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Guidance for Industry 

Labeling for Human Prescription 

Drug and Biological Products — 

Implementing the New Content and 

Format Requirements 

DRAFT GUIDANCE

This guidance document is being distributed for comment purposes only.

Comments and suggestions regarding this draft document should be submitted within 90 days of 

publication in the Federal Register of the notice announcing the availability of the draft 

guidance. Submit comments to the Division of Dockets Management (HFA-305), Food and 

Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All comments 

should be identified with the docket number listed in the notice of availability that publishes in 

the Federal Register. 

For questions regarding this draft document contact (CDER) Janet Norden at 301-796-2270, or 

(CBER) Toni Stifano at 301-827-6190. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

January 2006 

Labeling 
J:\!GUIDANC\6005dft.doc 

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Guidance for Industry

Labeling for Human Prescription 

Drug and Biological Products — 

Implementing the New Content and 

Format Requirements 

Additional copies are available from: 

Office of Training and Communications 

Division of Drug Information, HFD-210 

5600 Fishers Lane 

Rockville, MD 20857 

(Tel) 301-827-4573 

(Internet) http://www.fda.gov/cder/guidance/index.htm 

or 

 Office of Communication, Training and 

Manufacturers Assistance, HFM-40 

Center for Biologics Evaluation and Research 

 Food and Drug Administration 

1401 Rockville Pike, Rockville, MD 20852-1448 

(Tel) 800-835-4709 or 301-827-1800 

(Internet) http://www.fda.gov/cber/guidelines.htm. 

U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

January 2006 

Labeling
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TABLE OF CONTENTS 

I. INTRODUCTION............................................................................................................. 1

II. BACKGROUND ............................................................................................................... 2

III. CONSIDERATIONS FOR REVISING LABELING.................................................... 3

A. General Principles..........................................................................................................................3

1. Developing New Sections.................................................................................................................4

2. Data Analyses ..................................................................................................................................4

3. Updating Claims ..............................................................................................................................4

B. Distributing Information Among Sections ..................................................................................5

1. Creating Hierarchy..........................................................................................................................5

2. Avoiding Redundancy .....................................................................................................................5

3. Using Cross-References...................................................................................................................6

4. Illustrative Example.........................................................................................................................6

IV. HIGHLIGHTS .................................................................................................................. 7

A. General Principles..........................................................................................................................7

B. Information in Highlights..............................................................................................................8

1. Initial U.S. Approval (§ 201.57(a)(3)) .............................................................................................8

2. Boxed Warning (§ 201.57(a)(4))......................................................................................................8

3. Recent Major Changes (§ 201.57(a)(5)).........................................................................................8

4. Indications and Usage (§ 201.57(a)(6)) ........................................................................................10

5. Dosage and Administration (§ 201.57(a)(7)) ................................................................................10

6. Dosage Forms and Strengths (§ 201.57(a)(8))..............................................................................11

7. Contraindications (§ 201.57(a)(9)) ...............................................................................................11

8. Warnings and Precautions (§ 201.57(a)(10))................................................................................11

9. Adverse Reactions (§ 201.57(a)(11)).............................................................................................11

10. Drug Interactions (§ 201.57(a)(12)) ...........................................................................................12

11. Use in Specific Populations (§ 201.57(a)(13))............................................................................13

V. PROCEDURAL INFORMATION................................................................................ 13

A. Applications Covered by the Final Rule ....................................................................................13

1. New NDAs, BLAs, and Efficacy Supplements................................................................................14

2. Approved and Pending Applications .............................................................................................14

B. Appending FDA-Approved Patient Labeling............................................................................15

C. Submitting Electronic Versions of Labeling..............................................................................16

D. Applying for a Waiver from Highlights’ One-Half Page Requirement ..................................16

E. Class Labeling ..............................................................................................................................16

1. Mandated Statements.....................................................................................................................16

2. Class Labeling Statements That Are Not Mandated by Regulation...............................................17

F. Abbreviated New Drug Application (ANDA) Products ...........................................................18

VI. FORMATTING............................................................................................................... 18
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A. Subheadings..................................................................................................................................18

B. Omitted Sections (§ 201.56(d)(4)) ...............................................................................................18

C. Cross-references...........................................................................................................................19

D. Type Size.......................................................................................................................................20

APPENDIX A — Frequently Asked Questions ....................................................................... 21

APPENDIX B — Prescription Drug Labeling Sections .......................................................... 24

APPENDIX C — Reorganizing Labeling Sections.................................................................. 25

APPENDIX D — Implementation Plan.................................................................................... 26

APPENDIX E — Type Size Requirements for Labeling and FDA-Approved Patient 

Labeling Included with Labeling............................................................................................... 27
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1 

Guidance for Industry1 2 

3 

4 Labeling for Human Prescription Drug and Biological Products — 

Implementing the New Content and Format Requirements2 5 

6 

7 

8 

9 This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current 

10 thinking on this topic. It does not create or confer any rights for or on any person and does not operate to 

11 bind FDA or the public. You can use an alternative approach if it satisfies the requirements of the 

12 applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff 

13 responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the 

14 appropriate number listed on the title page of this guidance. 

15 

16 

17 

18 I. INTRODUCTION

19 This guidance is intended to assist applicants in complying with the new content and format 

20 requirements of labeling for human prescription drug and biological products (21 CFR 201.56(d) 

and 201.57).3 21 FDA recognizes the broad scope and complexity of these new regulations and is 

22 issuing this guidance to provide recommendations for applicants revising labeling of already 

23 approved products and for applicants drafting labeling for new products to be submitted with a 

24 new drug application (NDA) or biologics license application (BLA). FDA also recognizes that, 

25 as both applicants and the Agency become more familiar with writing labeling that complies 

26 with these new regulations, good examples and practices will emerge. FDA has appended a list 

27 of Frequently Asked Questions (FAQs) (Appendix A) and has posted illustrative examples of 

28 labeling in the new format at www.fda.gov/cder/regulatory/physLabel/default.htm. The 

29 information at this Web site will be updated with new examples, if needed, as they become 

30 available. 

31 

32 This guidance provides recommendations on the following subjects: 

33 

 

1

 This guidance has been prepared by the Medical Policy Coordinating Committees in the Center for Drug 

Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) at the Food and Drug 

Administration. 

2

 See the final rule “Requirements on Content and Format of Labeling for Human Prescription Drug and Biological 

Products” published in the Federal Register in January 2006. 

3

 This guidance applies to drugs, including biological drug products. For the purposes of this guidance, drug or drug 

product will be used to refer to human prescription drug and biological products that are regulated as drugs. 
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34 • Issues to consider when revising labeling for approved products to meet the new content 

35 and format requirements, including: 

36 • how to distribute information among newly created sections 

37 • when it is important to repeat information in varying levels of detail in different 

38 sections 

39 • how to minimize redundancy 

40 • when to cross-reference 

41 • Issues to consider when developing “Highlights of Prescribing Information” (Highlights) 

42 • Procedural information, including: 

43 • how to determine which applications are covered 

44 • how to submit labeling 

45 • how to apply for a waiver 

46 • information about class labeling 

47 • information about abbreviated new drug applications (ANDAs) 

48 • How to format labeling, including the use of subheadings, cross-references, type size, and 

49 how to address omitted sections 

50 FDA has also made minor amendments to the regulations for labeling of prescription drug and 

51 biological products not subject to the new content and format requirements (see 21 CFR 

52 201.56(e) and 201.80 and sections V.A and V.B of this document). 

