Source: https://regulations.justia.com/regulations/fedreg/2017/01/06/2016-31862.html
Timestamp: 2020-08-12 13:37:35
Document Index: 444708952

Matched Legal Cases: ['art 51', 'art 884', 'art 807', '§ 860', '§ 876', '§ 878', '§ 884', '§ 884', '§ 884', '§ 884', '§ 884', '§ 878', '§ 884', '§ 860', '§ 884', 'art 807', 'art 801', '§ 884', '§ 884', 'arts 52', '§ 876', '§ 878', 'art 884', 'art 884', 'ART 884', 'art 884', '§ 884', 'art 807', 'art 801']

Obstetrical and Gynecological Devices; Reclassification of Surgical Instrumentation for Use With Urogynecologic Surgical Mesh, 1598-1603 [2016-31862] :: Food And Drug Administration :: Department Of Health And Human Services :: Regulation Tracker :: Justia
Justia Regulation Tracker Department Of Health And Human Services Food And Drug Administration Obstetrical and Gynecological Devices; Reclassification of Surgical Instrumentation for Use With Urogynecologic Surgical Mesh, 1598-1603 [2016-31862]
Obstetrical and Gynecological Devices; Reclassification of Surgical Instrumentation for Use With Urogynecologic Surgical Mesh, 1598-1603 [2016-31862]
Download as PDF 1598 Federal Register / Vol. 82, No. 4 / Friday, January 6, 2017 / Rules and Regulations (k) Material Incorporated by Reference (1) The Director of the Federal Register approved the incorporation by reference (IBR) of the service information listed in this paragraph under 5 U.S.C. 552(a) and 1 CFR part 51. (2) You must use this service information as applicable to do the actions required by this AD, unless this AD specifies otherwise. (i) Dassault Service Bulletin F20–789, also referred to as 789, dated December 9, 2014. (ii) Dassault Service Bulletin F50–531, also referred to as 531, dated December 9, 2014. (iii) Dassault Service Bulletin F200–133, also referred to as 133, dated December 9, 2014. (3) For service information identified in this AD, contact Dassault Falcon Jet Corporation, Teterboro Airport, P.O. Box 2000, South Hackensack, NJ 07606; telephone 201–440–6700; Internet http:// www.dassaultfalcon.com. (4) You may view this service information at the FAA, Transport Airplane Directorate, 1601 Lind Avenue SW., Renton, WA. For information on the availability of this material at the FAA, call 425–227–1221. (5) You may view this service information that is incorporated by reference at the National Archives and Records Administration (NARA). For information on the availability of this material at NARA, call 202–741–6030, or go to: http:// www.archives.gov/federal-register/cfr/ibrlocations.html. Issued in Renton, Washington, on December 23, 2016. Thomas Groves, Acting Manager, Transport Airplane Directorate, Aircraft Certification Service. [FR Doc. 2016–31871 Filed 1–5–17; 8:45 am] BILLING CODE 4910–13–P DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 884 [Docket No. FDA–2014–N–0297] Obstetrical and Gynecological Devices; Reclassification of Surgical Instrumentation for Use With Urogynecologic Surgical Mesh AGENCY: Food and Drug Administration, HHS. ACTION: Final order. The Food and Drug Administration (FDA or the Agency) is reclassifying surgical instrumentation for use with urogynecologic surgical mesh from class I (general controls) exempt from premarket notification to class II (special controls) and subject to premarket notification, and identifying them as ‘‘specialized surgical instrumentation for use with sradovich on DSK3GMQ082PROD with RULES SUMMARY: VerDate Sep<11>2014 17:18 Jan 05, 2017 Jkt 241001 urogynecologic surgical mesh.’’ FDA is designating special controls that are necessary to provide a reasonable assurance of safety and effectiveness of the device. FDA is reclassifying this device on its own initiative based on new information. DATES: This order is effective January 6, 2017. See further discussion in section V, ‘‘Implementation Strategy.’’ FOR FURTHER INFORMATION CONTACT: Sharon Andrews, Center for Devices and Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Rm. G110, Silver Spring, MD 20993, 301–796– 6529, Sharon.Andrews@fda.hhs.gov. SUPPLEMENTARY INFORMATION: I. Background—Regulatory Authorities The Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C. 301 et seq.), as amended, established a comprehensive system for the regulation of medical devices intended for human use. Section 513 of the FD&C Act (21 U.S.C. 360c) established three categories (classes) of devices, reflecting the regulatory controls needed to provide reasonable assurance of their safety and effectiveness. The three categories of devices are class I (general controls), class II (special controls), and class III (premarket approval). Devices that were in commercial distribution before the enactment of the 1976 amendments on May 28, 1976, are generally referred to as preamendments devices. Under section 513(d) of the FD&C Act, preamendments devices are classified after FDA has: (1) Received a recommendation from a device classification panel (an FDA advisory committee); (2) published the panel’s recommendation for comment, along with a proposed regulation classifying the device; and (3) published a final regulation classifying the device. FDA has classified most preamendments devices under these procedures. Devices that were not in commercial distribution prior to May 28, 1976, are generally referred to as postamendments devices. Postamendments devices are automatically classified into class III without any FDA rulemaking process (section 513(f) of the FD&C Act). Postamendments devices remain in class III and require premarket approval unless, and until, the device is reclassified into class I or II or FDA issues an order finding the device to be substantially equivalent, under section 513(i) of the FD&C Act, to a predicate device that does not require premarket approval. The Agency determines whether new devices are substantially equivalent to predicate devices by means of premarket notification PO 00000 Frm 00006 Fmt 4700 Sfmt 4700 procedures in section 510(k) of the FD&C Act (21 U.S.C. 360(k)) and 21 CFR part 807. On July 9, 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) (Pub. L. 112–144) was enacted. Section 608(a) of FDASIA amended section 513(e) of the FD&C Act, changing the mechanism for reclassifying a device from rulemaking to an administrative order. Section 513(e) of the FD&C Act provides that FDA may, by administrative order, reclassify a device based upon ‘‘new information.’’ FDA can initiate a reclassification under section 513(e) of the FD&C Act or an interested person may petition FDA to reclassify a device. The term ‘‘new information,’’ as used in section 513(e) of the FD&C Act, includes information developed as a result of a reevaluation of the data before the Agency when the device was originally classified, as well as information not presented, not available, or not developed at that time. (See, e.g., Holland-Rantos Co. v. United States Department of Health, Education, and Welfare, 587 F.2d 1173, 1174 n.1 (D.C. Cir. 1978); Upjohn v. Finch, 422 F.2d 944 (6th Cir. 1970); Bell v. Goddard, 366 F.2d 177 (7th Cir. 1966).) Reevaluation of the data previously before the Agency is an appropriate basis for subsequent action where the reevaluation is made in light of newly available authority (see Bell, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 F.Supp. 382, 388–391 (D.D.C. 1991)), or in light of changes in ‘‘medical science’’ (Upjohn, 422 F.2d at 951). Whether data before the Agency are old or new data, the ‘‘new information’’ to support reclassification under section 513(e) must be ‘‘valid scientific evidence,’’ as defined in section 513(a)(3) of the FD&C Act and § 860.7(c)(2) (21 CFR 860.7(c)(2)). (See, e.g., Gen. Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Mfrs. Assoc. v. FDA, 766 F.2d 592 (D.C. Cir. 1985), cert. denied, 474 U.S. 1062 (1986).) To be considered in the reclassification process, the ‘‘valid scientific evidence’’ upon which the Agency relies must be publicly available. Publicly available information excludes trade secret and/or confidential commercial information, e.g., the contents of a pending premarket approval application (PMA). (See section 520(c) of the FD&C Act (21 U.S.C. 360j(c)).) The process for issuing a final reclassification order is specified in section 513(e)(1) of the FD&C Act. Prior to the issuance of a final order reclassifying a device, the following must occur: (1) Publication of a proposed order in the Federal Register; E:\FR\FM\06JAR1.SGM 06JAR1 sradovich on DSK3GMQ082PROD with RULES Federal Register / Vol. 82, No. 4 / Friday, January 6, 2017 / Rules and Regulations (2) a meeting of a device classification panel described in section 513(b) of the FD&C Act; and (3) consideration of comments to a public docket. In the Federal Register of May 1, 2014, FDA published a proposed order to reclassify surgical mesh for transvaginal pelvic organ prolapse (POP) repair from class II to class III (79 FR 24634). In the same order, FDA also proposed to reclassify specialized surgical instrumentation for use with urogynecologic surgical mesh (hereafter referred to as urogynecologic surgical mesh instrumentation) from class I— regulated under § 876.4730 (21 CFR 876.4730) (manual gastroenterologyurology surgical instrument and accessories) and § 878.4800 (21 CFR 878.4800) (manual surgical instrument for general use)—to class II and subject to premarket notification. In the Federal Register of January 5, 2016, FDA published two final orders that: (1) Reclassified surgical mesh for transvaginal POP repair from class II to class III (81 FR 354) and (2) required the filing of a PMA or notice of completion of a product development protocol for surgical