Histoacryl, Histoacryl Blue and Histoacryl Flexible topical skin adhesives are intended for topical application to hold closed easily approximated skin edges of minimum-tension wounds from clean surgical incisions and simple, thoroughly cleansed, trauma-induced lacerations. Histoacryl Blue and Histoacryl Flexible may be used in conjunction with, but not in place of, deep dermal sutures.

Device Description

Histoacryl and Histoacryl Blue are sterile liquid topical skin adhesives composed of n-buty|-2cyanoacrylate monomer. The two products are different in only one respect: Histoacryl is provided as a colorless liquid, and Histoacryl Blue is colored with the dye D&C Violet #2 with intent to ease visualization of the device during application.

Histoacryl Flexible Topical Skin Adhesive is a sterile liquid topical skin adhesive composed of n-butyl-2-cyanoacrylate monomer, softener, stabilizer, and colorant (D&C Violet #2).

The Histoacryl, Histoacryl Blue and Histoacryl Flexible are provided in 0.5 ml single patient use plastic ampoules. Each ampoule is sealed within a foil pouch so the exterior of the ampoule can remain sterile. The applicator tip is packaged in a sterile blister pack. The plastic ampoules and applicator tips will be packaged together in a box. The tissue adhesives remain liquid until exposed to water or water-containing substances including tissue, after which it cures (polymerizes) and forms a film that bonds to the underlying surface.

The Histoacryl family will be packaged with a separate sterile blistered applicator tip. The applicator tip is an elastic elastomer which can be placed on the tip of the ampoule. The proposed devices will be packaged as a pack. Equal number of ampoules and applicator tips will be packaged together.

AI/ML Overview

The provided text describes a 510(k) submission for Histoacryl, Histoacryl Blue, and Histoacryl Flexible Topical Skin Adhesives with an Applicator Tip (K140343). This submission aims to demonstrate substantial equivalence to previously cleared predicate devices (K111959 and K121976), particularly regarding the addition of a separate applicator tip.

The document focuses on non-clinical performance testing rather than clinical studies with human participants. Therefore, information related to clinical study design, such as sample size for test sets, data provenance, number of experts for ground truth, adjudication methods, or MRMC studies, is not applicable or not provided.

Here's an analysis of the acceptance criteria and study as described:

1. Table of Acceptance Criteria and Reported Device Performance:

The document lists several performance tests conducted to demonstrate substantial equivalence, implying that meeting similar performance levels to the predicate devices for these tests serves as the acceptance criteria. Specific quantitative acceptance criteria (e.g., "peel adhesion strength must be >= X N/mm") are not explicitly stated within this summary; instead, the overall finding is that the new device is "substantially equivalent" in performance to the predicate.

Acceptance Criteria (Implied)	Reported Device Performance
Equivalent Wound closure strength (as per ASTM F2458-05)	Demonstrated substantially equivalent performance to predicate.
Equivalent Peel adhesion strength (as per ASTM F2256-05)	Demonstrated substantially equivalent performance to predicate.
Equivalent Lap-shear strength (as per ASTM F2255-05)	Demonstrated substantially equivalent performance to predicate.
Equivalent Flexibility	Demonstrated substantially equivalent performance to predicate.
Equivalent Heat of polymerization	Demonstrated substantially equivalent performance to predicate.
Equivalent Ease of Expression	Demonstrated substantially equivalent performance to predicate.
Equivalent Occlusion test results	Demonstrated substantially equivalent performance to predicate.
Equivalent Adhesive delivered per area	Demonstrated substantially equivalent performance to predicate.
Equivalent Film thickness	Demonstrated substantially equivalent performance to predicate.
Equivalent Set-time	Demonstrated substantially equivalent performance to predicate.
Retention of microbial barrier properties with applicator tip	Microbial barrier testing conducted; reported as an effective barrier as long as the film remains intact.
Biocompatibility of applicator tip (MEM Elution, Intracutaneous, Systemic Toxicity, Maximization, Cytotoxicity)	Raw material and finished applicator tip found non-cytotoxic and non-irritants.

