PICO Single Use Negative Pressure Wound Therapy System is indicated for patients who would benefit from a suction device (negative pressure wound therapy) as it may promote wound healing via removal of low to moderate levels of exudate and infectious materials. PICO Single Use Negative Pressure Wound Therapy Systems are suitable for use both in a hospital and homecare setting. Appropriate wound types include:

Chronic
Acute
Traumatic
Subacute and dehisced wounds
Partial-thickness burns
Ulcers (such as diabetic or pressure)
Flaps and grafts
Closed surgical incisions

When used on closed surgical incisions, PICO Single Use Negative Pressure Wound Therapy System is intended to aid in reducing the incidence of:

Superficial and deep incisional surgical site infections for high risk patients in Class II wounds
Post-operative seroma
Dehiscence

Note: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore. Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol.

PICO 7 Single Use Negative Pressure Wound Therapy System is indicated for patients who would benefit from a suction device (negative pressure wound therapy) as it may promote wound healing via removal of low to moderate levels of exudate and infectious materials. PICO 7 Single Use Negative Pressure Wound Therapy Systems are suitable for use both in a hospital and homecare setting. Appropriate wound types include:

Chronic
Acute
Traumatic
Subacute and dehisced wounds
Partial-thickness burns
Ulcers (such as diabetic or pressure)
Flaps and grafts
Closed surgical incisions

When used on closed surgical incisions, PICO 7 Single Use Negative Wound Therapy System is intended to aid in reducing the incidence of:

Superficial and deep incisional surgical site infections for high risk patients in Class II wounds
Post-operative seroma
Dehiscence

Note: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol.

PICO 7Y Single Use Negative Pressure Wound Therapy System is indicated for patients who would benefit from a suction device (negative pressure wound therapy) as it may promote wound healing via removal of low to moderate levels of exudate and infectious materials. PICO 7Y Single Use Negative Pressure Wound Therapy Systems are suitable for use both in a hospital and homecare setting. Appropriate wound types include:

Chronic
Acute
Traumatic
Subacute and dehisced wounds
Partial-thickness burns
Ulcers (such as diabetic or pressure)
Flaps and grafts
Closed surgical incisions

When used on closed surgical incisions, PICO 7Y Single Use Negative Pressure Wound Therapy System is intended to aid in reducing the incidence of:

Superficial incisional surgical site infections for high risk patients in Class I wounds
Post-operative seroma
Dehiscence

Note: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class II (Clean/ Contaminated), Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol.

PICO 14 Single Use Negative Pressure Wound Therapy System is indicated for patients who would benefit from a suction device (negative pressure wound therapy) as it may promote wound healing via removal of low to moderate levels of exudate and infectious materials. PICO 14 Single Use Negative Pressure Wound Therapy Systems are suitable for use both in a hospital and homecare setting. Appropriate wound types include:

Chronic
Acute
Traumatic
Subacute and dehisced wounds
Partial-thickness burns
Ulcers (such as diabetic or pressure)
Flaps and grafts
Closed surgical incisions

When used on closed surgical incisions for up to 7 days, PICO 14 Single Use Negative Pressure Wound Therapy is intended to aid in reducing the incidence of:

Superficial and deep incisional surgical site infections for high risk patients in Class II wounds
Post-operative seroma
Dehiscence

Note: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol.

Device Description

The PICO Family of devices, PICO (cleared under K163387), PICO 7 (cleared under K180698), PICO 7Y (cleared under K182323), PICO 14 (cleared under K191760) all have the same main function of management of fluid through dressing absorbency and evaporation with added benefit of negative pressure. The pump provides a -80mmHg nominal pressure under the dressing, applying Negative Pressure Wound Therapy (NPWT) to the wound. The PICO Single Use Negative Therapy Systems consist of:

PICO Pump
Dressing (s)
Fixation strips
Batteries
Connection tubing
Instructions for Use

The system is a canister-less system - fluid is managed by the dressing. The pump that delivers the NPWT is a portable, battery-powered, software-controlled system that can provide continuous application of negative pressure to the wound as a delivery pressure at a nominal value of -80mmHg. The PICO Systems are designed to be used at home or within a healthcare setting by an appropriate healthcare professional.

AI/ML Overview

The PICO family of devices (PICO, PICO 7, PICO 7Y, and PICO 14) are Negative Pressure Wound Therapy Systems intended for use in wound treatment.

1. A table of acceptance criteria and the reported device performance

The provided document does not explicitly state "acceptance criteria" with numerical thresholds for performance. Instead, it demonstrates the device's effectiveness through a systematic literature review and meta-analyses, aiming to show a "statistically significant reduction" in the incidence of certain wound complications compared to standard care. The reported device performance is presented as Odds Ratios (OR) with 95% Confidence Intervals (CI). A favorable effect is suggested by an OR less than 1.

Here's a summary of the meta-analysis results as reported:

Outcome	Device Performance (Odds Ratio [95% CI])	Interpretation (Favorable Effect if OR < 1)
Surgical Site Infections (SSI) - Overall	0.36 [0.27; 0.49]	Favorable
Superficial SSI	0.30 [0.17; 0.53]	Favorable
Deep SSI	0.67 [0.46; 0.96]	Favorable
Post-operative Seroma	0.37 [0.16; 0.86]	Favorable
Dehiscence	0.63 [0.43; 0.92]	Favorable

2. Sample sizes used for the test set and the data provenance

The "test set" for this submission is comprised of studies identified through a systematic literature review. This means the data is retrospective, as it relies on previously published research. The provenance of the data is global, as the literature review included studies from various researchers and institutions, not limited to a single country.

Overall SSI Meta-analysis:
- Evaluable patients: 2,737 in the PICO Family therapy group, 2,936 in the SOC (control) group.
- Total studies: 17 (12 RCTs, 5 prospective observational).
Superficial SSI Meta-analysis:
- Evaluable patients: 356 in the PICO Family therapy group, 367 in the SOC (control) group.
- Total studies: 8 (5 RCTs, 3 prospective observational).
Deep SSI Meta-analysis:
- Evaluable patients: 1,146 in the PICO Family therapy group, 1,138 in the SOC (control) group.
- Total studies: 6 (4 RCTs, 2 prospective observational).
Post-operative Seroma Meta-analysis:
- Evaluable patients: 608 in the PICO Family therapy group, 618 in the SOC (control) group.
- Total studies: 10 (7 RCTs, 3 prospective observational).
Dehiscence Meta-analysis:
- Evaluable patients: 551 in the PICO Family therapy group, 656 in the SOC (control) group.
- Total studies: 7 (6 RCTs, 1 prospective observational).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

The ground truth for the test set (the outcomes of the studies included in the meta-analysis) was established by the original researchers and clinicians who conducted each individual study. The document states:

"Two (2) independent reviewers performed the study selection."
"In case of disagreement a third reviewer made the final decision after reading the full text paper or conference abstract."
"Data was extracted from included studies by one reviewer using a predefined and standardized data extraction form and checked by a second reviewer for accuracy."

The qualifications of these specific reviewers are not provided in the document. However, the outcomes themselves (SSI, seroma, dehiscence) are medical diagnoses and complications identified by the healthcare professionals directly involved in the patient care and study follow-up within the original research for each of the 25 articles. These would typically be surgeons, nurses, and other medical personnel, under the guidance of the study investigators.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

For the selection of studies for inclusion in the meta-analysis:

"Two (2) independent reviewers performed the study selection."
"If either reviewer deemed an article as potentially relevant, then the article progressed to full text screening."
"In case of disagreement a third reviewer made the final decision after reading the full text paper or conference abstract."
This indicates a 2-reviewer initial screening with a third reviewer for adjudication in case of disagreement (2+1 method) for study selection.

For data extraction:

"Data was extracted from included studies by one reviewer using a predefined and standardized data extraction form and checked by a second reviewer for accuracy."
This implies a single reviewer for initial extraction with a second reviewer for verification, which is a form of 1+1 review.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

No MRMC comparative effectiveness study was done, nor is this device an AI-powered diagnostic tool. The document describes a medical device (Negative Pressure Wound Therapy System) and its clinical effectiveness compared to standard care through a meta-analysis of existing clinical trials, not an AI system. Therefore, details regarding human reader improvement with/without AI assistance are not applicable.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This refers to a medical device, a wound therapy system, not an algorithm or AI system. Therefore, the concept of "standalone algorithm performance" (without human-in-the-loop) is not applicable. The device operates independently of human interpretation in its direct therapeutic action (applying negative pressure), but its application and management involve healthcare professionals.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the effectiveness claims of the PICO family of devices (reduction in SSI, seroma, and dehiscence) is based on outcomes data from various clinical studies. These outcomes (e.g., incidence of infection, presence of seroma, occurrence of dehiscence) were reported by the original study investigators, presumably determined through clinical assessment, and potentially supported by other diagnostic methods (e.g., microbiology for infection, imaging for seroma, clinical examination for dehiscence), depending on the specific protocols of each individual study included in the meta-analysis. For infection, the CDC guidelines for defining SSI were used, which involve clinical criteria.

8. The sample size for the training set

This document describes a medical device and its clinical effectiveness evaluated through a meta-analysis of clinical studies, not an AI/machine learning algorithm that requires a "training set." Therefore, the concept of a training set sample size is not applicable here.

9. How the ground truth for the training set was established

As explained in point 8, the concept of a "training set" is not applicable to this submission.