mesh for transvaginal POP repair (81 FR 364). In the May 1, 2014 proposed order, FDA stated that it would convene a panel specifically to discuss reclassification of urogynecologic surgical mesh instrumentation before finalizing reclassification of those devices. FDA held a meeting on February 26, 2016 (81 FR 938, January 8, 2016), of the GastroenterologyUrology Devices Panel of the Medical Devices Advisory Committee (‘‘the Panel’’), a device classification panel described in section 513(b) of the FD&C Act. Prior to the meeting, all panel members were provided a comprehensive Executive Summary regarding the reclassification of urogynecologic surgical mesh instrumentation, which included information contained in the May 1, 2014, proposed order, a summary of comments submitted to the public docket on the proposed reclassification of urogynecologic surgical mesh instrumentation, and information regarding FDA’s risk-based classification and regulation of medical devices (Ref. 1). The Executive Summary also included a new FDA analysis of perioperative adverse events related to urogynecologic surgical mesh procedures. FDA conducted a new analysis to supplement the adverse event information discussed in the May 1, 2014, proposed order, which included adverse events related to POP procedures that were: (1) Reported in VerDate Sep<11>2014 17:18 Jan 05, 2017 Jkt 241001 clinical studies and systematic literature reviews in the published literature or (2) submitted to the Manufacturer and User Facility Device Experience (MAUDE) database between January 1, 2011, and December 31, 2013. FDA’s new analysis was a more comprehensive analysis of perioperative adverse events associated with stress urinary incontinence (SUI) procedures (retropubic, transobturator, mini-sling) and POP procedures (transvaginal repair and transabdominal repair (transabdominal POP repair is referred to as sacrocolpopexy)). Adverse events related to a urogynecologic surgical mesh procedure, and that might be attributable to the specialized instrumentation used during the procedure, are typically submitted to FDA or described in published literature with reference to the surgical mesh and not the instrumentation. Therefore, it can be difficult to distinguish adverse events related to the urogynecologic surgical mesh instrumentation from those related to the surgical mesh. As noted in the proposed order, FDA believes it is reasonable to assume that perioperative adverse events—i.e., those observed during the procedure or shortly thereafter (e.g., organ perforation, hemorrhage and bleeding, nerve injury and pain)—are caused by or related to the use of specialized surgical instrumentation to insert, place, fix, or anchor the surgical mesh during the urogynecologic procedure. Hereafter, the term ‘‘perioperative adverse events’’ will be used in this document to refer to adverse events that FDA believes are caused by or related to the specialized instrumentation that is the subject of this reclassification. In its new, more comprehensive analysis, FDA conducted a search of the relevant, scientific literature published between January 1, 1997, and December 8, 2015, to identify perioperative adverse events associated with urogynecologic surgical mesh procedures (see the 207 studies included as references in the Executive Summary provided to the Panel (Ref. 1). The search criteria consisted of a combination of terms related to adverse events (type, timing with respect to surgery), type of urogynecologic condition, type of surgical instrumentation, study design, device name, and manufacturer name. FDA then filtered the results to identify those studies that describe perioperative adverse events during one of the following urogynecologic surgical mesh procedures: SUI-retropubic, SUItransobturator, SUI-mini-sling, POPtransvaginal, and POP-sacrocolpopexy. All perioperative adverse events were PO 00000 Frm 00007 Fmt 4700 Sfmt 4700 1599 classified into one of the following categories: ‘‘organ perforation and injury,’’ ‘‘vascular injury and bleeding,’’ or ‘‘nerve injury and pain.’’ FDA then computed an adverse event rate for each study by dividing the number of patients that experienced one of these types of events by the total number of patients included in the study. FDA also conducted a search of the Medical Device Reporting (MDR) database for relevant adverse events reported between January 1, 2008, and December 2, 2015. There are no FDA product codes specifically assigned to urogynecologic surgical mesh instrumentation; therefore, FDA first identified reports that were associated with a product code assigned to urogynecologic surgical mesh. FDA filtered the resulting injury and death reports to identify and analyze those that described perioperative adverse events. By stratifying its analysis by product code for the urogynecologic surgical mesh, which depends, in part, on the procedure type (e.g., OTP is assigned to mesh used during POPtransvaginal procedures, OTN for mesh used during SUI-retropubic or transobturator procedures), FDA characterized the perioperative adverse events associated with the different kinds of urogynecologic surgical mesh instrumentation used during SUI and POP procedures. After completing its review of the published literature and MDR database, and aggregating its findings, FDA determined that perioperative adverse events occur during all types of urogynecologic surgical mesh procedures to treat female SUI and POP. Moreover, and as discussed in the Executive Summary (Ref. 1, Attachments 6–8), FDA made the following findings from its review of the published literature: • The rate of ‘‘vascular injury and bleeding’’ varied between 0.4–29.4 percent in studies describing retropubic SUI procedures; 0.2–11.9 percent in studies describing transobturator SUI procedures; 1–20.5 percent in studies describing mini-sling SUI procedures; 0.7–7.7 percent in studies describing transvaginal POP repair procedures; and 2.8 percent for one study describing sacrocolpoplexy procedures; • the rate of ‘‘organ perforation and injury’’ varied between 0.3–23.8 percent for retropubic SUI procedures; 0.2–5.8 percent for transobturator SUI procedures, 0.2–2.6 percent for minisling SUI procedures; 0.7–13.1 percent for transvaginal POP repair procedures; and 3.6 percent for one study describing sacrocolpoplexy procedures; and E:\FR\FM\06JAR1.SGM 06JAR1 sradovich on DSK3GMQ082PROD with RULES 1600 Federal Register / Vol. 82, No. 4 / Friday, January 6, 2017 / Rules and Regulations • the rate of ‘‘nerve injury and pain’’ varied between 0.1–5.3 percent for retropubic SUI procedures; 0.8–30.8 percent for transobturator SUI procedures, 1.1–4.1 percent for minisling SUI procedures; 6.0–39.1 percent for transvaginal POP repair procedures; and 14.9 percent for one study describing sacrocolpoplexy procedures. FDA presented a summary of the information contained in the Executive Summary during the February 26, 2016, panel meeting (Ref. 2). The Panel then discussed whether urogynecologic surgical mesh instrumentation should be reclassified, and if so, whether it should be reclassified from class I (general controls) to class II (special controls) or class III (premarket approval) (Ref. 3). The Panel discussed a variety of potential causes for the perioperative adverse events identified by FDA (e.g., instrumentation design, surgeon error, and surgeon experience). The Panel consensus was that the risks to health of urogynecologic surgical mesh instrumentation that FDA identified in the proposed order and Executive Summary (i.e., perioperative risks; damage to blood vessels, nerves, connective tissue, and other structures; adverse tissue reaction; and infection) was a complete and accurate list. The Panel agreed with FDA that the device is not purported or represented for a use in supporting or sustaining human life, or for a use which is of substantial importance in preventing impairment of human health, or presents a potential unreasonable risk of illness or injury. In light of this assessment, the Panel consensus was that urogynecologic surgical mesh instrumentation did not meet the definition of a class III device. The Panel also agreed with FDA that general controls alone are not sufficient to provide reasonable assurance of safety and effectiveness for the device, and that there is sufficient information to establish special controls to provide such assurance. When considering the specific special controls proposed by FDA, two Panel members requested that an additional special control be the submission of clinical data. However, after additional discussion, the Panel unanimously agreed that the special controls proposed by FDA, which did not include the submission of clinical data, would appropriately mitigate the risks to health of this device. As such, the Panel recommended that urogynecologic surgical mesh instrumentation be reclassified from class I (general controls) exempt from premarket notification to class II (special controls). VerDate Sep<11>2014 17:18 Jan 05, 2017 Jkt 241001 II. Key Changes From Proposed Order In the final order, FDA is modifying two of the special controls included in the proposed order. First, FDA is revising § 884.4910(b)(2) (21 CFR 884.4910(b)(2)) to require a demonstration that the device, if reusable, can be adequately reprocessed. Reprocessing validation will help to ensure that reusable urogynecologic surgical mesh instrumentation is fit for subsequent use after being previously used or contaminated. The validated processes are designed to remove soil and contaminants by cleaning and to inactivate microorganisms by disinfection or sterilization. Although FDA recognized in the proposed order that ‘‘the risk of infection due to inadequate sterilization and/or reprocessing instructions/procedures can be mitigated through sterilization validation testing and the inclusion of validated reprocessing instructions in the device labeling,’’ proposed § 884.4910(b)(2) addressed sterilization only. FDA believes this revised special control will help to mitigate the risks posed by infection from reusable urogynecologic surgical mesh instrumentation. Second, FDA is revising § 884.4910(b)(4) to require that nonclinical performance testing demonstrate that the device: (1) Meets all design specifications and performance requirements and (2) performs as intended under anticipated conditions of use. In the proposed order, FDA specified that ‘‘[b]ench and/or cadaver testing must demonstrate safety and effectiveness in expected-use conditions.’’ FDA has revised the reference to ‘‘bench and/or cadaver testing’’ to ‘‘non-clinical performance testing’’ to allow for additional types of non-clinical testing that will also mitigate the corresponding risks to health. FDA is making other revisions to this provision as noted previously to provide further clarity. III. Public Comments in Response to the Proposed Order FDA received comments regarding the proposed reclassification of urogynecologic surgical mesh instrumentation from class I to class II. A summary of the comments and FDA’s responses are provided in this section. Certain comments are grouped together under a single number because the subject matter is similar. The number assigned to each one is purely for organizational purposes and does not signify the comment’s value, importance, or the order in which it was received. PO 00000 Frm 00008 Fmt 4700 Sfmt 4700 (Comment 1) Several comments supported reclassification of urogynecologic surgical mesh instrumentation, with some comments supporting reclassification into class II and others supporting reclassification into class III. (Response 1) FDA agrees with comments supporting reclassification of urogynecologic surgical mesh instrumentation into class II and disagrees with comments that support reclassification into class III. Based on information set forth in the proposed order (79 FR 24634), FDA tentatively concluded in that order that certain specified special controls, in addition to general controls, were necessary to mitigate the risks to health for urogynecologic surgical mesh instrumentation, and as such, proposed to reclassify the device from class I to class II (79 FR 24634 at 24640). FDA continues to believe that there is sufficient information to establish special controls to provide a reasonable assurance of safety and effectiveness for this device, and thus does not believe this device should be reclassified into class III. FDA’s new, more comprehensive, adverse event analysis provides further support for the risks to health of this device that FDA identified in the proposed order (see section I; Ref. 1), and the special controls established by FDA are specifically intended to mitigate those risks. For example, FDA’s new MDR analysis revealed that failures of urogynecologic surgical mesh instrumentation (e.g., needle detachments, breaks, or bends; covering sheath breaks or tears) occur during both SUI and POP procedures, and these failures are associated with perioperative adverse events. The special control established at § 884.4910(b)(4) addresses these failures and the risk of perioperative injuries by requiring a demonstration that the device meets all design specifications and performance requirements. Based on all of this information, the Panel consensus was that urogynecologic surgical mesh instrumentation meets the statutory definition of a class II device and does not meet the statutory definition of a class III device (see section I; Ref. 3). Because FDA has determined that general controls alone are not sufficient to provide a reasonable assurance of safety and effectiveness for this device, and there is sufficient information to establish special controls to provide such an assurance, FDA is reclassifying the device into class II. (Comment 2) One comment requested that urogynecologic surgical mesh E:\FR\FM\06JAR1.SGM 06JAR1 sradovich on DSK3GMQ082PROD with RULES Federal Register / Vol. 82, No. 4 / Friday, January 6, 2017 / Rules and Regulations instrumentation have the same classification as the surgical mesh with which it is indicated to be used. (Response 2) Surgical mesh indicated for urogynecologic procedures is a class III device when it is indicated for transvaginal POP repair (see 81 FR 354; § 884.5980) and a class II device when it is indicated for all other urogynecologic procedures, such as sacrocolpopexy and treatment of female SUI (see § 878.3300). FDA characterized the risk profile of different kinds of urogynecologic surgical mesh instrumentation by analyzing adverse events associated with the use of this specialized instrumentation and stratifying them by the type of urogynecologic procedure for which they were used. The results indicate that the risk profile of urogynecologic surgical mesh instrumentation used with class III surgical mesh during transvaginal POP repair is comparable to that of urogynecologic surgical mesh instrumentation used with class II surgical mesh during other kinds of urogynecologic procedures (see section I; Ref. 1). Urogynecologic surgical mesh instrumentation used in all types of urogynecologic surgical mesh procedures appears to have a similar risk-benefit profile, and therefore FDA believes these devices should have the same classification. Moreover, as previously discussed, based on information included in the proposed order (79 FR 24634), FDA’s comprehensive adverse event analysis (see Ref. 1), and the Panel’s deliberations and determinations, FDA has determined that urogynecologic surgical mesh instrumentation is a class II device because general controls alone cannot provide a reasonable assurance of safety and effectiveness, but there is sufficient information to establish special controls to provide such assurance. As such, FDA is reclassifying these devices from class I to class II. (Comment 3) One comment stated that the scope of the urogynecologic surgical mesh instrumentation reclassification was unclear, and it could be interpreted that the reclassification applies only to instrumentation used for transvaginal POP repair rather than for instrumentation used for any urogynecologic surgical mesh procedure. (Response 3) FDA disagrees that the scope of the instrumentation reclassification was unclear in the May 1, 2014, proposed order. FDA included the description in the identification of urogynecologic surgical mesh instrumentation in proposed § 884.4910(a) stating that surgical VerDate Sep<11>2014 17:18 Jan 05, 2017 Jkt 241001 instrumentation for use with surgical mesh for urogynecological procedures is a prescription device used to aid in insertion, placement, fixation, or anchoring of surgical mesh for procedures including transvaginal POP repair, sacrocolpopexy (transabdominal POP repair), and treatment of female SUI. This description, which is not substantively changing in the final order, makes clear that all urogynecologic surgical mesh instrumentation—whether used for transvaginal POP repair or other urogynecologic surgical mesh procedures—falls under this reclassification. (Comment 4) One comment stated that data provided in the proposed order to support the instrumentation reclassification was based only on POP procedures, that valid scientific evidence had not been provided to support the instrumentation reclassification, and that no evidence was provided to support the risks that were identified in the proposed order. (Response 4) First, FDA acknowledges that the data provided to support the instrumentation reclassification in the May 1, 2014, proposed order derived only from surgical mesh procedures indicated for POP. FDA subsequently conducted a new, more comprehensive analysis of perioperative adverse events associated with a variety of SUI procedures (retropubic, transobturator, mini-sling) and POP procedures (transvaginal repair and sacrocolpoplexy) by reviewing adverse events included in the relevant, scientific, published literature and adverse events submitted to the MDR database. Based on this analysis, FDA determined that perioperative adverse events occur during all types of SUI and POP procedures (see section I; Ref. 1). FDA also discovered that in the published literature, the highest reported rates of ‘‘organ perforation and injury,’’ ‘‘vascular injury and bleeding,’’ and ‘‘nerve injury and pain’’ were distributed across different types of urogynecologic surgical mesh procedures rather than only occurring during one specific type, such as transvaginal POP repair. FDA believes these results provide further support for the reclassification of these devices into class II, and also supports the scope of this reclassification, which encompasses specialized instrumentation used during all types of urogynecologic surgical mesh procedures. After presenting the proposed order and this new information to the Panel at the February 26, 2016, meeting, the Panel recommended that urogynecologic surgical mesh instrumentation be PO 00000 Frm 00009 Fmt 4700 Sfmt 4700 1601 reclassified from class I (general controls) exempt from premarket notification to class II (special controls) (Ref. 3). FDA agrees with the Panel’s recommendations and is reclassifying these devices from class I to class II. Second, FDA disagrees that valid scientific evidence was not provided