CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas(PICS-AF)

K162388 · Curaseal, Inc. · FTM · Feb 3, 2017 · General, Plastic Surgery

Device Facts

• Record ID: K162388
• Device Name: CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas(PICS-AF)
• Applicant: Curaseal, Inc.
• Product Code: FTM · General, Plastic Surgery
• Decision Date: Feb 3, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 878.3300
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas (PICS-AFTM) is for implantation to reinforce soft tissue for the repair of anal and rectal fistulas.

Device Story

PICS-AF is a sterile, single-use, sphincter-sparing device for anorectal fistula repair. Components include a silicone Sealing Disk, Sheath, Dilator, bovine-derived cross-linked collagen matrices, and resorbable sutures. During minimally invasive surgery, the device is implanted into the fistula tract; the Sealing Disk covers the inner ostium to inhibit enteric matter entry, while collagen matrices provide a scaffold for tissue ingrowth. The Sealing Disk is designed to be expelled as waste or removed by a physician if discomfort occurs. The external fistula opening remains open for drainage. The device is used in a clinical setting by a physician. It benefits patients by providing a scaffold for wound healing and fistula closure while sparing the sphincter.

Clinical Evidence

Prospective, non-randomized clinical study (N=30) compared PICS-AF to historical controls (N=19). Primary endpoint: fistula closure at 6 months (MRI-adjudicated). Success rate: 46.67% (ITT) and 66.67% (PP). Safety endpoint: serious adverse events (SAE) through 6 months. SAE rate was acceptable; overall adverse event rate (50%) was not statistically different from historical controls (P=0.3955).

Technological Characteristics

Materials: Bovine dermis-derived cross-linked collagen, silicone. Components: Sealing Disk, Sheath, Dilator, resorbable sutures. Principle: Mechanical occlusion of inner ostium and biological scaffold for tissue ingrowth. Sterilization: Ethylene Oxide. Form factor: Two models (M1/M2) with varying disk/dowel sizes.

Indications for Use

Indicated for implantation to reinforce soft tissue for the repair of anal and rectal fistulas in patients requiring surgical intervention.

Regulatory Classification

Identification

Surgical mesh is a metallic or polymeric screen intended to be implanted to reinforce soft tissue or bone where weakness exists. Examples of surgical mesh are metallic and polymeric mesh for hernia repair, and acetabular and cement restrictor mesh used during orthopedic surgery.

Predicate Devices

• GORE BIO-A Fistula Plug (K083266)
• SIS Fistula Plug (K050337)

Reference Devices

• SURGISIS RVP Recto-Vaginal Fistula Plug (K062729)

Submission Summary (Full Text)

{0}------------------------------------------------

Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol that resembles a stylized caduceus or a representation of the human form.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

February 3, 2017

CuraSeal, Inc. % Mr. Kit Cariquitan Experien Group, LLC 755 North Mathilda Ave Sunnyvale, CA 94085

Re: K162388

Trade/Device Name: CuraSeal PICS Fistulae Closure Device -PICS - AF - M1™ PICS -AF - M2"M Regulation Number: 21 CFR 878.3300 Regulation Name: Surgical mesh Regulatory Class: Class II Product Code: FTM Dated: December 16, 2016 Received: December 19, 2016

Dear Mr. Cariquitan:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in

{1}------------------------------------------------

the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely.

Binita S. Ashar -S

Binita S. Ashar, M.D., M.B.A., F.A.C.S. Director Division of Surgical Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

#### DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

# Indications for Use

510(k) Number (if known)

K162388

Device Name

CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas (PICS-AFTM)

Indications for Use (Describe)

The CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas (PICS-AFTM) is for implantation to reinforce soft tissue for the repair of anal and rectal fistulas.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

# PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

# CONSTITUTION OF THE FOR FOR FOR FOR FOR FDA USE ONLY CONTRACTOR CONSULTION OF

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

This section applies only to requirements of the Paperwork Reduction Act of 1995.

