Guidance for Industry 

 
Toll-Free Number Labeling and Related 

Requirements for Over-the-Counter and 

Prescription Drugs Marketed With 

Approved Applications 

 
 
 
 
 
Small Entity Compliance Guide 

 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

 
June 2012 

Procedural 

 
   
Guidance for Industry 

 
Toll-Free Number Labeling and Related 

Requirements for Over-the-Counter and 

Prescription Drugs Marketed With 

Approved Applications 

 
Small Entity Compliance Guide 

 
Additional copies are available from: 

Office of Communications 
 
Division of  Drug Information, WO51, Room  2201 
 
10903 New Hampshire Ave. 

Silver Spring, MD 20993 
 
Phone: 301-796-3400;  Fax: 301-847-8714 
 
druginfo@fda.hhs.gov 
  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm  
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

 
June 2012 

Procedural 
 
   
TABLE OF CONTENTS 
 
 
I.	   INTRODUCTION............................................................................................................. 1 
 
II.	   BACKGROUND ............................................................................................................... 1 
 
III. 	  DISTRIBUTION OF SIDE EFFECTS STATEMENT BY AUTHORIZED 

DISPENSERS AND PHARMACISTS............................................................................ 2 
 
IV. 	  TOLL-FREE NUMBER LABEL STATEMENT REQUIREMENTS FOR 

OTC DRUGS..................................................................................................................... 4
  
 
 
 
 
 
 
 
 
  Contains Nonbinding Recommendations 
 
Guidance for Industry 
 
Toll-Free Number Labeling and Related Requirements for Over-the-

Counter and Prescription Drugs Marketed with Approved Applications 

 
 
 
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 help small businesses better understand and comply  with FDAs 
final rule regarding labeling of drugs with a toll-free number for adverse event reporting, 
which was published in the Federal Register on October 28, 2008 (73 FR 63886).  The Food 
and Drug Administration (FDA) has prepared this guidance in accordance with section 212 
of the Small Business Regulatory Enforcement Fairness Act (Public Law 104-121). 
 
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. 
 
 
II.   BACKGROUND 
 
FDA issued the toll-free number final rule (Final Rule) to comply with certain 
requirements of section 17 of the Best Pharmaceuticals for Children Act (BPCA), as 
amended by section 502(f) of the Food and Drug Administration Amendments Act of 
2007 (FDAAA). The BPCA (Public Law 107-109) directed FDA to issue a final rule 
requiring the labeling of each human drug product for which an application is approved 
under section 505 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) to include 
(1) a toll-free number maintained by FDA for the purpose of receiving reports of adverse 
events regarding drugs and (2) a statement that the number is to be used for reporting 
purposes only, and not to receive medical advice.   
 
The Final Rule became effective November 28, 2008, and requires that toll-free number 
labeling be: 
 
   
Contains Nonbinding Recommendations 
 
 
(1)  included in all FDA-approved Medication Guides for products approved 
under a New Drug Application (NDA) or an Abbreviated New Drug 
Application (ANDA) (i.e., approved under section 505),   
(2)  provided to patients by authorized dispensers or pharmacies with each 
prescription drug product approved under an NDA or ANDA (i.e., 
approved under section 505), and 
(3)  included in the labeling of certain over-the-counter (OTC) drugs approved 
under an NDA or ANDA (i.e., approved under section 505) (discussed in 
detail below). 
 
FDA has previously issued a guidance for industry entitled Medication GuidesAdding a 
Toll-Free Number for Reporting Adverse Events (June 2009)1 to assist new drug 
application holders with revising FDA-approved Medication Guides to comply with the 
first of these requirements.  Persons interested in the Medication Guide requirements 
should refer to that guidance document; it will not be further discussed here.   
 
This guidance is intended to assist small businesses and others with implementing the 
two other requirements in the Final Rule  distribution of toll-free number information 
to patients with each prescription (or refill), and adding toll-free number information to 
the labeling of certain OTC drugs. 
 