in the May 1, 2014, proposed order to support reclassification of urogynecologic surgical mesh instrumentation. Valid scientific evidence is defined in § 860.7(c)(2) as evidence from well-controlled investigations, other types of studies and 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. (See also section 513 of the FD&C Act). In the proposed order, FDA reviewed perioperative adverse events included in published studies of surgical mesh used during POP procedures. These publications constitute ‘‘valid scientific evidence’’ because they are controlled studies (Refs. 7–10, 12, 14) and collections of well-documented case histories conducted by qualified experts (Refs. 4–6, 11, 13). Finally, FDA disagrees that no evidence was provided to support the risks of urogynecologic surgical mesh instrumentation identified in the proposed order. In the proposed order, FDA specifically referenced clinical studies and systematic literature reviews in the published literature that included reports of perioperative adverse events (e.g., bleeding, hematoma, and blood loss; organ perforation; and neuromuscular problems) to support the proposed reclassification. Moreover, the risks of ‘‘perioperative injury’’ and ‘‘pelvic pain and neuromuscular problems’’ were also identified during FDA’s search of the MAUDE database. As discussed in the proposed order, 843 reports in the MAUDE database analysis related to bleeding, hematoma, and blood loss; 42 reports related to organ perforation; and 196 reports of neuromuscular problems. FDA acknowledges that no data were provided to support the identified risks of ‘‘infection’’ and ‘‘adverse tissue reaction.’’ Although there are many possible causes for ‘‘infection’’ and ‘‘adverse tissue reaction’’ during a urogynecologic surgical mesh procedure, as FDA noted in the proposed order (see 79 FR 24634 at 24639), FDA believes ‘‘infection’’ and ‘‘adverse tissue reaction’’ are general risks that apply to all devices that E:\FR\FM\06JAR1.SGM 06JAR1 1602 Federal Register / Vol. 82, No. 4 / Friday, January 6, 2017 / Rules and Regulations sradovich on DSK3GMQ082PROD with RULES contact the patient and need to be used sterile. As discussed throughout this document, FDA subsequently conducted a more comprehensive search of the relevant, scientific, published literature and MDR database to evaluate the risks of urogynecologic surgical mesh instrumentation. A summary of the findings from these reviews is in the Executive Summary (Ref. 1) and was provided in our presentation to the Panel on February 26, 2016 (Ref. 2). The findings from the literature review—which were confirmed by the MDR database review—provide further support for the risks identified and discussed in the proposed order. Based on this information, the Panel consensus was that the four risks to health of urogynecologic surgical mesh instrumentation that FDA identified in the proposed order is a complete and accurate list (Ref. 3). (Comment 5) One comment, which was submitted after the proposed order issued and before the Panel meeting was held, stated that the proposed order should be withdrawn until Panel input was obtained. (Response 5) FDA disagrees. The process followed by FDA in reclassifying this device is in accordance with section 513(e)(1) of the FD&C Act. This provision requires, in relevant part, that issuance of a final administrative order reclassifying a device be preceded by a proposed order and a meeting of a device classification panel. There is no requirement that a proposed order be ‘‘withdrawn’’ after its issuance but before the Panel meeting, and the rationale for doing so is not clear to FDA. IV. The Final Order Under section 513(e) of the FD&C Act, FDA is adopting its findings as published in the proposed order for urogynecologic surgical mesh instrumentation, with the modifications discussed in section II of this document. For the reasons set forth in the proposed order and in this document, FDA concludes that general controls are insufficient to provide a reasonable assurance of safety and effectiveness for urogynecologic surgical mesh instrumentation, and there is sufficient information to establish special controls to provide such assurance. FDA is issuing this final order to reclassify urogynecologic surgical mesh instrumentation from class I (general controls) exempt from premarket notification to class II (special controls) and subject to premarket notification, and identifying them as ‘‘specialized VerDate Sep<11>2014 17:18 Jan 05, 2017 Jkt 241001 surgical instrumentation for use with urogynecologic surgical mesh.’’ FDA is also establishing special controls, which are set forth in § 884.4910(b)(1) through (5). Section 510(m) of the FD&C Act provides that FDA may exempt a class II device from the premarket notification requirements under section 510(k) of the FD&C Act if FDA determines that premarket notification is not necessary to provide reasonable assurance of the safety and effectiveness of the device. FDA has determined that premarket notification is necessary to provide reasonable assurance of safety and effectiveness of urogynecologic surgical mesh instrumentation, and therefore, this device is not exempt from premarket notification requirements. V. Implementation Strategy The order is effective January 6, 2017. Manufacturers of urogynecologic surgical mesh instrumentation that have not been legally marketed prior to January 6, 2017, must obtain 510(k) clearance and demonstrate compliance with the special controls included in this final order before marketing the device. Manufacturers of urogynecologic surgical mesh instrumentation that have been legally marketed prior to January 6, 2017, must obtain 510(k) clearance and demonstrate compliance with the special controls included in this final order by January 8, 2018, for those devices if they wish to continue offering them for sale. VI. Analysis of Environmental Impact The Agency has determined under 21 CFR 25.34(b) that this action is of a type that does not individually or cumulatively have a significant effect on the human environment. Therefore, neither an environmental assessment nor an environmental impact statement is required. VII. Paperwork Reduction Act of 1995 This final order refers to previously approved collections of information found in FDA regulations. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501– 3520). The collections of information in 21 CFR part 807, subpart E, have been approved under OMB control number 0910–0120 and the collections of information under 21 CFR part 801 have been approved under OMB control number 0910–0485. PO 00000 Frm 00010 Fmt 4700 Sfmt 4700 VIII. Codification of Orders Prior to the amendments by FDASIA, section 513(e) of the FD&C Act provided for FDA to issue regulations to reclassify devices. Although section 513(e) of the FD&C Act as amended requires FDA to issue final orders rather than regulations, FDASIA also provides for FDA to revoke previously issued regulations by order. FDA will continue to codify classifications and reclassifications in the Code of Federal Regulations (CFR). Changes resulting from final orders will appear in the CFR as changes to codified classification determinations or as newly codified orders. Therefore, under section 513(e)(1)(A)(i) of the FD&C Act, as amended by FDASIA, in this final order, we are codifying the reclassification of specialized surgical instrumentation for use with urogynecologic surgical mesh into class II in § 884.4910. IX. References The following references are on display in the Division of Dockets Management (HFA–305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, and are available for viewing by interested persons between 9 a.m. and 4 p.m., Monday through Friday; they are also available electronically at https:// www.regulations.gov. FDA has verified the Web site addresses, as of the date this document publishes in the Federal Register, but Web sites are subject to change over time. 1. Executive Summary of the February 26, 2016, meeting of the GastroenterologyUrology Devices Panel (available at http:// www.fda.gov/downloads/ AdvisoryCommittees/ CommitteesMeetingMaterials/ MedicalDevices/ MedicalDevicesAdvisoryCommittee/ Gastroenterology-UrologyDevicesPanel/ UCM487224.pdf). 2. FDA presentation to Panel members at the February 26, 2016, meeting of the Gastroenterology-Urology Devices Panel (available at http://www.fda.gov/downloads/ AdvisoryCommittees/ CommitteesMeetingMaterials/ MedicalDevices/ MedicalDevicesAdvisoryCommittee/ Gastroenterology-UrologyDevicesPanel/ UCM490205.pdf). 3. Transcript of the February 26, 2016, meeting of the Gastroenterology-Urology Devices Panel (available at http:// www.fda.gov/downloads/ AdvisoryCommittees/ CommitteesMeetingMaterials/ MedicalDevices/ MedicalDevicesAdvisoryCommittee/ Gastroenterology-UrologyDevicesPanel/ UCM491862.pdf). 4. Caquant, F., et al., ‘‘Safety of Trans Vaginal Mesh Procedure: Retrospective Study E:\FR\FM\06JAR1.SGM 06JAR1 Federal Register / Vol. 82, No. 4 / Friday, January 6, 2017 / Rules and Regulations of 684 Patients,’’ Journal of Obstetrics and Gynecology Research, 34(4):449–456, 2008. 5. Maher, C.F., et al., ‘‘Surgical Management of Pelvic Organ Prolapse in Women,’’ Cochrane Database of Systematic Review, 4: CD004014, 2010. 6. Diwadkar, G.B., et al., ‘‘Complication and Reoperation Rates After Apical Vaginal Prolapse Surgical Repair: A Systematic Review,’’ Obstetrics & Gynecology, 113(2 Pt. 1):67–73, 2009. 7. Maher, C.F., et al., ‘‘Laparoscopic Sacral Colpopexy Versus Total Vaginal Mesh for Vaginal Vault Prolapse: A Randomized Trial,’’ American Journal of Obstetrics & Gynecology, 204(4):360.e1–360.e7, 2011. 