CFR-2001-title21-vol1 FDA.pdf

8/10/2019 CFR-2001-title21-vol1 FDA.pdf

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21Parts 1 to 99

Revised as of April 1, 2001

Food and Drugs

Containing a codification of documents

of general applicability and future effect

As of April 1, 2001

With Ancillaries

Published by

Office of the Federal Register

National Archives and Records

Administration

A Special Edition of the Federal Register

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U.S. GOVERNMENT PRINTING OFFICE

WASHINGTON : 2001

For sale by the Superintendent of Documents, U.S. Government Printing Office

Internet: bookstore.gpo.gov Phone: (202) 512-1800 Fax: (202) 512-2250

Mail: Stop SSOP, Washington, DC 204020001



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Table of ContentsPage

Explanation ................................................................................................ v

Title 21:

Chapter IFood and Drug Administration, Department of Healthand Human Services .................................................................... 3

Finding Aids:

Material Approved for Incorporation by Reference ............................ 457

Table of CFR Titles and Chapters ....................................................... 459

Alphabetical List of Agencies Appearing in the CFR ......................... 477

List of CFR Sections Affected ............................................................. 487



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Cite this Code: CFR

To cite the regulations in

this volume use title,

part and section num-

ber. Thus,21 CFR 1.1refers to title 21, part 1,

section 1.



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Explanation

The Code of Federal Regulations is a codification of the general and permanent

rules published in the Federal Register by the Executive departments and agen-

cies of the Federal Government. The Code is divided into 50 titles which represent

broad areas subject to Federal regulation. Each title is divided into chapters

which usually bear the name of the issuing agency. Each chapter is further sub-divided into parts covering specific regulatory areas.

Each volume of the Code is revised at least once each calendar year and issued

on a quarterly basis approximately as follows:

Title 1 through Title 16..............................................................as of January 1

Title 17 through Title 27 .................................................................as of April 1

Title 28 through Title 41 ..................................................................as of July 1

Title 42 through Title 50 .............................................................as of October 1

The appropriate revision date is printed on the cover of each volume.

LEGAL STATUS

The contents of the Federal Register are required to be judicially noticed (44

U.S.C. 1507). The Code of Federal Regulations is prima facie evidence of the text

of the original documents (44 U.S.C. 1510).

HOW TO USE THE CODE OF FEDERAL REGULATIONS

The Code of Federal Regulations is kept up to date by the individual issues

of the Federal Register. These two publications must be used together to deter-

mine the latest version of any given rule.

To determine whether a Code volume has been amended since its revision date

(in this case, April 1, 2001), consult the List of CFR Sections Affected (LSA),

which is issued monthly, and the Cumulative List of Parts Affected, which

appears in the Reader Aids section of the daily Federal Register. These two lists

will identify the Federal Register page number of the latest amendment of any

given rule.

EFFECTIVE AND EXPIRATION DATES

Each volume of the Code contains amendments published in the Federal Reg-

ister since the last revision of that volume of the Code. Source citations for

the regulations are referred to by volume number and page number of the Federal

Register and date of publication. Publication dates and effective dates are usu-

ally not the same and care must be exercised by the user in determining the

actual effective date. In instances where the effective date is beyond the cut-

off date for the Code a note has been inserted to reflect the future effective

date. In those instances where a regulation published in the Federal Register

states a date certain for expiration, an appropriate note will be inserted following

the text.

OMB CONTROL NUMBERS

The Paperwork Reduction Act of 1980 (Pub. L. 96511) requires Federal agencies

to display an OMB control number with their information collection request.



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Many agencies have begun publishing numerous OMB control numbers as amend-

ments to existing regulations in the CFR. These OMB numbers are placed as

close as possible to the applicable recordkeeping or reporting requirements.

OBSOLETE PROVISIONS

Provisions that become obsolete before the revision date stated on the cover

of each volume are not carried. Code users may find the text of provisions in

effect on a given date in the past by using the appropriate numerical list of

sections affected. For the period before January 1, 1986, consult either the List

of CFR Sections Affected, 19491963, 19641972, or 19731985, published in seven sep-

arate volumes. For the period beginning January 1, 1986, a List of CFR Sections

Affectedis published at the end of each CFR volume.

INCORPORATION BY REFERENCEWhat is incorporation by reference? Incorporation by reference was established

by statute and allows Federal agencies to meet the requirement to publish regu-

lations in the Federal Register by referring to materials already published else-

where. For an incorporation to be valid, the Director of the Federal Register

must approve it. The legal effect of incorporation by reference is that the mate-

rial is treated as if it were published in full in the Federal Register (5 U.S.C.

552(a)). This material, like any other properly issued regulation, has the force

of law.

What is a proper incorporation by reference? The Director of the Federal Register

will approve an incorporation by reference only when the requirements of 1 CFR

part 51 are met. Some of the elements on which approval is based are:

(a) The incorporation will substantially reduce the volume of material pub-

lished in the Federal Register.

(b) The matter incorporated is in fact available to the extent necessary to

afford fairness and uniformity in the administrative process.(c) The incorporating document is drafted and submitted for publication in

accordance with 1 CFR part 51.

Properly approved incorporations by reference in this volume are listed in the

Finding Aids at the end of this volume.

What if the material incorporated by reference cannot be found? If you have any

problem locating or obtaining a copy of material listed in the Finding Aids of

this volume as an approved incorporation by reference, please contact the agency

that issued the regulation containing that incorporation. If, after contacting the

agency, you find the material is not available, please notify the Director of the

Federal Register, National Archives and Records Administration, Washington DC

20408, or call (202) 5234534.

CFR INDEXES AND TABULAR GUIDES

A subject index to the Code of Federal Regulations is contained in a separate

volume, revised annually as of January 1, entitled CFR I NDEX AND FINDING AIDS.This volume contains the Parallel Table of Statutory Authorities and Agency

Rules (Table I). A list of CFR titles, chapters, and parts and an alphabetical

list of agencies publishing in the CFR are also included in this volume.

An index to the text of Title 3The Presidentis carried within that volume.

The Federal Register Index is issued monthly in cumulative form. This index

is based on a consolidation of the Contents entries in the daily Federal Reg-

ister.

A List of CFR Sections Affected (LSA) is published monthly, keyed to the

revision dates of the 50 CFR titles.



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THIS TITLE

Title 21FOOD AND DRUGS is composed of nine volumes. The parts in these

volumes are arranged in the following order: Parts 199, 100169, 170199, 200299,

300499, 500599, 600799, 8001299 and 1300end. The first eight volumes, containing

parts 11299, comprise Chapter IFood and Drug Administration, Department of

Health and Human Services. The ninth volume, containing part 1300 to end, in-cludes Chapter IIDrug Enforcement Administration, Department of Justice, and

Chapter IIIOffice of National Drug Control Policy. The contents of these vol-

umes represent all current regulations codified under this title of the CFR as

of April 1, 2001.

Redesignation tables for Chapter IFood and Drug Administration appear in

the Finding Aids section for the volumes containing parts 170199 and 500599.



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Title 21Food and

Drugs(This book contains parts 1 to 99)

Part

CHAPTER IFood and Drug Administration, Department of

Health and Human Services ............................................... 1

CROSS REFERENCES: Food Safety and Inspection Service, Department of Agriculture: 9 CFR

chapter III.

Federal Trade Commission: See Commercial Practices, 16 CFR chapter I.

U.S. Customs Service, Department of the Treasury: See Customs Duties, 19 CFR chapter I.

Internal Revenue Service, Department of the Treasury: See Internal Revenue, 26 CFR chap-

ter I.Bureau of Alcohol, Tobacco, and Firearms, Department of the Treasury: See Alcohol, To-

bacco Products and Firearms, 27 CFR chapter I.

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CHAPTER IFOOD AND DRUG

ADMINISTRATION, DEPARTMENT OF HEALTH

AND HUMAN SERVICES

SUBCHAPTER AGENERAL

Part Page

1 General enforcement regulations ............................ 5

2 General administrative rulings and decisions ......... 143 Product jurisdiction ................................................ 20

5 Delegations of authority and organization ............. 247 Enforcement policy ................................................. 72

10 Administrative practices and procedures ................ 8111 Electronic records; electronic signatures ............... 119

12 Formal evidentiary public hearing ......................... 122

13 Public hearing before a public board of inquiry ...... 14014 Public hearing before a public advisory committee 14415 Public hearing before the Commissioner ................ 171

16 Regulatory hearing before the Food and Drug Ad-ministration ......................................................... 174

17 Civil money penalties hearings ............................... 180

19 Standards of conduct and conflicts of interest ....... 192

20 Public information .................................................. 19421 Protection of privacy .............................................. 223

25 Environmental impact considerations .................... 23926 Mutual recognition of pharmaceutical good manu-

facturing practice reports, medical device qual-ity system audit reports, and certain medical de-vice product evaluation reports: United States

and The European Community ............................. 25050 Protection of human subjects ................................. 28254 Financial disclosure by clinical investigators ........ 291

56 Institutional Review Boards ................................... 29458 Good laboratory practice for nonclinical labora-

tory studies .......................................................... 30260 Patent term restoration .......................................... 31670 Color additives ........................................................ 32471 Color additive petitions .......................................... 331



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21 CFR Ch. I (4101 Edition)

Part Page

73 Listing of color additives exempt from certifi-cation ................................................................... 338

74 Listing of color additives subject to certification .. 38580 Color additive certification ..................................... 42481 General specifications and general restrictions for

provisional color additives for use in foods,drugs, and cosmetics ............................................ 430

82 Listing of certified provisionally listed colors andspecifications ....................................................... 437

8398 [Reserved]

99 Dissemination of information on unapproved/newuses for marketed drugs, biologics, and devices ... 442

EDITORIAL NOTE: For nomenclature changes to chapter I see 59 FR 14366, Mar. 28, 1994.



