ 

(Comment 24) A number of comments 

suggested modifications to FDA policies 

that the comments sometimes refer to as 

‘‘safe harbors’’ for certain kinds of 

medical product communications. Some 

comments suggested the establishment 

of a ‘‘safe harbor’’ for scientific 

exchange, whereby scientific exchange 

would be excluded from determinations 

of intended use. Other comments 

suggested the creation of ‘‘safe harbors’’ 

for other types of communications, 

including discussions with healthcare 

providers about investigational uses, 

discussions held in the course of 

providing training or demonstrations to 

healthcare providers, market research 

about unapproved uses, and 

communications related to the 

collection of postmarket data. Another 

comment urged that FDA ‘‘codify in 

binding regulations its policies 

regarding manufacturer communication 

of scientific and medical information,’’ 

noting that guidance documents are not 

binding on enforcement authorities 

including the Department of Justice. 

(Response) FDA welcomes and will 

continue to consider these comments 

related to ‘‘safe harbors.’’ However, the 

recommendations made in these 

comments go beyond the scope of this 

rulemaking, which is ‘‘to conform 

§§ 201.128 and 801.4 to reflect how the 

Agency currently applies them to drugs 

and devices,’’ 80 FR 57756 (2015). This 

rule, as proposed and as finalized, does 

not reflect a change in FDA’s policies 

and practices regarding the types of firm 

communications that ordinarily would 

not, on their own, establish a new 

intended use. Expanding the scope of 

this rule to codify FDA’s acknowledged 

‘‘safe harbors’’ or to acknowledge 

additional ‘‘safe harbors,’’ as suggested 

in these comments, might warrant 

reproposing the rule to solicit additional 

input, unduly delaying the Agency’s 

clarification of its regulations on 

intended use. Therefore, while FDA will 

continue to consider the issues raised by 

these comments, the Agency declines 

the present suggestions to modify its 

acknowledged ‘‘safe harbors’’ or codify 

them in the intended use regulation. 

With regard to the suggestion that the 

Agency establish a ‘‘safe harbor’’ for 

scientific exchange, whereby scientific 

exchange would be excluded from 

determinations of intended use: the 

Agency notes that if all scientific 

exchange were excluded from 

determinations of intended use, 

companies might have an incentive to 

create and promote new intended uses 

for marketed products based on 

incomplete or otherwise flawed data. 

That outcome would not serve the 

public health. At the same time, FDA 

recognizes the importance of scientific 

exchange, including information 

regarding unapproved uses of products 

that healthcare providers may choose to 

take into account when making 

professional judgments regarding the 

use of medical products that are 

approved, cleared, granted marketing 

authorization, or exempted from 

premarket notification. Balancing these 

public health considerations, some of 

which are in tension with each other, is 

a complex and important task. FDA 

believes this rulemaking, the purpose of 

which is to finalize amendments to the 

intended use regulations, is not the 

appropriate forum to resolve separate 

questions relating to scientific exchange. 

As noted in the NPRM, FDA has issued 

several guidance documents that 

describe circumstances in which the 

Agency does not intend to object to a 

firm’s medical product communications 

or to view such communications as 

evidence of a new intended use. See 85 

FR 59718 at 59723 n.7. This final rule 

does not disturb any of FDA’s 

acknowledged ‘‘safe harbors,’’ including 

those that encompass various types of 

scientific exchange. In addition, as 

discussed in the preamble to the 

proposed rule, a firm’s knowledge of 

off-label use plus safe-harbored 

communication would not, without 

more, be determinative of a new 

intended use. See 85 FR 59718 at 59725. 

H. Comments and Responses Regarding 

Examples 

(Comment 25) One comment requests 

that FDA clarify, consistent with the 

Government’s brief filed in Par 

Pharmaceutical Inc. v. United States, 

1:11-cv-01820 (D.D.C.), that the example 

of ‘‘repeated proactive detailing’’ in the 

preamble to the proposed rule would 

not create a new intended use if the 

firm’s communications with the 

healthcare professionals are consistent 

with the approved labeling. 

(Response) FDA declines the 

suggestion because FDA does not 

believe the proposed clarification is 

warranted. As explained in the 

preamble, the revisions to the intended 

use regulations do not reflect a change 

in FDA’s policies and practices, 

including as articulated in various 

guidance documents, regarding the 

types of firm communications that 

ordinarily would not, on their own, 

establish the firm’s intent that a medical 

product that is approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification 

be used for an unapproved use (see 85 

FR 59718 at 59723). The NPRM 

references guidance documents 

including FDA Guidance for Industry, 

‘‘Medical Product Communications That 

Are Consistent With the FDA-Required 

Labeling—Questions and Answers,’’ 

June 2018 (see id. Ref. 5). As explained 

in that guidance, FDA does not intend 

to rely exclusively on a firm’s 

communication of information that is 

consistent with a medical product’s 

FDA-required labeling to establish a 

new intended use. The example in the 

NPRM, however, describes a 

circumstance involving a patient 

population that does not fall within the 

product’s approved population (see 85 

FR 59718 at 59725) and, to the extent 


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3As described in the preamble to the proposed 

rule, these types of evidence include express claims 

and representations; implied claims; product 

characteristics and design; and the circumstances of 

the product’s sale or distribution (see 85 FR 59718 

at 59725). In fulfilling its mission to protect the 

public health, FDA will evaluate the individual and 

unique circumstances of each case in determining 

a product’s intended use. In some cases, a single 

piece of evidence may be dispositive of a product’s 

intended use. In others, several elements combined 

may establish a product’s intended use. 

the communication relates to a patient 

population outside the approved patient 

population reflected in the FDArequired labeling, the communication 

may not be considered consistent with 

the approved labeling. The Par brief 

cited in the comment confirms that a 

manufacturer’s communication of 

information regarding an approved use 

to a physician whose patients do not fall 

within the product’s approved 

population would not by itself establish 

a new intended use, but may be relevant 

together with other evidence in 

establishing the manufacturer’s intent to 

distribute the product for an 

unapproved use (Ref. 3 at 17–18). 