53 

54 FDA's guidance documents, including this guidance, do not establish legally enforceable 

55 responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should 

56 be viewed only as recommendations, unless specific regulatory or statutory requirements are 

57 cited. The use of the word should in Agency guidances means that something is suggested or 

58 recommended, but not required. 

59 

60 II. BACKGROUND 

61 

62 In January 2006, the Agency published a final rule that amended the requirements for the content 

63 and format of labeling for human prescription drug and biological products. The new regulations 

64 are designed to make information in prescription drug labeling easier for health care practitioners 

65 to access, read, and use, thereby facilitating practitioners’ use of labeling to make prescribing 

66 decisions. Changes to the labeling format include the addition of introductory prescribing 

67 information, entitled “Highlights of Prescribing Information” (Highlights), and a “Table of 

68 Contents” (Contents) for the “Full Prescribing Information” (FPI). Highlights contains selected 

69 information from the FPI that health care practitioners most commonly reference and consider 

70 most important. The Contents lists the sections and subsections of the FPI. The final rule also 

71 reorders and reorganizes the FPI, makes minor changes to the content of the FPI, and sets 
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72 minimum graphical requirements for the format of the labeling. For the purpose of this 

73 guidance, the term new format refers to labeling that meets the content and format requirements 

74 at §§ 201.56(d) and 201.57. The term old format refers to labeling formatted to meet the 

requirements of the 1979 final rule (former §§ 201.56 and 201.57).4 75 See Appendix B for a listing 

76 of prescription drug labeling sections in the old and new formats. 

77 

78 This guidance focuses on the major issues applicants may face when developing new labeling or 

79 when revising labeling to meet the new requirements and provides procedural information 

80 important for implementation. FDA expects that the most challenging aspects of this new 

81 regulation will be developing Highlights and distributing information among sections that have 

82 been substantially affected by this rule, particularly when the information must be culled from 

83 the labeling in the old format. Therefore, the guidance focuses primarily on these issues and not 

84 on developing sections that have not been changed by this rule. Additional guidance documents 

85 that address content and format for specific FPI sections are available and should be consulted 

when developing labeling.5 86 

87 

88 

89 III. CONSIDERATIONS FOR REVISING LABELING 

90 

91 A. General Principles 

92 

93 The FPI in the new format contains substantially the same information as labeling in the 

94 old format, typically with reordering and reorganization of the information. For example, 

95 new labeling sections (e.g., DRUG INTERACTIONS, USE IN SPECIFIC 

96 POPULATIONS, PATIENT COUNSELING INFORMATION) contain information 

97 formerly included in the PRECAUTIONS section. Certain sections (e.g., CLINICAL 

98 STUDIES, NONCLINICAL TOXICOLOGY) that were previously optional are now 

99 required (§ 201.56(d)). Therefore, although labeling in the old format for approved 

100 products does not contain the new section headings, most of the content already is 

101 included in the labeling under different headings or subheadings. For example, 

102 information from the old WARNINGS section and old PRECAUTIONS section is 

103 consolidated into a single new section (WARNINGS AND PRECAUTIONS) and 

104 information in certain old PRECAUTIONS subsections (e.g., Information for Patients, 

105 Drug Interactions, Pregnancy, Labor and Delivery, Nursing Mothers, Pediatric Use, 

 

4

 See 44 FR 37434, “Labeling and Prescription Drug Advertising; Content and Format for Human Prescription 

Drugs,” Final Rule, June 26, 1979. 

5

 See the following FDA guidances for industry: Adverse Reactions Section of Labeling for Human Prescription 

Drug and Biological Products — Content and Format and Clinical Studies Section of Labeling for Human 

Prescription Drugs and Biological Products — Content and Format. FDA has issued a draft guidance, Warnings 

and Precautions, Contraindications, and Boxed Warning Sections of Labeling for Human Prescription Drug and 

Biological Products — Content and Format. Once finalized, it will represent the Agency’s thinking on this topic. 

We update guidances periodically. To make sure you have the most recent version of a guidance, check the CDER 

guidance page at http://www.fda.gov/cder/guidance/index.htm 
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106 Geriatric Use) is relocated to new labeling sections (e.g., PATIENT COUNSELING 

107 INFORMATION, DRUG INTERACTIONS, USE IN SPECIFIC POPULATIONS). 

108 

109 FDA recommends following these general principles when revising labeling in the old 

110 format. 

111 

112 1. Developing New Sections 

113 

114 FDA expects that most sections or subsections from labeling in the old format can be 

115 moved, with little or no modification, to corresponding sections in the new format. See 

116 Appendix C for information on how to reorganize labeling sections and subsections 

117 within the new format. 

118 

119 In some cases, however, the labeling in the old format may not include the information 

120 specified by the new regulations or the content of a section may be inadequate. If the 

121 information or section in the old format is inadequate, it must be revised (§ 201.56(a)). 

122 

123 If the labeling in the old format lacks an entire section that is required in the new format, 

124 then the section must be developed unless it is clearly inapplicable (§ 201.56(d)). For 

125 example, if the labeling in the old format does not contain an Information for Patients

126 subsection in the PRECAUTIONS section, the applicant must develop a PATIENT 

127 COUNSELING INFORMATION section unless the section is clearly inapplicable to use 

128 of the drug. 

129 

130 2. Data Analyses 

131 

132 FDA recognizes that revising labeling to comply with the new regulations is an excellent 

133 opportunity to update labeling content to ensure that it accurately reflects current 

134 knowledge. FDA expects that, in most cases, the revisions will involve limited rewriting 

135 aimed at clarifying text, eliminating redundancies, and updating outdated terminology. 

136 FDA emphasizes that no new data analyses of the information in the old format are 

137 required as long as the labeling that is developed is truthful and accurate. However, if 

138 new information is available that causes the labeling to be inaccurate, the labeling must 

139 be updated to incorporate the new information (§ 201.56(a)(2)). In some cases, new data 

140 analyses may be necessary. 

141 

142 3. Updating Claims 

143 

144 Although the content of information in labeling in the old format will not significantly 

145 change when converted to the new format, the process of updating labeling provides a 

146 unique opportunity for the applicant to systematically evaluate information in labeling to 

147 identify unsubstantiated claims or outdated information and revise it accordingly. By 

148 regulation, all express or implied claims in labeling must be supported by substantial 
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evidence.6 149 If unsubstantiated claims currently exist in labeling, the applicant must revise 

150 the labeling to remove such claims (§ 201.56(a)(3)). 

151 

152 B. Distributing Information Among Sections 

153 

154 When revising labeling in the old format to comply with the new regulations, applicants 

155 will face many decisions about where to put information and whether to repeat 

156 information in more than one section. Often sections or subsections can be moved with 

157 little or no modification (see Appendix C). In some cases, it will be more appropriate to 

158 move certain information from a labeling section in the old format to a different labeling 

159 section in the new format or to consolidate similar issues under a new subheading. In 

160 other cases, it will be appropriate to divide portions of information in a single labeling 

161 section among two or more sections. The following general principles and examples are 

162 offered to help applicants make decisions about where to locate information in the new 

163 format. 

164 

165 1. Creating Hierarchy 

166 

167 It is often important to repeat information in varying levels of detail in different labeling 

168 sections, based on the type and clinical relevance of the information. Important clinical 

169 information relevant to prescribing decisions should be identified, prioritized, and located 

170 in the labeling section that most appropriately communicates the type of information 

171 being considered. 

