[Federal Register Volume 73, Number 2 (Thursday, January 3, 2008)]
[Rules and Regulations]
[Pages 402-404]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E7-25426]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 201, 208, and 209

[Docket No. 2003N-0342]
RIN 0910-AC35


Toll-Free Number for Reporting Adverse Events on Labeling for 
Human Drug Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Interim final rule.

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SUMMARY: The Food and Drug Administration (FDA) is issuing an interim 
final rule to codify the provisions of the proposed rule entitled 
``Toll-Free Number for Reporting Adverse Events on Labeling for Human 
Drug Products'' (69 FR 21778, April 22, 2004) (the toll-free number 
proposed rule or proposed rule) that, under the Food and Drug 
Administration Amendments Act of 2007 (FDAAA), became effective by 
operation of law on January 1, 2008. This interim final rule requires 
the addition of a statement on the labeling of certain human drug 
products for which an application is approved under the Federal Food, 
Drug, and Cosmetic Act (the act). The added statement includes a toll-
free number and advises that the number is to be used only for 
reporting side effects and is not intended for medical advice (the side 
effects statement). As mandated by FDAAA, this interim final rule does 
not apply to over-the-counter drug products approved as new drugs under 
the act if the product packaging includes a manufacturer's or 
distributor's toll-free number for reporting complaints.

DATES: Effective Date: This rule is effective January 1, 2008.
    Compliance Date: The agency anticipates that affected entities, 
including manufacturers, authorized dispensers, and pharmacies, will 
need time to update labeling and systems to comply with the new 
requirements. Therefore, FDA intends to exercise its enforcement 
discretion and not take enforcement actions with regard to these 
regulations until January 1, 2009.

FOR FURTHER INFORMATION CONTACT: Carol Drew, Center for Drug Evaluation 
and Research (HFD-7), Food and Drug Administration, 5600 Fishers Lane, 
Rockville, MD 20857, 301-594-2041.

SUPPLEMENTARY INFORMATION:

I. Background

    On September 27, 2007, the President signed into law FDAAA (Public 
Law 110-85). Among other things, FDAAA reauthorized the Best 
Pharmaceuticals for Children Act (BPCA). When enacted in 2001, 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. Collectively, we refer to the toll-free number and reporting 
statement as the ``side effects statement.'' The BPCA stated that the 
final rule must reach the broadest consumer audience and minimize the 
cost to the pharmacy profession.
    As required, FDA issued a proposed rule entitled ``Toll-Free Number 
for Reporting Adverse Events on Labeling for Human Drug Products'' (69 
FR 21778, April 22, 2004). FDA received 22 comments on this proposed 
rule and was in the process of analyzing the comments and conducting 
research on consumer comprehension of the side effects statement when 
FDAAA was enacted (see section IV of this document).

II. FDAAA Requirements

    Section 502(f) of FDAAA states 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.
    FDAAA mandates one change to the proposed rule. As described in 
section III of this document, section 502(f)(2) of FDAAA states that 
the toll-free number proposed rule shall not apply to over-the-counter 
(OTC) drugs marketed with an application approved under section 505 of 
the act (application OTC drug products) if these application OTC drug 
products meet certain labeling requirements. (Neither the BPCA, the 
proposed rule, nor this interim final rule addresses OTC drugs marketed 
without approved applications.)
    Because the agency's rulemaking process is ongoing, for the reasons 
explained in section IV of this document, this interim rule codifies 
the provisions of the proposed rule as modified by FDAAA. As mandated 
by FDAAA, these provisions came into effect on January 1, 2008. The 
agency is publishing this interim final rule to codify the modified 
toll-free number proposed rule that has now come into effect.

[[Page 403]]

III. Description of the Interim Final Rule

    Consistent with the mandates of the BPCA, FDA proposed to require 
that the side effects statement be included in FDA-approved Medication 
Guides for drug products approved under section 505 of the act. We also 
proposed that the side effects statement be distributed with each 
prescription drug product approved under section 505 of the act and 
dispensed to consumers by pharmacies and authorized dispensers in an 
outpatient setting. In addition, as described in the toll-free number 
proposed rule, FDA interpreted the BPCA to apply to application OTC 
drug products. Accordingly, FDA also proposed to require the side 
effects statement in the labeling for application OTC drug products.
    Section 502(f)(2) of FDAAA states that the proposed rule shall not 
apply to a drug: (1) For which an application is approved under section 
505 of the act; (2) that is not described under section 503(b)(1) of 
the act (21 U.S.C. 353(b)(1)); and (3) the packaging of which includes 
a toll-free number through which consumers can report complaints to the 
manufacturer or distributor of the drug. This provision means that the 
proposed rule as it has come into effect by operation of law in 
accordance with FDAAA does not apply to an application OTC drug product 
if the product's packaging includes a manufacturer's or distributor's 
toll-free number for reporting complaints. Accordingly, this interim 
final rule includes a modified Sec.  201.66(c)(5)(vii) reflecting the 
change to the proposed rule mandated by FDAAA.

