[Federal Register Volume 79, Number 84 (Thursday, May 1, 2014)]
[Proposed Rules]
[Pages 24634-24642]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2014-09907]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 884

[Docket No. FDA-2014-N-0297]


Reclassification of Surgical Mesh for Transvaginal Pelvic Organ 
Prolapse Repair and Surgical Instrumentation for Urogynecologic 
Surgical Mesh Procedures; Designation of Special Controls for 
Urogynecologic Surgical Mesh Instrumentation

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed order.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
proposing to reclassify surgical mesh for transvaginal pelvic organ 
prolapse (POP) repair from class II to class III. FDA is proposing this 
reclassification based on the tentative determination that general 
controls and special controls together are not sufficient to provide 
reasonable assurance of safety and effectiveness for this device. In 
addition, FDA is proposing to reclassify urogynecologic surgical mesh 
instrumentation from class I to class II. The Agency is also proposing 
to establish special controls for surgical instrumentation for use with 
urogynecologic surgical mesh. FDA is proposing this action, based on 
the tentative determination that general controls by themselves are 
insufficient to provide reasonable assurance of the safety and 
effectiveness of these devices, and there is sufficient information to 
establish special controls to provide such assurance. The Agency is 
reclassifying both the surgical mesh for transvaginal repair and the 
urogynecologic surgical mesh instrumentation on its own initiative 
based on new information.

DATES: Submit either electronic or written comments on this proposed 
order by July 30, 2014. Please see section XIII for the proposed 
effective date of any final order that may publish based on this 
proposal.

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ADDRESSES: You may submit comments, identified by Docket No. FDA-2014-
N-0297, by any of the following methods:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following ways:
     Mail/Hand delivery/Courier (for paper submissions): 
Division of Dockets Management (HFA-305), Food and Drug Administration, 
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and Docket No. FDA-2014-N-0297 for this rulemaking. All comments 
received may be posted without change to http://www.regulations.gov, 
including any personal information provided. For additional information 
on submitting comments, see the ``Comments'' heading of the 
SUPPLEMENTARY INFORMATION section of this document.
    Docket: For access to the docket to read background documents or 
comments received, go to http://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Melissa Burns, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. 1646, Silver Spring, MD 20993, 301-796-5616, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended 
by the Medical Device Amendments of 1976 (the 1976 amendments) (Pub. L. 
94-295), the Safe Medical Devices Act of 1990 (Pub. L. 101-629), the 
Food and Drug Administration Modernization Act of 1997 (Pub. L. 105-
115), the Medical Device User Fee and Modernization Act of 2002 (Pub. 
L. 107-250), the Medical Devices Technical Corrections Act of 2004 
(Pub. L. 108-214), the Food and Drug Administration Amendments Act of 
2007 (Pub. L. 110-85), and the Food and Drug Administration Safety and 
Innovation Act (FDASIA) (Pub. L. 112-144), establishes 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) establishes 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).
    Under section 513 of the FD&C Act, devices that were in commercial 
distribution before the enactment of the 1976 amendments, May 28, 1976 
(generally referred to as 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.
    Section 513(a)(1) of the FD&C Act defines three classes of devices. 
Class I devices are those devices for which the general controls of the 
FD&C Act (controls authorized by or under sections 501, 502, 510, 516, 
518, 519, or 520 of the FD&C Act (21 U.S.C. 351, 352, 360, 360f, 360h, 
360i, and 360j), or any combination of such sections) are sufficient to 
provide reasonable assurance of safety and effectiveness; or those 
devices for which insufficient information exists to determine that 
general controls are sufficient to provide reasonable assurance of 
safety and effectiveness or to establish special controls to provide 
such assurance, but because the devices are not purported or 
represented to be for a use in supporting or sustaining human life or 
for a use that is of substantial importance in preventing impairment of 
human health, and do not present a potential unreasonable risk of 
illness or injury, are to be regulated by general controls (section 
513(a)(1)(A) of the FD&C Act). Class II devices are those devices for 
which the general controls by themselves are insufficient to provide 
reasonable assurance of safety and effectiveness, but for which there 
is sufficient information to establish special controls to provide such 
assurance, including the issuance of performance standards, postmarket 
surveillance, patient registries, development and dissemination of 
guidelines, recommendations, and other appropriate actions the Agency 
deems necessary to provide such assurance (section 513(a)(1)(B) of the 
FD&C Act; see also Sec.  860.3(c)(2) (21 CFR 860.3(c)(2))). Class III 
devices are those devices for which insufficient information exists to 
determine that general controls and special controls would provide 
reasonable assurance of safety and effectiveness, and are purported or 
represented for a use in supporting or sustaining human life or for a 
use that is of substantial importance in preventing impairment of human 
health, or present a potential unreasonable risk of illness or injury 
(section 513(a)(1)(C) of the FD&C Act).
    Section 513(e)(1) 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) 
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 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 regulatory action where the 
reevaluation is made in light of newly available regulatory authority 
(see Bell v. Goddard, supra, 366 F.2d at 181; Ethicon, Inc. v. FDA, 762 
F. Supp. 382, 389-91 (D.D.C. 1991)), or in light of changes in 
``medical science'' (See Upjohn v. Finch, supra, 422 F.2d at 951.). 
Whether data before the Agency are past or new data, the ``new 
information'' to support reclassification under section 513(e) must be 
``valid scientific evidence,'' as defined in Sec.  860.7(c)(2). (See, 
e.g., General 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).
    Section 513(e)(1) of the FD&C Act sets forth the process for 
issuing a final reclassification order. Specifically, 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; (2) 
a meeting of a device classification