8. Altman, D., et al., ‘‘Anterior Colporrhaphy Versus Transvaginal Mesh for Pelvic-Organ Prolapse,’’ New England Journal of Medicine, 364:1826–1836, 2011. 9. Iglesia, C.B., et al., ‘‘Vaginal Mesh for Prolapse: A Randomized Controlled Trial,’’ Obstetrics & Gynecology, 116(2 Pt. 1):293– 303, 2010. 10. Withagen, M.I., et al., ‘‘Trocar-Guided Mesh Compared With Conventional Vaginal Repair in Recurrent Prolapse: A Randomized Controlled Trial,’’ Obstetrics & Gynecology, 117(2 Pt. 1):242–250, 2011. 11. Sung, V.W., et al., Society of Gynecologic Surgeons Systematic Review Group. ‘‘Graft Use in Transvaginal Pelvic Organ Prolapse and Urinary Incontinence,’’ Obstetrics & Gynecology, 112(5):1131–1142, 2008. 12. Hiltunen, R., et al., ‘‘Low-Weight Polypropylene Mesh for Anterior Vaginal Wall Prolapse: A Randomized Controlled Trial,’’ Obstetrics & Gynecology, 110(2 Pt. 2):455–462, 2007. 13. Jia, X., et al., ‘‘Efficacy and Safety of Using Mesh or Grafts in Surgery for Anterior and/or Posterior Vaginal Wall Prolapse: Systematic Review and Meta-Analysis,’’ British Journal of Obstetrics and Gynecology, 115:1350–1361, 2008. 14. Sivaslioglu, A.A., E. Unlubilgin, and I. Dolen, ‘‘A Randomized Comparison of Polypropylene Mesh Surgery With SiteSpecific Surgery in the Treatment of Cystocoele,’’ International Urogynecology Journal and Pelvic Floor Dysfunction, 19(4):467–471, 2008. § 884.4910 Specialized surgical instrumentation for use with urogynecologic surgical mesh. ENVIRONMENTAL PROTECTION AGENCY 40 CFR Parts 52 and 81 ■ (a) Identification. Specialized surgical instrumentation for use with urogynecologic surgical mesh is a prescription device specifically intended for use as an aid in the insertion, placement, fixation, or anchoring of surgical mesh during urogynecologic procedures. These procedures include transvaginal pelvic organ prolapse repair, sacrocolpopexy (transabdominal pelvic organ prolapse repair), and treatment of female stress urinary incontinence. Examples of specialized surgical instrumentation include needle passers and trocars, needle guides, fixation tools, and tissue anchors. This device is not a manual gastroenterology-urology surgical instrument and accessories (§ 876.4730) or a manual surgical instrument for general use (§ 878.4800). (b) Classification. Class II (special controls). The special controls for specialized surgical instrumentation for use with urogynecologic surgical mesh are: (1) The device must be demonstrated to be biocompatible; (2) The device must be demonstrated to be sterile and, if reusable, it must be demonstrated that the device can be adequately reprocessed; (3) Performance data must support the shelf life of the device by demonstrating package integrity and device functionality over the requested shelf life; (4) Non-clinical performance testing must demonstrate that the device meets all design specifications and performance requirements, and that the device performs as intended under anticipated conditions of use; and (5) Labeling must include: (i) Information regarding the mesh design that may be used with the device; (ii) Detailed summary of the clinical evaluations pertinent to use of the device; (iii) Expiration date; and (iv) Where components are intended to be sterilized by the user prior to initial use and/or are reusable, validated methods and instructions for sterilization and/or reprocessing of any reusable components. Authority: 21 U.S.C. 351, 360, 360c, 360e, 360j, 371. Dated: December 28, 2016. Leslie Kux, Associate Commissioner for Policy. List of Subjects in 21 CFR Part 884 Medical devices. Therefore, under the Federal Food, Drug, and Cosmetic Act and under authority delegated to the Commissioner of Food and Drugs, 21 CFR part 884 is amended as follows: PART 884—OBSTETRICAL AND GYNECOLOGICAL DEVICES sradovich on DSK3GMQ082PROD with RULES 1603 1. The authority citation for part 884 continues to read as follows: 2. Add § 884.4910 to subpart E to read as follows: ■ VerDate Sep<11>2014 17:18 Jan 05, 2017 Jkt 241001 [FR Doc. 2016–31862 Filed 1–5–17; 8:45 am] BILLING CODE 4164–01–P PO 00000 Frm 00011 Fmt 4700 Sfmt 4700 [EPA–R05–OAR–2016–0396; FRL–9957–80– Region 5] Air Plan Approval; Ohio; Redesignation of the Cleveland, Ohio Area to Attainment of the 2008 Ozone Standard Environmental Protection Agency (EPA). ACTION: Final rule. AGENCY: The Environmental Protection Agency (EPA) finds that the ClevelandAkron-Lorain, Ohio area (Cleveland area) is attaining the 2008 ozone National Ambient Air Quality Standard (NAAQS or standard) and is redesignating the area to attainment for the 2008 ozone NAAQS, because the area meets the statutory requirements for redesignation under the Clean Air Act (CAA). The Cleveland area includes Ashtabula, Cuyahoga, Geauga, Lake, Lorain, Medina, Portage, and Summit counties. EPA is also approving, as a revision to the Ohio State Implementation Plan (SIP), the state’s plan for maintaining the 2008 ozone standard through 2030 in the Cleveland area. Finally, EPA finds adequate and is approving the state’s 2020 and 2030 volatile organic compound (VOC) and oxides of nitrogen (NOX) Motor Vehicle Emission Budgets (MVEBs) for the Cleveland area. The Ohio Environmental Protection Agency (Ohio EPA) submitted the SIP revision and redesignation request on July 6, 2016. DATES: This final rule is effective January 6, 2017. ADDRESSES: EPA has established a docket for this action under Docket ID No. EPA–R05–OAR–2016–0396. All documents in the docket are listed in the http://www.regulations.gov Web site. Although listed in the index, some information is not publicly available, e.g., Confidential Business Information or other information whose disclosure is restricted by statute. Certain other material, such as copyrighted material, is not placed on the Internet and will be publicly available only in hard copy form. Publicly available docket materials are available either through http://www.regulations.gov, or please contact the person identified in the FOR FURTHER INFORMATION CONTACT section for additional availability information. FOR FURTHER INFORMATION CONTACT: Jenny Liljegren, Physical Scientist, Attainment Planning and Maintenance Section, Air Programs Branch (AR–18J), SUMMARY: E:\FR\FM\06JAR1.SGM 06JAR1
[Pages 1598-1603]
[FR Doc No: 2016-31862]
Obstetrical and Gynecological Devices; Reclassification of
Surgical Instrumentation for Use With Urogynecologic Surgical Mesh
reclassifying surgical instrumentation for use with urogynecologic
surgical mesh from class I (general controls) exempt from premarket
notification to class II (special controls) and subject to premarket
notification, and identifying them as ``specialized surgical
instrumentation for use with urogynecologic surgical mesh.'' FDA is
designating special controls that are necessary to provide a reasonable
assurance of safety and effectiveness of the device. FDA is
reclassifying this device on its own initiative based on new
DATES: This order is effective January 6, 2017. See further discussion
in section V, ``Implementation Strategy.''
FOR FURTHER INFORMATION CONTACT: Sharon Andrews, Center for Devices and
Radiological Health, 10903 New Hampshire Ave., Bldg. 66, Rm. G110,
Silver Spring, MD 20993, 301-796-6529, Sharon.Andrews@fda.hhs.gov.
The Federal Food, Drug, and Cosmetic Act (the FD&C Act) (21 U.S.C.
301 et seq.), as amended, established a comprehensive system for the
regulation of medical devices intended for human use. Section 513 of
the FD&C Act (21 U.S.C. 360c) established three categories (classes) of
devices, reflecting the regulatory controls needed to provide
Devices that were in commercial distribution before the enactment
of the 1976 amendments on May 28, 1976, are generally referred to as
preamendments devices. Under section 513(d) of the FD&C Act,
preamendments devices are classified after FDA has: (1) Received a
committee); (2) published the panel's recommendation for comment, along
with a proposed regulation classifying the device; and (3) published a
1976, are generally referred to as postamendments devices.
Postamendments devices are automatically classified into class III
without any FDA rulemaking process (section 513(f) of the FD&C Act).
Postamendments devices remain in class III and require premarket
approval unless, and until, the device is reclassified into class I or
II or FDA issues an order finding the device to be substantially
equivalent, under section 513(i) of the FD&C Act, to a predicate device
of premarket notification procedures in section 510(k) of the FD&C Act
(21 U.S.C. 360(k)) and 21 CFR part 807.
On July 9, 2012, the Food and Drug Administration Safety and
Innovation Act (FDASIA) (Pub. L. 112-144) was enacted. Section 608(a)
of FDASIA amended section 513(e) of the FD&C Act, changing the
a device. The term ``new information,'' as used in section 513(e) of
the FD&C Act, includes information developed as a result of a
reevaluation of the data before the Agency when the device was
originally classified, as well as information not presented, not
FD&C Act and Sec.  860.7(c)(2) (21 CFR 860.7(c)(2)). (See, e.g., Gen.
Medical Co. v. FDA, 770 F.2d 214 (D.C. Cir. 1985); Contact Lens Mfrs.
Assoc. v. FDA, 766 F.2d 592 (D.C. Cir. 1985), cert. denied, 474 U.S.
1062 (1986).) To be considered in the reclassification process, the
``valid scientific evidence'' upon which the Agency relies must be
publicly available. Publicly available information excludes trade
secret and/or confidential commercial information, e.g., the contents
of a pending premarket approval application (PMA). (See section 520(c)
of the FD&C Act (21 U.S.C. 360j(c)).)