#### "DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."

The burden time for this collection of information is estimated to average 79 hours per response, including the lime to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

> Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff [e-mail]

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

{3}------------------------------------------------

#### 510(k) Notification K

K162388, pg. 1 of 11

#### GENERAL INFORMATION [807.92(a)(1)]

#### Applicant:

CuraSeal, Inc. 2231 Calle de Luna Santa Clara, CA 95054 USA Phone: [phone] Fax: [phone]

#### Contact Person:

Kit Cariquitan Chief Regulatory Officer Experien Group, LLC 755 N. Mathilda Ave, Suite 100 Sunnyvale, CA 94085 USA Phone: [phone] Fax: [phone]

# Date Prepared: August 12, 2016

# DEVICE INFORMATION [807.92(a)(2)]

The CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas (PICS-AF") is a medical device consisting of a Sealing Disk, Sheath, Dilator, Collagen Matrices and resorbable sutures. The PICS-AF Closure System is designed as a sphincter-sparing device that inhibits the movement of enteric matter into the anorectal fistula tract and to provide a scaffold for tissue ingrowth to occur to close the anorectal fistula.

#### Trade Name:

CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas (PICS-AF")

Generic/Common Name: Surgical Mesh

Classification: 21 CFR§878.3300, Class II

Product Code: FTM

{4}------------------------------------------------

# PREDICATE DEVICE(S) [807.92(a)(3)]

# K162388, pg. 2 of 11

- W.L. Gore & Associates, GORE BIO-A Fistula Plug (K083266)
- . Cook Biotech, SIS Fistula Plug (K050337)

The Cook Biotech, SURGISIS® RVP™ Recto-Vaginal Fistula Plug (K062729) is added as a reference device due to its same intended use and similar technological characteristics.

The predicate devices have not been subject to a design-related recall.

# DEVICE DESCRIPTION [807.92(a)(4)]

The PICS-AF Closure System is a sterile, single-use medical device that is designed to be implanted, using a minimally invasive surgical technique, to reinforce soft tissue for the repair of anal and rectal fistulas like the predicate devices. As the PICS-AF Closure System is specifically designed to be sphincter sparing, it does not preclude performing a repeat PICS-AF procedure or any other fistula repair procedure, if required. The key features of the CuraSeal PICS-AF Closure System include the Sealing Disk, Sheath, Dilator, Collagen Matrices and resorbable sutures. There are two models of the PICS-AF device (M1 and M2). Model M1 has a smaller Sealing Disk and smaller diameter Collagen Matrices than Model M2. The Collagen Matrices consist of up to six collagen dowels that are implanted in the fistula tract. After placement, any excess collagen dowels are removed or trimmed at the time of surgery. Placement of the PICS-AF device to cover the inner ostium opening of the fistula tract inhibits the movement of enteric matter into the fistula tract and the collagen provides a scaffold for wound healing to occur to close the anorectal fistula. The Collagen Matrices are delivered directly into the fistula tract and are secured to the fistula tract or the surrounding tissue by resorbable sutures. The Collagen Matrices are resorbed by the body during the natural healing process. The silicone Sealing Disk is designed to be expelled from the body as waste once the resorbable sutures have resorbed. Alternatively, the silicone Sealing Disk can be removed by the physician during the first two months following the procedure if the Sealing Disk appears in the patient's anal canal or causes any discomfort. Similar to the predicate devices, the external fistula opening (EFO) is left open during the healing process to allow for drainage to prevent infection or abscess formation.

# INDICATIONS FOR USE [807.92(a)(5)]

The CuraSeal Percutaneous Intraluminal Closure System for Anorectal Fistulas (PICS-AF") is for implantation to reinforce soft tissue for the repair of anal and rectal fistulas.

# TECHNOLOGICAL CHARACTERISTICS [807.92(a)(6)]

The technological characteristics of the CuraSeal PICS-AF Closure System are similar and substantially equivalent to the predicate devices. Table 1 lists the technological characteristics of the PICS-AF device and the predicate devices. Table 1 also provides the rationale to support a determination of substantial equivalence. Any differences between the devices do not raise different questions of safety or effectiveness. Performance data, including clinical testing, were provided to support the determination

{5}------------------------------------------------

of substantial equivalence. Clinical testing was performed by CuraSeal. The results from the clinical testing support the safe and effective use of the PICS-AF Closure System for anal and rectal fistula repair and further establish the substantial equivalence to the predicate devices.

