[Federal Register Volume 62, Number 147 (Thursday, July 31, 1997)]
[Notices]
[Pages 41061-41063]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 97-20247]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 97N-0289]
Content and Format of Labeling for Human Prescription Drugs;
Pregnancy Labeling; Public Hearing
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice of public hearing; request for comments.
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SUMMARY: The Food and Drug Administration (FDA) is announcing a public
hearing regarding requirements for the content and format of the
pregnancy subsection of labeling for human prescription drugs. The
public hearing will focus on the requirement that each drug product be
classified in one of five pregnancy categories intended to aid
clinicians and patients with decisions about drug therapy. Public
comments and FDA's preliminary review of the pregnancy category
designations for marketed drugs suggest that the categories may be
misleading and confusing, may not accurately reflect reproductive and
developmental risk, and may be used inappropriately by clinicians in
making decisions about drug therapy in pregnant women and women of
childbearing potential and also in making decisions about how to
respond to inadvertent fetal exposure. The hearing is intended to
elicit comments on the practical utility, effects, and limitations of
the current pregnancy labeling categories in order to help the agency
identify the range of problems associated with the categories and to
identify and evaluate options that might address identified problems,
and to hear the views of groups most affected.
DATES: The public hearing will be held on Friday, September 12, 1997,
from 9 a.m. to 5 p.m. Submit written notices of participation and
comments for consideration at the hearing by August 28, 1997. Written
comments will be accepted after the hearing until November 12, 1997.
ADDRESSES: The hearing will be held at the Holiday Inn Bethesda, 8120
Wisconsin Ave.,Versailles I and II, Bethesda, MD 20814. Submit written
notices of participation and comments to the Advisors and Consultants
Staff, Center for Drug Evaluation and Research (HFD-21), ATTN:
Pregnancy Labeling Hearing--Robin M. Spencer or Kimberly L. Topper,
Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857,
FAX 301-443-0699. Federal Express deliveries need to use the following
street address: 1901 Chapman Ave., rm. 200, Rockville, MD 20852.
Transcripts of the hearing will be available from the Freedom of
Information Office (HFI-35), Food and Drug Administration, 5600 Fishers
Lane, Rockville, MD 20857, FAX 301-443-1726, approximately 15 business
days after the hearing at a cost of 10 cents per page. Requests can
also be made for microfiche or computer disk copies in place of paper
copies.
FOR FURTHER INFORMATION CONTACT: Rose E. Cunningham, Center for Drug
Evaluation and Research (HFD-6), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-594-6779, or FAX 301-594-5493;
or Kimberly L. Topper, Advisors and
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Consultants Staff (address above), 301-443-5455, or FAX 301-443-0699.
SUPPLEMENTARY INFORMATION:
I. Background
Under the Federal Food, Drug, and Cosmetic Act (the act), FDA has
responsibility for ensuring that prescription drug and biological
products are accompanied by labeling (prescribing information) that
summarizes essential scientific information needed for their safe and
effective use. Unless a drug is not absorbed systemically and is not
known to have a potential for indirect harm to a fetus, its labeling
must include a ``Pregnancy subsection'' containing narrative
information on the drug's teratogenic effects and other effects on
reproduction and pregnancy, and, when relevant, effects on later
growth, development, and functional maturation of the child (21 CFR
201.57(f)(6)). The regulation also requires that each product be
classified under one of five pregnancy categories (A, B, C, D, or X) on
the basis of risk of reproductive and developmental adverse effects or,
for certain categories, on the basis of such risk weighed against
potential benefit. A drug's pregnancy category is identified at the
beginning of its pregnancy labeling subsection.
Clinicians who treat pregnant women and women of childbearing
potential, academic and specialty medical organizations, women's health
organizations and others have expressed to FDA concern that the
information contained in the typical pregnancy labeling subsection, and
the manner in which such information is presented, are not sufficient
to adequately inform decisions about drug therapy in pregnant women and
women of childbearing potential, or decisions about how to respond to
inadvertent fetal drug exposure.
In response to these concerns and FDA's growing awareness of the
limitations of the pregnancy subsection of the labeling, FDA is
currently engaged in a comprehensive evaluation of the way the agency
assesses reproductive and developmental toxicities associated with
human drugs and biologics, and the way the agency communicates this
information to clinicians and patients. This evaluation is focused on
assessing the adequacy of animal and human exposure data currently
developed or maintained, developing consistency in interpretation of
reproductive and developmental risk from animal and human exposure
data, and identifying means to optimize communication of this risk
information.