172 

173 2. Avoiding Redundancy 

174 

175 Detailed information about a particular topic should be consolidated in a single labeling 

176 section. Often, other sections of labeling should more briefly describe or refer to the 

177 topic, but not repeat the same level of detail. For example, clinically relevant information 

178 about a drug interaction that rises to the level of a warning will typically be described in 

179 the WARNINGS AND PRECAUTIONS section, with supporting detail in the DRUG 

180 INTERACTIONS section and other sections as appropriate (e.g., DOSAGE AND 

181 ADMINISTRATION section if a dosage modification is necessary). 

182 

183 In some instances, information repeated in different sections of labeling in the old format 

184 can be combined in the new format. For example, the old WARNINGS and old 

185 PRECAUTIONS sections sometimes each contained information about a similar issue; 

186 this information can now be consolidated under one subheading in the new WARNINGS 

187 AND PRECAUTIONS section. When moving and consolidating information in labeling, 

188 optional subheadings can be ordered to reflect the importance and relative public health 

189 significance of the information. 

190 

 

6

 See § 201.56(a)(3). See also §§ 201.57(c)(2)(iii), (c)(2)(iv), (c)(2)(v), (c)(7)(iii), and (c)(15)(i), and 

201.80(c)(2)(i), (c)(2)(ii), (g)(4), and (m)(1)(i). 
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191 3. Using Cross-References 

192 

193 When information about the same topic is contained in more than one section, the section 

194 with greatest clinical relevance (i.e., containing the most important information relevant 

195 to prescribing) will typically include a succinct description and will cross-reference the 

196 related sections that contain additional detail. If the detailed information is appropriately 

197 divided into more than one section, those sections should cross-reference each other. In 

198 some cases, cross-references are required (e.g., § 201.57(c)(1), (c)(6)(iv), and (c)(15)(ii)). 

199 

200 4. Illustrative Example 

201 

202 The Agency expects that distributing information among certain sections may present 

203 special challenges. Based on our experience in developing mock labeling, we have 

204 identified several basic principles. The following discussion of distributing information 

205 among labeling sections illustrates these principles. Although drug interaction 

206 information has been selected for this example, these principles also apply to other 

207 labeling sections. 

208 

209 • Drug interaction information typically appears in the CLINICAL 

210 PHARMACOLOGY and DRUG INTERACTIONS sections. Frequently, there is 

211 a subset of information that is clinically relevant and essential for prescribing 

212 decisions. That subset of information may be distributed among several sections, 

213 including the BOXED WARNING, CONTRAINDICATIONS, WARNINGS 

214 AND PRECAUTIONS, and DOSAGE AND ADMINISTRATION 

215 (§ 201.57(c)(3)(i)(H) and (c)(8)). FDA recommends using a descriptive header of 

216 summary concepts preceding a discussion of specific information (e.g., “CYP3A 

217 inhibitor”). 

218 

219 • When drug interaction information rises to the level of a warning, precaution, or 

220 contraindication or necessitates a dosage adjustment, this information should be 

221 discussed briefly in the applicable section(s), with details in the DRUG 

222 INTERACTIONS section (§ 201.57(c)(8)). 

223 

224 • The DRUG INTERACTIONS section contains clinically relevant information, 

225 such as the need to modify a dose or regimen. It can include information about 

226 the observed absence of a drug interaction if that interaction would otherwise be 

227 anticipated or is of special concern (e.g., other drugs in the class need a dosage 

228 adjustment or if the drugs are commonly coadministered). 

229 

230 • More detail about drug interaction studies, including negative results of drug 

231 interaction studies, and any clinically relevant, nonclinical data should be 

232 included in the CLINICAL PHARMACOLOGY section. 

233 

234 
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235 IV. HIGHLIGHTS 

236 

237 A. General Principles 

238 

239 The purpose of Highlights is to provide immediate access to the information that 

240 practitioners most commonly refer to and view as most important. Highlights is intended 

241 to serve as an information tool, drawing attention to this information and guiding the 

242 practitioner to the section in the FPI where detailed information can be obtained. 

243 Highlights is not a verbatim repetition of selected information from the FPI, or simply a 

244 repetition of the Contents, but a concise, informative summary of crucial prescribing 

245 information. Rarely, it may be appropriate to repeat information verbatim from the FPI 

246 (e.g., a succinct boxed warning statement or short indication statement), but in most 

247 cases, the information should be summarized and presented in an easily accessible format 

248 (e.g., bulleted, tabular). 

249 

250 It is critical that the summarized content of Highlights be consistent with the more 

251 detailed information in the FPI, but not all of that information will be included in 

252 Highlights. Selecting the information to include in Highlights requires judgment about 

253 the data in relation to the clinical setting in which the drug is used. The information 

254 considered of greatest importance will vary, depending on factors such as differences in 

255 safety profiles or dosing considerations for different indications or populations. 

256 

257 Information about a topic, or similar topics, extracted from the FPI should be grouped 

258 together and summarized with a brief, clear statement. For example, several warnings 

259 from the FPI about a similar issue could be condensed into one bulleted item under the 

260 Warnings and Precautions heading in Highlights. 

261 

262 Summarized information should be presented in direct language that is succinct and 

263 imparts a complete piece of information (e.g., for a warning: a description of the risk, its 

264 consequences, and the actions to take to prevent or mitigate it). In some cases, the 

265 information can be summarized in a few words, while in others, a few short phrases or 

266 sentences are more appropriate. Each summarized statement should be located under the 

267 appropriate Highlights heading and must cross-reference the section(s) or subsection(s) of 

268 the FPI that contains more detailed information (§ 201.56(d)(3)). 
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269 

270 B. Information in Highlights 

271 

272 1. Initial U.S. Approval (§ 201.57(a)(3)) 

273 

274 On the line immediately beneath the established name (or for biologics, the proper name 

275 of the product), the verbatim statement “Initial U.S. Approval” must be presented, 

276 followed by the four-digit year in which FDA initially approved the new molecular 

277 entity, the new biological product, or the new combination of active ingredients (e.g., 

278 Initial U.S. Approval: 2004). 

279 

280 Multiple dates should not be listed for products with multiple formulations approved or 

281 licensed in different years. For these products, list the initial approval date of the new 

282 molecular entity, new biologic product, or new combination of active ingredients. 

283 

284 2. Boxed Warning (§ 201.57(a)(4)) 

285 

286 The Boxed Warning in Highlights must contain a concise summary of the information 

287 from the BOXED WARNING in the FPI, and is limited in length to 20 lines. Because 

288 the BOXED WARNING in the FPI is an abbreviated description of the drug’s most 

289 important warnings and contraindications, the Boxed Warning in Highlights serves to 

290 emphasize such information, as well as to direct attention to the complete box and to the 

291 sections in the FPI that contain more detailed information. 

292 

293 FDA recommends that the information under the Boxed Warning heading in Highlights 

294 be summarized in a bulleted format, with each bullet communicating a discrete warning 

295 or contraindication. In rare instances, the BOXED WARNING in the FPI may be 

296 sufficiently concise to warrant repeating the statement verbatim in the Boxed Warning in 

297 Highlights. 

298 

299 3. Recent Major Changes (§ 201.57(a)(5)) 

300 

301 When substantive labeling changes are made to any of the following sections of the FPI, 

302 the heading(s) of the changed section(s) must be listed in Highlights under the heading 

303 Recent Major Changes: 

304 

305 • Boxed Warning 

306 • Indications and Usage 

307 • Dosage and Administration 

308 • Contraindications 

309 • Warnings and Precautions 

310 

311 Minor corrections, such as typographical errors or grammatical changes, are not 

312 considered substantive labeling changes. 