[[Page 24636]]

panel described in section 513(b) of the FD&C Act; and (3) 
consideration of comments to a public docket. FDA has held a meeting of 
a device classification panel described in section 513(b) of the FD&C 
Act with respect to surgical mesh for transvaginal POP repair and, 
therefore, has met this requirement under section 513(e)(1) of the FD&C 
Act. As explained further in section VIII, a meeting of a device 
classification panel described in section 513(b) of the FD&C Act took 
place in 2011 to discuss whether surgical mesh for transvaginal POP 
repair should be reclassified to class III or remain in class II, and 
the panel recommended that the device be reclassified into class III 
because general controls and special controls would not be sufficient 
to provide a reasonable assurance of safety and effectiveness. FDA is 
not aware of new information since the 2011 panel that would provide a 
basis for a different recommendation or findings. The 2011 panel 
meeting did not include a specific discussion of surgical 
instrumentation for use with urogynecologic surgical mesh and hence FDA 
will convene a panel to discuss this issue prior to finalizing 
reclassification of instrumentation for this use.
    Section 513(e)(1)(A)(i) of the FD&C Act requires that the proposed 
reclassification order set forth the proposed reclassification and a 
substantive summary of the valid scientific evidence concerning the 
proposed reclassification, including the public health benefits of the 
use of the device; the nature and if known, incidence of the risk of 
the device; and in the case of reclassification from class II to class 
III, why general controls and special controls together are not 
sufficient to provide reasonable assurance of safety and effectiveness 
for the device.
    In accordance with section 513(e)(1), the Agency is proposing, 
based on new information that has come to the Agency's attention since 
the original classification of surgical mesh, to reclassify surgical 
mesh for transvaginal POP repair, based on the tentative determination 
that general controls and special controls are not sufficient to 
provide a reasonable assurance of safety and effectiveness. Also, the 
Agency is proposing, based on new information, to reclassify 
urogynecologic surgical mesh instrumentation from class I to class II, 
and as part of the proposed reclassification and consistent with 
section 513(a)(1)(B), is proposing to establish special controls for 
urogynecologic surgical mesh instrumentation. FDA tentatively 
determines that the general controls by themselves are insufficient to 
provide reasonable assurance of safety and effectiveness of this 
instrumentation, and there is sufficient information to establish 
special controls to provide such assurance. FDA is proposing 
reclassification of both devices based on its review of information 
received through multiple sources. These sources include: (1) 
Postmarket surveillance of medical device reports (MDRs), (2) concerns 
raised by the clinical community and citizens, and (3) the published 
literature.
    Section 515(b) of the FD&C Act (21 U.S.C. 360e) provides that for 
any class III preamendments device, FDA shall by order require such 
device to have approval of a PMA or notice of completion of a product 
development protocol (PDP). Elsewhere in this issue of the Federal 
Register, FDA is proposing to require the filing of a PMA or notice of 
completion of a PDP, which will only be finalized if FDA reclassifies 
surgical mesh for transvaginal POP repair to class III.

II. Regulatory History of the Devices

    Surgical mesh is a preamendments device classified into class II 
(Sec.  878.3300 (21 CFR 878.3300)). Beginning in 1992, FDA cleared 
premarket notification (510(k)) submissions for surgical mesh indicated 
for POP repair under the general surgical mesh classification 
regulation, Sec.  878.3300. FDA has cleared over 100 510(k) submissions 
for surgical meshes with a POP indication. Urogynecologic surgical mesh 
instrumentation is currently classified as a class I device under Sec.  
876.4730 (21 CFR 876.4730) (manual gastroenterology-urology surgical 
instrument and accessories) or Sec.  878.4800 (manual surgical 
instrument for general use).

III. Device Description

    Surgical mesh can be placed abdominally or transvaginally to repair 
POP. When placed transvaginally, surgical mesh can be placed in the 
anterior vaginal wall to aid in the correction of cystocele (anterior 
repair), in the posterior vaginal wall to aid in correction of 
rectocele (posterior repair), or attached to the vaginal wall and 
pelvic floor ligaments to correct uterine prolapse or vaginal apical 
prolapse (apical repair). These devices are made of synthetic material, 
non-synthetic material, or a combination of both. They are marketed as 
either stand-alone mesh products or mesh kits (i.e., the product 
includes mesh and instrumentation to aid insertion, placement, 
fixation, and/or anchoring).
    This proposed order does not include surgical mesh indicated for 
surgical treatment of stress urinary incontinence, sacrocolpopexy 
(transabdominal POP repair), hernia repair, and other non-
urogynecologic indications.
    Many mesh products include instrumentation specifically designed to 
aid in insertion, placement, fixation, and anchoring of the mesh in the 
body. Instrumentation can also be provided separately from the mesh 
implant. This instrumentation is typically composed of a stainless-
steel needle attached to a plastic handle and is similar to trocar 
needles used in general surgery. The needles used in mesh-augmented 
urogynecologic repair are designed to aid transvaginal or 
transabdominal insertion and placement of the mesh. Instrumentation for 
mesh-augmented POP repair can also be designed for a specific 
anatomical compartment.

IV. Proposed Reclassification

    FDA is proposing that surgical mesh for transvaginal POP repair be 
reclassified from class II to class III. FDA is also proposing that 
urogynecologic surgical mesh instrumentation be reclassified from class 
I to class II with special controls. In accordance with sections 
513(e)(1) of the FD&C Act, FDA, on its own initiative, is proposing to 
reclassify these devices based on new information.

V. Dates New Requirements Apply

    FDA is proposing that any final order based on this proposal become 
effective on the date of its publication in the Federal Register or at 
a later date if stated in the final order. If FDA finalizes this order, 
surgical mesh for transvaginal POP repair will be reclassified into 
class III and urogynecologic surgical mesh instrumentation will be 
reclassified into class II with special controls.

VI. Public Health Benefits and Risks to Health

    As required by section 513(e)(1)(A)(I) of the FD&C Act, FDA is 
providing a substantive summary of the valid scientific evidence 
regarding the public health benefit of the use of surgical mesh for 
transvaginal POP repair and urogynecologic surgical mesh 
instrumentation, and the nature and, if known, incidence of the risk of 
the devices.
    The devices have the potential to benefit the public health by 
aiding in the correction of cystocele (anterior repair), rectocele 
(posterior repair), uterine prolapse, and vaginal apical prolapse 
(apical repair).