(Comment 26) Several comments 

requested modification to or 

clarification of the examples provided 

in section V.C. of the preamble to the 

proposed rule. 

(Response) We decline to make the 

requested modifications to the 

examples. These examples were 

provided to illustrate evidence that, 

standing alone, would not be 

determinative of intended use, and they 

remain illustrative of that point. 

Although one comment suggested that 

the examples caused further confusion, 

most commenters indicated that the 

examples were helpful and encouraged 

FDA to offer additional examples. We 

continue to believe the examples 

provided in the preamble to the NPRM 

are helpful, and we are providing 

additional examples below. The list of 

examples in the proposed rule is not 

intended to be comprehensive or 

restrictive. Each scenario described in 

the preamble is fact-specific, and, under 

other circumstances or in other 

contexts, similar material may be 

evaluated differently. 

(Comment 27) Several comments 

requested that FDA describe the 

intended use framework from the device 

industry perspective and provide 

additional device-specific examples. 

(Response) The examples FDA 

provided in the preamble to the 

proposed rule were provided for 

illustrative purposes only and were not 

intended to be comprehensive or 

restrictive. In our responses to 

comments 7, 8, and 9 in this final rule 

preamble, we have provided additional 

examples of types of evidence 3 related 

to product design and composition that 

may be relevant when determining a 

medical device’s intended use. Those 

examples describe evidence that may be 

relevant, but is not necessarily 

determinative, to establishing intended 

use. 

To further clarify this regulation as it 

applies to devices, we are providing 

here additional device-specific 

examples of types of evidence that may 

be relevant, but are not necessarily 

determinative, in establishing intended 

use. As with the examples in the 

preamble to the proposed rule, the 

following examples are fact-specific and 

are provided for illustrative purposes 

only. 

• Marketing a medical device with a 

name that implies a use to affect a 

particular organ or system of the body. 

Example: ‘‘CardioCalm.’’ 

• Designing a non-vascular stent with 

a coating clinically known to change 

calcification of blood vessels. 

• Marketing a device that uses 

ultrasonic waves as a therapeutic 

massager, despite the fact that ultrasonic 

waves do not physically massage tissue 

but rather affect the underlying tissue 

through a sonic mechanism. 

I. Comments on Codified Text and FDA 

Responses 

(Comment 28) In the NPRM, FDA 

proposed to amend §§ 201.128 and 

801.4 to provide that a firm would not 

be regarded as intending an unapproved 

new use for an approved drug or for a 

device approved, cleared, granted 

marketing authorization, or exempted 

from premarket notification based solely 

on that firm’s knowledge that such drug 

or device was being prescribed or used 

by healthcare providers for such use. 

One commenter argued that FDA should 

delete ‘‘solely’’ from the regulations on 

intended use because this phrasing 

suggests that a firm’s knowledge of 

unapproved use could be used in 

combination with other factors to 

determine the intended use of a 

product. Another commenter suggested 

that FDA should replace ‘‘solely’’ with 

a term that would clarify that such 

knowledge would be relevant only if 

such use is widespread and if a 

company’s promotional activities are a 

primary reason for this widespread offlabel use. This commenter also 

maintained that the final rule should be 

clear that only activities that are, at their 

core, promotional should be relevant for 

determining intended use. 

(Response) FDA disagrees with these 

comments. The use of the word ‘‘solely’’ 

in §§ 201.128 and 801.4 is intended to 

convey that FDA does not intend to 

consider a firm’s knowledge that a 

healthcare provider has used or 

prescribed the firm’s medical product 

that has been approved, cleared, granted 

marketing authorization, or is exempt 

from 510(k) for an unapproved use, by 

itself, as sufficient to establish intended 

use. The removal of the word ‘‘solely’’ 

from the regulation and the suggestion 

that FDA consider only activities that 

are fundamentally promotional in 

determining intended use would be 

inconsistent with the Agency’s 

longstanding position that determining 

a product’s intended use is a factspecific inquiry and that FDA may 

consider all relevant sources of 

evidence. These sources of evidence 

may include a firm’s knowledge that a 

healthcare provider has used or 

prescribed the firm’s medical product 

that is approved, cleared, granted 

marketing authorization, or exempted 

from premarket notification for an 

unapproved use, and may include 

activities that are not strictly 

promotional in nature. In short, direct 

promotion of the use is not necessary to 

establish intended use. 

(Comment 29) One comment asked 

FDA to change ‘‘article’’ to ‘‘device’’ 

throughout § 801.4. 

(Response) FDA disagrees with this 

suggestion. The use of the term ‘‘article’’ 

in §§ 201.128 and 801.4 is consistent 

with the use of that term in section 201 

of the FD&C Act. 

(Comment 30) A comment suggested 

deleting the phrase ‘‘or used’’ from the 

fourth sentence of § 801.4, asserting that 

a healthcare provider’s use is not 

‘‘under the control of the firm.’’ 

(Response) FDA disagrees with the 

comment’s suggestion because, although 

the healthcare provider’s use is not 

under the firm’s control, what may be 

relevant to intended use is the firm’s 

knowledge that the article is being used 

by the healthcare provider. As discussed 

above, both legislative history and the 

case law support reliance on actual use 

by healthcare providers as relevant to 

intended use. See, e.g., United States v. 