 
III. 	  DISTRIBUTION OF SIDE EFFECTS STATEMENT BY AUTHORIZED 
DISPENSERS AND PHARMACISTS 
 
Under the toll-free number Final Rule, each authorized dispenser or pharmacy must 
distribute a side effects statement with each prescription drug product approved under 
section 505 of the FD&C Act that they dispense, including both new and refill 
prescriptions.  Side effects statement is defined as the following verbatim statement:  
Call your doctor for medical advice about side effects.  You may report side effects to 
FDA at 1-800-FDA-1088 (21 CFR 209.2). 
 
A. 	  Authorized Dispenser or Pharmacy  
 
Under FDA regulations at 21 CFR 209.2, as amended by the Final Rule, an authorized 
dispenser means an individual licensed, registered, or otherwise permitted by the 
jurisdiction in which the individual practices to provide drug products on prescription in 
the course of professional practice, including licensed physicians and pharmacists.  The 
Final Rule defines pharmacy as including, but not limited to, a retail, mail order, 
Internet, hospital, university, or clinic pharmacy, or a public health agency, that is 
regularly and lawfully engaged in dispensing prescription drugs.  FDA regulations, as 
                                                 
1 Available on the Internet at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances. 
  2
 
 
   
Contains Nonbinding Recommendations 
 
amended by the Final Rule, require any authorized dispenser providing a prescription 
drug that is approved under section 505 to a patient to provide the side effects statement 
with each new and refill prescription (21 CFR 209.11(a)). 
 
B.   Distribution of Side Effects Statement 
 
The regulations require the dispenser to choose one or more of the following options to 
distribute the side effects statement (21 CFR 209.11(b)): 
 
(1)  Distribute the side effects statement on a sticker attached to the unit 
package, vial, or container of the drug product; 
(2)  Distribute the side effects statement on a preprinted pharmacy prescription 
vial cap; 
(3)  Distribute the side effects statement on a separate sheet of paper;  
(4)  Distribute the side effects statement as part of other consumer medication 
information (written information voluntarily provided to consumers by 
dispensing pharmacists as part of patient medication counseling activities); 
or 
(5)  Distribute an appropriate FDA-approved Medication Guide that contains 
the side effects statement. 
 
FDA has received a number of questions about whether the regulations require the side  
effects statement to be provided to patients in situations where the authorized dispenser 
or pharmacy is located in a hospital, nursing home, or similar health care facility.  As 
adopted by the Final Rule, 21 CFR 209.1 excludes from the requirements authorized 
dispensers dispensing or administering prescription drug products to inpatients in a 
hospital or health care facility under an order of a licensed practitioner, or as part of 
supervised home health care.  FDAs position is that when the drug is being 
administered in the presence of a trained health care provider, usually a single dose at a 
time, the requirement to provide the side effects statement does not apply.  Generally, in 
such circumstances the patient is relying on the health care provider to monitor and report 
any adverse events. Such patients would also not ordinarily receive printed patient 
counseling information provided by most commercial pharmacies.  For example, a nurse 
administering a single dose of medication at bedside to a patient in a nursing home wing 
of an independent living/nursing home facility would not be required to provide the side 
effects statement.  Similarly, the regulations do not require providing a side effects 
statement each time a medication is administered to a patient by a home health care 
provider. 
 
On the other hand, if the dispensary in the same independent living/nursing home facility 
fills a doctors prescription for a 30-day supply of a medication for an independent living 
resident which the patient will self-administer (in her own apartment within or outside the 
facility), the Final Rule would require that the patient receive, along with the prescription, 
the side effects statement with instructions for reporting adverse events to FDA (in the 
same way as would a patient filling the prescription at a local pharmacy for home use).  
  3
 
 
   
Contains Nonbinding Recommendations 
 
The materials would need to be provided to these patients in one of the formats described 
in section III of this guidance. 
 
 
IV. 	  TOLL-FREE NUMBER LABEL STATEMENT REQUIREMENTS FOR 
OTC DRUGS 
 
OTC drugs can be marketed under an application approved under section 505 of the 
FD&C Act, or without an approved application under an OTC monograph.  Because the 
toll-free labeling requirements of the BPCA and the Final Rule apply only to drug 
products approved under section 505, under the terms of the FD&C Act, OTC drugs 
marketed under a monograph are subject to different labeling requirements.  The 
differences in the requirements for application versus monograph OTC drugs are 
explained below. 
 