| Feature | CuraSeal<br>PICS-AF | W.L. Gore &<br>Associates,<br>GORE BIO-A<br>Fistula Plug<br>(Predicate) | Cook Biotech,<br>SIS Fistula Plug<br>(Predicate) | Cook Biotech,<br>Modified SIS<br>Fistula Plug<br>(Reference) | Substantial<br>Equivalence<br>Rationale |
|---------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 510(k)<br>Number | TBD | K083266 | K050337 | K062729 | -- |
| Indications<br>for Use | The CuraSeal<br>Percutaneous<br>Intraluminal<br>Closure System<br>for Anorectal<br>Fistulas<br>(PICS-AF™) is<br>for implantation<br>to reinforce soft<br>tissue for the<br>repair of anal<br>and rectal<br>fistulas. | The GORE<br>BIO-A™<br>Fistula Plug<br>device is<br>intended for<br>use in the<br>reinforcement<br>of soft tissue<br>for the repair of<br>anorectal<br>fistulas. | The SIS Fistula<br>Plug is for<br>implantation to<br>reinforce soft<br>tissue where a<br>rolled<br>configuration is<br>required, for<br>repair of anal,<br>rectal, and<br>enterocutaneous<br>fistulas. The<br>device is<br>supplied sterile<br>and is intended<br>for one-time use. | The Modified<br>SIS Fistula Plug<br>is for<br>implantation to<br>reinforce soft<br>tissue for repair<br>of recto-vaginal<br>fistulas. The<br>device is<br>supplied sterile<br>and is intended<br>for one-time<br>use. | Like the predicate<br>devices, the<br>PICS-AF device<br>reinforces soft<br>tissue for the repair<br>of anal and rectal<br>fistulas. It is also<br>supplied sterile and<br>is intended for<br>one-time use. The<br>minor differences in<br>the indications for<br>use statements do<br>not affect the safety<br>and effectiveness of<br>the PICS-AF<br>device. |
| Classification/<br>Product Code | §878.3300<br>FTM | §878.3300<br>FTL | §878.3300<br>FTM | §878.3300<br>FTM | Same classification.<br>Same or similar<br>Product Code |
| Anatomical<br>Location | Anal and rectal<br>fistulas | Anal and rectal<br>fistulas | Anal, rectal, or<br>enterocutaneous<br>fistulas | Rectal and<br>vaginal fistulas | Same or similar<br>anatomical location |
| Feature | CuraSeal<br>PICS-AF | W.L. Gore &<br>Associates,<br>GORE BIO-A<br>Fistula Plug<br>(Predicate) | Cook Biotech,<br>SIS Fistula Plug<br>(Predicate) | Cook Biotech,<br>Modified SIS<br>Fistula Plug<br>(Reference) | Substantial<br>Equivalence<br>Rationale |
| | Bovine dermis-<br>derived, cross-<br>linked collagen | Synthetic<br>PGA/TMC<br>copolymer | Porcine-derived<br>small intestine<br>submucosa | Porcine-derived<br>small intestine<br>submucosa | Like the predicate<br>devices, the<br>resorbable material<br>acts as a scaffold to<br>specifically<br>reinforce soft tissue<br>and promote<br>healing of the<br>fistula tract. Design<br>verification and<br>clinical testing<br>demonstrate that the<br>PICS-AF device is<br>safe and performs<br>as intended. The<br>PICS-AF is<br>substantially<br>equivalent to the<br>predicate devices. |
| Resorbable<br>Plug Shape | Round dowels,<br>segmented up to<br>6 dowels/device | One piece<br>device consists<br>of Cap and six<br>round hollow<br>tube segments.<br>Tube segments<br>are cut to<br>length and/or<br>cut off to suit<br>fistula<br>diameter. | Tapered rolled<br>sheet, one piece<br>cut to length | Tapered rolled<br>sheet, one piece<br>cut to length | All devices have<br>plugs that occupy<br>the fistula tract and<br>any excess material<br>is trimmed from the<br>device at the time<br>of surgery. The<br>PICS-AF is<br>substantially<br>equivalent to the<br>predicate devices. |
| Attachment<br>Mechanism | Internal disk and<br>resorbable<br>sutures | Internal cap<br>and resorbable<br>sutures | Resorbable<br>sutures | Internal disk<br>and resorbable<br>sutures | All devices have<br>similar attachment<br>mechanism. Design<br>verification and<br>clinical testing<br>demonstrate that the<br>PICS-AF device is<br>safe and performs<br>as intended. The<br>PICS-AF is<br>substantially<br>equivalent to the<br>predicate devices. |
| Feature | CuraSeal<br>PICS-AF | W.L. Gore &<br>Associates,<br>GORE BIO-A<br>Fistula Plug<br>(Predicate) | Cook Biotech,<br>SIS Fistula Plug<br>(Predicate) | Cook Biotech,<br>Modified SIS<br>Fistula Plug<br>(Reference) | Substantial<br>Equivalence<br>Rationale |
| Disk Design | Sealing Disk | Disk | N/A | Button/Flange | Like the GORE<br>BIO-A Fistula Plug,<br>the internal opening<br>of the ostium is<br>closed to mitigate<br>enteric fluids from<br>entering the fistula<br>tract. Design<br>verification and<br>clinical testing<br>demonstrate that the<br>PICS-AF device is<br>safe and performs<br>as intended. The<br>PICS-AF is<br>substantially<br>equivalent to the<br>predicate devices. |
| Delivery<br>Sheath Design | Protects<br>collagen and<br>keeps it clean<br>when pulled into<br>tract | N/A | N/A | N/A | Design verification<br>and clinical testing<br>demonstrate that the<br>addition of the<br>Sheath/Dilator for<br>the PICS-AF device<br>does not increase<br>the risk to the<br>patient and is<br>therefore<br>substantially<br>equivalent to the<br>predicate devices. |
| Sterilization<br>Method | Ethylene Oxide<br>Gas | Gamma<br>Irradiation | Ethylene Oxide<br>Gas | Ethylene Oxide<br>Gas | Same sterility<br>assurance level,<br>same or similar<br>sterilization method |

