[Code of Federal Regulations]
[Title 21, Volume 8]
[Revised as of April 1, 2006]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR812]
[Page 98-116]
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN
SERVICES (CONTINUED)
PART 812_INVESTIGATIONAL DEVICE EXEMPTIONS
Subpart A_General Provisions
Sec.
812.1 Scope.
812.2 Applicability.
812.3 Definitions.
812.5 Labeling of investigational devices.
812.7 Prohibition of promotion and other practices.
812.10 Waivers.
812.18 Import and export requirements.
812.19 Address for IDE correspondence.
Subpart B_Application and Administrative Action
812.20 Application.
812.25 Investigational plan.
812.27 Report of prior investigations.
812.30 FDA action on applications.
812.35 Supplemental applications.
812.36 Treatment use of an investigational device.
812.38 Confidentiality of data and information.
Subpart C_Responsibilities of Sponsors
812.40 General responsibilities of sponsors.
812.42 FDA and IRB approval.
812.43 Selecting investigators and monitors.
812.45 Informing investigators.
812.46 Monitoring investigations.
812.47 Emergency research under Sec. 50.24 of this chapter.
Subpart D_IRB Review and Approval
812.60 IRB composition, duties, and functions.
812.62 IRB approval.
812.64 IRB's continuing review.
812.65 [Reserved]
812.66 Significant risk device determinations.
Subpart E_Responsibilities of Investigators
812.100 General responsibilities of investigators.
812.110 Specific responsibilities of investigators.
812.119 Disqualification of a clinical investigator.
Subpart F [Reserved]
Subpart G_Records and Reports
812.140 Records.
812.145 Inspections.
812.150 Reports.
Authority: 21 U.S.C. 331, 351, 352, 353, 355, 360, 360c-360f, 360h-
360j, 371, 372, 374, 379e, 381, 382, 383; 42 U.S.C. 216, 241, 262, 263b-
263n.
Source: 45 FR 3751, Jan. 18, 1980, unless otherwise noted.
Subpart A_General Provisions
Sec. 812.1 Scope.
(a) The purpose of this part is to encourage, to the extent
consistent with the protection of public health and safety and with
ethical standards, the discovery and development of useful devices
intended for human use, and to that end to maintain optimum freedom for
scientific investigators in their pursuit of this purpose. This part
provides procedures for the conduct of clinical investigations of
devices. An approved investigational device exemption (IDE) permits a
device that otherwise would be required to comply with a performance
standard or to have premarket approval to be shipped lawfully for the
purpose of conducting investigations of that device. An IDE approved
under Sec. 812.30 or considered approved under Sec. 812.2(b) exempts a
device from the requirements of the following sections of the Federal
Food, Drug, and Cosmetic Act (the act) and regulations issued
thereunder: Misbranding under section 502 of the act, registration,
listing, and premarket notification under section 510, performance
standards under section 514, premarket approval under section 515, a
banned device regulation under section 516, records and reports
under section 519, restricted device requirements under section 520(e),
good manufacturing practice requirements under section 520(f) except for
the requirements found in Sec. 820.30, if applicable (unless the
sponsor states an intention to comply with these requirements under
Sec. 812.20(b)(3) or Sec. 812.140(b)(4)(v)) and color additive
requirements under section 721.
(b) References in this part to regulatory sections of the Code of
Federal Regulations are to chapter I of title 21, unless otherwise
noted.
[45 FR 3751, Jan. 18, 1980, as amended at 59 FR 14366, Mar. 28, 1994; 61
FR 52654, Oct. 7, 1996]
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Sec. 812.2 Applicability.
(a) General. This part applies to all clinical investigations of
devices to determine safety and effectiveness, except as provided in
paragraph (c) of this section.
(b) Abbreviated requirements. The following categories of
investigations are considered to have approved applications for IDE's,
unless FDA has notified a sponsor under Sec. 812.20(a) that approval of
an application is required:
(1) An investigation of a device other than a significant risk
device, if the device is not a banned device and the sponsor:
(i) Labels the device in accordance with Sec. 812.5;
(ii) Obtains IRB approval of the investigation after presenting the
reviewing IRB with a brief explanation of why the device is not a
significant risk device, and maintains such approval;
(iii) Ensures that each investigator participating in an
investigation of the device obtains from each subject under the
investigator's care, informed consent under part 50 and documents it,
unless documentation is waived by an IRB under Sec. 56.109(c).
(iv) Complies with the requirements of Sec. 812.46 with respect to
monitoring investigations;
(v) Maintains the records required under Sec. 812.140(b) (4) and
(5) and makes the reports required under Sec. 812.150(b) (1) through
(3) and (5) through (10);
(vi) Ensures that participating investigators maintain the records
required by Sec. 812.140(a)(3)(i) and make the reports required under
Sec. 812.150(a) (1), (2), (5), and (7); and
(vii) Complies with the prohibitions in Sec. 812.7 against
promotion and other practices.
(2) An investigation of a device other than one subject to paragraph
(e) of this section, if the investigation was begun on or before July
16, 1980, and to be completed, and is completed, on or before January
19, 1981.
(c) Exempted investigations. This part, with the exception of Sec.
812.119, does not apply to investigations of the following categories of
devices:
(1) A device, other than a transitional device, in commercial
distribution immediately before May 28, 1976, when used or investigated
in accordance with the indications in labeling in effect at that time.
(2) A device, other than a transitional device, introduced into
commercial distribution on or after May 28, 1976, that FDA has
determined to be substantially equivalent to a device in commercial
distribution immediately before May 28, 1976, and that is used or
investigated in accordance with the indications in the labeling FDA
reviewed under subpart E of part 807 in determining substantial
equivalence.
(3) A diagnostic device, if the sponsor complies with applicable
requirements in Sec. 809.10(c) and if the testing:
(i) Is noninvasive,
(ii) Does not require an invasive sampling procedure that presents
significant risk,
(iii) Does not by design or intention introduce energy into a
subject, and
(iv) Is not used as a diagnostic procedure without confirmation of
the diagnosis by another, medically established diagnostic product or
procedure.
(4) A device undergoing consumer preference testing, testing of a
modification, or testing of a combination of two or more devices in
commercial distribution, if the testing is not for the purpose of
determining safety or effectiveness and does not put subjects at risk.
(5) A device intended solely for veterinary use.
(6) A device shipped solely for research on or with laboratory
animals and labeled in accordance with Sec. 812.5(c).
(7) A custom device as defined in Sec. 812.3(b), unless the device
is being used to determine safety or effectiveness for commercial
distribution.
(d) Limit on certain exemptions. In the case of class II or class
III device described in paragraph (c)(1) or (2) of this section, this
part applies beginning on the date stipulated in an FDA regulation or
order that calls for the submission of premarket approval applications
for an unapproved class III device, or establishes a performance
standard for a class II device.
(e) Investigations subject to IND's. A sponsor that, on July 16,
1980, has an effective investigational new drug application (IND) for an
investigation of a device shall continue to comply with the requirements
of part 312 until 90 days after that date. To continue the investigation
after that date, a sponsor shall comply with paragraph (b)(1) of this
section, if the device is not a significant risk device, or shall have
obtained FDA approval under Sec. 812.30 of an IDE application for the
investigation of the device.
[45 FR 3751, Jan. 18, 1980, as amended at 46 FR 8956, Jan. 27, 1981; 46
FR 14340, Feb. 27, 1981; 53 FR 11252, Apr. 6, 1988; 62 FR 4165, Jan, 29,
1997; 62 FR 12096, Mar. 14, 1997]
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Sec. 812.3 Definitions.
