Professional Documents
Culture Documents
Pt. 814
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814.1
General.
Postapproval requirements.
Reports.
Subparts FG [Reserved]
Subpart HHumanitarian Use Devices
814.100 Purpose and scope.
814.102 Designation of HUD status.
814.104 Original applications.
814.106 HDE amendments and resubmitted
HDEs.
814.108 Supplemental applications.
814.110 New indications for use.
814.112 Filing an HDE.
814.114 Timeframes for reviewing an HDE.
814.116 Procedures for review of an HDE.
814.118 Denial of approval or withdrawal of
approval of an HDE.
814.120 Temporary suspension of approval of
an HDE.
814.122 Confidentiality of data and information.
814.124 Institutional Review Board requirements.
814.126 Postapproval requirements and reports.
AUTHORITY: 21 U.S.C. 351, 352, 353, 360, 360c
360j, 371, 372, 373, 374, 375, 379, 379e, 381.
SOURCE: 51 FR 26364, July 22, 1986, unless
otherwise noted.
Subpart AGeneral
814.1 Scope.
(a) This part implements section 515
of the act by providing procedures for
the premarket approval of medical devices intended for human use.
(b) References in this part to regulatory sections of the Code of Federal
Regulations are to chapter I of title 21,
unless otherwise noted.
(c) This part applies to any class III
medical device, unless exempt under
section 520(g) of the act, that:
(1) Was not on the market (introduced or delivered for introduction into
commerce for commercial distribution)
before May 28, 1976, and is not substan-
Purpose.
Definitions.
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814.9
master file may contain detailed information on a specific manufacturing facility, process, methodology, or component used in the manufacture, processing, or packaging of a medical device.
(e) PMA means any premarket approval application for a class III medical device, including all information
submitted with or incorporated by reference therein. PMA includes a new
drug application for a device under section 520(1) of the act.
(f) PMA amendment means information an applicant submits to FDA to
modify a pending PMA or a pending
PMA supplement.
(g) PMA supplement means a supplemental application to an approved
PMA for approval of a change or modification in a class III medical device,
including all information submitted
with or incorporated by reference
therein.
(h) Person includes any individual,
partnership, corporation, association,
scientific or academic establishment,
Government agency, or organizational
unit thereof, or any other legal entity.
(i) Statement of material fact means a
representation that tends to show that
the safety or effectiveness of a device
is more probable than it would be in
the absence of such a representation. A
false affirmation or silence or an omission that would lead a reasonable person to draw a particular conclusion as
to the safety or effectiveness of a device also may be a false statement of
material fact, even if the statement
was not intended by the person making
it to be misleading or to have any probative effect.
(j) 30-day PMA supplement means a
supplemental application to an approved PMA in accordance with
814.39(e).
(k) Reasonable probability means that
it is more likely than not that an event
will occur.
(l) Serious, adverse health consequences
means any significant adverse experience, including those which may be either life-threatening or involve permanent or long term injuries, but excluding injuries that are nonlife-threatening and that are temporary and reasonably reversible.
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814.9
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814.20
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814.20
a list of all countries in which the device has been marketed and a list of all
countries in which the device has been
withdrawn from marketing for any reason related to the safety or effectiveness of the device. The description
shall include the history of the marketing of the device by the applicant
and, if known, the history of the marketing of the device by any other person.
(v) Summary of studies. An abstract of
any information or report described in
the PMA under paragraph (b)(8)(ii) of
this section and a summary of the results of technical data submitted under
paragraph (b)(6) of this section. Such
summary shall include a description of
the objective of the study, a description of the experimental design of the
study, a brief description of how the
data were collected and analyzed, and a
brief description of the results, whether positive, negative, or inconclusive.
This section shall include the following:
(A) A summary of the nonclinical
laboratory studies submitted in the application;
(B) A summary of the clinical investigations involving human subjects
submitted in the application including
a discussion of subject selection and
exclusion criteria, study population,
study period, safety and effectiveness
data, adverse reactions and complications, patient discontinuation, patient
complaints, device failures and replacements, results of statistical analyses of
the clinical investigations, contraindications and precautions for use of
the device, and other information from
the clinical investigations as appropriate (any investigation conducted
under an IDE shall be identified as
such).