Table 1: Summary of Technological Characteristics

{6}------------------------------------------------

{7}------------------------------------------------

{8}------------------------------------------------

# SUBSTANTIAL EQUIVALENCE

The indications for use for the CuraSeal PICS-AF Closure System is substantially equivalent to the indications for use of the predicate devices. Any differences in the technological characteristics between the devices do not raise different questions of safety or effectiveness. Thus, the CuraSeal PICS-AF Closure System is substantially equivalent to the predicate devices.

# PERFORMANCE DATA [807.92(b)]

All necessary bench and clinical testing were conducted on the CuraSeal PICS-AF Closure System to support a determination of substantial equivalence to the predicate devices.

#### TESTING IN SUPPORT OF SUBSTANTIAL EQUIVALENCE DETERMINATION

All necessary bench and clinical testing were conducted on the CuraSeal PICS-AF Closure System to support a determination of substantial equivalence to the predicate devices.

# Non-clinical Testing Summary [807.92(b)(1)]:

The non-clinical, bench testing included:

- . Design verification and bench validation studies, including dimensional analysis
- Physician simulated use
- Biocompatibility ●
- Sterilization ●
- Packaging and shelf-life

The collective results of the non-clinical testing demonstrate that the materials chosen, the manufacturing processes utilized and the design of the CuraSeal PICS-AF Closure System meet the established specifications necessary for consistent performance during its intended use. In addition, the collective bench testing demonstrate that the CuraSeal PICS-AF Closure System does not raise different questions of safety or effectiveness for the repair of anorectal fistulas when compared to the predicate devices.

{9}------------------------------------------------

# Clinical Testing Summary [807.92(b)(2)]:

A prospective, non-randomized clinical study was conducted to evaluate the safety and effectiveness of the PICS-AF Closure System for repair of anorectal fistulas. The safety and effectiveness rates for the PICS-AF devices were compared to historical control data generated from commercially available anorectal fistula repair devices.

The PICS-AF Closure System was used in 30 subjects enrolled in the study from one clinical site in Europe. Eight different investigators treated the 30 PICS-AF subjects. There were also 19 Historical Control subjects that were treated using a commercially available fistula plug (GORE BIO-A Fistula Plug) at this same clinical site and were evaluated as part of the PICS-AF clinical study.

The primary effectiveness endpoint for this study was fistula closure success at 6 months defined as complete healing of the fistula tract and associated external opening without drainage or abscess. Fistula closure success for the PICS-AF device was assessed using MRIs from Month 6. The MRI results were reviewed and adjudicated by three independent U.S. radiologists. The rate of the PICS-AF closure success at 6 months was 46.67% (14/30) based on the Intent-to-Treat (ITT) population results and 66.67% (14/21) based on the Per Protocol (PP) population results. Nine subjects had inclusion/exclusion deviations, based on the independent MRI assessment, and thus should have been disqualified from participating in the PICS-AF study.

