As recently reported, the U.S. Food and Drug Administration (FDA) is proposing to simplify the way it classifies and reclassifies medical devices, opting to do so by administrative order rather the cumbersome rulemaking process. It published in the Federal Register the proposed changes to conform to provisions in the FDA Safety and Innovation Act (FDASIA).
According to the agency: “FDA is proposing these revisions to update its regulations to reflect these and other changes, and to ensure classification of devices in the lowest regulatory class consistent with the protection of the public health and the statutory scheme for device regulation,” as stated in the proposed rule.
The changes also would set up five categories of devices in class III, the most high-risk class, including:
(1) Devices that present known risks that cannot be controlled;
(2) Devices for which the risk-benefit profile is unknown or unfavorable;
(3) Devices for which a full review of manufacturing information is necessary;
(4) Devices for which premarket review of any change affecting safety or effectiveness is necessary;
(5) Combination products (where the primary mode of action for combination includes a drug for which a finding is required that the drug is safe and effective or a biological product for which a finding is required that it is safe, pure, and potent.
I. BACKGROUND
FDA is proposing to revise the regulations in part 860 (21 CFR part 860) to conform to recent changes made in FDASIA to sections 513(e) and 515(b) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 360c(e) and 360e(b)), which became effective on July 9, 2012. These provisions established processes for reclassification of devices by administrative order instead of by regulation. FDA also proposes to update other reclassification provisions and to clarify the meaning of certain terms related to device classification and reclassification.
II. COMMENTS AND INFORMATION
Submit either electronic or written comments on the proposed rule by June 23, 2014. For further information, contact: Marjorie Shulman, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. 1536, Silver Spring, MD 20993, 301-796-6572; or Stephen Ripley, Center for Biologics Evaluation and Research (HFM-17), Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448, 301-827-6210.
III. PROPOSED REVISIONS
FDASIA changed the procedures for reclassification of devices under section 513(e) of the FD&C Act, and for requiring PMAs for preamendments class III devices from notice and comment rulemaking under section 553 of the Administrative Procedure Act to an administrative order process. FDA is proposing these revisions to update its regulations to reflect these and other changes, and to ensure classification of devices in the lowest regulatory class consistent with the protection of the public health and the statutory scheme for device regulation.
A. Proposed Amendments to 21 CFR 860.3—Definitions
This section provides the key definitions for part 860. FDA proposes to amend § 860.3 to remove the paragraph designations and to list the definitions alphabetically. This proposed amendment would simplify adding any new definitions to this part. FDA is also proposing to change the term from “life-supporting or life-sustaining device” to the term “supporting or sustaining human life” to conform to the language of section 513 of the FD&C Act.
1. Definitions of Class I, II, and III
FDA proposes to amend the definitions of class I, class II, and class III by revising the definitions to reflect a key principle underlying device classification, namely, that a reasonable assurance of safety and effectiveness is necessary for all three device classes; however, the level of regulation necessary to provide such assurance should be closely tailored to the risk presented by a type of device. Explanatory language about general and special controls has been removed from the definitions of class I and II, respectively, to avoid repetition with the new proposed definitions for the terms “general controls” and “special controls”. Other minor changes are intended to improve the clarity and structure of these definitions.
FDA is also proposing changes to the definition of class III to provide greater clarity regarding which devices fall within this class, and to improve transparency and predictability in device classification and reclassification decisions. Section 513(a)(1)(C) of the FD&C Act provides a definition for class III devices.
An important aspect of this definition is that FDA must first determine that a device falls into one of the three categories that make the device potentially high risk to be eligible to be classified by FDA in class III because the FD&C Act explicitly reserves class III to devices that are intended for use in supporting or sustaining human life, of substantial importance in preventing impairment of health, or that present a potential unreasonable risk of illness or injury. The proposed definition retains this concept, reserving class III for devices that present heightened potential risks because they fall into one of three statutory categories. As a shorthand, this preamble will refer to devices described by section 513(a)(1)(C)(ii) of the FD&C Act as potentially high risk devices, although in some cases, such devices may be known to be high risk. Importantly, the proposed definition of class III refers to the initial statutory classification of postamendment (21 U.S.C. 360c(f)) and transitional devices (21 U.S.C. 360j(l)(1)) to make clear that such devices are placed into class III automatically, rather than by operation of the definition of class III at section 513(a)(1)(C) of the FD&C Act. Thus, the second part of the proposed definition of class III (under paragraph (b)) will apply to initial classification of preamendments devices and reclassification decisions for a type of device, but will not control classification decisions FDA renders in reviewing a premarket notification under section 510(k) of the FD&C Act.