Summary

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Image /page/0/Picture/0 description: The image shows the logo for the U.S. Food and Drug Administration (FDA). On the left is the Department of Health and Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue box. Underneath that is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

December 14, 2021

Smith and Nephew Medical Limited Steeve Lamvohee Director, Regulatory Affairs, Advanced Wound Management 101 Hessle Road Hull, Yorkshire HU3 2BN United Kingdom

Re: K203716

Trade/Device Name: PICO Single Use Negative Pressure Wound Therapy System, PICO 7 Single Use Negative Pressure Wound Therapy System, PICO 7Y Single Use Negative Pressure Wound Therapy System, PICO 14 Single Use Negative Pressure Wound Therapy System Regulation Number: 21 CFR 878.4783 Regulation Name: Negative Pressure Wound Therapy Device For Reduction Of Wound Complications Regulatory Class: Class II Product Code: OFC Dated: June 1, 2021 Received: June 14, 2021

Dear Steeve Lamvohee:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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

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 of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

for Julie Morabito, Ph.D. Assistant Director DHT4B: Division of Infection Control and Plastic Surgery Devices OHT4: Office of Surgical and Infection Control Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known) K203716

Device Name

PICO Single Use Negative Pressure Wound Therapy System

Indications for Use (Describe)

Chronic
· Acute
Traumatic
Subacute and dehisced wounds
· Partial-thickness burns
· Ulcers (such as diabetic or pressure)
Flaps and grafts
· Closed surgical incisions

When used on closed surgical incisions, PICO Single Use Negative Pressure Wound Therapy System is intended to aid in reducing the incidence of:

· Superficial and deep incisional surgical site infections for high risk patients in Class II wounds
· Post-operative seroma
· Dehiscence

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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

510(k) Number (if known) K203716

Device Name

PICO 7 Single Use Negative Pressure Wound Therapy System

Indications for Use (Describe)

Chronic
· Acute
Traumatic
Subacute and dehisced wounds
· Partial-thickness burns
· Ulcers (such as diabetic or pressure)
Flaps and grafts
· Closed surgical incisions

When used on closed surgical incisions, PICO 7 Single Use Negative Wound Therapy System is intended to aid in reducing the incidence of:

· Superficial and deep incisional surgical site infections for high risk patients in Class II wounds
· Post-operative seroma
· Dehiscence

Note: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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.

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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

510(k) Number (if known) K203716

Device Name

PICO 7Y Single Use Negative Pressure Wound Therapy System

Indications for Use (Describe)

Chronic
· Acute
Traumatic
Subacute and dehisced wounds
· Partial-thickness burns
· Ulcers (such as diabetic or pressure)
Flaps and grafts
· Closed surgical incisions

When used on closed surgical incisions, PICO 7Y Single Use Negative Pressure Wound Therapy System is intended to aid in reducing the incidence of:

· Superficial incisional surgical site infections for high risk patients in Class I wounds
· Post-operative seroma
· Dehiscence

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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.

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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

510(k) Number (if known) K203716

Device Name

PICO 14 Single Use Negative Pressure Wound Therapy System

Indications for Use (Describe)

Chronic
· Acute
Traumatic
Subacute and dehisced wounds
· Partial-thickness burns
· Ulcers (such as diabetic or pressure)
Flaps and grafts
· Closed surgical incisions

When used on closed surgical incisions for up to 7 days, PICO 14 Single Use Negative Pressure Wound Therapy is intended to aid in reducing the incidence of:

· Superficial and deep incisional surgical site infections for high risk patients in Class II wounds
· Post-operative seroma
Dehiscence

Note: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol.

Type of Use (Select one or both, as applicable)X Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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.

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

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

510(k) Summary

21 CFR 807.92 (a)(1): Submitter's Information
510(k) Owner Name	Smith & Nephew Medical Ltd
Address	101 Hessle Road, Hull, HU3 2BN, United Kingdom
EstablishmentRegistration Number	8043484
Contact Name	Dr Steeve Lamvohee, Regulatory Affairs Director
Date Prepared	23 Sept 2021
21 CFR 807.92 (a)(2): Device Information
Device Name(Trade/Proprietary Name)	PICO Single Use Negative Pressure Wound Therapy SystemPICO 7 Single Use Negative Pressure Wound Therapy SystemPICO 7Y Single Use Negative Pressure Wound Therapy SystemPICO 14 Single Use Negative Pressure Wound Therapy System
Common Name	Negative pressure wound therapy device for reduction of woundcomplications
Review Panel	General and Plastic Surgery
Regulation Number	21 CFR 878.4783
Regulatory Class	Class II
Product Code	QFC
21 CFR 807.92 (a)(3):Legally marketed device towhich equivalence isclaimed	DeNovo Number: DEN180013Device Name: PREVENATM 125 and PREVENA PLUSTM125 (PREVENA)

21 CFR 807.92 (a)(4): Device Description

PICO Pump
· Dressing (s)
· Fixation strips
· Batteries
· Connection tubing
Instructions for Use

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

The dressing and amount of negative pressure delivered across all systems remain the same. Table 1 provides details of products within the PICO Family.

In the context of the proposed Indications for Use, see the definitions provided:

According to the latest recommendations (CDC 2020), superficial and deep incisional SSIs are defined as follows:

A superficial incisional SSI involves only skin and subcutaneous tissue of the incision . and occurs within 30 days after any National Healthcare Safety Network (NHSN) operative procedure.
A deep incisional SSI involves deep soft tissues of the incision (for example, fascial and . muscle layers) and occurs within 30 or 90 days after the NHSN operative procedure.

Reference:

CDC 2020. SSI – Procedure-associated Module 2020. Available from: https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf. [Accessed 04/11/2020].

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	PICO(PICO 1.6)	PICO 7	PICO 7Y	PICO 14
Indications forUse	PICO Single Use Negative PressureWound Therapy System is indicatedfor patients who would benefit froma suction device (negative pressurewound therapy) as it may promotewound healing via removal of lowto moderate levels of exudate andinfectious materials. PICO SingleUse Negative Pressure WoundTherapy Systems are suitable for useboth in a hospital and homecaresetting. Appropriate wound typesinclude:• Chronic• Acute• Traumatic• Subacute and dehisced wounds• Partial-thickness burns• Ulcers (such as diabetic orpressure)• Flaps and grafts• Closed surgical incisionsWhen used on closed surgicalincisions, PICO Single UseNegative Pressure Wound TherapySystem is intended to aid inreducing the incidence of:• Superficial and deepincisional surgical site	Same as PICO (PICO 1.6)	PICO 7Y Single Use NegativePressure Wound Therapy System isindicated for patients who wouldbenefit from a suction device(negative pressure wound therapy)as it may promote wound healingvia removal of low to moderatelevels of exudate and infectiousmaterials. PICO 7Y Single UseNegative Pressure Wound TherapySystems are suitable for useboth in a hospital and homecaresetting. Appropriate wound typesinclude:• Chronic• Acute• Traumatic• Subacute and dehisced wounds• Partial-thickness burns• Ulcers (such as diabetic orpressure)• Flaps and grafts• Closed surgical incisionsWhen used on closed surgicalincisions, PICO 7Y Single UseNegative Pressure Wound TherapySystem is intended to aid inreducing the incidence of:• Superficial incisional surgical site	PICO 14 Single Use NegativePressure Wound Therapy System isindicated for patients who wouldbenefit from a suction device(negative pressure wound therapy)as it may promote wound healingvia removal of low to moderatelevels of exudate and infectiousmaterials. PICO 14 Single UseNegative Pressure Wound TherapySystems are suitable for useboth in a hospital and homecaresetting. Appropriate wound typesinclude:• Chronic• Acute• Traumatic• Subacute and dehisced wounds• Partial-thickness burns• Ulcers (such as diabetic orpressure)• Flaps and grafts• Closed surgical incisionsWhen used on closed surgicalincisions for up to 7 days, PICO 14Single Use Negative PressureWound Therapy is intended to aidin reducing the incidence of:• Superficial and deep incisional
	PICO(PICO 1.6)	PICO 7	PICO 7Y	PICO 14
	infections for high riskpatients in Class I and ClassII wounds		infections for high risk patients inClass I wounds	surgical site infections for high riskpatients in Class I and Class IIwounds
	• Post-operative seroma		• Post-operative seroma	• Post-operative seroma
	• Dehiscence		• Dehiscence	• Dehiscence
	Note: When used on closedincisions for the reduction of SSI,the safety and effectiveness forClass III (contaminated) and ClassIV (Dirty/Infected) wounds havenot been demonstrated.Furthermore, Class IV surgicalwounds are not expected to beclosed primarily. The device has notbeen demonstrated to reduce organspace surgical site infections. Thedevice is intended to aid in reducingthe incidence of, but not treat,seroma, dehiscence, or infectedwounds - the use of PICO does notpreclude the need to develop andfollow a comprehensive infectionmanagement protocol.		Note: When used on closedincisions for the reduction of SSI,the safety and effectiveness forClass II (Clean/Contaminated),Class III (contaminated) and ClassIV (Dirty/Infected) wounds havenot been demonstrated.Furthermore, Class IV surgicalwounds are not expected to beclosed primarily. The device has notbeen demonstrated to reduce organspace surgical site infections. Thedevice is intended to aid in reducingthe incidence of, but not treat,seroma, dehiscence, or infectedwounds - the use of PICO does notpreclude the need to develop andfollow a comprehensive infectionmanagement protocol.	Note: When used on closedincisions for the reduction of SSI,the safety and effectiveness forClass III (contaminated) and ClassIV (Dirty/Infected) wounds havenot been demonstrated.Furthermore, Class IV surgicalwounds are not expected to beclosed primarily. The device has notbeen demonstrated to reduce organspace surgical site infections. Thedevice is intended to aid in reducingthe incidence of, but not treat,seroma, dehiscence, or infectedwounds - the use of PICO does notpreclude the need to develop andfollow a comprehensive infectionmanagement protocol.
Technologicalprincipal fordelivering thenegative pressurewound therapy	Removal of air fromdressing and wound creatingNPWT effect. Dressingabsorbs exudate from woundwhich then evaporates	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)
	PICO(PICO 1.6)	PICO 7	PICO 7Y	PICO 14
Physical componentsof the pumps	Electric motor driven twin-diaphragm vacuum pump controlled by Microprocessor	Custom designed "voice-coil" Pump containing a magnet controlled by Microprocessor	Same as PICO 7	Same as PICO 7
Physical componentsof Dressing	Dressing: High Moisture Vapor Permeability polyurethane (MVP PU) top film, polyester spacer layer, air laid super absorbent, silicone wound contact layer, Soft Port tubeSecondary fixation strips: High MVP film with acrylic adhesive	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)
Tubing/Dressingconnector	Single – used to connect a single dressing to the device using PVC tubing	Same as PICO (PICO 1.6)	Y shaped - used to connect two dressings to the device using two sets of PVC tubing; same amount of negative pressure delivered to each wound as PICO (PICO 1.6), PICO 7, and PICO 14	Same as PICO (PICO 1.6)
Batteries	AA Lithium (2)	AA Alkaline (2)	Same as PICO (PICO 1.6)	AA Alkaline (2) + 2 spares provided
Software Controlled	Yes	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)
Dressing Wear Time	Up to 7 Days	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)
Pump Lifetime	7 Days	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	14 Days
User Interface	After dressing application, the user would interact with the pump device that is attached to the dressing via a soft-port. The pump	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)
	PICO(PICO 1.6)	PICO 7	PICO 7Y	PICO 14
	device has a start/stop therapybutton and indicators.
Electrical Safety andElectro-magneticCompatibility (EMC)	Complies with IEC 60601-1, IEC60601-1-2, IEC 60601-1-11, IEC60601-1-6, IEC 62366	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)
Dimensions	63mm x 70mm x 18mm	2.6 x 3.2 x 0.9"	Same as PICO 7	Same as PICO 7
Operating Pressure atWound TreatmentLocation	Nominal -80mmHg	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)	Same as PICO (PICO 1.6)

