(280 days)
Not Found
No
The device description focuses on the physical components of the stent and delivery system, and there is no mention of AI, ML, or any software-driven analytical capabilities. The performance studies report clinical outcomes, not algorithmic performance metrics.
Yes.
The device is a biliary stent indicated for the treatment of benign biliary strictures, which means it is used to treat a medical condition.
No
The device is a stent system used for treating benign biliary strictures, which is a therapeutic function, not diagnostic.
No
The device description clearly outlines physical components including a metallic stent and a delivery device, indicating it is a hardware medical device, not software-only.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is for the treatment of benign biliary strictures by indwelling a stent. This is a therapeutic intervention performed in vivo (within the body).
- Device Description: The device is a physical implantable stent and its delivery system. It is designed to mechanically open a stricture.
- Lack of IVD Characteristics: IVD devices are used to examine specimens derived from the human body (like blood, urine, tissue) to provide information for diagnosis, monitoring, or screening. This device does not perform any such analysis of biological samples.
The device is a medical device used for a therapeutic procedure, not an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The WallFlex Biliary RX Fully Covered Stent System RMV is indicated for indwell up to 12 months in the treatment of benign biliary strictures secondary to chronic pancreatitis.
Product codes
PNB
Device Description
The WallFlex Biliary RX Fully Covered Stent System RMV consists of 2 components: the implantable fully covered self-expanding metallic biliary stent (FC-SEMBS) and the Rapid Exchange (RX) delivery device.
The FC-SEMBS is made out of Nitinol monofilament wire with a radiopaque platinum core, braided in a tubular mesh configuration. The stent has proximal and distal flares at each end to aid in preventing migration. The proximal flare also contains the biliary stent retrieval loop. The retrieval loop is used for removal during the initial placement procedure in the event of incorrect placement. The retrieval loop is also used for removal from the bile duct.
The biliary stent is covered with a Permalume™ silicone covering along its entire length except for 2 mm on the retrieval loop end.
The RX delivery device (see Figure 2) is a coaxial tube design. The exterior tube is used to constrain the biliary stent before deployment and re-constrain the biliary stent, if biliary stent repositioning is necessary, after partial deployment. The exterior tube has a clear section so that the constrained stent is visible. A yellow transition zone on the inner tube of the delivery system is visible between the stent and the blue outer sheath. There are four radiopaque (RO) markers to aid in the deployment of the stent while using fluoroscopy.
There are two RO markers on the inner tube of the delivery system identifying the ends of the constrained biliary stent. Between these RO markers is an additional RO marker that indicates at what point re-constrainment is no longer possible. The fourth RO marker at the leading end of the exterior tube indicates how far the biliary stent has been deployed. There is one visual marker on the interior tube between the handles to aid in the deployment of the biliary stent. The visual marker indicates the point at which re-constrainment is no longer possible. The interior tube has a single central lumen to accommodate a 0.035 inch (0.86 mm) guidewire.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Biliary strictures (bile duct)
Indicated Patient Age Range
Age 18 or older
Intended User / Care Setting
Prescription use / Not specified, but procedures involving ERCP are typically done in a hospital or specialized clinic.
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)
A prospective, nonrandomized clinical study (clinicaltrials.gov Identifier: NCT01014390) was conducted to determine the effectiveness and safety of WallFlex Biliary Fully Covered Stent System in the treatment of benign biliary stricture secondary to chronic pancreatitis (CP), post-liver transplant (OLT), and post-abdominal surgery (CCY). Only the CP cohort consisting of 127 subjects was evaluated for the de novo request.
The study was a large prospective multinational study utilizing 13 centers in 11 countries outside of the US (OUS).
Primary Endpoint: Stent removability, defined as ability to remove the stent endoscopically without serious stent removal related adverse events as assessed from the time of stent removal to 1 month post-stent removal. Per-protocol stent removal occurred at 11 ± 1 month for CP patients.
Key Results:
- Stent removability was successful in 72.4% (92/127) ITT patients and 78.0% (92/118) PP patients.
- Removal success was achieved in 84.3% (107/127) ITT patients and 90.7% (107/118) PP patients.
- Stent functionality during stent indwell was obtained in 77.2% (98/127) ITT patients and in 83.1% (98/118) PP patients.
- Stricture resolution without the need for restenting was achieved in 74.0% (94/127) ITT patients and in 79.7% (94/118) PP patients.
- Over a median follow-up period of 19.0 months (range 0.9-29.7 months) after stent removal, 85.1% (80/94) ITT patients and 85.1% (80/94) PP patients with stricture resolution at time of removal did not experience stricture recurrence.
- Bilirubin and alkaline phosphatase levels decreased during the study.