The process for issuing a final reclassification order is specified
in section 513(e)(1) of the FD&C Act. Prior to the issuance of a final
of a proposed order in the Federal Register;
(2) a meeting of a device classification panel described in section
513(b) of the FD&C Act; and (3) consideration of comments to a public
In the Federal Register of May 1, 2014, FDA published a proposed
order to reclassify surgical mesh for transvaginal pelvic organ
prolapse (POP) repair from class II to class III (79 FR 24634). In the
same order, FDA also proposed to reclassify specialized surgical
instrumentation for use with urogynecologic surgical mesh (hereafter
referred to as urogynecologic surgical mesh instrumentation) from class
I--regulated under Sec.  876.4730 (21 CFR 876.4730) (manual
gastroenterology-urology surgical instrument and accessories) and Sec.
878.4800 (21 CFR 878.4800) (manual surgical instrument for general
use)--to class II and subject to premarket notification. In the Federal
Register of January 5, 2016, FDA published two final orders that: (1)
Reclassified surgical mesh for transvaginal POP repair from class II to
class III (81 FR 354) and (2) required the filing of a PMA or notice of
completion of a product development protocol for surgical mesh for
transvaginal POP repair (81 FR 364).
In the May 1, 2014 proposed order, FDA stated that it would convene
a panel specifically to discuss reclassification of urogynecologic
surgical mesh instrumentation before finalizing reclassification of
those devices. FDA held a meeting on February 26, 2016 (81 FR 938,
January 8, 2016), of the Gastroenterology-Urology Devices Panel of the
Medical Devices Advisory Committee (``the Panel''), a device
classification panel described in section 513(b) of the FD&C Act. Prior
to the meeting, all panel members were provided a comprehensive
Executive Summary regarding the reclassification of urogynecologic
surgical mesh instrumentation, which included information contained in
the May 1, 2014, proposed order, a summary of comments submitted to the
public docket on the proposed reclassification of urogynecologic
surgical mesh instrumentation, and information regarding FDA's risk-
The Executive Summary also included a new FDA analysis of
perioperative adverse events related to urogynecologic surgical mesh
procedures. FDA conducted a new analysis to supplement the adverse
event information discussed in the May 1, 2014, proposed order, which
included adverse events related to POP procedures that were: (1)
Reported in clinical studies and systematic literature reviews in the
published literature or (2) submitted to the Manufacturer and User
Facility Device Experience (MAUDE) database between January 1, 2011,
and December 31, 2013. FDA's new analysis was a more comprehensive
analysis of perioperative adverse events associated with stress urinary
incontinence (SUI) procedures (retropubic, transobturator, mini-sling)
and POP procedures (transvaginal repair and transabdominal repair
(transabdominal POP repair is referred to as sacrocolpopexy)).
Adverse events related to a urogynecologic surgical mesh procedure,
and that might be attributable to the specialized instrumentation used
during the procedure, are typically submitted to FDA or described in
published literature with reference to the surgical mesh and not the
instrumentation. Therefore, it can be difficult to distinguish adverse
events related to the urogynecologic surgical mesh instrumentation from
those related to the surgical mesh. As noted in the proposed order, FDA
believes it is reasonable to assume that perioperative adverse events--
i.e., those observed during the procedure or shortly thereafter (e.g.,
organ perforation, hemorrhage and bleeding, nerve injury and pain)--are
caused by or related to the use of specialized surgical instrumentation
to insert, place, fix, or anchor the surgical mesh during the
urogynecologic procedure. Hereafter, the term ``perioperative adverse
events'' will be used in this document to refer to adverse events that
FDA believes are caused by or related to the specialized
instrumentation that is the subject of this reclassification.
In its new, more comprehensive analysis, FDA conducted a search of
the relevant, scientific literature published between January 1, 1997,
and December 8, 2015, to identify perioperative adverse events
associated with urogynecologic surgical mesh procedures (see the 207
studies included as references in the Executive Summary provided to the
Panel (Ref. 1). The search criteria consisted of a combination of terms
related to adverse events (type, timing with respect to surgery), type
of urogynecologic condition, type of surgical instrumentation, study
design, device name, and manufacturer name. FDA then filtered the
results to identify those studies that describe perioperative adverse
events during one of the following urogynecologic surgical mesh
procedures: SUI-retropubic, SUI-transobturator, SUI-mini-sling, POP-
transvaginal, and POP-sacrocolpopexy. All perioperative adverse events
were classified into one of the following categories: ``organ
perforation and injury,'' ``vascular injury and bleeding,'' or ``nerve
injury and pain.'' FDA then computed an adverse event rate for each
study by dividing the number of patients that experienced one of these
types of events by the total number of patients included in the study.
FDA also conducted a search of the Medical Device Reporting (MDR)
database for relevant adverse events reported between January 1, 2008,
and December 2, 2015. There are no FDA product codes specifically
assigned to urogynecologic surgical mesh instrumentation; therefore,
FDA first identified reports that were associated with a product code
assigned to urogynecologic surgical mesh. FDA filtered the resulting
injury and death reports to identify and analyze those that described
perioperative adverse events. By stratifying its analysis by product
code for the urogynecologic surgical mesh, which depends, in part, on
the procedure type (e.g., OTP is assigned to mesh used during POP-
transvaginal procedures, OTN for mesh used during SUI-retropubic or
transobturator procedures), FDA characterized the perioperative adverse
events associated with the different kinds of urogynecologic surgical
mesh instrumentation used during SUI and POP procedures.
After completing its review of the published literature and MDR
database, and aggregating its findings, FDA determined that
perioperative adverse events occur during all types of urogynecologic
surgical mesh procedures to treat female SUI and POP. Moreover, and as
discussed in the Executive Summary (Ref. 1, Attachments 6-8), FDA made
the following findings from its review of the published literature:
The rate of ``vascular injury and bleeding'' varied
between 0.4-29.4 percent in studies describing retropubic SUI
procedures; 0.2-11.9 percent in studies describing transobturator SUI
procedures; 1-20.5 percent in studies describing mini-sling SUI
procedures; 0.7-7.7 percent in studies describing transvaginal POP
repair procedures; and 2.8 percent for one study describing
sacrocolpoplexy procedures;
the rate of ``organ perforation and injury'' varied
between 0.3-23.8 percent for retropubic SUI procedures; 0.2-5.8 percent
for transobturator SUI procedures, 0.2-2.6 percent for mini-sling SUI
procedures; 0.7-13.1 percent for transvaginal POP repair procedures;
and 3.6 percent for one study describing sacrocolpoplexy procedures;
5.3 percent for retropubic SUI procedures; 0.8-30.8 percent for
transobturator SUI procedures, 1.1-4.1 percent for mini-sling SUI
procedures; 6.0-39.1 percent for transvaginal POP repair procedures;
and 14.9 percent for one study describing sacrocolpoplexy procedures.
FDA presented a summary of the information contained in the
Executive Summary during the February 26, 2016, panel meeting (Ref. 2).
The Panel then discussed whether urogynecologic surgical mesh
instrumentation should be reclassified, and if so, whether it should be
reclassified from class I (general controls) to class II (special
controls) or class III (premarket approval) (Ref. 3). The Panel
discussed a variety of potential causes for the perioperative adverse
events identified by FDA (e.g., instrumentation design, surgeon error,
and surgeon experience). The Panel consensus was that the risks to
health of urogynecologic surgical mesh instrumentation that FDA
identified in the proposed order and Executive Summary (i.e.,
perioperative risks; damage to blood vessels, nerves, connective
tissue, and other structures; adverse tissue reaction; and infection)
was a complete and accurate list.
The Panel agreed with FDA that the device is not purported or
represented for a use in supporting or sustaining human life, or for a
human health, or presents a potential unreasonable risk of illness or
injury. In light of this assessment, the Panel consensus was that
urogynecologic surgical mesh instrumentation did not meet the
definition of a class III device. The Panel also agreed with FDA that
general controls alone are not sufficient to provide reasonable
assurance of safety and effectiveness for the device, and that there is
sufficient information to establish special controls to provide such
assurance. When considering the specific special controls proposed by
FDA, two Panel members requested that an additional special control be
the submission of clinical data. However, after additional discussion,
the Panel unanimously agreed that the special controls proposed by FDA,
which did not include the submission of clinical data, would
appropriately mitigate the risks to health of this device. As such, the
Panel recommended that urogynecologic surgical mesh instrumentation be
reclassified from class I (general controls) exempt from premarket
notification to class II (special controls).
In the final order, FDA is modifying two of the special controls
included in the proposed order. First, FDA is revising Sec.
