GUIDANCE DOCUMENT
Device Labeling Guidance #G91-1 (Blue Book Memo) March 1991
- Docket Number:
- FDA-2020-D-0957
- Issued by:
-
Guidance Issuing OfficeCenter for Devices and Radiological Health
This guidance was written prior to the February 27, 1997 implementation of FDA's Good Guidance Practices, GGP's. It does not create or confer rights for or on any person and does not operate to bind FDA or the public. An alternative approach may be used if such approach satisfies the requirements of the applicable statute, regulations, or both. This guidance will be updated in the next revision to include the standard elements of GGP's.
General Program Memorandum #G91-1
Date: March 8, 1991
From: Director, Office of Device Evaluation (HFZ-400)
Subject: Device Labeling Guidance
To: ODE Review Staff
Purpose
The primary purpose of this memorandum is to formalize guidance to ODE
reviewers concerning their review of labeling in device marketing
submissionsr especially premarket approval applications (PhAs). This
guidance is intended to ensure the adequacy of, and consistency in,
device labeling information. The guidance is also intended for industry
use in preparing device labeling.
Background
General labeling requirements for medical devices have been established
in 21 CFR Part 801. Detailed and specific labeling requirements for in
vitro diagnostic products were promulgated under 21 CFR 809.10. Neither
of these, however, provide specific definitions or explanations of some
significant terms such as warnings, precautions, contraindications and
adverse reactions. The lack of definitions for such terms leads to
misunderstandings and disagreements between PMA applicants and the ODE
review staff. Because labeling content is a key factor in the CDRH
determination of whether there is reasonable assurance that a device is
safe and effective for its intended user such disputes have unnecessarily
prolonged PMA review times.
Scope and Application of the Guidance
Portions of the attached "Device Labeling Guidance" that are based upon
definitions and requirements in the act and applicable regulations
include appropriate references thereto. Guidance on "Indications for
Use," "Contraindications," "Warnings," "Precautions" and "Adverse
Reactions" paraphrase applicable provisions in the labeling requirements
for prescription drugs (21 CFR Part 201). Consistency between drug and
device labeling content and the terminology therein will help minimize
misunderstandings by medical practitioners and patients.
While this guidance is primarily intended to ensure the adequacy of, and
the consistency in, the labeling information for devices subject to
premarket approval, it may also contribute to premarket notification
reviews. As indicated in the "Blue Book" 510(k) Memorandum #86-3 dated
June 30, 1986, a premarket notification must normally only contain
proposed labeling sufficient to describe the device's intended use.
Accordingly, the Sl0(k) decision letter finding a device to be
substantially equivalent advises that this finding does not connote
approval of the proposed labeling. Nevertheless, in the case of in vitro
diagnostic devices, devices with special labeling requirements under
Subpart H of 21 CFR Part 801, and devices for which the inclusion of
specific directions for use, contraindications, warnings, etc. in the
labeling may be critical to a finding of equivalence, the ODE premarket
notification labeling review includes an evaluation of the compliance of
the proposed labeling, or portions thereof, with applicable requirements
under 21 CFR Parts 801 and 809, as appropriate.
This guidance was prepared by Charles H. Kyper, Assistant to the
Director, Office of Device Evaluation, with input from the CDRH Office of
Compliance and Surveillance, Office of Health Affairs, and Office of
Training and Assistance.
It should be understood that the attached guidance is not a regulation
and that, as such, variations can occur and should be given appropriate
consideration. Based upon the preceding discussion, the need for and
usefulness of this guidance should be apparent. ODE reviewers are
encouraged to refer to this guidance during labeling reviews and to
provide it in correspondence and meetings with representatives of the
device industry when appropriate. Reviewers should also keep in mind
that this guidance is not intended to limit the consideration of factors
that may be specific to the device when reviewing its labeling.
Effective Date: This memorandum is effective immediately.