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SUBCHAPTER AGENERAL

PART 1GENERAL ENFORCEMENTREGULATIONS

Subpart AGeneral Provisions

Sec.

1.1 General.

1.3 Definitions.

1.4 Authority citations.

Subpart BGeneral Labeling Requirements

1.20 Presence of mandatory label informa-

tion.

1.21 Failure to reveal material facts.

1.23 Procedures for requesting variations

and exemptions from required label

statements.

1.24 Exemptions from required label state-

ments.

Subparts CD [Reserved]

Subpart EImports and Exports

1.83 Definitions.

1.90 Notice of sampling.

1.91 Payment for samples.

1.94 Hearing on refusal of admission.

1.95 Application for authorization to relabel

and recondition.1.96 Granting of authorization to relabel

and recondition.

1.97 Bonds.

1.99 Costs chargeable in connection with re-

labeling and reconditioning inadmissible

imports.

AUTHORITY: 15 U.S.C. 1453, 1454, 1455; 21

U.S.C. 321, 343, 352, 355, 360b, 362, 371; 42 U.S.C.

216.

SOURCE: 42 FR 15553, Mar. 22, 1977, unless

otherwise noted.


1.1 General.

(a) The provisions of regulations pro-

mulgated under the Federal Food,Drug, and Cosmetic Act with respect tothe doing of any act shall be applicable

also to the causing of such act to bedone.

(b) The definitions and interpreta-

tions of terms contained in section 201of the Federal Food, Drug, and Cos-metic Act shall be applicable also to

such terms when used in regulationspromulgated under that act.

(c) The definition of package in 1.20

and ofprincipal display panel in 101.1,

201.60, 501.1, 701.10 and 801.60 of this

chapter; and the requirements per-

taining to uniform location, lack of

qualification, and separation of the net

quantity declaration in 101.105(f),

201.62(e), 501.105(f), 701.13(f) and 801.62(e)

of this chapter to type size require-

ments for net quantity declaration in

101.105(i), 201.62(h), 501.105(i), 701.13(i)and 801.62(h) of this chapter, to initial

statement of ounces in the dual dec-

laration of net quantity in 101.105(j)

and (m), 201.62(i) and (k), 501.105(j) and

(m), 701.13(j) and (m) and 801.62(i) and

(k) of this chapter, to initial statement

of inches in declaration of net quantity

in 201.62(m), 701.13(o) and 801.62(m) of

this chapter, to initial statement of

square inches in declaration of net

quantity in 201.62(n), 701.13(p) and

801.62(n) of this chapter, to prohibition

of certain supplemental net quantity

statements in 101.105(o), 201.62(o),

501.105(o), 701.13(q) and 801.62(o) of this

chapter, and to servings representa-

tions in 501.8 of this chapter are pro-vided for solely by the Fair Packaging

and Labeling Act. The other require-

ments of this part are issued under

both the Fair Packaging and Labeling

Act and the Federal Food, Drug, and

Cosmetic Act, or by the latter act sole-

ly, and are not limited in their applica-

tion by section 10 of the Fair Pack-

aging and Labeling Act.

[42 FR 15553, Mar. 22, 1977, as amended at 58

FR 17085, Apr. 1, 1993]

1.3 Definitions.

(a) Labeling includes all written,

printed, or graphic matter accom-

panying an article at any time whilesuch article is in interstate commerce

or held for sale after shipment or deliv-

ery in interstate commerce.

(b) Label means any display of writ-

ten, printed, or graphic matter on the

immediate container of any article, or

any such matter affixed to any con-

sumer commodity or affixed to or ap-

pearing upon a package containing any

consumer commodity.



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21 CFR Ch. I (4101 Edition) 1.4

1.4 Authority citations.

(a) For each part of its regulations,

the Food and Drug Administration in-

cludes a centralized citation of all of

the statutory provisions that provide

authority for any regulation that is in-

cluded in that part.

(b) The agency may rely on any one

or more of the authorities that are list-

ed for a particular part in imple-

menting or enforcing any section in

that part.

(c) All citations of authority in this

chapter will list the applicable sectionsin the organic statute if the statute is

the Federal Food, Drug, and Cosmetic

Act, the Public Health Service Act, or

the Fair Packaging and Labeling Act.

References to an act or a section there-

of include references to amendments to

that act or section. These citations

will also list the corresponding United

States Code (U.S.C.) sections. For ex-

ample, a citation to section 701 of the

Federal Food, Drug, and Cosmetic Act

would be listed: Sec. 701 of the Federal

Food, Drug, and Cosmetic Act (21

U.S.C. 371).

(d) If the organic statute is one other

than those specified in paragraph (c) ofthis section, the citations of authority

in this chapter generally will list only

the applicable U.S.C. sections. For ex-

ample, a citation to section 552 of the

Administrative Procedure Act would be

listed: 5 U.S.C. 552. The agency may,

where it determines that such meas-

ures are in the interest of clarity and

public understanding, list the applica-

ble sections in the organic statute and

the corresponding U.S.C. section in the

same manner set out in paragraph (c)

of this section. References to an act or

a section thereof include references to

amendments to that act or section.

(e) Where there is no U.S.C. provi-

sion, the agency will include a citation

to the U.S. Statutes at Large. Cita-

tions to the U.S. Statutes at Large will

refer to volume and page.

(f) The authority citations will in-

clude a citation to executive delega-

tions (i.e., Executive Orders), if any,

necessary to link the statutory author-

ity to the agency.

[54 FR 39630, Sept. 27, 1989]

Subpart BGeneral LabelingRequirements

1.20 Presence of mandatory label in-formation.

The term package means any con-tainer or wrapping in which any food,

drug, device, or cosmetic is enclosedfor use in the delivery or display ofsuch commodities to retail purchasers,

but does not include:(a) Shipping containers or wrappings

used solely for the transportation of

any such commodity in bulk or inquantity to manufacturers, packers,processors, or wholesale or retail dis-

tributors;(b) Shipping containers or outer

wrappings used by retailers to ship or

deliver any such commodity to retailcustomers if such containers and wrap-pings bear no printed matter per-

taining to any particular commodity;or

(c) Containers subject to the provi-sions of the Act of August 3, 1912 (37

Stat. 250, as amended; 15 U.S.C. 231233), the Act of March 4, 1915 (38 Stat.1186, as amended; 15 U.S.C. 234236), the

Act of August 31, 1916 (39 Stat. 673, asamended; 15 U.S.C. 251256), or the Actof May 21, 1928 (45 Stat. 635, as amend-

ed; 15 U.S.C. 257257i).(d) Containers used for tray pack dis-

plays in retail establishments.

(e) Transparent wrappers or con-tainers which do not bear written,printed, or graphic matter obscuring

the label information required by thispart.

A requirement contained in this partthat any word, statement, or other in-formation appear on the label shall not

be considered to be complied with un-less such word, statement, or informa-tion also appears on the outer con-tainer or wrapper of the retail package

of the article, or, as stated in para-graph (e) of this section, such informa-tion is easily legible by virtue of the

transparency of the outer wrapper orcontainer. Where a consumer com-modity is marketed in a multiunit re-

tail package bearing the mandatorylabel information as required by thispart and the unit containers are not in-

tended to be sold separately, the netweight placement requirement of



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Food and Drug Administration, HHS 1.24

101.105(f) applicable to such unit con-

tainers is waived if the units are incompliance with all the other require-ments of this part.

1.21 Failure to reveal material facts.

(a) Labeling of a food, drug, device,or cosmetic shall be deemed to be mis-leading if it fails to reveal facts that

are:(1) Material in light of other rep-

resentations made or suggested by

statement, word, design, device or anycombination thereof; or

(2) Material with respect to con-sequences which may result from use ofthe article under: (i) The conditionsprescribed in such labeling or (ii) suchconditions of use as are customary or

usual.(b) Affirmative disclosure of material

facts pursuant to paragraph (a) of this

section may be required, among otherappropriate regulatory procedures, by

(1) Regulations in this chapter pro-

mulgated pursuant to section 701(a) ofthe act; or

(2) Direct court enforcement action.