To address the need for greater clarity and promote consistent expectations about device classification, FDA is proposing to identify those potentially high risk devices for which insufficient information exists to determine that special and general controls would provide RASE. Under section 513(a)(2)(C) of the FD&C Act, the safety and effectiveness of a device are determined by evaluating its risks and benefits; thus, after FDA has determined a device is potentially high risk, FDA must still determine the risks, benefits, and appropriate regulatory controls to determine whether the device should be classified into class III. The proposed regulation would identify five categories of devices for classification into class III based on the risks, benefits, and available controls for the three device classes:
Devices that present known risks that cannot be controlled. This category encompasses devices that have a favorable benefit- risk profile even though they present significant risks that cannot be adequately controlled through general and special controls. Because special controls cannot fully address the risks presented, the highest level of regulation is necessary to minimize those risks.
Devices for which the risk-benefit profile is unknown or unfavorable. For most devices that enter the market each year after premarket review by FDA, FDA evaluates the safety and effectiveness of the device—and its risks and benefits—by determining in the context of the review of a premarket notification under section 510(k) of the FD&C Act whether the device is substantially equivalent to a legally marketed predicate device; thus, FDA assesses safety and effectiveness through a comparison to a predicate. FDA believes comparison to a predicate device is appropriate for the overwhelming majority of devices subject to premarket review, including many devices that are intended for use in supporting or sustaining human life, of substantial importance in preventing impairment of health, or that present a potential unreasonable risk of illness or injury.
For certain potentially high risk technologies, however, the risks or benefits may not be sufficiently well understood to allow meaningful comparison of a device to a predicate device. If the risks and benefits of a device are unknown, FDA may be unable to identify the performance parameters relevant to risks and benefits that would allow FDA to assess safety and effectiveness through a comparison to a predicate. On the other hand, if FDA does have information concerning the risks and/or benefits of a type of device, but the known benefits do not justify the known risks, there cannot be sufficient information to determine that general controls and special controls are sufficient to provide RASE, unless the applicant provides additional valid scientific evidence independently establishing a favorable benefit/risk profile for the device. The proposed rule would provide clear language classifying into class III potentially high risk devices for which the risk/benefit profile is unknown or unfavorable.
Devices for which a full review of manufacturing information is necessary. Even when the risk/benefit profile of a device is well-established, for certain potentially high risk devices, the risks may be of a type or degree that can only be adequately addressed by relatively stringent controls. Among the relatively stringent controls applied to class III devices are, in addition to the requirement for approval of an application containing valid scientific evidence independently establishing RASE for the device, the requirement to provide full manufacturing information about a device for FDA review before it may enter the market. FDA may be aware, for example, from experience with a particular device type, that certain aspects of the manufacturing process are critical to the safety or effectiveness of the device, which makes review of the manufacturing process necessary prior to marketing.
Devices for which premarket review of any change affecting safety or effectiveness is necessary. Similarly, when approval of a premarket submission for any change to a device that affects safety or effectiveness is necessary to provide RASE, general and special controls are insufficient to provide RASE, and classification in class III is necessary. Section 515(d)(6) of the FD&C Act provides explicit authority to require premarket approval of a supplemental application for any change to an approved device that affects safety or effectiveness (with the exception of changes to certain manufacturing methods or procedures, for which a notice to FDA must be submitted 30 days prior to implementation). FDA considers this to be a regulatory control reserved for class III devices. For higher risk devices with unique design characteristics or manufacturing processes, it is essential for FDA to assess any change that affects safety or effectiveness premarket to ensure that RASE is maintained, for example because of the cumulative impact that multiple changes may have on the safety or effectiveness of the device over time. FDA proposes that devices for which premarket review of any change that affects safety or effectiveness is necessary to provide RASE be classified in class III.
Combination products. The last proposed category of class III devices are devices that provide the primary mode of action for combination products that include a drug constituent part for which a finding is required that the drug constituent part be safe and effective, or include a biological product constituent part for which a finding is required that the biological product constituent part be safe, pure, and potent, and such a finding has not been made. Accordingly, the proposed rule would classify such devices in class III, subject to premarket approval.
2. Other Definitions
FDA proposes to amend the definition of generic type of device to address confusion about the inter-relationship among product code (procode), generic type, and classification regulation. In general, these represent levels of device categorization, with the lowest range of differences at the procode level and the highest range of differences at the classification regulation level, though sometimes the levels are coextensive. The terms “device,” “device type,” and “generic device type” are often used in the FD&C Act and implementing regulations interchangeably. As explained in the guidance entitled “Medical Device Classification Product Codes—Guidance for Industry and Food and Drug Administration Staff,” CDRH assigns three letter “procodes” to devices to group and track them for various purposes.