TABLE 1: Comparison of PICO Family

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21 CFR 807.92 (a)(5): Intended Use / Indications for Use

PICO and PICO 7

PICO/PICO 7 Single Use Negative Pressure Wound Therapy System is indicated for patients who would benefit from a suction device (negative pressure wound therapy) as it may promote wound healing via removal of low to moderate levels of exudate and infectious materials. PICO / PICO 7 Single Use Negative Pressure Wound Therapy Systems are suitable for use

both in a hospital and homecare setting. Appropriate wound types include:

Chronic
Acute
Traumatic
Subacute and dehisced wounds
Partial-thickness burns
· Ulcers (such as diabetic or pressure)
Flaps and grafts
· Closed surgical incisions

When used on closed surgical incisions, PICO/ PICO 7 Single Use Negative Pressure Wound Therapy System is intended to aid in reducing the incidence of:

· Superficial and deep incisional surgical site infections for high risk patients in Class I and Class II wounds

Post-operative seroma
Dehiscence

PICO 7Y

Chronic
Acute
Traumatic
Subacute and dehisced wounds
Partial-thickness burns
· Ulcers (such as diabetic or pressure)
Flaps and grafts
Closed surgical incisions

When used on closed surgical incisions, PICO 7Y Single Use Negative Pressure Wound Therapy System is intended to aid in reducing the incidence of:

· Superficial incisional surgical site infections for high risk patients in Class I wounds
· Post-operative seroma
Dehiscence

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PICO 14

both in a hospital and homecare setting. Appropriate wound types include:

Chronic
Acute
Traumatic
Subacute and dehisced wounds
· Partial-thickness burns
· Ulcers (such as diabetic or pressure)
Flaps and grafts
· Closed surgical incisions

When used on closed surgical incisions for up to 7 days, PICO 14 Single Use Negative Pressure Wound Therapy is intended to aid in reducing the incidence of:

· Superficial and deep incisional surgical site infections for high risk patients in Class I and Class II wounds

· Post-operative seroma
· Dehiscence

21 CFR 807.92 (a)(6): Comparison of Technological Characteristics between the Subject and Predicate Devices

The PICO Family and the cleared PREVENA device have very similar indications for use, similar technological characteristics and the same principles of operation. While there are minor technological differences between the PICO Family and PREVENA with respect to exudate management, therapeutic pressure setting, device sterility status and dimensions, these differences do not raise any new or different questions of safety and effectiveness compared to the predicate device, see Table 2 below.

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	PREVENA (Predicate Device)	PICO Family (Subject Device)
Product Type	Single patient / Disposable	Single patient / Disposable
Product Code	QFC (21 C.F.R. § 878.4783)	QFC (21 C.F.R. § 878.4783)
Product Classification	Reclassified as Class II	Class II
Exudate management system	Canister	Absorbent dressing
Therapeutic pressure	-125mmHg	-80mmHg
Dressing Wear Time	7 days	Up to 7 days
Intended Use	Indicated for patients who would benefit from a suction device(NPWT) to promote wound healing via removal of low to moderatelevels of exudate and infectious materials.	Indicated for patients who would benefit from a suction device(NPWT) to promote wound healing via removal of low to moderatelevels of exudate and infectious materials.
Indications for use	PREVENA 125 and PREVENA PLUS 125 Therapy Units managethe environment of closed surgical incisions and remove fluid awayfrom the surgical incision via the application of -125mmHgcontinuous negative pressure. When used with legally marketedcompatible dressings, PREVENA 125 and PREVENA PLUS 125Therapy Units are intended to aid in reducing the incidence ofseroma and, in patients at high risk for post-operative infections, aidin reducing the incidence of superficial surgical site infection inClass I and Class II wounds	PICO Single Use Negative Pressure Wound Therapy System isindicated for patients who would benefit from a suction device(negative pressure wound therapy) as it may promote wound healingvia removal of low to moderate levels of exudate and infectiousmaterials. PICO Single Use Negative Pressure Wound TherapySystems are suitable for use both in a hospital and homecare setting.Appropriate wound types include:• Chronic• Acute• Traumatic• Subacute and dehisced wounds• Partial-thickness burns· Ulcers (such as diabetic or pressure)• Flaps and grafts· Closed surgical incisions

Table 2: Comparison of PICO Family against PREVENA

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When used on closed surgical incisions, PICO Single Use Negative
Pressure Wound Therapy System is intended to aid in reducing the
incidence of:
· Superficial and deep incisional surgical site infections for high risk
patients in Class I and Class II wounds
· Post-operative seroma
• Dehiscence
PICO 7 Single Use Negative Pressure Wound Therapy System is
indicated for patients who would benefit from a suction device
(negative pressure wound therapy) as it may promote wound healing
via removal of low to moderate levels of exudate and infectious
materials. PICO 7 Single Use Negative Pressure Wound Therapy
Systems are suitable for use both in a hospital and homecare setting.
Appropriate wound types include:
• Chronic
• Acute
• Traumatic
• Subacute and dehisced wounds
• Partial-thickness burns
• Ulcers (such as diabetic or pressure)
• Flaps and grafts
• Closed surgical incisions
When used on closed surgical incisions, PICO 7 Single Use
Negative Pressure Wound Therapy System is intended to aid in
reducing the incidence of:
· Superficial and deep incisional surgical site infections for high risk
patients in Class I and Class II wounds
· Post-operative seroma
• Dehiscence
PICO 7Y Single Use Negative Pressure Wound Therapy System is
indicated for patients who would benefit from a suction device
(negative pressure wound therapy) as it may promote wound healing
via removal of low to moderate levels of exudate and infectious

materials. PICO 7Y Single Use Negative Pressure Wound Therapy
Systems are suitable for use both in a hospital and homecare setting.
Appropriate wound types include:
• Chronic
• Acute
• Traumatic
• Subacute and dehisced wounds
• Partial-thickness burns
• Ulcers (such as diabetic or pressure)
• Flaps and grafts
• Closed surgical incisions
When used on closed surgical incisions, PICO 7Y Single Use
Negative Pressure Wound Therapy System is intended to aid in
reducing the incidence of:
· Superficial incisional surgical site infections for high risk patients
in Class I wounds
· Post-operative seroma
• Dehiscence
PICO 14 Single Use Negative Pressure Wound Therapy System is
indicated for patients who would benefit from a suction device
(negative pressure wound therapy) as it may promote wound healing
via removal of low to moderate levels of exudate and infectious
materials. PICO 14 Single Use Negative Pressure Wound Therapy
Systems are suitable for use both in a hospital and homecare setting.
Appropriate wound types include:
• Chronic
• Acute
• Traumatic
• Subacute and dehisced wounds
• Partial-thickness burns
• Ulcers (such as diabetic or pressure)
• Flaps and grafts
• Closed surgical incisions

