K Number

Device Name

EndoRotor Device

Manufacturer

Interscope, Inc

Date Cleared

2020-12-23

(282 days)

Product Code

QNE

Regulation Number

876.4330

Intended Use

The EndoRotor device is indicated to resect and remove necrotic tissue in symptomatic Walled off pancreatic necrosis /Walled off necrosis (WOPN/WON) after having undergone endoscopic ultrasound (EUS) guided drainage.

Device Description

The EndoRotor ® is a powered resection tool intended to morcellate necrotic pancreatic tissue through the instrument biopsy channel of an endoscope. The device is to be used after a patient has undergone a procedure to drain any fluid accumulated in the pancreas due to pancreatitis.

More Information

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Center

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Date Received

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Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

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State

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ZIP

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Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

Not Found

Reference Devices

K170120, K181127

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a mechanical resection tool and does not mention any AI or ML components, image processing, or data training/testing related to AI/ML.

Therapeutic

Yes
The device is described as a "powered resection tool intended to morcellate necrotic pancreatic tissue," and its intended use is to "resect and remove necrotic tissue," which directly involves treating a medical condition.

Diagnostic

The device is indicated to resect and remove necrotic tissue, which is a treatment function, not a diagnostic one. The "Input Imaging Modality" section refers to methods used to guide the procedure or assess the condition, not performed by the device itself for diagnostic purposes.

SaMD (Software as a Medical Device)

The device description explicitly states it is a "powered resection tool intended to morcellate necrotic pancreatic tissue," indicating it is a physical, hardware-based device, not software only.

IVD (In Vitro Diagnostic)

No, the EndoRotor device is not an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use clearly states that the device is used to "resect and remove necrotic tissue" within the body. This is a therapeutic procedure performed directly on the patient.
Device Description: The description reinforces this by stating it's a "powered resection tool intended to morcellate necrotic pancreatic tissue through the instrument biopsy channel of an endoscope." This describes a physical intervention.
IVD Definition: In Vitro Diagnostics are devices used to examine specimens (like blood, urine, or tissue) taken from the human body to provide information for diagnosis, monitoring, or screening. The EndoRotor does not perform this function. It is a surgical/interventional device.

The information provided describes a device used for a therapeutic procedure, not for testing samples outside the body.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes (comma separated list FDA assigned to the subject device)

QNE

Device Description

There have been two versions of the device with 510(k) marketing clearance. Version 1 (K170120) was indicated to resect and remove residual tissue from the peripheral margins following EMR (Endoscopic Mucosal Resection). The subject device is identical to Version 2 (K181127). In Version 2 of the device, the sponsor made some minor design changes to the device (described below), and added the post-endoscopic mucosal resection (EMR) tissue persistence with a scarred base to the indications for use.

As shown in Figure 1, the device is composed of the:

1. Power Console
1. Foot Control
1. Resection Catheter (with XT Tip)
1. Specimen trap with pre-loaded filter (not pictured)

The Power Console includes the drive motor, vacuum control valve and a peristaltic irrigation pump, which provides the controls and positive function indicators.

The Foot Control is an actuator that enables and disables EndoRotor functions during the procedure.

The Resection Catheter is a disposable component that includes inner and outer debriding cutters (as pictured above). The Catheter can be used to perform lavage and aspiration from the site through the endoscope biopsy channel to the EndoRotor Specimen Trap. The Resection Cutter is available in various sizes and is compatible with various endoscope models as described below (Table 2). In Version 1 of the device, the Resection Catheter had a 3.0 mm2 window; in Version 2 of the device, the window was 4.4 mm². In addition, Version 1 of the device only had an inner cutter, whereas Version 2 of the device had both an inner and outer cutter. Other device specifications were similar.

