Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on a mechanical/magnetic anchoring system for endoscope guidance, with no mention of AI, ML, image processing, or data-driven decision making.

Therapeutic

No.
The device is an accessory to an endoscope, intended to facilitate positioning and progression of the endoscope, rather than directly treating a condition.

Diagnostic

No

ENDORAIL is an accessory to an endoscope intended to facilitate the physical progression and positioning of the endoscope during colonoscopy, not to provide diagnostic information itself. Its purpose is to aid in the completion of a diagnostic procedure (colonoscopy).

SaMD (Software as a Medical Device)

No

The device description clearly outlines physical components like a Balloon Guide, ferromagnetic fluid, and a magnetic Handpiece, indicating it is a hardware device with a mechanical function.

IVD (In Vitro Diagnostic)

Based on the provided information, the ENDORAIL device is not an In Vitro Diagnostic (IVD).

Here's why:

Intended Use: The intended use clearly states that ENDORAIL is an accessory to an endoscope and is intended to ensure positioning of the endoscope during endoscopy of the large intestine. This is a mechanical function related to guiding the endoscope within the body.
Device Description: The description details how the device works as a magnetic anchor to facilitate endoscope progression and straighten colon curves. This is a physical manipulation of the endoscope and the colon.
Lack of Biological Sample Analysis: IVD devices are designed to examine specimens derived from the human body (like blood, urine, tissue) to provide information for diagnosis, monitoring, or screening. The ENDORAIL device does not interact with or analyze any biological samples.
Anatomical Site: The device is used within the large intestine, which is an in-vivo application, not an in-vitro (outside the body) analysis of a sample.

Therefore, the ENDORAIL device is a medical device used in vivo to assist with an endoscopic procedure, not an IVD.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

ENDORAIL is an accessory to an endoscope and is intended to ensure positioning of a standard endoscope (i.e. an endoscope with an instrument channel that is at least 3.7mm diameter and is used for standard endoscopic visualization) during endoscopy of the large intestine.

Product codes

ODC

Device Description

ENDORAIL is a colonoscopy add-on device developed to be used without any modification to colonoscopes and peripheral devices currently utilized. It is an accessory for colonoscopy aimed at facilitating progression of the endoscope in the large intestine. The device works as a magnetic anchor that allows the operator to guide the colonoscope and to straighten colon curves and loops.

ENDORAIL includes a Balloon Guide that can be introduced, when needed, through the endoscope instrument channel during the colonoscopy, if this procedure becomes challenging. The system does not require to be premounted and does not interfere with the normal colon examination process. The Balloon Guide is advanced beyond the colonoscope tip where the balloon is filled with a ferromagnetic fluid and magnetically anchored to a magnetic Handpiece placed on the patient's abdomen. Once anchored, the colonoscope can be easily straightened and guided along the device, allowing a fast and safe inspection of the entire colon. Once the challenging segment of the colon is resolved, or the colonoscopy procedure is completed, the Balloon Guide can be retrieved.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

large intestine

Indicated Patient Age Range

22-75 years (inclusive)

Intended User / Care Setting

Specialized medical staff in hospitals or clinics.

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

A total of thirty-eight (38) patients were enrolled into the study, underwent the colonoscopy procedure with ENDORAIL, and were included in the statistical analysis. This was an interim analysis, originally planned once 40% of the total sample size was reached. The statistical significance of the sample was tested and found to be sufficient, leading to the termination of the trial.

Data source: Multicentre Post-Market Single Arm Open Label Interventional Study in Italy, Germany, and Belgium:

IRCCS Humanitas Research Hospital, Milan, Italy
GastroZentrum Lippe, Bad Salzuflen, Germany (affiliated with Universität Mainz)
University Hospitals Leuwen, Leuwen, Belgium

Annotation Protocol:

All data collected in this study, and documented in the eCRFs, were listed and summarized.
For quantitative variables: standard quantitative statistics (N, mean, standard deviation, median, interquartile range, minimum and maximum).
For qualitative variables: frequency distribution [number of non-missing observations (N) and percentages (%)].
Medical AEs and medical device AEs were collected.
All AEs were tabulated by System Organ Class (SOC) and Preferred Term (PT) after medical coding using the Medical Dictionary for Regulatory Activities (MedDRA) thesaurus version 24.1. The primary SOC and the PT were used for the analysis of the frequency distribution.
The frequency of occurrence of specific AEs (gastrointestinal bleedings, intestinal perforation, mucosal petechiae, abdominal pain) were assessed by means of default descriptive statistics.
The statistical analyses were carried out using R Statistical Software.

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

Study Type: Multicentre Post-Market Single Arm Open Label Interventional Study
Sample Size: 38 patients were enrolled and included in the statistical analysis.
Key Results:

Efficacy: All 38 patients (100%) successfully completed the colonoscopy with ENDORAIL, and no patient needed to interrupt the diagnostic procedure or be withdrawn from the study. In all patients, the endoscopist could reach and fully inspect the caecum. The colonoscopy incompletion rate was 0%. This successfully achieved the primary efficacy endpoint of a colonoscopy incompletion rate ≤ 10%.
Safety: No AE/SAE, no abnormal findings, and no overall change in the health status of any patient undergoing the colonoscopy with ENDORAIL were observed. This successfully achieved the primary safety objective of demonstrating that colonoscopy SAEs are not increased by using the device (absence of any device-related SAEs).
Statistical analysis showed that the observed percentage of "events" (procedure incomplete or serious adverse event) was 0% (95%CI: 0% - 7.6%) with a p-value

Regulation Number and Section

§ 876.1500 Endoscope and accessories.