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		When used on closed surgical incisions for up to 7 days, PICO 14Single Use Negative Pressure Wound Therapy is intended to aid inreducing the incidence of:
Limitations	The device is not intended to treat surgical site infection or seroma. Safety and effectiveness in pediatric population (<22 years old) have not been evaluated. Safety and effectiveness in Class III (Contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily, and the subject device should only be used on closed surgical incisions. The device has not been demonstrated to reduce deep incisional and organ space surgical site infections. The device has not been demonstrated to be effective in reducing the incidence of surgical site infection and seroma in all surgical procedures and patient populations; therefore, the device may not be recommended for routine use to reduce the incidence of surgical site infection and seroma.	Superficial and deep incisional surgical site infections for high risk patients in Class I and Class II wounds Post-operative seroma Dehiscence PICO, PICO 7, PICO 14Note: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol.PICO 7YNote: When used on closed incisions for the reduction of SSI, the safety and effectiveness for Class II (Clean/Contaminated), Class III (contaminated) and Class IV (Dirty/Infected) wounds have not been demonstrated. Furthermore, Class IV surgical wounds are not expected to be closed primarily. The device has not been demonstrated to reduce organ space surgical site infections. The device is intended to aid in reducing the incidence of, but not treat, seroma, dehiscence, or infected wounds - the use of PICO does not preclude the need to develop and follow a comprehensive infection management protocol

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21 CFR 807.92 (b)(1): Brief discussion of nonclinical tests submitted/referenced/ relied on in this submission to determine substantial equivalence

Non-clinical/bench test data (including biocompatibility, shelf life/stability, electrical safety and electromagnetic compatibility (EMC), software, performance testing, and human factors/usability testing) were referenced from the following previously-cleared 510(k) submissions of the PICO device: K163387, K180698, K182323, K191760.

Additional EMC testing on PICO 7 was conducted in accordance with IEC 60601-1-2:2014 to demonstrate that alternative suppliers of electrical components did not negatively impact EMC.

21 CFR 807.92 (b)(2): Brief discussion of clinical tests submitted/referenced/ relied on in this submission to determine substantial equivalence

1. CLINICAL DATA

A systematic literature review and associated meta-analyses were used to support the safety and effectiveness of the PICO Family over closed incisions in reducing the incidence of surgical site infections (SSIs), seromas and dehiscence versus conventional wound dressings.

Database search and study selection:

A comprehensive review of published PICO Family literature identiffed relevant articles to support a reduction in SSI, seroma, and dehiscence. Three databases (PubMed, EMBASE and the Cochrane Library) were used to identify published clinical studies. The exact search terms used for each of the three databases are detailed in Table 1. Registered studies at ClinicalTrials.gov were also reviewed using the same search terms for completed and terminated studies with results available (Table 1).

Database	Search query	Filters / Limits	Search hits
PubMed	("Negative PressureWound Therapy"[AllFields] OR "NPWT"[AllFields] OR "PICO"[AllFields] OR "TopicalNegative Pressure"[AllFields]) AND(2011/1/1:2021/4/19[pdat])	Date: 01/01/2011to 19/04/2021Searched: AllFields	6581
EMBASE	('negative pressure woundtherapy' OR 'npwt' OR'pico' OR 'topical negativepressure') AND [1-1-2011]/sd NOT [20-4-2021]/sd	Date: 01/01/2011to 19/04/2021(Date added toEMBASE)Searched: AllFields	7711

Table 1. Search strings and filters used for each of the database searches.
-----------------------------------------------------------------------------

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Cochrane Library	("Negative Pressure Wound Therapy" OR"NPWT" OR "PICO" OR"Topical Negative Pressure") (Wordvariations have been searched)	Date: Jan 2011 toApr 2021Searched: All Text	852
ClinicalTrials.gov	"Negative Pressure WoundTherapy" OR “NPWT”OR “PICO” OR “TopicalNegative Pressure"	Date: 01/01/2011to 19/04/2021'Results available'	139

Two (2) independent reviewers performed the study selection. Abstracts that met the search criteria were screened and assessed against inclusion criteria provided in Table 2. If either reviewer deemed an article as potentially relevant, then the article progressed to full text screening. In case of disagreement a third reviewer made the final decision after reading the full text paper or conference abstract. Included studies detailed outcomes following the use of PICO compared to standard care for closed surgical incisions. The standard of care was defined as the use of standard non-NPWT dressings.

Table 2. Inclusion and Exclusion Criteria.

Inclusion Criteria	Exclusion Criteria
PopulationPatients of any age with closed surgical incisions. Patients with any risk factors for complications were also included.	Patients with open surgical incisions or any non-surgical wound
InterventionPICO (single-use NPWT) applied post-operatively on a closed surgical incision. Participants undergoing any type of operation were eligible.	Other forms of NPWT (i.e. not PICO) were excluded.
ComparatorStandard care (any non-NPWT dressing)	Non-standard care
OutcomeSurgical site infections or seroma or dehiscence	N/A
Study designRandomised controlled trials or prospective observational studies with at least 10 patients in each treatment arm	Retrospective observational studies, case reports, case-series, studies with less than 10 patients in each treatment arm, letters, commentaries, notes, reviews and editorials
Language restrictionsEnglish	Not in English

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Searchdates	Studies published from 01 Jan2011 to 19 Apr 2021	Studies published before 2011
-----------------	------------------------------------------------------	-------------------------------

Data extraction and quality assessment:

Data was extracted from included studies by one reviewer using a predefined and standardized data extraction form and checked by a second reviewer for accuracy. Extracted data included descriptions of study design, location of study, the number of patients, patient demographic data, and the type of surgery. Outcomes pertaining to SSI, seroma and dehiscence in closed surgical incisions were also extracted and evaluated. Quality assessment of studies was made according to two well-established guidelines. Randomized controlled trials were assessed according to the quality criteria from the Centre for Reviews and Dissemination (CRD) guidelines ! Prospective observational studies were assessed according to adapted criteria from the Critical Appraisal Skills Programme (CASP)2.

Summary of the clinical data identified:

Ultimately, twenty-five (25)2-23,27-30 articles were deemed to be relevant to the systematic literature review and used for the meta-analysis for SSI, seroma and dehiscence characterization (SSC). This consisted of seventeen (17) randomized controlled trials and eight (8) prospective observational studies. A total of up to 5,673 evaluable patients were included in these meta-analyses with 2,737 in the PICO Family therapy (treatment) group and 2,936 in the SOC (control) group. A summary of the articles identified in the review and those eligible for meta-analysis is provided in Figure 1 and Figure 2.

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Image /page/21/Figure/1 description: This image is a flow chart that shows the process of identifying relevant studies from three databases: PubMed, EMBASE, and Cochrane Library. The flow chart shows the number of studies identified in each database, the number of studies excluded after title/abstract screening, the number of studies excluded after full-text review, and the number of relevant studies from each database. The flow chart also shows the final number of published studies included in evidence synthesis with at least one relevant outcome, which is 25, and the number of analyzed studies reported on, which are SSI = 19, SEROMA = 10, and DEHISCENCE = 13.

Figure 1: Study Selection for the Meta-Analysis of Reductions: Infections: Infection, Seroma and Dehiscence

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Figure 2: Study Selection from the ClinicalTrials.gov database

Image /page/22/Figure/2 description: The image shows a flow diagram for a study selection process. The database used was ClinicalTrials.Gov, and the search string was "Negative Pressure Wound Therapy" OR NPWT OR PICO OR "Topical Negative Pressure". The initial search yielded 139 studies, and after screening, several records were excluded for reasons such as being non-comparative (2), not closed surgical incisions (8), not PICO (38), not relevant (78), not relevant comparison and/or outcome (2), and insufficient detail (6). Finally, there were 5 potentially relevant studies, which are listed by their NCT numbers and reasons for their inclusion or exclusion.

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2. SURGICAL SITE INFECTION (SSI)

A systematic literature review is included to demonstrate that the PICO Family can reduce the incidence of surgical site infections in closed surgical incisions in high risk patients in Class I and Class II wounds. Clinical studies which followed-up patients for at least 30 days (as defined by CDC guidelines24) were included in the analysis. A study was considered to contain 'high risk' patients if the majority (> 50%) of patients treated with PICO in that study presented with at least one 'intrinsic' or 'extrinsic' risk factor, as defined by the American College of Surgeons (ACS) and Surgical Infection Society's Surgical Site Infection Guidelines25.

Literature Support (Reduction in SSI for High Risk Patients)

Meta-analysis of the seventeen (17) studies relevant to SSI demonstrates a statistically significant reduction in the odds of developing an infection when using PICO Family therapy in comparison to standard surgical dressing (SOC). Of the seventeen (17) prospective studies included in the meta-analysis for infection:

· Twelve (12) studies were randomized controlled trials and considered Level I evidence
· Five (5) studies were considered Level II evidence, which are non-randomized prospective observational studies

See Table 3 below for a complete description of these studies.

