Guidance for Industry 

and Review Staff 

Labeling for Human Prescription 

Drug and Biological Products — 

Determining Established 

Pharmacologic Class for Use in the 

Highlights of Prescribing Information 

Good Review Practice 

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) 

October 2009 

Labeling 
Guidance for Industry 

and Review Staff 

Labeling for Human Prescription 

Drug and Biological Products — 

Determining Established 

Pharmacologic Class for Use in the 

Highlights of Prescribing Information 

Good Review Practice 

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 Ave., Bldg. 51, rm. 2201 

Silver Spring, MD 20993-0002 

Tel: 301-796-3400; Fax: 301-847-8714; E-mail: druginfo@fda.hhs.gov 

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 

or 

Office of Communication, Outreach, and Development, 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

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.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) 

October 2009 

Labeling 
TABLE OF CONTENTS 

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

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

III. DEFINITIONS .................................................................................................................. 3

A. Pharmacologic Class......................................................................................................................3

B. Established Pharmacologic Class .................................................................................................3

IV. IDENTIFYING AN ESTABLISHED PHARMACOLOGIC CLASS ......................... 3

V. IDENTIFYING THE MOST APPROPRIATE TERM TO DESCRIBE AN 

ESTABLISHED PHARMACOLOGIC CLASS ............................................................ 6

VI. INCORPORATING ESTABLISHED PHARMACOLOGIC CLASS 

INFORMATION INTO THE HIGHLIGHTS SECTION............................................ 6
Contains Nonbinding Recommendations 

Guidance for Industry and Review Staff1

Labeling for Human Prescription Drug and Biological Products — 

Determining Established Pharmacologic Class for Use in the 

Highlights of Prescribing Information 

Good Review Practice 

This guidance represents the Food and Drug Administration’s (FDA’s) current thinking on this topic. It 

does not create or confer any rights for or on any person and does not operate to bind FDA or the public. 

You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 

and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 

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

number listed on the title page of this guidance. 

I. INTRODUCTION 

This guidance is intended to provide applicants and review staff with a definition of established 

pharmacologic class and to help them identify the most appropriate word (term) or phrase that 

describes the established pharmacologic class for a drug or biological product for inclusion in the 

Indications and Usage section of Highlights of Prescribing Information (Highlights) of approved 

labeling.2

 

Although not specifically required, the pharmacologic class can also appear in other sections of 

labeling. This guidance only applies to the use of the pharmacologic class in the Indications and 

Usage section of Highlights. 

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

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

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

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

recommended, but not required. Although guidance documents do not legally bind FDA, review 

 

1

 This guidance has been prepared by the Office of New Drugs in the Center for Drug Evaluation and Research 

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

Administration. 

2

 For the purposes of this guidance, drug and drug product are used to refer to human prescription drug and 

biological products that also meet the definition of drug under the Federal Food, Drug, and Cosmetic Act. 

1 
Contains Nonbinding Recommendations 

staff may depart from guidance documents only with appropriate justification and supervisory 

concurrence. 

II. BACKGROUND 

In January 2006, we published a final rule that amended the requirements for the content and 

format of approved labeling (prescribing information) for human prescription drug and 

biological products.3

 The new prescribing information format is intended to make it easier for 

health care professionals to access, read, and use to make prescribing decisions. 

The rule requires the following statement to appear under the Indications and Usage section of 

Highlights if a drug is a member of an established pharmacologic class:4

“(Drug) is a (name of class) indicated for (indication(s)).” 

If a drug does not have an established pharmacologic class as determined through the process 

described below, the name of class component of this statement should be omitted from the 

Indications and Usage section of Highlights. 

Knowing the established pharmacologic class can provide health care professionals with 

important information about what to expect from a drug and how it relates to other therapeutic 

options. Such information can also help reduce the risk of duplicative therapy and drug 

interactions, as well as provide important treatment information in cases of drug overdose. 

We are in the process of using structured product labeling (SPL) to index certain types of 

prescribing information content for all drug products.5 Because of its importance, 

pharmacologic class is being indexed in the first phase of this process. In general, we will m

indexing decisions based on the prescribing information and the selected terminologies.

ake 

n 

eling Resources.

