Medication Guides — Adding a Toll-Free Number for Reporting Adverse Events

Administrative guidance, not enacted legislation. This captured publisher edition preserves the listed document and attachments; later developments are not independently consolidated.

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 (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 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) FDA’s 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
FDA’s 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 FDA’s verbatim
statement. In accordance with FDA’s regulations (see 21 CFR 208.20(b)(8)), the manufacturer’s, packer’s, or
distributor’s 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 FDA’s required verbatim statement. Also, the additional language should not
modify the intent or meaning of FDA’s verbatim statement. We suggest the following language: “You may also
report side effects to (manufacturer) at (manufacturer’s 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.
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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.
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