[[Page 24637]]

    FDA has evaluated the risks to health associated with the use of 
surgical mesh indicated for transvaginal POP repair and has identified 
the following risks for this device:
    1. Perioperative risks. Organ perforation or injury and bleeding 
(including hemorrhage/hematoma).
    2. Vaginal mesh exposure (mesh visualized through the vaginal 
epithelium, e.g., separated incision line) (Ref. 1). Clinical sequelae 
include pelvic pain, infection, de novo dyspareunia (painful sex for 
patient or partner), de novo vaginal bleeding, atypical vaginal 
discharge, and the need for additional corrective surgeries (possibly 
including mesh excision).
    3. Mesh extrusion (passage of mesh into visceral organ, including 
the bladder or rectum) (Ref. 1). Clinical sequelae include pelvic pain, 
infection, de novo dyspareunia, fistula formation, and the need for 
additional corrective surgeries (possibly including suprapubic 
catheter, diverting colostomy).
    4. Other risks that can occur without mesh exposure or extrusion 
include vaginal scarring, shrinkage, and tightening (possibly caused by 
mesh/tissue contraction); pelvic pain; infection (including pelvic 
abscess); de novo dyspareunia; de novo voiding dysfunction (e.g., 
incontinence); recurrent prolapse; and neuromuscular problems 
(including groin and leg pain).
    FDA has also evaluated the risks to health associated with the use 
of urogynecologic surgical mesh instrumentation and has identified the 
following risks for this device:
    1. Perioperative risks. Organ perforation or injury and bleeding 
(including hemorrhage/hematoma).
    2. Damage to blood vessels, nerves, connective tissue, and other 
structures. This may be caused by improperly designed and/or misused 
surgical mesh instrumentation. Clinical sequelae include pelvic pain 
and neuromuscular problems.
    3. Adverse tissue reaction. This may be caused by non-biocompatible 
materials.
    4. Infection. This may be due to inadequate sterilization and/or 
reprocessing instructions or procedures.
    As discussed further in this document, these findings regarding the 
public health benefits and risks to health associated with surgical 
mesh for transvaginal POP repair and urogynecologic surgical mesh 
instrumentation are based on publicly available information, including 
the published literature and MDRs, and are supported by the reports and 
recommendations of the Obstetrics and Gynecological Devices Panel (the 
Panel) from the meeting on September 8 and 9, 2011.

VII. Summary of the Data Upon Which the Reclassification Is Based

A. Safety of Surgical Mesh Used for Transvaginal Repair of Pelvic Organ 
Prolapse

    In the published literature, mesh exposure (also referred to as 
erosion or extrusion in the published literature) is the most common 
and consistently reported mesh-related complication following 
transvaginal POP repair with mesh. In this document, we use the term 
``mesh exposure'' to refer to mesh visualized through the vaginal 
epithelium, and we use the term ``mesh extrusion'' to refer to passage 
of mesh into a visceral organ, including into the bladder or rectum.
    Mesh exposure can result in serious complications unique to mesh 
procedures and is not experienced by patients who undergo traditional 
repair. Mesh exposure may require mesh removal or excision to manage 
the sequelae (e.g., pelvic pain, infection (including pelvic abscess), 
and dyspareunia). This complication can be life altering for some women 
as mesh removal or excision may require multiple surgeries and sequelae 
may persist despite mesh removal (Ref. 2). Other clinical sequelae 
associated with mesh exposure include vaginal bleeding and vaginal 
discharge (Refs. 2 and 3).
    Less common is mesh extrusion partly or through the bladder or 
rectal mucosa (Ref. 4). In addition to the clinical sequelae previously 
described, the former may require a suprapubic catheter (Ref. 4), and 
when the latter occurs ``a diverting colostomy may be needed to excise 
and repair the erosion site and lead[s] to life-long morbidity for the 
patient'' (Ref. 5).
    A 2011 systematic review of the safety of transvaginal POP repair 
with mesh by Abed et al. cited a summary incidence of mesh exposure of 
10.3 percent (95 percent CI, 9.7-10.9 percent; range 0-29.7 percent 
within 12 months of surgery from 110 studies including 11,785 women in 
whom mesh was used for transvaginal POP repair) (Ref. 3). The incidence 
of mesh exposure did not differ between nonabsorbable synthetic mesh 
(10.3 percent) and biologic graft material (10.1 percent) (Ref. 3).
    For non-absorbable synthetic mesh exposures, 56 percent (448/795) 
of patients required surgical excision in the operating room with some 
women requiring two to three additional surgeries (Ref. 3). The one 
randomized controlled trial (RCT) with available long-term outcomes of 
anterior repair with nonabsorbable synthetic mesh found that 5 percent 
of patients had unresolved mesh exposure at 3 years of followup (Ref. 
6).
    Less information is available about management of exposure from 
biologic grafts. The review by Abed et al. found that, for the 35 women 
in which management of exposure from biologic grafts was discussed, 
half responded to local treatment with topical agents. For the 
remainder, management of the exposure was not discussed (Ref. 3).
    Mesh/tissue contraction, causing vaginal scarring, shrinkage, 
tightening, and/or pain in association with transvaginal POP repair 
with mesh, is another mesh-specific adverse event that has been 
reported in the literature (Refs. 7 and 8). However, vaginal scarring, 
shrinkage, and tightening can also occur following traditional repair.
    Other postoperative adverse events commonly reported in the 
literature that are associated with POP repair with mesh are pelvic 
pain, infection, de novo dyspareunia, de novo voiding dysfunction 
(e.g., incontinence), neuromuscular problems (including groin and leg 
pain), and additional corrective surgeries for complications or 
recurrent prolapse (Refs. 2, 7, 9, 10).
    These adverse events are not unique to POP procedures with mesh, 
but repeat surgery for complications appears to be highest for 
transvaginal POP repair with mesh, followed by sacrocolpopexy and 
traditional repair (Refs. 11 and 12). A systematic review of re-surgery 
rates following POP repair found that transvaginal surgery with mesh is 
associated with a higher rate of complications requiring reoperation 
compared to sacrocolpopexy (abdominal POP repair with mesh) or 
traditional transvaginal repair (7.2 percent vs. 4.8 percent vs. 1.9 
percent, respectively) (Ref. 11). (For transvaginal surgery with mesh, 
24 studies including 3,425 women with mean followup of 17 months were 
included in this systematic review. For sacrocolpopexy, 52 studies 
including 5,639 women with mean followup of 26 months were included, 
and for traditional transvaginal repair, 48 studies including 7,827 
women with mean followup of 32 months were included.) From the one RCT 
that directly compared sacrocolpopexy to transvaginal POP repair with 
mesh (both using synthetic nonabsorbable mesh), overall re-surgery 
within 2 years postoperative was significantly more common following 
transvaginal POP repair with mesh than laparoscopic sacrocolpopexy, 
with rates of 22 percent (12/55) and 5 percent (3/53), respectively 
(p=0.006) (Ref. 12). De novo

