Docket No. FDA-2013-N-1529; Proposed Rule on Medical Device Classification Procedures

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1 701 Pennsylvania Avenue, NW Suite 800 Washington, D.C Tel: Fax: Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Rm Rockville, MD Re: Docket No. ; Proposed Rule on Medical Device Classification Procedures Dear Sir or Madam: The Advanced Medical Technology Association (hereinafter referred to as AdvaMed ) provides these comments regarding the Food and Drug Administration (FDA) proposed rule on Medical Device Classification Procedures. AdvaMed is the world s largest association representing manufacturers of medical devices, diagnostic products, and medical information systems. AdvaMed s members produce nearly 90 percent of the health care technology purchased annually in the United States and more than 50 percent of such technology purchased annually around the world. AdvaMed members range from the smallest to the largest medical technology innovators and companies. Nearly 70 percent of our members have less than $30 million in domestic sales annually. GENERAL COMMENTS AdvaMed submits our comments on the Food and Drug Administration s ( FDA or Agency ) proposed regulation that would potentially amend the Agency s longstanding classification and reclassification regulations. FDA s stated reason for this proposed rulemaking is to conform [the current classification and reclassification regulations] to recent changes made in the Food and Drug Administration Safety and Innovation Act (FDASIA) to section 513(e) and 515(b) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) Fed. Reg (March 25, 2014). FDA states that it also proposes to update other reclassification provisions and to clarify the meaning of certain terms related to device classification and reclassification. Id. In our review, the proposed rule outlines reclassification provisions inconsistent with FDASIA and appears to implement a number of fundamental changes to the current classification process. This includes substantial rewriting of the device class definitions, changes in well-settled terminology, and new definitions with likely significant impact on the reclassification process. We are concerned that the proposal exceeds the FDASIA device amendments to sections 513(e) and 515(b) and undermines the procedural protections Congress put in place to balance the FDA s desire for administrative orders in lieu of rulemaking for reclassification Bringing innovation to patient care worldwide

2 Page 2 of 17 of pre-amendment devices and calls for PMAs for pre-amendment Class III devices. While the revisions are set forth as clarifications to terms related to classification and reclassification, the Agency is proposing revisions that are both unnecessary and concerning. We believe that unsettling longstanding understandings of the classification process and attempting to integrate decision-making criteria into definitions that do not need clarification is a dangerous practice that can create confusion, inefficiency and weak decision-making for both the regulators and regulated persons. In other words, we believe the proposed revisions will cause confusion where there was none. It is also important to recognize that the classification process for a device is separate from the FDA decision whether to clear or approve the medical device, and allow market access for the product. Simply stated in light of the extensive revisions proposed, many of which are unrelated to the FDASIA provisions, and our significant concerns outlined below, we respectfully request the following: 1) FDA should issue a revised rule consistent with and limited to implementation of the FDASIA reform provisions. Particular attention must be paid to assure due process protections, including issuance of a proposed order to the public docket prior to holding of an advisory panel. 2) All other proposed changes (non-fdasia) should be issued as a separate proposed rule along with clear rationale articulated for why such changes are necessary (or deemed non-significant or clarifying ) and the specific cost estimates for such changes for further review and consideration by impacted stakeholders 1 as they have created significant concern and confusion with respect to well-settled and understood definitions and to the overall classification process. 3) Prior to issuance of the latter referenced rule unrelated to FDASIA, a workshop should be held to discuss FDA thinking and solicit feedback from stakeholders and public dialogue on what changes may be helpful and/or needed with respect to the device classification process. Our specific comments follow with detailed legal analysis and recommendations on classification definitions and processes contained in this draft proposed rule. Apart from our overall recommendations, we would welcome further dialogue on how to best ensure reclassification processes consistent with the current well-established framework and procedural due process protections as recently enacted by Congress. 1 Based on review and our interpretation of the proposed rule, the economic impact may be significantly underestimated and does not reflect the potential for substantial expansion of scope of devices requiring approval of a premarket application and the related costs and resource burdens associated with these applications as a result of these proposed changes. See Attachment AdvaMed Comments to the Office of Management and Budget Re. Docket No. FDA-2013-N (Even excluding any new requirements for clinical testing and PMA review fees, resulting annual spending would be in excess of $100 million and well approaching expenditure under the Unfunded Mandates Reform Act of ).