The Specimen Trap is used for the collection of the resected tissue and is used in procedures for colon or esophagus. The Specimen trap is left empty for DEN procedures.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Pancreas

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Investigational Device Exemption, G180127:

Study Type: Single arm, prospective study
Sample Size: 30 subjects treated with the device (out of 37 consented and screened). 22 subjects in the per protocol (PP) population, 30 subjects in the Intent-to-treat (ITT) population.
Key Results:
- Effectiveness:
  - For the total PP population (N=22), the median of the percent reduction of volume was (0) (4)%, indicating most subjects experienced more than 98% volume reduction. The range was (b) (4) (b) (4)%. The mean percent reduction was 10%.
  - 18/22 (82%) of PP subjects had at least a ""% reduction in their WON size.
  - For the ITT population (N=30), the median volume reduction was b) (4) 0/0 -(b) (4) %; the range was (b) (4) %; the mean was .
  - 24/30 (80%) of ITT subjects had at least a ""% reduction in the WON Size.
  - Subjects received 63 procedures, averaging 2.1 treatments per subject.
  - The average time using the EndoRotor device was " minutes (standard deviation "" minutes, range (b) (4) minutes); the average total time needed for the procedure was (014) minutes (standard deviation minutes, range (b) (4) minutes).
- Safety:
  - 9 Serious Adverse Events (SAEs) reported.
  - 3 SAEs were adjudicated as procedure-related: 2 gastrointestinal bleeding events and 1 pneumoperitoneum.
  - One patient experienced pneumoperitoneum, subsequently had multi-system organ failure, and died.
  - No device-related SAEs and no Unanticipiated Adverse Device Effects (UADE).

Erasmus Investigator Study:

Study Type: Prospectively-defined cohort. Case series conducted in accordance with good clinical practice (GCP).
Sample Size: 12 subjects treated in total; 8 with Version 1, 4 with Version 2 (the subject device).
Key Results:
- Effectiveness: For the 4 subjects treated with Version 2:
  - Mean procedure time was 37 minutes (median 33 minutes).
  - Mean number of procedures was 1.75 (median 1.5, range 1 to 3).
  - Complete removal of necrotic tissue assessed by visual endoscopic inspection.
  - FDA did not rely on this study for effectiveness assessment due to lack of additional effectiveness data.
- Safety:
  - 3 Serious Adverse Events reported: 1 Gastrointestinal Bleed, 1 Multiple Organ Failure Syndrome, 1 Death (Adenocarcinoma Progression).
  - No adverse events reported during the necrosectomy procedures or within the next 24 hours.
  - 3 subjects (27.2%) experienced adverse events within the course of their infected pancreatic necrosis.

Real World Data (RWD):

Study Type: Systematic review of published clinical studies and collection of real world clinical data from institutions outside the US.
Sample Size: 108 subjects (for whom 134 EndoRotor DEN/ETN procedures were performed). Data for 52/108 subjects (48%) regarding length of hospitalization.
Key Results:
- Effectiveness:
  - 14 subjects could not achieve complete WON resolution.
  - (b) (4) subjects had imaging at baseline and a follow up image.
  - (6) 4) subjects were initially included (CECT or MRI scans at baseline and follow up).
  - For (6) 4) subjects, a median reduction of "11%, with an overall mean percent decrease from baseline of "% in the size of the WOPN/WON (Range: 000000 (4) (4)%).
  - Average length of hospitalization was 31 days (range 0 - 119) for 52/108 subjects.
- Safety:
  - 5 Serious Adverse Events reported: 1 Acute respiratory failure, 1 Ischemic Stroke, 2 Gastrointestinal Bleed, 2 Multiple Organ Failure Syndrome, 3 Deaths.

Literature Comparison (5 articles reviewed for effectiveness and safety of current WOPN/WON therapies):

Effectiveness:
- Puli, 2013 (233 subjects): 81.84% clinical resolution, mean 4.09 procedures.
- Sharaiha, 2016 (124 subjects, 78 underwent DEN): 86.3% clinical success, median 2 procedures.
- Gardner, 2011 (104 subjects): 91% success, median 3 procedures.
- Thompson, 2015 (60 subjects): 86.7% clinical resolution, 1.58 ± 0.1 (SD) procedures.
- Kumar, 2014 (24 subjects, 12 in DEN group): 92% clinical resolution, 1.4 ± 0.2 (SD) procedures.
Safety:
- Puli, 2013 (233 subjects): 21.33% complications (bleeding, sepsis, perforation).
- Sharaiha, 2016 (124 subjects, 78 underwent DEN): Short term (

Regulation Number and Section

§ 876.4330 Endoscopic pancreatic debridement device.

