BONDEASE TOPICAL SKIN ADHESIVE

K141157 · Optmed, Inc. · MPN · Dec 22, 2015 · General, Plastic Surgery

Device Facts

• Record ID: K141157
• Device Name: BONDEASE TOPICAL SKIN ADHESIVE
• Applicant: Optmed, Inc.
• Product Code: MPN · General, Plastic Surgery
• Decision Date: Dec 22, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 878.4010
• Device Class: Class 2
• Attributes: Therapeutic, Pediatric

Intended Use

BondEase® Topical Skin Adhesive is intended for topical use only, to hold together the skin edges of incisions and lacerations that are under minimal tension and easily approximated. Where significant tension exists on incisions or lacerations, BondEase® Topical Skin Adhesive should be used in conjunction with deep dermal stiches.

Device Story

BondEase is a sterile, liquid topical skin adhesive composed of methylidene malonate monomer and D&C Green #6 colorant. Supplied in a single-use applicator (crushable glass ampoule in a plastic vial). Applied by clinician to approximated wound edges; liquid polymerizes into a film within minutes to bond edges and provide a bacterial barrier. Used in clinical settings for surgical incisions and traumatic lacerations. Acts as an alternative to conventional wound closure devices (sutures, staples, adhesive strips). Benefits include flexible wound closure and bacterial barrier protection while the film remains intact.

Clinical Evidence

Prospective, randomized, controlled, open-label study (N=159) compared BondEase to conventional wound closure devices (CWCD). Primary endpoint: 100% wound edge apposition at 10 days. ITT population results: 73.3% (BondEase) vs 77.8% (CWCD). Per-protocol population: 77.1% (BondEase) vs 80.4% (CWCD). Secondary endpoints included cosmesis scores at 28 days (mean 5.7/6.0 for BondEase vs 5.6/6.0 for CWCD). No significant differences in adverse events or efficacy outcomes between groups. Bench and animal testing confirmed bacterial barrier performance and biocompatibility per ISO 10993.

Technological Characteristics

Composition: methylidene malonate monomer and D&C Green #6. Form factor: single-use applicator with crushable glass ampoule in plastic vial. Polymerization: liquid-to-solid film upon application. Sterilization: sterile. Biocompatibility: tested per ISO 10993 (non-cytotoxic, non-irritating, non-pyrogenic, non-hemolytic, non-genotoxic).

Indications for Use

Indicated for topical closure of skin incisions and lacerations under minimal tension in patients at least one year of age. For wounds with significant tension, use with deep dermal sutures. Contraindicated in patients with significant multiple trauma, peripheral vascular disease, insulin-dependent diabetes, blood clotting disorders, history of keloid/hypertrophy, allergy to adhesive, burst/stellate lacerations, animal/human bites, HIV, decubitus ulcers, or heavily contaminated/infected wounds.

Regulatory Classification

Identification

A tissue adhesive for the topical approximation of skin is a device intended for topical closure of surgical incisions, including laparoscopic incisions, and simple traumatic lacerations that have easily approximated skin edges. Tissue adhesives for the topical approximation of skin may be used in conjunction with, but not in place of, deep dermal stitches.

Special Controls

*Classification.* Class II (special controls). The special control for this device is FDA's “Class II Special Controls Guidance Document: “Tissue Adhesive for the Topical Approximation of Skin.” See § 878.1(e) of this chapter for the availability of this guidance document.(b) *Tissue adhesive for non-topical use* —(1)*Identification.* A tissue adhesive for non-topical use, including adhesives intended for use in the embolization of brain arteriovenous malformation or for use in ophthalmic surgery, is a device used for adhesion of internal tissues and vessels.(2) *Classification.* Class III (premarket approval). As of May 28, 1976, an approval under section 515 of the act is required before this device may be commercially distributed. See § 878.3 of this chapter.

Predicate Devices

• DERMABOND® Topical Skin Adhesive (P960052)
• INDERMIL® Tissue Adhesive (P010002)

Submission Summary (Full Text)

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

December 22, 2015

OptMed, Inc. Stephanie Rais Regulatory Consultant 601 Lexington Avenue, Suite 5100 New York, New York 10022

Re: K141157

Trade/Device Name: BondEase Topical Skin Adhesive Regulation Number: 21 CFR 878.4010 Regulation Name: Tissue Adhesive Regulatory Class: Class II Product Code: MPN Dated: December 7, 2015 Received: December 8, 2015

Dear Ms. Rais:

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 device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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forth in the quality systems (QS) 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/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 yours,

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

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## Indications for Use

510(k) Number (if known) K141157

Device Name BondEase® Topical Skin Adhesive

#### Indications for Use (Describe)

BondEase® Topical Skin Adhesive is intended for topical use only, to hold together the skin edges of incisions and lacerations that are under minimal tension and easily approximated. Where significant tension exists on incisions or lacerations, BondEase® Topical Skin Adhesive should be used in conjunction with deep dermal stiches.