[[Page 24638]]

stress urinary incontinence has been reported to occur more frequently 
following anterior repair with mesh compared to traditional anterior 
repair (Ref. 13). Currently, there is no evidence in the literature 
that other postoperative adverse events occur more commonly following 
mesh repairs compared to non-mesh repairs.
    The findings within the literature are consistent with the types 
and relative frequency of adverse events that have been reported to FDA 
through the Manufacturer and User Facility Device Experience (MAUDE) 
database. Between January 1, 2011, and December 31, 2013, FDA received 
19,043 adverse events for surgical mesh used for POP repair. The most 
frequently reported adverse events were pain, erosion, and injury. 
Further discussion of the risks associated with surgical mesh for 
transvaginal POP repair is provided in FDA materials for the September 
2011 panel meeting (Ref. 14).

B. Effectiveness of Surgical Mesh Used for Transvaginal Repair of 
Pelvic Organ Prolapse

    The majority of trials evaluating effectiveness of POP repair use a 
primary effectiveness outcome of ideal anatomic support, defined as 
prolapse Stage 0 or 1 (i.e., the lowest point of prolapse is more than 
1 cm proximal to the vaginal opening) on the Pelvic Organ Prolapse 
Quantification (POP-Q) scale. This outcome measure was chosen as a 
means to provide a quantitative description of the degree of prolapse, 
but it is not correlated with POP symptoms or patient assessment of 
improvement (Ref. 15). Additionally, assessment of prolapse stage 
suffers from interobserver variability (Ref. 16).
    The published literature reveals that, although transvaginal POP 
repair with mesh often restores anatomy, it has not been shown to 
improve clinical benefit over traditional non-mesh repair and, given 
the risks associated with mesh, the probable benefits from use of the 
device do not outweigh the probable risks. This is particularly true 
for apical and posterior repair with mesh (Refs. 9, 10, 17-22).
    A systematic review of transvaginal mesh kits for apical repair 
found that they appear effective in restoring apical prolapse in the 
short term, but long-term outcomes are unknown (Ref. 23). Additionally, 
there is no evidence that transvaginal apical repair with mesh is more 
effective than traditional transvaginal apical repair. Specifically, 
only two RCTs have evaluated apical repair with mesh compared to 
traditional transvaginal repair, and neither found a significant 
improvement in anatomic outcome with mesh augmentation (Refs. 17 and 
18). Both of these RCTs evaluated synthetic nonabsorbable transvaginal 
mesh kits for multicompartment repair (i.e., anterior, posterior, or 
total (anterior and posterior) mesh placement). Of these two trials, 
Withagen et al. reported an anatomic benefit in the posterior 
compartment following posterior repair with mesh, but subjects in the 
trial who underwent posterior repair with mesh had less posterior 
prolapse at baseline than subjects who underwent traditional repair 
(Ref. 18). Therefore, the mesh arm of the Withagen et al. study was 
less ``challenged'' than the non-mesh arm. Iglesia et al. did not show 
an anatomic benefit in the posterior compartment following posterior 
repair with mesh augmentation (Ref. 17).
    The only RCT to compare posterior repair with mesh to traditional 
posterior repair (without multiple compartment repair) showed that 
subjects who underwent repair using a synthetic absorbable mesh had 
worse anatomic outcomes than those who underwent traditional repair 
(Ref. 19). Two other RCTs that compared combined anterior and posterior 
repair with mesh to traditional anterior and posterior repair found no 
additional anatomic benefit to mesh augmentation in the posterior 
compartment (Refs. 19 and 20). One of these used a synthetic absorbable 
mesh (Ref. 19) and the other used a synthetic nonabsorbable mesh (Ref. 
20).
    A 2010 review of management of posterior vaginal wall repair by 
Kudish and Iglesia states ``studies published to date do not support 
use of biologic or synthetic absorbable grafts in reconstructive 
surgical procedures of the posterior compartment as these repairs have 
not improved anatomic or functional outcomes over traditional posterior 
[repair]'' (Ref. 5). At the time of publication of this review, no 
studies comparing posterior repair with synthetic non-absorbable mesh 
to traditional posterior repair had been performed. However, as noted 
previously, reported outcomes in the three trials in which synthetic 
non-absorbable mesh was used in the posterior compartment (Refs. 17, 
18, 20) were generally consistent with the conclusions of Kudish and 
Iglesia (Ref. 5). These authors also note that, when erosion of vaginal 
mesh occurs in the posterior compartment, it often requires excision of 
exposed mesh.
    The literature does suggest that there may be an anatomic benefit 
to anterior repair with mesh augmentation (Refs. 6, 9, 10, 13, 18, 19, 
22, 24-30); however, there are significant limitations in the available 
data. The majority of the trials that showed an anatomic benefit to 
anterior repair with mesh augmentation compared to traditional repair 
used synthetic non-absorbable mesh, but only one used a synthetic 
absorbable material (Ref. 19) and one used a non-synthetic material 
(Ref. 28). Therefore, these results may not be generalizable to all 
mesh types. Only 2 of 11 peer-reviewed publications on anterior 
prolapse repair were evaluator-blinded prospective RCTs (Refs. 20, 27) 
such that evaluator bias was minimized, and these two RCTs reached 
different conclusions. One showed no anatomical improvement for the 
mesh cohort compared to the traditional non-mesh repair cohort (Ref. 
20). The second evaluator-blinded RCT did show an anatomic benefit for 
mesh in the anterior compartment, but this RCT was a single-center, 
single-investigator study (Ref. 27). Therefore, the outcomes from this 
study may not be representative of procedures performed at other 
centers by other operators.
    Although multiple trials reported in the literature report a 
benefit to POP repair with mesh compared to traditional repair, these 
trials were designed to evaluate an endpoint indicative of ideal 
anatomic support, rather than an outcome more representative of 
improvement in patient symptoms. A re-analysis of one RCT comparing 
three techniques for anterior repair (two without mesh and one with 
synthetic absorbable mesh augmentation) showed no differences in 
effectiveness across all study groups when less stringent (and 
arguably, more clinically meaningful) criterion for success, defined as 
prolapse at or above the vaginal opening, was applied (Ref. 31). The 
original trial defined recurrent prolapse as greater than Stage 1 at 1 
year postimplant and, using this definition, had concluded that 
subjects who had anterior repair with mesh augmentation were less 
likely to have recurrent prolapse.
    Additionally, patients who undergo traditional repair have 
equivalent improvement in quality of life (Refs. 20, 22, 27, 32) 
compared to patients who undergo transvaginal POP repair with mesh. The 
differential in reported success rates between mesh and non-mesh 
repairs is not reflected in the comparison of quality of life outcomes 
where no difference was observed, indicating that use of a non-symptom 
related outcome measure (i.e., ideal pelvic support determined by POP-
Q) likely accounts for this differential.