FDA has created a multidisciplinary task force to explore these
issues. This group intends to develop, for use by FDA reviewers and
industry, a guidance document on interpretation of reproductive and
developmental toxicity data from animals and a guidance document on
interpretation of human exposure data. The task force will also
consider other possible actions that may be necessary to make pregnancy
labeling content more consistent, informative, and accessible
including: (1) Changing, or creating alternatives to, the pregnancy
labeling categories; (2) clearly distinguishing in labeling between
information that addresses whether to prescribe a therapeutic option
during pregnancy, whether to prescribe a therapeutic option in a woman
of childbearing potential, and the potential consequences of
inadvertent fetal exposure; and (3) attempting to better delineate the
different types of reproductive and developmental risks associated with
a product. This hearing is intended to gather information to inform
future task force recommendations.
II. The Pregnancy Categories
FDA's information gathering and evaluation to date have identified
the pregnancy categories as a source of concern for those who use or
are affected by pregnancy labeling. The categories have been criticized
for being confusing and misleading because they convey the impression
that there is a gradation of reproductive risk from drug exposure
across categories (i.e., that risk increases from A to B to C to D to
X) and that there is similar risk within any given category, but the
criteria for designating drugs in particular categories are not
consistent with these impressions.
The confusion concerning gradation of risk across categories is
believed to be due, in part, to the fact that the criteria for
inclusion in categories A, B, and to a certain extent C, are based
primarily on risk with risk increasing from A to C, while criteria for
inclusion in categories D, X, and to a certain extent C, are based on
risk weighed against potential benefit. Thus, while it is intended that
there be gradation of risk for categories A through C, drugs designated
D, X, and in some cases C, may pose a very similar risk, but be
categorized differently on the basis of potential benefit.
The impression that there is similar risk for drugs within the same
category is undercut by inclusion criteria that permit a broad range of
risk within certain categories. For example, category C (the largest
category) is intended to include both drugs with demonstrated adverse
reproductive effects in animals and drugs for which there are no animal
studies at all, situations that may be quite different in terms of
risk. For the category C drugs that were tested in animals, moreover,
there is a wide range of severity of adverse effects and often no
distinction between teratogenic and other toxic effects.
The confusion inherent in the current category designations may be
exacerbated by inconsistent application of category classifications in
certain instances, such that drugs with similar risk, or with similar
risk-benefit assessments, may be found in different categories.
Some who expressed concern to the agency about pregnancy labeling
argue that failure of the category designations to accurately reflect
reproductive and developmental risk, either across categories or within
a category, presents potentially serious public health consequences.
They maintain that many clinicians assume the categories reflect
gradation of risk from category A through X, that any given category is
homogenous in terms of risk, and based on those assumptions make
decisions based largely or entirely on category designation rather than
on careful evaluation of the available data. They also argue that, in
addition to the potential for category designations to be misleading,
the mere presence of category designations affords an overly simplistic
evaluation of a complex problem that can deter the clinician from
seeking additional information that could lead to a better informed
decision. They maintain that clinicians making decisions based on
category designation alone are more likely to overestimate risk, with
potentially profound consequences. For example, decisions based on an
overestimation of teratogenic risk may result in unnecessary
withholding of beneficial therapy or in termination of wanted
pregnancies.
III. Scope of the Hearing
Because of the breadth and complexity of issues involved in
assessing, interpreting, and communicating information that bears on
therapeutic use and exposure to drugs in pregnancy and in women of
childbearing potential, this part 15 (21 CFR part 15) hearing will
focus on the pregnancy categories. To guide its future decision making,
the agency is seeking public comment and data on the practical utility
and effects of the pregnancy categories, problems associated with the
categories, and the
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means to address problems associated with the categories, including
possible alternatives to the categories for communicating information
on reproductive and developmental toxicity. The agency is specifically
seeking comment and data on the following:
(1) The extent to which the category designations are relied upon
in making decisions about drug therapy in pregnant women and women of
childbearing potential and decisions about inadvertent fetal exposure,
the extent to which such reliance may be misplaced, and the extent to
which such reliance may have untoward public health consequences;
(2) The extent to which current pregnancy labeling (category
designation and accompanying narrative text) is effective in
communicating risk of reproductive and developmental toxicity;
(3) The extent to which current pregnancy labeling may not
adequately address the range of issues that may bear on decisions about
drug therapy in pregnant women and women of childbearing potential and
decisions about inadvertent fetal exposure (e.g., indication-specific
concerns, pregnancy status, magnitude of exposure, incidental exposure,
chronic exposure, timing of exposure);
(4) Additional information (data or interpretation of data) that
could be included in pregnancy labeling to better address the range of
issues that bear on decisions about drug therapy in pregnant women and
women of childbearing potential and decisions about inadvertent fetal
exposure; and
(5) Options to improve communication of reproductive and
developmental risk in labeling, which could include alternatives to the
categories (both content and format options) or efforts to make the
current category scheme and accompanying narrative text more consistent
and informative.
