[Code of Federal Regulations]
[Title 21, Volume 8]
[Revised as of April 1, 2003]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR860.7]

[Page 168-171]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 860--MEDICAL DEVICE CLASSIFICATION PROCEDURES--Table of Contents
 
                           Subpart A--General
 
Sec. 860.7  Determination of safety and effectiveness.

    (a) The classification panels, in reviewing evidence concerning the 
safety and effectiveness of a device and in preparing advice to the 
Commissioner, and the Commissioner, in making determinations concerning 
the safety and effectiveness of a device, will apply the rules in this 
section.
    (b) In determining the safety and effectiveness of a device for 
purposes of classification, establishment of performance standards for 
class II devices, and premarket approval of class III devices, the 
Commissioner and the classification panels will consider the following, 
among other relevant factors:
    (1) The persons for whose use the device is represented or intended;
    (2) The conditions of use for the device, including conditions of 
use prescribed, recommended, or suggested in the labeling or advertising 
of the device, and other intended conditions of use;
    (3) The probable benefit to health from the use of the device 
weighed against any probable injury or illness from such use; and
    (4) The reliability of the device.
    (c)(1) Although the manufacturer may submit any form of evidence to 
the Food and Drug Administration in an attempt to substantiate the 
safety and effectiveness of a device, the agency relies upon only valid 
scientific evidence to determine whether there is reasonable assurance 
that the device is safe and effective. After considering the nature of 
the device and the rules in this section, the Commissioner will

[[Page 169]]

determine whether the evidence submitted or otherwise available to the 
Commissioner is valid scientific evidence for the purpose of determining 
the safety or effectiveness of a particular device and whether the 
available evidence, when taken as a whole, is adequate to support a 
determination that there is reasonable assurance that the device is safe 
and effective for its conditions of use.
    (2) Valid scientific evidence is evidence from well-controlled 
investigations, partially controlled studies, studies and objective 
trials without matched controls, well-documented case histories 
conducted by qualified experts, and reports of significant human 
experience with a marketed device, from which it can fairly and 
responsibly be concluded by qualified experts that there is reasonable 
assurance of the safety and effectiveness of a device under its 
conditions of use. The evidence required may vary according to the 
characteristics of the device, its conditions of use, the existence and 
adequacy of warnings and other restrictions, and the extent of 
experience with its use. Isolated case reports, random experience, 
reports lacking sufficient details to permit scientific evaluation, and 
unsubstantiated opinions are not regarded as valid scientific evidence 
to show safety or effectiveness. Such information may be considered, 
however, in identifying a device the safety and effectiveness of which 
is questionable.
    (d)(1) There is reasonable assurance that a device is safe when it 
can be determined, based upon valid scientific evidence, that the 
probable benefits to health from use of the device for its intended uses 
and conditions of use, when accompanied by adequate directions and 
warnings against unsafe use, outweigh any probable risks. The valid 
scientific evidence used to determine the safety of a device shall 
adequately demonstrate the absence of unreasonable risk of illness or 
injury associated with the use of the device for its intended uses and 
conditions of use.
    (2) Among the types of evidence that may be required, when 
appropriate, to determine that there is reasonable assurance that a 
device is safe are investigations using laboratory animals, 
investigations involving human subjects, and nonclinical investigations 
including in vitro studies.
    (e)(1) There is reasonable assurance that a device is effective when 
it can be determined, based upon valid scientific evidence, that in a 
significant portion of the target population, the use of the device for 
its intended uses and conditions of use, when accompanied by adequate 
directions for use and warnings against unsafe use, will provide 
clinically significant results.
    (2) The valid scientific evidence used to determine the 
effectiveness of a device shall consist principally of well-controlled 
investigations, as defined in paragraph (f) of this section, unless the 
Commissioner authorizes reliance upon other valid scientific evidence 
which the Commissioner has determined is sufficient evidence from which 
to determine the effectiveness of a device, even in the absence of well-
controlled investigations. The Commissioner may make such a 
determination where the requirement of well-controlled investigations in 
paragraph (f) of this section is not reasonably applicable to the 
device.
    (f) The following principles have been developed over a period of 
years and are recognized by the scientific community as the essentials 
of a well-controlled clinical investigation. They provide the basis for 
the Commissioner's determination whether there is reasonable assurance 
that a device is effective based upon well-controlled investigations and 
are also useful in assessing the weight to be given to other valid 
scientific evidence permitted under this section.
    (1) The plan or protocol for the study and the report of the results 
of a well-controlled investigation shall include the following:
    (i) A clear statement of the objectives of the study;
    (ii) A method of selection of the subjects that:
    (a) Provides adequate assurance that the subjects are suitable for 
the purposes of the study, provides diagnostic criteria of the condition 
to be treated or diagnosed, provides confirmatory laboratory tests where 
appropriate and, in the case of a device to prevent