[[Page 24639]]

C. Safety and Effectiveness of Surgical Instrumentation for Use With 
Surgical Mesh for Transvaginal Pelvic Organ Prolapse Repair and Other 
Urogynecologic Procedures

    Implantation of surgical mesh for urogynecologic procedures, such 
as POP repair, is a complex procedure, and specialized surgical 
instrumentation has been developed to aid the insertion, placement, 
fixation, and anchoring of the surgical mesh. The procedure is 
performed ``blind,'' such that the surgeon cannot directly visualize 
placement of the surgical mesh, and is reliant on the surgical 
instrumentation, palpation of anatomic landmarks, and experience for 
accessing critical ligaments and attaching anchors and other devices 
needed to secure the mesh. Because adverse events related to surgical 
mesh are typically submitted with reference to the product code for the 
mesh itself, it is difficult to distinguish adverse events related to 
the surgical instrumentation from those directly related to the 
surgical mesh. However, as was discussed by the Panel (see section 
VIII), there is a concern that the use of surgical instrumentation, 
such as long trocars, can result in significant adverse events to 
patients. From January 1, 2011, to December 31, 2013, FDA received 843 
reports related to bleeding, hematoma, and blood loss, 42 reports 
related to organ perforation, and 196 reports of neuromuscular problems 
through the MAUDE database for surgical mesh indicated for POP. In 
addition, clinical studies, case reports, and systematic literature 
reviews in the published literature have reported similar perioperative 
adverse events (Refs. 7, 9, 11-13, 17, 18, 22, 24-25, 29). Given the 
nature of these adverse events, it is reasonable to assume that they 
were caused by or related to the use of instrumentation to insert, 
place, fix, or anchor the surgical mesh perioperatively.
    In addition, use of surgical instrumentation may lead to adverse 
tissue reaction as a result of using non-biocompatible materials. It 
may also lead to infection due to inadequate sterilization, inadequate 
reprocessing procedures, or use beyond the labeled expiration date. 
These are general risks that apply to devices that have patient 
contact, are provided sterile, and are reusable.
    FDA tentatively concludes that appropriately designed and labeled 
instrumentation is critical to the safe and effective use of surgical 
mesh for female urological and gynecological procedures, and that 
surgical instrumentation for this use must be adequately tested prior 
to marketing.

VIII. 2011 Classification Panel Meeting

    In October 2008, as a result of over 1,000 adverse events received, 
FDA issued a Public Health Notification (PHN) informing clinicians and 
their patients of the adverse event findings related to use of 
urogynecologic surgical mesh (Ref. 33). The PHN also provided 
recommendations for clinicians on how to mitigate the risks associated 
with these devices and information for their patients. On July 13, 
2011, based on an updated adverse event search, FDA issued a Safety 
Communication titled ``UPDATE on Serious Complications Associated With 
Transvaginal Placement of Surgical Mesh for Pelvic Organ Prolapse'' 
(Ref. 34). On the same date, FDA also issued a white paper titled 
``Urogynecologic Surgical Mesh: Update on the Safety and Effectiveness 
of Transvaginal Placement for Pelvic Organ Prolapse'' (Ref. 35). The 
continued reports of adverse events also prompted FDA to consider the 
information available regarding the use of surgical mesh for 
transvaginal POP repair and to evaluate whether the classification of 
this device type should be reconsidered.
    In accordance with section 513(e)(1) of the FD&C Act and 21 CFR 
part 860, subpart C, on September 8 and 9, 2011, FDA referred the 
proposed reclassification to the Panel for its recommendations on the 
proposed change in the device's classification from class II to class 
III, among other related questions (Ref. 14). The Panel consensus was 
that a favorable benefit-risk profile for surgical mesh used for 
transvaginal POP repair has not been well established. The Panel 
discussed the number of serious adverse events associated with the use 
of these devices and concluded that their safety is in question. In 
addition, the Panel consensus was that the effectiveness of surgical 
mesh for transvaginal POP repair has not been well established, and the 
device may not be more effective for this use than traditional non-mesh 
surgery, especially for the apical and posterior vaginal compartments.
    The Panel consensus was that premarket clinical data are needed for 
surgical mesh for transvaginal POP repair. The majority of panel 
members recommended that these devices be evaluated against a control 
arm of traditional ``native-tissue'' (nonmesh) repair to demonstrate a 
reasonable assurance of safety and effectiveness for the devices. Panel 
members also emphasized that these studies should evaluate both 
anatomic outcomes and patient satisfaction and that the duration of 
followup should be at least 1 year, with additional followup in a 
postmarket setting.
    The Panel's consensus was that each individual mesh device should 
undergo a comparison to native tissue repair in order to establish a 
reasonable assurance of safety and effectiveness. The Panel's consensus 
was that general controls and special controls together would not be 
sufficient to provide reasonable assurance of the safety and 
effectiveness of surgical mesh indicated for transvaginal POP repair, 
and that these devices should be reclassified from class II to class 
III. Panel members also expressed concern that the use of surgical 
instrumentation, such as long trocars, can result in significant 
adverse events to patients.
    Panel members also concluded that manufacturers of surgical mesh 
indicated for transvaginal POP repair should conduct postmarket studies 
of currently marketed devices. Beginning on January 3, 2012, FDA issued 
postmarket surveillance study orders to manufacturers under section 522 
of the FD&C Act (21 U.S.C. 360l) (``section 522 orders'') for 
transvaginal POP mesh products that are already legally marketed. As of 
the date of this order, FDA had issued 126 section 522 orders to 33 
manufacturers of transvaginal POP mesh products.
    The Panel also emphasized that additional work should be focused on 
patient labeling and informed consent, including providing benefit-risk 
information on available treatment options for POP--surgical and 
nonsurgical options--so patients understand long-term safety and 
effectiveness outcomes. Panel members also recommended mandatory 
registration of implanted devices, as well as surgeon training and 
credentialing. They encouraged FDA to work with other stakeholders, 
such as clinical professional organizations and industry, and to use 
existing databases and new data collection tools (e.g., registries) to 
develop a meaningful database on postmarket clinical outcomes.