IV. Ongoing Research on the Side Effects Statement

    FDA is in the process of conducting research on the wording of the 
side effects statement published in the toll-free number proposed rule. 
FDA initiated this research after reviewing the comments on the 
proposed rule. Among the reasons cited in these comments for testing 
the statement were: (1) To determine the best and most precise wording 
for the statement; (2) to evaluate consumer comprehension of the 
proposed statement; and (3) to address concerns that consumers who read 
the statement will mistakenly call FDA in search of medical advice.
    FDA designed a two-part study in response to these comments. Part 
one consisted of focus groups held to narrow the field of potential 
statement alternatives. This research was completed in 2006 (OMB 
Control No. 0910-0497). The second part of this research is a labeling 
comprehension experiment to be conducted over the Internet (OMB Control 
No. 0910-0603). FDA plans to complete this research. Then, based on the 
results of the data collected from the research and the comments 
received on the proposed rule, the agency will determine whether to 
finalize this interim final rule as published or to publish a final 
rule that amends this interim final rule. The effective date and 
implementation schedule for the final rule will be designed to minimize 
the burden of any additional regulatory changes for affected entities 
who must comply with this interim final rule.

V. Legal Authority

    Section 502(f) of FDAAA states that the toll-free number proposed 
rule shall take effect on January 1, 2008, unless the agency publishes 
a final rule prior to that date. FDA determined that the research being 
undertaken to inform the proposed side effects statement could not be 
completed in time for FDA to publish a final rule prior to January 1, 
2008, and that this research needed to be completed for the agency to 
respond fully to the comments received on the toll-free number proposed 
rule. Therefore, FDA did not publish a final rule before January 1, 
2008, and the toll-free number proposed rule, as modified by FDAAA, 
came into effect by operation of law on that date.
    FDA has received comments on the proposed rule addressing issues 
including the scope of the rule, the content and presentation of the 
side effects statement, the reporting provisions, the costs and 
benefits of the rule, implementation of the rule, and compliance with 
it. As part of the final rulemaking that the agency will undertake 
after completing the research on the side effects statement (see 
section IV in this document), FDA will consider and address all 
comments submitted to the docket for the toll-free number proposed 
rule.

VI. Effective Date/Compliance Date

    As mandated by FDAAA, the effective date of the interim final rule 
is January 1, 2008. In the preamble to the toll-free number proposed 
rule, the agency proposed that all manufacturers, dispensers and 
pharmacies subject to the rule be in compliance not more than 1 year 
after the effective date of the final rule. FDA explained that the 
agency anticipated these entities would require time to update labeling 
and systems to comply with the new requirements.
    FDAAA does not address timing needs for affected entities to come 
into compliance with the rule. The only change FDAAA makes to the 
agency's proposal is to limit the scope of the proposed rule to make 
the rule inapplicable to certain application OTC drug products. 
Accordingly, FDA concludes that FDAAA was not intended to make any 
other changes to the agency's proposal, including with regard to 
addressing the anticipated needs of affected entities for time to come 
into compliance with the rule.
    FDA continues to anticipate that affected entities, including 
manufacturers of drug products, authorized dispensers, and pharmacies, 
will need time to update labeling and systems to comply with the new 
requirements. Therefore, consistent with the agency's proposal, the 
agency intends to exercise its enforcement discretion with regard to 
these regulations until January 1, 2009. That is, the agency does not 
intend to take enforcement action with regard to this interim final 
rule before that date.

List of Subjects

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 208

    Labeling, Prescription drugs, Reporting and recordkeeping 
requirements.

21 CFR Part 209

    Authorized dispensers, Drugs, Pharmacies, Prescription drugs.