2. Sample Size Used for the Test Set and Data Provenance:

Sample Size for Test Set: The document does not specify exact sample sizes for each of the performance tests (e.g., number of samples for peel adhesion, wound closure, etc.). It only states that "Testing was performed."
Data Provenance: The studies are in vitro (laboratory-based) performance tests, not clinical studies involving human patients. Therefore, terms like "country of origin of the data" or "retrospective or prospective" are not applicable in their usual sense. The tests were conducted to specific ASTM standards in a laboratory setting.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

Not applicable. As these are in vitro performance tests against specific engineering standards (ASTM), "ground truth" in the sense of expert medical opinion is not established. The "ground truth" for these tests comes from the objective measurements defined by the standardized test methods.

4. Adjudication Method for the Test Set:

Not applicable. There is no human interpretation or decision-making in the performance tests that would require adjudication. The results are based on objective measurement against established test standards.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

No, an MRMC comparative effectiveness study was not done. This device is a topical skin adhesive, and the submission focuses on its physical and biological performance characteristics, not on diagnostic or interpretative capabilities that would involve human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

This question is typically relevant for AI/ML-driven diagnostic devices. For a medical device like a topical skin adhesive, a "standalone algorithm performance" is not applicable. The performance is assessed through its physical and biological properties.

7. The Type of Ground Truth Used:

The "ground truth" for the performance tests is derived from objective measurements against established ASTM standards and ISO standards (for biocompatibility). For example, wound closure strength or peel adhesion strength is measured quantitatively according to the specified ASTM methods. For microbial barrier testing, the "ground truth" is the observed penetration or non-penetration of specified organisms.

8. The Sample Size for the Training Set:

Not applicable. This device is a topical skin adhesive, not an AI/ML algorithm that requires a training set.

9. How the Ground Truth for the Training Set Was Established:

Not applicable, as there is no training set for this type of device.

Summary

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		K140343
		Page 1 of 3
B.	510(k) SUMMARY (as required by 21 CFR 807.92)
	Histoacryl, Histoacryl Blue and Histoacryl FlexibleTopical Skin Adhesive with Applicator TipFebruary 10, 2014	MAY 1 3 2014
COMPANY:	Aesculap®, Inc.3773 Corporate ParkwayCenter Valley, PA 18034Establishment Registration Number: 2916714
CONTACT:	Kathy A. Racosky610-984-9291 (phone)610-791-6882 (fax)kathy.racosky@aesculap.com
TRADE NAME:	Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical SkinAdhesives
COMMON NAME:	Topical Skin Adhesive
REGULATION NUMBER:	878.4010 - Tissue adhesive
PRODUCT CODE:	MPN
REVIEW PANEL:	General & Plastic Surgery

SUBSTANTIAL EQUIVALENCE

Aesculap, Inc. believes that the Aesculap Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives with Applicator Tip are substantially equivalent to Aesculap's current Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives (K111959 and K121976).

DEVICE DESCRIPTION

Histoacryl Flexible Topical Skin Adhesive is a sterile liquid topical skin adhesive composed of n-butyl-2-cyanoacrylate monomer, softener, stabilizer, and colorant (D&C Violet #2).

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K140343 Page 2 of 3

In vitro studies have shown that Histoacryl acts as a barrier to microbial penetration as long as the adhesive film remains intact. Clinical studies were not conducted to demonstrate microbial barrier properties and a correlation between microbial barrier properties and a reduction in infection have not been established.

INDICATIONS FOR USE

Histoacryl. Histoacryl Blue and Histoacryl Flexible topical skin adhesives are intended for topical application to hold closed easily approximated skin edges of minimum-tension wounds from clean surgical incisions and simple, thoroughly cleansed, trauma-induced lacerations. Histoacryl, Histoacryl Blue and Histoacryl Flexible may be used in conjunction with, but not in place of, deep dermal sutures.

TECHNOLOGICAL CHARACTERISTICS(compared to Predicate(s)}

The technological characteristics of the Aesculap Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives with Applicator Tip are equivalent in performance to the predicate devices Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives (K111959 and K121976). The subject device is shown to be substantially equivalent and has the same performance characteristic to the predicate devices through comparison in technology, Indication For Use, mechanism of action, intended application and performance. Both Histoacryl and Histoacryl Blue Topical Skin Adhesive and Histoacryl Flexible Topical Skin Adhesive devices use n-butyl-2-cyanoacrylate to facilitate wound closure. Histoacryl Flexible is designed to bond to the skin to provide flexible wound closure maintaining wound approximation.

The differences between the proposed devices Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives with Applicator Tip and Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives are:

. The Histoacryl family will be packaged with a separate sterile blistered applicator tip. The applicator tip is an elastic elastomer which can be placed on the tip of the ampoule. The proposed devices will be packaged as a pack. Equal number of ampoules and applicator tips will be packaged together.