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Attachment
Attachment - Page 1
DEVICE LABELING GUIDANCE
Table of Contents
I. Definitions V. Warnings
Label VI. Precautions
Labeling VII. Special Patient Populations
Intended Uses VIII. Adverse Reactions
Directions for Use IX. Prescription Devices
II. Safety and Effectiveness X. Restricted Devices
Considerations XI. Patient Information Labeling
III. Indications for Use XII. Disclaimer of Liability
IV. Contraindications XIII. Misbranding
XIV. Prohibited Acts
I. Definitions
Label: A "label" is a display of written, printed or
graphic matter upon the immediate container of
any article.[section 201(k).]
Labeling: "Labeling" includes all labels and other
written, printed or graphic matter (1) upon
any article or any of its containers or
wrappers, or (2) accompanying such article.
[section 201(m).]
Intended Uses: The term "intended uses" refers to the
objective intent of the persons legally
responsible for the labeling of the device.
The intent is determined by their expressions
or may be shown by the circumstances
surrounding the distribution of the device.
This objective intent may, for example, be
shown by labeling claims, advertising matter,
or oral or written statements by such
representatives. It may be shown by the
offering or the using of the device, with the
knowledge of such persons or their
representatives, for a purpose for which it is
neither labeled nor advertised. (21 CFR
801.4)
Directions for Use: The term "Directions for use" provides
directions under which the practitioner or
layman (e.g., patient or unlicensed health
care provider), as appropriate, can use
the device safely and for the purposes for
which it is intended. Directions for use
also include indications for use and
appropriate contraindications, warnings,
precautions and adverse reaction
information. Directions for use
requirements applicable to prescription
and over-the-counter devices appear
throughout 21 CFR Part 801 and, in the
case of in vitro diagnostic products,
under 21 CFR 809.10.
II. Safety and Effectiveness Considerations (21 CFR 860.7)
In determining the safety and effectiveness of a device for
its intended use, the following factors are to be considered
and addressed in the device's labeling by the inclusion of
appropriate information:
The persons for whose use the device is represented or intended
- The conditions of use for the device, including conditions of
use prescribed, recommended or suggested in the labeling or
advertising of the device, and other intended conditions of use;
The probable benefit to health from the use of the device
weighed against any probable injury or illness from such use;
The reliability of the device; and,
Other relevant factors.
III. Indications for Use
General Statement of Indications for Use
The general statement of the "Indications for Use" identifies the
target population in a significant portion of which sufficient
valid scientific evidence has demonstrated that the device as
labeled will provide clinically significant results and at the same
time does not present an unreasonable risk of illness or injury
associated with the use of the device. As appropriate, the
labeling should state that the device (trade name) is "indicated"
or "intended for use"
(1) in the treatment, mitigation, prevention or diagnosis of a
recognized disease or condition or an important
manifestation of a disease or condition; and/or,
(2) in the relief or mitigation of symptoms associated with a
disease or condition; and/or,
(3) as an aid or adjunct to a mode of therapy or diagnosis.
Additional Information
When indicated or intended for use in selected subgroups of a
population with a disease, symptom, or syndrome, the labeling
should
(1) describe the available evidence and state the
limitations of usefulness of the device;
(2) identify specific tests needed for the selection or
monitoring of the patients;
(3) if available, provide information on the
approximate kind, degree and duration of improvement
to be anticipated; and
(4) if relevant, include information regarding the
recommended intervals between device use, the usual
duration of treatment, or any modifications of such.
When safety considerations are such that the device should be
reserved or restricted for use in certain situations
(e.g., cases not responsive to other devices, surgical
procedures or drugs), this information shall be stated.
When there are specific conditions that should be met before the
device is used on a long-term basis (e.g., demonstration of
responsiveness to the device in a short term trial), the
labeling should identify the conditions or, if the indications
for long-term use are different from those for short-term use,
the labeling shall identify the specific indications for each
use.
When there is a common belief that the device may be effective
for a certain use or there is a common use of the device for a
condition but the preponderance of evidence related to the use
or condition demonstrates that the device is ineffective, FDA
may require that the labeling state that there is a lack of
evidence that the device is effective for that use or condition.
IV. Contraindications
This section describes situations in which the device should not
be used because the risk of use clearly outweights any possible
benefit. Examples that may, but not always, contraindicate the
use of a device include:
Hypersensitivity to an ingredient of a permanently
implanted device;
Substantial risk of being harmed because of age, sex,
concomitant therapy, disease state or other condition; or,
Continued use in the face of an unacceptably hazardous
adverse reaction.