313 
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314 • What must be included 

315 

316 — At a minimum, the section heading, identifying number, and the date on which the 

317 change was incorporated in the labeling in month/year format (e.g., 6/2005 or 

318 June 2005) 

319 

320 — If appropriate, the section subheading (e.g., when there are multiple subheading 

321 listings for a section) 

322 

323 • Multiple labeling changes 

324 

325 — If there are changes in more than one section of the labeling, the sections in 

326 Recent Major Changes should be listed in the same order as they appear in the 

327 FPI. 

328 

329 — If there is more than one change in the same labeling section during the 1-year 

330 period listed and the change is to the content under the same subheading, the date 

331 that supersedes the previous one should be listed. For example, if a new 

332 indication (hypertension) was added to the labeling in March 2005, and a 

333 limitation to the hypertension indication was added in June 2005, the change 

334 under the Recent Major Changes heading should be listed as: 

335 

336 Indications and Usage, Hypertension (1.2) 6/2005 

337 

338 — If there is more than one change in the same labeling section during the 1-year 

339 period listed, but the change is to the content under different subheadings, each 

340 section heading, subheading, identifying number, and date should be listed 

341 separately. For example: 

342 

343 Indications and Usage, Hypertension (1.2) 6/2005 

344 Indications and Usage, Heart Failure (1.3) 9/2005 

345 

346 • Listing related information from different FPI sections 

347 When a drug product is approved for a new indication, new information is often 

348 added to other sections of labeling (e.g., DOSAGE AND ADMINISTRATION, 

349 WARNINGS AND PRECAUTIONS, CLINICAL STUDIES). If there are changes in 

350 any of the five applicable sections, each changed section should be listed under the 

351 Recent Major Changes heading. For example: 

352 

353 Indications and Usage, Hypertension (1.2) June 2005

354 Dosage and Administration, Hypertension (2.2) June 2005

355 Warnings and Precautions, Hyperkalemia (5.6) June 2005

356 

357 • Marking text in the FPI with a vertical line 

358 The corresponding new or modified text in the FPI sections listed under Recent Major 

359 Changes must be marked with a vertical line on the left edge (§ 201.57(d)(9)). It is 
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360 unusual for information to be completely deleted from labeling (e.g., removing a 

361 warning as opposed to moving the warning to a different section), but if this occurs, 

362 the review division will determine how best to identify this change. 

363 

364 • Initial submission of revised labeling in the new format 

365 The Agency acknowledges that whether to include the Recent Major Changes 

366 heading when converting labeling to the new format may be unclear because it is 

367 difficult to anticipate if the 1-year time period for listing the changed labeling section 

368 will elapse before the labeling in the new format is approved. Therefore, applicants 

369 should include any substantive labeling changes under the Recent Major Changes 

370 heading in the draft labeling submitted for review. At the time of approval, the 

371 review division will determine whether the section is still applicable. 

372 

373 • Removing a listing from Recent Major Changes 

374 A changed section must be listed under Recent Major Changes for at least 1 year after 

375 the date the labeling change was approved and can continue to be listed until the 

376 labeling is reprinted for the first time after the 1-year period. When the 1-year time 

377 period expires, the applicant can choose (1) to reprint labeling immediately to remove 

378 the listing or (2) to wait until the next reprinting to remove the listing. FDA 

379 recommends that applicants notify the Agency in their Annual Report about removal 

380 of a listing from Recent Major Changes and the corresponding vertical line in the FPI 

381 (see 21 CFR 314.70(b)(2)(v)(C)(1) and 601.12(f)(3)(i)(D)(1)). 

382 

383 4. Indications and Usage (§ 201.57(a)(6)) 

384 

385 Information under the Indications and Usage heading must include a concise statement of 

386 each of the drug’s indications, briefly noting any major limitations. FDA recommends 

387 that the information be presented in a bulleted format. In unusual circumstances, it may 

388 be appropriate to present the indications verbatim from the FPI (e.g., when a product has 

389 one indication and the statement in the FPI is sufficiently concise). For a product with 

390 limitations of use that are applicable to all of the product’s indications or with a major 

391 safety concern associated with all its uses, it is appropriate to list those limitations or 

392 concerns together, under an appropriately titled subheading (e.g., Important Limitations). 

393 

394 If the drug is a member of an established pharmacologic class, the information under 

395 Indications and Usage must include the statement “(Drug) is a (name of class) indicated 

396 for (indication(s)).” If the drug is not a member of an established pharmacologic class, 

397 the statement should be omitted. 

398 

399 5. Dosage and Administration (§ 201.57(a)(7)) 

400 

401 Information under the Dosage and Administration heading must contain a concise 

402 summary of the recommended dosage regimen, starting dose, dose range, critical 

403 differences among population subsets, monitoring recommendations, if any, and other 

404 clinically significant clinical pharmacology information that affects dosing 
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405 recommendations (e.g., dosing adjustments recommended for concomitant therapy, 

406 specific populations with coexisting conditions, clinically relevant food effects). FDA 

407 recommends a tabular format to enhance accessibility of information (e.g., when there are 

408 different dosing regimens for different indications). When applicable and important, 

409 special storage or handling information can be mentioned under this heading (e.g., special 

410 handling of chemotherapeutic agents, need for refrigeration, reconstitution prior to 

411 administration of the drug). 

412 

413 6. Dosage Forms and Strengths (§ 201.57(a)(8)) 

414 

415 Information under the Dosage Forms and Strengths heading must include a concise 

416 summary of the dosage form and strength and whether the drug product is scored. If a 

417 drug product has numerous dosage forms, bulleted subheadings (e.g., capsules, tablets, 

418 injectable, suspension) or tabular presentations are recommended. 

419 

420 7. Contraindications (§ 201.57(a)(9)) 

421 

422 Information under the Contraindications heading must include either a concise summary 

423 of the situations in which the drug should not be used because the risk clearly outweighs 

424 any possible therapeutic benefit or the statement “none” if no contraindicated situations 

425 have been identified. “Relative contraindications” (i.e., circumstances under which the 

426 drug may be used with caution) are not true contraindications and are not appropriate for 

427 inclusion under this heading. 

428 

429 8. Warnings and Precautions (§ 201.57(a)(10)) 

430 

431 Information under the Warnings and Precautions heading must include a concise 

432 summary of the most clinically significant safety concerns that affect decisions about 

433 whether to prescribe the drug, recommendations for patient monitoring to ensure safe use 

434 of the drug, and measures that can be taken to prevent or mitigate harm. Thus, although 

435 it is unlikely that all of the safety information listed in the FPI will be included in 

436 Highlights, the most clinically significant safety concerns should be addressed. 

437 

438 9. Adverse Reactions (§ 201.57(a)(11)) 

439 

440 • Most frequently occurring adverse reactions 

441 

442 Information under the Adverse Reactions heading must include a listing of the most 

443 frequently occurring adverse reactions, even if they are included elsewhere in Highlights, 

444 and the criteria used to determine inclusion (e.g., incidence rate). The listing should be 

445 concise, not lengthy or comprehensive. This listing may include adverse reactions that 

446 are important for reasons other than frequency (e.g., leading to discontinuation or dosage 

447 adjustments) unless they are included elsewhere in Highlights (e.g., under Warnings and 

448 Precautions or Contraindications). 

449 
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450 The adverse reactions listed as most frequently occurring or most common should be 

451 selected from the table of adverse reactions from clinical trials in the FPI. Rates of most 

452 common adverse reactions vary, but should be appropriate to the nature of a drug’s 

453 adverse reactions profile and the size and composition of the safety database. The criteria 

454 for determining inclusion must be identified along with the listing (e.g., >2%). If adverse 

455 reaction profiles vary significantly for different indications, list the most common adverse 

456 reactions by indication. Also note if different criteria for determining inclusion are used 

457 for different indications. 

