81_FR_365 81 FR 363 - Effective Date of Requirement for Premarket Approval for Surgical Mesh for Transvaginal Pelvic Organ Prolapse Repair

81 FR 363 - Effective Date of Requirement for Premarket Approval for Surgical Mesh for Transvaginal Pelvic Organ Prolapse Repair

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 81, Issue 2 (January 5, 2016)

Page Range363-370
FR Document2015-33163

The Food and Drug Administration (FDA or the Agency) is issuing a final order to require the filing of a premarket approval application (PMA) or notice of completion of a product development protocol (PDP) for surgical mesh for transvaginal pelvic organ prolapse (POP) repair.

Federal Register, Volume 81 Issue 2 (Tuesday, January 5, 2016) 
[Federal Register Volume 81, Number 2 (Tuesday, January 5, 2016)]
[Rules and Regulations]
[Pages 363-370]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-33163]



[[Page 363]]

Vol. 81

Tuesday,

No. 2

January 5, 2016

Part IV





Department of Health and Human Services





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Food and Drug Administration





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21 CFR Part 884





 Effective Date of Requirement for Premarket Approval for Surgical Mesh 
for Transvaginal Pelvic Organ Prolapse Repair; Final Rule

Federal Register / Vol. 81 , No. 2 / Tuesday, January 5, 2016 / Rules 
and Regulations

[[Page 364]]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 884

[Docket No. FDA-2014-N-0298]


Effective Date of Requirement for Premarket Approval for Surgical 
Mesh for Transvaginal Pelvic Organ Prolapse Repair

AGENCY: Food and Drug Administration, HHS.

ACTION: Final order.

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SUMMARY: The Food and Drug Administration (FDA or the Agency) is 
issuing a final order to require the filing of a premarket approval 
application (PMA) or notice of completion of a product development 
protocol (PDP) for surgical mesh for transvaginal pelvic organ prolapse 
(POP) repair.

DATES: This order is effective on January 5, 2016.

FOR FURTHER INFORMATION CONTACT: Sharon Andrews, Center for Devices and 
Radiological Health, Food and Drug Administration, 10903 New Hampshire 
Ave., Bldg. 66, Rm. G110, Silver Spring, MD 20993, 301-796-6529, 
[email protected].

SUPPLEMENTARY INFORMATION:

I. Background--Regulatory Authorities

    The Federal Food, Drug, and Cosmetic Act (the FD&C Act), as 
amended, 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) 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).
    Under section 513(d) 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.
    A preamendments device that has been classified into class III and 
devices found substantially equivalent by means of premarket 
notification (section 510(k) of the FD&C Act (21 U.S.C. 360(k)) 
procedures to such a preamendments device or to a device within that 
type (both the preamendments and substantially equivalent devices are 
referred to as preamendments class III devices) may be marketed without 
submission of a PMA until FDA issues a final order under section 515(b) 
of the FD&C Act (21 U.S.C. 360e(b)) requiring premarket approval. 
Section 515(b)(1) of the FD&C Act directs FDA to issue an order 
requiring premarket approval for a preamendments class III device.
    Under section 515(f) of the FD&C Act, the manufacturer of a 
preamendments class III device may comply with a call for PMAs by 
filing a PMA or notice of completion of a PDP. In practice, however, 
the option of filing a notice of completion of a PDP has rarely been 
used. For simplicity, although the PDP option remains available to 
manufacturers in response to a final order under section 515(b) of the 
FD&C Act, this document will refer only to the requirement for the 
filing and obtaining approval of a PMA.
    On July 9, 2012, the Food and Drug Administration Safety and 
Innovation Act (FDASIA) (Pub. L. 112-144) was enacted. Section 608(b) 
of FDASIA amended section 515(b) of the FD&C Act, changing the process 
for requiring premarket approval for a preamendments class III device 
from rulemaking to an administrative order.
    Section 515(b)(1) of the FD&C Act sets forth the process for 
issuing a final order requiring premarket approval. Specifically, prior 
to the issuance of a final order requiring premarket approval for a 
preamendments class III device, the following must occur: (1) 
Publication 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 from all affected 
stakeholders, including patients, payors, and providers. FDA published 
a proposed order to require PMAs for surgical mesh for transvaginal POP 
repair in the Federal Register of May 1, 2014 (79 FR 24642), and 
convened a meeting of a device classification panel (the ``Panel'') as 
discussed in the proposed order preamble and in this document. FDA 
received and has considered approximately 25 comments on this proposed 
order, as discussed in section III.
    Section 515(b)(3) of the FD&C Act provides that FDA shall, after 
the close of the comment period on the proposed order, consideration of 
any comments received, and a meeting of a device classification panel 
described in section 513(b) of the FD&C Act, issue a final order to 
require premarket approval or publish a document terminating the 
proceeding together with the reasons for such termination.
    A preamendments class III device may be commercially distributed 
without a PMA until 90 days after FDA issues a final order (a final 
rule issued under section 515(b) of the FD&C Act prior to the enactment 
of FDASIA is considered to be a final order for purposes of section 
501(f) of the FD&C Act (21 U.S.C. 351(f))) requiring premarket approval 
for the device, or 30 months after final classification of the device 
under section 513 of the FD&C Act, whichever is later. For surgical 
mesh for transvaginal POP repair, the later of these two time periods 
is 30 months after final classification of the device.
    Therefore, section 501(f)(2)(B) of the FD&C Act requires that a PMA 
for such devices be filed by the last day of the 30th calendar month 
following the effective date of the final order to reclassify these 
devices into class III. If a PMA is not filed by this date, then the 
device would be deemed adulterated under section 501(f) of the FD&C 
Act.
    Also, a preamendments device subject to the order process under 
section 515(b) of the FD&C Act is not required to have an approved 
investigational device exemption (IDE) (see part 812 (21 CFR part 812)) 
contemporaneous with its interstate distribution until the date 
identified by FDA in the final order requiring the filing of a PMA for 
the device. At that time, an IDE is required only if a PMA has not been 
filed. If the manufacturer, importer, or other sponsor of the device 
submits an IDE application and FDA approves it, the device may be 
distributed for investigational use. If a PMA is not filed by the later 
of the two dates, and the device is not distributed for investigational 
use under an IDE, the device is deemed to be adulterated within the 
meaning of section 501(f)(1)(A) of the FD&C Act, and subject to seizure 
and condemnation under section 304 of the FD&C Act (21 U.S.C. 334) if 
its distribution continues. Other enforcement actions include, but are 
not limited to, the following: Shipment of devices in interstate 
commerce may be subject to injunction under section 302 of the FD&C Act 
(21 U.S.C. 332), and the individuals responsible for such shipment may 
be subject to prosecution under section 303 of the FD&C Act (21 U.S.C. 
333). FDA requests that manufacturers take action

[[Page 365]]

to prevent the further use of devices for which no PMA has been filed.

II. Regulatory History of the Device

    Surgical mesh is a preamendments device, which was classified into 
class II (Sec.  878.3300 (21 CFR 878.3300)) in 1988. 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 mesh with a POP repair indication.
    In September 2011, FDA 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 (Ref. 1). The Panel discussed 
a number of serious adverse events associated with use of surgical mesh 
for transvaginal POP repair. The Panel consensus was that the safety of 
surgical mesh for transvaginal POP repair is not well established and 
that, depending on the compartment, vaginal placement of surgical mesh 
for POP repair may not be more effective than traditional ``native-
tissue'' repair without mesh. As such, the Panel concluded that the 
risk/benefit profile of surgical mesh for transvaginal POP repair is 
not well established. The Panel 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 (Ref. 1). FDA is not aware of 
new information since the Panel meeting that would provide a basis for 
a different recommendation or findings. FDA published proposed orders 
to reclassify surgical mesh for transvaginal POP repair from class II 
to class III (the 513(e) proposed order) and to require the filing of a 
PMA if the reclassification is finalized (the 515(b) proposed order) in 
the Federal Register of May 1, 2014 (79 FR 24634; 79 FR 24642). 
Elsewhere in this issue of the Federal Register, FDA is issuing a final 
order to reclassify these devices from class II to class III.