Known hazards and not theoretical possibilities are to be
listed, e.g., if hypersensitivity to an ingredient in the device
has not been demonstrated, it should not be listed as a
contraindication. The "Contraindications" section shall
immediately follow the "Indications for Use" section of the
labeling. If no contraindications are known, this section of
the labeling should state "None known."
V. Warnings
Describe serious adverse reactions and potential safety hazards,
limitations in use imposed by them, and steps that should be
taken if they occur.
Include an appropriate warning if there is reasonable evidence
of an association of a serious hazard with the use of the
device. A causal relationship need not have been proved.
A warning is appropriate when the device is commonly used for a
disease or condition for which there is a lack of valid
scientific evidence of effectiveness for that disease or
condition and such usage is associated with a serious risk or
hazard.
VI. Precautions
Include information regarding any special care to be exercised
by the practitioner and/or patient for the safe and effective
use of the device, for example:
- Indicate or emphasize any need for protective wear during
use.
- Identify any laboratory tests or other evaluations that
may be helpful in following the patient's response or in
identifying adverse reactions and, if appropriate,
specify the frequency of such tests or evaluations
before, during and after use of the device.
The "Precautions" section of the labeling includes precautionary
statements not appropriate for inclusion under other sections of
the labeling. Additional guidance regarding precautions will be
found in the "Special Patient Populations" section below.
VII. Special Patient Populations
Limitations on the usage of a device may be necessary for
various reasons including lack of long-term safety and
effectiveness data, lack of safety and effectiveness data for
specific patient populations (e.g., pregnant women), growth
processes still occurring in the body, and anatomical or
physiological limitations on the effectiveness of the device.
If the safety and effectiveness of the device for use in
specific patient populations have not been established on the
basis of valid scientific evidence, the "Indications for Use"
section shall specifically identify the persons for whose use
the device is indicated and the "Precautions" section shall
include the following statement:
"Safety and effectiveness in (e.g., pregnant women,
children under the age of ..., etc.) have not been
established."
If use of the device in a certain patient population is
associated with a specific hazard, the hazard shall be described
in the "Precautions" section or, if appropriate, the hazard
shall be stated in the "Warnings" or "Contraindications" section
and the "Precautions" section of the labeling shall refer to it,
e.g., "See 'Warnings' section for information on....."
VIII. Adverse Reactions
An adverse reaction is an undesirable effect, reasonably
associated with the use of the device, that may occur as part of
the effect of the device or may be unpredictable in its
occurrence.
This section includes all adverse reactions reasonably
associated with the use of the device, including those mentioned
in the "Contraindications", "Warnings" and "Precautions"
sections of the labeling. The listing of the adverse reactions
should be followed, if appropriate, by statements directing the
reader to other sections of the labeling for additional
information regarding these adverse reactions and any steps that
should be taken.
Adverse reactions should be listed in descending order according
to their clinical significance as determined by their severity
and frequency. Provide frequency data from adequately reported
clinical studies when the data is not well known to the device
user (practitioner and/or patient) and/or when needed in
deciding between the use of the device and an alternative
procedure or approach.
IX. Prescription Devices
A prescription device is, by definition under 21 CFR 801.109, a
device which, because of any potentiality for harmful effect, or
the method of its use, or the collateral measures necessary to
its use, is not safe except under the supervision of a
practitioner licensed by law to direct the use of the device,
and hence for which "adequate directions for use" (21 CFR 801.5)
cannot be prepared.
A prescription device, other than surgical instruments, is
misbranded if its label does not bear:
(1) the statement, "Caution: Federal law restricts this
device to sale by or on the order of a ",
the blank to be filled with the word "physician",
"dentist", or with the descriptive designation of any
other practitioners licensed by the law of the
State in which that person practices to use or order
the use of the device; and
(2) the method of application or use of the device.