- Biliary obstructive symptoms decreased from 51.2% at baseline to 6.2% at 24 months post-removal.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Stent removability: 72.4% (92/127) ITT, 78.0% (92/118) PP
- Removal success: 84.3% (107/127) ITT, 90.7% (107/118) PP
- Stent functionality during stent indwell: 77.2% (98/127) ITT, 83.1% (98/118) PP
- Stricture resolution: 74.0% (94/127) ITT, 79.7% (94/118) PP
- No stricture recurrence (among those with resolution): 85.1% (80/94) ITT, 85.1% (80/94) PP
- SAEs (patients with at least one SAE): 36.2% (46/127) ITT, 36.4% (43/118) PP
Predicate Device(s)
Not Found
Reference Device(s)
K083627, K061231, K112543, K000281
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 876.5011 Metallic biliary stent system for benign strictures.
(a)
Identification. A metallic biliary stent system for benign strictures is a prescription device intended for the treatment of benign biliary strictures. The biliary stents are intended to be left indwelling for a limited amount of time and subsequently removed. The device consists of a metallic stent and a delivery system intended to place the biliary stent in the bile duct. This device type is not intended for use in the vasculature.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing must demonstrate or provide the following:
(i) The ability to safely place and subsequently remove the stent after the maximum labeled indwell period.
(ii) All adverse event data including bile duct obstruction and trauma to the bile duct.
(iii) The stent resolves strictures during the maximum labeled indwell period.
(iv) Stricture resolution is maintained post-stent removal.
(2) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be demonstrated:
(i) Corrosion testing to demonstrate that the stent maintains its integrity during indwell and does not release potentially toxic levels of leachables.
(ii) Stent dimensional testing supports the intended use.
(iii) Compression and expansion forces must be characterized.
(iv) The delivery catheter must deliver the stent to the intended location and the stent must not be adversely impacted by the delivery catheter during deployment and catheter withdrawal.
(v) The delivery system must withstand clinically anticipated forces.
(vi) Compatibility in a magnetic resonance environment.
(3) All patient contacting components of the device must be demonstrated to be biocompatible.
(4) Performance data must demonstrate the sterility of the device components intended to be provided sterile.
(5) Shelf life testing must demonstrate that the device maintains its performance characteristics and that packaging maintains sterility for the duration of the labeled shelf life.
(6) Labeling for the device must include:
(i) A detailed summary of the clinical testing including device effectiveness, and device- and procedure-related adverse events.
(ii) Appropriate warning(s) to accurately ensure usage of the device for the intended patient population.
(iii) Shelf life.
(iv) Compatibility information for use in the magnetic resonance environment.
(v) Stent foreshortening information supported by dimensional testing.
0
DE NOVO CLASSIFICATION REQUEST FOR WALLFLEX BILIARY RX FULLY COVERED STENT SYSTEM RMV
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Metallic Biliary Stent System for Benign Strictures: A metallic biliary stent system for benign strictures is a prescription device intended for the treatment of benign biliary strictures. The biliary stents are intended to be left indwelling for a limited amount of time and subsequently removed. The device consists of a metallic stent and a delivery system intended to place the biliary stent in the bile duct. This device type is not intended for use in the vasculature.
NEW REGULATION NUMBER: 21 CFR 876.5011
CLASSIFICATION: II
PRODUCT CODE: PNB
BACKGROUND
DEVICE NAME: WallFlex Biliary RX Fully Covered Stent System RMV
SUBMISSION NUMBER: DEN150040
DATE OF DE NOVO: August 28, 2015
- BOSTON SCIENTIFIC CORPORATION CONTACT: 100 BOSTON SCIENTIFIC WAY MARLBOROUGH, MA 01752
REQUESTER'S RECOMMENDED CLASSIFICATION: Class II
INDICATIONS FOR USE
The WallFlex Biliary RX Fully Covered Stent System RMV is indicated for indwell up to 12 months in the treatment of benign biliary strictures secondary to chronic pancreatitis.
LIMITATIONS
The sale, distribution, and use of the device are restricted to prescription use in accordance with 21 CFR §801.109.
1
Contraindications:
- The WallFlex Biliary RX Fully Covered Stent should not be placed in strictures that cannot be dilated enough to pass the delivery system, in a perforated duct, or in very small intrahepatic ducts.
- The WallFlex Biliary RX Fully Covered Stent System RMV should not be used in patients for whom endoscopic techniques are contraindicated.
Warnings:
The safety and effectiveness of the stent has not been established for indwell periods exceeding 12 months.
The WallFlex Biliary RX Fully Covered Stent System RMV is for single-use only.
The safety and effectiveness of the WallFlex Biliary RX Fully Covered Stent System RMV for use in the vascular system has not been established.