III. Public Comments in Response to the Proposed Order

    In response to the 515(b) proposed order, FDA received 26 comments. 
The comments and FDA's responses to the comments are summarized in this 
section. Certain comments are grouped together under a single number 
because the subject matter of the comments is similar. The number 
assigned to each comment is purely for organizational purposes and does 
not signify the comment's value or importance or the order in which it 
was submitted.
    (Comment 1) Nine comments were received from individuals or family 
members of individuals who underwent mesh repair for POP and/or stress 
urinary incontinence (SUI) and reported complications or adverse events 
experienced during or after their procedures. The complications and 
adverse events reported including organ perforation, mesh exposure, or 
extrusion into the vagina and/or visceral organs (in some cases 
requiring additional surgery), chronic pain, infection, lack of 
mobility, painful sexual intercourse, self-catheterization, recurrent 
prolapse and/or incontinence, blood loss during surgery (in some cases 
requiring transfusion), nerve damage, need for mesh removal and/or 
additional corrective surgery, and other permanent and/or life-altering 
adverse events.
    (Response) FDA appreciates the comments received from individuals 
sharing their experiences following surgical mesh repair for POP and 
SUI. The complications and adverse events reported by these commenters 
are consistent with those addressed in the 513(e) and 515(b) proposed 
order preambles, and discussed at the 2011 meeting of the Panel. The 
comments did not identify any adverse event information that was not 
already considered by FDA and the Panel.
    (Comment 2) Thirteen comments requested reclassification of 
surgical mesh for indications other than transvaginal POP repair, 
including for SUI and hernia.
    (Response) Surgical mesh for indications other than transvaginal 
POP repair are outside the scope of the proposed order and this final 
order. As stated in the 513(e) proposed order preamble, ``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.''
    (Comment 3) Eight comments requested a ban, recall, or ``suspension 
of use'' of all surgical mesh devices.
    (Response) As stated previously, surgical mesh for indications 
other than transvaginal POP repair is outside the scope of this final 
order. For the reasons discussed in this document, FDA does not believe 
that a ban, recall, or suspension of use of surgical mesh indicated for 
transvaginal POP repair is warranted at this time.
    Section 516 of the FD&C Act (21 U.S.C. 360f) authorizes FDA to ban 
a device when, on the basis of all available data and information, FDA 
finds that the device presents substantial deception or an unreasonable 
and substantial risk of illness or injury and, where such deception or 
risk could be corrected or eliminated by labeling or change in labeling 
and with respect to which the Secretary of the Department of Health and 
Human Services (Secretary) provided written notice to the manufacturer 
specifying the deception or risk of illness or injury, the labeling or 
change in labeling to correct the deception or eliminate or reduce such 
risk, and the period within which such labeling or change in labeling 
was to be done, such labeling or change in labeling was not done within 
such period.
    As stated earlier in this document, FDA issued a proposed order (79 
FR 24642) under section 515(b) of the FD&C Act to require the filing of 
PMAs for these devices following reclassification, which would require 
an individual demonstration of a reasonable assurance of safety and 
effectiveness for surgical mesh for transvaginal POP repair. In the 
515(b) proposed order preamble, FDA recognized the recommendations from 
the Panel that additional work should be focused on patient labeling 
and providing patients with benefit-risk information on available 
treatment options for POP, including surgical and nonsurgical options, 
so patients understand potential long-term safety and effectiveness 
outcomes. In the 515(b) proposed order, FDA tentatively asserted that 
it expects PMAs for these devices to include professional and patient 
labeling, and that the patient labeling include, among other things, 
the risks and benefits of the device and all available treatment 
options. These findings are adopted, in part, in the final order (see 
section IV, ``The Final Order'').
    Therefore, FDA does not believe that there is sufficient evidence 
at this time to support the banning of this device. Based on a review 
of the published literature as described in the 513(e) proposed order 
preamble and this document, input from clinical organizations, and the 
Panel's recommendations, FDA has determined that the safety and 
effectiveness of surgical mesh for transvaginal POP repair has not been 
established and that the collection of additional clinical evidence on 
these devices is needed. Such additional evidence may provide 
information to allow FDA to impose controls to mitigate the risks and 
more clearly characterize the benefits of these devices. In addition, 
FDA believes there are potential benefits from surgical

[[Page 366]]

mesh used for transvaginal POP repair including treatment of POP in 
appropriately selected women with severe or recurrent prolapse. As 
such, FDA has not determined that this device presents ``an 
unreasonable and substantial risk of illness or injury.''
    FDA also does not believe that there is sufficient evidence at this 
time to support a mandatory recall of this device. Under section 
518(e)(1) of the FD&C Act (21 U.S.C. 360h(e)(1)) if the Secretary finds 
that there is a reasonable probability that a device intended for human 
use would cause serious, adverse health consequences or death, the 
Secretary shall issue an order requiring the appropriate person 
(including the manufacturers, importers, distributors, or retailers of 
the device) to immediately cease distribution of such device and to 
immediately notify health professionals and device user facilities of 
the order and to instruct such professionals and facilities to cease 
use of such device.
    FDA does not believe a mandatory recall of all currently marketed 
surgical mesh for transvaginal POP repair is warranted. Based on a 
review of the published literature as described in the 513(e) proposed 
order preamble and this document, input from clinical organizations, 
and the Panel's recommendations, FDA believes that there is not 
sufficient evidence at this time to support a finding that there is a 
reasonable probability that surgical mesh for transvaginal repair of 
POP would cause serious adverse health consequences or death. As 
described in the 513(e) proposed order preamble and discussed at the 
2011 Panel meeting, the safety and effectiveness of surgical mesh for 
transvaginal repair of POP has not been established and 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.
    It is unclear what commenters were referencing when they asked FDA 
to ``suspend the use'' of these devices. As stated previously, FDA does 
not believe a ban or recall is warranted at this time, and as stated in 
this document, there are other actions FDA has taken and may take in 
the future to ensure that there is a reasonable assurance of safety and 
effectiveness of surgical mesh for transvaginal POP repair based on 
valid scientific evidence.
    FDA believes other regulatory actions it has taken will help the 
Agency to better understand the risk-benefit profile of these devices. 
FDA issued postmarket surveillance orders to manufacturers of surgical 
mesh for transvaginal POP repair starting on January 3, 2012. The 
postmarket surveillance orders allow FDA to continue to evaluate the 
benefit-risk profile of the device. Further, by reclassifying these 
devices to class III and requiring PMA approval, FDA can require an 
independent demonstration that a reasonable assurance of safety and 
effectiveness exists for each device within this type.
    FDA will consider other regulatory actions relating to this device 
as appropriate in the future.
    (Comment 4) Two comments were related to the need for testing prior 
to marketing, including an evaluation of the polypropylene material 
used to fabricate surgical mesh. One commenter stated that 
polypropylene material is inappropriate for implantation.
    (Response) FDA believes that a thorough evaluation of the material 
used to fabricate the surgical mesh is needed to provide a reasonable 
assurance of safety and effectiveness of the device. FDA discussed in 
the 515(b) proposed order preamble information that should be submitted 
in a PMA to address these issues. FDA is adopting these findings, in 
part, in the final order (see section IV, ``The Final Order'').
    Specifically, in the proposed order, FDA stated that manufacturers 
should provide biocompatibility, preclinical bench testing and 
preclinical animal studies, among other information, to demonstrate 
reasonable assurance of safety and effectiveness of surgical mesh for 
transvaginal POP repair. Such performance data, which may generally 
include assessment of the mesh chemical and physical characteristics, 
in vitro chemical characterization studies, and in vivo preclinical 
implantation studies, will be reviewed by FDA to determine whether the 
risks associated with implantation of the polypropylene material are 
appropriately mitigated. The proposed order preamble also states that a 
PMA would need to include the information required by section 515(c)(1) 
of the FD&C Act, which includes manufacturing information. FDA's review 
of such manufacturing information will allow the Agency to evaluate 
whether the polypropylene material is safe and effective for 
transvaginal POP repair. FDA is adopting these findings in the final 
order (see section IV, ``The Final Order'').
    (Comment 5) Two comments were related to the timeline for requiring 
PMAs and requested that the requirement for premarket approval be 
immediately implemented. One commenter requested that the PMA 
requirement be retroactively applied to devices currently on the 
market.
    (Response) Section 501(f)(2)(B) of the FD&C Act outlines the 
timeframe in which a PMA must be filed by manufacturers of currently 
marketed devices that are subject to a 515(b) order for the 
manufacturers to continue legally marketing their device. For devices 
subject to a 515(b) order, the provision states that a PMA must be 
submitted by the 90th day after the date the order to require PMAs is 
issued or the last day of the 30th calendar month beginning after the 
month in which the classification in class III becomes effective, 
whichever occurs later. For surgical mesh for transvaginal POP repair, 
the later of these two time periods is 30 months after final 
classification of the device. FDA must abide by the timeframe outlined 
in the FD&C Act, and therefore may not require manufacturers of devices 
subject to the final order to submit a PMA immediately.
    (Comment 6) One comment suggested that the timeframe for filing a 
PMA (within 30 months of the final reclassification) may not allow for 
adequate patient followup of ongoing clinical studies and requested 
that FDA consider the current status of clinical studies that may be 
used to support PMA submission.
    (Response) FDA has carefully considered the current status of 
ongoing clinical studies of currently marketed surgical mesh for 
transvaginal POP repair, including studies being conducted in response 
to FDA postmarket surveillance study orders issued starting on January 
3, 2012, under section 522 of the FD&C Act (21 U.S.C. 360l), and has 
concluded that the statutory timeframe for filing a PMA (the last day 
of the 30th calendar month beginning after the month in which the 
classification in class III becomes effective) is appropriate to allow 
adequate patient followup of ongoing clinical studies. In the 515(b) 
proposed order preamble, FDA stated the expectation that ``[a]t least 1 
year of outcome data should be provided in the PMA and an additional 2-
4 years of followup should be conducted postmarket.'' FDA believes it 
is reasonable to expect that a manufacturer of surgical mesh who is 
subject to a section 522 postmarket surveillance study order issued in 
2012 or 2013 will be able to collect 1 year of outcome data within 30 
months of the final reclassification.
    (Comment 7) One comment addressed FDA's ability to review a PMA 
submitted for surgical mesh for transvaginal POP repair within 180 
days. The comment stated that a 180-day PMA review commitment may not