[[Page 170]]

a disease or condition, provides evidence of susceptibility and exposure 
to the condition against which prophylaxis is desired;
    (b) Assigns the subjects to test groups, if used, in such a way as 
to minimize any possible bias;
    (c) Assures comparability between test groups and any control groups 
of pertinent variables such as sex, severity or duration of the disease, 
and use of therapy other than the test device;
    (iii) An explanation of the methods of observation and recording of 
results utilized, including the variables measured, quantitation, 
assessment of any subject's response, and steps taken to minimize any 
possible bias of subjects and observers;
    (iv) A comparison of the results of treatment or diagnosis with a 
control in such a fashion as to permit quantitative evaluation. The 
precise nature of the control must be specified and an explanation 
provided of the methods employed to minimize any possible bias of the 
observers and analysts of the data. Level and methods of ``blinding,'' 
if appropriate and used, are to be documented. Generally, four types of 
comparisons are recognized:
    (a) No treatments. Where objective measurements of effectiveness are 
available and placebo effect is negligible, comparison of the objective 
results in comparable groups of treated and untreated patients;
    (b) Placebo control. Where there may be a placebo effect with the 
use of a device, comparison of the results of use of the device with an 
ineffective device used under conditions designed to resemble the 
conditions of use under investigation as far as possible;
    (c) Active treatment control. Where an effective regimen of therapy 
may be used for comparison, e.g., the condition being treated is such 
that the use of a placebo or the withholding of treatment would be 
inappropriate or contrary to the interest of the patient;
    (d) Historical control. In certain circumstances, such as those 
involving diseases with high and predictable mortality or signs and 
symptoms of predictable duration or severity, or in the case of 
prophylaxis where morbidity is predictable, the results of use of the 
device may be compared quantitatively with prior experience historically 
derived from the adequately documented natural history of the disease or 
condition in comparable patients or populations who received no 
treatment or who followed an established effective regimen (therapeutic, 
diagnostic, prophylactic).
    (v) A summary of the methods of analysis and an evaluation of the 
data derived from the study, including any appropriate statistical 
methods utilized.
    (2) To insure the reliability of the results of an investigation, a 
well-controlled investigation shall involve the use of a test device 
that is standardized in its composition or design and performance.
    (g)(1) It is the responsibility of each manufacturer and importer of 
a device to assure that adequate, valid scientific evidence exists, and 
to furnish such evidence to the Food and Drug Administration to provide 
reasonable assurance that the device is safe and effective for its 
intended uses and conditions of use. The failure of a manufacturer or 
importer of a device to present to the Food and Drug Administration 
adequate, valid scientific evidence showing that there is reasonable 
assurance of the safety and effectiveness of the device, if regulated by 
general controls alone, or by general controls and performance 
standards, may support a determination that the device be classified 
into class III.
    (2) The Commissioner may require that a manufacturer, importer, or 
distributor make reports or provide other information bearing on the 
classification of a device and indicating whether there is reasonable 
assurance of the safety and effectiveness of the device or whether it is 
adulterated or misbranded under the act.
    (3) A requirement for a report or other information under this 
paragraph will comply with section 519 of the act. Accordingly, the 
requirement will state the reason or purpose for such request; will 
describe the required report or information as clearly as possible; will 
not be imposed on a manufacturer, importer, or distributor of a 
classified device that has been exempted from such a requirement in 
accordance with

[[Page 171]]

Sec. 860.95; will prescribe the time for compliance with the 
requirement; and will prescribe the form and manner in which the report 
or information is to be provided.
    (4) Required information that has been submitted previously to the 
Center for Devices and Radiological Health need not be resubmitted, but 
may be incorporated by reference.

[43 FR 32993, July 28, 1978, as amended at 53 FR 11253, Apr. 6, 1988]