The primary safety endpoint for this study was the proportion of subjects experiencing a serious adverse event (i.e., an infection, enlargement of the fistula, an allergic reaction to the PICS-AF device, etc.) through 6 months of post-procedure follow-up. There were three subjects who experienced a Serious Adverse Event during this study (two subjects had a fistula abscess and the third subject had a seton placed). The two subjects with a fistula abscess have recovered without sequelae and the subject with the seton is stable. The PICS-AF safety results have demonstrated that the overall primary safety endpoint was met. The PICS-AF safety data was comparable to the Historical Control group. The overall PICS-AF adverse event data was 50% as compared to 36.84% for the Historical Controls; however, this difference was not statistically significant (P=0.3955).

Table 2 provides the baseline demographics and characteristics for the control (GORE BIO-A Fistula Plug) and PICS-AF treatment groups.

| Characteristic | Control<br>N=19 | PICS-AF<br>N=30 | P-value |
|----------------------|-------------------|-------------------|---------|
| Gender: n/N (% Male) | 17/19 (89.47%) | 23/30 (76.67%) | 0.4511a |
| Age: Mean (SD) N | 50.11 (7.522) 18c | 53.70 (12.086) 30 | 0.2112b |
| Median (Min, Max) | 49.5 (35, 64) | 56.5 (31, 76) | |
| Smoker: n/N (%) | 5/19 (26.32%) | 11/30 (36.67%) | 0.5412a |
| Obese: n/N (%) | 4/19 (21.05%) | 7/30 (23.33%) | 1.0000a |
| Diabetes: n/N (%) | 5/19 (26.32%) | 2/30 (6.67%) | 0.0926a |

Table 2: Baseline Demographics and Characteristics

aTwo-sided Fisher's exact test.

bTwo-sided unequal variance t-test.

One Historical Control subject did not record age.

{10}------------------------------------------------

Table 3 provides a comparison of the fistula variables at baseline for the control (GORE BIO-A Fistula Plug) and PICS-AF treatment groups.

| Characteristic | Control<br>N=19 | PICS-AF<br>N=30 |
|---------------------------------------------------------|---------------------------|---------------------------|
| Onset of Fistula: Mean (Min, Max) | 32.6 mo. (5 mo., 121 mo.) | 57.2 mo. (4 mo., 246 mo.) |
| Type of Fistula: Transsphincteric | 19/19 (100%) | 30/30 (100%) |
| Length of Fistula Tract (cm):<br>Mean (SD) N | 4.1000 (1.8529) 10ª | 5.6733 (2.4057) 30 |
| Median (Min, Max) | 4.00 (2.00, 8.00) | 5.25 (2.50, 12.00) |
| No. of Fistula Openings: n/N (%)<br>Internal 1 opening: | 19/19 (100%) | 30/30 (100%) |
| Internal 2 openings: | -- | -- |
| External 1 opening: | 16/19 (84%) | 26/30 (87%) |
| External 2 openings: | 3/19 (16%) | 4/30 (13%) |
| Inner Fistula Diameter (cm):<br>Mean (SD) | Not Reported | 0.6017 (0.8391) |
| Median (Min, Max) | -- | 0.30 (0.05, 3.80) |
| Outer Fistula Diameter (cm):<br>Mean (SD) | Not Reported | 0.6137 (0.7834) |
| Median (Min, Max) | -- | 0.50 (0.01, 4.00) |
| Recurrent Fistula: n/N (%) | 12/19 (63%) | 20/30 (66.67%) |
| No. of Previous Fistula Treatments | 16 | 93 |
| Incontinence Score: Mean (Min, Max) | Not Performed | -- |
| Solid | -- | 0.23 (0, 4) |
| Liquid | -- | 0.67 (0, 4) |
| Gas | -- | 0.33 (0, 3) |
| Wears Pad | -- | 0.40 (0, 4) |
| Lifestyle Alteration | -- | 0.57 (0, 4) |
| Pain Scale:<br>Mean (Min, Max) | Not Performed | 3.83 (0, 8) |

Table 3: Comparison of Fistula Variables at Baseline

4Nine Historical Control subjects did not have fistula length recorded.

Incontinence Scale: 0=Never, 1=Rarely, 2=Sometimes, 3=Usually, 4=Always

Pain Scale: 0-10 (0=No pain, 5=Moderate pain, 10=Worst pain)

Table 4 provides the Month 6 fistula closure results for the control (GORE BIO-A Fistula Plug) and PICS-AF treatment groups.