(c) Paragraph (a) of this section doesnot:

(1) Permit a statement of differences

of opinion with respect to warnings (in-cluding contraindications, precautions,adverse reactions, and other informa-

tion relating to possible product haz-ards) required in labeling for food,drugs, devices, or cosmetics under the

act.(2) Permit a statement of differences

of opinion with respect to the effective-

ness of a drug unless each of the opin-ions expressed is supported by substan-tial evidence of effectiveness as defined

in sections 505(d) and 512(d) of the act.

1.23 Procedures for requesting vari-ations and exemptions from re-quired label statements.

Section 403(e) of the act (in this part1, the term act means the FederalFood, Drug, and Cosmetic Act) pro-

vides for the establishment by regula-tion of reasonable variations and ex-emptions for small packages from the

required declaration of net quantity ofcontents. Section 403(i) of the act pro-vides for the establishment by regula-

tion of exemptions from the requireddeclaration of ingredients where such

declaration is impracticable, or results

in deception or unfair competition.Section 502(b) of the act provides forthe establishment by regulation of rea-

sonable variations and exemptions forsmall packages from the required dec-laration of net quantity of contents.

Section 602(b) of the act provides forthe establishment by regulation of rea-sonable variations and exemptions for

small packages from the required dec-laration of net quantity of contents.Section 5(b) of the Fair Packaging andLabeling Act provides for the establish-

ment by regulation of exemptions fromcertain required declarations of netquantity of contents, identity of com-

modity, identity and location of manu-facturer, packer, or distributor, andfrom declaration of net quantity of

servings represented, based on a find-ing that full compliance with such re-quired declarations is impracticable or

not necessary for the adequate protec-tion of consumers, and a further find-ing that the nature, form, or quantity

of the packaged consumer commodityor other good and sufficient reasonsjustify such exemptions. The Commis-

sioner, on his own initiative or on peti-tion of an interested person, may pro-

pose a variation or exemption basedupon any of the foregoing statutoryprovisions, including proposed findingsif section 5(b) of the Fair Packaging

and Labeling Act applies, pursuant toparts 10, 12, 13, 14, 15, 16, and 19 of thischapter.

1.24 Exemptions from required labelstatements.

The following exemptions are grant-ed from label statements required bythis part:

(a) Foods. (1) While held for sale, afood shall be exempt from the requireddeclaration of net quantity of contentsspecified in this part if said food is re-

ceived in bulk containers at a retail es-tablishment and is accurately weighed,measured, or counted either within the

view of the purchaser or in compliancewith the purchasers order.

(2) Random food packages, as defined

in 101.105(j) of this chapter, bearing la-bels declaring net weight, price perpound or per specified number of

pounds, and total price shall be exemptfrom the type size, dual declaration,



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(6)(i) Ice cream, french ice cream, icemilk, fruit sherbets, water ices, quies-cently frozen confections (with or with-out dairy ingredients), special dietaryfrozen desserts, and products made insemblance of the foregoing, whenmeasured by and packaged in 12-liquidpint and 12-gallon measure-containers,as defined in the Measure ContainerCode of National Bureau of StandardsHandbook 44, Specifications, Toler-ances, and Other Technical Require-ments for Weighing and Measuring De-vices, Sec. 4.45 Measure-Containers,

which is incorporated by reference, areexempt from the requirements of 101.105(b)(2) of this chapter to the ex-tent that net contents of 8fluid ouncesand 64fluid ounces (or 2 quarts) maybe expressed as 12 pint and 12 gallon,respectively. Copies are available fromthe Center for Food Safety and AppliedNutrition (HFS150), Food and DrugAdministration, 200 C St. SW., Wash-ington, DC 20204, or available for in-spection at the Office of the FederalRegister, 800 North Capitol Street NW.,suite 700, Washington, DC.

(ii) The foods named in paragraph(a)(6)(i) of this section, when measuredby and packaged in 1liquid pint, 1liq-

uid quart, and 12-gallon measure-con-tainers, as defined in the MeasureContainer Code of National Bureau ofStandards Handbook 44, Specifica-tions, Tolerances, and Other TechnicalRequirements for Weighing and Meas-uring Devices, Sec. 4.45 Measure-Con-tainers,which is incorporated by ref-erence, are exempt from the dual net-contents declaration requirement of 101.105(j) of this chapter. Copies areavailable from the Center for FoodSafety and Applied Nutrition (HFS150), Food and Drug Administration,200 C St. SW., Washington, DC 20204, oravailable for inspection at the Office ofthe Federal Register, 800 North Capitol

Street NW., suite 700, Washington, DC.(iii) The foods named in paragraph

(a)(6)(i) of this section, when measuredby and packaged in 12-liquid pint, 1liq-uid pint, 1liquid quart, 12-gallon, and1gallon measured-containers, as de-fined in the Measure Container Codeof National Bureau of Standards Hand-book 44, Specifications, Tolerances,and Other Technical Requirements forWeighing and Measuring Devices, Sec.

4.45 Measure-Containers,which is in-corporated by reference, are exemptfrom the requirement of 101.105(f) ofthis chapter that the declaration of netcontents be located within the bottom30 percent of the principal displaypanel. Copies are available from theCenter for Food Safety and Applied Nu-trition (HFS150), Food and Drug Ad-ministration, 200 C St. SW., Wash-ington, DC 20204, or available for in-spection at the Office of the FederalRegister, 800 North Capitol Street NW.,suite 700, Washington, DC.

(7)(i) Milk, cream, light cream, coffeeor table cream, whipping cream, lightwhipping cream, heavy or heavy whip-ping cream, sour or cultured sourcream, half-and-half, sour or culturedhalf-and-half, reconstituted or recom-bined milk and milk products, con-centrated milk and milk products,skim or skimmed milk, vitamin D milkand milk products, fortified milk andmilk products, homogenized milk, fla-vored milk and milk products, butter-milk, cultured buttermilk, culturedmilk or cultured whole buttermilk,low-fat milk (0.5 to 2.0 percent but-terfat), and acidified milk and milkproducts, when packaged in containers

of 8 and 64fluidounce capacity, areexempt from the requirements of 101.105(b)(2) of this chapter to the ex-tent that net contents of 8 fluid ouncesand 64 fluid ounces (or 2 quarts) may beexpressed as 12 pint and 12 gallon, re-spectively.

(ii) The products listed in paragraph(a)(7)(i) of this section, when packagedin glass or plastic containers of 12-pint,1pint, 1quart, 12-gallon, and 1galloncapacities are exempt from the place-ment requirement of 101.105(f) of thischapter that the declaration of netcontents be located within the bottom30 percent of the principal displaypanel, provided that other required

label information is conspicuously dis-played on the cap or outside closureand the required net quantity of con-tents declaration is conspicuouslyblown, formed, or molded into or per-manently applied to that part of theglass or plastic container that is at orabove the shoulder of the container.

(iii) The products listed in paragraph(a)(7)(i) of this section, when packagedin containers of 1pint, 1quart, and 12-



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gallon capacities are exempt from thedual net-contents declaration require-ment of 101.105(j) of this chapter.

(8) Wheat flour products, as definedby 137.105, 137.155, 137.160, 137.165,137.170, 137.175, 137.180, 137.185, 137.200,and 137.205 of this chapter, packaged:

(i) In conventional 2, 5, 10, 25, 50, and 100pound packages are exemptfrom the placement requirement of 101.105(f) of this chapter that the dec-laration of net contents be locatedwithin the bottom 30 percent of thearea of the principal display panel of

the label; and(ii) In conventional 2pound packages

are exempt from the dual net-contentsdeclaration requirement of 101.105(j)of this chapter provided the quantity ofcontents is expressed in pounds.

(9)(i) Twelve shell eggs packaged in acarton designed to hold 1 dozen eggsand designed to permit the division ofsuch carton by the retail customer atthe place of purchase into two portionsof one-half dozen eggs each are exemptfrom the labeling requirements of thispart with respect to each portion ofsuch divided carton if the carton, whenundivided, is in conformance with thelabeling requirements of this part.

(ii) Twelve shell eggs packaged in acarton designed to hold 1 dozen eggsare exempt from the placement re-quirements for the declaration of con-tents prescribed by 101.105(f) of thischapter if the required content declara-tion is otherwise placed on the prin-cipal display panel of such carton andif, in the case of such cartons designedto permit division by retail customersinto two portions of one-half dozeneggs each, the required content dec-laration is placed on the principal dis-play panel in such a manner that thecontext of the content declaration isdestroyed upon division of the carton.