3 Page 3 of 17 SPECIFIC COMMENTS I. CLASSIFICATION DEFINITIONS FDA proposes to amend the definitions of Class I, Class II, and Class III devices to reflect a key principle underlying device classification; namely, that a reasonable assurance of safety and effectiveness is necessary for all three device classes and to ensure that the level of regulation is closely tailored to the risk presented by a type of device. 79 Fed. Reg. at 16252, AdvaMed believes that proposed revisions to the Class I definition are unnecessary and include subjective intent criteria inappropriate for inclusion. Further, the proposed definition for Class II as outlined would prohibit classification or reclassification of devices for which special controls are not established at the time of classification or reclassification. We are also concerned with the proposed revisions to the Class III definition because the inclusion of not substantially equivalent (NSE) and transitional devices into the definition conflicts with the statute s mechanism for automatically classifying NSE and transitional devices into Class III. Moreover, we believe that the proposed Class III definition invites substantial subjectivity into the device classification process by including numerous criteria that alter the FD&C Act s Class III definition. Importantly, the proposed changes to the FD&C Act s classification definitions through administrative rather than legislative mechanisms is inconsistent with the law and, we fear, will likely create uncertainty without benefit after decades of reliance on well-settled regulatory principles. A. The added subjective intent criteria for a Class I device could affect the types of devices that would qualify as Class I. AdvaMed believes that the proposed revisions to the Class I definition are not needed because the current definition is well-settled and, to date, has not presented issues. Importantly, AdvaMed believes that the proposed changes could affect the types of devices that qualify as Class I by making the classification judgment subjective. The new Class I definition proposes modifications to the criteria that must be fulfilled for a device to be considered Class I when there is insufficient information to determine that general controls are sufficient to provide reasonable assurance of the device s safety and effectiveness, or to establish special controls to establish such assurance. 79 Fed. Reg. at This modification introduces an intent criteria that could affect the Class I classification process. Specifically, instead of the current criteria that the device not be life-supporting or lifesustaining, the new definition requires that the device not be intended for a use in supporting or sustaining human life. See id. Similarly, instead of the current definitional requirement that the device not be for a use which is of substantial importance in preventing impairment of human health, the proposed new definition requires that the device not be intended for a use that is of substantial importance in preventing impairment of human health. See id. The intent criteria that the proposed definition introduces does not reflect the statutory requirement that the device is not purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance in preventing impairment of human health. See 513(a)(1)(A)(ii)(I) (emphasis added). Adding the intent criteria could affect the types of devices that qualify as Class I devices, and would make the classification judgment subjective, a departure from the FD&C Act s objective

4 Page 4 of 17 standard, i.e., purported or represented.... For example, an intent element would permit the Agency to challenge the purported or represented use of a device. AdvaMed believes that there is no need to modify a well-settled definition that, to date, has not presented issues for FDA or the regulated industry. Importantly, AdvaMed requests that FDA remove the proposed intent criteria that could potentially affect the types of devices that qualify as Class I by making the classification judgment subjective. B. The proposed revisions to the Class II definition would inappropriately prohibit classification/reclassification of devices for which special controls are not established at the time of the classification/reclassification order. AdvaMed believes that the proposed modifications to the Class II definition would improperly prohibit the classification or reclassification of devices for which no special controls are established at the time of the regulatory action. This revision of the Class II definition is contrary to the law and clear legislative intent. Under the FD&C Act s reclassification provisions, as long as there is sufficient evidence in the record to identify special controls that, in conjunction with general controls, would provide reasonable assurance of safety and effectiveness, the device type can be classified or reclassified. Accordingly, AdvaMed requests that FDA remove this novel requirement from the proposed regulation or modify its wording for which special controls could be but are not yet established. FD&C Act s Class II definition only requires sufficient information to establish special controls to provide [reasonable] assurance [of safety and effectiveness], 513(a)(1)(B), yet the proposed new definition for Class II devices omits the current regulation s introductory language to the Class II definition: Class II means the class of devices that is or eventually will be subject to special controls see 79 Fed. Reg. at 16260, and thereby appears to require the establishment of special controls in the reclassification order. It also makes several editorial revisions, including replacing... the Commissioner shall examine and identify the special controls with the Commissioner shall examine and establish the special controls. 2 Id. (emphasis added). The proposed new definition also deletes the listing of examples of special controls, e.g., performance standards and postmarket surveillance, and instead lists those special controls in the proposed definition of special controls. Id. We are concerned that deleting the definition s introductory language that includes devices that will eventually be subject to special controls appears to prohibit classifications or reclassifications of devices for which special controls are not established at the time of the final regulatory action. This concern is further emphasized by the proposed revision that directs the Commissioner to establish the special controls, instead of to identify those controls. See 79 Fed. Reg. at This is contrary to 1976 legislative history that states 2 The revised language includes additional editorial revisions that AdvaMed believes are unnecessary, including replacing and there is sufficient information to establish special controls with and for which sufficient information exists to establish special controls, and using the term reasonable assurance of safety and effectiveness instead of adequate assurance of safety and effectiveness. Id.