458 

459 • Adverse reaction reporting contact information 

460 

461 Highlights must also contain adverse reaction reporting contact information that includes: 

462 1. The verbatim statement “To report SUSPECTED ADVERSE REACTIONS, 

463 contact” followed by the manufacturer’s name and phone number for adverse 

464 reaction reporting, 

465 2. the manufacturer’s Web address of the direct link to its Web site for voluntary 

reporting of adverse reactions (if available),7 466 and 

467 3. FDA’s phone number and Web address for voluntary reporting of adverse 

468 reactions (see below). 

469 

470 FDA’s phone numbers and Web addresses for voluntary 

471 reporting of adverse reactions: 

472 

473 MedWatch (for drug products other than vaccines) 

474 Phone number – 1-800-FDA-1088 

475 Web address – www.fda.gov/medwatch 

476 

477 VAERS (for vaccines) 

478 Phone number – 1-800-822-7967 

Web address – www.fda.gov/vaers8 479 

480 

481 10. Drug Interactions (§ 201.57(a)(12)) 

482 

483 Information under the Drug Interactions heading includes a concise summary of: 

484 • a list of other drugs (or classes of drugs) or foods that interact or are predicted 

485 to interact in clinically significant ways with the drug 

486 • practical instructions for preventing or decreasing the likelihood of the 

487 interaction 

488 

 

7

 If a manufacturer does not have a Web site for voluntary reporting of adverse reactions, the manufacturer is not 

required to create one. 

8

 For vaccines, this Web address is also used for required reporting by health care providers. 
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489 Descriptive subheadings of summary concepts (e.g., CYP3A inhibitor) may precede 

490 specific information. In general, drugs that were found not to interact or to interact in a 

491 nonclinically relevant way should not be included under this heading, nor should details 

492 of drug interaction studies. However, it may be appropriate to include pertinent negative 

493 findings of drug interaction studies under this heading if the interaction would otherwise 

494 be anticipated or is of special concern (e.g., other drugs in the class need a dosage 

495 adjustment or if the drugs are commonly coadministered). A tabular format is 

496 recommended for presentation of drug interaction information for drugs with numerous 

497 clinically significant interactions. 

498 

499 Interactions with particularly serious clinical consequences that are summarized under the 

500 Contraindications or Warnings and Precautions heading in Highlights would be described 

501 in greater detail in the DRUG INTERACTIONS section in the FPI. 

502 

503 Because some drugs are associated with a large number of clinically significant drug 

504 interactions, it may not be possible to concisely summarize all the critical information in 

505 Highlights. In these instances, include a statement under the Drug Interactions heading in 

506 Highlights that alerts the prescriber to the presence and significance of the drug 

507 interaction information in the FPI. 

508 

509 11. Use in Specific Populations (§ 201.57(a)(13)) 

510 

511 Information under the Use in Specific Populations heading includes a concise summary 

512 of any clinically important differences in response or recommendations for use of the 

513 drug in specific populations (e.g., differences between adult and pediatric responses, need 

514 for specific monitoring in patients with hepatic impairment, need for dosing adjustments 

515 in patients with renal impairment). Typically, information under this heading includes 

516 limitations or precautions for specific populations or established differences in response. 

517 

518 Ordinarily, the absence of information about the safety and effectiveness of a drug in a 

519 specific population (e.g., pregnant women, children) should not be included under this 

520 heading. It may be appropriate to include some information about use in specific 

521 populations under other headings in Highlights (e.g., Contraindications, Warnings and 

522 Precautions, Dosage and Administration) based on the type and clinical relevance of the 

523 information. 

524 

525 

526 V. PROCEDURAL INFORMATION 

527 

528 A. Applications Covered by the Final Rule 

529 

530 Section 201.56(b)(1) provides that the final rule applies to prescription drug products 

531 with an NDA, BLA, or efficacy supplement that: 

532 • is submitted on or after the effective date of the final rule, 

533 • is pending on the effective date of the final rule, or 
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534 • has been approved in the 5 years prior to the effective date of the final rule. 

535 

536 Although FDA recognizes the effort involved in revising labeling, the Agency strongly 

537 believes that the new format is a significant advance in communicating drug information. 

538 Therefore, we encourage applicants with products to which the final rule does not apply 

539 to voluntarily revise the labeling of their products to comply with the new content and 

540 format requirements. 

541 

542 1. New NDAs, BLAs, and Efficacy Supplements 

543 

544 After the effective date of the final rule, draft labeling submitted with new NDAs, BLAs, 

545 and efficacy supplements must be in the new format. Consistent with current practice, 

546 the labeling will be reviewed with the application or supplement. 

547 

548 The following efficacy supplements trigger the requirement to revise labeling to the new 

549 format: 

550 

551 • A new indication or a significant modification of an existing indication, including 

552 removal of a major limitation of use 

553 • A new dosage regimen, including an increase or decrease in daily dosage or a 

554 change in frequency of administration 

555 • A comparative efficacy or comparative pharmacokinetics claim naming another 

556 drug 

557 • A change expected to significantly affect the size of the patient population to be 

558 given the drug, either broadening or narrowing the population (e.g., pediatrics, 

559 geriatrics) 

560 • Clinical data to verify and describe the clinical benefit for a drug approved based 

561 on a surrogate endpoint or on an effect on a clinical endpoint other than survival 

562 or irreversible morbidity (see 21 CFR 314.510 and 601.41) 

• A labeling supplement with clinical data9 563 

564 

565 2. Approved and Pending Applications 

566 

567 The timing for submitting labeling in the new format is based on the implementation plan 

568 (see § 201.56(c) and Appendix D), but an applicant can voluntarily convert product 

569 labeling to the new format prior to the date specified in the implementation plan. For an 

570 approved application, the labeling would be submitted as a prior approval labeling 

supplement.10 571 Applicants voluntarily revising older labeling would also submit draft 

572 labeling as a prior approval labeling supplement. Under § 201.56(c)(2), for applications 

 

9

 See FDA’s draft guidance for industry Submitting Separate Marketing Applications and Clinical Data for the 

Purposes of Assessing User Fees for the definition of clinical data. Once finalized, this guidance will represent the 

Agency’s thinking on this topic. 

10 See §§ 314.70(b) and 601.12(f) about supplements requiring FDA approval before the change is made. 
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573 pending when the rule becomes effective, FDA would approve labeling in the old format 

574 and the applicant then would have the implementation period to submit a prior approval 

575 labeling supplement. When more than one approval for the same product occurred in the 

576 5 years prior to the effective date of the final rule (e.g., NDA and efficacy supplement), 

577 the date of the most recent approval determines the timing of submission of labeling in 

578 the new format according to the implementation plan. After labeling is approved in the 

579 new format, any subsequent changes to Highlights, other than identified minor 

580 exceptions, require submission of a prior approval supplement (§§ 314.70(b) and (c) and 

581 601.12(f)). 