IX. Summary of Reasons for Reclassification

    Based on the information reviewed by FDA relating to the safety and 
effectiveness of surgical mesh for transvaginal POP repair, including 
the valid scientific evidence discussed in section VII, FDA tentatively 
concludes that surgical mesh for transvaginal POP repair should be 
reclassified from class II to class III. As established in section

[[Page 24640]]

513(a)(1)(C) of the FD&C Act and Sec.  860.3(c)(3), a device is in 
class III if insufficient information exists to determine that general 
controls and special controls together are sufficient to provide 
reasonable assurance of its safety and effectiveness and the device is 
purported or represented to be for a use that is life-supporting or 
life-sustaining, or for a use which is of substantial importance in 
preventing impairment of human health, or if the device presents a 
potential unreasonable risk of illness or injury. FDA tentatively 
agrees with the Panel consensus that the safety and effectiveness of 
this device type has not been established and that these devices should 
be evaluated in clinical studies that compare the device to native 
tissue repair in order to establish a reasonable assurance of safety 
and effectiveness. Therefore, FDA tentatively concludes that general 
and special controls together are not sufficient to provide a 
reasonable assurance of the safety and effectiveness of surgical mesh 
intended for transvaginal POP repair. In addition, in the absence of an 
established positive benefit-risk profile, the risks to health 
associated with the use of surgical mesh for transvaginal POP repair 
identified previously present a potential unreasonable risk of illness 
or injury.
    Based on FDA's tentative determination that general controls and 
special controls together are not sufficient to provide reasonable 
assurance of safety and effectiveness of surgical mesh intended for 
transvaginal POP repair and that the device presents a potential 
unreasonable risk of illness or injury, FDA proposes to reclassify 
surgical mesh for transvaginal POP repair from class II to class III.
    The procedure for implanting surgical mesh typically involves use 
of surgical instrumentation, some of which is specifically designed and 
labeled for urogynecologic procedures, including transvaginal POP 
procedures. Instrumentation for this use is currently classified under 
existing regulations for class I devices, including Sec.  876.4730 
(manual gastroenterology-urology surgical instrument and accessories) 
or Sec.  878.4800 (manual surgical instrument for general use).
    FDA tentatively concludes that valid scientific evidence 
demonstrates that special controls, in addition to the general 
controls, are necessary to provide a reasonable assurance of safety and 
effectiveness for surgical instrumentation used for implanting surgical 
mesh for urogynecological use.
    Therefore, FDA proposes to reclassify instrumentation used for 
implanting surgical mesh for urogynecological use from class I to class 
II (special controls). If the proposed reclassification is finalized, a 
premarket notification submission that addresses, among other things, 
the special controls established for the device, would be required 
prior to marketing the device.

X. Special Controls

    FDA tentatively concludes that the following special controls, in 
addition to general controls, are sufficient to mitigate the risks to 
health described in section VI attributable to the surgical 
instrumentation for implanting surgical mesh for urogynecological 
procedures:
     The device must be demonstrated to be biocompatible;
     The device must be demonstrated to be sterile;
     Performance data must support the shelf life of the device 
by demonstrating package integrity and device functionality over the 
requested shelf life;
     Bench and/or cadaver testing must demonstrate safety and 
effectiveness in expected-use conditions; and
     Labeling must include:
    [cir] Information regarding the mesh design that may be used with 
the device;
    [cir] Detailed summary of the clinical evaluations pertinent to use 
of the device;
    [cir] Expiration date; and
    [cir] 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.
    Table 1 shows how the risks to health identified in section VI 
associated with urogynecological surgical mesh instrumentation can be 
mitigated by the proposed special controls.

    Table 1--Health Risk and Mitigation Measure for Urogynecological
                      Surgical Mesh Instrumentation
------------------------------------------------------------------------
              Identified risk                     Special controls
------------------------------------------------------------------------
Perioperative Injury......................  Bench and/or Cadaver
                                             Testing.
                                            Labeling.
                                            Shelf Life Testing.
Pelvic Pain and Neuromuscular Problems....  Bench and/or Cadaver
                                             Testing.
                                            Shelf Life Testing.
                                            Labeling.
Infection.................................  Sterilization Validation.
                                            Shelf Life Testing.
                                            Labeling
Adverse Tissue Reaction...................  Biocompatibility.
------------------------------------------------------------------------

    FDA believes that bench and/or cadaver testing can help ensure that 
urogynecologic surgical mesh instrumentation is appropriately designed 
and limits damage to blood vessels, nerves, connective tissue, and 
other structures. Also, such evaluation may help limit the adverse 
events, such as perioperative injury (organ perforation or injury and 
bleeding), pelvic pain, and neuromuscular problems, reported to the 
MAUDE database and described in the published literature as discussed 
in section VII. In addition, labeling specifying the mesh type that may 
be used with the device and provision of a detailed summary of the 
clinical evaluations pertinent to use of the device will also mitigate 
these risks. Lastly, shelf life testing demonstrating that the device 
maintains its functionality over the duration of its shelf life will 
also mitigate damage to blood vessels, nerves, connective tissue, and 
other structures, and perioperative risks.
    Also, the risk of adverse tissue reaction as a result of using non-
biocompatible materials can be mitigated by biocompatibility testing. 
FDA finds 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. In addition, FDA 
believes that shelf life testing and inclusion of an expiration date on 
the labeling will mitigate the risk of infection by ensuring that the 
device maintains its sterility over the duration of its shelf life. The 
expiration date may prevent use of the device after its validated shelf 
life.
    FDA clarifies here that these special controls are specific to 
surgical instrumentation specifically intended to be used with surgical 
mesh for urogynecological procedures. FDA intends to evaluate 
instrumentation provided with a mesh kit as part of the review of that 
surgical mesh.
    In addition, the surgical instrumentation used for implanting 
surgical mesh for urogynecological procedures are prescription devices 
within the meaning of 21 CFR 801.109.