A prescription device is misbranded if its labeling does not
bear:
(1) information for use including indications, effects,
routes, methods, frequency and duration of
administration, and any relevant hazards,
contraindications, side effects, and precautions under
which practitioners licensed by law to administer the
device can use the device safely and for the purpose
for which it is intended, including all purposes for
which it is advertised or represented, with the
exceptions that
(a) such information may be omitted from the
dispensing package if, but only if, the
directions, hazards, warnings, and other
information are commonly known to
practitioners licensed by law to use the
device and the FDA Commissioner is requested
to offer an opinion on a written proposal
stating reasonable grounds to omit such
information from the dispensing package;
(b) such information will not be required on so
called reminder-piece labeling which calls
attention to the name of the device but does
not include indications or other use
information; and
(2) the date of the issuance or the latest revision of the
labeling, except for labels and cartons, that bears
directions for the use of the device.
X. Restricted Device
Under the authority of section 515(d)(1)(B)(ii) of the Federal
Food, Drug, and Cosmetic Act (the act), the approval order for a
premarket approval application (PMA) may require, as a condition
of approval, that the sale, distribution and use of the device
be restricted but only to the extent permitted under section
520(e) of the act. Under section 520(e) of the act, FDA may
require that a device be restricted to sale, distribution and
use only upon the written or oral authorization of a
practitioner licensed by law to administer or use such devices
(i.e., prescription device) or upon such other conditions that
FDA may prescribe. Such a requirement must be based upon a
determination by FDA that, because of the device's potentiality
for harmful effect or the collateral measures necessary to its
use, there cannot otherwise be reasonable assurance of its
safety and effectiveness. If the device is restricted to use by
persons with specific training or experience in its use or by
persons for use in certain facilities, FDA must determine that
such a restriction is required for the safe and effective use of
the device. A person cannot be excluded from using a device,
however, solely because that person does not have the training
and experience to make him/her eligible for certification by a
certifying board recognized by the American Board of Medical
Specialties or has not been certified by such a Board.
When the sale, distribution and use of a device are restricted
in a PMA approval order or by regulation under section 520(e) of
the act, the label must include appropriate statements of the
restrictions imposed by FDA (e.g., restrictions on the sale,
distribution and use of the device or restrictions on the use of
the device to persons with specific training or experience in
its use or to persons for use in certain facilities). The
label shall bear the statement, "Caution: Federal law restricts
this device to sale, distribution and use by or on the order of
a ", the blank to be filled with the word
"physician", "dentist", or with the descriptive designation of
any other practitioners licensed by the law of the State in
which that person practices to use or order the use of the
device and, if applicable, followed by a descriptive phrase of
the training or experience required (e.g.,"trained and/or
experienced in ",the blank to be filled with, as
appropriate, "the use of this device" or specified therapeutic
or diagnostic procedures) and/or the facilities to which use is
restricted.
In accordance with the provisions of section 502(r) of the act,
advertisements and other descriptive printed material issued by
the manufacturer, packer or distributor with respect to a
restricted device must include the following among other
things:
(1) a true statement of the device's established name
(common or usual name unless there is an official name
designated by FDA or recognized in an official
compendium), printed prominently and in type at least
half as large as that for any trade or brand name for
the device; and
(2) a brief statement of the intended uses of the device
and relevant warnings, precautions, side effects, and
contraindications.
Except in extraordinary circumstances, FDA cannot require prior
approval of the content of any advertisement except in the case
of any printed matter which FDA determines to be labeling as
defined in section 201(m) of the act.
XI. Patient Information Labeling
Patient information labeling includes labeling directed to the
patient as well as family members and others who administer home
use devices to patients, e.g., care providers who oversee the
use of infant apnea monitors and nebulizers. In determining
whether patient information labeling is appropriate for a
prescription device, the following factors, among others, should
be considered:
- Should the patient be aware of alternative(s) to
the use of the device if a choice is available?
Are substantial risks or discomforts associated with
the use of the device?
Is the need for strict patient adherence to a specific
treatment regimen required?
Does substantial public or professional controversy
exist about the device and its related procedures?
Patient information labeling shall include the indications for
use and relevant contraindications, warnings, precautions and
adverse reactions using terminology well known and understood by
the average layman. Technical terms should be kept to a minimum
and should be defined when necessary. If applicable, directions
to ensure safe and effective use of the device by the patient
shall be included. Patient information labeling, if possible,
should not exceed the seventh grade reading comprehension level.