5 Page 5 of 17 that classifications for pre-amendment devices could occur without Class II and III controls being in place, see H. REP. NO , at 56 (1976) ( Following receipt of a panel s recommendation with respect to the classification of an old device, the Secretary is to promulgate a regulation classifying the device. In the case of a device classified into Class II or Class III, the Secretary is required to establish priorities which he may use in applying requirements with respect to performance standards and premarket clearance. ); see also H. REP. NO , at 26, 27 (1976) ( Devices classified into Class II eventually will be required to conform to performance standards. [... ] First, the Committee recognizes that a considerable period of time may elapse between classification of a device into Class II and development of a performance standard for it. ). The preamble to Part 860 of FDA s regulations also confirms that classifications can occur without controls in place. See 43 Fed. Reg (July 28, 1978) ( The legislative history reveals both that Congress recognized that considerable time may elapse between classification into Class II and the development of a performance standard for the device... and that FDA has ample latitude to classify a device into the premarket approval category in instances in which use of the device poses public health concerns. ) In some instances, for example, in the de novo context, requiring special controls at the time of classifying many devices may be appropriate to ensure that special controls exist for a novel device that will be the basis of a wholly new device regulation. Indeed, in that context, FDA s expeditious development of special controls should be encouraged for appropriate regulation of lower risk, novel devices for which classification into Class II would make the most sense for the public health. However, controls are not always required to be in place prior to device classification or reclassification. As a result, the introductory language of the current regulation should remain. AdvaMed urges that maintaining consistency with express Congressional intent in the regulations regarding the timing of special controls is required and important to facilitate reclassifications to maintain appropriate and efficient regulation of devices. FDA controls the classification process and can use its considerable discretion regarding the immediate need for a special control wisely. Accordingly, FDA should withdraw its proposed amendment to the Class II definition. C. The proposed revisions to the Class III definition conflicts with the current statutory classification mechanism, adds subjective intent criteria, and may be read to inappropriately expand the Class III definition. i. The proposed definition conflicts with the statutory classification mechanisms for classifying transitional and new, novel devices. In approaching a discussion on classification, it is important to recognize that, practically speaking, the classification process for a device is separate from the FDA decision whether to clear through 510(k) or approve through PMA, and to provide market access for that product. The risk/benefit assessment for a device applies to the decision to allow a device to be placed on the U.S. market, and devices whose risks outweigh its benefits are not and should not be permitted to be placed on the U.S. market. Regardless of the classification of a device, FDA has various legal mechanisms available to prevent its introduction into commercial distribution. The following discussion, which is detailed and legalistic in nature due to the

6 Page 6 of 17 complexities of classification and reclassification, should not be read to presume that AdvaMed supports the introduction of devices other than those that provide a positive contribution to the public health. FDA s proposed definition of Class III device that incorporates NSE post-amendment devices and transitional devices conflicts with the non-definitional statutory mechanisms for classifying these devices into Class III, and is inconsistent with the risk-based, or de novo, classification of NSE devices into Class II or I. See 79 Fed. Reg. at Therefore, we request that FDA remove the revision of the Class III definition from the proposed regulation. FDA explains that the inclusion of NSE and transitional devices into the Class III definition is proposed 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. Id. at It is inappropriate to include NSE and transitional devices into the Class III definition because the statute s mechanism for classifying NSE and transitional devices into Class III is separate and distinct from the Class III definition. See FD&C Act 513(f)(1) and 520(l)(1). In other words, a mechanism for classifying NSE and transitional devices into Class III exists under the law and this mechanism is not definitional. Rather, a device s NSE or transitional status results in an automatic Class III status and a premarket approval requirement, notwithstanding the definition of a Class III device. Moreover and importantly, including all NSE devices in the Class III definition would conflict with section 513(f)(2) of the FD&C Act that provides for the risk-based, or de novo, classification of NSE devices. Simply put, the process in section 513(f)(2) of the FD&C Act permits for an NSE device to be classified into Class II or I. Defining Class III as including NSE devices assumes an NSE determination is tantamount to a final classification status; however, this ignores the de novo classification process that evaluates NSE devices to determine whether a lower classification than Class III would be appropriate. The NSE status is not definitional and should be removed from FDA s proposed Class III definition. At a minimum, if the Agency insists on including NSE devices in the proposed definition, language must be added that makes the change consistent with the structure of the law, i.e., here, the existence of the FD&C Act s de novo provision. It should also be noted that the new proposed definition for Class III also reverses the statutory and current regulation s order of the criteria for defining a Class III device. Specifically, the proposed definition reverses the statutory order of criteria for defining Class III devices by first requiring that the devices meet certain substantive thresholds, e.g., intended for use in supporting or sustaining human life, and then considering whether there is insufficient information to show that general controls and/or special controls will provide a reasonable assurance of safety or effectiveness. See 79 Fed. Reg. at However, all things may not be equal, and the reordering of the FD&C Act s and the current regulation s criteria for the definition of a Class III device could subordinate the important Class III criteria of insufficient information to determine whether general and special controls are adequate. In other words, once FDA determines that, for example, a device is intended to support or sustain human life, it may more likely conclude that there is insufficient