(a) Act means the Federal Food, Drug, and Cosmetic Act (sections
201-901, 52 Stat. 1040 et seq., as amended (21 U.S.C. 301-392)).
(b) Custom device means a device that:
(1) Necessarily deviates from devices generally available or from an
applicable performance standard or premarket approval requirement in
order to comply with the order of an individual physician or dentist;
(2) Is not generally available to, or generally used by, other
physicians or dentists;
(3) Is not generally available in finished form for purchase or for
dispensing upon prescription;
(4) Is not offered for commercial distribution through labeling or
advertising; and
(5) Is intended for use by an individual patient named in the order
of a physician or dentist, and is to be made in a specific form for that
patient, or is intended to meet the special needs of the physician or
dentist in the course of professional practice.
(c) FDA means the Food and Drug Administration.
(d) Implant means a device that is placed into a surgically or
naturally formed cavity of the human body if it is intended to remain
there for a period of 30 days or more. FDA may, in order to protect
public health, determine that devices placed in subjects for shorter
periods are also ``implants'' for purposes of this part.
(e) Institution means a person, other than an individual, who
engages in the conduct of research on subjects or in the delivery of
medical services to individuals as a primary activity or as an adjunct
to providing residential or custodial care to humans. The term includes,
for example, a hospital, retirement home, confinement facility, academic
establishment, and device manufacturer. The term has the same meaning as
``facility'' in section 520(g) of the act.
(f) Institutional review board (IRB) means any board, committee, or
other group formally designated by an institution to review biomedical
research involving subjects and established, operated, and functioning
in conformance with part 56. The term has the same meaning as
``institutional review committee'' in section 520(g) of the act.
(g) Investigational device means a device, including a transitional
device, that is the object of an investigation.
(h) Investigation means a clinical investigation or research
involving one or more subjects to determine the safety or effectiveness
of a device.
(i) Investigator means an individual who actually conducts a
clinical investigation, i.e., under whose immediate direction the test
article is administered or dispensed to, or used involving, a subject,
or, in the event of an investigation conducted by a team of individuals,
is the responsible leader of that team.
(j) Monitor, when used as a noun, means an individual designated by
a sponsor or contract research organization to oversee the progress of
an investigation. The monitor may be an employee of a sponsor or a
consultant to the sponsor, or an employee of or
consultant to a contract research organization. Monitor, when used as a
verb, means to oversee an investigation.
(k) Noninvasive, when applied to a diagnostic device or procedure,
means one that does not by design or intention: (1) Penetrate or pierce
the skin or mucous membranes of the body, the ocular cavity, or the
urethra, or (2) enter the ear beyond the external auditory canal, the
nose beyond the nares, the mouth beyond the pharynx, the anal canal
beyond the rectum, or the vagina beyond the cervical os. For purposes of
this part, blood sampling that involves simple venipuncture is
considered noninvasive, and the use of surplus samples of body fluids or
tissues that are left over from samples taken for noninvestigational
purposes is also considered noninvasive.
(l) Person includes any individual, partnership, corporation,
association, scientific or academic establishment, Government agency or
organizational unit of a Government agency, and any other legal entity.
(m) Significant risk device means an investigational device that:
(1) Is intended as an implant and presents a potential for serious
risk to the health, safety, or welfare of a subject;
(2) Is purported or represented to be for a use in supporting or
sustaining human life and presents a potential for serious risk to the
health, safety, or welfare of a subject;
(3) Is for a use of substantial importance in diagnosing, curing,
mitigating, or treating disease, or otherwise preventing impairment of
human health and presents a potential for serious risk to the health,
safety, or welfare of a subject; or
(4) Otherwise presents a potential for serious risk to the health,
safety, or welfare of a subject.
(n) Sponsor means a person who initiates, but who does not actually
conduct, the investigation, that is, the investigational device is
administered, dispensed, or used under the immediate direction of
another individual. A person other than an individual that uses one or
more of its own employees to conduct an investigation that it has
initiated is a sponsor, not a sponsor-investigator, and the employees
are investigators.
(o) Sponsor-investigator means an individual who both initiates and
actually conducts, alone or with others, an investigation, that is,
under whose immediate direction the investigational device is
administered, dispensed, or used. The term does not include any person
other than an individual. The obligations of a sponsor-investigator
under this part include those of an investigator and those of a sponsor.
(p) Subject means a human who participates in an investigation,
either as an individual on whom or on whose specimen an investigational
device is used or as a control. A subject may be in normal health or may
have a medical condition or disease.
(q) Termination means a discontinuance, by sponsor or by withdrawal
of IRB or FDA approval, of an investigation before completion.
(r) Transitional device means a device subject to section 520(l) of
the act, that is, a device that FDA considered to be a new drug or an
antibiotic drug before May 28, 1976.
(s) Unanticipated adverse device effect means any serious adverse
effect on health or safety or any life-threatening problem or death
caused by, or associated with, a device, if that effect, problem, or
death was not previously identified in nature, severity, or degree of
incidence in the investigational plan or application (including a
supplementary plan or application), or any other unanticipated serious
problem associated with a device that relates to the rights, safety, or
welfare of subjects.
[45 FR 3751, Jan. 18, 1980, as amended at 46 FR 8956, Jan. 27, 1981; 48
FR 15622, Apr. 12, 1983]
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Sec. 812.5 Labeling of investigational devices.
(a) Contents. An investigational device or its immediate package
shall bear a label with the following information: the name and place of
business of the manufacturer, packer, or distributor (in accordance with
Sec. 801.1), the quantity of contents, if appropriate, and the
following statement: ``CAUTION--Investigational device. Limited by
Federal (or United States) law to investigational use.'' The label
or other labeling shall describe all relevant contraindications,
hazards, adverse effects, interfering substances or devices, warnings,
and precautions.
(b) Prohibitions. The labeling of an investigational device shall
not bear any statement that is false or misleading in any particular and
shall not represent that the device is safe or effective for the
purposes for which it is being investigated.
(c) Animal research. An investigational device shipped solely for
research on or with laboratory animals shall bear on its label the
following statement: ``CAUTION--Device for investigational use in
laboratory animals or other tests that do not involve human subjects.''
[45 FR 3751, Jan. 18, 1980, as amended at 45 FR 58842, Sept. 5, 1980]
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Sec. 812.7 Prohibition of promotion and other practices.
A sponsor, investigator, or any person acting for or on behalf of a
sponsor or investigator shall not:
(a) Promote or test market an investigational device, until after
FDA has approved the device for commercial distribution.
(b) Commercialize an investigational device by charging the subjects
or investigators for a device a price larger than that necessary to
recover costs of manufacture, research, development, and handling.
(c) Unduly prolong an investigation. If data developed by the
investigation indicate in the case of a class III device that premarket
approval cannot be justified or in the case of a class II device that it
will not comply with an applicable performance standard or an amendment
to that standard, the sponsor shall promptly terminate the
investigation.
(d) Represent that an investigational device is safe or effective
for the purposes for which it is being investigated.
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Sec. 812.10 Waivers.
(a) Request. A sponsor may request FDA to waive any requirement of
this part. A waiver request, with supporting documentation, may be
submitted separately or as part of an application to the address in
Sec. 812.19.
(b) FDA action. FDA may by letter grant a waiver of any requirement
that FDA finds is not required by the act and is unnecessary to protect
the rights, safety, or welfare of human subjects.