(a)
Identification. An endoscopic pancreatic debridement device is inserted via an endoscope and placed through a cystogastrostomy fistula into the pancreatic cavity. It is intended for removal of necrotic tissue from a walled off pancreatic necrosis (WOPN) cavity.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use, including evaluation of debridement of walled off pancreatic necrosis and 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) The patient-contacting components of the device must be demonstrated to be non-pyrogenic.
(5) Performance testing must support the shelf life of device components provided sterile by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
(6) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Testing of rotational speeds and vacuum pressure;
(ii) Functional testing including testing with all device components and the ability to torque the device; and
(iii) Functional testing in a relevant tissue model to demonstrate the ability to resect and remove tissue.
(7) Performance data must demonstrate the electromagnetic compatibility (EMC) and electrical safety of the device.
(8) Software verification, validation, and hazard analysis must be performed.
(9) Training must be provided so that upon completion of the training program, the user can resect and remove tissue of interest while preserving non-target tissue.
(10) Labeling must include the following:
(i) A summary of the clinical performance testing conducted with the device;
(ii) Instructions for use, including the creation of a conduit for passage of endoscope and device into a walled off pancreatic necrotic cavity;
(iii) Unless clinical performance data demonstrates that it can be removed or modified, a boxed warning stating that the device should not be used in patients with known or suspected pancreatic cancer;
(iv) The recommended training for safe use of the device; and
(v) A shelf life for any sterile components.

Summary

DE NOVO CLASSIFICATION REQUEST FOR ENDOROTOR®

REGULATORY INFORMATION

FDA identifies this generic type of device as:

Endoscopic pancreatic debridement device. An endoscopic pancreatic debridement device is inserted via an endoscope and placed through a cystogastrostomy fistula into the pancreatic cavity. It is intended for removal of necrotic tissue from a walled off pancreatic necrosis (WOPN) cavity.

NEW REGULATION NUMBER: 21 CFR 876.4330

CLASSIFICATION: Class II

PRODUCT CODE: QNE

BACKGROUND

DEVICE NAME: EndoRotor

SUBMISSION NUMBER: DEN200016

DATE DE NOVO RECEIVED: March 31, 2020

Interscope, Inc. CONTACT: 100 Main Street, Suite 108 Whitinsville, MA 01588

INDICATIONS FOR USE

LIMITATIONS

The sale, distribution, and use of the EndoRotor device are restricted to prescription use in accordance with 21 CFR 801.109.

The device is not intended for uses other than that described in the labeling.

PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.

DEVICE DESCRIPTION

As shown in Figure 1, the device is composed of the:

1. Power Console
1. Foot Control
1. Resection Catheter (with XT Tip)
1. Specimen trap with pre-loaded filter (not pictured)

Image /page/1/Figure/8 description: The image shows two separate images, each with a number. The first image, labeled with the number 1, shows a medical device on a stand with wheels. The second image, labeled with the number 3, shows a close-up of a surgical tool.

Figure 1. EndoRotor Device and its components. 1. Power Console , 2. Foot Controls. 3. Resection Catheter (XT Tip).

The Power Console includes the drive motor, vacuum control valve and a peristaltic irrigation pump, which provides the controls and positive function indicators

The Foot Control is an actuator that enables and disables EndoRotor functions during the procedure.

The Specimen Trap is used for the collection of the resected tissue and is used in procedures for colon or esophagus. The Specimen trap is left empty for DEN procedures.

Table 1 describes the specifications of the EndoRotor device:

Device Specification	Attribute
Window Size	4.4. mm2
Cutter Design	Inner and Outer Cutters
Operating Speed	High : 1750 RPM
Low : 1000 RPM
Flow Rate	5 mL/min
Vacuum	50-432 mmHg (facility regulated vacuum)
Operating Environment	Temperature 15- 40 °C (60 - 100 °F)
RH 10-95%
Pressure 500 - 1060 kPa
Transport and Storage
Environment	Catheter
Storage Room Temperature
Transport: 29 - 60 °C and 30% to 85% RH
Console
Storage and transport: - 40 °C to +70 °C
10-95% RH,
500 to 1060 kPa Pressure
Size	Console D: 25.72 cm x W 18.42 cm x H 33.65 cm

Table 1. EndoRotor specifications (Version 2)

| The Carl Contract Concess of Concerner Commend Commend Commend Commend Comments Comments of Comments of Comments of Comments of Comments of Comments of Comments of Concerners
Weight | a market and consideration of the comments of the comments of the many of the many of the many of the many of
· Weight: 6.17 kg
onsole | |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------|--|
| | | |

Table 2. EndoRotor catheter sizes and compatible gastroscopes for the necrosectomy indication only (Version 2)

