Medical Devices
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Assessing the Safety and Effectiveness of Home-Use In Vitro Diagnostic Devices (IVDs): Draft Points to Consider Regarding Labeling and Premarket Submissions (Text Only)
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.
Assessing the Safety and Effectiveness of Home-Use
In Vitro Diagnostic Devices (IVDs):
Draft Points to Consider
Regarding Labeling and Premarket Submissions
Center for Devices and Radiological Health
October 1988
I. Purpose
The purpose of this document is to assist prospective
manufacturers, producers, and marketers (hereinafter called
manufacturers) of home-use in vitro diagnostic devices
(IVDs) in complying with existing labeling regulations,
e.g., 21 CFR 801.5, 809.3(a) and 809.10, and premarket
clearance requirements, e.g., Sections 510(k) and 515 of the
Federal Food, Drug, and Cosmetic Act (the Act), and
regulations including 21 CFR Parts 807 and 814. This
document addresses home-use testing kits and home-use
mail-in specimen collection kits.
II. Background
In vitro diagnostic devices (IVDs) as defined in 21 CFR
809.3(a) are those reagents, instruments, and systems
intended for use in the diagnosis of disease or other
conditions, including a determination of the state of
health, in order to cure, mitigate, treat, or prevent
disease or its sequelae. These products are intended for
use in the collection, preparation, and examination of
specimens taken from the human body.
Traditionally, IVDs have been used primarily by hospitals,
clinical laboratories and physicians' offices. In recent
years, however, there has been increasing interest in
home-use IVDs, where no physician is involved to interpret
the test results.
Because of this growing interest, FDA's Center for Devices
and Radiological Health (CDRH) anticipates receiving an
increasing number of premarket product submissions, i.e.,
premarket notifications or premarket approval applications,
for these devices. Consequently, CDRH believes that uniform
evaluation criteria for home-use IVDs are needed to better
ensure that these devices are regulated in a consistent
fashion and that consumers are provided with reliable,
useful, and adequately labeled products. To this end, in
the spring of 1985, CDRH solicited views from various
industry, consumer, and health professional organizations to
help identify the issues to be resolved by CDRH in
developing evaluation criteria for home-use IVDs. In
addition, on September 9, 1985, CDRH convened a public
meeting of the chairpersons, the consumer representatives,
and the industry representatives of the Immunology Devices
Panel, the Microbiology Devices Panel, the Hematology and
Pathology Devices Panel, and the Clinical Chemistry and
Clinical Toxicology Devices Panel. The purpose of this
meeting was to solicit the views of these individuals and
other interested persons regarding general issues of the
safety and effectiveness of home-use IVDs.
The present document reflects CDRH's views on key points to
be considered in establishing the safe and effective use of
home-use IVDs. These views are significantly based on the
input CDRH has received from the aforementioned outreach
activities.
III. Factors CDRH will Consider in Evaluating the Safety and
Effectiveness of Home-use IVDs
A. Performance Considerations
A key factor CDRH must consider in assessing the safety
and effectiveness of home-use IVDs is test performance.
Because the great majority of proposed home-use IVDs
are likely to be derived from professional-use IVDs, it
is expected that there will be a clear and established
relationship between the analyte to be tested using the
home-use IVD and a specific medical disorder or
condition. Because home-use IVDs function essentially
the same as professional-use IVDs, their performance
characteristics can be defined in terms of traditional
performance parameters such as sensitivity,
specificity, accuracy, and reproducibility of test
results. Nevertheless, the performance of the device in
the hands of skilled users may not reflect the device's
performance in the hands of lay users. Consequently,
manufacturers of home-use IVDs should focus their
attention on the following performance considerations:
1. For a given intended use, the ability of the
home-use IVD to detect and/or measure a particular
analyte of interest (analytical performance)
should be comparable to the performance of IVDs
intended for the same purpose that are used by
professionals in clinical settings;
2. Home-use IVDs should be designed with a view to
ensuring that the device's performance will not be
appreciably affected by anticipated variation in
user technique; and,
3. Home-use IVDs should include a simple method by
which the user can reasonably verify that the
product's performance meets its design
specifications at the time of use. Ideally, a
user quality control test should be provided or
"built into" each home-use IVD (see 21 CFR
809.10(a)(6).) Omission of such a test or other
reasonable means of verifying product performance
should be justified based on scientific merit.
B. Risk/Benefit Considerations
Home-use IVDs are different from clinical laboratory
devices in four important ways: (1) the person
performing the test or reviewing the results returned
from a clinical laboratory likely lacks the necessary
medical training to evaluate other related medical
information, such as, pertinent personal or family
medical history, other analyte levels, and the results
of a complete physical examination; (2) the person
performing the test may lack the technical training of
laboratory technologists who traditionally have
performed laboratory tests and may not interpret
directions carefully; (3) the person performing the
test may or may not carry out necessary follow-up
actions on the basis of test results; and (4) the
person collecting a sample of a body specimen and
mailing it to a clinical laboratory generally lacks the
technical training of persons who traditionally have
collected or supervised the collection of body
specimens, and supervised the transport of the
specimens to the test laboratory. Thus the person may
not ensure that the specimen that arrives at the
clinical laboratory is in the same condition as it was
when it was collected (e.g. ensuring that the analyte
to be measured does not degrade because of passage of a
long period of time from specimen collection until
analysis, or ensuring that a specimen is not exposed to
extremes of hot or cold temperatures or other
environmental hazards that may affect the test
results).