(10) Butter as defined in 42 Stat. 1500

(excluding whipped butter):(i) In 8ounce and in 1pound pack-

ages is exempt from the requirementsof 101.105(f) of this chapter that thenet contents declaration be placedwithin the bottom 30 percent of thearea of the principal display panel;

(ii) In 1pound packages is exemptfrom the requirements of 101.105(j)(1)of this chapter that such declaration bein terms of ounces and pounds, to per-

mit declaration of 1pound or onepound; and

(iii) In 4ounce, 8ounce, and 1poundpackages with continuous label copywrapping is exempt from the require-ments of 101.3 and 101.105(f) of thischapter that the statement of identityand net contents declaration appear inlines generally parallel to the base onwhich the package rests as it is de-signed to be displayed, provided thatsuch statement and declaration are notso positioned on the label as to be mis-leading or difficult to read as the pack-

age is customarily displayed at retail.(11) Margarine as defined in 166.110

of this chapter and imitations thereofin 1pound rectangular packages, ex-cept for packages containing whippedor soft margarine or packages thatcontain more than four sticks, are ex-empt from the requirement of 101.105(f) of this chapter that the dec-laration of the net quantity of contentsappear within the bottom 30 percent ofthe principal display panel and fromthe requirement of 101.105(j)(1) of thischapter that such declaration be ex-pressed both in ounces and in pounds topermit declaration of 1-pound orone pound, provided an accurate

statement of net weight appears con-spicuously on the principal displaypanel of the package.

(12) Corn flour and related products,as they are defined by 137.211, 137.215,and 137.230 through 137.290 of thischapter, packaged in conventional 5,10, 25, 50, and 100pound bags are ex-empt from the placement requirementof 101.105(f) of this chapter that thedeclaration of net contents be locatedwithin the bottom 30 percent of thearea of the principal display panel ofthe label.

(13)(i) Single strength and less thansingle strength fruit juice beverages,imitations thereof, and drinking water

when packaged in glass or plastic con-tainers of 12-pint, 1pint, 1quart, 12-gallon, and 1gallon capacities are ex-empt from the placement requirementof 101.105(f) of this chapter that thedeclaration of net contents be locatedwithin the bottom 30 percent of theprincipal display panel: Provided, Thatother required label information isconspicuously displayed on the cap oroutside closure and the required net



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quantity of contents declaration isconspicuously blown, formed, or mold-ed into or permanently applied to thatpart of the glass or plastic containerthat is at or above the shoulder of thecontainer.

(ii) Single strength and less than sin-gle strength fruit juice beverages, imi-tations thereof, and drinking waterwhen packaged in glass, plastic, orpaper (fluid milk type) containers of 1pint, 1quart, and 12-gallon capacitiesare exempt from the dual net-contentsdeclaration requirement of 101.105(j)

of this chapter.(iii) Single strength and less than

single strength fruit juice beverages,imitations thereof, and drinking waterwhen packaged in glass, plastic, orpaper (fluid milk type) containers of 8and 64fluid-ounce capacity, are ex-empt from the requirements of 101.105(b)(2) of this chapter to the ex-tent that net contents of 8 fluid ouncesand 64 fluid ounces (or 2 quarts) may beexpressed as 12 pint (or half pint) and 12gallon (or half gallon), respectively.

(14) The unit containers in a multi-unit or multicomponent retail foodpackage shall be exempt from regula-tions of section 403 (e)(1), (g)(2), (i)(2),

(k), and (q) of the act with respect tothe requirements for label declarationof the name and place of business ofthe manufacturer, packer, or dis-tributor; label declaration of ingredi-ents; and nutrition information when:

(i) The multiunit or multicomponentretail food package labeling meets allthe requirements of this part;

(ii) The unit containers are securelyenclosed within and not intended to beseparated from the retail packageunder conditions of retail sale; and

(iii) Each unit container is labeledwith the statement This Unit Not La-beled For Retail Salein type size notless than one-sixteenth of an inch in

height. The word Individualmay beused in lieu of or immediately pre-ceding the word Retailin the state-ment.

(b) Drugs. Liquid over-the-counterveterinary preparations intended forinjection shall be exempt from the dec-laration of net quantity of contents interms of the U.S. gallon of 231 cubicinches and quart, pint, and fluid-ouncesubdivisions thereof as required by

201.62 (b), (i), and (j) of this chapter,and from the dual declaration require-ments of 201.62(i) of this chapter, ifsuch declaration of net quantity ofcontents is expressed in terms of theliter and milliliter, or cubic centi-meter, with the volume expressed at 68F (20 C).

(c) Cosmetics. Cosmetics in packagescontaining less than one-fourth ounceavoirdupois or one-eighth fluid ounceshall be exempt from compliance withthe requirements of section 602(b)(2) ofthe Federal Food, Drug, and Cosmetic

Act and section 4(a)(2) of the FairPackaging and Labeling Act:

(1) When such cosmetics are affixedto a display card labeled in conform-ance with all labeling requirements ofthis part; or

(2) When such cosmetics are sold atretail as part of a cosmetic packageconsisting of an inner and outer con-tainer and the inner container is notfor separate retail sale and the outercontainer is labeled in conformancewith all labeling requirements of thispart.

[42 FR 15553, Mar. 22, 1977, as amended at 47FR 946, Jan. 8, 1982; 47 FR 32421, July 27, 1982;49 FR 13339, Apr. 4, 1984; 54 FR 9033, Mar. 3,

1989; 58 FR 2174, Jan. 6, 1993; 61 FR 14478, Apr.2, 1996]

Subparts CD [Reserved]

Subpart EImports and Exports

1.83 Definitions.

For the purposes of regulations pre-scribed under section 801(a), (b), and (c)of the Federal Food, Drug, and Cos-metic Act:

(a) The term owner or consigneemeans the person who has the rights ofa consignee under the provisions of sec-tions 483, 484, and 485 of the Tariff Actof 1930, as amended (19 U.S.C. 1483, 1484,

1485).(b) The term district director means

the director of the district of the Foodand Drug Administration having juris-diction over the port of entry throughwhich an article is imported or offeredfor import, or such officer of the dis-trict as he may designate to act in hisbehalf in administering and enforcingthe provisions of section 801 (a), (b),and (c).



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1.90 Notice of sampling.

When a sample of an article offeredfor import has been requested by thedistrict director, the collector of cus-toms having jurisdiction over the arti-cle shall give to the owner or consigneeprompt notice of delivery of, or inten-tion to deliver, such sample. Upon re-ceipt of the notice, the owner or con-signee shall hold such article and notdistribute it until further notice fromthe district director or the collector ofcustoms of the results of examinationof the sample.

1.91 Payment for samples.

The Food and Drug Administrationwill pay for all import samples whichare found to be in compliance with therequirements of the Federal Food,Drug, and Cosmetic Act. Billing for re-imbursement should be made by theowner or consignee to the Food andDrug Administration district head-quarters in whose territory the ship-ment was offered for import. Paymentfor samples will not be made if the ar-ticle is found to be in violation of theact, even though subsequently broughtinto compliance under the terms of anauthorization to bring the article intocompliance or rendered not a food,drug, device, or cosmetic as set forth in 1.95.

1.94 Hearing on refusal of admission.

(a) If it appears that the article maybe subject to refusal of admission, thedistrict director shall give the owner orconsignee a written notice to that ef-fect, stating the reasons therefor. Thenotice shall specify a place and a pe-riod of time during which the owner orconsignee shall have an opportunity tointroduce testimony. Upon timely re-quest giving reasonable grounds there-for, such time and place may bechanged. Such testimony shall be con-fined to matters relevant to the admis-sibility of the article, and may be in-troduced orally or in writing.

(b) If such owner or consignee sub-mits or indicates his intention to sub-mit an application for authorization torelabel or perform other action tobring the article into compliance withthe act or to render it other than afood, drug, device, or cosmetic, suchtestimony shall include evidence in

support of such application. If such ap-plication is not submitted at or priorto the hearing, the district directorshall specify a time limit, reasonablein the light of the circumstances, forfiling such application.

1.95 Application for authorization torelabel and recondition.

Application for authorization torelabel or perform other action tobring the article into compliance withthe act or to render it other than afood, drug, device or cosmetic may be

filed only by the owner or consignee,and shall:

(a) Contain detailed proposals forbringing the article into compliancewith the act or rendering it other thana food, drug, device, or cosmetic.

(b) Specify the time and place wheresuch operations will be carried out andthe approximate time for their comple-tion.