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be attainable and the timeline does not allow for panel review. The 
commenter requested clarification regarding what actions will be taken 
should the PMA not be approved within the 180-day review period.
    (Response) Under section 515(d)(1)(A) of the FD&C Act, unless an 
exception applies, FDA must either issue an order approving or deny 
approval of a PMA within 180 days after receipt of a PMA. FDA can 
provide an extension for review when a major amendment is submitted by 
the applicant or requested by FDA (21 CFR 814.37(c)(1)). The extended 
time period for submitting an amendment allows for, among other things, 
additional time for panel review of specific device data. Generally, a 
major amendment includes a previously unreported study, significant 
updated data from a previously reported study, detailed new analyses of 
previously submitted data, or required information previously omitted.
    FDA intends to review any submitted PMA for this device type within 
the required timeframe. As soon as it completes its review of a PMA, 
FDA will issue an approval order (Sec.  814.45(d) (21 CFR 814.45(d))), 
an approvable letter (Sec.  814.45(e)), a not approvable letter (Sec.  
814.45(e)), or an order denying approval (Sec.  814.45(a)). FDA 
strongly encourages manufacturers to meet with the Agency early through 
the presubmission program for any assistance in preparation of their 
PMA to help to expedite the PMA review process.
    (Comment 8) One comment questioned FDA's reviewing urogynecologic 
surgical mesh instrumentation in a PMA if the instrumentation is 
packaged with the surgical mesh versus reviewing instrumentation in a 
510(k) notification if the instrumentation is packaged separately from 
the surgical mesh. The commenter stated that the regulatory 
requirements for instrumentation should be based on indication and not 
its packaging configuration.
    (Response) FDA agrees that the regulatory requirements for 
urogynecological surgical mesh instrumentation should be based upon the 
indications for use of the instruments and the risk of the 
instrumentation when used as intended. Based on the indications for use 
and the risks posed by these devices, in the 515(e) proposed order, FDA 
proposed to reclassify these devices from class I to class II and 
establish special controls. FDA is not finalizing this proposed 
reclassification and special controls at this time. On February 26, 
2016, FDA will convene a panel to discuss these devices prior to 
finalizing their reclassification. These devices are currently 
classified as class I under (21 CFR 876.4730) (Manual gastroenterology-
urology surgical instrument and accessories) and may be legally 
marketed without premarket review, but would require 510(k) 
notification if the proposed reclassification of the devices is 
finalized.
    When these devices and surgical mesh for transvaginal POP repair 
are packaged together, after 510(k) notification is required for the 
instrumentation, manufacturers may wish to include both products in a 
PMA for convenience. Manufacturers are permitted but not required to do 
so. If such instrumentation is included in a PMA, FDA is clarifying 
that information regarding the manufacturing process of the 
instrumentation does not need to be submitted in a premarket 
submission, as previously stated in the 515(b) proposed order preamble 
(see section IV, ``The Final Order'').
    (Comment 9) One comment related to the types of bench testing FDA 
outlined in the 515(b) proposed order that should be included in a PMA 
and whether the various type of tests apply to all mesh types. For 
example, the commenter noted that many currently marketed surgical 
meshes indicated for transvaginal POP repair use integrated anchors or 
are self-fixating and do not utilize sutures; therefore suture pullout 
strength, which was identified in the 515(b) proposed order as a mesh 
characteristic that should be evaluated, would not be a relevant 
performance specification for these types of meshes. The commenter 
requested that FDA allow manufacturers to include a justification as to 
why certain testing is not relevant to performance specifications of a 
particular device design.
    (Response) FDA recognizes that the data required to support 
premarket approval may vary by device. In the 515(b) proposed order 
preamble, FDA identified the information that should be included in a 
PMA to provide a reasonable assurance of safety and effectiveness of 
surgical mesh for transvaginal POP repair, including evaluation of 
specific mechanical characteristics. FDA agrees that manufacturers 
should be allowed to justify why specific tests are not relevant to 
their specific mesh design in lieu of testing. As noted in the 515(b) 
proposed order preamble, FDA strongly encourages manufacturers to meet 
with the Agency early through the presubmission program for any 
assistance in preparation of their PMA.
    (Comment 10) One comment related to FDA's expectations regarding 
biocompatibility and preclinical animal study evaluation. The commenter 
requested clarification regarding why FDA recommended conducting 
biocompatibility testing prior to initiation of animal studies. The 
commenter also noted that in the 515(b) proposed order, FDA identified 
a biocompatibility test (haemocompatibility), which is not outlined in 
the Center for Devices and Radiological Health (CDRH) Blue Book Memo 
#G-95-1--``Use of International Standard ISO-10993, `Biological 
Evaluation of Medical Devices Part 1: Evaluation and Testing,' '' as a 
test for consideration for a permanent implant with tissue/bone 
contact. The commenter seeks clarity regarding the specific 
biocompatibility testing FDA believes should be conducted and a 
rationale for any testing not outlined in the Blue Book Memo.
    (Response) The biocompatibility testing outlined in the 515(b) 
proposed order preamble is consistent with that recommended in the FDA 
guidance document ``Guidance for Industry and/or for FDA Reviewers/
Staff and/or Compliance: Guidance for the Preparation of a Premarket 
Notification Application for a Surgical Mesh'' issued on March 2, 1999 
(Ref. 2). There are two biocompatibility studies recommended in the 
guidance document (and the 515(b) proposed order) that are not included 
in CDRH's Blue Book Memorandum #G95-1--``Use of International Standard 
ISO-10993, `Biological Evaluation of Medical Devices Part 1: Evaluation 
and Testing,' '' dated May 1, 1995 (Ref. 3)--pyrogenicity and 
hemolysis. FDA recommended pyrogenicity testing to help protect 
patients from the risk of febrile reaction (Ref. 4). FDA recommended 
hemolysis testing on surgical mesh for transvaginal POP repair because 
red blood lysis in the surgical field may adversely affect the healing 
process.
    FDA generally recommends that biocompatibility testing be completed 
prior to preclinical animal study evaluation to ensure that the 
preclinical animal study evaluation results are valid and can be used 
to support the final device design. If biocompatibility testing and the 
preclinical animal study evaluation are conducted simultaneously and 
biocompatibility testing results are problematic or identify a safety 
concern resulting in changes to the device design or materials, the 
preclinical animal study evaluation may need to be repeated. In 
addition, the results of biocompatibility

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testing may prompt the need for additional preclinical evaluation. As 
noted in the 515(b) proposed order preamble, FDA strongly encourages 
manufacturers to meet with the Agency early through the presubmission 
program for any assistance in preparation of their PMA.
    (Comment 11) One comment stated that the preclinical animal study 
requirements outlined in the 515(b) proposed order are not clearly 
defined and requested that FDA provide additional information on study 
design and animal model selection as well as the risks that are 
intended to be mitigated by the proposed animal study.
    (Response) Preclinical animal studies are intended to evaluate the 
safety of the device, specifically the local and systemic effects of 
the device. Preclinical animal studies may not be needed to evaluate 
all surgical mesh for transvaginal POP repair; however, preclinical 
animal studies may be appropriate in some situations, for example, to 
evaluate a new mesh material or characterize the resorption rate of a 
resorbable surgical mesh product. FDA strongly encourages manufacturers 
to meet with the Agency early through the presubmission program to 
receive feedback regarding the need for preclinical animal studies, 
study design, and animal model selection to evaluate a specific 
surgical mesh for transvaginal POP repair.
    (Comment 12) One comment stated that the use of postmarket 
surveillance studies to fulfill clinical requirements for the PMA 
creates confusion regarding how such a study can have two purposes 
(postmarket surveillance and PMA approval) without compromising the 
study design and statistical rigor of the study. The comment also 
stated that the 5-year followup implied in the 515(b) proposed order is 
not in line with 3-year followup requested in the postmarket 
surveillance orders.
    (Response) In the 515(b) proposed order preamble, FDA outlined 
expectations for data collection, safety and effectiveness outcomes, 
and study followup. FDA noted that we intend to consider proposals for 
different study designs and will decide on a case-by-case basis whether 
each proposed study design is likely to generate data adequate to 
support a PMA (79 FR 24642 at 24647). In addition, we noted that FDA 
intends to consider the use of study data collected by manufacturers in 
response to FDA issued postmarket surveillance study orders (79 FR 
24642 at 24647). FDA believes that data from the section 522 postmarket 
surveillance studies may be able to fulfill the clinical requirements 
to support PMA approval--in addition to fulfilling the regulatory 
requirements of the orders issued under section 522 of the FD&C Act--if 
appropriately designed. However, as noted in the 515(b) proposed order 
preamble, FDA strongly encourages manufacturers to meet with the Agency 
to discuss specific proposals utilizing the presubmission program.
    In addition, FDA noted the following in the postmarket surveillance 
orders issued under section 522 of the FD&C Act: ``Although FDA has not 
come to a final decision on reclassification, you may wish to consider 
the data requirements for a PMA in deciding the design of your 522 
study. If you are interested in utilizing data collected to fulfill 
this 522 order to also fulfill a possible future PMA, we suggest you 
indicate your interest on the cover letter of your 522 study plan and 
discuss with FDA possible 522 study designs that may be sufficient to 
support a PMA application.'' For those manufacturers who indicated 
interest in using a 522 study to support a future PMA, FDA's review of 
their 522 protocol assessed both the requirements of the 522 order and 
the ability to generate sufficient data to support premarket approval.
    FDA also notes that the 522 orders requested collection of safety 
and effectiveness outcomes for surgical mesh for transvaginal POP 
repair at 6 months, 12 months, 18 months, 24 months, and 36 months 
following surgery. Therefore, FDA expects that the 522 studies should 
be designed to collect the 1-year outcomes requested to support 
premarket approval. FDA acknowledges that the 522 orders requested 3-
year followup. However, FDA notes that based on its detailed review of 
the information provided in a PMA, we may request additional postmarket 
followup.
    (Comment 13) One comment stated that FDA's expectation, set forth 
in the 515(b) proposed order, that patient labeling include a notice of 
availability of an FDA Safety Communication could be ``conflicting'' 
and lead to confusion because it is unclear how a reference to this 
communication would be appropriate for a device with an approved PMA 
establishing its safety and effectiveness. The commenter stated that 
the patient labeling should be focused on the benefit-risk profile of 
each product as established in the related PMA and requested that FDA 
consider alternative methods for providing the information found in the 
FDA communication to patients.
    (Response) FDA agrees that patient labeling should be reflective of 
the risks and benefits of individual devices. FDA also believes that 
there is important, relevant information in FDA's Safety Communication 
that may be helpful to patients even after PMAs are approved for this 
device type (Ref. 5). For example, the Safety Communication included 
information regarding the potential risks of surgical mesh for 
transvaginal POP repair, nonsurgical options, and recommended questions 
that patients should ask their surgeon, which may be relevant even 
after PMAs are approved for this device type. However, FDA acknowledges 
that including the notice of availability of the Safety Communication 
may not be the best way to provide patients with the relevant 
information. As a result, FDA is revising this expectation and is now 
recommending that patient labeling include relevant information from 
FDA's Safety Communication and/or FDA's Urogynecologic Surgical Mesh 
Implants Web page (Ref. 6), including but not limited to, recommended 
patient questions for their surgeon, FDA activities related to surgical 
mesh for transvaginal POP repair, and FDA contact information.
    To help ensure that patients are adequately informed, FDA also 
recommends that a link to FDA's Urogynecologic Surgical Mesh Implants 
Web page be included in the patient labeling because it provides timely 
and transparent information to the public, including appropriate 
stakeholders and patients.
    (Comment 14) One comment regarding the patient identification card 
discussed in the 515(b) proposed order noted that the card can be 
easily provided by the manufacturer, compliance with use of the card is 
dependent on the implanting physician, and should not lead to followup 
activities for the manufacturer.
    (Response) FDA recognizes that a successful identification system 
requires support from parties other than the manufacturer, such as the 
implanting physician and patient. FDA's expectation, as set forth in 
the 515(b) proposed order preamble, was that patient labeling include a 
patient identification card, which would be initially provided by the 
manufacturer. FDA does not anticipate further followup actions by the 
manufacturer. These findings are adopted, in part, in the final order 
(see section IV, ``The Final Order'').