Catheter (diameter = 3.2 mm)		Compatible Endoscope(s)*
SKU #	Working Length (mm)	*All endoscopes shall have a working channel diameter ≥ 3.2 mm
ER 10-03-OP-S	1240	Olympus gastroscopes with 1030 mm working length
Pentax gastroscopes with 1050 mm working length
ER 10-03-F-S	1270	Fuji gastroscopes with 1100 mm working length
ER 10-01-OP-S	1890	Olympus colonoscope with 1680 mm working length
Pentax colonoscope with 1700 mm working length

To use the EndoRotor device, first, a cystogastrostomy is performed, in which a transluminal conduit is created between the pancreas and the stomach or duodenum, and is typically held . with a luminal apposing metal stent (LAMS). Necrosectomy may be performed two days following the placement of the stent, according to the assessment of the treating physician. On the day of the necrosectomy procedure, an endoscope is then advanced into a transluminal. cystogastrostomy. Once the endoscope passes the transluminal orifice and the first resection area is identified, the EndoRotor Console is brought to a functional state. The setup process includes the following:

. Powering on the console, placing the foot pedal into position, unpacking and attaching the appropriate EndoRotor Catheter and catheter lock;
. Connecting the proximal connections of the EndoRotor Catheter to the EndoRotor Console:
. Preparing the lavage fluid for use.

Once all set up steps have been fully executed, the physician inserts the selected EndoRotor Catheter into the working-channel of the selected scope. Lavage fluid flow, cutting tip rotation, and aspiration are initiated using the foot pedal.

When the EndoRotor is operational, and vacuum actuated, the physician resects and removes tissue by placing the cutting surface against the necrotic tissue. The user makes small sweeping movements followed by slight articulation of the endoscope to reposition the device for optimal tissue removal as needed. When resecting tissue, the system connects to an in-suite vacuum that

is controlled by a user actuated pinch valve, restricting vacuum to on demand . to suction material from the procedure site through the catheter and back to the specimen trap.

After the procedure is completed, the EndoRotor Catheter is removed and discarded; the console and foot control are cleaned/stored per the instructions for use.

SUMMARY OF NONCLINICAL/BENCH STUDIES

BIOCOMPATIBILITY/MATERIALS

The device components of the EndoRotor (Version 2) device were evaluated according to the FDA guidance (2016), "Use of International Standard ISO 10993-1, Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process," and the ISO 10993-4:2017, "Biological evaluation of medical devices - Part 4: Selection of tests for interactions with blood." From the evaluations and supporting information, the components of the device were found to be biocompatible for its use.

SHELF LIFE/STERILITY

The EndoRotor Catheter is a sterile, single use system. The catheter component is a single use device provided sterile to the end user. Device components in contact with blood were also tested for pyrogenicity using the USP Chapter Pyrogenicity Test method.

Sterilization methods for the EndoRotor device have been validated in accordance with ISO 11135-1:2007 "Sterilization of Health Care Products- Ethylene Oxide - Part 1: Requirements for Development, Validation and Routine Control of a Sterilization Process for Medical Devices," to ensure a sterility assurance level of 10-6 before the device is marketed.

Accelerated aging to support a 2-year shelf life was performed for the EO sterilized EndoRotor device per ASTM F1980-07. Standard Guidance for Accelerated Aging of Sterile Medical Device Packages. The expiration date of 2 years was verified by demonstrating package integrity through dye penetration and bubble leak testing on the stored products. Version 1 of the device was tested and was found to be sufficient for the 510(k) clearance of Version 2.

PERFORMANCE TESTING - BENCH

Non-clinical performance data was generated to mitigate the risk associated with the failure of the device components and/or materials. Functional and torque testing were conducted on Version 2 of the device, to evaluate the critical functions of the device (including device power testing, ability to prime the device, ability to use the device with foot controls, ability to use the irrigation pump, and the ability to torque the device) as well as design verification/validation testing.

PERFORMANCE TESTING - ANIMAL TESTING

Animal testing was conducted for Version 1 of the device (K170120). Version 1 of the device was cleared to resect and remove tissue from the peripheral margins following EMR (Endoscopic Mucosal Resection). The animal testing conducted was deemed to be sufficient for the 510(k) clearance of Version 2 of the device.

No additional animal testing was conducted for Version 2 for the subject indication.