(c) Effect of request. Any requirement shall continue to apply
unless and until FDA waives it.
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Sec. 812.18 Import and export requirements.
(a) Imports. In addition to complying with other requirements of
this part, a person who imports or offers for importation an
investigational device subject to this part shall be the agent of the
foreign exporter with respect to investigations of the device and shall
act as the sponsor of the clinical investigation, or ensure that another
person acts as the agent of the foreign exporter and the sponsor of the
investigation.
(b) Exports. A person exporting an investigational device subject to
this part shall obtain FDA's prior approval, as required by section
801(e) of the act or comply with section 802 of the act.
[45 FR 3751, Jan. 18, 1980, as amended at 62 FR 26229, May 13, 1997]
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Sec. 812.19 Address for IDE correspondence.
If you are sending an application, supplemental application, report,
request for waiver, request for import or export approval, or other
correspondence relating to matters covered by this part, you must
address it to the Center for Devices and Radiological Health, Document
Mail Center (HFZ-401), Food and Drug Administration, 9200 Corporate
Blvd., Rockville, MD 20850. You must state on the outside wrapper of
each submission what the submission is, for example, an ``IDE
application,'' a ``supplemental IDE application,'' or a ``correspondence
concerning an IDE (or an IDE application).''
[65 FR 17137, Mar. 31, 2000]
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Subpart B_Application and Administrative Action
Sec. 812.20 Application.
(a) Submission. (1) A sponsor shall submit an application to FDA if
the sponsor intends to use a significant risk device in an
investigation, intends to conduct an investigation that involves an
exception from informed consent under Sec. 50.24 of this chapter, or if
FDA notifies the sponsor that an application is required for an
investigation.
(2) A sponsor shall not begin an investigation for which FDA's
approval of an application is required until FDA has approved the
application.
(3) A sponsor shall submit three copies of a signed ``Application
for an Investigational Device Exemption'' (IDE application), together
with accompanying materials, by registered mail or by hand to the
address in Sec. 812.19. Subsequent correspondence concerning an
application or a supplemental application shall be submitted by
registered mail or by hand.
(4)(i) A sponsor shall submit a separate IDE for any clinical
investigation involving an exception from informed consent under Sec.
50.24 of this chapter. Such a clinical investigation is not permitted to
proceed without the prior written authorization of FDA. FDA shall
provide a written determination 30 days after FDA receives the IDE or
earlier.
(ii) If the investigation involves an exception from informed
consent under Sec. 50.24 of this chapter, the sponsor shall prominently
identify on the cover sheet that the investigation is subject to the
requirements in Sec. 50.24 of this chapter.
(b) Contents. An IDE application shall include, in the following
order:
(1) The name and address of the sponsor.
(2) A complete report of prior investigations of the device and an
accurate summary of those sections of the investigational plan described
in Sec. 812.25(a) through (e) or, in lieu of the summary, the complete
plan. The sponsor shall submit to FDA a complete investigational plan
and a complete report of prior investigations of the device if no IRB
has reviewed them, if FDA has found an IRB's review inadequate, or if
FDA requests them.
(3) A description of the methods, 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 good manufacturing practices can make a
knowledgeable judgment about the quality control used in the manufacture
of the device.
(4) An example of the agreements to be entered into by all
investigators to comply with investigator obligations under this part,
and a list of the names and addresses of all investigators who have
signed the agreement.
(5) A certification that all investigators who will participate in
the investigation have signed the agreement, that the list of
investigators includes all the investigators participating in the
investigation, and that no investigators will be added to the
investigation until they have signed the agreement.
(6) A list of the name, address, and chairperson of each IRB that
has been or will be asked to review the investigation and a
certification of the action concerning the investigation taken by each
such IRB.
(7) The name and address of any institution at which a part of the
investigation may be conducted that has not been identified in
accordance with paragraph (b)(6) of this section.
(8) If the device is to be sold, the amount to be charged and an
explanation of why sale does not constitute commercialization of the
device.
(9) A claim for categorical exclusion under Sec. 25.30 or 25.34 or
an environmental assessment under Sec. 25.40.
(10) Copies of all labeling for the device.
(11) Copies of all forms and informational materials to be provided
to subjects to obtain informed consent.
(12) Any other relevant information FDA requests for review of the
application.
(c) Additional information. FDA may request additional information
concerning an investigation or revision in the investigational plan. The
sponsor
may treat such a request as a disapproval of the application for
purposes of requesting a hearing under part 16.
(d) Information previously submitted. Information previously
submitted to the Center for Devices and Radiological Health in
accordance with this chapter ordinarily need not be resubmitted, but may
be incorporated by reference.
[45 FR 3751, Jan. 18, 1980, as amended at 46 FR 8956, Jan. 27, 1981; 50
FR 16669, Apr. 26, 1985; 53 FR 11252, Apr. 6, 1988; 61 FR 51530, Oct. 2,
1996; 62 FR 40600, July 29, 1997; 64 FR 10942, Mar. 8, 1999]
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Sec. 812.25 Investigational plan.
The investigational plan shall include, in the following order:
(a) Purpose. The name and intended use of the device and the
objectives and duration of the investigation.
(b) Protocol. A written protocol describing the methodology to be
used and an analysis of the protocol demonstrating that the
investigation is scientifically sound.
(c) Risk analysis. A description and analysis of all increased risks
to which subjects will be exposed by the investigation; the manner in
which these risks will be minimized; a justification for the
investigation; and a description of the patient population, including
the number, age, sex, and condition.
(d) Description of device. A description of each important
component, ingredient, property, and principle of operation of the
device and of each anticipated change in the device during the course of
the investigation.
(e) Monitoring procedures. The sponsor's written procedures for
monitoring the investigation and the name and address of any monitor.
(f) Labeling. Copies of all labeling for the device.
(g) Consent materials. Copies of all forms and informational
materials to be provided to subjects to obtain informed consent.
(h) IRB information. A list of the names, locations, and
chairpersons of all IRB's that have been or will be asked to review the
investigation, and a certification of any action taken by any of those
IRB's with respect to the investigation.
(i) Other institutions. The name and address of each institution at
which a part of the investigation may be conducted that has not been
identified in paragraph (h) of this section.
(j) Additional records and reports. A description of records and
reports that will be maintained on the investigation in addition to
those prescribed in subpart G.
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Sec. 812.27 Report of prior investigations.
(a) General. The report of prior investigations shall include
reports of all prior clinical, animal, and laboratory testing of the
device and shall be comprehensive and adequate to justify the proposed
investigation.
(b) Specific contents. The report also shall include:
(1) A bibliography of all publications, whether adverse or
supportive, that are relevant to an evaluation of the safety or
effectiveness of the device, copies of all published and unpublished
adverse information, and, if requested by an IRB or FDA, copies of other
significant publications.
(2) A summary of all other unpublished information (whether adverse
or supportive) in the possession of, or reasonably obtainable by, the
sponsor that is relevant to an evaluation of the safety or effectiveness
of the device.
(3) If information on nonclinical laboratory studies is provided, a
statement that all such studies have been conducted in compliance with
applicable requirements in the good laboratory practice regulations in
part 58, or if any such study was not conducted in compliance with such
regulations, a brief statement of the reason for the noncompliance.
Failure or inability to comply with this requirement does not justify
failure to provide information on a relevant nonclinical test study.
[45 FR 3751, Jan. 18, 1980, as amended at 50 FR 7518, Feb. 22, 1985]
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Sec. 812.30 FDA action on applications.