IV. The Final Order

    Under section 515(b)(3) of the FD&C Act, FDA is adopting its 
findings, in part, as published in the preamble of the 515(b) proposed 
order (79 FR 24642) and issuing this final order to require the filing 
of a PMA for surgical mesh for

[[Page 369]]

transvaginal POP repair. As discussed in this document, FDA is amending 
certain previous findings. The Agency now finds that: (1) Manufacturing 
process information of the specialized instrumentation should not be 
included in a premarket submission and (2) patient labeling should 
include relevant information from FDA's Safety Communication and/or 
FDA's Urogynecologic Surgical Mesh Implants Web page rather than the 
notice of availability of FDA's Safety Communication. The patient 
labeling should also include a link to the FDA's Urogynecologic 
Surgical Mesh Implants Web page. This final order will revise 21 CFR 
part 884.
    Under the final order, a PMA for surgical mesh for transvaginal POP 
repair is required to be filed on or before July 5, 2018, for any 
preamendments class III devices that were in commercial distribution 
before May 28, 1976, or that has been found by FDA to be substantially 
equivalent to such a device on or before July 5, 2018. Any other device 
subject to this order is required to have an approved PMA in effect 
before it may be marketed.
    If a PMA for any of the preamendments class III devices subject to 
this order is not filed by this date, that device will be deemed 
adulterated under section 501(f)(1)(A) of the FD&C Act, and commercial 
distribution of the device must cease immediately.
    The device may, however, be distributed for investigational use, if 
the applicable requirements of the IDE regulations (part 812), 
including obtaining IDE approval, are met on or before 30 months after 
the effective date of this order. There will be no extended period for 
filing an IDE, nor exemption from the IDE requirements (see Sec.  
812.2(d)), and studies may not be initiated without appropriate IDE 
approvals, as required.

V. 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.

VI. 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; 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 part 812 
have been approved under OMB control number 0910-0078; the collections 
of information under 21 CFR 822 have been approved under OMB control 
number 0910-0449; and the collections of information under 21 CFR 801 
have been approved under OMB control number 0910-0485.

VII. Codification of Orders

    Prior to the amendments by FDASIA, section 515(b) of the FD&C Act 
provided for FDA to issue regulations to require PMA approval for 
preamendments devices or devices found substantially equivalent to 
preamendments devices. Section 515(b) of the FD&C Act, as amended by 
FDASIA, provides for FDA to require PMA approval for such devices by 
issuing a final order following the issuance of a proposed order in the 
Federal Register. FDA will continue to codify the requirement for a PMA 
approval in the Code of Federal Regulations. Therefore, under section 
515(b)(1)(A) of the FD&C Act, as amended by FDASIA, in this final 
order, we are requiring PMA approval for surgical mesh for transvaginal 
POP repair and we are making the language in 21 CFR 884.5980 consistent 
with this final order.

VIII. 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 http://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. FDA Meeting of the Obstetrics & Gynecological Devices Panel, 
September 8-9, 2011. Available at http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ObstetricsandGynecologyDevices/ucm262488.htm.
2. ``Guidance for Industry and/or for FDA Reviewers/Staff and/or 
Compliance: Guidance for the Preparation of a Premarket Notification 
Application for a Surgical Mesh'' issued on March 2, 1999. Available 
at http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm073791.pdf.
3. Blue Book Memorandum #G95-1--''Use of International Standard ISO-
10993, 'Biological Evaluation of Medical Devices Part 1: Evaluation 
and Testing' '' issued on May 1, 1995. Available at http://www.fda.gov/RegulatoryInformation/Guidances/ucm080735.htm.
4. ``Guidance for Industry Pyrogen and Endotoxins Testing: Questions 
and Answers,'' June 2012. Available at http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm310098.pdf.
5. ``Update on Serious Complications Associated with Transvaginal 
Placement of Surgical Mesh for Pelvic Organ Prolapse: FDA Safety 
Communication'' issued on July 13, 2011. Available at http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm262435.htm.
6. FDA's Urogynecologic Surgical Mesh Implants Web page. Available 
at http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ImplantsandProsthetics/UroGynSurgicalMesh/default.htm.

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

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 paragraph (c) to Sec.  884.5980 to read as follows:


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

* * * * *
    (c) Date premarket application approval or notice of completion of 
a product development protocol is required. A premarket application 
approval or notice of completion of a product development protocol for 
a device is required to be filed with the Food and Drug Administration 
on or before July 5, 2018, for any surgical mesh described in paragraph 
(a) of this section that was in commercial distribution before May 28, 
1976, or that has, on or before July 5, 2018, been found substantially 
equivalent to a surgical mesh described in paragraph (a) of this 
section that was in commercial distribution before May 28, 1976. Any 
other surgical mesh for transvaginal

[[Page 370]]

pelvic organ prolapse repair shall have an approved premarket 
application or declared completed product development protocol in 
effect before being placed in commercial distribution.

    Dated: December 30, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-33163 Filed 1-4-16; 8:45 am]
 BILLING CODE 4164-01-P

Vol. 81 Tuesday, No. 2 January 5, 2016 Part IV Department of Health and Human Services Food and Drug Administration 21 CFR Part 884 Effective Date of Requirement for Premarket Approval for Surgical Mesh for Transvaginal Pelvic Organ Prolapse Repair; Final Rule asabaliauskas on DSK5VPTVN1PROD with RULES VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00001 Fmt 4717 Sfmt 4717 E:\FR\FM\05JAR4.SGM 05JAR4