(a)
Identification. An endoscope and accessories is a device used to provide access, illumination, and allow observation or manipulation of body cavities, hollow organs, and canals. The device consists of various rigid or flexible instruments that are inserted into body spaces and may include an optical system for conveying an image to the user's eye and their accessories may assist in gaining access or increase the versatility and augment the capabilities of the devices. Examples of devices that are within this generic type of device include cleaning accessories for endoscopes, photographic accessories for endoscopes, nonpowered anoscopes, binolcular attachments for endoscopes, pocket battery boxes, flexible or rigid choledochoscopes, colonoscopes, diagnostic cystoscopes, cystourethroscopes, enteroscopes, esophagogastroduodenoscopes, rigid esophagoscopes, fiberoptic illuminators for endoscopes, incandescent endoscope lamps, biliary pancreatoscopes, proctoscopes, resectoscopes, nephroscopes, sigmoidoscopes, ureteroscopes, urethroscopes, endomagnetic retrievers, cytology brushes for endoscopes, and lubricating jelly for transurethral surgical instruments. This section does not apply to endoscopes that have specialized uses in other medical specialty areas and that are covered by classification regulations in other parts of the device classification regulations.(b)
Classification —(1)Class II (special controls). The device, when it is an endoscope disinfectant basin, which consists solely of a container that holds disinfectant and endoscopes and accessories; an endoscopic magnetic retriever intended for single use; sterile scissors for cystoscope intended for single use; a disposable, non-powered endoscopic grasping/cutting instrument intended for single use; a diagnostic incandescent light source; a fiberoptic photographic light source; a routine fiberoptic light source; an endoscopic sponge carrier; a xenon arc endoscope light source; an endoscope transformer; an LED light source; or a gastroenterology-urology endoscopic guidewire, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 876.9.(2) Class I for the photographic accessories for endoscope, miscellaneous bulb adapter for endoscope, binocular attachment for endoscope, eyepiece attachment for prescription lens, teaching attachment, inflation bulb, measuring device for panendoscope, photographic equipment for physiologic function monitor, special lens instrument for endoscope, smoke removal tube, rechargeable battery box, pocket battery box, bite block for endoscope, and cleaning brush for endoscope. The devices subject to this paragraph (b)(2) are exempt from the premarket notification procedures in subpart E of part 807of this chapter, subject to the limitations in § 876.9.

Summary

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March 15, 2024

Endostart s.r.l. % Fabio Pasquale Sr. Director, OA/RA QA & RA Medical Device Consulting, Ltd. 842 Clarke Road Brentwood Bay, BC V8M 2G1 Canada

Re: K232327

Trade/Device Name: Endorail Regulation Number: 21 CFR 876.1500 Regulation Name: Endoscope And Accessories Regulatory Class: Class II Product Code: ODC Dated: February 16, 2024 Received: February 16, 2024

Dear Fabio Pasquale:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

1

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 mediation-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).

2

Sincerely,

Shanil P. Haugen -S

Shanil P. Haugen, Ph.D. Assistant Director DHT3A: Division of Renal, Gastrointestinal, Obesity and Transplant Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

3

Indications for Use

510(k) Number (if known) K232327

Device Name ENDORAIL

Indications for Use (Describe)

ENDORAIL is an accessory to an endoscope and is intended to ensure positioning of a standard endoscope (i.e. an endoscope with an instrument channel that is at least 3.7mm diameter and is used for standard endoscopic visualization) during endoscopy of the large intestine.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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Section 8 - 510(k) Summary

(in accordance with 21 CFR 807.92)

510(k) Number:

l. Applicant Information

Applicant:	Endostart s.r.l.
	Via delle Regioni 265
	50052 Certaldo (FI)
	ITALY
Contact Person:	Alessandro Tozzi
	CEO
	Endostart s.r.l.
	Tel: +39-0571-843-033
	e-mail: a.tozzi@endostart.com
Application Correspondent:	Fabio De Pasquale
	Sr. Director QA/RA
	QA & RA Medical Device Consulting, Ltd.
	Tel: 1-250-920-6501
	e-mail: ga.ra.meddev@outlook.com

July 28, 2023 Date Prepared:

ll. Subject Device Identification

Proprietary Name:

ENDORAIL

Classification Name: Endoscope Channel Accessory Regulation Name: Endoscope and Accessories Regulation Number: 21 CFR 876.1500 Product Code: ODC

Regulatory Class: Classification Panel:

Class II Gastroenterology/Urology

lll. Predicate Devices

The subject device, the ENDORAIL, is substantially equivalent to the following two cleared predicate devices. The subject and predicate device have the same fundamental scientific technology and intended use.

