Guidance for Industry 

Clinical Pharmacology Section of 

Labeling for Human Prescription Drug 

and Biological Products— 

Content and Format 

DRAFT GUIDANCE
 

This guidance document is being distributed for comment purposes only.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) Paul Hepp at 301-796-1538 or Lei 

Zhang at 301-796-1635; or (CBER) the Office of Communication, Outreach and Development at 

301-827-1800 or 800-835-4709. 

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) 

February 2009 

Labeling 
 

 

Guidance for Industry 

Clinical Pharmacology Section of 

Labeling for Human Prescription Drug 

and Biological Products— 

Content and Format 

Additional copies are available from: 

Office of Communications, Division of Drug Information
 

Center for Drug Evaluation and Research
 

Food and Drug Administration 

10903 New Hampshire Avenue 

Building 51, Room 2201
 

Silver Spring, MD 20993-0002
 

(Tel) 301-796-3400
 

http://www.fda.gov/cder/guidance/index.htm 

or 

 Office of Communication, Outreach and 

Development, HFM-40 

Center for Biologics Evaluation and Research 

Food and Drug Administration 

1401 Rockville Pike, Suite 200N
 

Rockville, MD 20852-1448
 

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

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) 

February 2009 

Labeling
 
Contains Nonbinding Recommendations 

Draft — Not for Implementation 

TABLE OF CONTENTS 

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

II. CLINICAL PHARMACOLOGY SECTION................................................................. 2
 

A. Mechanism of Action (How Therapeutic and Adverse Effects Occur).....................................3
 

B. Pharmacodynamics........................................................................................................................3
 

C. Pharmacokinetics...........................................................................................................................6
 

1. Absorption and Distribution (or Distribution for Intravenously Administered Entities).................6
 

2. Metabolism and Excretion ...............................................................................................................7
 

D. Microbiology...................................................................................................................................9
 

E. Pharmacogenomics........................................................................................................................9
 

F. Use of Pharmacokinetic, Dose-Response, and/or PK/PD Graphs and Tables........................11
 
 

 

 

Contains Nonbinding Recommendations 

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1 Guidance for Industry1
 

2 

3 Clinical Pharmacology Section of Labeling 

4 for Human Prescription Drug and Biological Products— 

5 Content and Format 

6 

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

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

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

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

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

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

13 

14 

15 

16 

17 I. INTRODUCTION 

18 

19 This guidance is intended to assist applicants in preparing the Clinical Pharmacology section of 

20 product labeling to meet the requirements of FDA regulations (21 CFR 201.57) and to facilitate 

21 communication about this sometimes complicated labeling information. This guidance is also 

22 intended to ensure consistency in clinical pharmacology labeling for all prescription drug 

23 products approved in CDER and CBER. The guidance provides recommendations to applicants 

24 submitting new drug applications (NDAs) (including applications submitted under section 

25 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b)(2)), abbreviated new 

26 drug applications (ANDAs), supplements to approved NDAs, biologics license applications 

27 (BLAs), and supplements to BLAs, who intend to prepare or amend the Clinical Pharmacology 

28 section of the labeling for human prescription drug or biological products. This guidance does 

29 not pertain to 21 CFR 201.57(c)(13)(ii) (13.2 Clinical pharmacology), which relates to the 

30 conditions for including in the labeling in vitro or animal test information that has not been 

31 shown by adequate and well-controlled clinical studies to be pertinent to clinical use. 

32 

33 This guidance provides a general framework and set of recommendations that should be adapted 

34 to specific drugs and their conditions of use. Not all of the information identified in this 

35 guidance for inclusion in the Clinical Pharmacology section of product labeling will be 

36 applicable for every drug. Only information that is important for safe and effective use of the 

37 drug should be included. 

38 

1 This guidance has been prepared by the Office of Clinical Pharmacology in the Center for Drug Evaluation and 

Research (CDER) in consultation with the Center for Biologics Evaluation and Research (CBER) at the Food and 

Drug Administration (FDA). 

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

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

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

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

43 recommended, but not required. 