XI. Environmental Impact

    The Agency has determined under 21 CFR 25.34(b) that this proposed 
reclassification 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.

[[Page 24641]]

XII. Paperwork Reduction Act of 1995

    This proposed 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; the collections of 
information in 21 CFR part 814, subpart B, have been approved under OMB 
control number 0910-0231; the collections of information in 21 CFR part 
812 have been approved under OMB control number 0910-0078; the 
collections of information under 21 CFR part 822 have been approved 
under OMB control number 0910-0449; and the collections of information 
under 21 CFR part 801 have been approved under OMB control number 0910-
0485.

XIII. Proposed Effective Date

    FDA is proposing that any final order based on this proposal become 
effective on the date of its publication in the Federal Register or at 
a later date if stated in the final order.

XIV. 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. Section 
513(e) as amended requires FDA to issue a final order rather than a 
regulation. FDA will codify reclassifications resulting from changes 
issued in final orders 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 proposed order we are proposing to codify the 
reclassification of surgical mesh for transvaginal pelvic organ 
prolapse repair into class III and proposing to codify the 
reclassification of specialized surgical instrumentation for use with 
urogynecologic surgical mesh devices into class II (special controls).

XV. Comments

    Interested persons may submit either electronic comments regarding 
this proposed order to http://www.regulations.gov or written comments 
to the Division of Dockets Management (see ADDRESSES). It is only 
necessary to send one set of comments. Identify comments with the 
docket number found in brackets in the heading of this document. 
Received comments may be seen in the Division of Dockets Management 
between 9 a.m. and 4 p.m., Monday through Friday, and will be posted to 
the docket at http://www.regulations.gov.

XVI. References

    FDA has placed the following references on display in the Division 
of Dockets Management (see ADDRESSES). Interested persons may see them 
between 9 a.m. and 4 p.m., Monday through Friday, and online at http://www.regulations.gov. (FDA has verified all the Web site addresses in 
this reference section, but we are not responsible for any subsequent 
changes to the Web sites after this document publishes in the Federal 
Register.)

1. Haylen, B.T., et al., ``An International Urogynecological 
Association (IUGA)/International Continence Society (ICS) Joint 
Terminology and Classification of the Complications Related Directly 
to the Insertion of Prostheses (Meshes, Implants, Tapes) and Grafts 
in Female Pelvic Floor Surgery,'' International Urogynecology 
Journal, 22(3): pp. 3-15, 2011.
2. Margulies, R.U., et al., ``Complications Requiring Reoperation 
Following Vaginal Mesh Kit Procedures for Prolapse,'' American 
Journal of Obstetrics and Gynecology, 199: pp. 678.e1-678.e4, 2008.
3. Abed, H., et al., ``Incidence and Management of Graft Erosion, 
Wound Granulation, and Dyspareunia Following Vaginal Prolapse Repair 
With Graft Materials: A Systematic Review,'' International 
Urogynecology Journal, 22(7): pp. 789-798, 2011.
4. Firoozi, F. and H. Goldman, ``Transvaginal Excision of Mesh 
Erosion Involving the Bladder After Mesh Placement Using a Prolapse 
Kit: A Novel Technique,'' Urology, 75(1): pp. 203-206, 2010.
5. Kudish, B.I. and C.B. Iglesia, ``Posterior Wall Prolapse and 
Repair,'' Clinical Obstetrics and Gynecology, 53(1): pp. 59-71, 
2010.
6. Nieminen, K., et al., ``Outcomes After Anterior Vaginal Wall 
Repair With Mesh: A Randomized, Controlled Trial with a 3 Year 
Follow-Up,'' American Journal of Obstetrics and Gynecology, 203(3): 
p. 235.e1-235.e8, 2010.
7. Caquant, F., et al., ``Safety of Trans Vaginal Mesh Procedure: 
Retrospective Study of 684 Patients,'' Journal of Obstetrics and 
Gynecology Research, 34(4): pp. 449-456, 2008.
8. Feiner, B., et al., ``Vaginal Mesh Contraction: Definition, 
Clinical Presentation, and Management,'' Obstetrics & Gynecology, 
115(2 Pt. 1): pp. 325-330, 2010.
9. Maher, C.F., et al., ``Surgical Management of Pelvic Organ 
Prolapse in Women,'' Cochrane Database of Systematic Review, 4: 
CD004014, 2010.
10. Maher, C.F., et al., ``Surgical Management of Pelvic Organ 
Prolapse in Women,'' Cochrane Database of Systematic Review, 4: 
CD004014, 2013.
11. Diwadkar, G.B., et al., ``Complication and Reoperation Rates 
After Apical Vaginal Prolapse Surgical Repair: A Systematic 
Review,'' Obstetrics & Gynecology, 113(2 Pt. 1): pp. 67-73, 2009.
12. 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): p. 360.e1-
360.e7, 2011.
13. Altman, D., et al., ``Anterior Colporrhaphy Versus Transvaginal 
Mesh for Pelvic-Organ Prolapse,'' New England Journal of Medicine, 
364: pp. 1826-1836, 2011.
14. FDA Meeting of the Obstetrics and Gynecological Devices Panel, 
September 8 and 9, 2011, available at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/ucm262488.htm. 
15. Barber, M.D., et al., ``Defining Success After Surgery for 
Pelvic Organ Prolapse,'' Obstetrics & Gynecology, 114(3): pp. 600-
609, 2009.
16. Whiteside J.L., et al., ``Clinical Evaluation of Anterior 
Vaginal Wall Support Defects: Interexaminer and Intraexaminer 
Reliability,'' American Journal Obstetrics and Gynecology, 191(1): 
pp. 100-104, 2004.
17. Iglesia, C.B., et al., ``Vaginal Mesh for Prolapse: A Randomized 
Controlled Trial,'' Obstetrics & Gynecology, 116(2 Pt. 1): pp. 293-
303, 2010.
18. 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): pp. 242-
250, 2011.
19. Sand, P.K., et al., ``Prospective Randomized Trial of 
Polyglactin 910 Mesh to Prevent Recurrence of Cystoceles and 
Rectoceles,'' American Journal of Obstetrics and Gynecology, 184(7): 
pp. 1357-1364, 2001.
20. Carey, M., et al., ``Vaginal Repair With Mesh Versus 
Colporrhaphy for Prolapse: A Randomised Controlled Trial,'' British 
Journal of Obstetrics and Gynecology, 116(10): pp. 1380-1386, 2009.
21. Paraiso, M.F.R., et al., ``Rectocele Repair: A Randomized Trial 
of Three Surgical Techniques Including Graft Augmentation,'' 
American Journal of Obstetrics and Gynecology, 195(6): pp. 1762-
1771, 2006.
22. 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): pp. 1131-
1142, 2008.
23. Feiner, B., et al., ``Efficacy and Safety of Transvaginal Mesh 
Kits in the Treatment of Prolapse of the Vaginal Apex: A Systematic 
Review,'' British Journal of Obstetrics and Gynecology, 116(1): pp. 
15-24, 2009.