A. 	  OTC Drugs With Approved Applications Under Section 505 
 
The toll-free number Final Rule requires OTC drugs with approved applications (NDAs 
or ANDAs) to comply with the toll-free labeling requirement in either of the following 
two ways: (1) by including on their packaging a toll-free number through which 
consumers can report complaints directly to the manufacturer or distributor, or (2) by 
including a specified label statement in the OTC drug facts format containing FDAs toll-
free number for reporting adverse events (FDAs MedWatch telephone number).  The 
label statement must be worded exactly as follows:  [Bullet] side effects occur.  You 
may report side effects to FDA at 1-800-FDA-1088.  21 CFR 201.66(c)(5)(vii).2  In 
other words, unless the drugs label contains a toll-free number for reporting adverse 
events directly to the manufacturer or distributor, the label must include the specified 
label statement including the 1-800-FDA-1088 number.  If the label contains a toll-free 
number for reporting adverse events to the manufacturer or distributor, the specified label 
statement and FDA MedWatch phone number are not required.   
 
B. 	  OTC Drugs Marketed Under a Monograph 
 
OTC drugs marketed under an OTC monograph and not under an approved application 
are not subject to the requirements of the toll-free labeling Final Rule.  OTC monograph 
drugs are subject instead to different labeling requirements established under the Dietary 
Supplement and Nonprescription Drug Consumer Protection Act of 2006 (DSNDCPA) 
(Public Law 109-462). Section 2(d) of DSNDCPA added section 502(x) to the FD&C Act to 
require the label of an OTC drug marketed in the United States without an approved 
application to contain the domestic address or phone number at which the manufacturer or 
                                                 
2 Under 21 CFR 201.66(c)(5)(vii), the information is placed in the warning section of the drug facts label.   
  4
 
 
   
Contains Nonbinding Recommendations 
 
other responsible person3 may receive a report of a serious adverse event associated 
with the use of a drug product. In September 2009, FDA issued a guidance on these 
requirements entitled Labeling of Nonprescription Human Drug Products Marketed 
Without an Approved Application as Required by the Dietary Supplement and 
Nonprescription Drug Consumer Protection Act: Questions and Answers.4  Persons 
interested in more information about that requirement should refer to that guidance.    
C.   Summary Table For OTC Products 
The following table clarifies the type of OTC drug products affected by each statutory 
provision and answers specific questions about each of the requirements applicable to 
each category of drugs. 
DSNDCPA and September 
  Toll-Free Number Final Rule 
2009 Labeling Guidance 
To which  OTC products marketed under  OTC drug products marketed 
OTC drug  applications approved under section 505  without an approved 
products  of the FD&C Act (NDAs or ANDAs).  application. 
does this 
initiative  
apply?  
What must  Unless the packaging includes a toll- The domestic address or 
be on the  free number through which consumers  phone number at which the 
drug  can report complaints to the  manufacturer or other 
products  manufacturer or distributor, the drug  responsible person may 
label?   facts label must contain a statement in  receive a report of a serious 
the content and format specified in 21   adverse event associated with 
CFR 201.66(c)(5)(vii) that includes  the use of a drug product. 
FDAs toll-free MedWatch telephone 
number. 
What is the  Best Pharmaceuticals for Children Act  Dietary Supplement and 
legislative  of 2001 (BPCA) and Food and Drug  Nonprescription Drug 
origin of this  Administration Amendments Act of  Consumer Protection Act of 
initiative?   2007 (FDAAA).  2006 (DSNDCPA). 
What is the  The toll-free number Final Rule became  The DSNDCPA requirements 
effective  effective November 28, 2008.  became effective December 
date?   22, 2007. 
                                                 
3 Responsible  person is  defined in the DSNDCPA as The manufacturer, packer, or  distributor  whose 
name (pursuant to section  502(b)(1)) appears on the label of a nonprescription  drug marketed in the United  
States (section 760(b)(1)).   
4 Available on the Internet at Available on the Internet at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances. 
  5