44 

45 II. CLINICAL PHARMACOLOGY SECTION 

46 

47 As stated in 21 CFR 201.56, the Clinical Pharmacology section of labeling is one of the sections 

48 that appear in the Full Prescribing Information. When clinical pharmacology information has 

49 important implications for safe and effective use, it will often appear in other sections of labeling 

50 such as Drug Interactions, Warnings and Precautions, Dosage and Administration, or 

51 Contraindications, and it could appear in the Highlights of Prescribing Information. Where 

52 specific clinical pharmacology information appears in multiple sections of labeling, cross53 referencing should be used. To the extent possible, repetition of detailed information in multiple 

54 sections should be avoided. 

55 

56 Specific content and format requirements for the Clinical Pharmacology section of the labeling 

57 are described in § 201.57(c)(13)(i), which states the following: 

58 

59 (13) 12 Clinical pharmacology. (i) This section must contain information relating to the human 

60 clinical pharmacology and actions of the drug in humans. Pharmacologic information based on in 

61 vitro data using human biomaterials or pharmacologic animal models, or relevant details about in 

62 vivo study designs or results (e.g., drug interaction studies), may be included in this section if 

63 essential to understand dosing or drug interaction information presented in other sections of the 

64 labeling. This section must include the following subsections: 

65 (A) 12.1 Mechanism of action. . . . 

66 (B) 12.2 Pharmacodynamics. . . . 

67 (C) 12.3 Pharmacokinetics. . . . 

68 

69 Generally, the Clinical Pharmacology section should include information on both positive 

70 findings and pertinent negative findings. A lack of specific information should be noted only 

71 when the absence of that information is clinically pertinent. The information should be 

72 presented in a way that is understandable to practitioners who may not be well-versed in clinical 

73 pharmacology. The information presented must not be speculative or promotional in any manner 

74 (21 CFR 201.56(a)(2)). When appropriate, additional subheadings within the three subsections 

75 should be created to help organize the information. For example, a Drug Interactions 

76 subheading could be included in the Pharmacokinetics subsection where there is a large amount 

77 of drug interaction information that should be included in labeling. 

78 

79 Information about the parent drug, active metabolites, and enantiomers that lead to the intended 

80 therapeutic effects or unintended effects (e.g., toxicities) should be presented in the Clinical 

81 Pharmacology section of labeling. Intended or unintended effects due to additives (adjuvants, 

82 excipients, or preservatives) present in the product should also be included in this section of the 

83 labeling. Generally, for purposes of this guidance, parent drug or metabolites that are thought to 

84 contribute 20 percent or more of the overall efficacy or toxicity of a product should be 

85 considered of potential interest for discussion. In certain cases, however, multiple substances or 

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86 metabolites that contribute to activity to a small degree individually (i.e., less than 20 percent), 

87 may also be of interest. In some cases, analytical methodology may not be available to measure 

88 the parent drug or all active metabolites for certain products, so reporting their concentrations 

89 would not be possible. When this situation exists, it should be addressed in the labeling. If the 

90 drug is a racemate, a brief description of the racemic mixture followed by information about the 

91 clinical pharmacology of each enantiomer should be included if both are active and have 

92 different types of activity or different pharmacokinetics. 

93 

94 A. Mechanism of Action (How Therapeutic and Adverse Effects Occur) 

95 

96 This subsection of the labeling should summarize what is known about the established 

97 mechanism or mechanisms of action in humans, focusing on the desired and adverse effects of 

98 the drug. The mechanism of action should be discussed at various levels, including the cellular, 

99 receptor, or membrane level (with a description of selectivity where important), the physiologic 

100 system level (target organ), and the whole body level, depending on what is known. Only 

101 reasonably well-characterized mechanisms should be described, and care must be taken to avoid 

102 speculative and undocumented suggestions of therapeutic advantages (21 CFR 201.56(a)(2)). If 

103 the relationship of the drug’s mechanism of action to the desired effects is unknown, this also 

104 should be stated. Information from animals and in vitro studies can be included where helpful 

105 and clearly relevant to the human response. Although not generally needed, a brief description 

106 of disease pathophysiology can sometimes facilitate an understanding of the drug’s 

107 pharmacology and its impact on that process. Speculation on the mechanism of drug action must 

108 be avoided (21 CFR 201.56(a)(2)). Any relevant pharmacogenomic factors affecting drug action 

109 should be included as well as whether established serologic correlates can be used to infer 

110 vaccine-induced protection against an infectious agent. 