1.96 Granting of authorization torelabel and recondition.

(a) When authorization contemplatedby 1.95 is granted, the district directorshall notify the applicant in writing,

specifying:(1) The procedure to be followed;

(2) The disposition of the rejected ar-ticles or portions thereof;

(3) That the operations are to be car-ried out under the supervision of an of-ficer of the Food and Drug Administra-tion or the U.S. Customs Service, asthe case may be;

(4) A time limit, reasonable in thelight of the circumstances, for comple-tion of the operations; and

(5) Such other conditions as are nec-essary to maintain adequate super-vision and control over the article.

(b) Upon receipt of a written requestfor extension of time to complete such

operations, containing reasonablegrounds therefor, the district directormay grant such additional time as hedeems necessary.

(c) An authorization may be amendedupon a showing of reasonable groundstherefor and the filing of an amendedapplication for authorization with thedistrict director.

(d) If ownership of an article coveredby an authorization changes before the



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operations specified in the authoriza-tion have been completed, the originalowner will be held responsible, unlessthe new owner has executed a bond andobtained a new authorization. Any au-thorization granted under this sectionshall supersede and nullify any pre-viously granted authorization with re-spect to the article.

[42 FR 15553, Mar. 22, 1977, as amended at 54FR 9033, Mar. 3, 1989]

1.97 Bonds.

(a) The bonds required under section801(b) of the act may be executed bythe owner or consignee on the appro-priate form of a customs single-entryor term bond, containing a conditionfor the redelivery of the merchandiseor any part thereof upon demand of thecollector of customs and containing aprovision for the performance of condi-tions as may legally be imposed for therelabeling or other action necessary tobring the article into compliance withthe act or rendering it other than afood, drug, device, or cosmetic, in suchmanner as is prescribed for such bondin the customs regulations in force onthe date of request for authorization.The bond shall be filed with the col-lector of customs.

(b) The collector of customs may can-cel the liability for liquidated damagesincurred under the above-mentionedprovisions of such a bond, if he receivesan application for relief therefrom,upon the payment of a lesser amountor upon such other terms and condi-tions as shall be deemed appropriateunder the law and in view of the cir-cumstances, but the collector shall notact under this regulation in any caseunless the district director is in fullagreement with the action.

1.99 Costs chargeable in connectionwith relabeling and reconditioning

inadmissible imports.The cost of supervising the relabeling

or other action in connection with animport of food, drugs, devices, or cos-metics which fails to comply with theFederal Food, Drug, and Cosmetic Actshall be paid by the owner or consigneewho files an application requestingsuch action and executes a bond, pursu-ant to section 801(b) of the act, asamended. The cost of such supervision

shall include, but not be restricted to,the following:

(a) Travel expenses of the supervisingofficer.

(b) Per diem in lieu of subsistence ofthe supervising officer when away fromhis home station, as provided by law.

(c) The charge for the services of thesupervising officer, which shall includeadministrative support, shall be com-puted at a rate per hour equal to 266percent of the hourly rate of regularpay of a grade GS11/4 employee, exceptthat such services performed by a cus-

toms officer and subject to the provi-sions of the act of February 13, 1911, asamended (sec. 5, 36 Stat. 901, as amend-ed (19 U.S.C. 267)), shall be calculatedas provided in that act.

(d) The charge for the service of theanalyst, which shall include adminis-trative and laboratory support, shall becomputed at a rate per hour equal to266 percent of the hourly rate of reg-ular pay of a grade GS12/4 employee.The rate per hour equal to 266 percentof the equivalent hourly rate of regularpay of the supervising officer (GS11/4)and the analyst (GS12/4) is computedas follows:

Hours

Gross number of working hours in 52 40hr weeks 2,080Less:

9 legal public holidaysNew Years Day, Wash-ingtons Birthday, Memorial Day, IndependenceDay, Labor Day, Columbus Day, Veterans Day,Thanksgiving Day, and Christmas Day .............. 72

Annual leave26 d ................................................ 208Sick leave13 d .................................................... 104

Total ................................................................ 384Net number of working hours ......................... 1,696

Gross number of working hours in 52 40-hr weeks .. 2,080Working hour equivalent of Government contribu-

tions for employee retirement, life insurance, andhealth benefits computed at 812 pct. of annualrate of pay of employee ......................................... 176

Equivalent annual working hours .................... 2,256

Support required to equal to 1 man-year .................. 2,256Equivalent gross annual working hours

charged to Food and Drug appropriation .... 4,512

NOTE: Ratio of equivalent gross annualnumber of working hours charged to Foodand Drug appropriation to net number of an-nual working hours 4,512/1,696=266 pct.

(e) The minimum charge for servicesof supervising officers and of analystsshall be not less than the charge for 1hour, and time after the first hourshall be computed in multiples of 1



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21 CFR Ch. I (4101 Edition)Pt. 2

hour, disregarding fractional parts lessthan 12 hour.

PART 2GENERAL ADMINISTRATIVERULINGS AND DECISIONS


Sec.2.5 Imminent hazard to the public health.2.10 Examination and investigation sam-

ples.2.19 Methods of analysis.

Subpart BHuman and Animal Foods

2.25 Grain seed treated with poisonous sub-stances; color identification to preventadulteration of human and animal food.

2.35 Use of secondhand containers for theshipment or storage of food and animalfeed.

Subparts CE [Reserved]

Subpart FCaustic Poisons

2.110 Definition of ammonia under FederalCaustic Poison Act.

Subpart GProvisions Applicable to Spe-cific Products Subject to the FederalFood, Drug, and Cosmetic Act

2.125 Use of chlorofluorocarbon propellantsin self-pressurized containers.

AUTHORITY: 21 U.S.C. 321, 331, 335, 342, 346a,348, 351, 352, 355, 360b, 361, 371, 372, 374; 15U.S.C. 402, 409.

SOURCE: 42 FR 15559, Mar. 22, 1977, unlessotherwise noted.


2.5 Imminent hazard to the publichealth.

(a) Within the meaning of the Fed-eral Food, Drug, and Cosmetic Act animminent hazard to the public healthis considered to exist when the evi-dence is sufficient to show that a prod-

uct or practice, posing a significantthreat of danger to health, creates apublic health situation (1) that shouldbe corrected immediately to preventinjury and (2) that should not be per-mitted to continue while a hearing orother formal proceeding is being held.The imminent hazard may be declaredat any point in the chain of eventswhich may ultimately result in harmto the public health. The occurrence of

the final anticipated injury is not es-sential to establish that an imminenthazard of such occurrence exists.

(b) In exercising his judgment onwhether an imminent hazard exists, theCommissioner will consider the num-ber of injuries anticipated and the na-ture, severity, and duration of the an-ticipated injury.

2.10 Examination and investigationsamples.

(a)(1) When any officer or employeeof the Department collects a sample ofa food, drug, or cosmetic for analysisunder the act, the sample shall be des-ignated as an official sample if recordsor other evidence is obtained by him orany other officer or employee of theDepartment indicating that the ship-ment or other lot of the article fromwhich such sample was collected wasintroduced or delivered for introduc-tion into interstate commerce, or wasin or was received in interstate com-merce, or was manufactured within aTerritory. Only samples so designatedby an officer or employee of the De-partment shall be considered to be offi-cial samples.

(2) For the purpose of determiningwhether or not a sample is collected foranalysis, the term analysis includes ex-aminations and tests.

(3) The owner of a food, drug, or cos-metic of which an official sample iscollected is the person who owns theshipment or other lot of the articlefrom which the sample is collected.

(b) When an officer or employee ofthe Department collects an officialsample of a food, drug, or cosmetic foranalysis under the act, he shall collectat least twice the quantity estimatedby him to be sufficient for analysis, un-less:

(1) The amount of the article avail-

able and reasonably accessible for sam-pling is less than twice the quantity soestimated, in which case he shall col-lect as much as is available and reason-ably accessible.

(2) The cost of twice the quantity soestimated exceeds $150.

(3) The sample cannot by diligent useof practicable preservation techniquesavailable to the Food and Drug Admin-istration be kept in a state in which it



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could be readily and meaningfully ana-lyzed in the same manner and for thesame purposes as the Food and DrugAdministrations analysis.

(4) The sample is collected from ashipment or other lot which is beingimported or offered for import into theUnited States.

(5) The sample is collected from aperson named on the label of the arti-cle or his agent, and such person is alsothe owner of the article.

(6) The sample is collected from theowner of the article, or his agent, and

such article bears no label or, if itbears a label, no person is named there-on.

In addition to the quantity of sampleset forth in this paragraph, the officeror employee shall, if practicable, col-lect such further amount as he esti-mates will be sufficient for use as trialexhibits.