7 Page 7 of 17 information that Class I and II controls are adequate to provide a reasonable assurance of safety and effectiveness. The changes with respect to reordering are unnecessary and confusing.. ii. The revised definition and intent criteria for Class III device departs from currently used terminology and makes judgment subjective. The proposed rule revises terminology and adds an intent criteria (as in the case of the Class I definition) that could potentially affect the types of devices that qualify as Class III. Instead of the Class III definition s current language that states:... the device is life-supporting or life sustaining, or for a use which is of substantial importance in preventing impairment of human health, the proposed revision states that a Class III device [i]s intended for a use in supporting or sustaining human life, or [i]s intended for a use that is of substantial importance in preventing impairment of human health. 79 Fed. Reg. at In particular, we note that this revision would make the classification judgment subjective, a departure from the FD&C Act s objective standard, i.e., purported or represented to be for a use in supporting or sustaining human life or for a use which is of substantial importance use in preventing impairment of human health. See FD&C Act 513(a)(1)(C). This revision could also create greater confusion in the classification process, such as classification of components used with a device system (which are subject to separate classification) as the risk of such accessory may differ from that of a device. We request that the current Class III definition remain unchanged. Alternatively, the subjective intent criteria should be removed and FDA should make explicit that the definition of supporting and sustaining human life is not meant to expand the meaning of the term under the statute. iii. Of foremost concern, the proposed Class III definition can be interpreted to inappropriately expand this class. These provisions raise the greatest concern amongst all of the proposed definitional changes. Notably, the proposal appears to create subjective rules to govern whether there is sufficient information that Class I or II controls will provide a reasonable assurance of safety and effectiveness will greatly expand the FD&C Act s definition of a Class III device. Specifically, applying the proposed rule s five non-statutory criteria or categories for classification into Class III based on the risks, benefits, and available controls for the three device classes could lead to Class III designations for many devices that currently would not be considered Class III devices. See id. at As a result, we have concern with introducing categories that would provide a basis for the Commissioner to conclude that there is insufficient information to determine that general or special controls will provide a reasonable assurance of safety and effectiveness. Id. at FDA explains that it is proposing these categories [t]o address the need for greater clarity and promote consistent expectations about device classification. Id. at AdvaMed believes the creation of these criteria is confusing and will not promote consistency because it will introduce regulatory tests into scientific questions for purposes of defining a regulatory classification. We are concerned that regulatory costs will also greatly increase and the use