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Study	Studydesign	SurgicalProcedure	Identifiedpotential riskfactors forsurgical siteinfections	Studyduration	Incisionaldressings used	No. ofSubjects	Treatmentduration
Gillespie etal 2015	RCT	Electiveprimary hiparthroplastypatients	The majority ofpatients had aASA score of ≥2	6 weeks	PICO dressing	35	5 days
					Comfeeldressingreinforced with2 absorbentdressings, andthen with aself-adhesive,non-woventape	35	Left intact andpatients weredischarged withtheir originaldressing
Hyldig et al2018	RCT	Elective andemergencycaesareansection patients	Inclusioncriterion of BMI≥30kg/m²	30 days	PICO dressing	432	5 days
					Standardpostoperativedressing	444	The dressing wasleft in situ for atleast 24 hours
Karlakki etal 2016	RCT	Patientsundergoingelective hip andkneearthroplasty	The majority ofpatients had araised BMI andASA score.The mean age ofparticipants was>65 years old	6 weeks	PICO dressing	102	4 days or longer
					Comfeeldressing	107	Dressing was lefton for 4 days, orlonger if drainagecontinued, unlesssoiled ordislodged.
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
O'Leary et al 2017	RCT	Laparotomy patients who received open abdominal surgery	The majority of patients had a raised BMI and ASA scoreType of surgery	30 days	PICO dressingTransparent waterproof dressing(Smith & Nephew)	2425	4 days4 days
Uchino et al 2016	RCT	Patients with ulcerative colitis undergoing elective ileostomy closure	All patients had a raised ASA score; inclusion criterion of patients with ulcerative colitis	Patients visited the clinic 4 weeks after the discharge, and every 4 weeks thereafter if they presented with complications	PICO dressingSimple adhesive plaster	2831	Continued for 2 weeks, with exchange every 3-4 daysNot Reported
Witt-Majchrzak et al 2015	RCT	Patients undergoing coronary artery bypass grafting surgery	The majority of patients had a raised BMI and co-morbidities; Prolonged	6 weeks	PICO dressing	40	Applied for up to 6 days. Dressing changed on day 2 or 3 and removed on day 5 or 6 after surgery
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
			duration of surgery		Conventional dressing	40	Dressings changed daily
					Conventional dressing	92	Dressings remained in situ for seven days, or until the day of discharge if they went home earlier, unless there was suspicion of infection or the dressing was soaked or leaking.
Hasselmann et al 2019	RCT	Patients undergoing elective open vascular surgery with inguinal incisions	The majority of patients had pre-existing co-morbidities	90 days	PICO dressing	78	The PICO device and dressing was left in place for seven days post-operatively, after which patients were instructed to remove it
					Vitri Pad; ViTri Medical,	80	Unless an unplanned change
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
					Saltsjö-Boo, Sweden or OPSITE Post-Op Visible; Smith and Nephew, London, UK		had to be conducted, the standard dressing was left in place for at least 48 hours, although changes due to moisture build-up was an issue on the standard dressing side and dressing changes did sometimes happen prior to 48 hours post-operatively
Keeney et al 2019	RCT	Patients undergoing primary or revision lower extremity TJA	43.0% of hip patients and 55.5% of knee patients had a BMI > 35 kg/m $^{2}$	35 days	PICO dressingNon-adherent incisional cover (Adaptic or Xeroform gauze)	185213	Initial period of 7 daysDressings were changed on postoperative day 2 with subsequent dressing changes performed at 3- to
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
							5-day intervals until the incision was dry
Dingemanset al 2018	Prospective andhistoricalcontrolled	Patients with foot or ankle fractures	Type of surgery	30 days	PICO dressingConventional surgical dressings	4747	7 daysFor the control arm of the study, patients received a pressure bandage with gauze placed underneath, usually for three days duration.
Pellino et al2014a	Prospective observational study	Patients (50 undergoing breast surgery, 50 colorectal surgery)	Type of surgeryProlonged duration of surgery	3 months	PICO dressingBasic wound contact absorbent dressings	5050	7 daysSterile removal for control after 48 h. On post-operative day 3, gauzes were removed sterilely and wounds left
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
Pellino et al 2014b	Prospective observational	Crohn's disease patients undergoing small bowel resection	Type of surgery The majority of patients had co-morbidities and raised ASA score	3 months	PICO dressingBasic wound contact absorbent dressings	1317	exposed if no complications occurred.7 daysSterile removal for control after 48 h. On postoperative day 3, gauzes were removed sterilely and wounds left exposed if no complications occurred
Selvaggi et al 2014	Prospective observational study	Crohn's disease patients undergoing abdominal surgery	Type of surgery The majority of patients had co-morbidities	3 months	PICO dressingBasic wound contact absorbent dressings	2525	7 daysSterile removal for control after 48 h. On postoperative day 3, gauzes were removed sterilely and wounds left.
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
Tuuli et al 2017	RCT / Conference Abstract	Caesarean section patients	Inclusion criterion of a $BMI ≥30kg/m²$	30 days	PICO dressing	60	Removed at discharge (usually on day 4)
					Standard wound dressing	60	The dressing was removed after hours
Martin and O'Neil 2020	RCT / Conference Abstract	Patients undergoing hepatectomy and pancreatectomy.	The average age among all participants was 60.82 years and $BMI$ was 31.7.	1 year	PICO dressing	20	For the PICO arm of the study, the PICO device was left in place for a total of 7 days.
					Sterile island dressing	20	For the control arm of the study, the length of time the dressing was left in place for was a median on 5 days (range 2-5 days).
Helito et al 2020	Prospective and historical controlled	Patients undergoing total knee arthroplasty	The majority of patients (51.7%) had at least one risk factor for	12 months	PICO dressing	97	Applied with an intentional duration of 7 days.
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
			surgical wound complications		Conventional surgical dressings	199	Applied with an intentional duration of 7 days.
Costa et al 2020	RCT	Patients undergoing surgery for lower limb fractures associated with major trauma	Type of surgery	6 months	PICO dressing	770	Applied according to surgeon's normal practice and the manufacturer's instructions (up to 7 days of treatment).
					Sterile dressings (varied by treatment centre – details not given)	749	Varied based on routine local care.
Masters et al 2021	RCT	Patients undergoing surgery for hip fractures	Type of surgery, median age (>84 years)	120 days	PICO dressing	232	Applied according to surgeon's normal practice and the manufacturer's
Study	Studydesign	SurgicalProcedure	Identifiedpotential riskfactors forsurgical siteinfections	Studyduration	Incisionaldressings used	No. ofSubjects	Treatmentduration
		associated withtrauma					instructions (up to7 days oftreatment).Varied based onroutine local care.
					Steriledressings(varied bytreatmentcentre – detailsnot given)	230
Bueno-Lledo et al2020	RCT	Patientsundergoingincisionalhernia repair	Obese patientsundergoingincisional herniarepair (BMI >30; total pop:n=37/150)	30 days	PICO dressing	72	Applied with anintentionalduration of sixdays.
					Conventionalsterile dressing(MEPORE pro;Molnlycke,Goteborg,Sweden)	74	Applied with anintentionalduration of sixdays.
Andrianelloet al 2020	RCT	Patientsundergoingpancreaticresection	Type of surgery	90 days	PICO dressing	46	Applied with anintentionalduration of sevendays
Study	Study design	Surgical Procedure	Identified potential risk factors for surgical site infections	Study duration	Incisional dressings used	No. of Subjects	Treatment duration
					Sterile gauze until post-op day 3, then sterile island dressing (OPSITE Post-Op Visible; Smith & Nephew)	49	Dressing (OPSITE) was changed according to clinical judgement.

Table 3. Published Studies Evaluating Reduction in Infection for High Risk Patients

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Together, the seventeen (17) studies contained 1,354 evaluable patients receiving the PICO Family (treatment group) and 1,516 patients receiving conventional wound dressings (control group). The conventional wound dressings used in each study can be seen in Table 3 and ranged from standard transparent dressings to basic wound contact absorbent dressings. The endpoint in the studies was the incidence of infection in the treatment group compared to the control group, with follow-up of patients for at least 30 days following surgery as per CDC guidance. The treatment effect for each study was summarized using odds ratio (OR), which was calculated using the following formula: OR = AD/BC, where

· A = the number of subjects with Infection events for the treatment group
· B = the number of subjects without Infection events for the treatment group
· C = the number of subjects with Infection events for the control group
· D = the number of subjects without Infection events for the control group

An OR of less than 1 suggests a favorable effect by the treatment in reducing the incidence of infection in high risk patients, whereas an OR greater than 1 suggests a favorable effect by the conventional wound dressings. The 95% confidence interval (95% CI) for the odds ratio is calculated based on the standard error of Log(OR).

As demonstrated in Figure 3, there is an observable trend supporting a favorable effect by the PICO Family in reducing the incidence of infection compared to the control group.

Study	Experimental		Control		Odds Ratio	OR	95%-CI	Weight
	Events	Total	Events	Total
Gillespie et al 2015	2	35	3	35		0.65	[0.10; 4.13]	1.8%
Hasselmann et al 2019	8	78	22	80		0.30	[0.12; 0.73]	12.6%
Hyldig et al 2018	20	432	41	444		0.48	[0.27; 0.83]	24.9%
Karlakki et al 2016	1	102	6	107		0.17	[0.02; 1.41]	3.7%
Keeney et al 2019	7	185	8	213		1.01	[0.36; 2.83]	4.6%
O'Leary et al 2017	2	24	8	25		0.19	[0.04; 1.03]	4.6%
Uchino et al 2016	3	28	1	31		3.60	[0.35; 36.80]	0.5%
Witt-Majchrzak et al 2015	1	40	7	40		0.12	[0.01; 1.03]	4.4%
Dingemans et al 2018	2	47	7	47		0.25	[0.05; 1.29]	4.3%
Selvaggi et al 2014	2	25	12	25		0.09	[0.02; 0.49]	7.1%
Pellino et al 2014a	4	50	20	50		0.13	[0.04; 0.42]	11.9%
Pellino et al 2014b	1	13	8	17		0.09	[0.01; 0.89]	4.1%
Tuuli et al 2017	3	60	2	60		1.53	[0.25; 9.48]	1.2%
Martin & O'Neil 2019	3	20	6	20		0.41	[0.09; 1.95]	3.3%
Helito et al 2020	0	97	7	199		0.13	[0.01; 2.33]	3.2%
Andrianello et al 2020	5	46	6	49		0.87	[0.25; 3.09]	3.3%
Bueno-Lledo et al 2020	0	72	6	74		0.07	[0.00; 1.31]	4.1%
Fixed effect model		1354		1516		0.36 [0.27; 0.49]		100.0%
Heterogeneity: I2 = 34%, τ2 = 0.2474, p = 0.09
					0.01	0.1	1	10 100

					Figure 3: Forest plot showing Infections in patients treated with PICO compared to SOC

Adverse events (AEs) or other potential device-related problems, ranging from patient reported noise concerns and vacuum failure to reports of pain and adverse skin reactions, were detailed in

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fifteen (15) of the seventeen (17) studies included in the meta-analyses.