SUMMARY OF CLINICAL INFORMATION

There were three sources of data for this submission: The main source of data was an Investigational Device Exemption (IDE) study, G180127, approved by FDA. There were two additional sources of supporting data: The Erasmus Study, conducted in the Netherlands, and Real World Evidence (RWE), provided by the firm with data obtained from institutions that use the device for the indication of walled off pancreatic necrosis, outside the US. A literature search was also used to assess compare current treatment options with the subject device.

Investigational Device Exemption, G180127:

The EndoRotor DEN trial was a single arm, prospective study to demonstrate the safety of the EndoRotor device for Direct Endoscopic Necrosectomy (DEN). The study was a multicenter and multinational trial, with ten centers. Thirty-seven subjects were consented and screened for symptomatic pancreatic necrosis due to acute pancreatitis. These subjects were assessed to see if they had an indication to undergo endoscopic necrosectomy after having undergone EUS-guided drainage. There were 7 screen failures, and 30 subjects treated with the device. Twenty three out of 30 (77%) subjects were treated in U.S. centers. A single patient was unable to finish the study questionnaire due to a death as discussed below. Subjects could have multiple EndoRotor procedures; there were a total of 63 procedures in this study.

The primary endpoint evaluated device safety. Secondary endpoints evaluated device and procedure effectiveness by assessing the following: 1) successful debridement of at least 70% necrosis by volume measured with a high-resolution, contrast -enhanced CT (CECT) at a 21 (± 7) -day follow up after the last DEN procedure was performed, 2)assessment of total procedure time to achieve clearance of necrosis for all procedures, 3)assessment of adequacy of debridement, 4) assessment of total number of procedures to achieve clearance of necrosis, 5)assessment of length of hospital stay and utilization, and 6) quality of life (SF-36 questionnaire). FDA considered the most objective endpoints for its regulatory decision- making process; that is, those with the least amount of confounding variables (Please see Effectiveness section for additional information.)

Prior to treatment with the EndoRotor device, subjects underwent either traditional cystogastrostomy with balloon dilation or cystogastrostomy via the FDA-approved LAMS, and they must have continued to remain symptomatic following EUS-guided drainage. Symptomatic necrosis caused by necrotizing pancreatitis was first determined by imaging such as CECT showing impaired pancreatic perfusion and then symptoms such as the presence of intolerable pain was confirmed. To confirm the presence of infection, a positive culture obtained by fine needle aspiration (FNA) was required. The protocol required investigators to use the Atlanta

Classification in the determination of all necrotic collections on CECT. To be included in the study, the collection had to have greater than 30% necrosis content and a diameter at least 6 cm and not more than 22 cm. Infected necrosis was suspected in necrotizing pancreatitis subjects with clinical signs of persistent sepsis or progressive clinical deterioration despite maximal support in the intensive care unit (ICU) without other causes for infection. Exclusion criteria included but were not limited to documented evidence of pseudoaneurysm and intervening varices. Seven of the 37 consented subjects did not meet these screening criteria.

Subjects were treated with the device following cystogastrostomy creation and /or at least two days following the time of LAMS placement. According to the protocol, subjects could receive a maximum of 4 EndoRotor procedures. A minimum of 2 days was required between EndoRotor procedures, and all procedures needed to be completed within a 21-day period. Follow-up was completed 21(±7) days after the last EndoRotor debridement, at which time subjects had another contrast-enhanced CT to measure remaining collection volume. At the 21-day follow-up, a physical examination was completed, as well as an assessment of adverse events. Subjects also completed a quality-of-life questionnaire (SF-36).

Erasmus Investigator Study

The Erasmus patient population was a prospectively-defined cohort that followed European Society of Gastrointestinal Endoscopy (ESGE) Guidelines in management of subjects recommended for Endoscopic Transgastric Necrosectomy (ETN)/Direct Endoscopic Necrosectomy (DEN).

Only subjects who met these guidelines were included. The case series was conducted in accordance with good clinical practice (GCP) as described in 21 CFR 812.28(a)(1). Technical feasibility, safety and clinical outcomes were evaluated and scored. . Twelve subjects were treated, 8 of whom were treated with Version 1 of the device, and 4 of whom were treated with the subject version (Version 2) .