BIOCOMPATIBILITY:

The biocompatibility testing of the adhesive that was previously conducted for the currently marketed devices, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives (K111959 and K121976) per ISO-10993, "Biological Evaluation of Medical Devices Part-1: Evaluation and Testing" is deemed supportive of the proposed devices. Aesculap Histoacryl. Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives with Applicator Tip. There were no changes to the formulation of the adhesive; therefore, no additional biocompatibility testing of the adhesive was conducted.

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K140343

Page 3 of 3

Testing was conducted in accordance to USP 31, <661> Containers. Plastics and <88> Biological Reactivity Tests, In Vivo. Biocompatibility testing within this submission was performed on the raw material from which the applicator tip is manufactured which includes the following: MEM Elution cytotoxicity (ISO 10993-5), intracutaneous irritation (ISO 10993-10), systemic toxicity (ISO 10993-11) and maximization (ISO 10993-10). In addition cytotoxicity testing was performed on the finished applicator tip. Based on the results from these studies, the proposed device is considered to be non-cytotoxic and non-irritants

PERFORMANCE TESTING

Testing was performed in accordance to FDA's Class II Special control Guidance Document for Tissue Adhesive for the Topical Approximation of Skin to demonstrate that the Aesculap Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives with Applicator Tip is substantially equivalent to other predicate devices. The following comparative testing demonstrated substantially equivalent performance to Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives.

. Wound closure strength (ASTM F2458-05)
Peel adhesion strength (ASTM F2256-05) .
Lap-shear strength (ASTM F2255-05) .
. Flexibility
Heat of polymerization ◆
Ease of Expression .
. Occlusion test
� Adhesive delivered per area
Film thickness �
. Set-time

Microbial barrier testing was conducted using Histoacry] and Histoacry] Flexible applied with the applicator tip. The method was a strike through test that was conducted with common organisms known to cause infections and represent gram positive, gram negative, motile and non-motile as well as fungi. The challenge was at a minimum concentration of 1 x 108 cfu.

STERILIZATION AND SHELF-LIFE:

Sterilization of Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives remains the same as the predicates (K111959 and K121976). The sterilization process consists of 1) ETO sterilization of the ampoule, 2) gamma radiation sterilization of the aluminum pouch: both are sterilized before 3 ) the sterility of the liquid topical skin adhesive which is guaranteed by membrane filtration and aseptic filling.

The applicator tip is blister packed and sterilized by ethylene oxide. Accelerated aging data for the applicator tip has been generated to support this submission.

CONCLUSION:

Based on the nonclinical testing Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives with Applicator Tip have been demonstrated to be substantially equivalent to Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives.

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Image /page/3/Picture/0 description: The image shows the seal of the Department of Health & Human Services - USA. The seal is circular and contains the department's emblem in the center. The emblem consists of a stylized caduceus, a symbol often associated with medicine and healthcare. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged around the perimeter of the circle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

May 13, 2014

Aesulap® Incorporated Ms. Kathy A. Racosky Senior Regulatory Affairs Specialist 3773 Corporate Parkway Center Valley, Pennsylvania 18034

Re: K140343

Trade/Device Name: Histoacryl, Histoacryl Blue and Histoacryl Flexible Topical Skin Adhesives with Applicator Tip Regulation Number: 21 CFR 878.4010 Regulation Name: Tissue adhesive Regulatory Class: Class II Product Code: MPN Dated: February 12, 2014 Received: February 14, 2014

Dear Ms. Racosky:

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

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Page 2 - Ms. Kathy A. Racosky

device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set 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 (800) 638-2041 or (301) 796-7100 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" (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 (800) 638-2041 or (301) 796-7100 or at its Internet address

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

Sincerely yours,

David Krause -S

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

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

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

510(k) Number (if known) K140343

Device Name

Histoacryl, Histoacryl Blue and Histoacry| Flexible Topical Skin Adhesives with Applicator Tip

Indications for Use (Describe)

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

2 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,

FOR FDA USE ONLY

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

Joseph Nielsen -S 2014.05.13 07:16:03 -04 00

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 time 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:

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Regulation Number and Section

§ 878.4010 Tissue adhesive.

(a)
Tissue adhesive for the topical approximation of skin —(1)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.(2)
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.