Hence, in evaluating home-use IVDs, CDRH must consider
probable health benefits to be gained in the use of
such devices compared to the probable risks associated
with their use. In this context, consideration of
benefit and risk is inherent in the evaluation of
safety and effectiveness.
When the use of an in-home IVD can be demonstrated to
be substantially equivalent, in terms of safety and
effectiveness, to a clinical laboratory device when
used by a health professional, and the device meets all
labeling and other regulatory and statutory
requirements, it will generally satisfy requirements
for market clearance. When unique issues of safety and
effectiveness arise and substantial equivalence cannot
be demonstrated, CDRH will nonetheless evaluate benefit
and risk factors in making determinations with respect
to the marketability of in-home IVDs. For purpose of
assessing these benefit and risk factors CDRH will
consider the following questions and encourage
applicants to provide relevant information in their
submissions.
Benefits
1. What is the clinical benefit of the test to the
patient or society (public health) in terms of
screening, diagnosing, or monitoring a particular
disease, condition, or risk factor?
2. What are the benefits to the patient or society of
having the test available for home-use as opposed
to having the test performed only by health care
professionals?
Risks
1. What is the impact on the user or to society of a
false-positive or false-negative test result e.g.,
in terms of user follow-up or adverse medical
conditions?
2. What are the risks to the user or society in terms
of delay in obtaining a professional examination
if a proposed home-use IVD that is intended for
use on symptomatic subjects gives a false or
equivocal result?
CDRH recognizes that for evaluation purposes, responses
to these questions can vary based on the type of
product being considered.
C. Labeling Considerations
Acceptability of home-use IVD labeling will depend upon
whether such labeling meets the criteria for "adequate
directions for use" as provided for in section
502(f)(1) of the Act and defined by 21 CFR 801.5, and
the requirements of Subpart C of 21 CFR Part 801. In
addition, home-use IVDs will be deemed to be in
compliance with the requirements for adequate
directions for use if they meet the requirements of 21
CFR 809.10-Labeling for In Vitro Diagnostic Products.
Inherent in the concept of "adequate directions for
use" is the need for the labeling of home-use IVDs to
be simple, concise, easy to understand, make liberal
use of illustrations and drawings, use bold print or
other methods to highlight warnings and precautions,
and provide color coding of reagent containers whenever
practicable.
Labeling for IVDs intended for home and professional
use are covered by 21 CFR 809.10. The following
elaborates on the application of the regulation to the
home-use situation and suggests means of accomplishing
compliance:
Section 809.10(a)
1. The intended use statement (section 809.10(a)(2))
should clearly indicate on the outside packaging
container the type of procedure that is offered,
i.e., screening, monitoring, or diagnostic, and
the specific disorder, condition, or risk factor
of interest for which the test is intended. In
addition, a statement also should be presented
indicating who should use the test and the
conditions for its use, followed by a
contraindication statements), if necessary.
2. The quantity, proportion, concentration, or
activity of each reactive ingredient included with
the test kit need only be presented as specified
by section 809.10(a)(3) when information is
necessary for proper lay use of the test.
Section 809.10(b)
The order and scope of the information specified by
this section should be as follows:
1. The intended use statement should reiterate the
information required under section 809 10(a).
2. Section 809.10(b)(3), summary and explanation of
the test, may be combined with section
809.10(b)(4), principles of the procedure. This
combination of sections should include a
discussion of both the medical benefits and
limitations of the test with respect to its
intended use in addition to providing a simple
explanation of how the test works. Presentation
of chemical reactions or formulas are not
necessary but may be referenced in the
bibliography (section 809.10(b)(13)).
3. A separate information section relating to
interpretation of test results, should be
presented and include information specified by
section 809.10(b)(10), limitations of the
procedure. This section should indicate the
significance of the test results in light of the
test's intended use and provide specific
information as to what appropriate follow-up
action should be taken by the user. Additionally,
this section should explain the meaning of
false-positive and false-negative test results and
cite possible sources and implications of false
results.
4. A separate information section should be presented
which identifies any foods, medications, or other
possible interfering substances that would affect
test results. Such information should specify what
substances should be avoided and for how long
prior to testing.