FDA proposes to amend the definition of “generic type of device” to make clear that a generic type may include one or more procodes, and a single classification regulation may include one or more generic types of device and may even, in some instances, straddle device classes.
FDA proposes to remove the definitions for classification questionnaire and supplemental data sheet because FDA is proposing to remove the requirement that this form be included as part of the reclassification procedures under § 860.84 and a reclassification petition under § 860.123. FDA believes the proposed definitions, when finalized, will clarify the classification criteria for panels, FDA, and all stakeholders and thus obviate the need for this form.
FDA proposes to add a definition of general controls for medical devices that harmonizes with the definition in section 513(a)(1)(A) of the FD&C Act. While explanations of general controls have been provided in guidance, adding the definition to this regulation will provide another opportunity to clarify which controls are included as general controls.
FDA proposes to replace the term “implant” with the term “implantable device,” which FDA proposes to have the same definition as “implant.”
FDA proposes to add a definition of special controls to clarify the regulatory significance of special controls as the controls necessary to provide RASE for a type of device classified in class II, which must be met for a device to be in class II.
FDA proposes to add a definition of “special controls guideline.” Under section 513(a) of the FD&C Act, a special controls guideline is a means for providing RASE for a class II device. While the guideline establishes a mandatory level of regulatory controls that must be met for the device to be in class II, manufacturers may comply with the guideline either by following the particular controls described in the guideline or by using alternative mitigation measures but demonstrating to the Agency’s satisfaction that those alternative measures provide the same or greater level of assurance of safety and effectiveness.
B. Proposed Amendments to 21 CFR 860.7—Determination of Safety and Effectiveness
This section provides the relevant factors FDA and classification panels will consider in reviewing evidence of device safety and effectiveness. The proposed provision clarifies class II classification or reclassification requirements for safety and effectiveness. FDA proposes to amend § 860.7(b) and (g)(1) to include establishment of special controls for class II devices, replacing the term performance standards because special controls include performance standards. Under section 513(a)(1)(B) of the FD&C Act, special controls includes the issuance of performance standards, postmarket surveillance, patient registries, development and dissemination of guidelines (including guidelines for the submission of clinical data in premarket notification of submissions in accordance with section 510(k)), recommendations and other appropriate actions as the FDA deems necessary to provide such assurance.
FDA is proposing additional minor changes in paragraphs § 860.7(c)(2) and (d)(2) to update terminology and to reflect changes in the FD&C Act.
C. Proposed Amendments to 21 CFR Part 860.84—Classification Procedures for “Preamendments Devices”
This section explains the procedures and criteria for original classification of preamendments devices. FDA proposes to amend § 860.84 by removing the term “old devices” as a reference to medical devices in commercial distribution before May 28, 1976. The terminology FDA more commonly uses is “preamendments devices.” May 28, 1976, is the date of enactment of the Medical Device Amendments of 1976.
FDA further proposes removing the requirement to answer the classification questionnaire and provide information using the supplemental data sheet. The classification questionnaire provides recommendations and information for FDA to consider during the classification process. The supplemental data sheet is information compiled by a classification panel or submitted in a petition for reclassification. As FDA has gained experience with the classification processes, questions concerning the utility of the classification questionnaire and supplemental data sheet have arisen. FDA believes that a more efficient use of FDA and petitioner resources would be to focus on the information the petitioner provides concerning review of available valid scientific evidence, appropriate regulatory controls given the risks presented by the device, and regulatory standards to understand whether general controls are sufficient to provide RASE or whether general controls and special controls are sufficient to provide RASE.
FDA proposes to amend § 860.84(d)(5) and (g)(2) to include establishment of special controls for class II devices. “Special controls” is the more inclusive term. Under section 513(a)(1)(B) of the FD&C Act, special controls includes the issuance of performance standards, postmarket surveillance, patient registries, development and dissemination of guidelines (including guidelines for the submission of clinical data in premarket notification of submissions in accordance with section 510(k)), recommendations, and other appropriate actions as the FDA deems necessary to provide such assurance.
FDA proposes additional minor changes to § 860.84(a), (d)(4), (d)(6), (e), and (g)(3) to reflect the changes in the FD&C Act and to update terminology.
D. Proposed New 21 CFR 860.90—Consultation With Panels
FDA proposes to add a new section to explain how FDA consults with panels regarding classification of preamendments devices. This provision for the most part mirrors § 860.125, which outlines the means by which FDA consults with panels for reclassifications.