111 

112 B. Pharmacodynamics2 

113 

114 For all of the topics discussed under Pharmacodynamics, there is particular interest in dose115 response (D-R) and in pharmacokinetic/pharmacodynamic (PK/PD) (i.e., concentration116 response) analyses. This subsection should include a description of all pharmacologic effects 

117 that are reasonably well-established as pertinent to the therapeutic action of the drug or to drug 

118 toxicity. The subsection can include effects on mechanistically important biomarkers, for 

119 example, biological product-induced antibodies or angiotensin II activity for an antihypertensive 

120 that acts via this pathway. For the pharmacodynamic effects described, and in addition to 

121 pertinent D-R and PK/PD information, this section should provide information about the time 

122 course of action and other information, such as tolerance, withdrawal effects, and differences in 

123 PD effects in specific populations. The subsection should also describe pertinent PD negatives 

124 (therapeutic and potentially toxic pharmacologic effects that might be expected of a member of a 

125 drug class, but that have not been observed). Examples of pertinent PD negatives would include 

2

 For additional information on pharmacodynamics (PD), see also the CDER/CBER guidance for industry ExposureResponse Relationships – Study Design, Data Analysis, and Regulatory Applications. We update guidances 

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

(http://www.fda.gov/cder/guidance/index.htm) or the CBER guidance Page 

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

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126 failure of a calcium channel blocker to increase heart rate or prolong the PR interval, or lack of 

127 antipyretic activity for a nonsteroidal anti-inflammatory drug (NSAID). An example of a 

128 pertinent negative for a potentially toxic drug effect for almost any drug would be a lack of effect 

129 on QTc. Similarly, a biological therapeutic product that does not produce the sort of 

130 autoantibodies observed with other mechanistically similar products would also be an example of 

131 pertinent PD negative. Important pharmacologic effects other than the main desired effect 

132 should be described. This subsection of the labeling should contain a summary of dose-response 

133 studies and the related exposure-response relationships for pharmacologic effects pertinent to 

134 effectiveness and safety (dose-response information for clinical effectiveness and safety 

135 endpoints would be in the Clinical Studies, Warnings and Precautions, Adverse Reactions, or 

136 other sections). Finally, this subsection should be used only to modify and provide further 

137 information pertinent to the demonstrated benefits of the drug; it must not be used to suggest 

138 additional claims of effectiveness (21 CFR 201.56(a)(2)). 

139 

140 If data exist and are pertinent to drug use, the following information should be discussed for the 

141 parent and active metabolites: 

142 

143 • The principal PD effects of the drug; information regarding undesired PD effects 

144 could also appear in other sections of labeling such as the Warnings and Precautions, 

145 Adverse Reactions, or Contraindications. Potentially clinically important effects that 

146 have not been observed for a drug or biologic within a particular class (e.g., QT 

147 prolongation or induction of autoantibodies) should also be included. 

148 

149 • Receptor selectivity when there are data to suggest that receptor selectivity may be 

150 related to toxicity or effectiveness. Information on whether the PD effects are 

151 irreversible and information pertaining to resistance, tolerance, and phenotypic 

152 variability should be included. 

153 

154 • The magnitude and duration of the principal clinically relevant PD effects and how 

155 these effects relate to dose or changes in blood concentration, including any clinically 

156 important differences related to regimen, input rate, or titration regimen. Information 

157 should be included regarding the time to return to pretreatment PD activity (baseline) 

158 after the drug is discontinued, whether effects persist throughout the dosing interval, 

159 the time required to reach desired therapeutic effect and whether this time is related to 

160 the attainment of steady state blood levels or reflects hysteresis (i.e., a delay between 

161 attainment of effective plasma concentration and drug effect). 

