Guidance for Industry 

 
Medication Guides  Adding 

a Toll-Free Number for 

Reporting Adverse Events 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

 
 
June 2009 

Procedural 

 
 
   
Guidance for Industry 

Medication Guides Adding 

a Toll-Free Number for 

Reporting Adverse Events 
  
 
 
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/cder/guidance/index.htm 

 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

 
June 2009 

Procedural 

 
  Contains Nonbinding Recommendations 
TABLE OF CONTENTS 
 
 
 
I.   INTRODUCTION............................................................................................................. 1 
 
II.   BACKGROUND ............................................................................................................... 2 
 
III.   HOW TO COMPLY WITH THE REGULATIONS .................................................... 3 
 
A.   Format and Placement of Required Side Effects Statement......................................................3
  
B.   Submission of Change....................................................................................................................4
  
  Guidance for Industry1
  
Medication Guides Adding a Toll-Free Number for Reporting 

Adverse Events 

 
 
This guidance represents the Food and Drug Administration's (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 assist manufacturers of prescription drugs approved under section 
505 of the Federal Food, Drug, and Cosmetics Act (the Act) (21 U.S.C. 355) that are required to 
have an FDA-approved Medication Guide. On July 1, 2009, FDA expects affected entities to be 
in compliance with 21 CFR 208.20(b)(7)(iii), which requires that Medication Guides contain a 
verbatim statement that includes:  (1) FDAs toll-free MedWatch phone number and (2) a 
statement that the number is to be used for reporting purposes only, not to receive medical advice 
(the side effects statement).  Manufacturers must also notify the Agency that the side effects 
statement has been added to their Medication Guides.  
 
This guidance explains: 
	   the content and format of the side effects statement,  
	   where in the Medication Guide to add the side effects statement, and  
	   how to report to the Agency that the side effects statement has been added to a Medication 
Guide. 
 
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.  
 
 
 
 
                                                 
1 This  guidance has been  prepared by the Center for Drug Evaluation and Research (CDER) at the Food and Drug 
Administration.   Contains Nonbinding Recommendations 
 
II.  BACKGROUND  

 
The requirement to add a side effects statement to Medication Guides is the result of a series of 
statutory and regulatory actions. These actions are outlined briefly here. 
 
	   In 2001, the Best Pharmaceuticals for Children Act (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 Act (21 U.S.C. 355) 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, not to receive medical advice. 
	   On April 22, 2004 (69 FR 21778), FDA published a proposed rule entitled Toll-Free Number 
for Reporting Adverse Events on Labeling for Human Drug Products. 
	   On September 27, 2007, the President signed into law the Food and Drug Administration 
Amendments Act of 2007 (FDAAA) (Public Law  110-85).  Section 502(f) of FDAAA stated 
that the proposed rule *** Toll-Free Number for Reporting Adverse Events on Labeling for 
Human Drug Products***shall take effect on January 1, 2008, unless FDA issues a final 
rule before that date. 
	   FDA did not issue a final rule prior to January 1, 2008, so by operation of law, the proposed 
rule took effect on January 1, 2008. 
	   On January 3, 2008 (73 FR 402), FDA issued an interim final rule, which established a 
compliance date of January 1, 2009, for including the side effects statement in the labeling 
for human drug products subject to the rule.  The interim final rule stated that FDA 
anticipated that affected entities would need time to update labeling and systems to comply 
with the new requirements and that FDA intended to exercise its enforcement discretion and 
not take action to enforce the requirements in the toll-free number interim final rule until 
January 1, 2009. The interim final rule codified the modifications made by FDAAA to the 
proposed rule, including changes to certain requirements for over-the-counter drug products.  
The rule also stated that FDA planned to complete research begun on the proposed labeling 
statements and issue a final rule taking into account the results of that research. 
	   On October 28, 2008 (73 FR 63886), FDA issued a final rule with an effective date of  
November 28, 2008 and a compliance date of July 1, 2009.  FDA delayed the compliance 
date until July 1, 2009 because of the short time interval between the publication date of the 
final rule and the original compliance date of January 1, 2009.  All affected entities are 
required to be in compliance by July 1, 2009.    
  2
 