E. Proposed Amendments to 21 CFR 860.93—Classification of Implantable
Devices and Devices Intended for a Use in Supporting or Sustaining Human Life
This section explains the special requirements for classifying any implantable device or device intended for a use in supporting or sustaining human life. FDA proposes to replace the term “implant” with the newly proposed term “implantable device” throughout this section. We also propose to add clarifying provisions that any class II classification recommendation for any implantable device or device intended for a use in supporting or sustaining human life from a classification device panel must identify and describe any special controls that are necessary to provide RASE. For any implantable device or device intended for a use in supporting or sustaining human life the Commissioner of Food and Drugs classifies or reclassifies into class II, the Commissioner must identify and describe any special controls that are necessary to provide RASE.
F. Proposed Amendments to 21 CFR 860.95—Exemptions From Sections 510, 519, and 520(f) of the FD&C Act
This section discusses exemptions from registration, product listing, and premarket notification in section 510 of the FD&C Act, records and reports in section 519 of the FD&C Act (21 U.S.C. 360i), and good manufacturing practice requirements in section 520(f) of the FD&C Act. FDA proposes additional changes to paragraphs § 860.95(a) and (b) to reflect changes in the FD&C Act that a class II device may be exempted from the premarket notification requirements if premarket notification is not necessary to assure the safety and effectiveness of the device.
G. Proposed Amendments to 21 CFR 860.120—General
This section explains the criteria for reclassifying medical devices under sections 513(e), 513(f), 514(b) (21 U.S.C. 360d(b)), 515(b), and 520(l) of the FD&C Act. FDA proposes to remove the term “substantial equivalence” in § 860.120(b) to clarify that reclassifying one device within a generic type of device reclassifies all devices within a generic type of device. As clarified in the proposed amendment to the definition of “generic type of device,” a classification may include more than one generic type. Thus a reclassification may reclassify all of the devices within a classification (either because a classification only includes one generic type or because FDA has decided to reclassify more than one generic type) or only one or more generic types within a classification. FDA proposes to revise § 860.120(c) to clarify that the Commissioner may reclassify class I, class II, and class III devices into any of the other of the three classes and to add provisions that list the sections of the FD&C Act under which the Commissioner may initiate reclassification of a medical device.
H. Proposed Amendments to 21 CFR 860.123—Reclassification Petition: Content and Form
This section provides the form and content of reclassification petitions. FDA proposes to remove the requirement to include in a reclassification petition a completed classification questionnaire and supplemental data sheet. The classification questionnaire provides recommendations and information for FDA to consider during the classification process. The supplemental data sheet is information compiled by a classification panel or submitted in a petition for reclassification.
In paragraph § 860.123(b)(2), FDA proposes to clarify a reference to section 513(f) in the FD&C Act to the more specific section 513(f)(3).
I. Proposed Amendments to 21 CFR 860.125—Consultation With Panels
This section provides the procedures under which FDA’s Commissioner consults with classification panels in the context of reclassification. FDA proposes to add language to clarify when consultation with a panel is required and when consultation is optional. In particular, FDA proposes to add language to § 860.125(c) to reflect the FDASIA change that requires FDA to convene a classification panel meeting prior to reclassifying a device under section 513(e) of the FD&C Act.
J. Proposed Amendments to 21 CFR 860.130—General Procedures Under Section 513(e) of the FD&C Act
This section provides the procedures for reclassifying a device based on new information under section 513(e) of the FD&C Act. FDA proposes to revise the procedure in § 860.130(c) to reflect the FDASIA requirement that devices reclassified under section 513(e) of the FD&C Act be reclassified using an administrative order procedure. FDA also proposes to add language to clarify that the Commissioner may reclassify class I, class II, and class III devices into any of the other of the three classes under the criteria set forth in § 860.3 for each class of device.
In § 860.130(d) FDA proposes revisions to reflect the FDASIA process that FDA will use to reclassify a device under section 513(e) of the FD&C Act. Prior to the publication of a final order, FDA must also publish a proposed order in the Federal Register and consider any comments submitted on the proposed order. FDA must, in addition, hold a device classification panel meeting (21 U.S.C. 360c(b)). The panel meeting must occur before the final order is published, and may occur either before or after the proposed order is published. The proposed order must include the following: (1) A substantive summary of valid scientific evidence, including the public health benefits and risks of the device; (2) when reclassifying from class II to class III, an explanation that general and special controls are insufficient to reasonably assure safety and effectiveness; and (3) when reclassifying from class III to class II an explanation that general and special controls are sufficient to reasonably assure safety and effectiveness.
FDA proposes revisions to § 860.130 (f) and (g) to reflect the change to an administrative order process. FDA further proposes to revise § 860.130(g) to reflect that the administrative order may establish special controls to provide RASE of the device.