5

Primary Predicate Device (#1):

510(k) Number:	K111760
Proprietary Name:	NaviAid BGC (later renamed "NaviAid ABC")
Manufacturer Name:	Smart Medical Systems, Ltd.
Common/Usual Name:	NaviAid Balloon Guided Colonoscopy
Classification Name:	Endoscope Channel Accessory
Requlation Name:	Endoscope and Accessories
Regulation Number:	21 CFR 876.1500
Product Code:	ODC
Regulatory Class:	Class II
Classification Panel:	Gastroenterology/Urology

Predicate Device (#2):

510(k) Number:
Proprietary Name:
Manufacturer Name:
Common/Usual Name:
Classification Name:
Regulation Name:
Regulation Number:
Product Code:
Regulatory Class:
Classification Panel:

K183057 PUMA-G System

CoapTech LLC Gastrointestinal Tube Accessory Tube, Gastro-Enterostomy Gastrointestinal Tube and Accessories 21 CFR 876.5980 KGC Class II Gastroenterology/Urology

IV. Subiect Device Description

ENDORAIL is a colonoscopy add-on device developed to be used without any modification to colonoscopes and peripheral devices currently utilized. It is an accessory for colonoscopy aimed at facilitating progression of the endoscope in the large intestine. The device works as a magnetic anchor that allows the operator to quide the colonoscope and to straighten colon curves and loops.

ENDORAIL includes a Balloon Guide that can be introduced, when needed, through the endoscope instrument channel during the colonoscopy, if this procedure becomes challenging. The system does not require to be premounted and does not interfere with the normal colon examination process. The Balloon Guide is advanced beyond the colonoscope tip where the balloon is filled with a ferromagnetic fluid and magnetically anchored to a magnetic Handpiece placed on the patient's abdomen. Once anchored, the colonoscope can be easily straightened and guided along the device, allowing a fast and safe inspection of the entire colon. Once the challenging segment of the colon is resolved, or the colonoscopy procedure is completed, the Balloon Guide can be retrieved.

As discussed in the following sections, the intended use, technological characteristics, principles of operation and materials of the subject device are substantially equivalent to the respective ones of the predicate devices.

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V. Indications for Use

ENDORAIL is an accessory to an endoscope and is intended to ensure positioning of a standard endoscope (i.e., an endoscope with an instrument channel that is at least 3.7mm diameter and is used for standard endoscopic visualization) during endoscopy of the large intestine.

VI. Substantial Equivalence

Intended Use/Indications for Use

ENDORAIL and its Primary Predicate device have substantially equivalent Intended Use/Indications for Use, with the minor difference being that the primary predicate device is meant to facilitate positioning of standard endoscopes in both the small and large intestine, whereas ENDORAIL is meant to ensure positioning of standard endoscopes exclusively in the large intestine.

Technological Characteristics

The Substantial Equivalence Comparison Table provided in the following pages includes a comparison of each of the technological features of the ENDORAIL device with those of the primary predicate and the reference devices.

The following two main differences in technological characteristics between the subject and the predicate devices are summarized in the following sections.

The Primary Predicate device (NaviAid BGC) achieves its balloon anchoring function by inflating the balloon with air and stretching it beyond the diameter of the colon, whereas the subject ENDORAIL achieves its balloon anchoring function by filling the balloon with a ferromagnetic fluid in combination with the placement of a permanent maqnet externally over the patient abdomen.

The magnetic anchoring of the ENDORAIL balloon functions in a similar fashion to the magnetic anchoring system utilized by the Reference device, the PUMA-G System, which is an accessory to enteral feeding tubes that enables ultrasound-based placement of percutaneous gastrostomy feeding tubes.

The following table summarizes the substantial equivalence comparison between the subject and the predicate devices.

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Substantial Equivalence Comparison Table