364 Federal Register / Vol. 81, No. 2 / Tuesday, January 5, 2016 / Rules and Regulations DEPARTMENT OF HEALTH AND found substantially equivalent by means received, and a meeting of a device HUMAN SERVICES of premarket notification (section 510(k) classification panel described in section of the FD&C Act (21 U.S.C. 360(k)) 513(b) of the FD&C Act, issue a final Food and Drug Administration procedures to such a preamendments order to require premarket approval or device or to a device within that type publish a document terminating the 21 CFR Part 884 (both the preamendments and proceeding together with the reasons for [Docket No. FDA–2014–N–0298] substantially equivalent devices are such termination. referred to as preamendments class III A preamendments class III device Effective Date of Requirement for devices) may be marketed without may be commercially distributed Premarket Approval for Surgical Mesh submission of a PMA until FDA issues without a PMA until 90 days after FDA for Transvaginal Pelvic Organ Prolapse a final order under section 515(b) of the issues a final order (a final rule issued Repair FD&C Act (21 U.S.C. 360e(b)) requiring under section 515(b) of the FD&C Act premarket approval. Section 515(b)(1) of prior to the enactment of FDASIA is AGENCY: Food and Drug Administration, the FD&C Act directs FDA to issue an considered to be a final order for HHS. order requiring premarket approval for a purposes of section 501(f) of the FD&C ACTION: Final order. preamendments class III device. Act (21 U.S.C. 351(f))) requiring Under section 515(f) of the FD&C Act, premarket approval for the device, or 30 SUMMARY: The Food and Drug the manufacturer of a preamendments months after final classification of the Administration (FDA or the Agency) is class III device may comply with a call device under section 513 of the FD&C issuing a final order to require the filing for PMAs by filing a PMA or notice of Act, whichever is later. For surgical of a premarket approval application completion of a PDP. In practice, mesh for transvaginal POP repair, the (PMA) or notice of completion of a however, the option of filing a notice of later of these two time periods is 30 product development protocol (PDP) for completion of a PDP has rarely been months after final classification of the surgical mesh for transvaginal pelvic used. For simplicity, although the PDP device. organ prolapse (POP) repair. option remains available to Therefore, section 501(f)(2)(B) of the DATES: This order is effective on January manufacturers in response to a final 5, 2016. FD&C Act requires that a PMA for such order under section 515(b) of the FD&C FOR FURTHER INFORMATION CONTACT: devices be filed by the last day of the Act, this document will refer only to the Sharon Andrews, Center for Devices and 30th calendar month following the requirement for the filing and obtaining Radiological Health, Food and Drug effective date of the final order to approval of a PMA. Administration, 10903 New Hampshire On July 9, 2012, the Food and Drug reclassify these devices into class III. If Ave., Bldg. 66, Rm. G110, Silver Spring, Administration Safety and Innovation a PMA is not filed by this date, then the MD 20993, 301–796–6529, Act (FDASIA) (Pub. L. 112–144) was device would be deemed adulterated sharon.andrews@fda.hhs.gov. enacted. Section 608(b) of FDASIA under section 501(f) of the FD&C Act. SUPPLEMENTARY INFORMATION: amended section 515(b) of the FD&C Also, a preamendments device subject Act, changing the process for requiring to the order process under section I. Background—Regulatory Authorities 515(b) of the FD&C Act is not required premarket approval for a The Federal Food, Drug, and Cosmetic preamendments class III device from to have an approved investigational Act (the FD&C Act), as amended, rulemaking to an administrative order. device exemption (IDE) (see part 812 (21 establishes a comprehensive system for Section 515(b)(1) of the FD&C Act sets CFR part 812)) contemporaneous with the regulation of medical devices forth the process for issuing a final order its interstate distribution until the date intended for human use. Section 513 of requiring premarket approval. identified by FDA in the final order the FD&C Act (21 U.S.C. 360c) Specifically, prior to the issuance of a requiring the filing of a PMA for the established three categories (classes) of final order requiring premarket approval device. At that time, an IDE is required devices, reflecting the regulatory for a preamendments class III device, only if a PMA has not been filed. If the controls needed to provide reasonable the following must occur: (1) manufacturer, importer, or other assurance of their safety and Publication of a proposed order in the sponsor of the device submits an IDE effectiveness. The three categories of Federal Register; (2) a meeting of a application and FDA approves it, the devices are class I (general controls), device classification panel described in device may be distributed for class II (special controls), and class III section 513(b) of the FD&C Act; and (3) investigational use. If a PMA is not filed (premarket approval). consideration of comments from all by the later of the two dates, and the Under section 513(d) of the FD&C Act, affected stakeholders, including device is not distributed for devices that were in commercial patients, payors, and providers. FDA investigational use under an IDE, the distribution before the enactment of the published a proposed order to require device is deemed to be adulterated 1976 amendments, May 28, 1976 PMAs for surgical mesh for transvaginal within the meaning of section (generally referred to as preamendments POP repair in the Federal Register of 501(f)(1)(A) of the FD&C Act, and devices), are classified after FDA has: (1) May 1, 2014 (79 FR 24642), and subject to seizure and condemnation Received a recommendation from a convened a meeting of a device under section 304 of the FD&C Act (21 device classification panel (an FDA classification panel (the ‘‘Panel’’) as U.S.C. 334) if its distribution continues. advisory committee); (2) published the discussed in the proposed order Other enforcement actions include, but panel’s recommendation for comment, preamble and in this document. FDA are not limited to, the following: asabaliauskas on DSK5VPTVN1PROD with RULES along with a proposed regulation received and has considered Shipment of devices in interstate classifying the device; and (3) published approximately 25 comments on this commerce may be subject to injunction a final regulation classifying the device. proposed order, as discussed in section under section 302 of the FD&C Act (21 FDA has classified most III. U.S.C. 332), and the individuals preamendments devices under these Section 515(b)(3) of the FD&C Act responsible for such shipment may be procedures. provides that FDA shall, after the close subject to prosecution under section 303 A preamendments device that has of the comment period on the proposed of the FD&C Act (21 U.S.C. 333). FDA been classified into class III and devices order, consideration of any comments requests that manufacturers take action VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00002 Fmt 4701 Sfmt 4700 E:\FR\FM\05JAR4.SGM 05JAR4

Federal Register / Vol. 81, No. 2 / Tuesday, January 5, 2016 / Rules and Regulations 365 to prevent the further use of devices for purposes and does not signify the available data and information, FDA which no PMA has been filed. comment’s value or importance or the finds that the device presents order in which it was submitted. substantial deception or an II. Regulatory History of the Device (Comment 1) Nine comments were unreasonable and substantial risk of Surgical mesh is a preamendments received from individuals or family illness or injury and, where such device, which was classified into class members of individuals who underwent deception or risk could be corrected or II (§ 878.3300 (21 CFR 878.3300)) in mesh repair for POP and/or stress eliminated by labeling or change in 1988. Beginning in 1992, FDA cleared urinary incontinence (SUI) and reported labeling and with respect to which the premarket notification (510(k)) complications or adverse events Secretary of the Department of Health submissions for surgical mesh indicated experienced during or after their and Human Services (Secretary) for POP repair under the general procedures. The complications and provided written notice to the surgical mesh classification regulation adverse events reported including organ manufacturer specifying the deception (§ 878.3300). FDA has cleared over 100 perforation, mesh exposure, or extrusion or risk of illness or injury, the labeling 510(k) submissions for surgical mesh into the vagina and/or visceral organs or change in labeling to correct the with a POP repair indication. (in some cases requiring additional deception or eliminate or reduce such In September 2011, FDA held a surgery), chronic pain, infection, lack of risk, and the period within which such meeting of a device classification panel mobility, painful sexual intercourse, labeling or change in labeling was to be described in section 513(b) of the FD&C self-catheterization, recurrent prolapse done, such labeling or change in Act with respect to surgical mesh for and/or incontinence, blood loss during labeling was not done within such transvaginal POP repair (Ref. 1). The surgery (in some cases requiring period. Panel discussed a number of serious transfusion), nerve damage, need for As stated earlier in this document, adverse events associated with use of mesh removal and/or additional FDA issued a proposed order (79 FR surgical mesh for transvaginal POP corrective surgery, and other permanent 24642) under section 515(b) of the FD&C repair. The Panel consensus was that and/or life-altering adverse events. Act to require the filing of PMAs for the safety of surgical mesh for (Response) FDA appreciates the these devices following reclassification, transvaginal POP repair is not well comments received from individuals which would require an individual established and that, depending on the sharing their experiences following demonstration of a reasonable assurance compartment, vaginal placement of surgical mesh repair for POP and SUI. of safety and effectiveness for surgical surgical mesh for POP repair may not be The complications and adverse events mesh for transvaginal POP repair. In the more effective than traditional ‘‘native- reported by these commenters are 515(b) proposed order preamble, FDA tissue’’ repair without mesh. As such, consistent with those addressed in the recognized the recommendations from the Panel concluded that the risk/ 513(e) and 515(b) proposed order the Panel that additional work should benefit profile of surgical mesh for preambles, and discussed at the 2011 be focused on patient labeling and transvaginal POP repair is not well meeting of the Panel. The comments did providing patients with benefit-risk established. The Panel consensus was not identify any adverse event information on available treatment that general controls and special information that was not already options for POP, including surgical and controls together would not be sufficient considered by FDA and the Panel. nonsurgical options, so patients to provide reasonable assurance of the (Comment 2) Thirteen comments understand potential long-term safety safety and effectiveness of surgical mesh requested reclassification of surgical and effectiveness outcomes. In the indicated for transvaginal POP repair, mesh for indications other than 515(b) proposed order, FDA tentatively and that these devices should be transvaginal POP repair, including for asserted that it expects PMAs for these reclassified from class II to class III (Ref. SUI and hernia. devices to include professional and 1). FDA is not aware of new information (Response) Surgical mesh for patient labeling, and that the patient since the Panel meeting that would indications other than transvaginal POP labeling include, among other things, provide a basis for a different repair are outside the scope of the the risks and benefits of the device and recommendation or findings. FDA proposed order and this final order. As all available treatment options. These published proposed orders to reclassify stated in the 513(e) proposed order findings are adopted, in part, in the final surgical mesh for transvaginal POP preamble, ‘‘This proposed order does order (see section IV, ‘‘The Final repair from class II to class III (the not include surgical mesh indicated for Order’’). 513(e) proposed order) and to require surgical treatment of stress urinary Therefore, FDA does not believe that the filing of a PMA if the reclassification incontinence, sacrocolpopexy there is sufficient evidence at this time is finalized (the 515(b) proposed order) (transabdominal POP repair), hernia to support the banning of this device. in the Federal Register of May 1, 2014 repair, and other non-urogynecologic Based on a review of the published (79 FR 24634; 79 FR 24642). Elsewhere indications.’’ literature as described in the 513(e) in this issue of the Federal Register, (Comment 3) Eight comments proposed order preamble and this FDA is issuing a final order to reclassify requested a ban, recall, or ‘‘suspension document, input from clinical these devices from class II to class III. of use’’ of all surgical mesh devices. organizations, and the Panel’s (Response) As stated previously, recommendations, FDA has determined III. Public Comments in Response to the surgical mesh for indications other than that the safety and effectiveness of Proposed Order transvaginal POP repair is outside the surgical mesh for transvaginal POP In response to the 515(b) proposed scope of this final order. For the reasons repair has not been established and that asabaliauskas on DSK5VPTVN1PROD with RULES order, FDA received 26 comments. The discussed in this document, FDA does the collection of additional clinical comments and FDA’s responses to the not believe that a ban, recall, or evidence on these devices is needed. comments are summarized in this suspension of use of surgical mesh Such additional evidence may provide section. Certain comments are grouped indicated for transvaginal POP repair is information to allow FDA to impose together under a single number because warranted at this time. controls to mitigate the risks and more the subject matter of the comments is Section 516 of the FD&C Act (21 clearly characterize the benefits of these similar. The number assigned to each U.S.C. 360f) authorizes FDA to ban a devices. In addition, FDA believes there comment is purely for organizational device when, on the basis of all are potential benefits from surgical VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00003 Fmt 4701 Sfmt 4700 E:\FR\FM\05JAR4.SGM 05JAR4