An Article of Device Toftness Radiation 

Detector, 731 F.2d 1253, 1257 (7th Cir. 

1984); United States v. 22 Rectangular 

or Cylindrical Finished Devices, 714 F. 

Supp. 1159, 1165 (D. Utah 1989); United 

States v. Device Labeled ‘‘Cameron 

Spitler Amblyo-Syntonizer,’’ 261 F. 

Supp. 243, 245 (D. Neb. 1966); H.R. Rep. 

No. 853, 94th Cong., 2d Sess. 14 (1976). 

However, a firm’s knowledge that 

healthcare providers are prescribing or 

using its product that has been 

approved, cleared, granted marketing 

authorization, or is 510(k)-exempt for an 


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4FDA generally does not seek to interfere with 

the exercise of the professional judgment of 

healthcare providers in prescribing or using, for 

unapproved uses for individual patients, most 

legally marketed medical products. This 

longstanding position has been codified with 

respect to devices (see 21 U.S.C. 396). Although 

FDA generally does not seek to interfere with the 

exercise of the professional judgment of 

veterinarians, certain unapproved uses of drugs in 

animals are not permitted (see section 512(a)(4) and 

(5)) of the FD&C Act (21 U.S.C. 360b(a)(4) and (5) 

and 21 CFR part 530) and result in the drug being 

deemed ‘‘unsafe’’ and therefore adulterated under 

sections 512 and 501(a)(5) (21 U.S.C. 351(a)(5)) of 

the FD&C Act. 

5See 21 U.S.C. 331(d), 351(f), 352(f)(1), 355(a). 

The position described in the text does not apply 

to products that are not already legally marketed as 

medical products for at least one use. Similarly, 

nothing in this regulation or preamble is intended 

to impact the application of 21 U.S.C. 333(e), 

which, subject to limited exceptions, penalizes 

anyone who ‘‘knowingly distributes, or possesses 

with intent to distribute, human growth hormone 

for any use in humans other than the treatment of 

disease or other recognized medical conditions, 

where such use has been authorized by the 

Secretary of Health and Human Services under 

section 505 and pursuant to the order of a 

physician.’’ Further, Congress or the Agency could 

promulgate other provisions regarding specific 

products or classes of medical products that 

recognize knowledge as sufficient evidence of a 

particular element of a prohibited act. 

unapproved use would not, by itself, 

automatically trigger an obligation to 

provide labeling for that unapproved 

use. 

(Comment 31) One comment 

suggested that FDA explain how § 801.4 

applies to modifications of 510(k)- 

cleared devices. 

(Response) FDA declines to adopt this 

suggestion because it is beyond the 

scope of this rulemaking. 

(Comment 32) One comment stated 

that section 513(i)(1)(E) of the FD&C Act 

(21 U.S.C. 360c(i)(1)(E)) constrains how 

FDA ‘‘responds to an intended use not 

reflected in device labeling when 

reviewing a 510(k)’’ and that FDA 

‘‘cannot require that the company obtain 

clearance or approval of another 

potential unapproved use.’’ The 

comment also suggested FDA 

disassociate intended use regulations for 

devices from drugs and add a reference 

to section 513(i)(1)(E) of the FD&C Act 

in the codified text of § 801.4. 

(Response) FDA’s application of 

section 513(i)(1)(E) of the FD&C Act is 

beyond the scope of this rulemaking. 

J. Comments Recommending That FDA 

Expand the Scope of This Rulemaking 

(Comment 33) A number of comments 

urged FDA to expand this rulemaking 

beyond the scope of the proposed rule. 

For example, one comment urged FDA 

to ‘‘complete its long-promised 

‘comprehensive review’ of regulations to 

assess alignment with constitutional 

and statutory requirements.’’ Another 

comment proposed that FDA adopt a 

regulatory approach to manufacturer 

speech consistent with the ‘‘Principles 

on Responsible Sharing of Truthful and 

NonMisleading Information About 

Medicines with Health Care 

Professionals and Payers’’ developed by 

Pharmaceutical Research and 

Manufacturers of America and the 

Biotechnology Innovation Organization. 

(Response) Although FDA welcomes 

the submission of ideas regarding a 

broader list of suggested policy changes, 

we decline to adopt the suggestions in 

these comments because they are 

beyond the scope of this rulemaking. 

Expanding the scope of this rule as 

suggested in these comments would 

potentially delay FDA’s clarification of 

its regulations on intended use. FDA has 

been engaged in a continuing review of 

regulations and policies regarding 

communications with healthcare 

providers and payors (and other similar 

entities with knowledge and expertise 

in healthcare economic analysis) 

regarding medical products, and has 

taken other initiatives as part of that 

effort. 

(Comment 34) One comment 

contended that the regulatory 

requirements for premarket approval 

and authorization are too burdensome 

so that it is unreasonable to require that 

manufacturers conduct studies and 

submit applications for every intended 

use. 

(Response) This comment also raises 

issues that are different from and 

beyond the scope of this rulemaking. To 

the extent this comment is suggesting 

that the best way to address complex 

questions concerning premarket 

authorization is through limiting the 

scope of intended use, we disagree that 

this is an appropriate tool. 

(Comment 35) One comment 

requested that FDA acknowledge that 

healthcare providers may prescribe and 

use approved/cleared medical products 

for unapproved uses when they judge 

that the unapproved use is medically 

appropriate for their patients and that 

manufacturers are not required to 

confirm the nature of a healthcare 

provider’s planned use for an approved 

medical product before distributing 

such product to the healthcare provider. 