| Comparison
Elements | Subject Device: | Primary Predicate Device
(#1): (K111760) | Reference Device (#2):
(K183057) |
|---------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | ENDORAIL | NaviAid BGC
(renamed "NaviAid ABC") | PUMA-G System |
| Product Code | ODC | ODC | KGC
(N/A) |
| Regulation # | 876.1500 | 876.1500 | 876.5980
(N/A) |
| Class | II | II | II |
| Intended Use | ENDORAIL is an
accessory to an endoscope
and is intended to ensure
positioning of a standard
endoscope (i.e., an
endoscope that has an
instrument channel that is
at least 3.7mm diameter
and is used for standard
endoscopic visualization)
during endoscopy of the
large intestine. | The NaviAid BGC is an
accessory to an endoscope
and is intended to ensure
positioning of a standard
endoscope (i.e., an
endoscope that has an
instrument channel that is
at least 3.7mm diameter
and is used for standard
endoscopic visualization)
during endoscopy of the
small and large intestine. | The new PUMA-G system
is an accessory to enteral
feeding tubes that enables
ultrasound-based
placement of
percutaneous gastrostomy
feeding tubes.
(N/A) |
| Indications for Use | ENDORAIL is an
accessory indicated for a
fast and easy colonoscopy | The NaviAid BGC is an
accessory indicated for fast
and easy colonoscopy,
ileoscopy and upper | The new PUMA-G system
is an accessory to enteral
feeding tubes that enables
ultrasound-based |
| Comparison
Elements | Subject Device: | Primary Predicate Device
(#1): (K111760) | Reference Device (#2):
(K183057) |
| | ENDORAIL | NaviAid BGC
(renamed "NaviAid ABC") | PUMA-G System |
| | procedure with a standard
endoscope. | enteroscopy procedures
with a standard endoscope. | placement of
percutaneous gastrostomy
feeding tubes.
(N/A) |
| | The device allows keeping
all the advantages of an
endoscopic procedure, such
as back-and-forth
navigation, real-time
operation, video imaging, or
the capability to stop
propagation if needed, and
to use an instrument
channel for patient
treatment as necessary. | The device allows keeping
all the advantages of an
endoscopic procedure,
such as back-and-forth
navigation, real-time
operation, video imaging,
or the capability to stop
propagation if needed, and
to use an instrument
channel for patient
treatment as necessary. | |
| Sterility and
Reusability | The Balloon Catheter
component of ENDORAIL is
supplied as "non-sterile"
and for "single-use". | The NaviAid BGC system is
supplied as "non-Sterile"
and for "single use". | The procedural kit
(guidewire, balloon
catheter and other
accessories) is supplied as
"sterile" and for "single-
use". |
| Comparison
Elements | Subject Device: | Primary Predicate Device
(#1): (K111760) | Reference Device (#2):
(K183057) |
| | ENDORAIL | NaviAid BGC
(renamed "NaviAid ABC") | PUMA-G System |
| | The ENDORAIL Handpiece
(external magnet) is
supplied as "non-sterile"
and "re-usable". | | The External Magnet
component is supplied as
"non-sterile" and "re-
usable". |
| Environment of
Use | ENDORAIL is intended for
use in hospitals or clinics by
specialized medical staff. | The NaviAid BGC is for use
in hospitals or clinics by
specialized medical staff. | The PUMA-G system is for
use in hospitals or clinics
by specialized medical
staff. |
| Limitations of Use | To be used during
endoscopy of the large
intestine only. | To be used during
endoscopy of the small and
large intestine. | None known. |
| Principles of
Operation | ENDORAIL facilitates the
advancement and
placement of an intestinal
endoscope. | The NaviAid BGC facilitates
the advancement and
placement of an intestinal
endoscope. | The PUMA-G System
facilitates feeding tube
insertion that can be
performed at a patient's
bedside. |
| | The system utilizes a
specialized balloon, inserted
in the endoscope using an
inflation tube catheter,
which is alternately inflated
and deflated in order to | The system utilizes a
specialized balloon,
inserted in the endoscope
using an inflation tube
catheter, which is
alternately inflated and | The system relies on a
balloon catheter
containing a small
magnetic needle that is fed
through a patient's mouth
and guided into the |
| Comparison
Elements | Subject Device: | Primary Predicate Device
(#1): (K111760) | Reference Device (#2):
(K183057) |
| | ENDORAIL | NaviAid BGC
(renamed "NaviAid ABC") | PUMA-G System |
| | allow the proper
progression and to ensure a
suitable positioning of the
endoscope in the intestine. | deflated in order to allow
the proper progression and
to ensure a suitable
positioning of the
endoscope in the intestine. | stomach using an external
magnet. The balloon is
made to be "grabbed" by
an external magnet placed
over the patient stomach. |
| | ENDORAIL uses a single
disposable balloon. The
balloon traverses ahead of
the endoscope through the
endoscope's instrument
channel and thus it can be
applied on demand without
the need for a pre-
procedure preparation of
the device. | The NaviAid BGC uses a
single disposable balloon.
The balloon traverses ahead
of the endoscope through
the endoscope's instrument
channel and thus it can be
applied on demand without
the need for a pre-
procedure preparation of
the device. | The balloon is inflated with
saline and ultrasound
guides the treating
physician as they insert a
needle through the
stomach and into the
balloon. The balloon
catches a wire that is then
pulled back up and out the
mouth as the balloon is
removed. A feeding tube |
| | The balloon is connected to
a dedicated inflation tube
that runs inside the
instrument channel of the
endoscope and is connected
at its proximal (user) end to | The balloon is connected to
a dedicated inflation tube
that runs inside the
instrument channel of the
endoscope and is
connected at its proximal | can then be pushed back
down over the wire and
safely out the stomach. |
| Comparison
Elements | Subject Device: | Primary Predicate Device
(#1): (K111760) | Reference Device (#2):
(K183057) |
| | ENDORAIL | NaviAid BGC
(renamed "NaviAid ABC") | PUMA-G System |
| | an inflation/deflation
system. | (user) end to an
inflation/deflation system. | |
| | The user manually operates
and controls the inflation
and deflation of the balloon
through the
inflation/deflation system. | The user manually operates
and controls the inflation
and deflation of the balloon
through the
inflation/deflation system. | |
| | The balloon can be
advanced ahead of the
endoscope tip or pulled
back through a
pushing/pulling action on
the inflation tube at its
proximal end, outside the
patient's body. | The balloon can be
advanced ahead of the
endoscope tip or pulled
back through a
pushing/pulling action on
the inflation tube at its
proximal end, outside the
patient's body. | |
| | The balloon and inflation
tube do not compromise in
a significant way the
endoscope's flexibility, its
field of view or the | The balloon and inflation
tube do not compromise in
a significant way the
endoscope's flexibility, its
field of view or the | |
| Comparison
Elements | Subject Device: | Primary Predicate Device
(#1): (K111760) | Reference Device (#2):
(K183057) |
| | ENDORAIL | NaviAid BGC
(renamed "NaviAid ABC") | PUMA-G System |
| | manoeuvrability of its tip,
and do not limit the usage
of any standard endoscopy
tools such as biopsy forceps,
snare, needle etc. The
balloon catheter system can
be pulled back at any time
during the procedure in
order to allow use of
therapy tools. | manoeuvrability of its tip,
and do not limit the usage
of any standard endoscopy
tools such as biopsy
forceps, snare, needle etc.
The balloon catheter
system can be pulled back
at any time during the
procedure in order to allow
use of therapy tools. | |
| | When the balloon is
advanced beyond the
endoscope distal end,
inflated and anchored, it
behaves as a distal "anchor"
towards which the
endoscope tip is advanced.
Endoscope advancement is
thus performed using the
inflation tube as a guide
wire, allowing the
endoscope to be more | When the balloon is
advanced beyond the
endoscope distal end,
inflated and anchored, it
behaves as a distal
"anchor" towards which
the endoscope tip is
advanced. Endoscope
advancement is thus
performed using the
inflation tube as a guide
wire, allowing the | |
| Comparison
Elements | Subject Device:
ENDORAIL | Primary Predicate Device
(#1): (K111760) | Reference Device (#2):
(K183057) |
| | | NaviAid BGC
(renamed "NaviAid ABC") | PUMA-G System |
| | easily guided through the
straightened curves and
loops of the colon. | endoscope to be more
easily guided through the
straightened curves and
loops of the colon. | |
| | The ENDORAIL balloon is
filled with a
magnetorheological
ferromagnetic fluid
composed of solid
micrometric carbonyl iron
powder dispersed in a water
solution of Sodium Chloride
and Sodium Citrate, by
means of a syringe. | The NaviAid BGC balloon is
filled with ambient air using
an air supply unit and
control pump. | The PUMA-G balloon is
filled with saline solution
using a syringe. |
| | The balloon is inflated with
a ferromagnetic fluid and
"anchored" to the colon
wall. | The balloon is inflated with
air increasing the balloon
volume until its diameter is
enough large to fill the
entire intestine lumen. | The balloon is inflated with
saline solution and
"anchored" to the stomach
wall. |
| | | | |
| Comparison
Elements | Subject Device:
ENDORAIL | Primary Predicate Device
(#1): (K111760)
NaviAid BGC
(renamed "NaviAid ABC") | Reference Device (#2):
(K183057)
PUMA-G System |
| | The "anchoring" of the
balloon is ensured by
magnetic force using an
external magnet over the
patient abdomen in
correspondence of the
balloon.