5. Information specified in sections
809.10(b)(5),(6),(7), and (8) may be combined into
a single information section, i.e., test
procedure. All information specified by these
individual sections should be presented in the
combined section, if applicable, in addition to
the following:
a. as previously stated, the quantity,
proportion, concentration, or activity of
each reactive ingredient included in the test
kit need not be presented unless this
information is necessary for proper use of
the test. However, such information should
be presented elsewhere in a premarket
submission for CDRH review.
b. discussion of specimen collection,
preparation, and analysis steps should be
enhanced by the use of pictures and
illustrations, preferably in color.
6. Information specified by section 809.10(b)(9),
test results, should be presented. This section
also should include trouble-shooting information
where applicable.
7. Information specified by sections 809.10(b)(11)
and (12) may be combined into a single information
section, i.e., test performance characteristics.
m is section should summarize the data
(separately) from both the laboratory evaluation
and the consumer field evaluation (see III
Premarket Evaluation Considerations) and should
include a concise discussion of the study
protocols used to evaluate the test's performance.
Also, discussion and/or presentation of data
relative to the test's accuracy should be
presented and include false-positive and
false-negative levels. Such information should be
presented for both the laboratory and the consumer
field evaluations.
8. Sections 809.10(b)(13), (14), and (15) should be
addressed in the same manner as other IVDs.
In addition, CDRH recommends that manufacturers provide
users with a toll-free telephone number or an address to
write to should questions occur concerning the use of the
device.
Finally, CDRH is concerned that consumers be aware of
significant changes in home-use IVD labeling; particularly
labeling accompanying high frequency use devices such as
home-use glucose test devices. CDRH advises manufacturers to
alert consumers of significant labeling changes by including
special inserts with device packaging which highlight key
labeling changes. Moreover, CDRH advises manufacturers that
labeling changes that significantly impact on a device's
safe and effective use may require premarket review and
clearance by CDRH before commercial distribution of devices
bearing such labeling.
D. Premarket Evaluation Considerations
Given the above considerations CDRH recommends that
prospective manufacturers of home-use IVDs conduct the
following performance studies and submit results to
CDRH for review in an appropriate premarket submission:
A. A laboratory evaluation of the analytical
performance of the device, e.g., analytical
sensitivity, analytical specificity, accuracy, and
reproducibility, should be done by performing
standard laboratory measurements using appropriate
reference tests. The purpose of this evaluation
is to establish the "true" performance
characteristics of the device as determined under
controlled laboratory conditions; and,
A consumer field evaluation of the device should
be conducted to determine the device's performance
when used by lay users, unassisted, following
instructions provided in the labeling.
CDRH places considerable importance on the outcome of
the consumer field evaluation (item B above) in
assessing the safety and effectiveness of home-use
IVDs. Consequently, the following additional
suggestions are offered with respect to the goals,
conduct, and analysis of such studies.
1. The primary goal of the consumer field evaluation
should be to establish comparable levels of test
performance for a particular home-use IVD when
comparison-tested by both intended users and
trained laboratory personnel. It is suggested
that split clinical samples be tested by both lay
users and trained laboratory personnel with both
groups using the home-use IVD. Such testing will
simultaneously validate the technical performance
characteristics of the device and the device's
labeling based on user experience.
2. In order to assess the ability of lay users to
properly perform and interpret test results, CDRH
recommends that manufacturers provide simple
questionnaires to study participants as part of
the consumer field evaluation to determine if lay
users can read and understand the labeling. For
example, a questionnaire could be used to
determine if the user understands the purpose of
the test, the conditions for its use, the test's
limitations, the meaning of the results and
appropriate follow-up
It is recommended that samples of such
questionnaires be included in a premarket
submission, as well as a tabulation of all study
participants' responses to each question.
3. Lay users selected for study should be
representative of target users for which a test is
intended. A representative study population may
require the selection of individuals of varied
background, education levels, and age groups.
Consequently, subjects should be selected for
testing based on carefully developed selection
criteria. The basis for establishing the
selection criteria should be submitted to CDRH
along with the study protocol and test results.
4. The number of subjects selected for testing should
be sufficient to substantiate that all targeted
lay user populations can perform and interpret the
test. It is highly recommended that the number of
subjects selected for study be based on a
statistically valid sampling of relevant lay users
and should take into account appropriate
demographic factors. Moreover, test results
should be analyzed using appropriate statistical
methods to demonstrate correlation between lay
users and trained technologists performing the
test.
5. Ideally, to avoid potential problems of bias
during data collection and evaluation of the
consumer field study, a double blind design should
be used. However, in studies where such a design
is impossible or impractical, a single blind
approach and other measures to reduce potential
bias may be acceptable. The manufacturer should
be careful to select the appropriate type of study
to ensure that the study will provide appropriate
information.
CDRH believes that both prospective manufacturers of
home-use IVDs and CDRH reviewers will be better able to
evaluate the safety and effectiveness of these devices when
supporting information based on the above considerations is
submitted to CDRH in an appropriate premarket submission.
Moreover, CDRH believes that as a result of these
considerations the general public health will be better
served by the availability of meaningful and reliable
home-use IVDs.
10/5/88
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