(Response) Healthcare providers 

prescribe or use medical products that 

are approved, cleared, granted 

marketing authorization, or exempted 

from premarket notification for 

unapproved uses based on their medical 

judgment regarding any potential 

benefits and risks of the unapproved use 

for their individual patients.4 In these 

limited circumstances, FDA’s 

longstanding position is that the Agency 

does not consider a firm’s knowledge 

that a healthcare provider has used or 

prescribed its medical product that is 

approved, cleared, granted marketing 

authorization, or exempted from 

premarket notification for an 

unapproved use, by itself, as sufficient 

to establish the intended use element of 

a prohibited act based on failing to meet 

applicable premarket requirements for 

that use or failing to provide adequate 

directions for use.5

VI. Effective Date 

This final rule will become effective 

30 days after the date of its publication 

in the Federal Register. 

VII. Economic Analysis of Impacts 

A. Introduction and Summary 

1. Introduction 

We have examined the impacts of the 

final rule under Executive Order 12866, 

Executive Order 13563, the Regulatory 

Flexibility Act (5 U.S.C. 601–612), and 

the Unfunded Mandates Reform Act of 

1995 (Pub. L. 104–4). Executive Orders 

12866 and 13563 direct us to assess all 

costs and benefits of available regulatory 

alternatives and, when regulation is 

necessary, to select regulatory 

approaches that maximize net benefits 

(including potential economic, 

environmental, public health and safety, 

and other advantages; distributive 

impacts; and equity). This final rule is 

not a significant regulatory action as 

defined by Executive Order 12866. 

The Regulatory Flexibility Act 

requires us to analyze regulatory options 

that would minimize any significant 

impact of a rule on small entities. We 

cannot predict how many companies 

may revise labeling, advertising, or 

other materials, or otherwise modify 

their behavior, following issuance of 

this rule. However, this rule would 

merely clarify, but not change, the types 

of evidence relevant to determining 

manufacturers’ intended use of 

products. Because the rule would not 

extend FDA’s authority to additional 

products or impose any additional 

requirements on currently regulated 

products, we expect the rule will 

impose negligible costs, if any. As a 

result, we certify that the final rule will 

not have a significant economic impact 

on a substantial number of small 

entities. 

The Unfunded Mandates Reform Act 

of 1995 (section 202(a)) requires us to 

prepare a written statement, which 

includes an assessment of anticipated 

costs and benefits, before proposing 

‘‘any rule that includes any Federal 


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mandate that may result in the 

expenditure by State, local, and tribal 

governments, in the aggregate, or by the 

private sector, of $100,000,000 or more 

(adjusted annually for inflation) in any 

one year.’’ The current threshold after 

adjustment for inflation is $158 million, 

using the most current (2020) Implicit 

Price Deflator for the Gross Domestic 

Product. This final rule would not result 

in an expenditure in any year that meets 

or exceeds this amount. 

2. Summary of Costs and Benefits 

The final rule clarifies but does not 

change FDA’s interpretation and 

application of existing intended use 

regulations for medical products. 

The benefits of this rule are additional 

clarity and certainty for manufacturers 

and stakeholders regarding evidence 

that is relevant in evaluating whether an 

article is intended for use as a drug or 

device. 

This final rule is not expected to 

impose any significant additional costs 

on firms. Although this rule may impact 

firms’ future marketing, product 

development, and communication 

strategies, firms are not required to 

make any changes to labeling, marketing 

materials, or operating procedures. 

Additionally, this rule does not extend 

FDA’s jurisdiction to any new products. 

TABLE 1—SUMMARY OF BENEFITS, COSTS, AND DISTRIBUTIONAL EFFECTS OF FINAL RULE

Category Primary 

estimate 

Low 

estimate 

High 

estimate 

Units 

Notes Year 

dollars 

Discount 

rate 

(%) 

Period 

covered 

Benefits: 

Annualized Monetized $millions/year .............................................. .................. .................. .................. .................. 7 ..................

.................. .................. .................. .................. 3 ..................

Annualized Quantified ...................................................................... .................. .................. .................. .................. 7 ..................

.................. .................. .................. .................. 3 ..................

Qualitative ........................................................................................ Clarification of intended use 

interpretation and application 

Costs: 

Annualized Monetized $millions/year .............................................. .................. .................. .................. .................. 7 ..................

.................. .................. .................. .................. 3 ..................

Annualized Quantified ...................................................................... .................. .................. .................. .................. 7 ..................

.................. .................. .................. .................. 3 ..................

Qualitative ........................................................................................ Negligible costs, if any 

Transfers: 

Federal Annualized Monetized $millions/year ................................. .................. .................. .................. .................. 7 ..................

.................. .................. .................. .................. 3 ..................

From/To ............................................................................................ From: To: 

Other Annualized Monetized $millions/year .................................... .................. .................. .................. .................. 7 ..................

.................. .................. .................. .................. 3 ..................

From/To ............................................................................................ From: To: 

Effects: 

State, Local or Tribal Government: None. 

Small Business: None. 

Wages: None. 

Growth: None. 

3. Comments on the Preliminary 

Economic Analysis of Impacts and Our 

Response 

We did not receive any comments on 

the Preliminary Economic Analysis of 

Impacts. 

4. Summary of Changes 

We have made no significant changes 

from the Preliminary Economic 

Analysis of Impacts. 

B. Final Economic Analysis of Impacts 

1. Background 

This rule clarifies FDA’s longstanding 

position that the intended use of a drug 

or device product can be based on any 

relevant source of evidence by 

describing types of evidence relevant to 

the intended use of a product and types 

of evidence that, standing alone, are not 

determinative of intended use. 