The anchoring of the
balloon allows the
straightening of the colon
curves and loops, facilitating
the endoscope progression. | The "anchoring" of the
balloon is ensured by the
friction force exerted by the
filled balloon against the
intestine wall.

The anchoring of the
balloon allows the
straightening of the colon
curves and loops,
facilitating the endoscope
progression. | The "anchoring" of the
balloon is ensured by
magnetic force using an
external magnet over the
patient abdomen in
correspondence of the
balloon. |
| Orifice of Use | The ENDORAIL catheter is
passed via the colonoscope
through anus into the
colon. | The NaviAid BGC catheter is
passed via the colonoscope
through anus into the
colon. | The PUMA-G catheter is
passed through the mouth
into the stomach of the
patient.
(N/A) |
| Balloon
Inflation/Deflation
Mechanism | The user may manually
operate and control the
inflation and deflation of | The user may manually
operate and control the
inflation and deflation of | The user may manually
operate and control the
inflation and deflation of |
| Comparison
Elements | Subject Device: | Primary Predicate Device (#1): (K111760) | Reference Device (#2): (K183057) |
| | ENDORAIL | NaviAid BGC
(renamed “NaviAid ABC”) | PUMA-G System |
| | the balloon through the
syringe. | the balloon through the
power air supply/foot
pedal control system.
(N/A) | the balloon through the
syringe. |

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9

10

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12

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VII. Non-Clinical Performance Data

Endostart s.r.l. has conducted extensive verification and validation testing of ENDORAIL, as an accessory for colonoscopy capable of facilitating progression of the endoscope in the large intestine. The subject device was tested to ensure that it can provide all the capabilities necessary to operate safely and effectively.

Acceptance criteria have been established to ensure that the subject device performs in a manner that is substantially equivalent to the cited predicate devices. Testing was conducted to verify the safety and performance requirements of the subject device and the test results support substantial equivalence to the predicate devices. The following table lists the nonclinical tests performed on the subject ENDORAIL for a determination of substantial equivalence.

ENDORAIL - Non-Clinical Tests Performed
Biocompatibility Testing
Electrical Safety Testing
Electromagnetic Compatibility Testing
Software Verification and Validation Testing
Mechanical Testing
Components Testing
Human Factors Validation Testing
Microbiological Bioburden Testing
Shelf Life and Stability Testing
Packaging Testing
Environmental Conditioning and Shipping Testing
Characterization and Functional Testing

ENDORAIL complies with all the applicable voluntary recognized standards related to its regulations and product code and successfully passed all respective testing.