Investigators measured effectiveness by recording procedure time and assessing the number of procedures to achieve removal of necrotic tissue. They also tracked adverse events. In the 4 subjects treated with Version 2 of the device, the mean procedure time was 37 minutes (median procedure duration was 33 minutes) the mean number of procedures was 1.75 ( the median number of procedures required was 1.5 (range 1 to 3)). Complete removal of necrotic tissue was assessed by visual endoscopic inspection. There were no additional effectiveness data provided in this study, and therefore, FDA did not rely on this study for assessment of the effectiveness of this device. However, FDA did consider this study when evaluating the safety of the device, as is explained further below.

Real World Data

There were two sources of RWD presented to FDA: (1) a systematic review of published clinical studies that evaluated the general safety and effectiveness of DEN procedures and (2) real world clinical data from institutions outside the US that have used the EndoRotor device for treating WOPN. All subjects were treated with Version 2 of the device.

The literature review was conducted according to guidelines and methods suggested by Egger, Smith, and Altman in their book, "Systematic Reviews in Health Care."

The literature search was conducted for indexed articles using eight query search terms, including broad relevant terms for endoscopic debridement of walled off pancreatic necrosis with current endoscopic accessories/tools (e.g. snares, baskets, balloons, etc.).The scientific literature databases PubMed and Embase were used by the applicant to perform a search for data published through August 23, 2018. The search yielded 520 articles from Pubmed and 2,007 articles from the Embase database, for a total of 2,527 articles.

After elimination of duplicates, the sponsor applied several inclusion and exclusion criteria (e.g. included if the article provided description of clinical trial and results; excluded if clinical data were not extractable for the device in the article, among others).

This narrowed down the search to 28 articles to review. FDA further narrowed these articles by the number of subjects treated per the article (excluded if less than 10 subjects), if the article was a duplicate because it was analyzed in a review article, whether safety and efficacy data were provided in the article for DEN procedures using current endoscopic tools (as opposed to drainage only procedures), and whether the article was a systematic literature search. Therefore, FDA utilized 5 articles to review the safety and effectiveness of current devices used to treat Walled Off Pancreatic Necrosis. It was the intent of FDA to qualitatively compare the data from these 5 articles to the results obtained by the sponsor with the collected clinical trial data discussed within.

For the collection of real world clinical data, Interscope collaborated with 39 sites using EndoRotor as standard of care outside the US. Data were collected for 134 EndoRotor DEN/ETN procedures in 108 subjects.

Data collected included length of hospital stay (LOS), need for multiple interventions, pre and post procedure assessment of percent of necrotic material, adverse events, and serious adverse events. Since the data were not collected as part of a formally designed retrospective clinical study, there were no pre-defined safety or efficacy endpoints.

Efficacy Results

Investigational Device Exemption, G180127:

As stated above, there were several effectiveness endpoints in the study protocol. The following results are addressed below: percent volume reduction, number of procedures, procedure time, Volume reduction is measured at follow-up by contrast-enhanced CT. This was measured by comparing the volume of the WON/WOPN collection calculated from the contrast-enhanced CT performed at baseline and at the 21 (± 7) day follow-up per Table 3.

The sponsor also assessed the EndoRotor procedure time, the adequacy of debridement (endoscopic assessment), the total number of procedures, the length of hospital stay (days), and subject quality of life (SF-36 Questionnaire). These secondary endpoints were not considered by FDA because of confounding variables which were thought to prohibit accurate assessment of outcomes data. For example, the assessment of adequacy of debridement were made via endoscopic visualization after each debridement. Because of potential subjectivity and thus

variability in percentage reduction in cavity size, this data was not considered. However, the CECT evaluations after the final DEN were considered. Finally, the assessment of length of hospital stay (LOS) and utilization, and the quality of life (OOL) SF-36 questionnaire data were not considered due to wide variability in the study subject's disease severity and thus varying LOS and OOL.

As stated above, subjects could receive multiple EndoRotor treatments depending on continued symptomatology (e.g. persistent necrosis, continued fever, sepsis, pain, etc.). Clinicians in the study determined whether additional treatments were required based upon clinical judgement. In this study, 30 subjects received 63 procedures, averaging 2.1 treatments per subject.