(a) Approval or disapproval. FDA will notify the sponsor in writing
of the date it receives an application. FDA may approve an investigation
as proposed, approve it with modifications, or disapprove it. An
investigation may not begin until:
(1) Thirty days after FDA receives the application at the address in
Sec. 812.19 for the investigation of a device other than a banned
device, unless FDA notifies the sponsor that the investigation may not
begin; or
(2) FDA approves, by order, an IDE for the investigation.
(b) Grounds for disapproval or withdrawal. FDA may disapprove or
withdraw approval of an application if FDA finds that:
(1) There has been a failure to comply with any requirement of this
part or the act, any other applicable regulation or statute, or any
condition of approval imposed by an IRB or FDA.
(2) The application or a report contains an untrue statement of a
material fact, or omits material information required by this part.
(3) The sponsor fails to respond to a request for additional
information within the time prescribed by FDA.
(4) There is reason to believe that the risks to the subjects are
not outweighed by the anticipated benefits to the subjects and the
importance of the knowledge to be gained, or informed consent is
inadquate, or the investigation is scientifically unsound, or there is
reason to believe that the device as used is ineffective.
(5) It is otherwise unreasonable to begin or to continue the
investigation owing to the way in which the device is used or the
inadequacy of:
(i) The report of prior investigations or the investigational plan;
(ii) The methods, facilities, and controls used for the
manufacturing, processing, packaging, storage, and, where appropriate,
installation of the device; or
(iii) Monitoring and review of the investigation.
(c) Notice of disapproval or withdrawal. If FDA disapproves an
application or proposes to withdraw approval of an application, FDA will
notify the sponsor in writing.
(1) A disapproval order will contain a complete statement of the
reasons for disapproval and a statement that the sponsor has an
opportunity to request a hearing under part 16.
(2) A notice of a proposed withdrawal of approval will contain a
complete statement of the reasons for withdrawal and a statement that
the sponsor has an opportunity to request a hearing under part 16. FDA
will provide the opportunity for hearing before withdrawal of approval,
unless FDA determines in the notice that continuation of testing under
the exemption will result in an unreasonble risk to the public health
and orders withdrawal of approval before any hearing.
[45 FR 3751, Jan. 18, 1980, as amended at 45 FR 58842, Sept. 5, 1980]
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Sec. 812.35 Supplemental applications.
(a) Changes in investigational plan--(1) Changes requiring prior
approval. Except as described in paragraphs (a)(2) through (a)(4) of
this section, a sponsor must obtain approval of a supplemental
application under Sec. 812.30(a), and IRB approval when appropriate
(see Sec. Sec. 56.110 and 56.111 of this chapter), prior to
implementing a change to an investigational plan. If a sponsor intends
to conduct an investigation that involves an exception to informed
consent under Sec. 50.24 of this chapter, the sponsor shall submit a
separate investigational device exemption (IDE) application in
accordance with Sec. 812.20(a).
(2) Changes effected for emergency use. The requirements of
paragraph (a)(1) of this section regarding FDA approval of a supplement
do not apply in the case of a deviation from the investigational plan to
protect the life or physical well-being of a subject in an emergency.
Such deviation shall be reported to FDA within 5-working days after the
sponsor learns of it (see Sec. 812.150(a)(4)).
(3) Changes effected with notice to FDA within 5 days. A sponsor may
make certain changes without prior approval of a supplemental
application under paragraph (a)(1) of this section if the sponsor
determines that these changes meet the criteria described in paragraphs
(a)(3)(i) and (a)(3)(ii) of this section, on the basis of credible
information defined in paragraph (a)(3)(iii) of this section, and the
sponsor provides notice to FDA within 5-working days of making these
changes.
(i) Developmental changes. The requirements in paragraph (a)(1) of
this section regarding FDA approval of a supplement do not apply to
developmental changes in the device (including manufacturing changes)
that do
not constitute a significant change in design or basic principles of
operation and that are made in response to information gathered during
the course of an investigation.
(ii) Changes to clinical protocol. The requirements in paragraph
(a)(1) of this section regarding FDA approval of a supplement do not
apply to changes to clinical protocols that do not affect:
(A) The validity of the data or information resulting from the
completion of the approved protocol, or the relationship of likely
patient risk to benefit relied upon to approve the protocol;
(B) The scientific soundness of the investigational plan; or
(C) The rights, safety, or welfare of the human subjects involved in
the investigation.
(iii) Definition of credible information. (A) Credible information
to support developmental changes in the device (including manufacturing
changes) includes data generated under the design control procedures of
Sec. 820.30, preclinical/animal testing, peer reviewed published
literature, or other reliable information such as clinical information
gathered during a trial or marketing.
(B) Credible information to support changes to clinical protocols is
defined as the sponsor's documentation supporting the conclusion that a
change does not have a significant impact on the study design or planned
statistical analysis, and that the change does not affect the rights,
safety, or welfare of the subjects. Documentation shall include
information such as peer reviewed published literature, the
recommendation of the clinical investigator(s), and/or the data gathered
during the clinical trial or marketing.
(iv) Notice of IDE change. Changes meeting the criteria in
paragraphs (a)(3)(i) and (a)(3)(ii) of this section that are supported
by credible information as defined in paragraph (a)(3)(iii) of this
section may be made without prior FDA approval if the sponsor submits a
notice of the change to the IDE not later than 5-working days after
making the change. Changes to devices are deemed to occur on the date
the device, manufactured incorporating the design or manufacturing
change, is distributed to the investigator(s). Changes to a clinical
protocol are deemed to occur when a clinical investigator is notified by
the sponsor that the change should be implemented in the protocol or,
for sponsor-investigator studies, when a sponsor-investigator
incorporates the change in the protocol. Such notices shall be
identified as a ``notice of IDE change.''
(A) For a developmental or manufacturing change to the device, the
notice shall include a summary of the relevant information gathered
during the course of the investigation upon which the change was based;
a description of the change to the device or manufacturing process
(cross-referenced to the appropriate sections of the original device
description or manufacturing process); and, if design controls were used
to assess the change, a statement that no new risks were identified by
appropriate risk analysis and that the verification and validation
testing, as appropriate, demonstrated that the design outputs met the
design input requirements. If another method of assessment was used, the
notice shall include a summary of the information which served as the
credible information supporting the change.
(B) For a protocol change, the notice shall include a description of
the change (cross-referenced to the appropriate sections of the original
protocol); an assessment supporting the conclusion that the change does
not have a significant impact on the study design or planned statistical
analysis; and a summary of the information that served as the credible
information supporting the sponsor's determination that the change does
not affect the rights, safety, or welfare of the subjects.
(4) Changes submitted in annual report. The requirements of
paragraph (a)(1) of this section do not apply to minor changes to the
purpose of the study, risk analysis, monitoring procedures, labeling,
informed consent materials, and IRB information that do not affect:
(i) The validity of the data or information resulting from the
completion of the approved protocol, or the relationship of likely
patient risk to benefit relied upon to approve the protocol;
(ii) The scientific soundness of the investigational plan; or
(iii) The rights, safety, or welfare of the human subjects involved
in the investigation. Such changes shall be reported in the annual
progress report for the IDE, under Sec. 812.150(b)(5).