The following quidance documents and standards were followed to determine appropriate methods for evaluating the performance of the subject device.

Guidance Documents and Recognized Standards Applicable to ENDORAIL
Standard/Guidance	Title
FDA Guidance	Design Control Guidance for Medical Device Manufacturers
FDA Guidance	Format for Traditional and Abbreviated 510(k)s
FDA Guidance	The 510(k) Program: Evaluating Substantial Equivalence in
Premarket Notifications [510(k)]
FDA Guidance	Recommended Content and Format of Non-Clinical Bench
Performance Testing Information in Premarket Submissions
Guidance Documents and Recognized Standards Applicable to ENDORAIL
Standard/Guidance	Title
FDA Guidance	Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process"
FDA Guidance	General Principles of Software Validation
FDA Guidance	Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices
FDA Guidance	Content of Premarket Submissions for Device Software Functions
FDA Guidance	Applying Human Factors and Usability Engineering to Medical Devices
FDA Guidance	Content of Human Factors Information in Medical Device Marketing Submissions [Draft]
FDA Guidance	Acceptance of Clinical Data to Support Medical Device Applications and Submissions: Frequently Asked Questions
FDA Guidance	Shelf-life of Medical Devices
FDA Guidance	Device Labeling Guidance #G91-1 (Blue Book Memo)
FDA Guidance	Testing and Labeling Medical Devices for Safety in the Magnetic Resonance (MR) Environment
FDA Guidance	Recommendations for Labeling Medical Products to Inform Users that the Product or Product Container is not Made with Natural Rubber Latex
FDA Guidance	Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical Devices
FDA Guidance	Refuse to Accept Policy for 510(k)s
FDA Guidance	Financial Disclosure by Clinical Investigators
FDA Guidance	eCopy Program for Medical Device Submissions
ANSI AAMI ES60601-
1:2005/(R)2012 &
A1:2012,
C1:2009/(R)2012 &
A2:2010/(R)2012	Medical Electrical Equipment - Medical Electrical Equipment - Part 1: General Requirements for Basic Safety and Essential Performance
ANSI AAMI IEC 60601-
1-2:2014	Medical Electrical Equipment - Part 1-2: General Requirements for Basic Safety and Essential Performance – Collateral Standard: Electromagnetic Disturbances – Requirements and Tests
IEC/TR 60601-4-2
Edition 1.0 2016-05	Medical electrical equipment - Part 4-2: Guidance and interpretation - Electromagnetic immunity: performance of medical electrical equipment and medical electrical systems
IEC 60601-1-6 Edition
3.2 2020-07	Medical Electrical Equipment-Part 1-6: General Requirements for Basic Safety and Essential Performance - Collateral Standard: Usability
ANSI AAMI IEC
62304:2006/A1:2016	Medical device software - Software Life Cycle Processes
ANSI AAMI IEC 62366-
1:2015+AMD1:2020
(Consolidated Text)	Medical Devices - Part 1: Application of Usability Engineering to Medical Devices
ISO 10993-1 Fifth
edition 2018-08	Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing within a Risk Management Process
Guidance Documents and Recognized Standards Applicable to ENDORAIL
Standard/Guidance	Title
ISO 10993-2 Second
edition 2006-07-15	Biological evaluation of Medical devices Part 2: Animal welfare
requirements
ISO 10993-5 Third
edition 2009-06-01	Biological evaluation of medical devices - Part 5: Tests for in vitro
cytotoxicity
ISO 10993-10 Fourth
edition 2021-11	Biological evaluation of medical devices - Part 10: Tests for skin
sensitization
ISO 10993-11 Third
edition 2017-09	Biological evaluation of medical devices - Part 11: Tests for
systemic toxicity
ISO 10993-12 Fifth
edition 2021-01	Biological evaluation of medical devices - Part 12: Sample
preparation and reference materials
ISO 10993-23 First
edition 2021-01	Biological evaluation of medical devices - Part 23: Tests for
irritation
ISO 20695 First edition
2020-03	Enteral feeding systems - Design and testing
ASTM F2528-06
(Reapproved 2014)	Standard Test Methods for Enteral Feeding Devices with a
Retention Balloon
ISO 80369-7 Second
edition 2021-05	Small-bore connectors for liquids and gases in healthcare
applications - Part 7: Connectors for intravascular or hypodermic
applications
ISO 11737-1 Third
edition 2018-01	Sterilization of health care products - Microbiological methods -
Part 1: Determination of a population of microorganisms on
product
ISO 7886-1 Second
edition 2017-05	Sterile hypodermic syringes for single use - Part 1: Syringes for
manual use
ISO 20696 First edition
2018-06; Corrected
2019-12	Sterile urethral catheters for single use
ASTM F1886/F1886M-
16	Standard Test Method for Determining Integrity of Seals for
Flexible Packaging by Visual Inspection
ASTM F1929-15	Standard Test Method for Detecting Seal Leaks in Porous Medical
Packaging by Dye Penetration – Method B
ASTM F88/F88M-21	Standard Test Method for Seal Strength of Flexible Barrier
Materials
ASTM D4332-14	Standard Practice for Conditioning Containers, Packages, Or
Packaging Components For Testing
ASTM F1980-21	Standard Guide for Accelerated Aging of Sterile Barrier Systems
for Medical Devices
ASTM D4169-22	Standard Practice for Performance Testing of Shipping Containers
and Systems
The United States
Pharmacopeia (USP)
and National Formulary
(NF) USP 42–NF 37;
M98900_01_01	Pyrogen Test (USP Rabbit Test)
ISO 14155 Third edition
2020-07	Clinical investigation of medical devices for human subjects - Good
clinical practice
Guidance Documents and Recognized Standards Applicable to ENDORAIL
Standard/Guidance	Title
ISO 15223-1 Fourth
edition 2021-07	Medical Devices - Symbols To Be Used With Medical Device
Labels, Labelling, And Information To Be Supplied - Part 1:
General Requirements
ISO 20417 First edition
2021-04 Corrected
version 2021-12	Medical devices - Information to be supplied by the manufacturer
ISO 14971 Third Edition
2019-12	Medical Devices - Application of Risk Management To Medical
Devices