8 Page 8 of 17 of newer medical technologies will be delayed to the detriment of patients. We ask that these proposed non-statutory categories be removed from any rulemaking. Our detailed concerns follow with respect to specific categories that FDA is proposing to find that general and/or special controls are insufficient to provide reasonable assurance of a device s safety and effectiveness. See 79 Fed. Reg. at We address each of these concerns below. a. FDA s proposal inappropriately bases a class III determination on a substantive judgment about the device s risk/benefit balance while ignoring substantial equivalence. FDA s proposed category for a Class III determination relates to a device that presents known risks that cannot be adequately controlled by general and special controls. 79 Fed. Reg. at 16255, This contemplates a judgment about the device s risk/benefit balance and ignores that such a judgment would be irrelevant to devices that are substantially equivalent to predicate devices. See 79 Fed. Reg. at 16255, In other words, the category ignores that a device with an unfavorable risk/benefit profile could be in Class II if it is substantially equivalent to a predicate device. These categories are concerning and at odds with the FD&C Act. FDA explains that [t]his category encompasses devices that have a favorable risk/benefit profile even though they present significant risks that cannot be adequately controlled through general and special controls. Id. at A second category refers to situations where a substantial equivalence review is not adequate to establish that the device has a favorable risk/benefit ratio because (A) the benefits of the device are unknown, (B) the risks of the device are unknown, or (C) the known benefits do not justify the known risks. Id. at 16255, FDA explains that although for most devices, comparison to a predicate is appropriate, [f]or certain potentially high risk devices, however, the risks or benefits may not be sufficiently well understood to allow meaningful comparison of a device to a predicate device. Id. at Applying these categories could lead to finding that historically substantially equivalent devices are NSE, and Class III, because of an unfavorable risk/benefit judgment for the new device. Such proposed categories would abandon the statutory definition of substantial equivalence in favor of a PMA-like standard that does not include a comparison to a predicate device, i.e., the benefit/risk assessment is not relative to a predicate, but focused solely on the new device. Specifically, a device is substantially equivalent to a predicate if (1) it has the same intended use and the same technological characteristics as the predicate; or (2) it has the same intended use as the predicate and has different technological characteristics, and the information submitted to FDA does not raise new types of questions of safety and effectiveness and demonstrates that the device is at least as safe and effective as the legally marketed device. In effect, the risk/benefit comparison is subsumed in this type of substantial equivalence comparison. Moreover, a conclusion that a device with an unfavorable risk/benefit profile is necessarily Class III, even where a non-class III predicate device exists, directly conflicts with the FD&C Act. See FD&C Act 510(k) & 513(f)(1).

9 Page 9 of 17 Even assuming a risk/benefit evaluation of new devices was appropriate in the context of 510(k) reviews of potentially high-risk technologies, concerns remain about the individual criteria that FDA identifies in the second category described above. Specifically, FDA s proposed category refers to situations where a 510(k) evaluation is not adequate because a favorable benefit/risk assessment cannot occur when: (A) the benefits of the device are unknown; (B) the risks of the device are unknown; and (C) the known benefits do not justify the known risks. 79 Fed. Reg. at The proposed criteria could be used to supplant the statutory criteria for substantial equivalence and justify a benefit/risk assessment that is not relative to a predicate, but focused solely on the new device. This type of risk/benefit conclusion makes an absolute judgment about the new device, and ignores that a substantial equivalence determination is based on a comparison of the new device to a predicate. Importantly, both the new device and the predicate device could have the same risk/benefit balance that FDA believes is unfavorable and yet legally, the new device could be found substantially equivalent to the predicate device. By applying the risk-benefit standard in the proposed manner, FDA would in effect be using a premarket process to affect a compliance remedy by barring the new device from commercial distribution without adequate process. Importantly, a finding of substantial equivalence is not a finding that the device complies with the FD&C Act, and FDA s substantial equivalence (SE) orders make this clear. If FDA has reason to believe that the device will likely be unsafe or ineffective, the Agency can alert the recipient of the SE order that the device may not be marketed because it is misbranded or adulterated. Simply put, the Agency has means to keep unsafe or ineffective devices off the market, and should not use the classification process to avoid burdens of proof for purposes of compliance. b. FDA s language could be read to inappropriately propose to classify devices into Class III to ensure GMP compliance. We are concerned that the proposed rule could be interpreted as using Class III as a means to ensure GMP compliance. In other words, it appears to inappropriately seek to achieve compliance through a premarket process instead of postmarket enforcement controls. In particular, we are concerned about the criteria for a Class III finding that the [r]eview of a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and, when relevant, packing and installation of, each device within the generic type is necessary to provide a reasonable assurance of safety and effectiveness. See 79 Fed. Reg. at , This criteria places devices that are otherwise eligible for a substantial equivalence review into the Class III category. FDA explains that the need for this criteria is based on its inability to practically review manufacturing in the 510(k) context, schedule inspections within the 90-day period for 510(k) reviews, and that under section 513(f)(5) of the FD&C Act, the Agency cannot withhold a substantial equivalence determination based on a failure to comply with GMPs. See id. at It appears that FDA would apply this category mainly to devices that are potentially high risk, see 79 Fed. Reg. at ( when a review of a full description of the methods used in, and the facilities and controls used for, the manufacture, processing, and when relevant, packing and installation, of a device is necessary to provide RASE (reasonable assurance of safety and