(b) IRB approval for new facilities. A sponsor shall submit to FDA a
certification of any IRB approval of an investigation or a part of an
investigation not included in the IDE application. If the investigation
is otherwise unchanged, the supplemental application shall consist of an
updating of the information required by Sec. 812.20(b) and (c) and a
description of any modifications in the investigational plan required by
the IRB as a condition of approval. A certification of IRB approval need
not be included in the initial submission of the supplemental
application, and such certification is not a precondition for agency
consideration of the application. Nevertheless, a sponsor may not begin
a part of an investigation at a facility until the IRB has approved the
investigation, FDA has received the certification of IRB approval, and
FDA, under Sec. 812.30(a), has approved the supplemental application
relating to that part of the investigation (see Sec. 56.103(a)).
[50 FR 25909, June 24, 1985; 50 FR 28932, July 17, 1985, as amended at
61 FR 51531, Oct. 2, 1996; 63 FR 64625, Nov. 23, 1998]
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Sec. 812.36 Treatment use of an investigational device.
(a) General. A device that is not approved for marketing may be
under clinical investigation for a serious or immediately life-
threatening disease or condition in patients for whom no comparable or
satisfactory alternative device or other therapy is available. During
the clinical trial or prior to final action on the marketing
application, it may be appropriate to use the device in the treatment of
patients not in the trial under the provisions of a treatment
investigational device exemption (IDE). The purpose of this section is
to facilitate the availability of promising new devices to desperately
ill patients as early in the device development process as possible,
before general marketing begins, and to obtain additional data on the
device's safety and effectiveness. In the case of a serious disease, a
device ordinarily may be made available for treatment use under this
section after all clinical trials have been completed. In the case of an
immediately life-threatening disease, a device may be made available for
treatment use under this section prior to the completion of all clinical
trials. For the purpose of this section, an ``immediately life-
threatening'' disease means a stage of a disease in which there is a
reasonable likelihood that death will occur within a matter of months or
in which premature death is likely without early treatment. For purposes
of this section, ``treatment use''of a device includes the use of a
device for diagnostic purposes.
(b) Criteria. FDA shall consider the use of an investigational
device under a treatment IDE if:
(1) The device is intended to treat or diagnose a serious or
immediately life-threatening disease or condition;
(2) There is no comparable or satisfactory alternative device or
other therapy available to treat or diagnose that stage of the disease
or condition in the intended patient population;
(3) The device is under investigation in a controlled clinical trial
for the same use under an approved IDE, or such clinical trials have
been completed; and
(4) The sponsor of the investigation is actively pursuing marketing
approval/clearance of the investigational device with due diligence.
(c) Applications for treatment use. (1) A treatment IDE application
shall include, in the following order:
(i) The name, address, and telephone number of the sponsor of the
treatment IDE;
(ii) The intended use of the device, the criteria for patient
selection, and a written protocol describing the treatment use;
(iii) An explanation of the rationale for use of the device,
including, as appropriate, either a list of the available regimens that
ordinarily should be tried before using the investigational device or an
explanation of why the use of the investigational device is preferable
to the use of available marketed treatments;
(iv) A description of clinical procedures, laboratory tests, or
other measures that will be used to evaluate the effects of the device
and to minimize risk;
(v) Written procedures for monitoring the treatment use and the name
and address of the monitor;
(vi) Instructions for use for the device and all other labeling as
required under Sec. 812.5(a) and (b);
(vii) Information that is relevant to the safety and effectiveness
of the device for the intended treatment use. Information from other
IDE's may be incorporated by reference to support the treatment use;
(viii) A statement of the sponsor's commitment to meet all
applicable responsibilities under this part and part 56 of this chapter
and to ensure compliance of all participating investigators with the
informed consent requirements of part 50 of this chapter;
(ix) An example of the agreement to be signed by all investigators
participating in the treatment IDE and certification that no
investigator will be added to the treatment IDE before the agreement is
signed; and
(x) If the device is to be sold, the price to be charged and a
statement indicating that the price is based on manufacturing and
handling costs only.
(2) A licensed practitioner who receives an investigational device
for treatment use under a treatment IDE is an ``investigator'' under the
IDE and is responsible for meeting all applicable investigator
responsibilities under this part and parts 50 and 56 of this chapter.
(d) FDA action on treatment IDE applications--(1) Approval of
treatment IDE's. Treatment use may begin 30 days after FDA receives the
treatment IDE submission at the address specified in Sec. 812.19,
unless FDA notifies the sponsor in writing earlier than the 30 days that
the treatment use may or may not begin. FDA may approve the treatment
use as proposed or approve it with modifications.
(2) Disapproval or withdrawal of approval of treatment IDE's. FDA
may disapprove or withdraw approval of a treatment IDE if:
(i) The criteria specified in Sec. 812.36(b) are not met or the
treatment IDE does not contain the information required in Sec.
812.36(c);
(ii) FDA determines that any of the grounds for disapproval or
withdrawal of approval listed in Sec. 812.30(b)(1) through (b)(5)
apply;
(iii) The device is intended for a serious disease or condition and
there is insufficient evidence of safety and effectiveness to support
such use;
(iv) The device is intended for an immediately life-threatening
disease or condition and the available scientific evidence, taken as a
whole, fails to provide a reasonable basis for concluding that the
device:
(A) May be effective for its intended use in its intended
population; or
(B) Would not expose the patients to whom the device is to be
administered to an unreasonable and significant additional risk of
illness or injury;
(v) There is reasonable evidence that the treatment use is impeding
enrollment in, or otherwise interfering with the conduct or completion
of, a controlled investigation of the same or another investigational
device;
(vi) The device has received marketing approval/clearance or a
comparable device or therapy becomes available to treat or diagnose the
same indication in the same patient population for which the
investigational device is being used;
(vii) The sponsor of the controlled clinical trial is not pursuing
marketing approval/clearance with due diligence;
(viii) Approval of the IDE for the controlled clinical investigation
of the device has been withdrawn; or
(ix) The clinical investigator(s) named in the treatment IDE are not
qualified by reason of their scientific training and/or experience to
use the investigational device for the intended treatment use.
(3) Notice of disapproval or withdrawal. If FDA disapproves or
proposes to withdraw approval of a treatment IDE, FDA will follow the
procedures set forth in Sec. 812.30(c).
(e) Safeguards. Treatment use of an investigational device is
conditioned upon the sponsor and investigators complying with the
safeguards of the
IDE process and the regulations governing informed consent (part 50 of
this chapter) and institutional review boards (part 56 of this chapter).
(f) Reporting requirements. The sponsor of a treatment IDE shall
submit progress reports on a semi-annual basis to all reviewing IRB's
and FDA until the filing of a marketing application. These reports shall
be based on the period of time since initial approval of the treatment
IDE and shall include the number of patients treated with the device
under the treatment IDE, the names of the investigators participating in
the treatment IDE, and a brief description of the sponsor's efforts to
pursue marketing approval/clearance of the device. Upon filing of a
marketing application, progress reports shall be submitted annually in
accordance with Sec. 812.150(b)(5). The sponsor of a treatment IDE is
responsible for submitting all other reports required under Sec.
812.150.
[62 FR 48947, Sept. 18, 1997]
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Sec. 812.38 Confidentiality of data and information.
(a) Existence of IDE. FDA will not disclose the existence of an IDE
unless its existence has previously been publicly disclosed or
acknowledged, until FDA approves an application for premarket approval
of the device subject to the IDE; or a notice of completion of a product
development protocol for the device has become effective.