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VIII. Clinical Performance Data

Clinical validation testing was conducted with ENDORAIL to confirm the safety and effectiveness of the device. A summary of the design of the Multicenter Post-Market Single Arm Open Label Interventional Study performed, together with a summary of the key results, are provided below. The following table summarizes the main elements of the study.

| Title | Multicentre Clinical Trial for the evaluation of the
safety and effectiveness of ENDORAIL in patients
with long-lasting colonoscopy |
|-----------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Short Title | ENDORAIL Clinical Study |
| Study Type | Multicentre post-market single arm open label
interventional study |
| Trial centres | 1. IRCCS Humanitas Research Hospital
Via Manzoni 56, I-20089 Rozzano (Milan, Italy)
(Principal Investigator: Prof. Alessandro Repici)

GastroZentrum Lippe
Lange Str 55 32105 Bad Salzuflen (Germany)
affiliated with Universit\u00e4t Mainz
Langenbeck Street 1, D-55131 Mainz (Germany)
(Principal Investigator: Prof. Helmut Neumann)
University Hospitals Leuwen
Herestraat 49, B-3000 Leuwen (Belgium)
(Principal Investigator: Prof. Raf Bisschops) |
| Sponsor / Manufacturer | Endostart s.r.l., Via delle Regioni 265, 50052
Certaldo (FI), ITALY |
| Trial period
(first subject in-last subject out) | First Patient In: 24 January 2023;
Last Patient In: 17 May 2023;
Last Patient Last Visit: 24 May 2023. |

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Background

This Multicenter Post-Market Single Arm Open Label Interventional Study was intended to expand the clinical knowledge in support of the safety and efficacy of the ENDORAIL device.

Reported incomplete colonoscopy rates range from 4% to 25% of all screened patients. However, while international guidelines recommend a rate of less than 10% for diagnostic colonoscopies, the risk is at least 20% in the more challenging subset of patients characterized by long-lasting procedures.

A colonoscopy can be defined as "long-lasting" when caecal intubation time is longer than 10 minutes. As data from literature shows that about 80% of all diagnostic colonoscopies are typically completed in less than 10 minutes, the long-lasting colonoscopy subset represents approx. 20% of the total procedures. Indeed, since virtually all incomplete colonoscopies are also long-lasting, the risk of incompleteness in this subset of patients increases nearly fivefold (i.e., for a 5X increase, the lower bound of the rate increases from 4% to 20%).

ENDORAIL is intended to facilitate the positioning of a standard colonoscope. One of the main advantages of this system is that it can be used "as needed" during the procedure to prevent incomplete procedures without requiring any "preloading" ahead of time. This makes ENDORAIL particularly indicated for patients in which caecal intubation time gets longer and the risk of incompletion increases.

The aim of this study is to test the efficacy of ENDORAIL in ensuring low incompletion rate in long-lasting colonoscopies.

Primary Objectives

Efficacy (Timeframe: day 1)

To validate the efficacy of ENDORAIL in long-lasting colonoscopies by reaching a colonoscopy incompletion rate ≤ 10%.

Safety (Timeframe: day 1 to day 7)

To validate the safety of ENDORAIL in long-lasting colonoscopies, by demonstrating that colonoscopy serious adverse events (SAEs) are not increased using the device (i.e., absence of any device-related SAEs).

Methodology

Multicentre, post-marketing, single-arm, open-label, interventional study: Outpatients of either sex aged between 22-75 years (inclusive), undergoing elective colonoscopy for diagnostic or surveillance procedure, who signed a written ICF and presenting caecal intubation time greater than 10 minutes, took part in the study.

The study plan included: a Screening/Baseline/Treatment visit (Visit 1/Day 1), during which colonoscopy with ENDORAIL was performed; and a phone follow-up visit (Visit 2), scheduled at 7 (± 1) days post-treatment with ENDORAIL.

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Sample Size Determination

Efficacy (first primary objective) is assessed by measuring the colonoscopy completion rate in long-lasting procedures, which is a measurable parameter of clinical value recognized by international medical societies. Safety (second primary objective) is assessed by measuring the rate of adverse events. Adverse events are classified into four groups: serious gastrointestinal events; myocardial infarction; stroke; and pneumonia. Based on the data from the literature; the adverse events occurrence rates for those 4 groups, for screening or surveillance colonoscopy, are 47, 4, 7 and 10 patients per 100,000, respectively.