[[Page 24642]]

24. Hiltunen, R., et al., ``Low-Weight Polypropylene Mesh for 
Anterior Vaginal Wall Prolapse: A Randomized Controlled Trial,'' 
Obstetrics & Gynecology, 110(2 Pt. 2): pp. 455-462, 2007.
25. 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: pp. 1350-1361, 2008.
26. Foon, R., et al., ``Adjuvant Materials in Anterior Vaginal Wall 
Prolapse Surgery: A Systematic Review of Effectiveness and 
Complications,'' International Urogyneacology Journal, 19: pp. 1697-
1706, 2008.
27. Nguyen, J.N. and R.J. Burchette, ``Outcome After Anterior 
Vaginal Prolapse Repair: A Randomized Controlled Trial,'' Obstetrics 
& Gynecology, 111(4): pp. 891-898, 2008.
28. Meschia, M., et al., ``Porcine Skin Collagen Implants to Prevent 
Anterior Vaginal Wall Prolapse Recurrence: A Multicenter, Randomized 
Study,'' Journal of Urology, 177(1): pp. 192-195, 2007.
29. 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): pp. 467-471, 2008.
30. Lunardelli, J.L., et al., ``Polypropylene Mesh vs. Site-Specific 
Repair in the Treatment of Anterior Vaginal Wall Prolapse: 
Preliminary Results of a Randomized Clinical Trial,'' Journal of the 
Brazilian College of Surgeons, 36(3): pp. 210-216, 2009.
31. Chmielewski, L., et al., ``Reanalysis of a Randomized Controlled 
Trial of Three Techniques of Anterior Colporrhaphy Using Clinically 
Relevant Definitions of Success,'' American Journal of Obstetrics 
and Gynecology, 205: 69.e1-69.e8, 2011.
32. Jia, X., et al., ``Systematic Review of the Efficacy and Safety 
of Using Mesh in Surgery for Uterine or Vaginal Vault Prolapse,'' 
International Urogynecology Journal, 21: pp. 1413-1431, 2010.
33. ``FDA Public Health Notification: Serious Complications 
Associated With Transvaginal Placement of Surgical Mesh in Repair of 
Pelvic Organ Prolapse and Stress Urinary Incontinence,'' October 20, 
2008, available at http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm061976.htm. 
34. ``FDA Safety Communication: UPDATE on Serious Complications 
Associated With Transvaginal Placement of Surgical Mesh for Pelvic 
Organ Prolapse,'' July 2011, available at http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm. 
35. FDA White Paper entitled ``Urogynecologic Surgical Mesh: Update 
on the Safety and Effectiveness of Transvaginal Placement for Pelvic 
Organ Prolapse,'' July 2011, available at http://www.fda.gov/downloads/medicaldevices/safety/alertsandnotices/ucm262760.pdf.

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, it is 
proposed that 21 CFR part 884 be amended as follows:

PART 884--OBSTETRICAL AND GYNECOLOGICAL DEVICES

0
1. The authority citation for 21 CFR part 884 continues to read as 
follows:

    Authority:  21 U.S.C. 351, 360, 360c, 360e, 360j, 371.

0
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. 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 pelvic organ prolapse repair, 
sacrocolpopexy (transabdominal pelvic organ prolapse repair), and 
treatment of female stress urinary incontinence. Examples of such 
surgical instrumentation include needle passers and trocars, needle 
guides, fixation tools, and tissue anchors. This device does not 
include manual gastroenterology-urology surgical instrument and 
accessories (Sec.  876.4730) nor manual surgical instrument for general 
use (Sec.  878.4800).
    (b) Classification. Class II (special controls). The special 
controls for this device are:
    (1) The device must be demonstrated to be biocompatible;
    (2) The device must be demonstrated to be sterile;
    (3) Performance data must support the shelf life of the device by 
demonstrating package integrity and device functionality over the 
requested shelf life;
    (4) Bench and/or cadaver testing must demonstrate safety and 
effectiveness in expected-use conditions; 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.

0
3. Add Sec.  884.5980 to Subpart F to read as follows:


Sec.  884.5980  Surgical mesh for transvaginal pelvic organ prolapse 
repair.

    (a) Identification. Surgical mesh for transvaginal pelvic organ 
prolapse repair is a prescription device intended to reinforce soft 
tissue in the pelvic floor. This device is a porous implant that is 
synthetic, non-synthetic, or both. This device does not include 
surgical mesh for other intended uses (Sec.  878.3300).
    (b) Classification. Class III (premarket approval).

    Dated: April 25, 2014.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2014-09907 Filed 4-29-14; 8:45 am]
BILLING CODE 4160-01-P