(vi) Conclusions drawn from the studies. A discussion demonstrating that
the data and information in the application constitute valid scientific evidence within the meaning of 860.7 and
provide reasonable assurance that the
device is safe and effective for its intended use. A concluding discussion
shall present benefit and risk considerations related to the device including a
discussion of any adverse effects of the
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814.20
device on health and any proposed additional studies or surveillance the applicant intends to conduct following
approval of the PMA.
(4) A complete description of:
(i) The device, including pictorial
representations;
(ii) Each of the functional components or ingredients of the device if the
device consists of more than one physical component or ingredient;
(iii) The properties of the device relevant to the diagnosis, treatment, prevention, cure, or mitigation of a disease or condition;
(iv) The principles of operation of the
device; and
(v) The methods used in, and the facilities and controls used for, the manufacture, processing, packing, storage,
and, where appropriate, installation of
the device, in sufficient detail so that a
person generally familiar with current
good manufacturing practice can make
a knowledgeable judgment about the
quality control used in the manufacture of the device.
(5) Reference to any performance
standard under section 514 of the act or
under section 534 of Subchapter C
Electronic Product Radiation Control
of the Federal Food, Drug, and Cosmetic Act (formerly the Radiation
Control for Health and Safety Act of
1968) in effect or proposed at the time
of the submission and to any voluntary
standard that is relevant to any aspect
of the safety or effectiveness of the device and that is known to or that
should reasonably be known to the applicant. The applicant shall
(i) Provide adequate information to
demonstrate how the device meets, or
justify any deviation from, any performance standard established under
section 514 of the act or under section
534 of Subchapter CElectronic Product Radiation Control of the Federal
Food, Drug, and Cosmetic Act (formerly the Radiation Control for Health
and Safety Act of 1968), and
(ii) Explain any deviation from a voluntary standard.
(6) The following technical sections
which shall contain data and information in sufficient detail to permit FDA
to determine whether to approve or
deny approval of the application:
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814.20
or part 813 concerning sponsors of clinical investigations and clinical investigators, or if the study was not conducted in compliance with those regulations, a brief statement of the reason
for the noncompliance.
(7) For a PMA supported solely by
data from one investigation, a justification showing that data and other
information from a single investigator
are sufficient to demonstrate the safety and effectiveness of the device and
to ensure reproducibility of test results.
(8)(i) A bibliography of all published
reports not submitted under paragraph
(b)(6) of this section, whether adverse
or supportive, known to or that should
reasonably be known to the applicant
and that concern the safety or effectiveness of the device.
(ii) An identification, discussion, and
analysis of any other data, information, or report relevant to an evaluation of the safety and effectiveness of
the device known to or that should reasonably be known to the applicant
from any source, foreign or domestic,
including information derived from investigations other than those proposed
in the application and from commercial marketing experience.
(iii) Copies of such published reports
or unpublished information in the possession of or reasonably obtainable by
the applicant if an FDA advisory committee or FDA requests.
(9) One or more samples of the device
and its components, if requested by
FDA. If it is impractical to submit a
requested sample of the device, the applicant shall name the location at
which FDA may examine and test one
or more devices.
(10) Copies of all proposed labeling
for the device. Such labeling may include, e.g., instructions for installation
and any information, literature, or advertising that constitutes labeling
under section 201(m) of the act.
(11) An environmental assessment
under 25.20(n) prepared in the applicable format in 25.40, unless the action
qualifies for exclusion under 25.30 or
25.34. If the applicant believes that
the action qualifies for exclusion, the
PMA shall under 25.15(a) and (d) provide information that establishes to
FDAs satisfaction that the action re-
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814.37
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814.39
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814.39
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814.40
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814.44
proval will be conditioned upon the applicant incorporating the specified labeling changes exactly as directed and
upon the applicant submitting to FDA
a copy of the final printed labeling before marketing. FDA will also give the
public notice of the order, including
notice of and opportunity for any interested persons to request review
under section 515(d)(3) of the act. The
notice of approval will be placed on
FDAs home page on the Internet
(http://www.fda.gov), and it will state
that a detailed summary of information respecting the safety and effectiveness of the device, which was the
basis for the order approving the PMA,
including information about any adverse effects of the device on health, is
available on the Internet and has been
placed on public display, and that copies are available upon request. FDA
will publish in the FEDERAL REGISTER
after each quarter a list of the approvals announced in that quarter. When a
notice of approval is published, data
and information in the PMA file will be
available for public disclosure in accordance with 814.9.