162 

163 • If established and clinically useful, the therapeutic window (or range), or threshold 

164 concentrations for efficacy or toxicity, and the role of plasma drug concentration or 

165 other exposure measures (such as area under the curve (AUC)) in monitoring for 

166 favorable or unfavorable effects. This information should be discussed further in the 

167 Dosage and Administration section of the labeling. 

168 

169 

170 

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171 • Compensatory mechanisms, such as an increase in heart rate when blood pressure 

172 falls or the effect of an angiotensin II receptor antagonist on plasma renin levels. The 

173 dose effect relationship of such phenomena may also be pertinent. 

174 

175 • Any differences in effect related to patient characteristics such as disease severity, 

176 hormonal status, concomitant drugs, age, gender, genetic or racial/ethnic factors, 

177 diurnal variation, menstrual cycle effects, environmental factors, and other known 

178 sources of variability. 

179 

180 • Whether it is useful to modify dose or dose interval by monitoring PD responses, 

181 favorable or unfavorable. Information on the magnitude, timing, initiation, and 

182 limitations of specific procedures to titrate a drug to individual patient needs should 

183 be further discussed in the Dosage and Administration section of labeling. 

184 

185 • PD effects of doses that may have been used in the clinical development program but 

186 that are greater than those ultimately approved for use, particularly when higher doses 

187 were associated with undesirable effects. This information might also appear in the 

188 Clinical Studies, Adverse Reactions, Dosage and Administration, and in some cases, 

189 the Warnings and Precautions sections of the labeling. 

190 

191 • Clinical results of doses that may have been used in the clinical development program 

192 but that are lower than those ultimately approved for use, particularly when the lower 

193 doses were associated with pharmacologic activity. This information might 

194 alternatively or also appear in the Clinical Studies section of the labeling. 

195 

196 • Tolerance, rebound, abuse or dependence, and withdrawal effects related to, for 

197 example, up- or down-regulation of receptors, if this information has been 

198 documented. 

199 

200 • Antibody formation and any resultant impact on the PD of the product. This 

201 information can be cross-referenced to other sections of the labeling, such as the 

202 Clinical Studies, Dosage and Administration, Adverse Reactions, and/or Warnings 

203 and Precautions sections. 

204 

205 • Additional information for diagnostic imaging products, including quality of imaging 

206 versus dose and/or concentration, development of antibodies, onset of satisfactory 

207 imaging, time to maximum imaging quality, imaging duration time, and imaging 

208 characteristics. Any toxicologic effects or dose and/or concentration versus toxicity 

209 relationships with a diagnostic agent should be discussed. This information can be 

210 cross-referenced to other sections of the labeling such as the Clinical Studies, Dosage 

211 and Administration, Adverse Reactions, and/or Warnings and Precautions sections. 

212 

213 • Additional information for photodynamic therapy products, including quality of 

214 therapy versus dose and/or concentration, development of antibodies, optimal time 

215 from dosage administration to light administration (laser or other source), optimal 

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216 wavelength and duration of light administration. Any toxicologic effects or dose 

217 and/or concentration versus toxicity relationships with a photodynamic therapy agent 

218 should be discussed. This information can be cross-referenced to other sections of the 

219 labeling such as the Clinical Studies, Dosage and Administration, Adverse Reactions, 

220 and/or Warnings and Precautions sections. 