0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, 21 CFR 
Chapter I is amended as follows:

PART 201--LABELING

0
1. The authority citation for 21 CFR part 201 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360, 
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.

0
2. Amend Sec.  201.66 by adding two sentences at the end of paragraph 
(c)(5)(vii) to read as follows:


Sec.  201.66  Format and content requirements for over-the-counter 
(OTC) drug product labeling.

* * * * *
    (c) * * *
    (5) * * *
    (vii) * * * For all OTC drug products under an approved drug 
application whose packaging does not include a toll-free number through 
which consumers can report complaints to the manufacturer or 
distributor of the drug product, the following text shall

[[Page 404]]

immediately follow the subheading: ``[Bullet] side effects occur. You 
may report side effects to FDA at 1-800-FDA-1088.'' The telephone 
number must appear in a minimum 6-point bold letter height or type 
size.
* * * * *

PART 208--MEDICATION GUIDES FOR PRESCRIPTION DRUG PRODUCTS

0
3. The authority citation for 21 CFR part 208 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 
360, 371, 374; 42 U.S.C. 262.

0
4. Amend Sec.  208.20 by adding paragraph (b)(7)(iii) to read as 
follows:


Sec.  208.20  Content and format of a Medication Guide.

* * * * *
    (b) * * *
    (7) * * *
    (iii) 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.''
* * * * *

0
5. Add part 209 to read as follows:

PART 209--REQUIREMENT FOR AUTHORIZED DISPENSERS AND PHARMACIES TO 
DISTRIBUTE A SIDE EFFECTS STATEMENT

Subpart A--General Provisions

Sec.
209.1 Scope and purpose.
209.2 Definitions.

Subpart B--Requirements

209.10 Content and format of the side effects statement.
209.11 Dispensing and distributing the side effects statement.

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360, 371; 42 
U.S.C. 241.

Subpart A--General Provisions


Sec.  209.1  Scope and purpose.

    (a) This part sets forth requirements for human prescription drug 
products approved under section 505 of the Federal Food, Drug, and 
Cosmetic Act and dispensed by authorized dispensers and pharmacies to 
consumers. This part requires distribution of a side effects statement 
and applies to new and refill prescriptions. This part is not intended 
to apply to 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.
    (b) The purpose of providing the side effects statement is to 
enable consumers to report side effects of prescription drug products 
to FDA.


Sec.  209.2  Definitions.

    For the purposes of this part, the following definitions apply:
    Act means the Federal Food, Drug, and Cosmetic Act (sections 201-
907 (21 U.S.C. 301-397)).
    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.
    Consumer medication information means written information 
voluntarily provided to consumers by dispensing pharmacists as part of 
patient medication counseling activities.
    Medication Guide means FDA-approved patient labeling conforming to 
the specifications set forth in part 208 of this chapter and other 
applicable regulations.
    Pharmacy includes, but is not limited to, a retail, mail order, 
Internet, hospital, university, or clinic pharmacy, or a public health 
agency, regularly and lawfully engaged in dispensing prescription 
drugs.
    Side effects statement means 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.''

Subpart B--Requirements


Sec.  209.10  Content and format of the side effects statement.

    (a) Content. The side effects statement provided with each 
prescription drug product approved under section 505 of the act must 
read: ``Call your doctor for medical advice about side effects. You may 
report side effects to FDA at 1-800-FDA-1088.''
    (b) Format. The side effects statement must be in a single, clear, 
easy-to-read type style. The letter height or type size used for the 
side effects statement in accordance with paragraphs (b)(1) and (b)(2) 
of Sec.  209.11 must be no smaller than 6 points (1 point = 0.0138 
inch). The letter height or type size for the side effects statement 
under paragraphs (b)(3), (b)(4), and (b)(5) of Sec.  209.11 must be no 
smaller than 10 points.


Sec.  209.11  Dispensing and distributing the side effects statement.

    (a) Each authorized dispenser or pharmacy must distribute the side 
effects statement with each prescription drug product approved under 
section 505 of the act and dispensed. The side effects statement must 
be distributed with new and refill prescriptions.
    (b) An authorized dispenser or pharmacy must choose one or more of 
the following options to distribute the side effects statement:
    (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 in consumer medication 
information; or
    (5) Distribute the appropriate FDA-approved Medication Guide that 
contains the side effects statement.

    Dated: December 21, 2007.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E7-25426 Filed 1-2-08; 8:45 am]
BILLING CODE 4160-01-S