884.4910(b)(2) (21 CFR 884.4910(b)(2)) to require a demonstration that
the device, if reusable, can be adequately reprocessed. Reprocessing
validation will help to ensure that reusable urogynecologic surgical
mesh instrumentation is fit for subsequent use after being previously
used or contaminated. The validated processes are designed to remove
soil and contaminants by cleaning and to inactivate microorganisms by
disinfection or sterilization. Although FDA recognized in the proposed
order that ``the risk of infection due to inadequate sterilization and/
or reprocessing instructions/procedures can be mitigated through
sterilization validation testing and the inclusion of validated
reprocessing instructions in the device labeling,'' proposed Sec.
884.4910(b)(2) addressed sterilization only. FDA believes this revised
special control will help to mitigate the risks posed by infection from
reusable urogynecologic surgical mesh instrumentation.
Second, FDA is revising Sec.  884.4910(b)(4) to require that non-
clinical performance testing demonstrate that the device: (1) Meets all
design specifications and performance requirements and (2) performs as
intended under anticipated conditions of use. In the proposed order,
FDA specified that ``[b]ench and/or cadaver testing must demonstrate
safety and effectiveness in expected-use conditions.'' FDA has revised
the reference to ``bench and/or cadaver testing'' to ``non-clinical
performance testing'' to allow for additional types of non-clinical
testing that will also mitigate the corresponding risks to health. FDA
is making other revisions to this provision as noted previously to
provide further clarity.
FDA received comments regarding the proposed reclassification of
urogynecologic surgical mesh instrumentation from class I to class II.
A summary of the comments and FDA's responses are provided in this
section. Certain comments are grouped together under a single number
because the subject matter is similar. The number assigned to each one
is purely for organizational purposes and does not signify the
comment's value, importance, or the order in which it was received.
(Comment 1) Several comments supported reclassification of
urogynecologic surgical mesh instrumentation, with some comments
supporting reclassification into class II and others supporting
reclassification into class III.
(Response 1) FDA agrees with comments supporting reclassification
of urogynecologic surgical mesh instrumentation into class II and
disagrees with comments that support reclassification into class III.
Based on information set forth in the proposed order (79 FR 24634), FDA
tentatively concluded in that order that certain specified special
controls, in addition to general controls, were necessary to mitigate
the risks to health for urogynecologic surgical mesh instrumentation,
and as such, proposed to reclassify the device from class I to class II
(79 FR 24634 at 24640). FDA continues to believe that there is
sufficient information to establish special controls to provide a
reasonable assurance of safety and effectiveness for this device, and
thus does not believe this device should be reclassified into class
FDA's new, more comprehensive, adverse event analysis provides
further support for the risks to health of this device that FDA
identified in the proposed order (see section I; Ref. 1), and the
special controls established by FDA are specifically intended to
mitigate those risks. For example, FDA's new MDR analysis revealed that
failures of urogynecologic surgical mesh instrumentation (e.g., needle
detachments, breaks, or bends; covering sheath breaks or tears) occur
during both SUI and POP procedures, and these failures are associated
with perioperative adverse events. The special control established at
Sec.  884.4910(b)(4) addresses these failures and the risk of
perioperative injuries by requiring a demonstration that the device
meets all design specifications and performance requirements.
Based on all of this information, the Panel consensus was that
urogynecologic surgical mesh instrumentation meets the statutory
definition of a class II device and does not meet the statutory
definition of a class III device (see section I; Ref. 3).
Because FDA has determined that general controls alone are not
effectiveness for this device, and there is sufficient information to
establish special controls to provide such an assurance, FDA is
reclassifying the device into class II.
instrumentation have the same classification as the surgical mesh with
which it is indicated to be used.
(Response 2) Surgical mesh indicated for urogynecologic procedures
is a class III device when it is indicated for transvaginal POP repair
(see 81 FR 354; Sec.  884.5980) and a class II device when it is
indicated for all other urogynecologic procedures, such as
sacrocolpopexy and treatment of female SUI (see Sec.  878.3300). FDA
characterized the risk profile of different kinds of urogynecologic
surgical mesh instrumentation by analyzing adverse events associated
with the use of this specialized instrumentation and stratifying them
by the type of urogynecologic procedure for which they were used. The
results indicate that the risk profile of urogynecologic surgical mesh
instrumentation used with class III surgical mesh during transvaginal
POP repair is comparable to that of urogynecologic surgical mesh
instrumentation used with class II surgical mesh during other kinds of
urogynecologic procedures (see section I; Ref. 1). Urogynecologic
surgical mesh instrumentation used in all types of urogynecologic
surgical mesh procedures appears to have a similar risk-benefit
profile, and therefore FDA believes these devices should have the same
Moreover, as previously discussed, based on information included in
the proposed order (79 FR 24634), FDA's comprehensive adverse event
analysis (see Ref. 1), and the Panel's deliberations and
determinations, FDA has determined that urogynecologic surgical mesh
instrumentation is a class II device because general controls alone
cannot provide a reasonable assurance of safety and effectiveness, but
there is sufficient information to establish special controls to
provide such assurance. As such, FDA is reclassifying these devices
from class I to class II.
(Comment 3) One comment stated that the scope of the urogynecologic
surgical mesh instrumentation reclassification was unclear, and it
could be interpreted that the reclassification applies only to
instrumentation used for transvaginal POP repair rather than for
instrumentation used for any urogynecologic surgical mesh procedure.
(Response 3) FDA disagrees that the scope of the instrumentation
reclassification was unclear in the May 1, 2014, proposed order. FDA
included the description in the identification of urogynecologic
surgical mesh instrumentation in proposed Sec.  884.4910(a) stating
that surgical instrumentation for use with surgical mesh for
urogynecological procedures is a prescription device used to aid in
insertion, placement, fixation, or anchoring of surgical mesh for
procedures including transvaginal POP repair, sacrocolpopexy
(transabdominal POP repair), and treatment of female SUI. This
description, which is not substantively changing in the final order,
makes clear that all urogynecologic surgical mesh instrumentation--
whether used for transvaginal POP repair or other urogynecologic
surgical mesh procedures--falls under this reclassification.
(Comment 4) One comment stated that data provided in the proposed
order to support the instrumentation reclassification was based only on
POP procedures, that valid scientific evidence had not been provided to
support the instrumentation reclassification, and that no evidence was
provided to support the risks that were identified in the proposed
(Response 4) First, FDA acknowledges that the data provided to
support the instrumentation reclassification in the May 1, 2014,
proposed order derived only from surgical mesh procedures indicated for
POP. FDA subsequently conducted a new, more comprehensive analysis of
perioperative adverse events associated with a variety of SUI
procedures (retropubic, transobturator, mini-sling) and POP procedures
(transvaginal repair and sacrocolpoplexy) by reviewing adverse events
included in the relevant, scientific, published literature and adverse
events submitted to the MDR database. Based on this analysis, FDA
determined that perioperative adverse events occur during all types of
SUI and POP procedures (see section I; Ref. 1). FDA also discovered
that in the published literature, the highest reported rates of ``organ
perforation and injury,'' ``vascular injury and bleeding,'' and ``nerve
injury and pain'' were distributed across different types of
urogynecologic surgical mesh procedures rather than only occurring
during one specific type, such as transvaginal POP repair. FDA believes
these results provide further support for the reclassification of these
devices into class II, and also supports the scope of this
reclassification, which encompasses specialized instrumentation used
during all types of urogynecologic surgical mesh procedures. After
presenting the proposed order and this new information to the Panel at
the February 26, 2016, meeting, the Panel recommended that
urogynecologic surgical mesh instrumentation be reclassified from class
I (general controls) exempt from premarket notification to class II
(special controls) (Ref. 3). FDA agrees with the Panel's
recommendations and is reclassifying these devices from class I to
Second, FDA disagrees that valid scientific evidence was not
provided in the May 1, 2014, proposed order to support reclassification
of urogynecologic surgical mesh instrumentation. Valid scientific
evidence is defined in Sec.  860.7(c)(2) as evidence from well-
controlled investigations, other types of studies and 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. (See also section 513 of the FD&C Act). In the
proposed order, FDA reviewed perioperative adverse events included in
published studies of surgical mesh used during POP procedures. These
publications constitute ``valid scientific evidence'' because they are
controlled studies (Refs. 7-10, 12, 14) and collections of well-
documented case histories conducted by qualified experts (Refs. 4-6,
Finally, FDA disagrees that no evidence was provided to support the
risks of urogynecologic surgical mesh instrumentation identified in the
proposed order. In the proposed order, FDA specifically referenced
clinical studies and systematic literature reviews in the published
literature that included reports of perioperative adverse events (e.g.,
bleeding, hematoma, and blood loss; organ perforation; and
neuromuscular problems) to support the proposed reclassification.