(c) After the Food and Drug Adminis-tration has completed such analysis ofan official sample of a food, drug, orcosmetic as it determines, in thecourse of analysis and interpretation ofanalytical results, to be adequate to es-tablish the respects, if any, in whichthe article is adulterated or mis-

branded within the meaning of the act,or otherwise subject to the prohibi-tions of the act, and has reserved anamount of the article it estimates to beadequate for use as exhibits in the trialof any case that may arise under theact based on the sample, a part of thesample, if any remains available, shallbe provided for analysis, upon writtenrequest, by any person named on thelabel of the article, or the owner there-of, or the attorney or agent of suchperson or owner, except when:

(1) After collection, the sample or re-maining part thereof has become de-composed or otherwise unfit for anal-ysis, or

(2) The request is not made within areasonable time before the trial of anycase under the act, based on the sampleto which such person or owner is aparty. The person, owner, attorney, oragent who requests the part of sampleshall specify the amount desired. A re-quest from an owner shall be accom-panied by a showing of ownership, anda request from an attorney or agent bya showing of authority from such per-

son or owner to receive the part ofsample. When two or more requests forparts of the same sample are receivedthe requests shall be complied with inthe order in which they were receivedso long as any part of the sample re-mains available therefor.

(d) When an official sample of food,drug, or cosmetic is the basis of a no-tice given under section 305 of the act,or of a case under the act, and the per-son to whom the notice was given, orany person who is a party to the case,has no right under paragraph (c) of thissection to a part of the sample, suchperson or his attorney or agent mayobtain a part of the sample upon re-quest accompanied by a written waiverof right under such paragraph (c) fromeach person named on the label of thearticle and owner thereof, who has notexercised his right under such para-graph (c). The operation of this para-graph shall be subject to the excep-tions, terms, and conditions prescribedin paragraph (c) of this section.

(e) The Food and Drug Administra-tion is authorized to destroy:

(1) Any official sample when it deter-mines that no analysis of such sample

will be made;(2) Any official sample or part there-of when it determines that no noticeunder section 305 of the act, and nocase under the act, is or will be basedon such sample;

(3) Any official sample or part there-of when the sample was the basis of anotice under section 305 of the act, andwhen, after opportunity for presen-tation of views following such notice,it determines that no other such no-tice, and no case under the act, is orwill be based on such sample;

(4) Any official sample or part there-of when the sample was the basis of acase under the act which has gone to

final judgment, and when it determinesthat no other such case is or will bebased on such sample;

(5) Any official sample or part there-of if the article is perishable;

(6) Any official sample or part there-of when, after collection, such sampleor part has become decomposed or oth-erwise unfit for analysis;

(7) That part of any official samplewhich is in excess of three times the



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quantity it estimates to be sufficient

for analysis.


FR 51299, Sept. 25, 1998]

2.19 Methods of analysis.

Where the method of analysis is not

prescribed in a regulation, it is the pol-

icy of the Food and Drug Administra-

tion in its enforcement programs to

utilize the methods of analysis of the

Association of Official Analytical

Chemists (AOAC) as published in the

latest edition (13th Ed., 1980) of theirpublication Official Methods of Anal-

ysis of the Association of Official Ana-

lytical Chemists,and the supplements

thereto (Changes in Methodsas pub-

lished in the March issues of the Jour-

nal of the Association of Official Ana-

lytical Chemists), which are incor-

porated by reference, when available

and applicable. Copies are available

from the Association of Official Ana-

lytical Chemists, 2200 Wilson Blvd.,

Suite 400, Arlington, VA 222013301, or

available for inspection at the Office of

the Federal Register, 800 North Capitol

Street NW., suite 700, Washington, DC.

In the absence of an AOAC method, theCommissioner will furnish a copy of

the particular method, or a reference

to the published method, that the Food

and Drug Administration will use in its

enforcement program. Other methods

may be used for quality control, speci-

fications, contracts, surveys, and simi-

lar nonregulatory functions, but it is

expected that they will be calibrated in

terms of the method which the Food

and Drug Administration uses in its

enforcement program. Use of an AOAC

method does not relieve the practioner

of the responsibility to demonstrate

that he can perform the method prop-

erly through the use of positive andnegative controls and recovery and re-

producibility studies.


FR 946, Jan. 8, 1982; 54 FR 9034, Mar. 3, 1989]

Subpart BHuman and AnimalFoods

2.25 Grain seed treated with poi-sonous substances; color identifica-tion to prevent adulteration ofhuman and animal food.

(a) In recent years there has devel-oped increasing use of poisonous treat-ments on seed for fungicidal and otherpurposes. Such treated seed, if con-sumed, presents a hazard to humansand livestock. It is not unusual forstocks of such treated food seeds to re-main on hand after the planting seasonhas passed. Despite the cautions re-quired by the Federal Seed Act (53Stat. 1275, as amended 72 Stat. 476, 7U.S.C. 1551 et seq.) in the labeling of thetreated seed, the Food and Drug Ad-ministration has encountered manycases where such surplus stocks oftreated wheat, corn, oats, rye, barley,and sorghum seed had been mixed withuntreated seed and sent to market forfood or feed use. This has resulted inlivestock injury and in legal actionsunder the Federal Food, Drug, and Cos-metic Act against large quantities offood adulterated through such admix-

ture of poisonous treated seeds withgood food. Criminal cases were broughtagainst some firms and individuals.Where the treated seeds are promi-nently colored, buyers and users orprocessors of agricultural food seed forfood purposes are able to detect the ad-mixture of the poisonous seed and thusreject the lots; but most such buyers,users, and processors do not have thefacilities or scientific equipment to de-termine the presence of the poisonouschemical at the time crops are deliv-ered, in cases where the treated seedshave not been so colored. A suitablecolor for this use is one that is in suffi-cient contrast to the natural color of

the food seed as to make admixture oftreated, denatured seeds with good foodeasily apparent, and is so applied thatit is not readily removed.

(b) On and after December 31, 1964,the Food and Drug Administration will



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regard as adulterated any interstateshipment of the food seeds wheat, corn,oats, rye, barley, and sorghum bearinga poisonous treatment in excess of arecognized tolerance or treatment forwhich no tolerance or exemption fromtolerance is recognized in regulationspromulgated pursuant to section 408 ofthe Federal Food, Drug, and CosmeticAct, unless such seeds have been ade-quately denatured by a suitable colorto prevent their subsequent inad-vertent use as food for man or feed foranimals.

(c) Attention is called to the labelingrequirements of the Federal HazardousSubstances Act, where applicable to de-natured seeds in packages suitable forhousehold use.

2.35 Use of secondhand containersfor the shipment or storage of foodand animal feed.

(a) Investigations by the Food andDrug Administration, the NationalCommunicable Disease Center of theU.S. Public Health Service, the Con-sumer and Marketing Service of theU.S. Department of Agriculture, and byvarious State public health agencieshave revealed practices whereby food

and animal feed stored or shipped insecondhand containers have been ren-dered dangerous to health. Such con-tamination has been the result of theoriginal use of these containers for thestorage and shipment of articles con-taining or bearing disease organisms orpoisonous or deleterious substances.

(b) The Commissioner concludes thatsuch dangerous or potentially dan-gerous practices include, but are notlimited to, the following:

(1) Some vegetable growers and pack-ers employ used poultry crates forshipment of fresh vegetables, includingcabbage and celery. Salmonella orga-nisms are commonly present on dressed

poultry and in excreta and fluidexudates from dressed birds. Thuswooden crates in which dressed poultryhas been iced and packed are potentialsources of Salmonella or otherenteropathogenic microorganisms thatmay contaminate fresh vegetableswhich are frequently consumed with-out heat treatment.

(2) Some potato growers and pro-ducers of animal feeds use secondhand

bags for shipment of these articles.Such bags may have originally beenused for shipping or storing pesticide-treated seed or other articles bearingor containing poisonous substances.Thus these secondhand bags are poten-tial sources of contamination of thefood or animal feed stored or shippedtherein.

(c) In a policy statement issued April11, 1968, the Food and Drug Administra-tion declared adulterated within themeaning of section 402(a) of the Fed-eral Food, Drug, and Cosmetic Act

shipments of vegetables or other ediblefood in used crates or containers thatmay render the contents injurious tohealth. This policy statement is ex-tended so that the Food and Drug Ad-ministration will regard as adulteratedwithin the meaning of section 402(a) ofthe act shipments of vegetables, otheredible food, or animal feed in usedcrates, bags, or other containers thatmay render the contents injurious tohealth.

Subparts CE [Reserved]

Subpart FCaustic Poisons

2.110 Definition of ammonia underFederal Caustic Poison Act.

For the purpose of determiningwhether an article containing ammo-nia is subject to the Federal CausticPoison Act, the ammonia content is tobe calculated as NH3.

Subpart GProvisions Applicableto Specific Products Subjectto the Federal Food, Drug,and Cosmetic Act

2.125 Use of chlorofluorocarbon pro-pellants in self-pressurized con-tainers.

(a) As used in this section:(1) Chlorofluorocarbon means any

fully halogenated chlorofluoroalkane.(2) Propellant means a liquefied or

compressed gas that is used in whole orin part to expel from the same self-pressurized container or from a sepa-rate container a liquid or solid mate-rial different from the propellant, butthe term does not include the use of achlorofluorocarbon as an aerating



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21 CFR Ch. I (4101 Edition) 2.125

agent for foamed or sprayed food prod-ucts.