One important clarification involves a 

manufacturer’s knowledge of 

unapproved uses of its approved 

product. Current versions of §§ 201.128 

and 801.4 specify that a manufacturer of 

a drug (§ 201.128) or device (§ 801.4) 

must include adequate labeling if it 

knows its product is used for an 

unapproved purpose. The September 

2015 proposed rule (80 FR 57756 at 

57764) removed the sentence regarding 

the requirement to provide adequate 

labeling if a firm knows its product is 

being used for an unapproved use. The 

amended January 2017 final rule (82 FR 

2193 at 2217) was intended to clarify 

FDA’s position by requiring 

manufacturers to include adequate 

labeling ‘‘if the totality of the evidence 

establishes that a manufacturer 

objectively intends that a drug 

introduced into interstate commerce by 

him is to be used for conditions, 

purposes, or uses other than ones for 

which it is approved (if any).’’ 

In the Federal Register of February 7, 

2017 (82 FR 9501), FDA delayed the 

effective date of the January 2017 final 

rule until March 2017. In February 

2017, various industry organizations 

filed a petition raising concerns with the 

January 2017 final rule, requesting 

reconsideration and a stay. The petition 

requested that FDA reconsider the 

amendments to the ‘‘intended use’’ 

regulations and issue a new final rule 

that, with respect to the intended use 

regulations at §§ 201.128 and 801.4, 

reverted to the language of the 

September 2015 proposed rule. The 


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41400 Federal Register / Vol. 86, No. 145 / Monday, August 2, 2021 / Rules and Regulations 

petition also requested that FDA 

indefinitely stay the rule because 

petitioners argued that the final rule was 

issued in violation of the fair notice 

requirement under the Administrative 

Procedure Act and that the ‘‘totality of 

the evidence’’ language in the 2017 final 

rule was a new and unsupported legal 

standard. 

In the Federal Register of March 20, 

2017 (82 FR 14319), FDA further 

delayed the effective date of the final 

rule until March 2018 and opened the 

docket for additional public comment. 

Following some comments supporting 

the delay and proposing specific 

changes to the language in §§ 201.128 

and 801.4, on March 16, 2018 (83 FR 

11639), FDA delayed the amendments 

to §§ 201.128 and 801.4 until further 

notice. This final rule adopts the general 

approach set forth in the September 

2015 proposed rule by deleting the final 

sentence; the final rule also clarifies 

FDA’s interpretation and application of 

evidence relevant to determining 

intended use. 

2. Benefits of the Final Rule 

The final rule clarifies FDA’s existing 

interpretation of the determination of 

the intended use of drugs and devices. 

This clarification should reduce 

manufacturer and stakeholder 

uncertainty regarding the scenarios in 

which specific types of evidence may or 

may not show a product is intended for 

a drug or device use. The removal of the 

final sentence in §§ 201.128 and 801.4 

and the inclusion of new clarifying 

clauses (‘‘provided, however, that a firm 

would not be regarded as intending an 

unapproved new use for [a medical 

product that is approved, cleared, 

granted marketing authorization, or 

exempted from premarket notification] 

based solely on that firm’s knowledge 

that such [product] was being 

prescribed or used by health care 

providers for such use’’) resolve 

questions about whether manufacturers 

need to think about developing an 

action plan or strategy related to a 

potential new intended use of their 

medical products that are approved, 

cleared, granted marketing 

authorization, or exempted from 

premarket notification simply because a 

manufacturer has knowledge of 

unapproved uses of these products by 

third parties. We believe this 

clarification is the benefit of the final 

rule. 

3. Costs of the Final Rule 

The final rule is not expected to 

impose significant additional costs on 

manufacturers and distributors of FDAregulated products. The final rule does 

not extend FDA’s regulatory authority to 

any new or additional products, nor 

does the rule change the current 

approach to evaluating intended use or 

impose any additional requirements on 

manufacturers or distributors. We do 

not have any reason to believe firms will 

change their marketing or operating 

procedures as a result of this rule. We 

do not have evidence that this final rule 

would impose costs on currently 

marketed products. 

C. Final Small Entity Analysis 

In table 2, we describe the Small 

Business Administration’s size 

thresholds for industries affected by the 

final rule. Based on U.S. Census data, at 

least 22.9 percent of businesses in 

NAICS code 21323 (Tobacco 

Manufacturing) are considered small; at 

least 17.5 percent of businesses in 

NAICS code 32541 (Pharmaceutical and 

Medicine Manufacturing) are 

considered small; and at least 32.6 

percent of businesses in NAICS code 

33911 (Medical Equipment and 

Supplies Manufacturing) are considered 

small. Because the final rule is not 

expected to impose costs on 

manufacturers or distributors of FDAregulated products, the final rule is also 

not expected to impose costs on small 

entities. Therefore, we certify that the 

final rule will not have a significant 

economic impact on a substantial 

number of small entities. 

TABLE 2—SMALL BUSINESS ADMINISTRATION SIZE STANDARDS FOR AFFECTED INDUSTRIES

NAICS code Industry description Small business threshold 

312230 .............. Tobacco Manufacturing ...................................... Fewer than 1,500 Employees. 

325411 .............. Medicinal and Botanical Manufacturing ............. Fewer than 1,000 Employees. 

325412 .............. Pharmaceutical Preparation Manufacturing ....... Fewer than 1,250 Employees. 

325413 .............. In-vitro Diagnostic Substance Manufacturing ..... Fewer than 1,250 Employees. 

325414 .............. Biological Product (except Diagnostic) Manufacturing.Fewer than 1,250 Employees. 