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

| <div> <span> <span style="font-size:16px">✖</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> |
|-------------------------------------------------------------------------------------------------------------------|
| <div> <span> <span style="font-size:16px">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> |

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Image /page/3/Picture/0 description: The image shows the logo for OptiMed. The logo is in blue and features the word "OPTIMED" in a serif font. The "M" in "OPTIMED" is stylized and is inside of a circular design with concentric circles.

#### 510(k) SUMMARY

| 510(k) Owner | OptMed, Inc.<br>601 Lexington Avenue, Suite 5100<br>New York, New York 10022<br>Telephone: [phone]<br>Fax: [phone] |
|---------------------|------------------------------------------------------------------------------------------------------------------------------|
| Contact Person | Alain Klapholz |
| Date | December 21, 2015 |
| Trade Name | BondEase® |
| Common Name | Topical Skin Adhesive |
| Classification Name | Tissue Adhesive for Topical Approximation of Skin |
| Review Panel | General & Plastic Surgery |
| Product Code | MPN |
| Regulation | Class II, 21 C.F.R. § 878.4010 |
| Predicate Devices: | DERMABOND® Topical Skin Adhesive (P960052)<br>INDERMIL® Tissue Adhesive (P010002) |

### Device Description

BondEase® Topical Skin Adhesive is a sterile, liquid topical skin closure device composed of a methylidene malonate monomer formulation and the colorant D&C Green #6. It is provided in a single-use applicator, packaged in a foil pouch. The applicator is comprised of a crushable glass ampoule contained within a plastic vial with attached applicator tip and handle.

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BondEase® is applied to the skin as a viscous liquid which polymerizes to bond approximated wound edges within minutes. In vitro studies have shown that BondEase® acts as a bacterial barrier as long as the adhesive film remains intact.

### Indications for Use

BondEase® Topical Skin Adhesive is intended for topical use only, to hold together the skin edges of incisions and lacerations that are under minimal tension and easily approximated. Where significant tension exists on incisions or lacerations. BondEase® Topical Skin Adhesive should be used in conjunction with deep dermal stiches.

### Technological Characteristics Compared to Predicates

The technological characteristics of BondEase® Topical Skin Adhesive are similar to those of the predicate devices in that they use similar polymerization mechanisms and have similar monomer structures. The predicate devices are cyanoacrylate formulations while BondEase® is formulated from methylidene malonate. For all products, the adhesives polymerize after being applied to the skin. BondEase® and the predicate devices are supplied in a dispensing applicator and are applied to the wound in a continuous film binding the approximated wound edges together. BondEase® and the predicate devices are supplied sterile and are for single use. As with the other topical skin adhesives. BondEase® is designed to bond approximated wound edges to provide flexible wound closure and provide a bacterial barrier as long as the adhesive remains intact. BondEase® and the predicate devices have substantially equivalent indications for use and mechanism of action.

### Nonclinical Performance Data

BondEase® Topical Skin Adhesive was evaluated in accordance with FDA's Guidance for Industry: Class II Special Controls Guidance Document: Tissue Adhesive for Topical Approximation of Skin.

Performance Bench Testing included various tests of adhesive strength and tests for degradation rate, heat of polymerization, and bacterial barrier performance. In these studies, BondEase® met all performance requirements.

Biocompatibility Testing was conducted per ISO 10993 guidelines and test results showed BondEase® to be non-cytotoxic, non-irritating, non-pyrogenic, with no toxicological affect 30 days post implantation. BondEase® was also found to be nonhemolytic and non-genotoxic. The full list of biocompatibility tests follows.

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Cytotoxicity Sensitization Irritation Systemic Toxicity - Acute Systemic & Material Mediated Pyrogen Implantation and Subchronic Toxicity Genotoxicity - Ames, Mouse Lymphoma & Mouse Micronucleus Hemolysis - Extract & Direct Contact Endotoxicity

In a porcine study conducted, results demonstrated that BondEase® did not inhibit normal wound closure and healing, and support that BondEase® may be used for the approximation of skin without the use of subcutaneous sutures on small, tensionless incisions. BondEase® Topical Skin Adhesive has demonstrated substantial equivalence to DERMABOND®, which was used as a control.