366 Federal Register / Vol. 81, No. 2 / Tuesday, January 5, 2016 / Rules and Regulations mesh used for transvaginal POP repair postmarket surveillance orders allow (Response) Section 501(f)(2)(B) of the including treatment of POP in FDA to continue to evaluate the benefit- FD&C Act outlines the timeframe in appropriately selected women with risk profile of the device. Further, by which a PMA must be filed by severe or recurrent prolapse. As such, reclassifying these devices to class III manufacturers of currently marketed FDA has not determined that this device and requiring PMA approval, FDA can devices that are subject to a 515(b) order presents ‘‘an unreasonable and require an independent demonstration for the manufacturers to continue substantial risk of illness or injury.’’ that a reasonable assurance of safety and legally marketing their device. For FDA also does not believe that there effectiveness exists for each device devices subject to a 515(b) order, the is sufficient evidence at this time to within this type. provision states that a PMA must be support a mandatory recall of this FDA will consider other regulatory submitted by the 90th day after the date device. Under section 518(e)(1) of the actions relating to this device as the order to require PMAs is issued or FD&C Act (21 U.S.C. 360h(e)(1)) if the appropriate in the future. the last day of the 30th calendar month Secretary finds that there is a reasonable (Comment 4) Two comments were beginning after the month in which the probability that a device intended for related to the need for testing prior to classification in class III becomes human use would cause serious, marketing, including an evaluation of effective, whichever occurs later. For adverse health consequences or death, the polypropylene material used to surgical mesh for transvaginal POP the Secretary shall issue an order fabricate surgical mesh. One commenter repair, the later of these two time requiring the appropriate person stated that polypropylene material is periods is 30 months after final (including the manufacturers, importers, inappropriate for implantation. classification of the device. FDA must distributors, or retailers of the device) to (Response) FDA believes that a abide by the timeframe outlined in the immediately cease distribution of such thorough evaluation of the material used FD&C Act, and therefore may not device and to immediately notify health to fabricate the surgical mesh is needed require manufacturers of devices subject professionals and device user facilities to provide a reasonable assurance of to the final order to submit a PMA of the order and to instruct such safety and effectiveness of the device. immediately. professionals and facilities to cease use FDA discussed in the 515(b) proposed (Comment 6) One comment suggested of such device. order preamble information that should that the timeframe for filing a PMA FDA does not believe a mandatory be submitted in a PMA to address these (within 30 months of the final recall of all currently marketed surgical issues. FDA is adopting these findings, reclassification) may not allow for mesh for transvaginal POP repair is in part, in the final order (see section IV, adequate patient followup of ongoing warranted. Based on a review of the ‘‘The Final Order’’). clinical studies and requested that FDA published literature as described in the Specifically, in the proposed order, consider the current status of clinical 513(e) proposed order preamble and this FDA stated that manufacturers should studies that may be used to support document, input from clinical provide biocompatibility, preclinical PMA submission. organizations, and the Panel’s bench testing and preclinical animal (Response) FDA has carefully recommendations, FDA believes that studies, among other information, to considered the current status of ongoing there is not sufficient evidence at this demonstrate reasonable assurance of clinical studies of currently marketed time to support a finding that there is a safety and effectiveness of surgical mesh surgical mesh for transvaginal POP reasonable probability that surgical for transvaginal POP repair. Such repair, including studies being mesh for transvaginal repair of POP performance data, which may generally conducted in response to FDA would cause serious adverse health include assessment of the mesh postmarket surveillance study orders consequences or death. As described in chemical and physical characteristics, issued starting on January 3, 2012, the 513(e) proposed order preamble and in vitro chemical characterization under section 522 of the FD&C Act (21 discussed at the 2011 Panel meeting, the studies, and in vivo preclinical U.S.C. 360l), and has concluded that the safety and effectiveness of surgical mesh implantation studies, will be reviewed statutory timeframe for filing a PMA for transvaginal repair of POP has not by FDA to determine whether the risks (the last day of the 30th calendar month been established and these devices associated with implantation of the beginning after the month in which the should be evaluated in clinical studies polypropylene material are classification in class III becomes that compare the device to native tissue appropriately mitigated. The proposed effective) is appropriate to allow repair in order to establish a reasonable order preamble also states that a PMA adequate patient followup of ongoing assurance of safety and effectiveness. would need to include the information clinical studies. In the 515(b) proposed It is unclear what commenters were required by section 515(c)(1) of the order preamble, FDA stated the referencing when they asked FDA to FD&C Act, which includes expectation that ‘‘[a]t least 1 year of ‘‘suspend the use’’ of these devices. As manufacturing information. FDA’s outcome data should be provided in the stated previously, FDA does not believe review of such manufacturing PMA and an additional 2–4 years of a ban or recall is warranted at this time, information will allow the Agency to followup should be conducted and as stated in this document, there are evaluate whether the polypropylene postmarket.’’ FDA believes it is other actions FDA has taken and may material is safe and effective for reasonable to expect that a manufacturer take in the future to ensure that there is transvaginal POP repair. FDA is of surgical mesh who is subject to a a reasonable assurance of safety and adopting these findings in the final section 522 postmarket surveillance effectiveness of surgical mesh for order (see section IV, ‘‘The Final study order issued in 2012 or 2013 will transvaginal POP repair based on valid Order’’). be able to collect 1 year of outcome data asabaliauskas on DSK5VPTVN1PROD with RULES scientific evidence. (Comment 5) Two comments were within 30 months of the final FDA believes other regulatory actions related to the timeline for requiring reclassification. it has taken will help the Agency to PMAs and requested that the (Comment 7) One comment addressed better understand the risk-benefit profile requirement for premarket approval be FDA’s ability to review a PMA of these devices. FDA issued postmarket immediately implemented. One submitted for surgical mesh for surveillance orders to manufacturers of commenter requested that the PMA transvaginal POP repair within 180 surgical mesh for transvaginal POP requirement be retroactively applied to days. The comment stated that a 180- repair starting on January 3, 2012. The devices currently on the market. day PMA review commitment may not VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00004 Fmt 4701 Sfmt 4700 E:\FR\FM\05JAR4.SGM 05JAR4