#### Table 4: Fistula Closure Results at Month 6

| Treatment Group | Fistula Not Closed<br>n/N (%) | Fistula Closed<br>n/N (%) |
|-----------------|-------------------------------|---------------------------|
| PICS-AF | 16/30 (53.33%) | 14/30a (46.67%) |
| Control | 17/18b (94.44%) | 1/18 (5.56%) |

'Nine subjects were determined to have inclusion deviations that were detected by independent MRI readings. These subjects should not have been enrolled into this study. None of these nine subjects had healed fistulas at Month 6. The fistula closure success rate was 14/21 (66.67%) for subjects who met all specified enrollment criteria. bone Historical Control subject did not have an outcome recorded at six months.

{11}------------------------------------------------

Table 5 provides an analysis of the impact on fistula closure results based on the baseline characteristics for the combined treatment groups.

| Baseline Characteristic | Covariate P-value | P-value (Combined<br>Treatment Groups) |
|----------------------------|-------------------|----------------------------------------|
| Age | 0.6973 | 0.0179 |
| Weight | 0.3005 | 0.0244 |
| Gender | 0.0400 | 0.0174 |
| History of Diabetes | 0.7948 | 0.0176 |
| History of Cardiac Disease | 0.5648 | 0.0133 |
| History of Renal Disease | 0.9801 | 0.0115 |
| History of Smoking | 0.3127 | 0.0111 |

Table 5: Logistic Regression for Baseline Characteristic Impact on Fistula Closure

Table 6 provides a comparison of Month 6 outcomes for the control (GORE BIO-A Fistula Plug) and PICS-AF treatment groups.

| Category | Control<br>N=19 | PICS-AF<br>N=30 |
|-------------------------------------|-----------------|-----------------|
| Fistula Healed: n/N (%) | 1/18ª (5.56%) | 14/30 (46.67%) |
| Incontinence Score: Mean (Min, Max) | Not Performed | |
| Solid | -- | 0.27 (0, 3) |
| Liquid | -- | 0.97 (0, 4) |
| Gas | -- | 1.03 (0, 4) |
| Wears Pad | -- | 1.30 (0, 4) |
| Lifestyle Alteration | -- | 1.00 (0, 4) |
| Pain Scale: | Not Performed | |
| Mean (Min, Max) | -- | 2.37 (0, 10) |

4One Historical Control subject did not have an outcome recorded at six months. Incontinence Scale: 0=Never, 1=Rarely, 2=Sometimes, 3=Usually, 4=Always

Pain Scale: 0-10 (0=No pain, 5=Moderate pain, 10=Worst pain)

{12}------------------------------------------------

Table 7 provides a summary of the adverse events (including serious adverse events) for the control (GORE BIO-A Fistula Plug) and PICS-AF treatment groups.

| Table 7: Adverse Events | |
|-------------------------|--|
|-------------------------|--|

| | Control | | PICS-AF | |
|--------------------------------------------------------------------|----------------------------------|------------------------|----------------------------------|------------------------|
| Adverse Event | Number of<br>Patients n/N<br>(%) | Number<br>of<br>Events | Number of<br>Patients n/N<br>(%) | Number<br>of<br>Events |
| Primary Safety Endpointa | 0/19 (0%) | 0 | 3/30 (10.00%) | 3 |
| Any Adverse Event | 7/19 (36.84%) | 7 | 15/30 (50.00%) | 17d |
| Hypertension | 0/19 (0%) | 0 | 1/30 (3.33%) | 1 |
| Fistula-related Infection | 0/19 (0%) | 0 | 2/30 (6.67%) | 2 |
| Skin Irritation | 0/19 (0%) | 0 | 1/30 (3.33%) | 1 |
| Pain and Discomfort | 0/19 (0%) | 0 | 4/30 (13.33%) | 4 |
| Other Fistula-related<br>Complicationb | 0/19 (0%) | 0 | 2/30 (6.67%) | 2 |
| Premature Pullout of the<br>Anchor Suture and Partial<br>Migration | 1/19 (5.26%) | 1 | 0/30 (0%) | 0 |
| Fistula Abscessc | 2/19 (10.53%) | 2 | 1/30 (3.33%) | 1 |
| New Fistula | 2/19 (10.53%) | 2 | 0/30 (0%) | 0 |
| Recurrence of Treated Fistula<br>Tract | 1/19 (5.26%) | 1 | 0/30 (0%) | 0 |
| Fistula Tract Bleeding | 1/19 (5.26%) | 1 | 0/30 (0%) | 0 |
| Infection – Fistula Tract | 0/19 (0%) | 0 | 1/30 (3.33%) | 1 |
| Other | 0/19 (0%) | 0 | 2/30 (6.67%) | 2 |

4Fistula abscess requiring IV antibiotics and extended hospitalization (SAE).

