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 
1
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 
 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) 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. 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances describe the Agencys 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 make 
indexing decisions based on the prescribing information and the selected terminologies.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 on 
Structured Product Labeling Resources.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. 
2  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 drugs 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 potassium-
sparing 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 
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 applicants 
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 products 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. 
6