Federal Register / Vol. 81, No. 2 / Tuesday, January 5, 2016 / Rules and Regulations 367 be attainable and the timeline does not devices prior to finalizing their (Comment 10) One comment related allow for panel review. The commenter reclassification. These devices are to FDA’s expectations regarding requested clarification regarding what currently classified as class I under (21 biocompatibility and preclinical animal actions will be taken should the PMA CFR 876.4730) (Manual study evaluation. The commenter not be approved within the 180-day gastroenterology-urology surgical requested clarification regarding why review period. instrument and accessories) and may be FDA recommended conducting (Response) Under section 515(d)(1)(A) legally marketed without premarket biocompatibility testing prior to of the FD&C Act, unless an exception review, but would require 510(k) initiation of animal studies. The applies, FDA must either issue an order notification if the proposed commenter also noted that in the 515(b) approving or deny approval of a PMA reclassification of the devices is proposed order, FDA identified a within 180 days after receipt of a PMA. finalized. biocompatibility test FDA can provide an extension for When these devices and surgical (haemocompatibility), which is not review when a major amendment is mesh for transvaginal POP repair are outlined in the Center for Devices and submitted by the applicant or requested packaged together, after 510(k) Radiological Health (CDRH) Blue Book by FDA (21 CFR 814.37(c)(1)). The notification is required for the Memo #G–95–1—‘‘Use of International extended time period for submitting an instrumentation, manufacturers may Standard ISO–10993, ‘Biological amendment allows for, among other wish to include both products in a PMA Evaluation of Medical Devices Part 1: things, additional time for panel review for convenience. Manufacturers are Evaluation and Testing,’ ’’ as a test for of specific device data. Generally, a permitted but not required to do so. If consideration for a permanent implant major amendment includes a previously such instrumentation is included in a with tissue/bone contact. The unreported study, significant updated PMA, FDA is clarifying that information commenter seeks clarity regarding the data from a previously reported study, regarding the manufacturing process of specific biocompatibility testing FDA detailed new analyses of previously the instrumentation does not need to be believes should be conducted and a submitted data, or required information submitted in a premarket submission, as rationale for any testing not outlined in previously omitted. previously stated in the 515(b) proposed the Blue Book Memo. FDA intends to review any submitted order preamble (see section IV, ‘‘The (Response) The biocompatibility PMA for this device type within the Final Order’’). testing outlined in the 515(b) proposed required timeframe. As soon as it (Comment 9) One comment related to order preamble is consistent with that completes its review of a PMA, FDA the types of bench testing FDA outlined recommended in the FDA guidance will issue an approval order (§ 814.45(d) in the 515(b) proposed order that should document ‘‘Guidance for Industry and/ (21 CFR 814.45(d))), an approvable letter be included in a PMA and whether the or for FDA Reviewers/Staff and/or (§ 814.45(e)), a not approvable letter various type of tests apply to all mesh Compliance: Guidance for the (§ 814.45(e)), or an order denying types. For example, the commenter Preparation of a Premarket Notification approval (§ 814.45(a)). FDA strongly noted that many currently marketed Application for a Surgical Mesh’’ issued encourages manufacturers to meet with surgical meshes indicated for on March 2, 1999 (Ref. 2). There are two the Agency early through the transvaginal POP repair use integrated biocompatibility studies recommended presubmission program for any anchors or are self-fixating and do not in the guidance document (and the assistance in preparation of their PMA utilize sutures; therefore suture pullout 515(b) proposed order) that are not to help to expedite the PMA review strength, which was identified in the included in CDRH’s Blue Book process. 515(b) proposed order as a mesh Memorandum #G95–1—‘‘Use of (Comment 8) One comment characteristic that should be evaluated, International Standard ISO–10993, questioned FDA’s reviewing would not be a relevant performance ‘Biological Evaluation of Medical urogynecologic surgical mesh specification for these types of meshes. Devices Part 1: Evaluation and instrumentation in a PMA if the The commenter requested that FDA Testing,’ ’’ dated May 1, 1995 (Ref. 3)— instrumentation is packaged with the allow manufacturers to include a pyrogenicity and hemolysis. FDA surgical mesh versus reviewing justification as to why certain testing is recommended pyrogenicity testing to instrumentation in a 510(k) notification not relevant to performance help protect patients from the risk of if the instrumentation is packaged specifications of a particular device febrile reaction (Ref. 4). FDA separately from the surgical mesh. The design. recommended hemolysis testing on commenter stated that the regulatory (Response) FDA recognizes that the surgical mesh for transvaginal POP requirements for instrumentation data required to support premarket repair because red blood lysis in the should be based on indication and not approval may vary by device. In the surgical field may adversely affect the its packaging configuration. 515(b) proposed order preamble, FDA healing process. (Response) FDA agrees that the identified the information that should FDA generally recommends that regulatory requirements for be included in a PMA to provide a biocompatibility testing be completed urogynecological surgical mesh reasonable assurance of safety and prior to preclinical animal study instrumentation should be based upon effectiveness of surgical mesh for evaluation to ensure that the preclinical the indications for use of the transvaginal POP repair, including animal study evaluation results are instruments and the risk of the evaluation of specific mechanical valid and can be used to support the instrumentation when used as intended. characteristics. FDA agrees that final device design. If biocompatibility Based on the indications for use and the manufacturers should be allowed to testing and the preclinical animal study asabaliauskas on DSK5VPTVN1PROD with RULES risks posed by these devices, in the justify why specific tests are not evaluation are conducted 515(e) proposed order, FDA proposed to relevant to their specific mesh design in simultaneously and biocompatibility reclassify these devices from class I to lieu of testing. As noted in the 515(b) testing results are problematic or class II and establish special controls. proposed order preamble, FDA strongly identify a safety concern resulting in FDA is not finalizing this proposed encourages manufacturers to meet with changes to the device design or reclassification and special controls at the Agency early through the materials, the preclinical animal study this time. On February 26, 2016, FDA presubmission program for any evaluation may need to be repeated. In will convene a panel to discuss these assistance in preparation of their PMA. addition, the results of biocompatibility VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00005 Fmt 4701 Sfmt 4700 E:\FR\FM\05JAR4.SGM 05JAR4

368 Federal Register / Vol. 81, No. 2 / Tuesday, January 5, 2016 / Rules and Regulations testing may prompt the need for approval—in addition to fulfilling the relevant information in FDA’s Safety additional preclinical evaluation. As regulatory requirements of the orders Communication that may be helpful to noted in the 515(b) proposed order issued under section 522 of the FD&C patients even after PMAs are approved preamble, FDA strongly encourages Act—if appropriately designed. for this device type (Ref. 5). For manufacturers to meet with the Agency However, as noted in the 515(b) example, the Safety Communication early through the presubmission proposed order preamble, FDA strongly included information regarding the program for any assistance in encourages manufacturers to meet with potential risks of surgical mesh for preparation of their PMA. the Agency to discuss specific proposals transvaginal POP repair, nonsurgical (Comment 11) One comment stated utilizing the presubmission program. options, and recommended questions that the preclinical animal study In addition, FDA noted the following that patients should ask their surgeon, requirements outlined in the 515(b) in the postmarket surveillance orders which may be relevant even after PMAs proposed order are not clearly defined issued under section 522 of the FD&C are approved for this device type. and requested that FDA provide Act: ‘‘Although FDA has not come to a However, FDA acknowledges that additional information on study design final decision on reclassification, you including the notice of availability of and animal model selection as well as may wish to consider the data the Safety Communication may not be the risks that are intended to be requirements for a PMA in deciding the the best way to provide patients with mitigated by the proposed animal study. design of your 522 study. If you are the relevant information. As a result, (Response) Preclinical animal studies interested in utilizing data collected to FDA is revising this expectation and is are intended to evaluate the safety of the fulfill this 522 order to also fulfill a now recommending that patient labeling device, specifically the local and possible future PMA, we suggest you include relevant information from systemic effects of the device. indicate your interest on the cover letter FDA’s Safety Communication and/or Preclinical animal studies may not be of your 522 study plan and discuss with FDA’s Urogynecologic Surgical Mesh needed to evaluate all surgical mesh for FDA possible 522 study designs that Implants Web page (Ref. 6), including transvaginal POP repair; however, may be sufficient to support a PMA but not limited to, recommended patient preclinical animal studies may be application.’’ For those manufacturers questions for their surgeon, FDA appropriate in some situations, for who indicated interest in using a 522 activities related to surgical mesh for example, to evaluate a new mesh study to support a future PMA, FDA’s transvaginal POP repair, and FDA material or characterize the resorption review of their 522 protocol assessed contact information. rate of a resorbable surgical mesh both the requirements of the 522 order To help ensure that patients are product. FDA strongly encourages and the ability to generate sufficient adequately informed, FDA also manufacturers to meet with the Agency data to support premarket approval. recommends that a link to FDA’s early through the presubmission FDA also notes that the 522 orders Urogynecologic Surgical Mesh Implants program to receive feedback regarding requested collection of safety and Web page be included in the patient the need for preclinical animal studies, effectiveness outcomes for surgical labeling because it provides timely and study design, and animal model mesh for transvaginal POP repair at 6 transparent information to the public, selection to evaluate a specific surgical months, 12 months, 18 months, 24 including appropriate stakeholders and mesh for transvaginal POP repair. months, and 36 months following patients. (Comment 12) One comment stated surgery. Therefore, FDA expects that the (Comment 14) One comment that the use of postmarket surveillance 522 studies should be designed to regarding the patient identification card studies to fulfill clinical requirements collect the 1-year outcomes requested to discussed in the 515(b) proposed order for the PMA creates confusion regarding support premarket approval. FDA noted that the card can be easily how such a study can have two acknowledges that the 522 orders provided by the manufacturer, purposes (postmarket surveillance and requested 3-year followup. However, compliance with use of the card is PMA approval) without compromising FDA notes that based on its detailed dependent on the implanting physician, the study design and statistical rigor of review of the information provided in a and should not lead to followup the study. The comment also stated that PMA, we may request additional activities for the manufacturer. the 5-year followup implied in the postmarket followup. (Response) FDA recognizes that a 515(b) proposed order is not in line with (Comment 13) One comment stated successful identification system requires 3-year followup requested in the that FDA’s expectation, set forth in the support from parties other than the postmarket surveillance orders. 515(b) proposed order, that patient manufacturer, such as the implanting (Response) In the 515(b) proposed labeling include a notice of availability physician and patient. FDA’s order preamble, FDA outlined of an FDA Safety Communication could expectation, as set forth in the 515(b) expectations for data collection, safety be ‘‘conflicting’’ and lead to confusion proposed order preamble, was that and effectiveness outcomes, and study because it is unclear how a reference to patient labeling include a patient followup. FDA noted that we intend to this communication would be identification card, which would be consider proposals for different study appropriate for a device with an initially provided by the manufacturer. designs and will decide on a case-by- approved PMA establishing its safety FDA does not anticipate further case basis whether each proposed study and effectiveness. The commenter stated followup actions by the manufacturer. design is likely to generate data that the patient labeling should be These findings are adopted, in part, in adequate to support a PMA (79 FR focused on the benefit-risk profile of the final order (see section IV, ‘‘The 24642 at 24647). In addition, we noted each product as established in the Final Order’’). asabaliauskas on DSK5VPTVN1PROD with RULES that FDA intends to consider the use of related PMA and requested that FDA study data collected by manufacturers consider alternative methods for IV. The Final Order in response to FDA issued postmarket providing the information found in the Under section 515(b)(3) of the FD&C surveillance study orders (79 FR 24642 FDA communication to patients. Act, FDA is adopting its findings, in at 24647). FDA believes that data from (Response) FDA agrees that patient part, as published in the preamble of the the section 522 postmarket surveillance labeling should be reflective of the risks 515(b) proposed order (79 FR 24642) studies may be able to fulfill the clinical and benefits of individual devices. FDA and issuing this final order to require requirements to support PMA also believes that there is important, the filing of a PMA for surgical mesh for VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00006 Fmt 4701 Sfmt 4700 E:\FR\FM\05JAR4.SGM 05JAR4