Literature Supports Reduction in Infection for Class I and II Wounds

To analyze the effect of the PICO Family on infection in wounds of different degrees of contamination, a wound classification designation was applied following the Center for Disease Control and Prevention (CDC) guidelines24 .

Literature Support: Reduction in Superficial and Deep Surgical Site Infection (Infection Depth) The definitions of "superficial" and "deep" incisional surgical site infections (SSIs) utilized within this analysis are based on the established and recognized definitions provided by the Centers for Disease Control and Prevention (CDC). According to the latest recommendations24, superficial and deep incisional SSIs are briefly defined as follows:

· A superficial incisional SSI involves only skin and subcutaneous tissue of the incision and occurs within 30 days after any NHSN operative procedure.
· A deep incisional SSI involves deep soft tissues of the incision (for example, fascial and muscle layers) and occurs within 30 or 90 days after the NHSN operative procedure.

Meta-analysis of appropriate studies from Class I or Class II wound studies show a reduction in infection for superficial and deep infection when using the PICO Family compared to standard surgical dressing (SOC).. Specifically, to analyze the effect of the PICO Family on infections of different depths, subgroup analyses were performed using studies where the authors stated the use of the CDC criteria discussed above for superficial and deep SSIs26.

Meta-analyses of the relevant studies show a statistically significant reduction in infection for both superficial and deep incisional infections for class I/II wounds when comparing use of the PICO Family to SOC (Figures 4 and 5). The meta-analysis for superficial SSI includes eight (8) studies (5 RCTs, 3 prospective observational) containing a total of 723 evaluable patients, of which 356 received the PICO Family (treatment group) and 367 received conventional wound dressings (control group). The deep SSI analysis includes six (6) studies (4 RCTs, 2 prospective observational) containing a total of 2,284 evaluable patients, of which 1,146 received the PICO Family (treatment group) and 1,138 received conventional wound dressings (control group). The conventional wound dressings used in each study can be found in Table 3 and range from standard transparent dressings to simple adhesive plasters. The endpoint in the studies was the incidence of SSI (superficial and/or deep) in the treatment group compared to the control group.

Figure 4: Forest plot showing superficial SSI defined in patients treated with PICO Family compared to SOC

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Study	Experimental		Control		OR	95%-CI	Weight
	Events	Total	Events	Total
Gillespie et al 2015	1	35	3	35	0.31	[0.03; 3.17]	6.1%
Hasselmann et al 2019	7	78	18	80	0.34	[0.13; 0.87]	33.6%
Selvaggi et al 2014	2	25	6	25	0.28	[0.05; 1.53]	11.5%
Pellino et al 2014b	1	13	4	17	0.27	[0.03; 2.78]	6.7%
Dingemans et al 2018	0	47	4	47	0.10	[0.01; 1.95]	9.3%
Witt-Majchrzak et al 2015	1	40	7	40	0.12	[0.01; 1.03]	14.2%
Andrianello et al 2020	4	46	3	49	1.46	[0.31; 6.91]	5.5%
Bueno-Lledo et al 2020	0	72	6	74	0.07	[0.00; 1.31]	13.2%
Fixed effect model		356		367	0.30	[0.17; 0.53]	100.0%
Heterogeneity: I2 = 0%, τ2 = 0, p = 0.52

Figure 5: Forest plot showing deep SSI defined in patients treated with PICO Family compared to SOC

Image /page/36/Figure/9 description: This image is a forest plot, displaying the results of a meta-analysis. The plot includes data from several studies, including Hasselmann et al 2019, Selvaggi et al 2014, Pellino et al 2014b, Masters et al 2021, Costa et al 2020, and Andrianello et al 2020. For each study, the plot shows the odds ratio (OR) with its 95% confidence interval (CI) and weight. The fixed effect model has an OR of 0.67 with a 95% CI of [0.46; 0.96] and a weight of 100.0%.

3. POST-OPERATIVE SEROMA

A review of literature is included to demonstrate that the PICO Family is intended to reduce the incidence of post-operative seroma for closed surgical incisions. Studies assessing seroma were only included if they had at least 10 days of follow-up time (see Table 4).

Literature Review

A meta-analysis of ten (10) studies demonstrated a statistically significant reduction in the odds of developing a seroma when using PICO in comparison to standard of care (SOC). Of the ten (10) prospective studies included in the meta-analysis for seroma:

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· Seven (7) studies were randomized controlled trials and considered Level I evidence.
· Three (3) studies were considered Level II evidence, which are non-randomized prospective observational studies.

See Table 4 below for a complete description of these studies.

The ten (10) studies contained 608 evaluable patients receiving the PICO Family (treatment group) and 618 patients receiving conventional wound dressings (control group). The conventional wound dressings used in each study can be found in Table 4 and range from standard transparent dressings to basic wound contact absorbent dressings. The endpoint in the studies was the incidence of postoperative seroma in the treatment group compared to the control group for at least 10 days following surgery.

As demonstrated in Figure 6, there is an observable trend supporting a favorable effect by the PICO Family in reducing the incidence of seroma.

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Study	Study design	Surgical Procedure	Follow up period	Incisional dressings used	No. of Subjects	Treatment duration
Chaboyer et al 2014	Randomized Controlled Trial (RCT)	Elective caesarean section patients	6 weeks	PICO dressingComfeel dressing	4443	4 days or moreDressing was left on for 4 days, or longer if drainage continued, unless soiled or dislodged
Galiano et al 2018	RCT	Bilateral reduction mammoplasty patients	21 days (90 days)	PICO dressing3M STERI-Strip(3M Health Care, St. Paul, Minn.).	185185	The overall duration of PICO treatment was a median of 7 daysNot reported
Gillespie et al 2015	RCT	Elective primary hip arthroplasty patients	6 weeks	PICO dressingComfeel dressing reinforced with 2 absorbent dressings, and then with a self-adhesive, non-woven tape	3535	5 daysLeft intact and patients were discharged with their original dressing
Hasselmann et al 2019	RCT	Patients undergoing	90 days	PICO dressing	78	The PICO device and dressing was left in
Study	Study design	Surgical Procedure	Follow up period	Incisional dressings used	No. of Subjects	Treatment duration
		elective open vascular surgery with inguinal incisions				place for seven days post-operatively, after which patients were instructed to remove it.
				Vitri Pad (ViTri Medical, Saltsjo"-Boo, Sweden or OPSITE Post-Op Visible; Smith and Nephew, London, UK)	80	The standard dressing was left in place for at least 48 hours, although changes due to moisture build-up was an issue on the standard dressing side and dressing changes did sometimes happen prior to 48 hours post-operatively.
Pellino et al 2014a	Prospective observational study	Patients (50 undergoing breast surgery, 50 colorectal surgery)	3 months	PICO dressing	50	7 days
				Basic wound contact absorbent dressings	50	Sterile removal for control after 48 h. On post-operative day 3, gauzes were removed sterilely and wounds left exposed if no complications occurred.
Pellino et al 2014b	Prospective observational	Crohn's disease patients	3 months	PICO dressing	13	7 days
Study	Study design	Surgical Procedure	Follow up period	Incisional dressings used	No. of Subjects	Treatment duration
		undergoingsmall bowelresection		Basic wound contactabsorbent dressings	17	Sterile removal forcontrol after 48 h. Onpost-operative day 3,gauzes were removedsterilely and wounds leftexposed if nocomplications occurred.
Selvaggi etal 2014	Prospectiveobservationalstudy	Crohn's diseasepatientsundergoingabdominalsurgery	3 months	PICO dressing	25	7 days
				Basic wound contactabsorbent dressings	25	Sterile removal forcontrol after 48 h. Onpost-operative day 3,gauzes were removedsterilely and wounds leftexposed if nocomplications occurred.
Tuuli et al2017	RCTConferenceAbstract	Caesareansection patients	30 days	PICO dressing	60	Removed at discharge(usually on day 4)
				Standard wounddressing	60	The dressing wasremoved 24 to 48 hours
Bueno-Lledo et al2020	RCT	Patientsundergoingincisional herniarepair	30 days	Conventional steriledressing (MEPOREpro; Molnlycke,Goteborg, Sweden)	74	Applied with anintentional duration ofsix days
Study	Study design	Surgical Procedure	Follow up period	Incisional dressings used	No. of Subjects	Treatment duration
				PICO dressing	72	Applied with an intentional duration of six days
Andrianello et al 2020	RCT	Patients undergoing pancreatic resection	90 days	Sterile gauze until post-op day 3, then sterile island dressing (OPSITE Post-Op Visible; Smith & Nephew)	49	Dressing (OPSITE) was changed according to clinical judgement.
				PICO dressing	46	Applied with an intentional duration of seven days

Table 4. Published Studies Evaluating Reduction in Seroma.