K. Proposed Amendments to 21 CFR 860.132—Procedures When the Commissioner Initiates a Performance Standard or Premarket Approval Proceeding Under Sections 514(b) or 515(b) of the FD&C Act
This section explains the procedures for an interested person to request reclassification of a device after FDA initiates a proceeding for the establishment of a performance standard or for requiring premarket approval. FDA proposes removing premarket approval proceedings from the process currently outlined in § 860.132(b) since the corresponding statutory requirement was removed by FDASIA (pre-FDASIA section 515(b)(2)(B)) of the FD&C Act). Instead, FDA proposes new § 860.132(b) and (c), providing that reclassification requests received during premarket approval proceedings will either be denied, if FDA does not agree that a change in classification is warranted, or granted, in which case FDA will follow the reclassification process under section 513(e) of the FD&C Act.
FDA proposes new § 860.132(d) for requests for reclassification during a performance standard proceeding, the process for which would remain largely unchanged. FDA proposes to remove the requirement in current § 860.132(b)(3) that a grant or denial of a petition to reclassify a device must be by order published in the Federal Register. Publishing the administrative order in the Federal Register is not required by statute and adds an unnecessary step to the process. FDA proposes to extend the time for filing a petition for reclassification in § 860.132(b)(1) to 30 days.
L. Proposed Addition of 21 CFR 860.133—Procedures When the Commissioner Initiates a Proceeding to Require Premarket Approval Under Section 515(b) of the FD&C Act
FDA proposes to add § 860.133 to describe the process for requiring the filing of a PMA for class III preamendments devices under section 515(b) of the FD&C Act (also referred to as a “call for PMAs”). FDASIA changes the process that FDA uses to require the filing of PMAs or completion of PDPs from a rulemaking process to an administrative order process. Under proposed § 860.133(b), a final order will include any recommendation to the Commissioner from a classification panel regarding the classification. Prior to the publication of a final order, FDA must also publish a proposed order in the Federal Register and consider any comments submitted on the proposed order. FDA must, in addition, hold a device classification panel meeting (21 U.S.C. 360c(b)). The panel meeting must occur before the final order is published, and may occur either before or after the proposed order is published. The proposed order must include the following: (1) A substantive summary of valid scientific evidence, including the public health benefits and risks of the device; (2) when reclassifying from class II to class III, an explanation that general and special controls are insufficient to reasonably assure safety and effectiveness; and (3) when reclassifying from class III to class II an explanation that general and special controls are sufficient to reasonably assure safety and effectiveness.
M. Proposed Amendments to 21 CFR 860.134—Procedures for “Postamendment Devices” Under Section 513(f)(3) of the FD&C Act and Reclassification of Certain Devices
This section explains the procedures for reclassifying postamendments devices that are class III by operation of section 513(f)(1) of the FD&C Act. FDA proposes to amend § 860.134 by removing the term “new devices” as a reference to medical devices in commercial distribution after May 28, 1976. The terminology FDA more commonly uses is “postamendment devices.” May 28, 1976, is the date of enactment of the Medical Device Amendments of 1976. FDA further proposes to clarify a reference to section 513(f) in the FD&C Act to the more specific section 513(f)(3) and to add a reference to “de novo” classification under section 513(f)(2) to § 860.134(a) to reflect a change made by FDASIA to section 513(f)(1).
FDA proposes to add new § 860.134(c), detailing the process where reclassification is initiated by FDA rather than a petition. This process would consist of a proposed reclassification order, optional panel consultation, and a final reclassification order published in the Federal Register following consideration of comments and any panel recommendations or comments. FDA further proposes to add new paragraph 860.134(d) to reflect that the administrative order may establish special controls to provide RASE of the device.
N. Proposed Amendments to 21 CFR 860.136—Procedures for Transitional Products Under Section 520(l) of the FD&C Act
FDA proposes to revise § 860.136(a) to add reclassification initiated by FDA and proposes to revise § 860.136(b) to apply to reclassification initiated by manufacturer or importer.
FDA proposes to add new § 860.136(c), detailing the process where reclassification is initiated by FDA rather than a petition. This process would consist of a proposed reclassification order, optional panel consultation, and a final reclassification order published in the Federal Register following consideration of comments and any panel recommendations or comments. The proposed amendments to § 860.136 also include provisions making clear that reclassification orders under this section may establish special controls for a device reclassified into class II to provide RASE of the device. FDA also proposes to remove the requirement for a part 16 hearing because we believe the process providing for a proposed order, panel consultation, consideration of comments, and final order provide sufficient opportunity for participation and review of reclassifications of transitional devices.