339112 .............. Surgical and Medical Instrument Manufacturing Fewer than 1,000 Employees. 

339113 .............. Surgical Appliance and Supplies Manufacturing Fewer than 750 Employees. 

339114 .............. Dental Equipment and Supplies Manufacturing Fewer than 750 Employees. 

339115 .............. Ophthalmic Goods Manufacturing ...................... Fewer than 1,000 Employees. 

339116 .............. Dental Laboratories ............................................ Fewer than 500 Employees. 

VIII. Analysis of Environmental Impact 

We have determined under 21 CFR 

25.30(h), (i), and (k) that this action is 

of a type that does not individually or 

cumulatively have a significant effect on 

the human environment. Therefore, 

neither an environmental assessment 

nor an environmental impact statement 

is required. 

IX. Paperwork Reduction Act of 1995 

This final rule contains no collection 

of information. Therefore, clearance by 

the Office of Management and Budget 

under the Paperwork Reduction Act of 

1995 is not required. 

X. Federalism 

We have analyzed this final rule in 

accordance with the principles set forth 

in Executive Order 13132. FDA has 

determined that the rule does not 

contain policies that have substantial 

direct effects on the States, on the 

relationship between the National 

Government and the States, or on the 

distribution of power and 

responsibilities among the various 

levels of government. Accordingly, we 

conclude that the rule does not contain 

policies that have federalism 

implications as defined in the Executive 

order and, consequently, a federalism 

summary impact statement is not 

required. 

XI. Consultation and Coordination With 

Indian Tribal Governments 

We have analyzed this rule in 

accordance with the principles set forth 

in Executive Order 13175. We have 

determined that the rule does not 

contain policies that have substantial 

direct effects on one or more Indian 

Tribes, on the relationship between the 

Federal Government and Indian Tribes, 

or on the distribution of power and 

responsibilities between the Federal 


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Government and Indian Tribes. 

Accordingly, we conclude that the rule 

does not contain policies that have 

tribal implications as defined in the 

Executive Order and, consequently, a 

tribal summary impact statement is not 

required. 

XII. References 

The following references are on 

display at the Dockets Management Staff 

(see ADDRESSES) and are available for 

viewing by interested persons between 

9 a.m. and 4 p.m., Monday through 

Friday; they are also available 

electronically at https://

www.regulations.gov. FDA has verified 

the website addresses, as of the date this 

document publishes in the Federal 

Register, but websites are subject to 

change over time. 

1. Regulations for the Enforcement of the 

Federal Food, Drug, and Cosmetic Act, 

17 FR 6818, 6820 (1952). 

2. U.S. Department of Justice, U.S. Attorney’s 

Office, Northern District of Georgia, 

‘‘Five Defendants Charged With Illegally 

Importing Male Enhancement Products,’’ 

May 29, 2014 (available at https://

www.justice.gov/usao-ndga/pr/fivedefendants-charged-illegally-importingmale-enhancement-products). 

3. Defendants’ Memorandum in Support of 

Motion to Dismiss or for Summary 

Judgment and in Opposition to Motion 

for Preliminary Injunction at 8, Par 

Pharmaceutical Inc. v. United States, 

1:11–cv–01820 (D.D.C. December 23, 

2011). 

4. Defendants’ Memorandum of Points and 

Authorities in Support of Motion to 

Dismiss or for Summary Judgment at 

8–9 n.5, Allergan Inc. v. United States, 

1:09–cv–01879–JDB, (D.D.C. January 11, 

2010). 

5. Plaintiff’s Motion for Summary Judgment 

at 20–26, United States v. Undetermined 

Quantities of Articles of Drug, Street 

Drug Alternatives, Identified in 

Attachment A, et al., Civil No. AW–00– 

1687 (D. Md. January 12, 2001). 

6. Government Trial Memorandum at 6, 

United States v. Teiman, Criminal No: 

7:00CR00054 (W.D. Va. September 29, 

2000). 

7. Letter from Steven B. Barber, District 

Director, Cincinnati District, FDA to 

Marc C. Sanchez, Esq., Mood and Mind, 

LLC, at 9–10 (April 6, 2017). 

8. Letter from Margaret M. Dotzel, Assoc. 

Commissioner for Policy, FDA to Daniel 

J. Popeo and Richard A. Samp, Wash. 

Legal Found., at 6, Docket No. 01P–0250 

(January 28, 2002). 

9. Letter from Ann Simoneau, J.D., Director, 

Office of Compliance and Enforcement, 

Center for Tobacco Products and Donald 

D. Ashley, J.D., Director, Office of 

Compliance, Center for Drug Evaluation 

and Research, FDA to HelloCig 

Electronic Technology Co., Ltd (October 

11, 2018). 

10. Letter from Ramon A. Hernandez, 

Director, San Juan District Office and 

Program Division Director, Office of 

Human and Animal Food Operations, 

Division IV East, FDA, to Ricardo MayoAlvarez, Duy Drugs, Inc. (August 28, 

2018). 

11. Letter from Daniel Solis, Director, Import 

Operations Branch, Los Angeles District 

to Carol A. Pratt, K&L Gates LLP 

(December 3, 2012). 

12. Letter from Alonza E. Cruse, District 

Director, Los Angeles District, FDA to 

Richard Carieri, Lifetech Resources Labs 

Inc. (April 18, 2011). 

13. Letter from Ronald M. Pace, District 

Director, New York District, FDA to Peter 

Erlikh, INZ Distributors, Inc. (August 23, 

2010). 