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Image /page/42/Figure/0 description: This image is a forest plot, which is a type of graph used in meta-analysis to display the results of multiple studies. The plot shows the odds ratio (OR) and 95% confidence interval (CI) for each study, as well as the overall effect size. The studies included are Chaboyer et al 2014, Galiano et al 2018, Gillespie et al 2015, Pellino et al 2014a, Pellino et al 2014b, Selvaggi et al 2014, Hasselmann et al 2019, Tuuli et al 2017, Andrianello et al 2020, and Bueno-Lledo et al 2020. The random effects model shows an overall effect size of 0.37 [0.16; 0.86] with a weight of 100.0%.

Figure 6: Forest plot showing Seroma in patients treated with PICO compared to SOC

Device related adverse events (AEs) or other potential device-related problems, ranging from sealing issues to reports of pain and adverse skin reactions, were reported in eight (8) of the ten (10) studies included in the meta-analysis.

4. DEHISCENCE

A review of literature is included to demonstrate that the PICO Family is intended to reduce the incidence of dehiscence in closed surgical incisions. Studies assessing dehiscence were only included if they had at least 10 days of follow-up time (see Table 5).

Literature Support

In accordance with the literature review process described above, seven (7) prospective studies demonstrated a statistically significant reduction in developing dehiscence when using PICO in comparison to standard of care. Of the seven (7) studies included in the meta-analysis for dehiscence:

· Six (6) studies were randomized controlled trials and considered Level I evidence.
· One (1) study was considered level II evidence, which are non-randomized prospective observational studies.

See Table 5 below for a complete description of these studies.

The seven (7) studies contained 551 evaluable patients receiving the PICO Family (treatment group) and 656 patients receiving conventional wound dressings (control group). The conventional wound dressings used in each study can be found in Table 5 and range from standard sterile dressings to fixation strips. The endpoint in the studies was the incidence of dehiscence in the treatment group compared to the control group for at least 10 days following surgery.

Page 37 of 46

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As demonstrated in Figure 7, there is an observable trend supporting a favorable effect by the PICO Family in reducing the incidence of dehiscence.

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Study	Study design	SurgicalProcedure	Followupperiod	Incisional dressingsused	No. ofSubjects	Treatment duration
Chaboyer etal 2014	RandomizedControlledTrial (RCT)	Elective caesareansection patients	6 weeks	PICO dressingComfeel dressing	4443	4 days or moreDressing was left on for 4days, or longer if drainagecontinued, unless soiled ordislodged
Galiano et al2018	RCT	Bilateral reductionmammoplastypatients	21 days(90days)	PICO dressing or 3MSTERI-Strip (3MHealth Care, St. Paul,Minn.).	185185	The overall duration of PICOtreatment was a median of 7daysNot Reported
Gillespie etal 2015	RCT	Elective primaryhip arthroplastypatients	6 weeks	PICO dressing orComfeel dressingreinforced with 2absorbent dressings,and then with a self-adhesive, non-woventape	3535417	5 daysLeft intact and patients weredischarged with their originaldressingThe dressing was left in situfor at least 24 hours
Witt-Majchrzak etal 2015	RCT	Patientsundergoingcoronary arterybypass graftingsurgery	6 weeks	PICO dressingConventional dressing	4040	Dressing changed on day 2 or3 and on day 5 or 6 aftersurgeryDressings changed daily
Study	Study design	Surgical Procedure	Follow up period	Incisional dressings used	No. of Subjects	Treatment duration
Hasselmannet al 2019	RCT	Patients undergoing elective open vascular surgery with inguinal incisions	90 days	PICO dressing	78	The PICO device and dressing was left in place for seven days post-operatively, after which patients were instructed to remove it.
				(Vitri Pad; ViTri Medical, Saltsjo¨-Boo, Sweden or OPSITE Post-Op Visible; Smith and Nephew, London, UK)	80	The standard dressing was left in place for at least 48 hours, although changes due to moisture build-up was an issue on the standard dressing side and dressing changes did sometimes happen prior to 48 hours post-operatively.
				Sterile island dressing	20	Not Reported
Helito et al 2020	Prospective and historical controlled	Patients undergoing total knee arthroplasty	12 months	PICO dressing	97	Applied with an intentional duration of 7 days.
				Conventional surgical dressings	199	Applied with an intentional duration of 7 days.
Bueno-Lledoet al 2020	RCT	Patients undergoing incisional hernia repair	30 days	Conventional sterile dressing (MEPORE pro; Molnlycke, Goteborg. Sweden)	74	Applied with an intentional duration of six days
Study	Study design	SurgicalProcedure	Followupperiod	Incisional dressingsused	No. ofSubjects	Treatment duration
				PICO dressing	72	Applied with an intentionalduration of six days

Table 5. Studies Evaluating Reduction in Dehiscence in Closed Surgical Incisions.

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Study	ExperimentalEvents	Total	ControlEvents	Total	OR	95%-CI	Weight
Chaboyer et al 2014	0	44	0	43			0.0%
Galiano et al 2018	32	185	52	185	0.53	[0.33; 0.88]	62.5%
Gillespie et al 2015	1	35	1	35	1.00	[0.06; 16.65]	1.4%
Witt-Majchrzak et al 2015	1	40	1	40	1.00	[0.06; 16.56]	1.4%
Hasselmann et al 2019	14	78	9	80	1.73	[0.70; 4.26]	10.6%
Helito et al 2020	3	97	20	199	0.29	[0.08; 0.99]	18.5%
Bueno-Lledo et al 2020	2	72	4	74	0.50	[0.09; 2.82]	5.6%
Fixed effect modelHeterogeneity: I2 = 29%, τ2 = 0.1449, p = 0.22		551		656	0.63	[0.43; 0.92]	100.0%

Figure 7: Forest plot showing dehiscence in patients treated with PICO compared to SOC

Device related adverse events (AEs) or other potential device-related problems, ranging from sealing issues to reports of pain and adverse skin reactions, were reported in five (5) of the seven (7) studies included in the meta-analysis.

5. LIMITATIONS OF THE CLINICAL EVIDENCE

There can be many inherent limitations to meta-analyses, such as publication bias, selection bias, and varying quality of the underlying studies. Efforts were made in the study identification and selection process to reduce potential biases by selecting higher quality level I and level II studies. The criteria used to assess quality within the identified studies is detailed earlier in the methodology of the systematic literature review (Section 1 and Table 2). Another potential bias affecting studies included in meta-analyses is publication bias, whereby studies with statistically significant results are more likely to be published. This may also occur in the context of selective outcome reporting in which only significant outcomes are reported at study publication. To address this, searches were also conducted on ClinicalTrials.gov to check for completed trials with results available that had not been published.

Most studies (16/25) included in the systematic literature review were at higher risk of bias or the risk for bias was unclear. Specifically, many level I studies failed to include an intention to treat (ITT) analysis and often only reported on the per protocol (PP) analysis. Deficiencies in level II prospective observational studies included a lack of reporting of confidence intervals or p-values. Additional sources of bias included the variability between studies in the length of follow-up time for assessment of surgical site complications such as SSI. While inclusion for analysis required a follow-up period of at least 30 days post-operatively (as per CDC definitions), some studies exceeded this threshold sometimes by a few weeks. As a result, this may have impacted on the number of detected SSIs during the specified clinical endpoint. Some studies (Van der Valk et al 2017; Dingemans et al 2018; Helito et al 2020) included in the analysis used a historical cohort

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group as the control arm. There can be problems with interpreting data based on historical comparators. Namely, clinical practice, such as the use of technologies, procedures or care pathways, may have changed over time since the original data was collected meaning that any clinical improvement in the intervention arm may be attributable to these medical advances, rather than just the intervention alone. The systematic literature review also only included studies published in the English language. As such, there is the possibility of excluding valid data published in a different language.

Although these limitations should be considered when examining the results from these metaanalyses, the depth and breadth of the evidence provided gives reassurance to the conclusions reached for each of the outcomes assessed for the proposed Indications For Use. In addition, by the very nature of the inclusion criteria used for the systematic literature review, only studies considered methodologically robust (i.e., prospective and comparative) were selected for these analyses.

The device has not been demonstrated to be effective in reducing the incidence of surgical site infection, seroma, and dehiscence in all surgical procedures and patient populations; therefore, the device may not be recommended for routine use to reduce surgical site infection, seroma, and dehiscence. Surgeons should continue to follow the 'Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection'31 and the 'American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines'33 for best practices in preventing surgical site infection.