221 

222 C. Pharmacokinetics 

223 

224 The Pharmacokinetics subsection should provide information that is important and useful to 

225 prescribers for a drug or biological product that is delivered systemically directly (i.e., 

226 intravenously) or absorbed systemically by other routes of administration (e.g., oral, sublingual, 

227 inhaled, buccal, transdermal) to an extent that permits measurement of parent drug and/or active 

228 metabolites (both toxic and therapeutic metabolites). Information should be included in cases 

229 where absorption is unintended, minimal, or not necessary for therapeutic effect, but is 

230 nonetheless sufficient for measurement of a parent or active metabolite (e.g., topical, 

231 intravesicular, intravaginal, intrauterine). Generally, study details other than identification of the 

232 population (e.g., normal, with disease, age, gender), and in some cases subject numbers, need not 

233 be provided. The average values and overall variability (percentage coefficient of variation) for 

234 critical pharmacokinetic (PK) parameters should be included. In cases where intrasubject 

235 variability is known for pharmacokinetic parameters, it may be useful to report this information 

236 and contrast it to the overall variability (e.g., large variability between subjects, but little 

237 variability within subjects). The range of individual pharmacokinetic parameter values may be 

238 helpful, for example, principally for clearance and half-life, particularly for drugs with narrow 

239 therapeutic ratios. If important PK information is not available, this should be noted. Generally, 

240 the focus should be on factors that explain and lead to altered critical measures, such as those 

241 that change maximum concentration (Cmax), minimum concentration (Cmin), time to maximum 

242 concentration (Tmax), AUC, half-life (t1/2), clearance (CL), and volumes of distribution (Vd). In 

243 most of these cases, the direction and magnitude of the changes (e.g., changing of AUC or Cmax) 

244 are of interest, not the actual values (of AUC or Cmax). In contrast, actual values of Tmax or half245 life are important. In some cases when the formulations are significantly different, information 

246 relative to the bioequivalence between the formulations of the marketed strengths and between 

247 clinically studied formulations and marketed formulations may be important. Subjective 

248 wording (e.g., fast, rapidly, or completely absorbed) must be avoided (21 CFR 201.56(a)(2)). 

249 

250 The Pharmacokinetics subsection should begin with a summary of the information that can 

251 influence treatment by the prescriber, and thus would be most useful in patient treatment. This 

252 information would usually include the extent and variability of bioavailability, the pertinent half253 life, major routes of elimination, metabolic pathways, major interactions, population differences 

254 (such as polymorphic metabolism), and any significant nonlinearity or time effects (e.g., from 

255 induction or inhibition of the drug’s metabolism). The summary should be followed by more 

256 detailed, clinically pertinent information as follows: 

257 

258 1. Absorption and Distribution (or Distribution for Intravenously Administered 

259 Entities) 

260 

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261 • The extent (i.e., absolute and/or relative bioavailability) and rate (e.g., Tmax and Cmax) 

262 of absorption. The presence, location (liver and/or intestine), and extent of first pass 

263 effect, or other mechanisms affecting bioavailability (e.g., chemical degradation), 

264 should be included. 

265 

266 • Whether absorption kinetics are linear or nonlinear over the range of clinical doses 

267 and concentrations. 

268 

269 • Time of maximum concentration (Tmax). 

270 

271 • Differential absorption of isomers in a racemate, if both enantiomers are active. 

272 

273 • Estimated volume of distribution (e.g., volume of distribution steady state (Vdss), 

274 volume of distribution/bioavailability (VD/F)) and how this relates to known values 

275 of physiological volumes. 

276 

277 y Extent and sources of variability of absorption between and within individuals, to the 

278 extent this is understood. This includes differences in absorption seen in specific 

279 populations, differences in genetics, and factors influencing drug uptake (e.g., 

280 transporters or CYP (cytochrome P450 oxidase) enzymes). Clinically important 

281 information related to the differences should also appear in the Use in Specific 

282 Populations section. 

283 

284 y Known effects or lack of effects of other drug or biological products, herbal products, 

285 food (including grapefruit juice), antacids, or chelating cations on absorption of orally 

286 administered entities should be mentioned here, and if important, described in more 

287 detail in the Drug Interactions section. 

288 

289 y Rate and extent of uptake by or transport to particular organs and observed 

290 multicompartment behavior, to the extent known, but only if clinically relevant. 

291 

292 • Plasma protein, erythrocyte, soluble factors, antibodies, and cellular constituents 

293 binding. 

