device, the classification panels and the Commissioner may consider safety and effectiveness data developed for another device in the same generic type, regardless of whether such data are regarded currently as confidential under paragraph (c)(1) of this section.

with

(d)(1) The fact of its existence and the contents of a petition for reclassification filed in accordance §860.130 or §860.132 are available for public disclosure at the time the petition is received by the Food and Drug Administration.

(2) The fact of the existence of a petition for reclassification filed in accordance with §860.134 or §860.136 is available for public disclosure at the time the petition is received by the Food and Drug Administration. The contents of such a petition are not available for public disclosure for the period of time following its receipt (not longer than 30 days) during which the petition is reviewed for any deficiencies preventing the Commissioner from making a decision on it. Once it is determined that the petition contains no deficiencies preventing the Commissioner from making a decision on it, the petition will be filed with the Dockets Management Branch and its entire contents will be available for public disclosure and subject to consideration by classification panels and by the Commissioner in making a decision on the petition. If, during this 30-day period of time, the petition is found to contain deficiencies that prevent the Commissioner from making a decision on it, the petitioner will be so notified and afforded an opportunity to correct the deficiencies.

Thirty days after notice to the petitioner of deficiencies in the petition, the contents of the petition will be available for public disclosure unless, within that 30 days, the petitioner submits supplemental material intended to correct the deficiencies in the petition. The Commissioner, in the Commissioner's discretion, may allow withdrawal of a deficient petition during the 30-day period provided for correcting deficiencies. Any supplemental material submitted by the petitioner, together with the material in the original petition, is considered as a new petition. The new petition is reviewed for

deficiencies in the same manner as the original petition, and the same procedures for notification and correction of deficiencies are followed. Once the petitioner has corrected the deficiencies, the entire contents of the petition will be available for public disclosure and subject to consideration by classification panels and by the Commissioner in making a decision on the petition. Deficient petitions which have not been corrected within 180 days after notification of deficiency will be returned to the petitioner and will not be considered further unless resubmitted.

(e) The Commissioner may not disclose, or use as the basis for reclassification of a device from class III to class II, any information reported to or otherwise obtained by the Commissioner under section 513, 514, 515, 516, 518, 519, 520(f), 520(g), or 704 of the act that falls within the exemption described in §20.61 of this chapter for trade secrets and confidential commercial information. The exemption described in § 20.61 does not apply to data or information contained in a petition for reclassification submitted in accordance with § 860.130 or §860.132, or in a petition submitted in accordance with §860.134 or §860.136 that has been determined to contain no deficiencies that prevent the Commissioner from making a decision on it. Accordingly, all data and information contained in such petitions may be disclosed by the Commissioner and used as the basis for reclassification of a device from class III to class II.

(f) For purposes of this section, safety and effectiveness data include data and results derived from all studies and tests of a device on animals and humans and from all studies and tests of the device itself intended to establish or determine its safety and effective

ness.

§ 860.7 Determination of safety and ef

fectiveness.

(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 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 exist

ence 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 wellcontrolled 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 wellcontrolled 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 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 § 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]

Subpart B-Classification

§ 860.84 Classification procedures for "old devices."

(a) This subpart sets forth the procedures for the original classification of a device that either was in commercial distribution before May 28, 1976, or is substantially equivalent to a device that was in commercial distribution before that date. Such a device will be classified by regulation into either class I (general controls), class II (special controls) or class III (premarket

approval), depending upon the level of regulatory control required to provide reasonable assurance of the safety and effectiveness of the device (§ 860.3(c)). This subpart does not apply to a device that is classified into class III by statute under section 513(f) of the act because the Food and Drug Administration has determined that the device is not "substantially equivalent" to any device subject to this subpart or under section 520(1) (1) through (3) of the act because the device was regarded previously as a new drug. In classifying a device under this section, the Food and Drug Administration will follow the procedures described in paragraphs (b) through (g) of this section.

(b) The Commissioner refers the device to the appropriate classification panel organized and operated in accordance with section 513 (b) and (c) of the act and part 14 of this chapter.