The agency encourages individuals, industry, consumer groups,
health care professionals, and researchers with particular expertise in
this area, as well as other interested persons, to respond to this
notice. The agency strongly encourages persons who cannot attend the
hearing to send information relevant to the topics and questions listed
above to the Dockets Management Branch (HFA-305), Food and Drug
Administration, 12420 Parklawn Dr., rm 1-23, Rockville, MD 20857. Two
copies of any comments are to be submitted, except that individuals may
submit one copy. Comments are to be identified with Docket No. 97N-
0289. Received comments may be seen in the office above between 9 a.m.
and 4 p.m., Monday through Friday.
IV. Notice Of Hearing Under Part 15
The Commissioner of Food and Drugs (the Commissioner) is announcing
that the public hearing will be held in accordance with part 15. The
presiding officer will be the Commissioner or his designee. The
presiding officer will be accompanied by a panel of Public Health
Service employees with relevant expertise.
Persons who wish to participate in the part 15 hearing must file a
written or facsimile notice of participation with the Advisors and
Consultants Staff by August 28, 1997. To ensure timely handling, the
outer envelope or facsimile cover sheet should be clearly marked with
Docket No. 97N-0289 and the statement ``Pregnancy Labeling Hearing.''
Groups should submit two copies. The notice of participation should
contain the speaker's name, address, telephone number, FAX number,
title, business affiliation, if any, a brief summary of the
presentation, and approximate amount of time requested for the
presentation.
The agency requests that persons or groups having similar interests
consolidate their presentations and present them through a single
representative. FDA will allocate the time available for the hearing
among the persons who properly file notices of participation. If time
permits, FDA may allow participation at the conclusion of the hearing
from interested persons attending the hearing who did not submit a
written notice of participation.
After reviewing the notices of participation and accompanying
information, FDA will schedule each appearance and notify each
participant by mail, telephone, or FAX, of the time allotted to the
person and the approximate time the person's presentation is scheduled
to begin. The hearing schedule will be available at the hearing. After
the hearing the schedule will be placed on file in the Dockets
Management Branch (address above) under Docket Number 97N-0289.
Under Sec. 15.30(f), the hearing is informal and the rules of
evidence do not apply. The presiding officer and any panel members may
question any person during or at the conclusion of their presentation.
No other person attending the hearing may question a person making a
presentation or interrupt the presentation of a participant.
Public hearings under part 15 are subject to FDA's guideline (part
10, subpart C (21 CFR part 10, subpart C)) concerning the policy and
procedures for electronic media coverage of FDA's public administrative
proceedings. Under Sec. 10.205, representatives of the electronic media
may be permitted, subject, to certain limitations, to videotape, film,
or otherwise record FDA's public administrative proceedings, including
presentations by participants. Representatives of the electronic media
are urged to provide advance notice of their planned attendance, to the
identified contact person for the hearing, so that their needs for
space and technical assistance can be anticipated and accommodated. The
hearing will be transcribed as required in Sec. 15.30(b). Orders for
copies of the transcript can be placed through the Dockets Management
Branch (address above).
Any disabled persons requiring special accommodations in order to
attend the hearing should direct those needs to the contact person
listed above.
To the extent that the conditions for the hearing, as described in
this notice, conflict with any provisions set out in part 15, this
notice acts as a waiver of those provisions as specified in
Sec. 15.30(h).
To permit time for all interested persons to submit data,
information, or views on this subject, the administrative record will
remain open following the hearing until November 12, 1997.
Dated: July 23, 1997.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 97-20247 Filed 7-30-97; 8:45 am]
BILLING CODE 4160-01-F