These two objectives are merged in one indicator for each subject, which is either equal to 1 if the procedure is incomplete or an adverse event occurs, or equal to 0 otherwise.

The non-completion rate of long-lasting colonoscopies conducted with ENDORAIL is expected to be around 10%. This will be compared to the above-mentioned threshold of 20% for incomplete procedures. It should be noted that this threshold is conservative and represents the most critical setting for comparison with respect to the art, as it is derived from the lower bound of the range from the literature.

When including the safety to provide the expected value of the indicator for ENDORAIL and the corresponding threshold, the above values of 10% minimally change, as the adverse event occurrence rate is 0.068% (given by the sum of the occurrence of the 4 events reported above per 100,000 persons, expressed in percentage).

With a significance level a of 5%, assuming a proportion of outcome of 10.1%, 85 patients allow to test with a power of 80% the H0: p ≥ 20%, where 20%, where 20% is the estimated percentage of incomplete procedure from literature.

The chosen number is then increased by the 10% to account for possible drop-out (e.g., cases to be discarded, losses to follow-up, etc.), resulting in 85/0.90 = 95 patients to be actually enrolled.

Inclusion and Exclusion Criteria

Inclusion Criteria

1. Patients of both sexes aged between 22 75 years (inclusive).
1. Outpatients undergoing long-lasting diagnostic or surveillance colonoscopy. A longlasting colonoscopy is defined as follows: colonoscopy completion (caecal intubation) not achieved after 10 minutes from endoscope insertion through the anal.
1. Patients have signed a written informed consent form (ICF) for participation in the study at the time of enrolment or before.
1. Patients able to understand the full nature and the purpose of the investigation, including possible risks and side effects, able to cooperate with the Investigator and to

22

comply with the requirements of the entire investigation based on Investigator's judgement.

Exclusion Criteria

1. Body mass index (BMI) > 30 kg/m².
1. Outpatients undergoing colonoscopy for colorectal cancer screening or therapeutic indication.
1. Patients in class >2 physical status of the classification system of American Society of Anaesthesiologists.
1. Any contraindication to colonoscopy.
1. Any contraindication to sedation.
1. Known allergy or hypersensitivity to any of the elements of the Endorail Set (e.g.: iron).
1. Patients with permanently or semi-permanently implanted medical devices (e.g., orthopaedic implants, trauma fixation devices, cardiac pacemakers, implantable cardioverter defibrillator, drug pumps, neurostimulators, vascular stents, cochlear implants, aneurysm clip).
1. Presence of dense diverticulosis.
1. Presence of diverticulitis.
1. Presence of ferromagnetic foreign body.
1. Presence of large abdominal hernias.
1. Urgent colonoscopy.
1. Presence of severe thrombocytopenia.
1. Presence of severe granulocytopenia.
1. Presence of severe coagulopathy.
1. Presence of peritonitis.
1. Presence of colonic wall ischemia or necrosis or injured mucosa.
1. Presence of peritoneal carcinomatosis.
1. Boston Bowel Preparation Scale Results: The principal safety and effectiveness results from the Multicenter clinical trial for the evaluation of safety and effectiveness of ENDORAIL in patients with long-lasting colonoscopy are presented below.

Efficacy Results: all patients enrolled into the clinical study successfully completed the colonoscopy with ENDORAIL and no patient needed to interrupt the diagnostic procedure or to be withdrawn from the study for any reason. More importantly, in all the patients (100%) the endoscopist could reach and fully inspect the last segment of the colon called caecum. In conclusion, the study results have achieved the primary efficacy endpoint, which was to validate the efficacy of ENDORAIL in long-lasting colonoscopies by reaching a colonoscopy incompletion rate ≤ 10%. In fact, the recorded coloscopy incompletion rate over the entire ENDORAIL study was 0%.

Safety Results: this clinical study was also conducted to assess the safety of ENDORAIL in long-lasting colonoscopies. No AE/SAE, no abnormal findings,

26

and no overall change in the health status of any patient undergoing the colonoscopy with ENDORAIL were observed in the course of the clinical study. The study has therefore successfully achieved the primary safety objective, which was to validate the safety of ENDORAIL in long-lasting colonoscopies by demonstrating that colonoscopy SAEs are not increased by using this investigational device (i.e., absence of any device-related SAEs).

Conclusions: The ENDORAIL study was aimed at testing the safety and efficacy of the device in ensuring a low incompletion rate in long-lasting colonoscopies. The multicenter clinical trial for the evaluation of safety and effectiveness of ENDORAIL in patients with long-lasting colonoscopy confirmed that ENDORAIL is safe and effective for its intended use.

IX. Statement of Substantial Equivalence

Based on substantially equivalent intended use, technological characteristics and the safety and performance of non-clinical and clinical testing, the ENDORAIL is deemed to be substantially equivalent to its primary predicate device, the NaviAid BGC (subsequently renamed as "NaviAid ABC") cleared under K111760.

The ENDORAIL, as designed and manufactured, does not raise new questions reqarding safety and effectiveness as compared to its predicate device and is concluded to be substantially equivalent to its predicate device.