°One mild external orifice and one anal canal ulcer.

6Excludes the two fistula abscesses that were primary safety endpoint events.

dTwo subjects had two Events each.

Table 8 summarizes the PICS-AF fistula healing outcomes based upon: subjects with adverse events and not healed fistulas; subjects with adverse events and healed fistulas; and subjects with no adverse events and not healed fistulas.

{13}------------------------------------------------

| PICS-AF Subjects with Adverse Events and Not Healed Fistulas (n=11) | | | | | |
|-----------------------------------------------------------------------|--------------------|----------------------------|------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------|----------------------------------|
| No. Subjects | No. Adverse Events | No. Serious Adverse Events | Type of Intervention n/N (%) | Solid Incontinence n/N (%) | Pain Scale Score Mean (Min, Max) |
| 11 | 11 | 2 | Sealing Disk removed = 3/11 (27%)<br>Setons placed = 1/11 (9%)<br>Drainage performed = 2/11 (18%)<br>Medications prescribed = 3/11 (27%) | 0=Never: 8/11 (73%)<br>1=Rarely: 2/11 (18%)<br>2=Sometimes: 0/11 (0%)<br>3=Usually: 1/11 (9%)<br>4=Always: 0/11 (0%) | 3.27 (0, 8) |
| PICS-AF Subjects with Adverse Events and Healed Fistulas (n=4) | | | | | |
| No. Subjects | No. Adverse Events | No. Serious Adverse Events | Type of Intervention n/N (%) | Solid Incontinence n/N (%) | Pain Scale Score Mean (Min, Max) |
| 4 | 3 | 1 | Sealing Disk removed = 1/4 (25%)<br>Setons placed = 0/4 (0%)<br>Drainage performed = 2/4 (50%)<br>Medications prescribed = 3/4 (75%) | 0=Never: 4/4 (100%)<br>1=Rarely: 0/4 (0%)<br>2=Sometimes: 0/4 (0%)<br>3=Usually: 0/4 (0%)<br>4=Always: 0/4 (0%) | 3.0 (0, 10) |
| PICS-AF Subjects with No Adverse Events and Not Healed Fistulas (n=5) | | | | | |
| No. Subjects | No. Adverse Events | No. Serious Adverse Events | Type of Intervention n/N (%) | Solid Incontinence n/N (%) | Pain Scale Score Mean (Min, Max) |
| 5 | 0 | 0 | Sealing Disk removed = 0/5 (0%)<br>Setons placed = 0/5 (0%)<br>Drainage performed = 0/5 (0%)<br>Medications prescribed = 0/5 (0%) | 0=Never: 5/5 (100%)<br>1=Rarely: 0/5 (0%)<br>2=Sometimes: 0/5 (0%)<br>3=Usually: 0/5 (0%)<br>4=Always: 0/5 (0%) | 1.6 (0, 5) |

| Table 8: Summary of PICS-AF Fistula Healing Outcomes at Month 6 | | | |
|-----------------------------------------------------------------|--|--|--|
| | | | |

In conclusion, the collective data from the PICS-AF Clinical Study support the overall safety and effectiveness of the PICS-AF Closure System for the repair of anorectal fistulas. The PICS-AF Closure System has been demonstrated to have favorable effectiveness results for fistula closure and to have an acceptable safety profile.

# CONCLUSIONS [807.92(b)(3)]

Extensive bench and clinical testing have been performed on the CuraSeal PICS-AF Closure System to evaluate the overall performance of the device. The collective results confirm that the CuraSeal PICS-AF Closure System is safe and effective, functions according to its specifications, is biocompatible and exhibits the appropriate mechanical and functional characteristics for an anorectal fistula repair device.

# SUMMARY

The CuraSeal PICS-AF Closure System is considered to be substantially equivalent to the predicate devices.