(b) Availability of summaries or data. (1) FDA will make publicly
available, upon request, a detailed summary of information concerning
the safety and effectiveness of the device that was the basis for an
order approving, disapproving, or withdrawing approval of an application
for an IDE for a banned device. The summary shall include information on
any adverse effect on health caused by the device.
(2) If a device is a banned device or if the existence of an IDE has
been publicly disclosed or acknowledged, data or information contained
in the file is not available for public disclosure before approval of an
application for premarket approval or the effective date of a notice of
completion of a product development protocol except as provided in this
section. FDA may, in its discretion, disclose a summary of selected
portions of the safety and effectiveness data, that is, clinical,
animal, or laboratory studies and tests of the device, for public
consideration of a specific pending issue.
(3) If the existence of an IDE file has not been publicly disclosed
or acknowledged, no data or information in the file are available for
public disclosure except as provided in paragraphs (b)(1) and (c) of
this section.
(4) Notwithstanding paragraph (b)(2) of this section, FDA will make
available to the public, upon request, the information in the IDE that
was required to be filed in Docket Number 95S-0158 in the Division of
Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852, for investigations involving an
exception from informed consent under Sec. 50.24 of this chapter.
Persons wishing to request this information shall submit a request under
the Freedom of Information Act.
(c) Reports of adverse effects. Upon request or on its own
initiative, FDA shall disclose to an individual on whom an
investigational device has been used a copy of a report of adverse
device effects relating to that use.
(d) Other rules. Except as otherwise provided in this section, the
availability for public disclosure of data and information in an IDE
file shall be handled in accordance with Sec. 814.9.
[45 FR 3751, Jan. 18, 1980, as amended at 53 FR 11253, Apr. 6, 1988; 61
FR 51531, Oct. 2, 1996]
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Subpart C_Responsibilities of Sponsors
Sec. 812.40 General responsibilities of sponsors.
Sponsors are responsible for selecting qualified investigators and
providing them with the information they need to conduct the
investigation properly, ensuring proper monitoring of the investigation,
ensuring that IRB review and approval are obtained, submitting an IDE
application to FDA, and ensuring that any reviewing IRB and FDA are
promptly informed of significant new information about an investigation.
Additional responsibilities of
sponsors are described in subparts B and G.
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Sec. 812.42 FDA and IRB approval.
A sponsor shall not begin an investigation or part of an
investigation until an IRB and FDA have both approved the application or
supplemental application relating to the investigation or part of an
investigation.
[46 FR 8957, Jan. 27, 1981]
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Sec. 812.43 Selecting investigators and monitors.
(a) Selecting investigators. A sponsor shall select investigators
qualified by training and experience to investigate the device.
(b) Control of device. A sponsor shall ship investigational devices
only to qualified investigators participating in the investigation.
(c) Obtaining agreements. A sponsor shall obtain from each
participating investigator a signed agreement that includes:
(1) The investigator's curriculum vitae.
(2) Where applicable, a statement of the investigator's relevant
experience, including the dates, location, extent, and type of
experience.
(3) If the investigator was involved in an investigation or other
research that was terminated, an explanation of the circumstances that
led to termination.
(4) A statement of the investigator's commitment to:
(i) Conduct the investigation in accordance with the agreement, the
investigational plan, this part and other applicable FDA regulations,
and conditions of approval imposed by the reviewing IRB or FDA;
(ii) Supervise all testing of the device involving human subjects;
and
(iii) Ensure that the requirements for obtaining informed consent
are met.
(5) Sufficient accurate financial disclosure information to allow
the sponsor to submit a complete and accurate certification or
disclosure statement as required under part 54 of this chapter. The
sponsor shall obtain a commitment from the clinical investigator to
promptly update this information if any relevant changes occur during
the course of the investigation and for 1 year following completion of
the study. This information shall not be submitted in an investigational
device exemption application, but shall be submitted in any marketing
application involving the device.
(d) Selecting monitors. A sponsor shall select monitors qualified by
training and experience to monitor the investigational study in
accordance with this part and other applicable FDA regulations.
[45 FR 3751, Jan. 18, 1980, as amended at 63 FR 5253, Feb. 2, 1998]
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Sec. 812.45 Informing investigators.
A sponsor shall supply all investigators participating in the
investigation with copies of the investigational plan and the report of
prior investigations of the device.
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Sec. 812.46 Monitoring investigations.
(a) Securing compliance. A sponsor who discovers that an
investigator is not complying with the signed agreement, the
investigational plan, the requirements of this part or other applicable
FDA regulations, or any conditions of approval imposed by the reviewing
IRB or FDA shall promptly either secure compliance, or discontinue
shipments of the device to the investigator and terminate the
investigator's participation in the investigation. A sponsor shall also
require such an investigator to dispose of or return the device, unless
this action would jeopardize the rights, safety, or welfare of a
subject.
(b) Unanticipated adverse device effects. (1) A sponsor shall
immediately conduct an evaluation of any unanticipated adverse device
effect.
(2) A sponsor who determines that an unanticipated adverse device
effect presents an unreasonable risk to subjects shall terminate all
investigations or parts of investigations presenting that risk as soon
as possible. Termination shall occur not later than 5 working days after
the sponsor makes this determination and not later than 15 working days
after the sponsor first received notice of the effect.
(c) Resumption of terminated studies. If the device is a significant
risk device, a sponsor may not resume a terminated investigation without
IRB and FDA approval. If the device is not a
significant risk device, a sponsor may not resume a terminated
investigation without IRB approval and, if the investigation was
terminated under paragraph (b)(2) of this section, FDA approval.
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Sec. 812.47 Emergency research under Sec. 50.24 of this chapter.
(a) The sponsor shall monitor the progress of all investigations
involving an exception from informed consent under Sec. 50.24 of this
chapter. When the sponsor receives from the IRB information concerning
the public disclosures under Sec. 50.24(a)(7)(ii) and (a)(7)(iii) of
this chapter, the sponsor shall promptly submit to the IDE file and to
Docket Number 95S-0158 in the Division of Dockets Management (HFA-305),
Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD
20852, copies of the information that was disclosed, identified by the
IDE number.
(b) The sponsor also shall monitor such investigations to determine
when an IRB determines that it cannot approve the research because it
does not meet the criteria in the exception in Sec. 50.24(a) of this
chapter or because of other relevant ethical concerns. The sponsor
promptly shall provide this information in writing to FDA, investigators
who are asked to participate in this or a substantially equivalent
clinical investigation, and other IRB's that are asked to review this or
a substantially equivalent investigation.
[61 FR 51531, Oct. 2, 1996, as amended at 64 FR 10943, Mar. 8, 1999]
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Subpart D_IRB Review and Approval
Sec. 812.60 IRB composition, duties, and functions.
An IRB reviewing and approving investigations under this part shall
comply with the requirements of part 56 in all respects, including its
composition, duties, and functions.
[46 FR 8957, Jan. 27, 1981]
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Sec. 812.62 IRB approval.
(a) An IRB shall review and have authority to approve, require
modifications in (to secure approval), or disapprove all investigations
covered by this part.
(b) If no IRB exists or if FDA finds that an IRB's review is
inadequate, a sponsor may submit an application to FDA.
[46 FR 8957, Jan. 27, 1981]
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Sec. 812.64 IRB's continuing review.
The IRB shall conduct its continuing review of an investigation in
accordance with part 56.
[46 FR 8957, Jan. 27, 1981]
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Sec. 812.65 [Reserved]
Sec. 812.66 Significant risk device determinations.