6. BIBLIOGRAPHY

1. CRD's guidance for undertaking reviews in health care systematic reviews. 2018. https://www.york.ac.uk/media/crd/Systematic Reviews.pdf. Accessed 19/11/2020.
Study Study Checklist. https://casp-uk.net/wp-2. CASP. CASP Cohort 2018. content/uploads/2018/03/CASP-Cohort-Study-Checklist-2018 fillable form.pdf. Accessed 19/11/2020.
1. Chaboyer W, Anderson V, Webster J, Sneddon A, Thalib L, Gillespie BM. Negative Pressure Wound Therapy on Surgical Site Infections in Women Undergoing Elective Caesarean Sections: A Pilot RCT. Healthcare (Basel). 2014;2(4):417-428.
1. Dingemans SA, Birnie MFN, Backes M, et al. Prophylactic negative pressure wound therapy after lower extremity fracture surgery: a pilot study. Int Orthop. 2018;42(4):747-753.
1. Galiano RD, Hudson D, Shin J, et al. Incisional Negative Pressure Wound Therapy for Prevention of Wound Healing Complications Following Reduction Mammaplasty. Plast Reconstr Surg Glob Open. 2018;6(1):e1560.

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1. Gillespie BM, Rickard CM, Thalib L, et al. Use of Negative-Pressure Wound Dressings to Prevent Surgical Site Complications After Primary Hip Arthroplasty: A Pilot RCT. Surg Innov. 2015;22(5):488-495.
1. Hasselmann J. Björk J. Svensson-Björk R. Acosta S. Inguinal Vascular Surgical Wound Protection by Incisional Negative Pressure Wound Therapy: A Randomized Controlled Trial-INVIPS Trial. Ann Surg. 2020;271(1):48-53.
1. Helito CP, Sobrado MF, Giglio PN, et al. The use of negative-pressure wound therapy after total knee arthroplasty is effective for reducing complications and the need for reintervention. BMC Musculoskeletal Disorders. 2020;21(1):490.
1. Holt R. Murphy J. PICO™ incision closure in oncoplastic breast surgery: a case series. Br J Hosp Med (Lond). 2015;76(4):217-223.
1. Hyldig N, Vinter CA, Kruse M, et al. Prophylactic incisional negative pressure wound therapy reduces the risk of surgical site infection after caesarean section in obese women: a pragmatic randomised clinical trial. Bjog. 2019;126(5):628-635.
1. Irwin GW, Boundouki G, Fakim B, et al. Negative Pressure Wound Therapy Reduces Wound Breakdown and Implant Loss in Prepectoral Breast Reconstruction. Plast Reconstr Surg Glob Open. 2020:8(2):e2667.
1. Karlakki SL, Hamad AK, Whittall C, Graham NM, Banerjee RD, Kuiper JH. Incisional negative pressure wound therapy dressings (iNPWTd) in routine primary hip and knee arthroplasties: A randomised controlled trial. Bone Joint Res. 2016;5(8):328-337.
1. Keeney JA, Cook JL, Clawson SW, Aggarwal A, Stannard JP. Incisional Negative Pressure Wound Therapy Devices Improve Short-Term Wound Complications, but Not Long-Term Infection Rate Following Hip and Knee Arthroplasty. J Arthroplasty. 2019;34(4):723-728.
1. O'Leary DP, Peirce C, Anglim B, et al. Prophylactic Negative Pressure Dressing Use in Closed Laparotomy Wounds Following Abdominal Operations: A Randomized, Controlled, Openlabel Trial: The P.I.C.O. Trial. Ann Surg. 2017;265(6):1082-1086.
1. O'Neill CH, Martin RCG, 2nd. Negative-pressure wound therapy does not reduce superficial SSI in pancreatectomy and hepatectomy procedures. J Surg Oncol. 2020;122(3):480-486.
1. Pellino G. Sciaudone G. Candilio G. Campitiello F. Selvaggi F. Canonico S. Effects of a new pocket device for negative pressure wound therapy on surgical wounds of patients affected with Crohn's disease: a pilot trial. Surg Innov. 2014;21(2):204-212.
1. Pellino G, Sciaudone G, Candilio G, et al. Preventive NPWT over closed incisions in general surgery: does age matter? Int J Surg. 2014;12 Suppl 2:S64-s68.
1. Selvaggi F, Pellino G, Sciaudone G, et al. New advances in negative pressure wound therapy (NPWT) for surgical wounds of patients affected with Crohn's disease. Surg Technol Int. 2014:24:83-89.
1. Tuuli MG, Martin S, Stout MJ, et al. 412: Pilot randomized trial of prophylactic negative pressure wound therapy in obese women after cesarean delivery. American Journal of Obstetrics & Gynecology. 2017;216(1):S245.

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1. Uchino M, Hirose K, Bando T, Chohno T, Takesue Y, Ikeuchi H. Randomized Controlled Trial of Prophylactic Negative-Pressure Wound Therapy at Ostomy Closure for the Prevention of Delayed Wound Healing and Surgical Site Infection in Patients with Ulcerative Colitis. Dig Surg. 2016;33(6):449-454.
1. van der Valk MJM, de Graaf EJR, Doornebosch PG, Vermaas M. Incisional Negative-Pressure Wound Therapy for Perineal Wounds After Abdominoperineal Resection for Rectal Cancer, a Pilot Study. Adv Wound Care (New Rochelle). 2017;6(12):425-429.
1. Witt-Majchrzak A, Zelazny P, Snarska J. Preliminary outcome of treatment of postoperative primarily closed sternotomy wounds treated using negative pressure wound therapy. Pol Przegl Chir. 2015;86(10):456-465.
1. Zotes V, Mier JM, Cortes G. P-187NEGATIVE PRESSURE WOUND THERAPY IN A POTENTIALLY INFECTED WOUND AFTER EMPYEMA SURGERY. Interactive CardioVascular and Thoracic Surgery. 2015;21(suppl 1):S51-S51.
Procedure-associated 24. CDC. देश Module. 2020. https://www.cdc.gov/nhsn/pdfs/pscmanual/9pscssicurrent.pdf. Accessed 04/11/2020.
1. Ban KA, Minei JP, Laronga C, et al. American College of Surgeons and Surgical Infection Society: Surgical Site Infection Guidelines, 2016 Update. J Am Coll Surg. 2017;224(1):59-74.
1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR, Committee HICPA. Guideline for prevention of surgical site infection, 1999. Infection Control & Hospital Epidemiology. 1999;20(4):247-280.
1. Andrianello S, Landoni L, Bortolato C, et al. Negative pressure wound therapy for prevention of surgical site infection in patients at high risk after clean-contaminated major pancreatic resections: A single-center, phase 3, randomized clinical trial. Surgerv. 2020.
1. Bueno-Lledó J, Franco-Bernal A, Garcia-Voz-Mediano MT, Torregrosa-Gallud A, Bonafé S. Prophylactic Single-use Negative Pressure Dressing in Closed Surgical Wounds After Incisional Hernia Repair: A Randomized, Controlled Trial. Ann Surg. 2020.
1. Costa ML, Achten J, Knight R, et al. Effect of Incisional Negative Pressure Wound Therapy vs Standard Wound Dressing on Deep Surgical Site Infection after Surgery for Lower Limb Fractures Associated with Major Trauma: The WHIST Randomized Clinical Trial. JAMA -Journal of the American Medical Association. 2020;323(6):519-526.
1. Masters J, Cook J, Achten J, Costa ML. A feasibility study of standard dressings versus negative-pressure wound therapy in the treatment of adult patients having surgical incisions for hip fractures: the WHISH randomized controlled trial. Bone Joint J. 2021;103-b(4):755-761.
1. Berríos-Torres SI, Umscheid CA, Bratzler DW, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection. 2017. JAMA Surg. 2017;152(8):784-791. doi:10.1001/jamasurg.2017.0904

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21 CFR 807.92 (b)(3): Conclusions drawn

Based on the clinical and non-clinical supporting information provided in this submission, the subject device is substantially equivalent to the legally marketed predicate device (PREVENA). To the extent that there are differences between the subject device and the predicate, these differences do not raise new or different questions of safety or effectiveness.

Regulation Number and Section

§ 878.4783 Negative pressure wound therapy device for reduction of wound complications.

(a)
Identification. A negative pressure wound therapy device for reduction of wound complications is a powered suction pump intended for wound management and reduction of wound complications via application of negative pressure to the wound, which removes fluids, including wound exudate, irrigation fluids, and infectious materials. This device type is intended for use with wound dressings classified under § 878.4780. This classification does not include devices intended for organ space wounds.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical data must demonstrate that the device performs as intended under anticipated conditions of use and evaluate the following:
(i) Wound complication rates; and
(ii) All adverse events.
(2) The patient-contacting components of the device must be demonstrated to be biocompatible.
(3) Performance data must demonstrate the sterility of the patient-contacting components of the device.
(4) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
(5) Usability testing must demonstrate that intended users can correctly use the device, based solely on reading the instructions for use.
(6) Non-clinical performance data must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested in a worst-case scenario for the intended use life:
(i) Ability to maintain pressure levels at the wound site under a worst-case scenario for the intended use life;
(ii) Fluid removal rate consistent with the wound types specified in the indications for use; and
(iii) Timely triggering of all alarms.
(7) Performance data must demonstrate the electrical safety and electromagnetic compatibility (EMC) of the device.
(8) Software verification, validation, and hazard analysis must be performed.
(9) Labeling must include the following:
(i) Instructions for use;
(ii) A summary of the device technical specifications, including pressure settings, modes (
e.g., continuous or intermittent), alarms, and safety features;(iii) Compatible components and devices;
(iv) A summary of the clinical evidence for the indications for use;
(v) A shelf life for sterile components; and
(vi) Use life and intended use environments.
(10) For devices intended for use outside of a healthcare facility, patient labeling must include the following:
(i) Information on how to operate the device and its components and the typical course of treatment;
(ii) Information on when to contact a healthcare professional; and
(iii) Use life.