(c) In order to make recommendations to the Commissioner on the class of regulatory control (class I, class II, or class III) appropriate for the device, the panel reviews the device for safety and effectiveness. In so doing, the panel:

(1) Considers the factors set forth in §860.7 relating to the determination of safety and effectiveness;

(2) Determines the safety and effectiveness of the device on the basis of the types of scientific evidence set forth in § 860.7;

(3) Answers the questions in the classification questionnaire applicable to the device being classified;

(4) Completes a supplemental data sheet for the device;

(5) Provides, to the maximum extent practicable, an opportunity for interested persons to submit data and views on the classification of the device in accordance with part 14 of this chapter.

(d) Based upon its review of evidence of the safety and effectiveness of the device, and applying the definition of each class in §860.3(c), the panel submits to the Commissioner a recommendation regarding the classification of the device. The recommendation will include:

(1) A summary of the reasons for the recommendation;

(2) A summary of the data upon which the recommendation is based,

(3) An identification of the risks to health (if any) presented by the device;

(4) In the case of a recommendation for classification into class I, a recommendation as to whether the device should be exempted from the requirements of one or more of the following sections of the act: section 510 (registration, product listing, and premarket notification) section 519 (records and reports) and section 520(f) (good manufacturing practice regulations) in accordance with § 860.95;

(5) In the case of a recommendation for classification into class II or class III, to the extent practicable, a recommendation for the assignment to the device of a priority for the application of a performance standard or a premarket approval requirement;

(6) In the case of a recommendation for classification of an implant or a life-supporting or life-sustaining device into class I or class II, a statement of why premarket approval is not necessary to provide reasonable assurance of the safety and effectiveness of the device, accompanied by references to supporting documentation and data satisfying the requirements of §860.7, and an identification of the risks to health, if any, presented by the device.

(e) A panel recommendation is regarded as preliminary until the Commissioner has reviewed it, discussed it with the panel if appropriate, and published a proposed regulation classifying the device. Preliminary panel recommendations are filed in the Dockets Management Branch's office upon receipt and are available to the public upon request.

(f) The Commissioner publishes the panel's recommendation in the FEDERAL REGISTER, together with a proposed regulation classifying the device, and other devices of that generic type, and provides interested persons an opportunity to submit comments on the recommendation and proposed regula

tion.

(g) The Commissioner reviews the comments and issues a final regulation classifying the device and other devices of that generic type. The regulation will:

(1) If classifying the device into class I, prescribe which, if any, of the requirements of sections 510, 519, and 520(f) of the act will not apply to the device and state the reasons for making the requirements inapplicable, in accordance with § 860.95;

(2) If classifying the device into class II or class III, at the discretion of the Commissioner, establish priorities for the application to the device of a performance standard or a premarket approval requirement;

(3) If classifying an implant, or lifesupporting or life-sustaining device, comply with §860.93(b).

[43 FR 32993, July 28, 1978, as amended at 57 FR 58404, Dec. 10, 1992; 64 FR 404, Jan. 5, 1999]

§860.93 Classification of implants, lifesupporting or life-sustaining devices.

(a) The classification panel will recommend classification into class III of any implant or life-supporting or lifesustaining device unless the panel determines that such classification is not necessary to provide reasonable assurance of the safety and effectiveness of the device. If the panel recommends classification or reclassification of such a device into a class other than class III, it shall set forth in its recommendation the reasons for so doing together with references to supporting documentation and data satisfying the requirements of §860.7, and an identification of the risks to health, if any, presented by the device.

(b) The Commissioner will classify an implant or life-supporting or life-sustaining device into class III unless the Commissioner determines that such classification is not necessary to provide reasonable assurance of the safety and effectiveness of the device. If the Commissioner proposes to classify or reclassify such a device into a class other than class III, the regulation or order effecting such classification or reclassification will be accompanied by a full statement of the reasons for so doing. A statement of the reasons for not classifying or retaining the device in class III may be in the form of concurrence with the reasons for the recommendation of the classification