Among the 30 subjects who were treated with the EndoRotor (Intent-to-treat (ITT)) population), there were 8 protocol deviations, leading to a per protocol (PP) population of 22 subjects:

3 subjects were excluded from the ITT population, because they had more than 4 . procedures, based on the clinician's assessment that additional treatment was necessary.
. 5 subjects were excluded from the ITT population, because of the following imaging deviations:
- l 3 subjects received conventional CT without contrast at baseline and 21-day follow-up due to renal insufficiency or contrast allergy.
- l 1 subjects had EUS at baseline and 21-day follow-up
- . 1 subjects had contrast-enhanced CT at baseline and endoscopy at 21-day followup in lieu of contrast-enhanced CT

Although these 5 subjects did not receive contrast-enhanced CT at baseline and follow up, all exams confirmed WON/WOPN resolution, although CECT volume measurements were not available for evaluation.

Table 3 shows the volume reduction results for the 22 PP subjects. As shown in the first row, for the total PP population, the median of the percent reduction of volume was (0) (4)%, which indicates that most subjects experienced more than 98% volume reduction. The range of (b) (4) (b) (4) indicates that at least one patient experienced an increase of volume, but other subjects experienced 100% reduction of volume. The mean percent reduction was 10%. Eleven subjects had one procedure; 6 subjects had two procedures; 5 subjects had 3-4 procedures. For the ITT population, the results were consistent with the PP population: the median volume reduction was b) (4) 0/0 -(b) (4) %; the range was (b) (4) %; the mean was

Out of the 22 subjects that were included in our PP analysis, 18/22 (82%) had at least a ""% reduction in their WON size. Out of the 30 subjects that were included in the ITT analysis, there were 24/30 (80%) subjects who had at least a ""% reduction in the WON Size.

Procedures Required per Patient (Per Protocol, N = 22)
# of DEN
Procedures
Required per
Patient	# of Subjects	Collection Size at
Baseline (cm³)
Mean (±SD)	Collection Size
21 days after
last treatment
(cm³) Mean
(±SD)	% Reduction of
WON Size
1-4
(all subjects)	22	(b) (4)
1	11
2	6
3	3
4	2

Table 3. Collection Volume at Baseline and 21 Day Follow up, Stratified by the Number of Procedures Required ner Patient (Per Protocol N = 22)

The sponsor also recorded the total procedure time (Table 4), including the debridment time it took for EndoRotor to resect and remove the WOPN/WON. As seen in Table 4, the average time using the EndoRotor device was " minutes (standard deviation "" minutes, range (b) (4) minutes); the average total time needed for the procedure was (014) minutes (standard deviation minutes, range (b) (4) minutes).

Table 4. Total EndoRotor time and Total Procedure Time in up t Procedures. (PP population, N=22)

| | Total EndoRotor
Time | Total Procedure
Time |
|--------|-------------------------|-------------------------|
| Mean | (b) (4) | |
| SD | | |
| Median | | |
| Range | | |

Real World Data (RWD)

For the collection of real world clinical data, clinicians accessed patient records for routinely recorded information (e.g. procedure time. discharge summary) for subjects who underwent a DEN procedure with the suject device. One hundred and eight records were obtained, in which (4) 0/0). there were 14 subjects who could not achieve complete WON resolution

(b) (4) subjects had imaging at baseline and a follow up image: 5 out of "" subjects had an indeterminate number of DEN procedures and were excluded from further analysis. Therefore, (6) 4) subjects were initially included; these pateitns had CECT or MRI scans at baseline and follow up. Twenty nine of "" patient had a known number of procedures and therefore the sponsor provided FDA an analysis of the data for [] subjects, stratified by the number of procedures with a cut off of "All " subjects had "or less procedures.

The sponsor also had data for 52/108 subjects (48%), for whom they reported an average length of hospitalization of 31 days (range 0 - 119).

Table 5 below shows the number of subjects requiring up to four procedures, and shows the baseline collection in cm2 (two dimensional data were collected). Follow up was conducted at several time points (unlike the IDE study that collected data after 21 (+7) days following the last EndoRotor procedure), ranging from 6 to 345 days.

Table 5. RWD Reduction in Collection Size stratified by total procedures required per patient (N=6)(4).

| # of DEN
Procedures
Required per
Patient | # of
Subjects | Collection Size at
Baseline (cm²) Mean (±SD) | Collection Size at
follow up(cm²)
Mean (±SD) | % Reduction in
WON Size |
|---------------------------------------------------|------------------|-------------------------------------------------|----------------------------------------------------|----------------------------|
| 1-4 | (b) (4) | | | |

	(b) (4)
1
2
3
4

N/A: Data not available due to a single data point.