582 

583 B. Appending FDA-Approved Patient Labeling 

584 

585 The final rule requires that, 1 year after the effective date, any FDA-approved patient 

586 labeling either accompany the labeling or be reprinted immediately following the last 

section of the labeling (§§ 201.57(c)(18) and 201.80(f)(2)).11 587 

588 

589 Prior to the final rule, the regulations required that any printed patient information or 

590 Medication Guide required to be distributed to patients be reprinted at the end of labeling. 

591 The final rule changes these requirements as follows: 

592 

593 • Any FDA-approved patient labeling, and not just labeling required by regulation 

594 to be distributed to patients, must be reprinted in or accompany the labeling. 

595 Because distribution of Medication Guides to patients has always been required 

596 (see 21 CFR part 208), the final rule does not change this requirement. 

597 • This requirement applies to the labeling of all drugs, not just those subject to the 

598 new format requirements. 

599 • The final rule provides the option of either reprinting the FDA-approved patient 

600 labeling (including Medication Guides) immediately following the last section of 

601 labeling or having the FDA-approved patient labeling accompany the labeling as 

602 a separate document. 

603 

604 When the only change to the labeling is the addition of FDA-approved patient labeling 

605 (either reprinted in or accompanying the labeling as a separate document), a labeling 

606 supplement is unnecessary. The Agency recommends notifying FDA of this change in 

607 the annual report (see §§ 314.81 and 601.12). If there are changes to the labeling other 

608 than those listed in the annual report, submit the appropriate labeling supplement (e.g., 

609 changes being effected (CBE) or prior approval). 

 

11 The term FDA-approved patient labeling refers to any labeling that has been reviewed and approved by the 

Agency that provides information for patients and is intended for distribution to patients who are prescribed a drug. 
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610 

611 C. Submitting Electronic Versions of Labeling 

612 

613 For information about submitting labeling electronically, applicants should consult the 

614 guidances for industry on Providing Regulatory Submissions in Electronic Format — 

615 Human Pharmaceutical Product Applications and Related Submissions Using the eCTD 

616 Specifications and Providing Regulatory Submissions in Electronic Format — Content of 

Labeling.

12 617 

618 

619 D. Applying for a Waiver from Highlights’ One-Half Page Requirement 

620 

621 The new regulations require that Highlights, excluding the boxed warning, be limited in 

622 length to one-half page (§ 201.57(d)(8)). FDA recognizes that under certain 

623 circumstances, particularly when a product has many indications or many serious 

624 warnings that merit inclusion in Highlights, it may not be possible to accommodate all 

625 the required information within one-half page. In this case, the applicant can submit a 

626 waiver request with the submission (e.g., NDA, BLA, efficacy supplement, or labeling 

627 supplement). (See 21 CFR 201.58.) The applicant should prominently identify the 

628 submission as one that includes a waiver request. In the waiver request, the applicant 

629 should explain why the one-half page requirement could not be met. The Agency will 

630 discuss the waiver request with the applicant during labeling negotiations and will 

631 formally document its decision in an action letter. 

632 

633 E. Class Labeling 

634 

635 1. Mandated Statements 

636 

637 In some instances, a statement(s) for a drug or class of drugs is required by regulation to 

638 be included in a particular section of the labeling. For example, 21 CFR 310.517 requires 

639 that labeling for oral hypoglycemics of the sulfonylurea class include a statement in the 

640 WARNINGS section. When converting labeling to the new format, the statement must 

641 be included in the corresponding section in the new format (e.g., a statement required to 

642 be included in the BOXED WARNING in the old format must be included in the 

643 BOXED WARNING in the new format). For sections that have been altered or 

644 eliminated, see Table 1 for the location of the statement in the new format. 

645 

 

12 We update guidances periodically. To make sure you have the most recent version of a guidance, check the 

CDER guidance page at http://www.fda.gov/cder/guidance/index.htm. 
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646 Table 1 — Location of Statements Required To Be Included in Labeling 

647 

Location in Old Format Location in FPI of New Format 

WARNINGS WARNINGS AND PRECAUTIONS 

PRECAUTIONS (General) WARNINGS AND PRECAUTIONS 

PRECAUTIONS (Drug Interactions) DRUG INTERACTIONS 

PRECAUTIONS (Special Populations) USE IN SPECIFIC POPULATIONS 

PRECAUTIONS (Information for Patients) PATIENT COUNSELING 

INFORMATION 

HOW SUPPLIED (or after HOW 

SUPPLIED) 

HOW SUPPLIED/STORAGE AND 

HANDLING 

648 

649 The Agency will consider, on a case-by-case basis, those instances where statements are 

650 required to be included in labeling in the new format, but not in a specific labeling 

651 section. Whether a specific statement required by regulation must appear in Highlights 

652 will be determined by the Agency. 

653 

654 2. Class Labeling Statements That Are Not Mandated by Regulation 

655 

656 In some cases, the labeling of all members of a class of drugs includes identical 

657 statements, even though they are not mandated by regulation. These class labeling

658 statements describe a risk or effect that is typically associated with members of the class, 

659 based on what is known about the pharmacology or chemistry of the drugs. For example, 

660 the boxed warning about the risk of using an ACE inhibitor during the second and third 

661 trimesters of pregnancy is uniformly presented in all labeling for this class of drugs. 

662 

663 To ensure consistent presentation of class labeling statements within drug classes, the 

664 Agency will determine during the labeling review and approval process: (1) the 

665 appropriate location of a class labeling statement in the FPI, (2) whether the information 

666 merits inclusion in Highlights, and (3) the content and location of the summarized 

667 statement in Highlights. Applicants should propose content and location of class labeling 

668 statements in the new format in the draft labeling submitted with their applications or 

669 supplements. 
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670 

671 F. Abbreviated New Drug Application (ANDA) Products 

672 

673 Under 21 CFR 314.94(a)(8), the labeling of a drug product submitted for approval under 

674 an ANDA must be the same as the labeling of the listed drug referenced in the ANDA, 

675 except for changes required because: 

676 

677 1. differences have been approved under a suitability petition filed under 21 CFR 

678 314.93 

679 2. the ANDA product and the reference listed drug are produced or distributed by 

680 different manufacturers 

681 3. aspects of the listed drug’s labeling are protected by patent or exclusivity 

682 

683 Thus, if the labeling of the reference listed drug is revised to comply with the final rule, 

684 the labeling of the ANDA product must also be revised in accordance with 21 CFR 

685 314.127(a)(7). 

686 

687 ANDA applicants are encouraged to consult the guidance for industry on revising ANDA 

688 labeling following revision of the reference listed drug labeling for information about 

when and how to submit labeling supplements.13 689 

690 

691 

692 VI. FORMATTING 

693 

694 The final rule includes certain formatting requirements (e.g., ordering, numbering, type size) that 

695 were designed to enhance readability and accessibility of labeling information (§ 201.57(d)). 

696 Beyond these requirements, the Agency expects that some flexibility in formatting will be 

697 necessary because of variability in the type and quantity of labeling information for different 

698 drugs. The Agency recommends the use of a two-column format for Highlights and Contents 

699 because this format enhances effective communication of the labeling information. Other 

700 general recommendations for specific formatting issues are described below. 