14. U.S. Department of Justice, ‘‘December 2, 

2016: Woman Arrested for Injecting 

Adulter[at]ed Liquid Silicone,’’ accessed 

December 23, 2020, https://

www.justice.gov/usao-pr/pr/womanarrested-injecting-adultered-liquidsilicone. 

15. U.S. Department of Justice, 2018, ‘‘March 

2, 2018: Woman Sentenced for Injecting 

Adulterated Liquid Silicone,’’ accessed 

December 23, 2020, https://

www.justice.gov/usao-pr/pr/womansentenced-injecting-adulterated-liquidsilicone. 

16. Robertson, C.T. ‘‘When Truth Cannot be 

Presumed: The Regulation of Drug 

Promotion Under An Expanding First 

Amendment,’’ 94 B.U.L. REV. 545, 549– 

50 (2014). 

17. Memorandum: Public Health Interests 

and First Amendment Considerations 

Related to Manufacturer 

Communications Regarding Unapproved 

Uses of Approved or Cleared Medical 

Products (January 2017) (available at 

https://www.regulations.gov/ 

document?D=FDA-2016-N-1149-0040). 

List of Subjects 

21 CFR Part 201 

Drugs, Labeling, Reporting and 

recordkeeping requirements. 

21 CFR Part 801 

Labeling, Medical devices, Reporting 

and recordkeeping requirements. 

Therefore, under the Federal Food, 

Drug, and Cosmetic Act, 21 CFR parts 

201 and 801 are amended as follows: 

PART 201—LABELING 

■ 1. The authority citation for part 201 

is revised to read as follows: 

Authority: 21 U.S.C. 321, 331, 343, 351, 

352, 353, 355, 358, 360, 360b, 360ccc, 

360ccc–1, 360ee, 360gg–360ss, 371, 374, 

379e; 42 U.S.C. 216, 241, 262, 264. 

■ 2. Revise § 201.128 to read as follows: 

§ 201.128 Meaning of intended uses. 

The words intended uses or words of 

similar import in §§ 201.5, 201.115, 

201.117, 201.119, 201.120, 201.122, and 

1100.5 of this chapter refer to the 

objective intent of the persons legally 

responsible for the labeling of an article 

(or their representatives). The intent 

may be shown by such persons’ 

expressions, the design or composition 

of the article, or by the circumstances 

surrounding the distribution of the 

article. This objective intent may, for 

example, be shown by labeling claims, 

advertising matter, or oral or written 

statements by such persons or their 

representatives. Objective intent may be 

shown, for example, by circumstances 

in which the article is, with the 

knowledge of such persons or their 

representatives, offered or used for a 

purpose for which it is neither labeled 

nor advertised; provided, however, that 

a firm would not be regarded as 

intending an unapproved new use for an 

approved drug based solely on that 

firm’s knowledge that such drug was 

being prescribed or used by health care 

providers for such use. The intended 

uses of an article may change after it has 

been introduced into interstate 

commerce by its manufacturer. If, for 

example, a packer, distributor, or seller 

intends an article for different uses than 

those intended by the person from 

whom he or she received the article, 

such packer, distributor, or seller is 

required to supply adequate labeling in 

accordance with the new intended uses. 

PART 801—LABELING 

■ 3. The authority citation for part 801 

continues to read as follows: 

Authority: 21 U.S.C. 321, 331, 351, 352, 

360d, 360i, 360j, 371, 374. 

■ 4. Revise § 801.4 to read as follows: 

§ 801.4 Meaning of intended uses. 

The words intended uses or words of 

similar import in §§ 801.5, 801.119, 

801.122, and 1100.5 of this chapter refer 

to the objective intent of the persons 

legally responsible for the labeling of an 

article (or their representatives). The 

intent may be shown by such persons’ 

expressions, the design or composition 

of the article, or by the circumstances 

surrounding the distribution of the 

article. This objective intent may, for 

example, be shown by labeling claims, 

advertising matter, or oral or written 

statements by such persons or their 

representatives. Objective intent may be 

shown, for example, by circumstances 

in which the article is, with the 

knowledge of such persons or their 

representatives, offered or used for a 

purpose for which it is neither labeled 

nor advertised; provided, however, that 

a firm would not be regarded as 

intending an unapproved new use for a 

device approved, cleared, granted 

marketing authorization, or exempted 

from premarket notification based solely 


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on that firm’s knowledge that such 

device was being prescribed or used by 

health care providers for such use. The 

intended uses of an article may change 

after it has been introduced into 

interstate commerce by its 

manufacturer. If, for example, a packer, 

distributor, or seller intends an article 

for different uses than those intended by 

the person from whom he or she 

received the article, such packer, 

distributor, or seller is required to 

supply adequate labeling in accordance 

with the new intended uses. 

Dated: July 14, 2021. 

Janet Woodcock, 

Acting Commissioner of Food and Drugs. 

Dated: July 22, 2021. 

Xavier Becerra, 

Secretary, Department of Health and Human 

Services. 

[FR Doc. 2021–15980 Filed 7–30–21; 8:45 am] 

BILLING CODE 4164–01–P 

DEPARTMENT OF HOMELAND 

SECURITY 

Coast Guard 

33 CFR Part 165 

[Docket Number USCG–2021–0480] 

RIN 1625–AA00 

Safety Zone; Lake of the Ozarks, Mile 

Markers 7, 10.5, 13, 16, 22, 26, 34, and 

42, Lake of the Ozarks, MO 

AGENCY: Coast Guard, DHS. 

ACTION: Temporary final rule. 