294 

295 • Passage across the blood brain barrier (placental transfer and secretion into breast 

296 milk) information should normally be placed in the Use in Special Populations, 

297 Pregnancy and Nursing Mothers section of the labeling. 

298 

299 2. Metabolism and Excretion 

300 

301 • Description of pharmacokinetic behavior, linear or nonlinear pharmacokinetics, and 

302 clinically relevant t1/2 values. In some cases, it may be useful to describe the 

303 absorption, alpha (distribution) and beta (terminal) half lives, but the half-life value 

304 should usually be the half-life based on time to reach steady state (i.e., the effective 

305 half-life). If a long terminal half-life is important from a toxicity standpoint or from 

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306 an effectiveness standpoint (persistent effect because of peripheral binding), this 

307 should be stated and elaborated upon in other appropriate sections of the labeling 

308 (e.g., Warnings and Precautions). The Pharmacokinetics subsection should discuss 

309 the range of linearity or nonlinearity in relation to clinically relevant dosage regimens 

310 and drug concentrations. It should also include clearance values and percentage of 

311 total clearance that is renal and nonrenal, time to steady state, accumulation ratio 

312 following multiple dosing, any changes in PK over time, and a brief discussion of 

313 important specific population differences or interactions for parent, active 

314 metabolites, and separate active enantiomers. Details of specific population 

315 differences and interactions should be placed in the Use in Specific Populations and 

316 Drug Interactions sections. 

317 

318 • Biotransformation pathways based on in vitro and in vivo findings (including 

319 contribution of specific enzymes) and known or expected effects of inducers or 

320 inhibitors of the pathway. Any pathways or interactions that have been ruled out by 

321 in vitro data should be identified. 

322 

323 • Major active metabolites formed, based on in vivo findings with quantitative data, if 

324 available, for active metabolites. 

325 

326 • Brief description of known or potential alteration in metabolism by other drugs or 

327 specific substances (food, juices, tobacco, herbal products), with important 

328 interactions listed in the Drug Interactions section. 

329 

330 • Effects of the drug on metabolizing enzymes and transporters. Clinically important 

331 inhibition or induction information should also appear in the Drug Interactions 

332 section. 

333 

334 • Variations in metabolism and effect on pharmacokinetics caused by factors such as 

335 age, gender, ethnicity, polymorphic metabolism (i.e., genetic-based differences in 

336 activity (e.g., with the cytochrome P450 2D6 genetic variants)), concomitant 

337 pathology (e.g., renal or hepatic insufficiency), diet, environment, and other factors, 

338 including pertinent negatives (i.e., factors not causing variations in metabolism and 

339 effect on pharmacokinetics). Clinically important information related to such 

340 differences should also appear in the Use in Specific Populations section. 

341 

342 • Modes and extent of parent and metabolites excretion from the body, as defined by 

343 chemical measures or radiolabel (mass balance) studies. 

344 

345 • Mechanisms of the various excretory routes, such as passive or active renal excretion, 

346 filtration, secretion, active reabsorption, and any other factors that may influence 

347 excretion (e.g., pH in renal excretion, azotemia, hepatic failure, enterohepatic 

348 circulation, or other drugs competing for the same excretory pathway). 

349 

350 • Effects on excretion and/or clearance (other than the metabolic-based differences 

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351 considered previously) caused by factors such as age, concomitant drugs, and 

352 concomitant pathology (e.g., renal or hepatic insufficiency or impairment). 

353 Information related to any of these effects that are clinically important should also 

354 appear in the Use in Specific Populations section. 

355 

356 • The effectiveness of chronic peritoneal dialysis and hemodialysis in clearing the 

357 parent and metabolites from the body. 

358 

359 • Information regarding antibody formation and any resultant impact on the PK of the 

360 product. This information can be cross-referenced to other sections of labeling, such 

361 as the Clinical Studies, Dosage and Administration, Adverse Reactions, and/or 

362 Warnings and Precautions sections. 

363 

364 D. Microbiology 

365 

366 For antimicrobial products, certain clinical pharmacology information that would ordinarily be 

367 included in the Mechanism of Action or Pharmacodynamics subsection should be consolidated 

368 under a subsection created specifically for microbiology information (i.e., 12.4 Microbiology). 