 

6

 

Therefore, it is important that the appropriate established pharmacologic class appear in 

Highlights. For more information about SPL, see the FDA Data Standards Council Web site o

Structured Product Lab 7

3

 See 21 CFR parts 201, 314, and 601 Requirements on Content and Format of Labeling for Human Prescription 

Drug and Biological Products (January 24, 2006; 71 FR 3922). 

4

 See 21 CFR 201.57(a)(6). 

5

 See the guidance for industry Indexing Structured Product Labeling

(http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm). 

6

 If an appropriate term is not available in an existing terminology, we will work with the relevant terminology 

maintenance organizations to identify a new term. 

7

 See http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. 

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Contains Nonbinding Recommendations 

III. DEFINITIONS 

A. Pharmacologic Class 

For purposes of this guidance, a pharmacologic class is a group of drugs that share scientifically 

documented properties. Specifically, for purposes of this guidance, pharmacologic class is 

defined on the basis of any one of the following three attributes of the drug: 

1. Mechanism of action (MOA) — Pharmacologic action at the receptor, membrane, or 

tissue level 

2. Physiologic effect (PE) — Pharmacologic effect at the organ, system, or whole body 

level 

3. Chemical structure (CS) 

B. Established Pharmacologic Class 

An established pharmacologic class is represented by a term or phrase that is scientifically valid 

and clinically meaningful according to the following definitions: 

• A scientifically valid pharmacologic class is supported by documented and submitted 

empiric evidence showing that the drug’s pharmacologic class is known, not theoretical, 

and relevant and specific to the indication. 

• A clinically meaningful pharmacologic class term or phrase enhances the ability of 

professionals to understand physiologic effects related to the indication or to anticipate 

undesirable effects that may be associated with the drug or pharmacologic class. 

IV. IDENTIFYING AN ESTABLISHED PHARMACOLOGIC CLASS 

It is often possible to identify multiple scientifically valid pharmacologic classes. However, only 

pharmacologic classes that are also clinically meaningful will be considered to be established 

pharmacologic classes. Consider the following examples: 

• Drug A 

MOA = Beta-adrenergic blocker 

PE = Negative inotropy and chronotropy 

CS = Benzeneacetamide 

In this case, the most clinically meaningful term is the MOA because the term 

immediately informs clinicians of the many physiologic effects that can be expected 

with this drug product, both desirable and undesirable. 

“Drug A is a beta-adrenergic blocker indicated for treatment of hypertension.” 

3 
Contains Nonbinding Recommendations 

• Drug B 

MOA = Inhibitor of reabsorption of sodium and chloride ions in the kidney 

PE = Loop diuretic 

CS = Anthranilic acid derivative 

In this case, the most clinically meaningful term is the PE because the MOA is 

localized in the kidney and the PE reflects the full activity of the drug product. 

“Drug B is a loop diuretic indicated for treatment of edema associated with 

congestive heart failure.” 

• Drug C 

MOA = GABA A and B Modulator 

PE = Increased GABA activity 

CS = Benzodiazepine 

In this case, the most clinically meaningful term is the CS because this chemical class 

is well known and the term immediately informs clinicians of the important 

physiologic effects with this drug product. 

“Drug C is a benzodiazepine indicated for management of anxiety disorders.” 

• Drug D 

MOA = Unknown 

PE = Altered neurotransmitter activity 

CS = Aminoketone 

In this case, the MOA is unknown and the PE and CS are not clinically meaningful. 

Therefore, an established pharmacologic class is not included in the Indications and 

Usage statement in Highlights. 

“Drug D is indicated as an aid to smoking cessation treatment.” 

• Drug E 

MOA = Cyclooxygenase inhibitor 

PE = Decreased prostaglandin production 

CS = Nonsteroidal anti-inflammatory drug 

In this case, all three terms are clinically meaningful, but the most commonly used 

grouping term is the CS. 

“Drug E is a nonsteroidal anti-inflammatory drug indicated for relief of acute pain 

and inflammation.” 

4 
Contains Nonbinding Recommendations 

It may be appropriate to include a combination of established pharmacologic classes if more than 

one attribute of the drug is clinically meaningful. For example, a drug may have clinically 

meaningful and scientifically valid MOA and PE terms that can be combined in the established 

pharmacologic class statement. 