701 

702 A. Subheadings 

703 

704 The use of subheadings, in addition to those required by the final rule to help organize 

705 information in the FPI, is encouraged (e.g., to identify individual warnings). Each 

706 subheading that is used must be assigned a decimal number that corresponds to its 

707 placement and order in the FPI (§§ 201.56(d)(2) and 201.57(c)). 

708 

709 B. Omitted Sections (§ 201.56(d)(4))

710 

711 Any required section, subsection, or specific information that is clearly inapplicable must 

712 be omitted from Highlights and the FPI. For example, if a drug is indicated for use only 

713 in males, and there are no preclinical or clinical data relevant to women of childbearing 

 

13 See FDA’s guidance for industry Revising ANDA Labeling Following Revision of the RLD Labeling. 
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714 potential, the Pregnancy, Labor and Delivery, and Nursing Mothers subsections would be 

715 omitted because they are not applicable. 

716 

717 When a section or subsection is omitted from the FPI, the section must also be omitted 

718 from the Contents (§ 201.56(d)(4)). The heading “Full Prescribing Information: 

719 Contents” must be followed by an asterisk and the following statement must appear at the 

720 end of the Contents: “*Sections or subsections omitted from the Full Prescribing 

721 Information are not listed” (§ 201.56(d)(4)). 

722 

723 In the example of a drug indicated for use only in males, the Contents heading appears as 

724 follows: 

725 

726 FULL PRESCRIBING INFORMATION: CONTENTS* 

727 

728 The numbering in the Contents and FPI appears as follows: 

729 

730 8 USE IN SPECIFIC POPULATIONS 

731 8.4 Pediatric Use 

732 8.5 Geriatric Use 

733 9 DRUG ABUSE AND DEPENDENCE 

734 

735 At the end of the Contents, the following statement appears: 

736 

737 *Sections or subsections omitted from the Full Prescribing Information 

738 are not listed. 

739 

740 In most cases when clinically relevant information about a drug is not available, the 

741 section or subsection should be omitted. Infrequently, describing the absence of data will 

742 provide important information for the prescriber and, therefore, the section or subsection 

743 should be included. For example, if a drug has not been adequately studied in a specific 

744 patient population (e.g., hepatically impaired), the labeling should include a Hepatic 

745 Impairment subsection that describes the lack of information. 

746 

747 C. Cross-references 

748 

749 Cross-referencing is encouraged, and in some cases required (e.g., § 201.57(c)(1), 

750 (c)(6)(iv), and (c)(15)(ii)), because it reduces the need to repeat detailed information 

751 about a similar issue in several different sections (see III.B.3 of this guidance for more 

752 information). The preferred presentation of cross-references in Highlights is the 

753 numerical identifier in parentheses following the summarized labeling information (e.g., 

754 (1.1)). The preferred presentation of cross-references in the FPI is the section heading 

755 followed by the numerical identifier (e.g., see Indications and Usage (1.1)). Because 

756 cross-references are embedded in the text in the FPI, the use of italics to achieve 

757 emphasis is encouraged. 

758 
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759 D. Type Size 

760 

761 The final rule requires different minimum type sizes for trade labeling (i.e., labeling on or 

762 within the package from which the drug is to be dispensed) and for labeling disseminated 

763 in other settings (e.g., labeling that accompanies prescription drug promotional 

764 materials). (See § 201.57(d)(6).) Appendix E shows minimum type size requirements 

765 for labeling in the new format (§ 201.57) and in the old format (§ 201.80), including 

766 requirements for FDA-approved patient labeling. The Agency encourages a minimum 

767 type size of 10 points for FDA-approved patient labeling. 

768 
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769 APPENDIX A — Frequently Asked Questions 

770 

771 

772 Where to Locate Information 

773 

774 Q1. Where should microbiology data be presented in the CLINICAL PHARMACOLOGY 

775 section? 

776 

777 A1. A subsection in the CLINICAL PHARMACOLOGY section can be created (e.g., 12.4 

778 Microbiology) and all of the microbiology information for antimicrobial products 

779 consolidated into that subsection. 

780 

781 

782 Q2. Labeling for some products includes disease-specific pathophysiology or epidemiology 

783 information. In the new format, where should this information be presented? 

784 

785 A2. In rare cases when a brief description of disease pathophysiology may facilitate 

786 understanding of a drug’s pharmacology, the information may be included in the 

787 Mechanism of Action subsection of the CLINICAL PHARMACOLOGY section 

788 (§ 201.57(c)(13)(i)(A)). Epidemiologic information is discouraged because it is quickly 

789 outdated and will therefore require the applicant to frequently update the product’s 

790 labeling. 

791 

792 

793 Q3. What section of the labeling should contain animal efficacy data when a drug is 

794 approved based on effectiveness data from studies in animals (§§ 314.610 and 601.91)? 

795 

796 A3. In general, the specifics about animal efficacy study results should be presented in the 

797 Animal Toxicology and/or Pharmacology subsection of the NONCLINICAL 

798 TOXICOLOGY section of labeling. However, other sections should disclose that 

799 effectiveness was derived solely from animal studies and explain why (e.g., 

800 INDICATIONS AND USAGE, CLINICAL STUDIES). For example, the CLINICAL 

801 STUDIES section should make it clear that no human efficacy studies were conducted 

802 due to ethical considerations and that approval was based solely on evidence of 

803 effectiveness in animals. This section should also include a cross-reference to the Animal 

804 Toxicology and/or Pharmacology subsection. In addition, the labeling provided to 

805 patients must explain that the drug’s approval was based on efficacy studies conducted in 

806 animals alone (§§ 314.610(b)(3) and 601.91(b)(3)). 

807 

808 

809 Q4. Can the proprietary (or proper) and established names be repeated at the beginning of 

810 the FPI? 

811 

812 A4. The proprietary and established names, as well as other product identification information 

813 must be presented in Highlights (§ 201.57(a)(2)). The proprietary and established names 
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814 can be repeated at the beginning of the FPI, or at the beginning of each page of the FPI 

815 (e.g., as a header), if this enhances product identification on subsequent pages of labeling. 

816 

817 

818 Scope 

819 

820 Q5. Are combination products subject to this new labeling rule? 

821 

822 A5. Combination products that are comprised of a prescription drug and biologic, a 

823 prescription drug and device, or a biologic and device that were reviewed under a BLA or 

824 NDA are subject to the new labeling rule, if the prescription drug component is subject to 

825 the new labeling rule (see § 201.56(b)). Applicants with these products must submit 

826 revised labeling to conform with the new requirements to the original NDA or BLA. In 

827 addition, applicants with combination products reviewed under device authorities should 

828 contact the Office of Combination Products regarding whether the drug or biological 

829 product component is subject to the prescription drug labeling rule. (See 21 CFR part 3.) 

830 

831 

832 Procedural 

833 

834 Q6. How should a labeling supplement be submitted for a product reviewed in more than 

835 one division? 

836 

837 A6. For a product with marketing applications in more than one review division, the applicant 

838 should continue to follow the procedures established with the divisions for submitting 

839 labeling supplements. If the applicant is uncertain about where to submit a supplement 

840 that converts labeling to the new format, the division where the original NDA or BLA 

841 was approved should be contacted for assistance. 

842 

843 

844 Q7. Does the adverse reaction reporting contact information have to be presented as part of 

845 the “fair balance” information in promotional materials? 