10 Page 10 of 17 effectiveness) for a potentially high risk device, general and special controls are inadequate to provide RASE and the device thus meets the statutory definition of Class III. ). The proposed rule should better reflect that 510(k) is a classification provision, not an approval authority. As such, and unlike PMAs, pre-clearance inspections have no relevance to the substantial equivalence question, and likewise, manufacturing information in 510(k)s will not address the equivalence issue, except for certain design information that is essential to a device description. We are concerned that FDA is seeking to achieve compliance through a premarket process where due process rights are greatly diminished, and where FDA carries no burden of proof to establish violations that will keep products off the market. Nonetheless, the Agency has statutory means to keep non-gmp compliant products off the market when certain public health criteria are met, and does not need to build this compliance goal into the device classification process. Rather than list information required in a premarket application, FDA can act with respect to GMP violations. If the failure to have compliant GMPs creates a serious risk to health, FDA can also withhold a substantial equivalence decision. However, the decision to not clear a medical device for this reason does not automatically place the product into Class III. c. FDA can review changes that affect safety or effectiveness without placing a device into Class III. We are also concerned about FDA s suggestion that all changes that affect a device s safety or effectiveness require a Class III premarket review. Specifically, FDA proposes a category for making a finding that general and/or special controls are insufficient to provide reasonable assurance of a device s safety and effectiveness that relates to changes to a device that affect safety or effectiveness. 79 Fed. Reg. at 16256, In this context, FDA states that [f]or higher risk devices with unique design characteristics or manufacturing processes, it is essential for FDA to assess any change that affects safety or effectiveness to ensure that RASE is maintained. Id. at As a result, 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. Id. This proposal appears to ignore that such device could be found substantially equivalent to a Class II device and changes to such device that significantly affects safety or effectiveness could be made through premarket notification, and does not necessitate that a device must be placed into Class III to protect the public health. d. A class III designation should not be preemptively assigned for combination products regulated as a device that incorporate a drug or biologic component, as FDA s proposal seems to suggest. The presence of a drug component should not define the device s classification status. FDA s proposal appears to inappropriately and without basis requires a Class III designation for a device with a drug or biologic component. Specifically, FDA proposes as a category of Class III devices those 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

11 Page 11 of 17 constituent part be safe and effective, or include a biological product constituent part for which a finding is required that the biological constituent part be safe, pure, and potent, and such a finding has not been made. 57 Fed. Reg. at 16256, This proposal ignores that combination products have no independent jurisdictional status and are regulated as drugs or devices, or under certain circumstances, both drug and device authorities. In implementing the 1990 amendments, the Agency stated that if a product is a combination of a drug and a device and the primary mode of action is attributed to the device, and the drug functions to enhance the device effect, the product will be regulated as a device. 56 Fed. Reg , (April 5, 1991). This statement makes it clear that combination products have no jurisdictional status under the FD&C Act and products are regulated as either drugs, devices or biologics; see also Intercenter Agreement Between the Center for Drug Evaluation and Research and the Center for Device and Radiological Health (stating that [a] device containing a drug substance as a component with the primary purpose of the combination being to fulfill a device function is a combination product and will be regulated as a device by CDRH. ). Where a combination product is regulated as a device, the fact that it contains a drug component is not presumptive of its classification status. The proposed language suggests that the medical device is Class III simply by fact that the device specific route of administration is not approved. In the case where the device itself is high-risk and/or novel and the new drug/biological entity is not approved, these products would be appropriately classified as Class III (unless placed in a lower classification through the de novo process). In other words, the device s drug component s safety and effectiveness profile should not have an independent impact on the classification of the device into which it is incorporated. Ultimately, the premarket review of the device should consider the device as a whole, including, of course, the drug component, consistent with the law. For these reasons and in conclusion, we ask that these proposed non-statutory categories be removed from any rulemaking. II. OTHER DEFINITIONS A. The proposed revision of Generic Type of Device definition is unnecessary and inconsistent with the law. AdvaMed believes that the proposed modifications to the Generic Type of Device definition is inconsistent with legal authority and would alter the classification process without justification. Therefore, we request that the Agency eliminate this proposed revision. The proposed regulation defines Generic Type of Device as follows: 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