If an IRB determines that an investigation, presented for approval
under Sec. 812.2(b)(1)(ii), involves a significant risk device, it
shall so notify the investigator and, where appropriate, the sponsor. A
sponsor may not begin the investigation except as provided in Sec.
812.30(a).
[46 FR 8957, Jan. 27, 1981]
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Subpart E_Responsibilities of Investigators
Sec. 812.100 General responsibilities of investigators.
An investigator is responsible for ensuring that an investigation is
conducted according to the signed agreement, the investigational plan
and applicable FDA regulations, for protecting the rights, safety, and
welfare of subjects under the investigator's care, and for the control
of devices under investigation. An investigator also is responsible for
ensuring that informed consent is obtained in accordance with part 50 of
this chapter. Additional responsibilities of investigators are described
in subpart G.
[45 FR 3751, Jan. 18, 1980, as amended at 46 FR 8957, Jan. 27, 1981]
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Sec. 812.110 Specific responsibilities of investigators.
(a) Awaiting approval. An investigator may determine whether
potential subjects would be interested in participating in an
investigation, but shall
not request the written informed consent of any subject to participate,
and shall not allow any subject to participate before obtaining IRB and
FDA approval.
(b) Compliance. An investigator shall conduct an investigation in
accordance with the signed agreement with the sponsor, the
investigational plan, this part and other applicable FDA regulations,
and any conditions of approval imposed by an IRB or FDA.
(c) Supervising device use. An investigator shall permit an
investigational device to be used only with subjects under the
investigator's supervision. An investigator shall not supply an
investigational device to any person not authorized under this part to
receive it.
(d) Financial disclosure. A clinical investigator shall disclose to
the sponsor sufficient accurate financial information to allow the
applicant to submit complete and accurate certification or disclosure
statements required under part 54 of this chapter. The investigator
shall promptly update this information if any relevant changes occur
during the course of the investigation and for 1 year following
completion of the study.
(e) Disposing of device. Upon completion or termination of a
clinical investigation or the investigator's part of an investigation,
or at the sponsor's request, an investigator shall return to the sponsor
any remaining supply of the device or otherwise dispose of the device as
the sponsor directs.
[45 FR 3751, Jan. 18, 1980, as amended at 63 FR 5253, Feb. 2, 1998]
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Sec. 812.119 Disqualification of a clinical investigator.
(a) If FDA has information indicating that an investigator has
repeatedly or deliberately failed to comply with the requirements of
this part, part 50, or part 56 of this chapter, or has repeatedly or
deliberately submitted false information either to the sponsor of the
investigation or in any required report, the Center for Devices and
Radiological Health will furnish the investigator written notice of the
matter under complaint and offer the investigator an opportunity to
explain the matter in writing, or, at the option of the investigator, in
an informal conference. If an explanation is offered and accepted by the
Center for Devices and Radiological Health, the disqualification process
will be terminated. If an explanation is offered but not accepted by the
Center for Devices and Radiological Health, the investigator will be
given an opportunity for a regulatory hearing under part 16 of this
chapter on the question of whether the investigator is entitled to
receive investigational devices.
(b) After evaluating all available information, including any
explanation presented by the investigator, if the Commissioner
determines that the investigator has repeatedly or deliberately failed
to comply with the requirements of this part, part 50, or part 56 of
this chapter, or has deliberately or repeatedly submitted false
information either to the sponsor of the investigation or in any
required report, the Commissioner will notify the investigator, the
sponsor of any investigation in which the investigator has been named as
a participant, and the reviewing IRB that the investigator is not
entitled to receive investigational devices. The notification will
provide a statement of basis for such determination.
(c) Each investigational device exemption (IDE) and each cleared or
approved application submitted under this part, subpart E of part 807 of
this chapter, or part 814 of this chapter containing data reported by an
investigator who has been determined to be ineligible to receive
investigational devices will be examined to determine whether the
investigator has submitted unreliable data that are essential to the
continuation of the investigation or essential to the approval or
clearance of any marketing application.
(d) If the Commissioner determines, after the unreliable data
submitted by the investigator are eliminated from consideration, that
the data remaining are inadequate to support a conclusion that it is
reasonably safe to continue the investigation, the Commissioner will
notify the sponsor who shall have an opportunity for a regulatory
hearing under part 16 of this chapter. If a
danger to the public health exists, however, the Commissioner shall
terminate the IDE immediately and notify the sponsor and the reviewing
IRB of the determination. In such case, the sponsor shall have an
opportunity for a regulatory hearing before FDA under part 16 of this
chapter on the question of whether the IDE should be reinstated.
(e) If the Commissioner determines, after the unreliable data
submitted by the investigator are eliminated from consideration, that
the continued clearance or approval of the marketing application for
which the data were submitted cannot be justified, the Commissioner will
proceed to withdraw approval or rescind clearance of the medical device
in accordance with the applicable provisions of the act.
(f) An investigator who has been determined to be ineligible to
receive investigational devices may be reinstated as eligible when the
Commissioner determines that the investigator has presented adequate
assurances that the investigator will employ investigational devices
solely in compliance with the provisions of this part and of parts 50
and 56 of this chapter.
[62 FR 12096, Mar. 14, 1997]
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Subpart F [Reserved]
Subpart G_Records and Reports
Sec. 812.140 Records.
(a) Investigator records. A participating investigator shall
maintain the following accurate, complete, and current records relating
to the investigator's participation in an investigation:
(1) All correspondence with another investigator, an IRB, the
sponsor, a monitor, or FDA, including required reports.
(2) Records of receipt, use or disposition of a device that relate
to:
(i) The type and quantity of the device, the dates of its receipt,
and the batch number or code mark.
(ii) The names of all persons who received, used, or disposed of
each device.
(iii) Why and how many units of the device have been returned to the
sponsor, repaired, or otherwise disposed of.
(3) Records of each subject's case history and exposure to the
device. Case histories include the case report forms and supporting data
including, for example, signed and dated consent forms and medical
records including, for example, progress notes of the physician, the
individual's hospital chart(s), and the nurses' notes. Such records
shall include:
(i) Documents evidencing informed consent and, for any use of a
device by the investigator without informed consent, any written
concurrence of a licensed physician and a brief description of the
circumstances justifying the failure to obtain informed consent. The
case history for each individual shall document that informed consent
was obtained prior to participation in the study.
(ii) All relevant observations, including records concerning adverse
device effects (whether anticipated or unanticipated), information and
data on the condition of each subject upon entering, and during the
course of, the investigation, including information about relevant
previous medical history and the results of all diagnostic tests.
(iii) A record of the exposure of each subject to the
investigational device, including the date and time of each use, and any
other therapy.
(4) The protocol, with documents showing the dates of and reasons
for each deviation from the protocol.
(5) Any other records that FDA requires to be maintained by
regulation or by specific requirement for a category of investigations
or a particular investigation.
(b) Sponsor records. A sponsor shall maintain the following
accurate, complete, and current records relating to an investigation:
(1) All correspondence with another sponsor, a monitor, an
investigator, an IRB, or FDA, including required reports.
(2) Records of shipment and disposition. Records of shipment shall
include the name and address of the consignee, type and quantity of
device, date of shipment, and batch number or code mark. Records of
disposition shall describe the batch number or code marks of any devices
returned to the sponsor,
repaired, or disposed of in other ways by the investigator or another
person, and the reasons for and method of disposal.
(3) Signed investigator agreements including the financial
disclosure information required to be collected under Sec. 812.43(c)(5)
in accordance with part 54 of this chapter.
