"Toll-Free Number Labeling and Related Requirements for Over-the-Counter and Prescription Drugs Marketed With Approved Applications"

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

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 FDA’s
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).
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.
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 Guides—Adding 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.
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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.” FDA’s 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 doctor’s 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).
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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 FDA’s toll-
free number for reporting adverse events (FDA’s 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 drug’s 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 person”3 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.
Toll-Free Number Final Rule DSNDCPA and September
2009 Labeling Guidance
To which
OTC drug
products
does this
initiative
apply?
OTC products marketed under
applications approved under section 505
of the FD&C Act (NDAs or ANDAs).
OTC drug products marketed
without an approved
application.
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
product’s 	manufacturer or distributor, the drug 	“responsible person” may
label? 	facts label must contain a statement in
the content and format specified in 21
CFR 201.66(c)(5)(vii) that includes
FDA’s toll-free MedWatch telephone
number.
receive a report of a serious
adverse event associated with
the use of a drug product.
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
effective
date?
The toll-free number Final Rule became
effective November 28, 2008.
The DSNDCPA requirements
became effective December
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