846 

847 A7. There is no requirement to include the adverse reaction reporting contact information in 

848 promotional materials. 

849 

850 

851 Formatting 

852 

853 Q8. Can the proprietary and established (or proper) names be presented on the same line in 

854 Highlights? 

855 

856 A8. To conserve space in Highlights, the proprietary and established names should be 

857 presented on the same line, unless they are too long. In that case, the established name 

858 should be presented on the line underneath the proprietary name. 

859 
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860 

861 Q9. Is there a preferred format for the revision date? 

862 

863 A9. The date of the most recent revision must be presented at the end of Highlights 

864 (§ 201.57(a)(15)). The preferred format is “Revised: Month Year” or “Revised: 

865 Month/Year” (i.e., Revised: June 2003 or Revised: 6/2003). 

866 

867 

868 Q10. Should Latin abbreviations be used in the DOSAGE AND ADMINISTRATION section 

869 (e.g., qd versus once daily)? 

870 

871 A10. The Agency recommends that Latin abbreviations be avoided because of the greater 

872 potential for medication errors should an abbreviation be misread. 

873 

874 

875 
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876 APPENDIX B — Prescription Drug Labeling Sections 

877 

878 

Old Format* New Format** 

Description 

Clinical Pharmacology 

Indications and Usage 

Contraindications 

Warnings 

Precautions 

Adverse Reactions 

Drug Abuse and Dependence 

Overdosage 

Dosage and Administration 

How Supplied 

Optional sections: 

 Animal Pharmacology 

 and/or Animal Toxicology 

 Clinical Studies 

 References 

HIGHLIGHTS OF PRESCRIBING INFORMATION 

 Product Names, Other Required Information 

 Boxed Warning 

 Recent Major Changes 

 Indications and Usage 

 Dosage and Administration 

 Dosage Forms and Strengths 

 Contraindications 

 Warnings and Precautions 

 Adverse Reactions 

 Drug Interactions 

 Use in Specific Populations 

FULL PRESCRIBING INFORMATION: CONTENTS 

FULL PRESCRIBING INFORMATION 

 Boxed Warning 

 1 Indications and Usage 

 2 Dosage and Administration 

 3 Dosage Forms and Strengths 

 4 Contraindications 

 5 Warnings and Precautions 

 6 Adverse Reactions 

 7 Drug Interactions 

 8 Use in Specific Populations 

 9 Drug Abuse and Dependence 

 10 Overdosage 

 11 Description 

 12 Clinical Pharmacology 

 13 Nonclinical Toxicology 

 14 Clinical Studies 

 15 References 

 16 How Supplied/Storage and Handling 

 17 Patient Counseling Information 

879 * As required by 21 CFR 201.56(e) and 201.80. 

880 **As required by 21 CFR 201.56(d) and 201.57 
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881 APPENDIX C — Reorganizing Labeling Sections 

882 

883 

884 Location in Old Format → Location in FPI in New Format 

885 

886 Boxed Warning → Boxed Warning 

887 Description → Description 

888 Clinical Pharmacology → Clinical Pharmacology 

889 Indications and Usage → Indications and Usage 

890 Contraindications → Contraindications 

891 Warnings → Warnings and Precautions 

892 Precautions 

893 General → Warnings and Precautions 

894 Information for Patients → Patient Counseling Information 

895 Laboratory Tests → Warnings and Precautions 

896 Drug Interactions → Drug Interactions 

897 Drug/Laboratory Test 

898 Interactions → Warnings and Precautions 

899 Carcinogenesis, Mutagenesis, 

900 Impairment of Fertility → Nonclinical Toxicology (Carcinogenesis, 

901 Mutagenesis, Impairment of Fertility) 

902 Pregnancy → Use in Specific Populations (Pregnancy) 

903 Labor and Delivery → Use in Specific Populations (Labor and Delivery) 

904 Nursing Mothers → Use in Specific Populations (Nursing Mothers) 

905 Pediatric Use → Use in Specific Populations (Pediatric Use) 

906 Geriatric Use → Use in Specific Populations (Geriatric Use) 

907 Adverse Reactions → Adverse Reactions 

908 Drug Abuse and Dependence → Drug Abuse and Dependence 

909 Overdosage → Overdosage 

910 Dosage and Administration → Dosage and Administration 

911 How Supplied → Dosage Forms and Strengths 

912 → How Supplied/Storage and Handling 

913 Animal Pharmacology 

914 and/or Animal Toxicology → Nonclinical Toxicology (Animal Toxicology and/or 

915 Pharmacology) 

916 Clinical Studies → Clinical Studies 

917 References → References 
Contains Nonbinding Recommendations

Draft — Not for Implementation 

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918 APPENDIX D — Implementation Plan 

919 

920 

921 

Applications (NDAs, BLAs, and Efficacy 

Supplements) Required to Conform to 

New Labeling Requirements 

Time by Which Conforming Labeling 

Must Be Submitted to the Agency for 

Approval 

Applications submitted on or after June 30, 

2006 

Applications pending on June 30, 2006 and 

applications approved any time from June 

30, 2005, up to and including June 30, 

2006 

Applications approved any time from June 

30, 2004, up to and including June 29, 

2005 

Applications approved any time from June 

30, 2003, up to and including June 29, 

2004 

Applications approved any time from June 

30, 2002, up to and including June 29, 

2003 

Applications approved any time from June 

30, 2001, up to and including June 29, 

2002 

Applications approved prior to June 30, 

2001 

Time of submission 

June 30, 2009 

June 30, 2010 

June 30, 2011 

June 30, 2012 

June 30, 2013 

Voluntarily at any time 

922 
Contains Nonbinding Recommendations

Draft — Not for Implementation 

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27

923 

924 APPENDIX E — Type Size Requirements for Labeling and FDA-Approved Patient 

925 Labeling Included with Labeling 

926 

 Type Size 

Requirements 

for Labeling 

FDA-Approved Patient Labeling 

Included 

with Labeling 

Type Size 

Requirements 

for FDA-Approved 

Patient Labeling 

New Format (21 CFR 201.57) 

FDA-approved patient labeling that 

is not for distribution to patients 

Minimum 6-point type 

Any FDA-approved patient labeling 

(except a Medication Guide) that is 

for distribution to patients 

Minimum 6-point type*

Trade Labeling 

(i.e., labeling 

on or within 

the package 

from which the 

drug is to be 

dispensed) 

Minimum 6-point 

type 

Medication Guide that is for 

distribution to patients

Minimum 10-point 

type 

FDA-approved patient labeling that 

is not for distribution to patients 

Minimum 8-point type 

Any FDA-approved patient labeling 

(except a Medication Guide) that is 

for distribution to patients

Minimum 8-point type*

Other Labeling 

(e.g., labeling 

accompanying 

promotional 

materials) 

Minimum 8-point 

type 

Medication Guide that is for 

distribution to patients

Minimum 10-point 

type 

Old Format (21 CFR 201.80) 

FDA-approved patient labeling that 

is not for distribution to patients 

No minimum 

requirement 

Any FDA-approved patient labeling 

(except a Medication Guide) that is 

for distribution to patients 

No minimum 

requirement*

Trade Labeling 

and 

Other Labeling 

No minimum 

requirement 

Medication Guide that is for 

distribution to patients

Minimum 10-point 

type 

927 

* 928 FDA does not require, but encourages a minimum type size of 10 points for this information. 

929