SUMMARY: The Coast Guard is 

establishing temporary safety zones in 

all navigable waters extending 420 feet 

in all directions around fireworks barges 

at eight different locations on the Lake 

of the Ozarks. These safety zones are 

needed to protect personnel, vessels, 

and the marine environment from 

potential hazards created by the 

fireworks displays. Entry of vessels or 

persons into these zones is prohibited 

unless specifically authorized by the 

Captain of the Port Sector Upper 

Mississippi River or a designated 

representative. 

DATES: This rule is effective on August 

10, 2021 at 10 p.m. to 10:30 p.m. 

ADDRESSES: To view documents 

mentioned in this preamble as being 

available in the docket, go to https://

www.regulations.gov, type USCG–2021– 

0480 in the search box and click 

‘‘Search.’’ Next, in the Document Type 

column, select ‘‘Supporting & Related 

Material.’’ 

FOR FURTHER INFORMATION CONTACT: If 

you have questions on this rule, call or 

email Lieutenant Commander Stephanie 

Moore, Sector Upper Mississippi River 

Waterways Management Division, U.S. 

Coast Guard; telephone 314–269–2560, 

email Stephanie.R.Moore@uscg.mil. 

SUPPLEMENTARY INFORMATION: 

I. Table of Abbreviations 

CFR Code of Federal Regulations 

DHS Department of Homeland Security 

FR Federal Register 

NPRM Notice of proposed rulemaking 

§ Section 

U.S.C. United States Code 

II. Background Information and 

Regulatory History 

The Coast Guard is issuing this 

temporary rule without prior notice and 

opportunity to comment pursuant to 

authority under section 4(a) of the 

Administrative Procedure Act (APA) (5 

U.S.C. 553(b)). This provision 

authorizes an agency to issue a rule 

without prior notice and opportunity to 

comment when the agency for good 

cause finds that those procedures are 

‘‘impracticable, unnecessary, or contrary 

to the public interest.’’ Under 5 U.S.C. 

553(b)(B), the Coast Guard finds that 

good cause exists for not publishing a 

notice of proposed rulemaking (NPRM) 

with respect to this rule because it is 

impracticable. We must establish this 

safety zone by August 10, 2021 and lack 

sufficient time to provide a reasonable 

comment period and then consider 

those comments before issuing the rule. 

Under 5 U.S.C. 553(d)(3), the Coast 

Guard finds that good cause exists for 

making this rule effective less than 30 

days after publication in the Federal 

Register. Delaying the effective date of 

this rule would be contrary to the public 

interest because immediate action is 

needed to respond to the potential 

safety hazards associated with the 

fireworks displays on August 10, 2021. 

III. Legal Authority and Need for Rule 

The Coast Guard is issuing this rule 

under authority in 46 U.S.C. 70034 

(previously 33 U.S.C. 1231). The 

Captain of the Port Sector Upper 

Mississippi River (COTP) has 

determined that potential hazards 

associated with the fireworks displays 

on August 10, 2021 will be a safety 

concern for anyone on the Lake of the 

Ozarks at the designated launch 

locations. This rule resulted from a 

marine event notification stating that 

there will be fireworks displays to 

celebrate a bicentinneal birthday on the 

Lake of the Ozarks. This rule is needed 

to protect personnel, vessels, and the 

marine environment in the navigable 

waters within the safety zone before, 

during, and after the fireworks display. 

IV. Discussion of the Rule 

This rule establishes safety zones on 

August 10, 2021 from 10 p.m. until 

10:30 p.m. The safety zones will be 

located on all navigable waters 

extending 420 feet in all directions 

around fireworks barges at the following 

locations on the Lake of the Ozarks at 

(1) mile marker 7 (38 12′35.20′′ N 92 

45′02.57′′ W), (2) mile marker 10.5 (38 

01′21.93′′ N 92 47′38.93′′ W), (3) mile 

marker 13 (38 11′01.86′′ N 92 41′19.32′′ 

W), (4) mile marker 16 (38 08′54.89′′ N 

92 38′29.53′′ W), (5) mile marker 22 (38 

08′54.89′′ N 92 41′18.95′′ W), (6) mile 

marker 26 (38 07′25.22′′ N 92 42′58.65′′ 

W), (7) mile marker 34 (38 07′25.22′′ N 

92 47′34.59′′ W) and (8) mile marker 42 

(38 08′55′′ N 92 52′23.30′′ W). The 

duration of these zones is intended to 

protect personnel, vessels, and the 

marine environment in these navigable 

waters before, during, and after the 

fireworks displays. No vessel or person 

will be permitted to enter the safety 

zones without obtaining permission 

from the COTP or a designated 

representative. A designated 

representative is a commissioned, 

warrant, or petty officer of the U.S. 

Coast Guard assigned to units under the 

operational control of USCG Sector 

Upper Mississippi River. The COTP or 

a designated representative will inform 

the public of the enforcement date and 

times for these safety zones, as well as 

any emergent safety concerns that may 

delay the enforcement of the zones. 

V. Regulatory Analyses 

We developed this rule after 

considering numerous statutes and 

Executive orders related to rulemaking. 

Below we summarize our analyses 

based on a number of these statutes and 

Executive orders, and we discuss First 

Amendment rights of protestors. 

A. Regulatory Planning and Review 

Executive Orders 12866 and 13563 

direct agencies to assess the costs and 

benefits of available regulatory 

alternatives and, if regulation is 

necessary, to select regulatory 

approaches that maximize net benefits. 

This rule has not been designated a 

‘‘significant regulatory action,’’ under 

Executive Order 12866. Accordingly, 

this rule has not been reviewed by the 

Office of Management and Budget 

(OMB). 

This regulatory action determination 

is based on size, location, and duration 

of the temporary safety zones. This 

action involves fireworks displays at 

multiple designated locations on the 


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