12 Page 12 of 17 effectiveness. Devices within a generic type of device are sometimes, but not always, grouped together under the same product code. Devices within a single classification sometimes, but not always, form a generic type of device. 79 Fed. Reg. at (emphasis added to the last two sentences). The italicized portion of the proposed definition (excluding the term Generic type of device ) represents the amendment of the longstanding definition of Generic type of device that has been in use since 1978 and defines the scope of each classification regulation. The proposed changes suggest a significant departure from the understanding of Generic Type of Device and its relationship to the classification process, as defined by the FD&C Act. FDA explains it 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. 79 Fed. Reg. at However, we are not aware of any confusion. A procode is a mechanism created, without legal basis, by FDA to identify, among other things, differing indications for use within the intended use of a predicate device that is already classified under a regulation. The Generic type of device defines the scope of a classification regulation through identification statements that describe the use and general technology associated with the Generic type of device. To justify the inclusion of informal procodes in the Generic type of device definition, FDA states, [it] proposes to amend the definition of generic type of device to make clear that a generic type may include one or more procodes,... However, we are not aware of any confusion. Procodes are routinely used to catalog and identify subgroups of devices within generic types of devices and often there are multiple informally created procodes within each classification regulation. Moreover, this purported clarification in itself could create significant confusion, particularly in how the revised definition may be used by FDA in the future. Rather than confuse a longstanding and important definition, FDA can employ the same means used to create procodes and prominently inform the public that classification regulations may include more than one procode. FDA attempts to justify the second portion of its proposed change to the Generic type of device definition by stating, [t]he terms device, device type, and generic device type are often used in the FD&C Act and implementing regulations interchangeably. 79 Fed. Reg. at This observation does not justify amending a longstanding regulation. Moreover, the term generic device type does not appear in the FD&C Act and is wellunderstood in the context of FDA s classification regulations as defined in section 860.3(i) since The term device is well-defined in the FD&C Act since And the term device type does not appear in Part 860, the Part of the regulations to which the term Generic Type of Device applies. Additionally, FDA states that [it] proposes to amend the definition of generic type of device to make clear that... a single classification regulation may include one or more generic types of device and may even, in some instances straddle device classes. 79 Fed. Reg. at This statement does not recognize that each classification regulation through its identification statement describes the Generic type of device that is subject to

13 Page 13 of 17 classification under the particular regulation, and that the term Generic type of device is synonymous with the scope of each classification regulation. See, e.g., 21 CFR (f) (stating 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 (g) (stating The Commissioner reviews the comments and issues a final regulation classifying the device and other devices of that generic type ). The suggestion that a classification regulation includes more than one generic type of device is in conflict with longstanding understanding of device classification and appears to inappropriately revise the FD&C Act with a regulation. In sum, we recommend that if FDA wishes to explain terms, this can be accomplished through a guidance. This is an appropriate mechanism to rely upon for this type of task. Attempting clarifications of this sort in a definition regulation is neither definitional nor helpful when the regulation is longstanding and at the core of the Agency s classification regulations. AdvaMed urges the Agency to withdraw this proposed language in the rule and develop guidance, if necessary, to better explain terms. B. FDA should clarify its proposed definition of special controls. The proposal deletes the enumeration of special controls that currently appears in the Class II definition and instead proposes a separate definition of the term special controls. 79 Fed. Reg. at We believe that this could create confusion. FDA defines special controls, in part, as the controls necessary to provide a reasonable assurance of safety and effectiveness for a generic type of device within Class II and that must be met to establish and maintain classification within the generic type. Id. This language appears to suggest that all Class II devices are currently subject to established special controls. However, devices that are now classified in Class II and are not currently subject to special controls would require a rulemaking to be subject to such controls to maintain their Class II status under the proposal. See FD&C Act 513(d) (the classification procedure for pre-amendment devices). FDA should revise the language to make clear that not all Class II devices are currently subject to special controls, e.g., the language could read:... the controls necessary to provide a reasonable assurance of safety and effectiveness for a generic type of device within Class II that must be met to establish and maintain classification within the generic type. C. AdvaMed supports the special controls guideline concept with confirmation regarding alternate acceptable measures. In its proposal, the Agency introduces the concept of a special controls guideline. 79 Fed. Reg. at FDA explains that [w]hile 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 by demonstrating to the Agency s satisfaction that those alternative measures provide the same or greater level of assurance of safety and effectiveness. Id. AdvaMed believes this definition is acceptable, and supports it