Federal Register / Vol. 81, No. 2 / Tuesday, January 5, 2016 / Rules and Regulations 369 transvaginal POP repair. As discussed in The collections of information in 21 downloads/MedicalDevices/ this document, FDA is amending certain CFR part 807, subpart E, have been DeviceRegulationandGuidance/ previous findings. The Agency now approved under OMB control number GuidanceDocuments/ucm073791.pdf. 0910–0120; the collections of 3. Blue Book Memorandum #G95–1—’’Use of finds that: (1) Manufacturing process International Standard ISO–10993, information of the specialized information in 21 CFR part 814, subpart ’Biological Evaluation of Medical instrumentation should not be included B, have been approved under OMB Devices Part 1: Evaluation and Testing’ in a premarket submission and (2) control number 0910–0231; the ’’ issued on May 1, 1995. Available at patient labeling should include relevant collections of information in part 812 http://www.fda.gov/ information from FDA’s Safety have been approved under OMB control RegulatoryInformation/Guidances/ Communication and/or FDA’s number 0910–0078; the collections of ucm080735.htm. Urogynecologic Surgical Mesh Implants information under 21 CFR 822 have 4. ‘‘Guidance for Industry Pyrogen and Web page rather than the notice of been approved under OMB control Endotoxins Testing: Questions and Answers,’’ June 2012. Available at http:// availability of FDA’s Safety number 0910–0449; and the collections www.fda.gov/downloads/drugs/ Communication. The patient labeling of information under 21 CFR 801 have guidancecompliance should also include a link to the FDA’s been approved under OMB control regulatoryinformation/guidances/ Urogynecologic Surgical Mesh Implants number 0910–0485. ucm310098.pdf. Web page. This final order will revise 21 5. ‘‘Update on Serious Complications VII. Codification of Orders CFR part 884. Associated with Transvaginal Placement Under the final order, a PMA for Prior to the amendments by FDASIA, of Surgical Mesh for Pelvic Organ surgical mesh for transvaginal POP section 515(b) of the FD&C Act provided Prolapse: FDA Safety Communication’’ repair is required to be filed on or before for FDA to issue regulations to require issued on July 13, 2011. Available at July 5, 2018, for any preamendments PMA approval for preamendments http://www.fda.gov/MedicalDevices/ Safety/AlertsandNotices/ class III devices that were in commercial devices or devices found substantially ucm262435.htm. distribution before May 28, 1976, or that equivalent to preamendments devices. 6. FDA’s Urogynecologic Surgical Mesh has been found by FDA to be Section 515(b) of the FD&C Act, as Implants Web page. Available at http:// substantially equivalent to such a device amended by FDASIA, provides for FDA www.fda.gov/MedicalDevices/ on or before July 5, 2018. Any other to require PMA approval for such ProductsandMedicalProcedures/ device subject to this order is required devices by issuing a final order ImplantsandProsthetics/ to have an approved PMA in effect following the issuance of a proposed UroGynSurgicalMesh/default.htm. before it may be marketed. order in the Federal Register. FDA will List of Subjects in 21 CFR Part 884 If a PMA for any of the continue to codify the requirement for a preamendments class III devices subject PMA approval in the Code of Federal Medical devices. to this order is not filed by this date, Regulations. Therefore, under section Therefore, under the Federal Food, that device will be deemed adulterated 515(b)(1)(A) of the FD&C Act, as Drug, and Cosmetic Act and under under section 501(f)(1)(A) of the FD&C amended by FDASIA, in this final order, authority delegated to the Commissioner Act, and commercial distribution of the we are requiring PMA approval for of Food and Drugs, 21 CFR part 884 is device must cease immediately. surgical mesh for transvaginal POP amended as follows: The device may, however, be repair and we are making the language distributed for investigational use, if the in 21 CFR 884.5980 consistent with this PART 884—OBSTETRICAL AND applicable requirements of the IDE final order. GYNECOLOGICAL DEVICES regulations (part 812), including VIII. References ■ 1. The authority citation for 21 CFR obtaining IDE approval, are met on or The following references are on part 884 continues to read as follows: before 30 months after the effective date of this order. There will be no extended display in the Division of Dockets Authority: 21 U.S.C. 351, 360, 360c, 360e, period for filing an IDE, nor exemption Management (HFA–305), Food and Drug 360j, 371. from the IDE requirements (see Administration, 5630 Fishers Lane, Rm. ■ 2. Add paragraph (c) to § 884.5980 to § 812.2(d)), and studies may not be 1061, Rockville, MD 20852 and are read as follows: initiated without appropriate IDE available for viewing by interested persons between 9 a.m. and 4 p.m., § 884.5980 Surgical mesh for transvaginal approvals, as required. Monday through Friday; they are also pelvic organ prolapse repair. V. Analysis of Environmental Impact available electronically at http:// * * * * * The Agency has determined under 21 www.regulations.gov. FDA has verified (c) Date premarket application CFR 25.34(b) that this action is of a type the Web site addresses, as of the date approval or notice of completion of a that does not individually or this document publishes in the Federal product development protocol is cumulatively have a significant effect on Register, but Web sites are subject to required. A premarket application the human environment. Therefore, change over time. approval or notice of completion of a neither an environmental assessment product development protocol for a 1. FDA Meeting of the Obstetrics & nor an environmental impact statement Gynecological Devices Panel, September device is required to be filed with the is required. 8–9, 2011. Available at http:// Food and Drug Administration on or www.fda.gov/AdvisoryCommittees/ before July 5, 2018, for any surgical VI. Paperwork Reduction Act of 1995 CommitteesMeetingMaterials/ mesh described in paragraph (a) of this asabaliauskas on DSK5VPTVN1PROD with RULES This final order refers to previously MedicalDevices/MedicalDevices section that was in commercial approved collections of information AdvisoryCommittee/Obstetricsand distribution before May 28, 1976, or that found in FDA regulations. These GynecologyDevices/ucm262488.htm. has, on or before July 5, 2018, been collections of information are subject to 2. ‘‘Guidance for Industry and/or for FDA found substantially equivalent to a Reviewers/Staff and/or Compliance: review by the Office of Management and Guidance for the Preparation of a surgical mesh described in paragraph (a) Budget (OMB) under the Paperwork Premarket Notification Application for a of this section that was in commercial Reduction Act of 1995 (44 U.S.C. 3501– Surgical Mesh’’ issued on March 2, 1999. distribution before May 28, 1976. Any 3520). Available at http://www.fda.gov/ other surgical mesh for transvaginal VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00007 Fmt 4701 Sfmt 4700 E:\FR\FM\05JAR4.SGM 05JAR4

370 Federal Register / Vol. 81, No. 2 / Tuesday, January 5, 2016 / Rules and Regulations pelvic organ prolapse repair shall have development protocol in effect before Dated: December 30, 2015. an approved premarket application or being placed in commercial Leslie Kux, declared completed product distribution. Associate Commissioner for Policy. [FR Doc. 2015–33163 Filed 1–4–16; 8:45 am] BILLING CODE 4164–01–P asabaliauskas on DSK5VPTVN1PROD with RULES VerDate Sep<11>2014 19:42 Jan 04, 2016 Jkt 238001 PO 00000 Frm 00008 Fmt 4701 Sfmt 9990 E:\FR\FM\05JAR4.SGM 05JAR4


Document Created: 2016-01-05 01:46:13
Document Modified: 2016-01-05 01:46:13
CategoryRegulatory Information
CollectionFederal Register
sudoc ClassAE 2.7:
GS 4.107:
AE 2.106:
PublisherOffice of the Federal Register, National Archives and Records Administration
SectionRules and Regulations
ActionFinal order.
DatesThis order is effective on January 5, 2016.
ContactSharon Andrews, Center for Devices and Radiological Health, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 66, Rm. G110, Silver Spring, MD 20993, 301-796-6529, [email protected]
FR Citation81 FR 363 
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