### Clinical Performance Data

A prospective, randomized, controlled, open-label study was conducted to evaluate the ability of BondEase® Topical Skin Adhesive to close approximated skin edges of traumatic lacerations and surgical incisions in comparison to Conventional Wound Closure Devices (CWCD) including sutures, staples, or adhesive strips, with or without sutures placed below the skin surface according to investigator judgment. The study was designed to demonstrate that BondEase is non-inferior to conventional wound closure devices (CWCD) in terms of 100% wound edge apposition of surgical incisions and traumatic lacerations.

The study population included patients at least one year of age, in good general health. Patients were excluded if presenting with: significant multiple trauma, peripheral vascular disease, insulin dependent diabetes mellitus, blood clotting disorder, keloid formation or hypertrophy history (patient or family), allergy to the adhesive, burst or stellate lacerations, animal or human bite. HIV, decubitus ulcer, heavily contaminated wounds and evidence of active infection or gangrene. Wound length and width were measured in millimeters; wound depth was not measured according to the study protocol. Types of wounds included traumatic lacerations and surgical incisions with and without deep dermal sutures. The study sample size was calculated based on the assumption of 95% wound apposition rate with BondEase compared to 96% wound apposition rate with CWCD. Based on this assumption, a total of 144 subjects would provide 80% statistical power to demonstrate equivalence with a clinically acceptable 10% margin and a onesided Type I error rate of 0.05. Table 1 summarizes the subject accountability and Table 2 summarizes the demographic characteristics and baseline wound types. The following

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factors had no impact on the performance of BondEase® Topical Skin Adhesive in terms of 100% wound edge apposition at day 10: wound type, gender, age, or race, the need for deep dermal sutures, and the location of the wound.

| | BondEase | CWCD | Total |
|----------------------------------|-------------|------------|-------------|
| Randomized* | 108 | 54 | 162 |
| Randomized and treatment applied | 105 (97.2%) | 54 (100%) | 159 (98.1%) |
| Completed the study | 100 (92.6%) | 51 (94.4%) | 151 (93.2%) |
| Early discontinuation** | 8 (7.4%) | 3 (5.6%) | 11 (6.8%) |
| Intent-to-treat population (ITT) | 105 (97.2%) | 54 (100%) | 159 (98.1%) |
| Per protocol population (PP) | 100 (92.6%) | 53 (98.1%) | 153 (94.4%) |

# Table 1: Subject Accountability

*20 BondEase and 10 CWCD subjects were enrolled in Part 1 of the clinical study. 88 BondEase and 44 CWCD subjects were enrolled in Part 2 of the clinical study.

**Reasons for early discontinuation included subjects that (1) were randomized but not treated, (2) voluntarily withdrew, (3) were non-compliant, (4) lost to follow-up, (5) had some other medical reason.

## Table 2: Demographic Characteristics and Baseline Wound Types by Treatment Group (ITT Population)

| | BondEase<br>N=105 | CWCD<br>N=54 | Total<br>N=159 |
|----------------------------------|-------------------|--------------|----------------|
| Age (years) | | | |
| Mean (SD) | 44.4 (23.1) | 47.7 (22.3) | 45.5 (22.8) |
| Median | 46 | 47 | 46 |
| Min-Max | 1 - 93 | 3 – 87 | 1 - 93 |
| Gender | | | |
| Male, n (%) | 56 (53.3%) | 30 (55.6%) | 86 (54.1%) |
| Female, n (%) | 49 (46.7%) | 24 (44.4%) | 73 (45.9%) |
| Race | | | |
| White or Caucasian, n (%) | 83 (79.0%) | 46 (85.2%) | 129 (81.1%) |
| Black or African American, n (%) | 16 (15.2%) | 7 (13.0%) | 23 (14.5%) |
| Asian, n (%) | 2 (1.9%) | 1 (1.9%) | 3 (1.9%) |
| Other, n (%) | 4 (3.8%) | 0 (0.0%) | 4 (2.5%) |
| Ethnicity | | | |
| Not Hispanic / Latino, n (%) | 84 (80.0%) | 49 (90.7%) | 133 (83.6%) |
| Hispanic or Latino, n (%) | 21 (20.0%) | 5 (9.3%) | 26 (16.4%) |
| Wound type | | | |
| Injury (Laceration) | 27 (25.7%) | 13 (24.1%) | 40 (25.2%) |
| Surgical incision | 78 (74.3%) | 41 (75.9%) | 119 (74.8%) |