Literature Comparison

From the literature search described above, 5 articles were utilized to determine the effectivness of current tools to treat WOPN/WON as shown in Table 6:

Table 6. Effectivness Outcomes Reported in the Literature for current WOPN/WON therapies

| Article
Reference
(Number of
subjects) | Number of
subjects (in
study/underwent
DEN) | Percent of subjects
achieving Clinical
Resolution of
pancreatic necrosis* | Mean number of endoscopic
procedures needed to resolve
pancreatic necrosis. |
|-------------------------------------------------|------------------------------------------------------|------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------|
| Puli, 2013 | 233/233 | 81.84% (95% CI:
76.73%, 86.44%) | 4.09 (95% CI: 2.31, 5.87) |

Sharaiha, 2016	124 /78	107/124 (86.3%)	Median 2 (range 1-9)
Gardner, 2011	104 /104	95 /104 (91%)	Median = 3
Thompson,
2015	60/60	86.7%	1.58 ± 0.1 (SD)
Kumar, 2014	24/12	11/12 (92%)	1.4 ± 0.2 (SD)

Each study had a slightly different definition of "clinical resolution" as described in the text.

As shown in the table above, the effectiveness of current treatment modalites for WOPN/WON varied from approximately 80 - 90%.

The publication from Puli, et al.was a meta-analysis comprising 233 subjects, reported 81.85% of subjects achieved clinical resoluton of their pancreatic necrosis after a mean of " procedures. In this article, success was defined as resolution of the necrotic cavity proven by radiology. In one of the articles reviewed in this meta-analysis, Seifert, et al. reported 80% clinical resolution of pancreatic necrosis, with a mean of 6 endoscopic procedures needed to resolve the necrosis.

Sharaiha et al. reported on 124 subjects that underwent endoscopic transmural drainage by using LAMS. The primary outcomes in this article were: 1) rates of technical success (succesful placement of the LAMS), 2) clinical success (resolution of WON, on the basis of image analysis, without the need for further intervention via surgery or interventional radiology). The authors reported that 114 subjects (91.9%) had transgastric drainage of their WON, and 10 subjects (8.1%) had transduodenal drainage. A needle knife or cystotome was used to form a tract in 13 cases. Subsequent DEN through the LAMS was performed in 78 subjects (62.9%). The median number of endoscopic interventions performed (index procedure and subsequent DEN) was 2 (range, 1–9); 30.6% of subjects (n =38) had 1 endoscopic session, 50.8% (n =63) had 2 or 3 sessions, and 18.6% (n =23) had 4 or more sessions to debride the WON. Technical success for placement of the LAMS was achieved in all 124 subjects (100%). Clinical success with successful endoscopic eradication of the WON was achieved in 107 subjects (86.3%); 34 subjects achieved complete resolution of the WON with a single endoscopic session.

Gardner, et al. reported on 104 subjects from 6 participating centers who underwent DEN during the study period. Necrotic pancreatic tissue identified via CT scan was removed by a combination of several endoscopic accesories. This article defined success as resolution or nearresolution (>90%) of cavity without operative or percutaneous drainage of the cavity. In this article, 91.3% (95/104) success rate was reported.

Thompson, et al. reported on 60 consecutive subjects who underwent an average of 1.58 ±0.1 DEN proceduress, with debridement accomplished on the initial procedure in 59/60 (98.3%) subjects In this study the primary outcome was clinical resolution of symptomatic WON after DEN, defined as resolution of primary symptom and absence of abdominal pain, nausea, vomiting, fever, leukocytosis, and sepsis. Clinical resolution occurred in 86.7%, with radiologic confirmation.

Kumar et al. conducted a matched cohort study using a prospective clinical registry. Twenty-four subjects were included. Twelve consecutive subjects from January 2009 to December 2010 were included in the DEN group. Subjects undergoing a step-up approach with primary percutaneous catheter drainage (PCD) were identified from the same registry and matched 1:1 with DEN subjects based on collection size and Charlson Comorbidity Index, a prospectively validated metric. Clinical resolution was defined as resolution of primary symptom and absence of abdominal pain, nausea, vomiting, fever, leukocytosis, and sepsis. The authors reported that 11 of 12 subjects (92%) had clinical resolution of WOPN/WON after DEN versus 3 of 12 (25%) step up approach subjects after drainage (p