Moreover, the risks of ``perioperative injury'' and ``pelvic pain and
neuromuscular problems'' were also identified during FDA's search of
the MAUDE database. As discussed in the proposed order, 843 reports in
the MAUDE database analysis related to bleeding, hematoma, and blood
loss; 42 reports related to organ perforation; and 196 reports of
neuromuscular problems. FDA acknowledges that no data were provided to
support the identified risks of ``infection'' and ``adverse tissue
reaction.'' Although there are many possible causes for ``infection''
and ``adverse tissue reaction'' during a urogynecologic surgical mesh
procedure, as FDA noted in the proposed order (see 79 FR 24634 at
24639), FDA believes ``infection'' and ``adverse tissue reaction'' are
general risks that apply to all devices that
As discussed throughout this document, FDA subsequently conducted a
more comprehensive search of the relevant, scientific, published
literature and MDR database to evaluate the risks of urogynecologic
surgical mesh instrumentation. A summary of the findings from these
reviews is in the Executive Summary (Ref. 1) and was provided in our
presentation to the Panel on February 26, 2016 (Ref. 2). The findings
from the literature review--which were confirmed by the MDR database
review--provide further support for the risks identified and discussed
in the proposed order.
Based on this information, the Panel consensus was that the four
risks to health of urogynecologic surgical mesh instrumentation that
FDA identified in the proposed order is a complete and accurate list
(Comment 5) One comment, which was submitted after the proposed
order issued and before the Panel meeting was held, stated that the
proposed order should be withdrawn until Panel input was obtained.
(Response 5) FDA disagrees. The process followed by FDA in
reclassifying this device is in accordance with section 513(e)(1) of
the FD&C Act. This provision requires, in relevant part, that issuance
of a final administrative order reclassifying a device be preceded by a
proposed order and a meeting of a device classification panel. There is
no requirement that a proposed order be ``withdrawn'' after its
issuance but before the Panel meeting, and the rationale for doing so
is not clear to FDA.
Under section 513(e) of the FD&C Act, FDA is adopting its findings
as published in the proposed order for urogynecologic surgical mesh
instrumentation, with the modifications discussed in section II of this
document. For the reasons set forth in the proposed order and in this
document, FDA concludes that general controls are insufficient to
provide a reasonable assurance of safety and effectiveness for
urogynecologic surgical mesh instrumentation, and there is sufficient
FDA is issuing this final order to reclassify urogynecologic
surgical mesh instrumentation from class I (general controls) exempt
from premarket notification to class II (special controls) and subject
to premarket notification, and identifying them as ``specialized
surgical instrumentation for use with urogynecologic surgical mesh.''
FDA is also establishing special controls, which are set forth in Sec.
884.4910(b)(1) through (5).
effectiveness of urogynecologic surgical mesh instrumentation, and
therefore, this device is not exempt from premarket notification
Manufacturers of urogynecologic surgical mesh instrumentation that
have not been legally marketed prior to January 6, 2017, must obtain
510(k) clearance and demonstrate compliance with the special controls
included in this final order before marketing the device.
have been legally marketed prior to January 6, 2017, must obtain 510(k)
clearance and demonstrate compliance with the special controls included
in this final order by January 8, 2018, for those devices if they wish
to continue offering them for sale.
approved under OMB control number 0910-0120 and the collections of
information under 21 CFR part 801 have been approved under OMB control
section 513(e) of the FD&C Act as amended requires FDA to issue final
orders rather than regulations, FDASIA also provides for FDA to revoke
previously issued regulations by order. FDA will continue to codify
classifications and reclassifications in the Code of Federal
Regulations (CFR). Changes resulting from final orders will appear in
the CFR as changes to codified classification determinations or as
newly codified orders. Therefore, under section 513(e)(1)(A)(i) of the
FD&C Act, as amended by FDASIA, in this final order, we are codifying
the reclassification of specialized surgical instrumentation for use
with urogynecologic surgical mesh into class II in Sec.  884.4910.
1. Executive Summary of the February 26, 2016, meeting of the
Gastroenterology-Urology Devices Panel (available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/Gastroenterology-UrologyDevicesPanel/UCM487224.pdf).
2. FDA presentation to Panel members at the February 26, 2016,
meeting of the Gastroenterology-Urology Devices Panel (available at
http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/Gastroenterology-UrologyDevicesPanel/UCM490205.pdf).
3. Transcript of the February 26, 2016, meeting of the
Gastroenterology-Urology Devices Panel (available at http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/Gastroenterology-UrologyDevicesPanel/UCM491862.pdf).
4. Caquant, F., et al., ``Safety of Trans Vaginal Mesh
Procedure: Retrospective Study
of 684 Patients,'' Journal of Obstetrics and Gynecology Research,
34(4):449-456, 2008.
5. Maher, C.F., et al., ``Surgical Management of Pelvic Organ
Prolapse in Women,'' Cochrane Database of Systematic Review, 4:
CD004014, 2010.
6. Diwadkar, G.B., et al., ``Complication and Reoperation Rates
After Apical Vaginal Prolapse Surgical Repair: A Systematic
Review,'' Obstetrics & Gynecology, 113(2 Pt. 1):67-73, 2009.
7. Maher, C.F., et al., ``Laparoscopic Sacral Colpopexy Versus
Total Vaginal Mesh for Vaginal Vault Prolapse: A Randomized Trial,''
American Journal of Obstetrics & Gynecology, 204(4):360.e1-360.e7,
8. Altman, D., et al., ``Anterior Colporrhaphy Versus
Transvaginal Mesh for Pelvic-Organ Prolapse,'' New England Journal
of Medicine, 364:1826-1836, 2011.
9. Iglesia, C.B., et al., ``Vaginal Mesh for Prolapse: A
Randomized Controlled Trial,'' Obstetrics & Gynecology, 116(2 Pt.
1):293-303, 2010.
10. Withagen, M.I., et al., ``Trocar-Guided Mesh Compared With
Conventional Vaginal Repair in Recurrent Prolapse: A Randomized
Controlled Trial,'' Obstetrics & Gynecology, 117(2 Pt. 1):242-250,
11. Sung, V.W., et al., Society of Gynecologic Surgeons
Systematic Review Group. ``Graft Use in Transvaginal Pelvic Organ
Prolapse and Urinary Incontinence,'' Obstetrics & Gynecology,
112(5):1131-1142, 2008.
12. Hiltunen, R., et al., ``Low-Weight Polypropylene Mesh for
Anterior Vaginal Wall Prolapse: A Randomized Controlled Trial,''
Obstetrics & Gynecology, 110(2 Pt. 2):455-462, 2007.
13. Jia, X., et al., ``Efficacy and Safety of Using Mesh or
Grafts in Surgery for Anterior and/or Posterior Vaginal Wall
Prolapse: Systematic Review and Meta-Analysis,'' British Journal of
Obstetrics and Gynecology, 115:1350-1361, 2008.
14. Sivaslioglu, A.A., E. Unlubilgin, and I. Dolen, ``A
Randomized Comparison of Polypropylene Mesh Surgery With Site-
Specific Surgery in the Treatment of Cystocoele,'' International
Urogynecology Journal and Pelvic Floor Dysfunction, 19(4):467-471,
884 is amended as follows:
2. Add Sec.  884.4910 to subpart E to read as follows:
Sec.  884.4910   Specialized surgical instrumentation for use with
urogynecologic surgical mesh.
(a) Identification. Specialized surgical instrumentation for use
with urogynecologic surgical mesh is a prescription device specifically
intended for use as an aid in the insertion, placement, fixation, or
anchoring of surgical mesh during urogynecologic procedures. These
procedures include transvaginal pelvic organ prolapse repair,
sacrocolpopexy (transabdominal pelvic organ prolapse repair), and
treatment of female stress urinary incontinence. Examples of
specialized surgical instrumentation include needle passers and
trocars, needle guides, fixation tools, and tissue anchors. This device
is not a manual gastroenterology-urology surgical instrument and
accessories (Sec.  876.4730) or a manual surgical instrument for
general use (Sec.  878.4800).
controls for specialized surgical instrumentation for use with
urogynecologic surgical mesh are:
(2) The device must be demonstrated to be sterile and, if reusable,
it must be demonstrated that the device can be adequately reprocessed;
(3) Performance data must support the shelf life of the device by
demonstrating package integrity and device functionality over the
requested shelf life;
(4) Non-clinical performance testing must demonstrate that the
device meets all design specifications and performance requirements,
and that the device performs as intended under anticipated conditions
(i) Information regarding the mesh design that may be used with the
(ii) Detailed summary of the clinical evaluations pertinent to use
(iv) Where components are intended to be sterilized by the user
prior to initial use and/or are reusable, validated methods and
instructions for sterilization and/or reprocessing of any reusable