21 C.F.R. Subpart A—General
Title 21 - Food and Drugs
(a) This part implements sections 513, 514(b), 515(b), and 520(l) of the act with respect to the classification and reclassification of devices intended for human use. (b) This part prescribes the criteria and procedures to be used by classification panels in making their recommendations and by the Commissioner in making the Commissioner's determinations regarding the class of regulatory control (class I, class II, or class III) appropriate for particular devices. Supplementing the general Food and Drug Administration procedures governing advisory committees (part 14 of this chapter), this part also provides procedures for manufacturers, importers, and other interested persons to participate in proceedings to classify and reclassify devices. This part also describes the kind of data required for determination of the safety and effectiveness of a device, and the circumstances under which information submitted to classification panels or to the Commissioner in connection with classification and reclassification proceedings will be available to the public. For the purposes of this part: (a) Act means the Federal Food, Drug, and Cosmetic Act. (b) Commissioner means the Commissioner of Food and Drugs, Food and Drug Administration, United States Department of Health and Human Services, or the Commissioner's designee. (c) Class means one of the three categories of regulatory control for medical devices, defined below: (1) Class I means the class of devices that are subject to only the general controls authorized by or under sections 501 (adulteration), 502 (misbranding), 510 (registration), 516 (banned devices), 518 (notification and other remedies), 519 (records and reports), and 520 (general provisions) of the act. A device is in class I if (i) general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device, or (ii) there is insufficient information from which to determine that general controls are sufficient to provide reasonable assurance of the safety and effectiveness of the device or to establish special controls to provide such assurance, but the device is not life-supporting or life-sustaining or for a use which is of substanial importance in preventing impairment of human health, and which does not present a potential unreasonable risk of illness of injury. (2) Class II means the class of devices that is or eventually will be subject to special controls. A device is in class II if general controls alone are insufficient to provide reasonable assurance of its safety and effectiveness and there is sufficient information to establish special controls, including the promulgation of performance standards, postmarket surveillance, patient registries, development and dissemination of guidance documents (including guidance on the submission of clinical data in premarket notification submissions in accordance with section 510(k) of the act), recommendations, and other appropriate actions as the Commissioner deems necessary to provide such assurance. For a device that is purported or represented to be for use in supporting or sustaining human life, the Commissioner shall examine and identify the special controls, if any, that are necessary to provide adequate assurance of safety and effectiveness and describe how such controls provide such assurance. (3) Class III means the class of devices for which premarket approval is or will be required in accordance with section 515 of the act. A device is in class III if insufficient information exists to determine that general controls are sufficient to provide reasonable assurance of its safety and effectiveness or that application of special controls described in paragraph (c)(2) of this section would provide such assurance and if, in addition, the device is life-supporting or life-sustaining, or for a use which is of substantial importance in preventing impairment of human health, or if the device presents a potential unreasonable risk of illness or injury. (d) Implant means a device that is placed into a surgically or naturally formed cavity of the human body. A device is regarded as an implant for the purpose of this part only if it is intended to remain implanted continuously for a period of 30 days or more, unless the Commissioner determines otherwise in order to protect human health. (e) Life-supporting or life-sustaining device means a device that is essential to, or that yields information that is essential to, the restoration or continuation of a bodily function important to the continuation of human life. (f) Classification questionnaire means a specific series of questions prepared by the Commissioner for use as guidelines by classification panels preparing recommendations to the Commissioner regarding classification and by petitioners submitting petitions for reclassification. The questions relate to the safety and effectiveness characteristics of a device and the answers are designed to help the Commissioner determine the proper classification of the device. (g) Supplemental data sheet means information compiled by a classification panel or submitted in a petition for reclassification, including: (1) A summary of the reasons for the recommendation (or petition); (2) A summary of the data upon which the recommendation (or petition) is based; (3) An identification of the risks to health (if any) presented by the device; (4) To the extent practicable in the case of a class II or class III device, a recommendation for the assignment of a priority for the application of the requirements of performance standards or premarket approval; (5) In the case of a class I device, a recommendation whether the device should be exempted from any of the requirements of registration, record-keeping and reporting, or good manufacturing practice regulations; (6) In the case of an implant or a life-supporting or life-sustaining device for which classification in class III is not recommended, a statement of the reasons for not recommending that the device be classified in class III; (7) Identification of any needed restrictions on the use of the device, e.g., whether the device requires special labeling, should be banned, or should be used only upon authorization of a practitioner licensed by law to administer or use such device; and (8) Any known existing standards applicable to the device, device components, or device materials. (h) Classification panel means one of the several advisory committees established by the Commissioner under section 513 of the act and part 14 of this chapter for the purpose of making recommendations to the Commissioner on the classification and reclassification of devices and for other purposes prescribed by the act or by the Commissioner. (i) Generic type of device means a grouping of devices that do not differ significantly in purpose, design, materials, energy source, function, or any other feature related to safety and effectiveness, and for which similar regulatory controls are sufficient to provide reasonable assurance of safety and effectiveness. (j) Petition means a submission seeking reclassification of a device in accordance with §860.123. [43 FR 32993, July 28, 1978, as amended at 57 FR 58403, Dec. 10, 1992; 65 FR 56480, Sept. 19, 2000] (a) This section governs the availability for public disclosure and the use by the Commissioner of data and information submitted to classification panels or to the Commissioner in connection with the classification or reclassification of devices under this part. (b) In general, data and information submitted to classification panels in connection with the classification of devices under §860.84 will be available immediately for public disclosure upon request. However, except as provided by the special rules in paragraph (c) of this section, this provision does not apply to data and information exempt from public disclosure in accordance with part 20 of this chapter: Such data and information will be available only in accordance with part 20. (c)(1) Safety and effectiveness data submitted to classification panels or to the Commissioner in connection with the classification of a device under §860.84, which have not been disclosed previously to the public, as described in §20.81 of this chapter, shall be regarded as confidential if the device is classified in to class III. Because the classification of a device under §860.84 may be ascertained only upon publication of a final regulation, all safety and effectiveness data that have not been disclosed previously are not available for public disclosure unless and until the device is classified into class I or II, in which case the procedure in paragraph (c)(2) of this section applies. (2) Thirty days after publication of a final regulation under §860.84 classifying a device into class I or class II, safety and effectiveness data submitted for that device that had been regarded as confidential under paragraph (c)(1) of this section will be available for public disclosure and placed on public display in the office of the Division of Dockets Management, Food and Drug Administration unless, within that 30-day period, the person who submitted the data demonstrates that the data still fall within the exemption for trade secrets and confidential commercial information described in §20.61 of this chapter. Safety and effectiveness data submitted for a device that is classified into class III by regulation in accordance with §860.84 will remain confidential and unavailable for public disclosure so long as such data have not been disclosed to the public as described in §20.81 of this chapter. (3) Because device classification affects generic types of devices, in making determinations under §860.84 concerning the initial classification of a 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. (d)(1) The fact of its existence and the contents of a petition for reclassification filed in accordance with §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 Division of Dockets Management 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 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 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 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]
Title 21: Food and Drugs
PART 860—MEDICAL DEVICE CLASSIFICATION PROCEDURES
Subpart A—General
§ 860.1 Scope.
§ 860.3 Definitions.
§ 860.5 Confidentiality and use of data and information submitted in connection with classification and reclassification.
§ 860.7 Determination of safety and effectiveness.