(b) Chlorofluorocarbons are widelyused in products subject to the FederalFood, Drug, and Cosmetic Act, withthe principal use being as propellantsin self-pressurized containers. Informa-tion recently developed indicates thatchlorofluorocarbons may reduce theamount of ozone in the stratosphereand thus increase the amount of ultra-violet radiation reaching the earth. Anincrease in ultraviolet radiation mayincrease the incidence of skin cancer,

change the climate, and produce othereffects of unknown magnitude on hu-mans, animals, and plants.Chlorofluorocarbons may also affectthe climate by increasing infrared ab-sorption in the atmosphere.

(c) Except as provided in paragraph(e) of this section, any food, drug, de-vice, or cosmetic in a self-pressurizedcontainer that contains a chlorofluoro-carbon propellant is adulterated and/ormisbranded in violation of the act, andany drug product in a self-pressurizedcontainer that contains a chlorofluoro-carbon propellant is a new drug or anew animal drug.

(d) The use of a chlorofluorocarbon as

a propellant in a self-pressurized con-tainer of a drug product will not resultin the drug product being adulteratedand/or misbranded provided a new drugapplication, a new animal drug applica-tion, or in the case of a certifiable anti-biotic an antibiotic application for thedrug product has been approved, a peti-tion has been filed as provided by para-graph (f) of this section, and paragraph(e) of this section has been amended tospecify the use as essential.

(e) The adulteration and misbrandingprovisions of paragraph (c) of this sec-tion shall not apply to the following es-sential uses of chlorofluorocarbons:

(1) Metered-dose steriod human drugs

for nasal inhalation,(2) Metered-dose steriod human drugs

for oral inhalation,(3) Metered-dose adrenergic broncho-

dilator human drugs for oral inhala-tion,

(4) Contraceptive vaginal foams forhuman use, and

(5) Metered-dose ergotamine tartratedrug products administered by oral in-halation for use in humans.

(6) Intrarectal hydrocortisone ace-tate for human use.

(7) Polymyxin B sulfate-bacitracinzinc-neomycin sulfate soluble anti-biotic powder without excipients, fortopical use on humans.

(8) Anesthetic drugs for topical useon accessible mucous membranes ofhumans where a cannula is used for ap-plication.

(9) Metered-dose nitroglycerin humandrugs administered to the oral cavity.

(10) Metered-dose cromolyn sodiumhuman drugs administered by oral in-

halation.(11) Metered-dose ipratropium bro-

mide for oral inhalation.(12) Metered-dose atropine sulfate

aerosol human drugs administered byoral inhalation.

(13) Metered-dose nedocromil sodiumhuman drugs administered by oral in-halation.

(14) Metered-dosed ipratropium bro-mide and albuterol sulfate, in combina-tion, administered by oral inhalationfor human use.

(15) Sterile aerosol talc administeredintrapleurally by thoracoscopy forhuman use.

(f) Any person may file a petition in

accordance with part 10 of this chapterto amend paragraph (e) of this sectionto specify a use of chlorofluorocarbonsin a product as not being subject to theadulteration and misbranding provi-sions in paragraph (c) of this section.The petition must be supported by anadequate showing that:

(1) There are no technically feasiblealternatives to the use of a chloro-fluorocarbon in the product,

(2) The product provides a substan-tial health benefit, environmental ben-efit, or other public benefit that wouldnot be obtainable without the use ofthe chlorofluorocarbon, and

(3) The use does not involve a signifi-

cant release of chlorofluorocarbonsinto the atmosphere or that the releaseis warranted in view of the con-sequence if the use were not permitted.

(g) Any holder of an approved newdrug application or new animal drugapplication for a drug product con-taining a chlorofluorocarbon in a self-pressurized container, except thosedrug products listed in paragraph (e) ofthis section, shall submit to the Food



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and Drug Administration on or beforeOctober 1, 1978, either a supplementalapplication providing for a revised for-mulation complying with the require-ments of 314.70 or 514.8 of this chap-ter or a letter requesting that a newdrug application or a new animal drugapplication for the drug product con-taining chlorofluorocarbon be with-drawn and that the right to a hearingon the withdrawal of the application iswaived.

(h)(1) Each manufacturer of a drugproduct listed in paragraph (e) of this

section that is not covered by an ap-proved new drug application shall sub-mit a new drug application in accordwith 314.50 of this chapter on or beforeJune 15, 1978.

(2) An abbreviated new drug applica-tion conforming to 314.94 of this chap-ter is acceptable in lieu of a full newdrug application for any product in-cluded in the classes of products inparagraph (e) of this section if theproduct is one that is described under 314.92 of this chapter. A finding hasbeen made that an abbreviated newdrug application may be submitted forthe following products included in theclasses of products listed in paragraph

(e) of this section:(i) Ergotamine tartrate supplied in a

metered-dose aerosol form suitable fororal inhalation for the treatment ofmigraine headaches. Each measureddose must deliver a dose of the activeingredient equivalent to that containedin the product that has been the sub-ject of a separate finding that an ab-breviated new drug application is suit-able.

(ii) Isoproterenol hydrochloride sup-plied in a metered-dose aerosol formsuitable for oral inhalation for use asan adrenergic bronchodilator. Eachmeasured dose must deliver a dose ofthe active ingredient equivalent to

that contained in the products thathave been the subject of a separatefinding that an abbreviated new drugapplication is suitable.

(iii) Epinephrine, epinephrinebitartrate, or epinephrine hydro-chloride (racemic) in a metered-doseaerosol form suitable for oral inhala-tion for use as an adrenergic broncho-dilator. Each measured dose must de-liver a dose of the active ingredient

equivalent to that specified in an OTCproposed or final monograph issuedunder the provisions of 21 CFR part 330.

(iv) Nonoxynol 9 in an aerosol foamsuitable for vaginal administration asa contraceptive foam. The aerosol foammust contain 8 to 12.5 percent ofnonoxynol 9.

(i) Any sponsor of an Investiga-tional New Drug Application(IND) orNotice of Claimed Exemption for aNew Animal Drug (INAD) for a drugproduct containing a chlorofluoro-carbon shall:

(1) Amend the IND or INAD on or be-fore December 15, 1978, to revise theformulation removing the chloro-fluorocarbon.

(2) Submit the information requiredunder paragraph (f) of this section toamend paragraph (e) of this section toshow that the use of chlorofluoro-carbon is essential, or

(3) Submit the information requiredunder paragraph (j) of this section re-questing that studies with the drugproduct containing a chlorofluoro-carbon propellant be allowed to be per-formed.

(j) Any sponsor of an IND or INAD

who wishes to initiate or continue astudy beyond December 15, 1978 on adrug product containing a chloro-fluorocarbon shall submit a petition inaccordance with part 10 of this chapterrequesting that studies be permitted tocollect the data to show that the use ofthe chlorofluorocarbon is an essentialuse. The petitions must be supportedby the following:

(1) A description of the drug product,

(2) An explanation why a chloro-fluorocarbon propellant is used in theproduct rather than another propellantor another dosage form of the product,and

(3) The benefit that the investiga-

tional product is believed to have andthat the sponsor hopes to demonstrateby the studies.

(k) The Commissioner will initiateaction to withdraw approval of an ap-plication or terminate an IND or INADnotice in accordance with the applica-ble provisions of section 505 of the actand parts 312 and 314 of this chapter, orsection 512 of the act and parts 511 and514 of this chapter upon failure of a



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21 CFR Ch. I (4101 Edition)Pt. 3

holder of an approved new drug appli-cation or approved new animal drug ap-plication or sponsor of an IND or INADnotice to comply with the applicableprovisions of this section.

(l) Food, drug, device, or cosmeticproducts manufactured or packaged onor after December 15, 1978, and finishedproducts initially introduced intointerstate commerce on or after April15, 1979, shall comply with this regula-tion.

[43 FR 11316, Mar. 17, 1978, as amended at 44FR 3961, Jan. 19, 1979; 44 FR 30334, May 26,

1979; 45 FR 22902, April 4, 1980; 51 FR 4591,Feb. 6, 1986; 52 FR 15717, Apr. 30, 1987; 54 FR9034, Mar. 3, 1989; 55 FR 39267, Sept. 26, 1990;57 FR 17980, Apr. 28, 1992; 58 FR 6088, Jan. 26,1993; 61 FR 15700, Apr. 9, 1996; 61 FR 25392,May 21, 1996]

PART 3PRODUCT JURISDICTION

Subpart AAssignment of Agency Com-ponent for Review of Premarket Appli-cations

Sec.3.1 Purpose.3.2 Definitions.3.3 Scope.3.4 Designated agency component.