369 This microbiology subsection should contain all information relevant to the microbiology 

370 characteristics of the drug (e.g., the mechanism of action, mechanism of resistance) and the 

371 pharmacodynamics as it relates to the effect of the drug on the microbe. For antimicrobial 

372 products, the microbiology information should appear as follows: 

373 

374 12.1 Mechanism of Action: The following statement should appear in subsection 12.1 

375 Mechanism of Action: “X is an anti- (e.g., bacterial, viral, as appropriate) drug (see 12.4 

376 Microbiology).” Subsection 12.4 Microbiology should include a description of the 

377 mechanism of action of the drug on the microbe. This information can be presented under 

378 subheadings (e.g., Mechanism of Action) within the Microbiology subsection to enhance 

379 labeling organization and readability. 

380 

381 12.2 Pharmacodynamics: Human pharmacodynamic data, including information on 

382 concentration-response and toxicity, should remain in subsection 12.2 Pharmacodynamics. 

383 If applicable, pharmacologic effects that are pertinent to the antimicrobial action of the drug, 

384 including important blood levels and impact on growth and resistance, should be contained in 

385 subsection 12.4 Microbiology. This information can be presented under a subheading (e.g., 

386 Pharmacodynamics) within the Microbiology subsection. 

387 

388 12.3 Pharmacokinetics: Pharmacokinetic information should remain in subsection 12.3. 

389 

390 All other microbiology information should be included in subsection 12.4 Microbiology. 

391 Additional subheadings within the Microbiology subsection should be created as appropriate. 

392 For additional information on this topic, see the CDER guidance Page 

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

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394 

395 E. Pharmacogenomics 

396 

397 When there is genetic information that would be useful to prescribers and that is more extensive 

398 than appropriate for the Pharmacokinetics or Pharmacodynamics subsection, a 

399 Pharmacogenomics subsection should be created to include the clinically relevant information 

400 on the effect of polymorphic variation in drug metabolizing enzymes, transporters, receptors, and 

401 other proteins on pharmacokinetics, pharmacodynamics, and/or clinical responses (both safety 

402 and efficacy). Pharmacogenomic information can include, but is not limited to, the following: 

403 

404 • Description of polymorphic enzymes (for example, genetic-based differences in enzyme 

405 activity such as reduced cytochrome P450 enzyme activity due to polymorphisms in a 

406 CYP gene). 

407 

408 • Subpopulation-based information on the prevalence or frequencies of alleles, genotypes, 

409 haplotypes, or other genomic markers. 

410 

411 • Positive and negative predictive values associated with the use of the genomic marker for 

412 safety and/or efficacy purposes. 

413 

414 • Clearance of the drug in relationship to the genotype. 

415 

416 • Pharmacogenomic studies performed that provide evidence of genetically based 

417 differences in drug metabolism. 

418 

419 • Changes in dose based on genotype. 

420 

421 • Other relevant information pertaining to genetic and genomic biomarkers associated with 

422 the safety and/or efficacy of the therapy. 

423 

424 When pharmacogenomic information has important implications for safe and effective use and 

425 the consequences of the genetic differences result in recommendations for restricted use, dosage 

426 adjustments, contraindications, or warnings, this information should be included in other sections 

427 of labeling as appropriate, such as the Indications and Usage, Dosage and Administration, Boxed 

428 Warning, Contraindications, Warnings and Precautions, and/or Drug Interactions sections and 

429 can be cross-referenced in the appropriate sections. 

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430 F. Use of Pharmacokinetic, Dose-Response, and/or PK/PD Graphs and Tables 

431 

432 Graphs and/or tables depicting PK attributes, exposure- or dose-response relationships, and/or 

433 PK/PD relationships can be helpful in simplifying and/or clarifying the labeling and their use is 

434 encouraged. When graphs or tables are used, variability measures should be included. 

435 

436 

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