  Contains Nonbinding Recommendations 
 
III. 	  HOW TO COMPLY WITH THE REGULATIONS 
 
A. 	 Format and Placement of Required Side Effects Statement 
 
Under section 208.20(b)(7)(iii) (21 CFR 208.20(b)(7)(iii)), the following verbatim statement 
must be added to FDA-approved Medication Guides for prescription drug products approved 
under section 505 of the Act: 
 
Call your doctor for medical advice about side effects.  
You may report side effects to FDA at 1-800-FDA-1088. 
 
All other provisions of section 208.20(a) (21 CFR 208.20(a)) regarding the content and format of 
a Medication Guide apply to this labeling statement (e.g., the letter height or type size of the 
statement should be no smaller than 10 points (1 point = 0.0138 inches) as required by 
208.20(a)(4)). No changes or additions may be made to the verbatim statement.2   
 
FDAs regulations require affected manufacturers of prescription drug products approved under 
section 505 of the Act to place the required side effects statement under the following heading in 
their FDA-approved Medication Guides (see 21 CFR 208.20(b)(7)): 
What are the possible or reasonably likely side effects of (name of drug)?  
As required by the regulations, this heading must be followed by:  
(1) 	  A statement of the adverse reactions reasonably likely to be caused by the drug 
product that are serious or occur frequently (21 CFR 208.20(b)(7)(i)), 
(2) 	  A statement of the risk, if there is one, of patients' developing dependence on the 
drug product (21 CFR 208.20(b)(7)(ii)), and 
(3) 	  For drug products approved under section 505 of the Act, 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 208.20(b)(7)(iii)). 
 
                                                 
2 In some circumstances a manufacturer may wish to include its own phone number for reporting side effects in this 
section  of a Medication  Guide.  Under section 208.20(b)(7)(iii), a manufacturer may not change  FDAs verbatim  
statement.  In accordance with FDAs regulations (see  21 CFR 208.20(b)(8)), the manufacturers, packers, or  
distributors contact information is included in a general  information section of the Medication Guide.  To reduce 
redundancy, we encourage manufacturers to list their contact information in this general information section  only.  
However, if a manufacturer elects to include a phone number for reporting side effects in  the section entitled What 
are the possible or reasonably likely side effects of... ? , it can  do so after the verbatim statement.  The additional 
language should  be separated from FDAs required verbatim statement.  Also, the additional language should not  
modify the intent or meaning of FDAs verbatim statement.  We suggest the following language: You  may also  
report  side effects to (manufacturer) at (manufacturers phone number).  If a manufacturer elects to add this 
language, it should notify  us of this change in an annual  report.   See Section III.B  of this  document.    
  3
 
  Contains Nonbinding Recommendations 
B.  Submission of Change 
 
For new drug applications (NDAs) and abbreviated new drug applications (ANDAs), regulations 
at 21 CFR 314.70(b)(2)(v)(B) generally require that any change to a Medication Guide under 
part 208 be submitted and approved prior to distribution of the product (i.e., in a prior approval 
supplement).   Notwithstanding this general requirement, 21 CFR 314.70(a)(3) requires an 
applicant to make such a change in accordance with a regulation or guidance that provides for a 
less burdensome notification of the change.    
 
Pursuant to 21 CFR 314.70(a)(3), notification of inclusion of the side effects statement in a 
Medication Guide should be provided in an annual report.  FDA regards the addition of the side 
effects statement to a Medication Guide to be a minor change in labeling under 314.70(d)(21 
CFR 314.70(d)), particularly since the format and content of the statement are specified by the 
statute and regulations.  A supplemental application should not be submitted to the Agency for 
preapproval. 
 
  
  4