3.5 Procedures for identifying the des-ignated agency component.

3.6 Product jurisdiction officer.3.7 Request for designation.3.8 Letter of designation.3.9 Effect of letter of designation.3.10 Stay of review time.

Subpart B [Reserved]

AUTHORITY: 21 U.S.C. 321, 351, 352, 353, 355,360, 360c360f, 360h360j, 360gg360ss, 371(a),379e, 381, 394; 42 U.S.C. 216, 262.

SOURCE: 56 FR 58756, Nov. 21, 1991, unlessotherwise noted.

Subpart AAssignment of Agen-cy Component for Review of

Premarket Applications

3.1 Purpose.

This regulation relates to agencymanagement and organization and hastwo purposes. The first is to implementsection 503(g) of the act, as added bysection 16 of the Safe Medical DevicesAct of 1990 (Pub. L. 101629), by speci-fying how FDA will determine the or-ganizational component within FDA

designated to have primary jurisdic-tion for the premarket review and reg-ulation of products that are comprisedof any combination of a drug and a de-vice; a device and a biological; a bio-logical and a drug; or a drug, a deviceand a biological. This determinationwill eliminate, in most cases, the needto receive approvals from more thanone FDA component for such combina-tion products. The second purpose ofthis regulation is to enhance the effi-ciency of agency management and op-erations by providing procedures for

determining which agency componentwill have primary jurisdiction for anydrug, device, or biological productwhere such jurisdiction is unclear or indispute. Nothing in this section pre-vents FDA from using any agency re-sources it deems necessary to ensureadequate review of the safety and effec-tiveness of any product, or the substan-tial equivalence of any device to apredicate device.

3.2 Definitions.

For the purpose of this part:

(a) Act means the Federal Food,Drug, and Cosmetic Act.

(b) Agency component means the Cen-ter for Biologics Evaluation and Re-search, the Center for Devices and Ra-diological Health, or the Center forDrug Evaluation and Research.

(c) Applicant means any person whosubmits or plans to submit an applica-tion to the Food and Drug Administra-tion for premarket review. For pur-poses of this section, the terms spon-sor and applicant have the samemeaning.

(d) Biological product has the meaninggiven the term in section 351(a) of thePublic Health Service Act (42 U.S.C.262(a)).

(e) Combination product includes:

(1) A product comprised of two ormore regulated components, i.e., drug/device, biologic/device, drug/biologic,or drug/device/biologic, that are phys-ically, chemically, or otherwise com-bined or mixed and produced as a singleentity;

(2) Two or more separate productspackaged together in a single packageor as a unit and comprised of drug anddevice products, device and biological



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products, or biological and drug prod-ucts;

(3) A drug, device, or biological prod-uct packaged separately that accordingto its investigational plan or proposedlabeling is intended for use only withan approved individually specifieddrug, device, or biological productwhere both are required to achieve theintended use, indication, or effect andwhere upon approval of the proposedproduct the labeling of the approvedproduct would need to be changed, e.g.,to reflect a change in intended use,

dosage form, strength, route of admin-istration, or significant change in dose;or

(4) Any investigational drug, device,or biological product packaged sepa-rately that according to its proposedlabeling is for use only with anotherindividually specified investigationaldrug, device, or biological productwhere both are required to achieve theintended use, indication, or effect.

(f) Device has the meaning given theterm in section 201(h) of the act.

(g) Drug has the meaning given theterm in section 201(g)(1) of the act.

(h) FDA means Food and Drug Ad-ministration.

(i) Letter of designation means thewritten notice issued by the productjurisdiction officer specifying the agen-cy component with primary jurisdic-tion for a combination product.

(j) Letter of request means an appli-cants written submission to the prod-uct jurisdiction officer seeking the des-ignation of the agency component withprimary jurisdiction.

(k) Premarket review includes the ex-amination of data and information inan application for premarket reviewdescribed in sections 505, 510(k), 513(f),515, or 520(g) or 520(l) of the act or sec-tion 351 of the Public Health ServiceAct of data and information contained

in any investigational new drug (IND)application, investigational device ex-emption (IDE), new drug application(NDA), biologics license application,device premarket notification, devicereclassification petition, and pre-market approval application (PMA).

(l) Product means any article thatcontains any drug as defined in section201(g)(1) of the act; any device as de-fined in section 201(h) of the act; or any

biologic as defined in section 351(a) ofthe Public Health Service Act (42U.S.C. 262(a)).

(m) Product jurisdiction officer is theperson or persons responsible for desig-nating the component of FDA with pri-mary jurisdiction for the premarket re-view and regulation of a combinationproduct or any product requiring a ju-risdictional designation under thispart.

(n) Sponsor means applicant (see 3.2(c)).

[56 FR 58756, Nov. 21, 1991 as amended at 64FR 398, Jan. 5, 1999; 64 FR 56447, Oct. 20, 1999]

3.3 Scope.

This section applies to:(a) Any combination product, or(b) Any product where the agency

component with primary jurisdiction isunclear or in dispute.

3.4 Designated agency component.

(a) To designate the agency compo-nent with primary jurisdiction for thepremarket review and regulation of acombination product, the agency shalldetermine the primary mode of actionof the product. Where the primarymode of action is that of:

(1) A drug (other than a biologicalproduct), the agency componentcharged with premarket review ofdrugs shall have primary jurisdiction;

(2) A device, the agency componentcharged with premarket review of de-vices shall have primary jurisdiction;

(3) A biological product, the agencycomponent charged with premarket re-view of biological products shall haveprimary jurisdiction.

(b) The designation of one agencycomponent as having primary jurisdic-tion for the premarket review and reg-ulation of a combination product doesnot preclude consultations by thatcomponent with other agency compo-

nents or, in appropriate cases, the re-quirement by FDA of separate applica-tions.

3.5 Procedures for identifying thedesignated agency component.

(a)(1) The Center for Biologics Eval-uation and Research, the Center forDevices and Radiological Health, andthe Center for Drug Evaluation and Re-search have entered into agreements



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(xi) Dose and route of administrationof drug or biologic;

(xii) Description of related products,including the regulatory status ofthose related products; and

(xiii) Any other relevant informa-tion.

(3) The sponsors recommendation asto which agency component shouldhave primary jurisdiction, with accom-panying statement of reasons.

(d) Where to file: all communicationspursuant to this subpart shall be ad-dressed to the attention of the product

jurisdiction officer. Such a request, inits mailing cover should be plainlymarked Request for Designation.

3.8 Letter of designation.

(a) Each request for designation willbe reviewed for completeness within 5working days of receipt. Any requestfor designation determined to be in-complete will be returned to the appli-cant with a request for the missing in-formation. The sponsor of an acceptedrequest for designation will be notifiedof the filing date.

(b) Within 60 days of the filing date ofa request for designation, the productjurisdiction officer will issue a letter of

designation to the sponsor, with copiesto the centers, specifying the agencycomponent designated to have primaryjurisdiction for the premarket reviewand regulation of the product at issue,and any consulting agency compo-nents. The product jurisdiction officermay request a meeting with the spon-sor during the review period to discussthe request for designation. If the prod-uct jurisdiction officer has not issued aletter of designation within 60 days ofthe filing date of a request for designa-tion, the sponsors recommendation ofthe center with primary jurisdiction,in accordance with 3.7(c)(3), shall be-come the designated agency compo-

nent.(c) Request for reconsideration bysponsor: If the sponsor disagrees withthe designation, it may request theproduct jurisdiction officer to recon-sider the decision by filing, within 15days of receipt of the letter of designa-tion, a written request for reconsider-

ation not exceeding 5 pages. No new in-

formation may be included in a request

for reconsideration. The product juris-

diction officer shall review and act on

the request in writing within 15 days of

its receipt.

3.9 Effect of letter of designation.

(a) The letter of designation con-

stitutes an agency determination that

is subject to change only as provided in

paragraph (b) of this section.

(b) The product jurisdiction officer

may change the designated agencycomponent with the written consent of

the sponsor, or without its consent to

protect the public health or for other

compelling reasons. A sponsor shall be

given 30 days written notice of any pro-

posed nonconsensual change in des-

ignated agency component. The spon-

sor may request an additional 30 days

to submit written objections, not to ex-

ceed 15 pages, to the proposed change,

and shall be granted, upon request, a

timely meeting with the product juris-

diction officer and appropriate center

officials. Within 30 days of receipt of

the sponsors written objections, the

product jurisdiction officer shall issueto the sponsor, with copies to appro-

priate center officials, a written deter-

mination setting forth a statement of

reasons for the proposed change in des-

ignated agency component. A non-

consensual change in the designated

agency component requires the concur-

rence of the Deputy Commissioner for

Op

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