(2) A request for copies of the current
PMA approvals and denials document
and for copies of summaries of safety
and effectiveness shall be sent in writing to the Division of Dockets Management (HFA305), Food and Drug Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852.
(e) FDA will send the applicant an
approvable letter if the application
substantially meets the requirements
of this part and the agency believes it
can approve the application if specific
additional information is submitted or
specific conditions are agreed to by the
applicant.
(1) The approvable letter will describe the information FDA requires to
be provided by the applicant or the
conditions the applicant is required to
meet to obtain approval. For example,
FDA may require, as a condition to approval:
(i) The submission of certain information identified in the approvable letter, e.g., final labeling;
(ii) An FDA inspection that finds the
manufacturing facilities, methods, and
controls in compliance with part 820
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814.45
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814.46
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814.47
General.
Postapproval requirements.
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814.84
814.84
Reports.
Subparts FG [Reserved]
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814.100
814.102
814.100
(a) This subpart H implements section 520(m) of the act. The purpose of
section 520(m) is, to the extent consistent with the protection of the public health and safety and with ethical
standards, to encourage the discovery
and use of devices intended to benefit
patients in the treatment or diagnosis
of diseases or conditions that affect or
are manifested in fewer than 4,000 individuals in the United States per year.
This subpart provides procedures for
obtaining:
(1) HUD designation of a medical device; and
(2) Marketing approval for the HUD
notwithstanding the absence of reasonable assurance of effectiveness that
would otherwise be required under sections 514 and 515 of the act.
(b) Although a HUD may also have
uses that differ from the humanitarian
use, applicants seeking approval of any
non-HUD use shall submit a PMA as required under 814.20, or a premarket
notification as required under part 807
of this chapter.
(c) Obtaining marketing approval for
a HUD involves two steps:
(1) Obtaining designation of the device as a HUD from FDAs Office of Orphan Products Development, and
(2) Submitting an HDE to the Office
of Device Evaluation (ODE), Center for
Devices
and
Radiological
Health
(CDRH), the Center for Biologics Evaluation and Research (CBER), or the
Center for Drug Evaluation and Research (CDER), as applicable.
(d) A person granted an exemption
under section 520(m) of the act shall
submit periodic reports as described in
814.126(b).
(e) FDA may suspend or withdraw approval of an HDE after providing notice
and an opportunity for an informal
hearing.
[61 FR 33244, June 26, 1996, as amended at 63
FR 59220, Nov. 3, 1998; 73 FR 49942, Aug. 25,
2008]
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814.104
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814.106
[specify disease or condition]. The effectiveness of this device for this use
has not been demonstrated; and
(5) The amount to be charged for the
device and, if the amount is more than
$250, a report by an independent certified public accountant, made in accordance with the Statement on Standards for Attestation established by the
American Institute of Certified Public
Accountants, or in lieu of such a report, an attestation by a responsible
individual
of
the
organization,
verifying that the amount charged does
not exceed the costs of the devices research, development, fabrication, and
distribution. If the amount charged is
$250 or less, the requirement for a report by an independent certified public
accountant or an attestation by a responsible individual of the organization is waived.
(c) Omission of information. If the applicant believes that certain information required under paragraph (b) of
this section is not applicable to the device that is the subject of the HDE, and
omits any such information from its
HDE, the applicant shall submit a
statement that identifies and justifies
the omission. The statement shall be
submitted as a separate section in the
HDE and identified in the table of contents. If the justification for the omission is not accepted by the agency,
FDA will so notify the applicant.
(d) Address for submissions and correspondence. Copies of all original HDEs
amendments and supplements, as well
as any correspondence relating to an
HDE, must be sent or delivered to the
following:
(1) For devices regulated by the Center for Devices and Radiological
Health, send to Document Mail Center,
10903 New Hampshire Ave., Bldg. 66, rm.
G609, Silver Spring, MD 209930002.