14 Page 14 of 17 to the extent companies can always satisfy a guideline s requirements with alternate measures acceptable to FDA. D. FDA should not remove the definitions for, and use of, the Classification Questionnaire and Supplemental Data Sheet. We are concerned with FDA s proposal to remove the definitions for classification questionnaire and supplemental data sheet because FDA is proposing to remove the requirement that these forms be included as part of the reclassification procedures under and a reclassification petition under See 79 Fed. Reg. at In its proposal, FDA states that [t]he classification questionnaire provides recommendations and information for FDA to consider during the classification process, and that [t]he supplemental data sheet is information compiled by a classification panel or submitted in a petition for reclassification. Id. at FDA explains that as the Agency has gained experience with the classification processes, questions concerning the utility of the classification questionnaire and supplemental data sheet have arisen, and that 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. Id. We believe that both the classification questionnaire and the supplemental data sheet are important in ensuring that panel members are fully informed with summaries of reclassification submissions and understand and follow the legal principles in developing and providing their expert opinion. The classification questionnaire lays out important criteria in determining the appropriate classification of a device, for example, whether there is sufficient information to establish special controls to provide reasonable assurance of safety and effectiveness, along with a listing of available special controls. See FDA Form In other words, it provides a framework for the expert panelists to apply their scientific expertise in the context of the legal requirements. Similarly, the supplemental data sheet is important because it provides a valuable means of digesting and summarizing the panel recommendations that lead to the recommended device classification. See FDA Form We believe that these documents constitute important guidance materials for panelists who often have no legal or regulatory background and require assistance in applying their expert knowledge to FDA s classification criteria. Not providing these guidelines to the panelists would likely decrease efficiency, prejudice the petitioner and bias the reclassification process. As a result, we do not support the proposal to remove these documents from the reclassification process, and request that the Agency continue the use of these documents. III. RECLASSIFICATION PROCESS AND CALLS FOR PMAs FDA s proposal appears to incorrectly interpret Section 608 of the Food and Drug Administration Safety and Innovation Act to essentially eliminate the requirement that an

15 Page 15 of 17 advisory panel review and comment on FDA proposed reclassification orders or call for PMAs for pre-amendment device orders. In the proposed rulemaking, FDA states its legal authority to reclassify Class III preamendment devices under section 513(e), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA) in The Agency states that in lieu of a regulation to reclassify such devices, now it may do so by administrative order. FDA elaborates that: 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 (citation omitted). The panel meeting must occur before the final order is published, and may occur either before or after the proposed order is published. 79 Fed. Reg. at (bolded text in original, underlining added for emphasis). FDA s decoupling of the panel meeting requirement from the publication of the proposed order appears to ignore the structure and language of the FDASIA amendment to sections 513(e) and 515(b) that requires panel review of proposed orders. Specifically, in both sections neither a final order for reclassification nor a call for PMAs may occur, unless it follow[s] publication of a proposed reclassification [or call for PMA] order in the Federal Register, a meeting of a device classification panel described in subsection (b), and consideration of comments to the public docket, (e)(1)(A)(i); see 515(b)(1). 3 These three conditions of: 1) publishing a proposed order, 2) holding a panel meeting and 3) considering comments in the public docket from interested persons and stakeholders describe a sequence that is triggered by the publication of the proposed order. By including the panel meeting between publication of the order for comment and considering comments, the provisions were designed by Congress to assure expert panels evaluate FDA s proposed orders and provide feedback prior to the orders becoming final. FDA s statement that the panel meeting can occur before or after the publication of the proposed order is concerning and undermines the panel protection Congress sought to include in the law to compensate for the change from rulemaking to administrative orders. Congress was careful to include the basic procedural notice and comment characteristics of rulemaking while relieving FDA of some of the other burdens associated with rulemaking. The provisions also tracked FDA s own regulatory procedures at the time of FDASIA in placing advisory panel review second in the sequence of required conditions that must precede a final order. Specifically, prior to FDASIA, where panel review under section 513(e) was discretionary, and not mandatory as it is under FDASIA, FDA s regulations state,... the Commissioner may secure a recommendation with respect to a proposed reclassification from the classification panel to which the device was last referred. The panel will consider a proposed reclassification submitted to it by the Commissioner in accordance with the consultation procedures of CFR (d) (emphasis added). It 3 The quoted language is from amended 513(e). Section 515(b)(1) has substantially similar language as 513(e) and includes the identical list of conditions that must precede a final order.