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Adverse events with BondEase were of the same type as seen with other tissue adhesives. In the clinical study, both treatments appeared to be well-tolerated. There were no deaths, no treatment-related serious adverse events, device-related complications or infections. There were no events of wound dehiscence requiring supplemental closure. All device-related adverse events were mild and appeared to have no impact on the cosmesis outcome. Signs of inflammation at the wound site were comparable between treatment groups. Table 3 summarizes these results.

| Table 3: Device-related adverse reactions encountered during the clinical study (ITT |
|--------------------------------------------------------------------------------------|
| Population) |

| Clinical Study Outcomes | BondEase® | Control (CWCD) |
|--------------------------------------------|-----------|----------------|
| | N (%) | N (%) |
| Dehiscence with No Need for<br>Retreatment | 2 (1.9%) | 0 (0%) |
| Mild Scar | 2 (1.9%) | 0 (0%) |
| Acute Inflammation at 10 days | | |
| Erythema | 7 (6.7%) | 4 (7.4%) |
| Edema | 1 (1.0%) | 0 (0.0%) |
| Pain | 2 (1.9%) | 2 (3.7%) |
| <b>Total AEs</b> | 14 | 6 |

Efficacy assessments included percent wound apposition as determined by the investigator and cosmetic outcome of the wound using a validated scale [Hollander JE, et al, 1995] as determined by a blinded clinician. The effectiveness outcomes measured were: (1) the proportion of subjects in whom 100% wound edge apposition was achieved at 10 days (± 3 days) post-procedure; (2) the incidence of >50% wound apposition at 10 days (± 3 days) post-procedure; (3) the incidence of wounds with an optimal cosmetic outcome (score of 6) at 28 days (± 5 days) and (4) the mean and median cosmesis scores at 28 days (± 5 days). The efficacy results are presented in Tables 4, 5 and 6.

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| | BondEase | CWCD | BondEase-<br>CWCD | 95% CI** |
|----------------------------|-------------------|------------------|-------------------|---------------|
| Per protocol population* | 77.1%<br>(74/96) | 80.4%<br>(41/51) | -0.03 | -0.13 to 0.11 |
| Intent-to-treat population | 73.3%<br>(77/105) | 77.8%<br>(42/54) | -0.04 | -0.13 to 0.10 |

## Table 4: 100% Wound Apposition at 10 Days by Treatment Group

*Primary analysis dataset

**The lower bound of the 95% confidence interval of the difference (BondEase-CWCD) is -0.13 which did not reach, but was very close to the pre-specified noninferiority margin of -0.1.

## Table 5: Summary of Secondary Endpoints (ITT Population)

| | BondEase* | CWCD* |
|---------------------------------------------------|----------------|---------------|
| > 50% wound apposition at 10 days, % (n/N) | 93.3% (98/105) | 96.3% (52/54) |
| Optimal cosmesis at 28 days (score of 6), % (n/N) | 70.5% (74/105) | 64.8% (35/54) |
| Cosmesis at 28 days (all scores), mean / median | 5.7 / 6.0 | 5.6 / 6.0 |

*There were no significant differences between treatment groups.

## Table 6: 100% Wound Apposition at 10 Days by Subgroup (PP Population)

| | 100% wound apposition | | BondEase-CWCD<br>(95% CI)* |
|--------------------------|-----------------------|---------------|----------------------------|
| | BondEase | CWCD | |
| Deep dermal sutures used | | | |
| Yes, n/N (%) | 63/78 (80.8%) | 31/39 (79.5%) | 0.01 (-0.14 – 0.17) |
| No, n/N (%) | 11/18 (61.1%) | 10/12 (83.3%) | -0.22 (-0.53 – 0.09) |
| Wound type | | | |
| Incision, n/N (%) | 60/72 (83.3%) | 32/40 (80.0%) | 0.03 (-0.12 – 0.18) |
| Injury, n/N (%) | 14/24 (58.3%) | 9/11 (81.8%) | -0.24 (-0.54 – 0.07) |

*There were no significant differences between treatment groups.

While investigators were paid to conduct the study, the value of compensation was not determined by the study outcome. None of the investigators had a proprietary interest or equity in the product.

## Conclusions Drawn from Nonclinical and Clinical Data

The results from extensive biocompatibility, animal and bench testing and clinical study confirm that BondEase® is substantially equivalent to the predicate devices.