(2) For devices regulated by the Center for Biologics Evaluation and Research, send this information to the
Document Control Center (HFM99),
Center for Biologics Evaluation and
Research, Food and Drug Administration, 1401 Rockville Pike, suite 200N,
Rockville, MD 208521448.
(3) For devices regulated by the Center for Drug Evaluation and Research,
send this information to the Central
Document Control Room, Center for
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814.116
initiative, and shall do so upon the request of an applicant, unless FDA determines that the application substantially duplicates information previously reviewed by a panel. If the HDE
is referred to a panel, the agency shall
follow the procedures set forth under
814.44, with the exception that FDA
will complete its review of the HDE
and the advisory committee report and
recommendations within 75 days from
receipt of an HDE that is accepted for
filing under 814.112 or the date of filing as determined under 814.106,
whichever is later. Within the later of
these two timeframes, FDA will issue
an approval order under paragraph (b)
of this section, an approvable letter
under paragraph (c) of this section, a
not approvable letter under paragraph
(d) of this section, or an order denying
approval of the application under
814.118(a).
(b) Approval order. FDA will issue to
the applicant an order approving an
HDE if none of the reasons in 814.118
for denying approval of the application
applies. FDA will approve an application on the basis of draft final labeling
if the only deficiencies in the application concern editorial or similar minor
deficiencies in the draft final labeling.
Such approval will be conditioned upon
the applicant incorporating the specified labeling changes exactly as directed and upon the applicant submitting to FDA a copy of the final printed
labeling before marketing. The notice
of approval of an HDE will be published
in the FEDERAL REGISTER in accordance with the rules and policies applicable to PMAs submitted under
814.20. Following the issuance of an
approval order, data and information
in the HDE file will be available for
public disclosure in accordance with
814.9(b) through (h), as applicable.
(c) Approvable letter. FDA will send
the applicant an approvable letter if
the application substantially meets the
requirements of this subpart and the
agency believes it can approve the application if specific additional information is submitted or specific conditions
are agreed to by the applicant. The approvable letter will describe the information FDA requires to be provided by
the applicant or the conditions the applicant is required to meet to obtain
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814.118
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814.126
814.126 Postapproval
requirements
and reports.
(a) An HDE approved under this subpart H shall be subject to the postapproval requirements and reports set
forth under subpart E of this part, as
applicable, with the exception of
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Pt. 820
814.82(a)(7). In addition, medical device reports submitted to FDA in compliance with the requirements of part
803 of this chapter shall also be submitted to the IRB of record.
(b) In addition to the reports identified in paragraph (a) of this section,
the holder of an approved HDE shall
prepare and submit the following complete, accurate, and timely reports:
(1) Periodic reports. An HDE applicant
is required to submit reports in accordance with the approval order. Unless
FDA specifies otherwise, any periodic
report shall include:
(i) An update of the information required under 814.102(a) in a separately
bound volume;
(ii) An update of the information required under 814.104(b)(2), (b)(3), and
(b)(5);
(iii) The number of devices that have
been shipped or sold since initial marketing approval under this subpart H
and, if the number shipped or sold exceeds 4,000, an explanation and estimate of the number of devices used per
patient. If a single device is used on
multiple patients, the applicant shall
submit an estimate of the number of
patients treated or diagnosed using the
device together with an explanation of
the basis for the estimate;
(iv) Information describing the applicants clinical experience with the device since the HDE was initially approved. This information shall include
safety information that is known or
reasonably should be known to the applicant, medical device reports made
under part 803 of this chapter, any data
generated from the postmarketing
studies, and information (whether published or unpublished) that is known or
reasonably expected to be known by
the applicant that may affect an evaluation of the safety of the device or
that may affect the statement of contraindications, warnings, precautions,
and adverse reactions in the devices
labeling; and
(v) A summary of any changes made
to the device in accordance with supplements submitted under 814.108. If
information provided in the periodic
reports, or any other information in
the possession of FDA, gives the agency reason to believe that a device
raises public health concerns or that
Scope.
Definitions.
Quality system.
Management responsibility.
Quality audit.
Personnel.
Design controls.
Document controls.
Purchasing controls.
Identification.
Traceability.
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