(4) For each investigation subject to Sec. 812.2(b)(1) of a device
other than a significant risk device, the records described in paragraph
(b)(5) of this section and the following records, consolidated in one
location and available for FDA inspection and copying:
(i) The name and intended use of the device and the objectives of
the investigation;
(ii) A brief explanation of why the device is not a significant risk
device:
(iii) The name and address of each investigator:
(iv) The name and address of each IRB that has reviewed the
investigation:
(v) A statement of the extent to which the good manufacturing
practice regulation in part 820 will be followed in manufacturing the
device; and
(vi) Any other information required by FDA.
(5) Records concerning adverse device effects (whether anticipated
or unanticipated) and complaints and
(6) Any other records that FDA requires to be maintained by
regulation or by specific requirement for a category of investigation or
a particular investigation.
(c) IRB records. An IRB shall maintain records in accordance with
part 56 of this chapter.
(d) Retention period. An investigator or sponsor shall maintain the
records required by this subpart during the investigation and for a
period of 2 years after the latter of the following two dates: The date
on which the investigation is terminated or completed, or the date that
the records are no longer required for purposes of supporting a
premarket approval application or a notice of completion of a product
development protocol.
(e) Records custody. An investigator or sponsor may withdraw from
the responsibility to maintain records for the period required in
paragraph (d) of this section and transfer custody of the records to any
other person who will accept responsibility for them under this part,
including the requirements of Sec. 812.145. Notice of a transfer shall
be given to FDA not later than 10 working days after transfer occurs.
[45 FR 3751, Jan. 18, 1980, as amended at 45 FR 58843, Sept. 5, 1980; 46
FR 8957, Jan. 27, 1981; 61 FR 57280, Nov. 5, 1996; 63 FR 5253, Feb. 2,
1998]
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Sec. 812.145 Inspections.
(a) Entry and inspection. A sponsor or an investigator who has
authority to grant access shall permit authorized FDA employees, at
reasonable times and in a reasonable manner, to enter and inspect any
establishment where devices are held (including any establishment where
devices are manufactured, processed, packed, installed, used, or
implanted or where records of results from use of devices are kept).
(b) Records inspection. A sponsor, IRB, or investigator, or any
other person acting on behalf of such a person with respect to an
investigation, shall permit authorized FDA employees, at reasonable
times and in a reasonable manner, to inspect and copy all records
relating to an investigation.
(c) Records identifying subjects. An investigator shall permit
authorized FDA employees to inspect and copy records that identify
subjects, upon notice that FDA has reason to suspect that adequate
informed consent was not obtained, or that reports required to be
submitted by the investigator to the sponsor or IRB have not been
submitted or are incomplete, inaccurate, false, or misleading.
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Sec. 812.150 Reports.
(a) Investigator reports. An investigator shall prepare and submit
the following complete, accurate, and timely reports:
(1) Unanticipated adverse device effects. An investigator shall
submit to the sponsor and to the reviewing IRB a report of any
unanticipated adverse device effect occurring during an investigation as
soon as possible, but in no event later than 10 working days after the
investigator first learns of the effect.
(2) Withdrawal of IRB approval. An investigator shall report to the
sponsor, within 5 working days, a withdrawal of approval by the
reviewing IRB of the investigator's part of an investigation.
(3) Progress. An investigator shall submit progress reports on the
investigation to the sponsor, the monitor, and the reviewing IRB at
regular intervals, but in no event less often than yearly.
(4) Deviations from the investigational plan. An investigator shall
notify the sponsor and the reviewing IRB (see Sec. 56.108(a) (3) and
(4)) of any deviation from the investigational plan to protect the life
or physical well-being of a subject in an emergency. Such notice shall
be given as soon as possible, but in no event later than 5 working days
after the emergency occurred. Except in such an emergency, prior
approval by the sponsor is required for changes in or deviations from a
plan, and if these changes or deviations may affect the scientific
soundness of the plan or the rights, safety, or welfare of human
subjects, FDA and IRB in accordance with Sec. 812.35(a) also is
required.
(5) Informed consent. If an investigator uses a device without
obtaining informed consent, the investigator shall report such use to
the sponsor and the reviewing IRB within 5 working days after the use
occurs.
(6) Final report. An investigator shall, within 3 months after
termination or completion of the investigation or the investigator's
part of the investigation, submit a final report to the sponsor and the
reviewing IRB.
(7) Other. An investigator shall, upon request by a reviewing IRB or
FDA, provide accurate, complete, and current information about any
aspect of the investigation.
(b) Sponsor reports. A sponsor shall prepare and submit the
following complete, accurate, and timely reports:
(1) Unanticipated adverse device effects. A sponsor who conducts an
evaluation of an unanticipated adverse device effect under Sec.
812.46(b) shall report the results of such evaluation to FDA and to all
reviewing IRB's and participating investigators within 10 working days
after the sponsor first receives notice of the effect. Thereafter the
sponsor shall submit such additional reports concerning the effect as
FDA requests.
(2) Withdrawal of IRB approval. A sponsor shall notify FDA and all
reviewing IRB's and participating investigators of any withdrawal of
approval of an investigation or a part of an investigation by a
reviewing IRB within 5 working days after receipt of the withdrawal of
approval.
(3) Withdrawal of FDA approval. A sponsor shall notify all reviewing
IRB's and participating investigators of any withdrawal of FDA approval
of the investigation, and shall do so within 5 working days after
receipt of notice of the withdrawal of approval.
(4) Current investigator list. A sponsor shall submit to FDA, at 6-
month intervals, a current list of the names and addresses of all
investigators participating in the investigation. The sponsor shall
submit the first such list 6 months after FDA approval.
(5) Progress reports. At regular intervals, and at least yearly, a
sponsor shall submit progress reports to all reviewing IRB's. In the
case of a significant risk device, a sponsor shall also submit progress
reports to FDA. A sponsor of a treatment IDE shall submit semi-annual
progress reports to all reviewing IRB's and FDA in accordance with Sec.
812.36(f) and annual reports in accordance with this section.
(6) Recall and device disposition. A sponsor shall notify FDA and
all reviewing IRB's of any request that an investigator return, repair,
or otherwise dispose of any units of a device. Such notice shall occur
within 30 working days after the request is made and shall state why the
request was made.
(7) Final report. In the case of a significant risk device, the
sponsor shall notify FDA within 30 working days of the completion or
termination of the investigation and shall submit a final report to FDA
and all reviewing the IRB's and participating investigators within 6
months after completion or termination. In the case of a device that is
not a significant risk device, the sponsor shall submit a final report
to all reviewing IRB's within 6 months after termination or completion.
(8) Informed consent. A sponsor shall submit to FDA a copy of any
report by an investigator under paragraph (a)(5)
of this section of use of a device without obtaining informed consent,
within 5 working days of receipt of notice of such use.
(9) Significant risk device determinations. If an IRB determines
that a device is a significant risk device, and the sponsor had proposed
that the IRB consider the device not to be a significant risk device,
the sponsor shall submit to FDA a report of the IRB's determination
within 5 working days after the sponsor first learns of the IRB's
determination.
(10) Other. A sponsor shall, upon request by a reviewing IRB or FDA,
provide accurate, complete, and current information about any aspect of
the investigation.
[45 FR 3751, Jan. 18, 1980, as amended at 45 FR 58843, Sept. 5, 1980; 48
FR 15622, Apr. 12, 1983; 62 FR 48948, Sept. 18, 1997]
PART 813 [RESERVED]
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