The following sources may provide useful information regarding
the information to be included as well as the terminology to be
used in patient information labeling:
1. U.S.P. Dispensing Information, Volume II, Advice for the
PatientR, Drug information in Lay Language
2. American Medical Association Drug Evaluations
XII. Disclaimer of Liability
Inclusion in the labeling of a disclaimer regarding the safety
and effectiveness of the device for its indicated or intended
use is to be avoided. Instead, labeling and promotional
material may include an objective and accurate representation
of the clinical experience with the device whereby the
practitioner and patient are made aware not to expect a
completely safe and effective outcome with the use of the
device in all cases.
Inclusion of disclaimers of liability for any medical expenses
or any direct or consequential damages resulting from or
caused by any defect, failure or malfunction of the device
will not inhibit FDA in imposing the notification and
otherremedies (repair, replacement or refund) provisions of
section 518 of the act. The provisions of section 518 may be
imposed whenever FDA determines that:
(1) The device presents an unreasonable risk of
substantial harm to the public health;
(2) There are reasonable grounds to believe that the
device was not properly designed and manufactured
within the state of the art; or
(3) There are reasonable grounds to believe that the
unreasonable risk was not caused by failure of a
person other than the manufacturer, importer,
distributor or retailer of the device to exercise
due care in the ... use of the device.
XIII. Misbranding
Pertinent provisions in the law and implementing regulations
related to medical device labeling and enforced by FDA appear
below. It is important that these provisions be kept in mind
both in the development of labeling by the device industry and
in the labeling review by CDRH.
Section 502 of the Federal Food,Drug, and Cosmetic Act (the
act) provides that a device shall be deemed misbranded if:
(1) Its labeling is false or misleading in any particular.
(2) The label does not bear the name and place of business
of the manufacturer, packer or distributor and an
accurate statement of the quantity of contents in
terms of weight, measure or numerical count.
(3) Any required word, statement or other information to
appear on the label or labeling is not prominently
placed thereon with such conspicuousness and in such
terms as to render it likely to be read and understood
by the ordinary individual under customary conditions
of purchase and use.
(4) Labeling does not bear adequate directions for use and
such adequate warnings against use in those
pathological conditions or by children where its use
may be dangerous to health, or against unsafe dosage
or methods or duration of administration or
application in such manner and form as are necessary
for the protection of users.
(5) In the case of a restricted device, its advertising is
false or misleading in any particular.
(6) In the case of a restricted device, advertisements and
other descriptive printed matter (other than labeling)
issued by the manufacturer, packer or distributor do
not include a brief statement of the intended uses of
the device and relevant warnings, precautions, side
effects and contraindications.
In determining whether a device is misbranded because the
labeling or advertising is misleading, section 201(n) of the
act permits the following to be taken into account among other
things:
(1) representations made or suggested by statement,
word, design, device, or any combination thereof; or
(2) the extent to which the labeling or advertising
fails to reveal facts material in the light of such
representations or material with respect to the
consequences which may result from the use of the
device to which the labeling or advertising
relates under the conditions of use prescribed in
the labeling or advertising or under such conditions
of use as are customary or usual.
Regulations applicable to medical devices provide that the
inclusion of any of the following representations in device
labeling constitutes misbranding of the device:
21 CFR 801.6 - False or misleading representation with respect
to another device or a drug
21 CFR 807.39 -Any representation that creates an impression
of official approval because of registration or
(e.g.,i clusion of FDA establishment
registration number)
21 CFR 807.97 - Any representation that creates an impression
of official approval because of complying with
the premarket notification regulations
(e.g., inclusion of premarket notification
reference number)
XIV. Prohibited Acts
Section 301(1) of the act prohibits the use in any labeling or
advertising for the device of any representation or suggestion
that approval of an application with respect to the device is
in effect under section 515 of the act (premarket approval) or
that the device complies with the provisions of section 515.
Submit Comments
You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))
If unable to submit comments online, please mail written comments to:
Dockets Management
Food and Drug Administration
5630 Fishers Lane, Rm 1061
Rockville, MD 20852
All written comments should be identified with this document's docket number: FDA-2020-D-0957.