“Drug F is an mTor inhibitor immunosuppressant indicated for prophylaxis of organ 

rejection.” 

Another example of appropriate use of multiple established pharmacologic classes is when the 

CS provides additional meaningful information to prescribers beyond that provided by MOA or 

PE alone. 

“Drug G is a thiazide diuretic indicated for treatment of edema associated with 

congestive heart failure.” 

Many drug products contain more than one drug. These drugs can be members of the same or 

different pharmacologic classes. These pharmacologic classes can apply to the same or different 

indications. The following examples illustrate different situations that may be encountered: 

• For products with more than one drug where all drugs are in the same pharmacologic 

class: 

“Product X is a combination of Drug H and Drug I, both HIV nucleoside analog 

reverse transcriptase inhibitors, indicated for use in combination with other 

antiretroviral agents for treatment of HIV infection.” 

• For products with more than one drug where the drugs are from different pharmacologic 

classes: 

“Product Y is a combination of Drug J, a thiazide diuretic, and Drug K, a potassiumsparing diuretic, indicated for hypertension.” 

Note: For drugs that are not combination products but are approved for use with other 

drug products named specifically by proprietary name or nonproprietary name in the 

Indications and Usage section, the pharmacologic class for the concomitant drug should 

not be included in this statement. However, the pharmacologic class for the concomitant 

drug can appear in a separate statement in the section. 

For most drug products, one established pharmacologic class will be identified. However, in rare 

cases, multiple indications may result in multiple established pharmacologic classes: 

“Drug L is an antidote indicated to prevent or lessen hepatic injury when administered 

intravenously within 8 to 10 hours after ingestion of a potentially hepatotoxic quantity of 

acetaminophen.” 

5 
Contains Nonbinding Recommendations 

6 

 

“Drug L is a mucolytic indicated as an adjuvant therapy for patients with abnormal, 

viscid, or inspissated mucous secretions in such conditions as chronic bronchopulmonary 

disease, acute bronchopulmonary disease, pulmonary complications of cystic fibrosis, 

tracheostomy care, pulmonary complications associated with surgery, use during 

anesthesia, post-traumatic chest conditions, atelectasis due to mucous obstruction, and 

diagnostic bronchial studies.” 

V. IDENTIFYING THE MOST APPROPRIATE TERM TO DESCRIBE AN 

ESTABLISHED PHARMACOLOGIC CLASS 

For new drugs that are undergoing review for marketing approval, we will review the applicant’s 

proposed established pharmacologic class and supporting evidence submitted based on the 

criteria defined in section III.B. 

When identifying a term to describe an established pharmacologic class for a drug, it is important 

to consider other drugs that share MOA, PE, or structural similarity. The use of misleading or 

potentially confusing pharmacologic class terms can be avoided by achieving consistency in 

terminology, where appropriate, across drugs used for similar purposes. The FDA has published 

a list of established pharmacologic class terms used for the established pharmacologic class in 

the Indications and Usage section of Highlights as well as a list of the related pharmacologic 

class MOA, PE, and CS indexing terms for use in SPL.8

 

VI. INCORPORATING ESTABLISHED PHARMACOLOGIC CLASS 

INFORMATION INTO THE HIGHLIGHTS SECTION 

According to 21 CFR 314.70(b)(2)(v)(C) and 21 CFR 601.12(f)(1), for approved drugs for which 

the applicant plans to update the labeling or convert the labeling to a format consistent with the 

final rule, the addition of an established pharmacologic class term to the Indications and Usage

section of Highlights of approved drug labeling is a change that must be proposed and submitted 

in a prior-approval labeling supplement. 

A new established pharmacologic class term that has not been previously approved for another 

drug product can be included in the Highlights of a drug product’s labeling at the time of final 

labeling approval if the pharmacologic class is scientifically valid and clinically meaningful. 

Parentheses should be used for common abbreviations in the following format: 

Examples: Proton Pump Inhibitor (PPI), Nucleoside Reverse Transcriptase Inhibitor 

(NRTI) 

Parentheses should not be used to indicate auxiliary or less-important pharmacologic class terms. 

8

 See http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162549.htm.