The safety and effectiveness of the WallFlex Biliary RX Fully Covered Stent System RMV has not been established in the treatment of benign biliary anastomotic strictures in liver transplant patients and benign biliary post abdominal surgery strictures.
Testing of overlapped stents has not been conducted.
The stent contains nickel, which may cause an allergic reaction in individuals with nickel sensitivity.
PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The WallFlex Biliary RX Fully Covered Stent System RMV consists of 2 components: the implantable fully covered self-expanding metallic biliary stent (FC-SEMBS) and the Rapid Exchange (RX) delivery device.
The FC-SEMBS is made out of Nitinol monofilament wire with a radiopaque platinum core, braided in a tubular mesh configuration. The stent has proximal and distal flares at each end to aid in preventing migration. The proximal flare also contains the biliary stent retrieval loop. The retrieval loop is used for removal during the initial placement procedure in the event of incorrect placement. The retrieval loop is also used for removal from the bile duct. See Figure 1 for a photograph of the FC-SEMBS.
The biliary stent is covered with a Permalume™ silicone covering along its entire length except for 2 mm on the retrieval loop end.
2
Image /page/2/Picture/0 description: The image shows a medical device called an FC SEMS, which stands for Fully Covered Self-Expanding Metal Stent. The device is a cylindrical mesh-like structure with a retrieval loop at one end and proximal and distal flares at either end. The proximal flare is labeled in the image, as is the retrieval loop and distal flare.
Figure 1 - FC-SEMBS
The following models of biliary stent (diameter and length) are part of this system.
| UPN | Description | Delivery
System
Working
Length
(cm) | Stent
Diameter
(mm) | Stent
Length
(mm) |
|-----------|-------------------------------------------------------|-------------------------------------------------|---------------------------|-------------------------|
| M00570340 | WallFlex Biliary Stent RX
Fully Covered System RMV | 194 | 8 | 60 |
| M00570350 | WallFlex Biliary Stent RX
Fully Covered System RMV | 194 | 8 | 80 |
| M00570360 | WallFlex Biliary Stent RX
Fully Covered System RMV | 194 | 10 | 40 |
| M00570370 | WallFlex Biliary Stent RX
Fully Covered System RMV | 194 | 10 | 60 |
| M00670380 | WallFlex Biliary Stent RX
Fully Covered System RMV | 194 | 10 | 80 |
The RX delivery device (see Figure 2) is a coaxial tube design. The exterior tube is used to constrain the biliary stent before deployment and re-constrain the biliary stent, if biliary stent repositioning is necessary, after partial deployment. The exterior tube has a clear section so that the constrained stent is visible. A yellow transition zone on the inner tube of the delivery system is visible between the stent and the blue outer sheath. There are four radiopaque (RO) markers to aid in the deployment of the stent while using fluoroscopy.
There are two RO markers on the inner tube of the delivery system identifying the ends of the constrained biliary stent. Between these RO markers is an additional RO marker that indicates at what point re-constrainment is no longer possible. The fourth RO marker at the leading end of the exterior tube indicates how far the biliary stent has been deployed. There is one visual marker on the interior tube between the handles to aid in the deployment of the biliary stent. The visual marker indicates the point at which re-constrainment is no longer
3
possible. The interior tube has a single central lumen to accommodate a 0.035 inch (0.86 mm) guidewire.
Image /page/3/Picture/1 description: The image shows a medical device with several labeled components. The device includes a distal handle, a visual marker, and a proximal handle. It also features a delivery system tip, multiple radiopaque marker bands labeled #1, #2, #3, and #4, and a yellow inner member jacket.
Figure 2 – RX Delivery Device
A schematic drawing (Figure 3) of the WallFlex Biliary RX Fully Covered Stent System RMV provides additional details for the primary design features.
Image /page/3/Figure/4 description: This image shows a diagram of a medical device, with several components labeled. The device includes a trailing handle, a leading handle, and a stainless steel tube. There are also several marker bands, including a visual marker band, a leading radiopaque marker band #1, a trailing radiopaque marker band #2, a limit marker band #3, and an exterior tube marker band #4. Other components include a stent, a shipping mandrel, an inner tube, an exterior tube, and a tip.
Figure 3 - Schematic of the WallFlex Biliary RX Fully Covered Stent System RMV
4
SUMMARY OF NONCLINICAL/BENCH STUDIES
As noted below in Table 2, the WallFlex Biliary RX Fully Covered Stent System RMV is identical in billiary stent design and delivery system to the WallFlex Biliary RX Covered stent and delivery system that was previously cleared for marketing (K083627) for a different intended use. Notations of non-clinical information that were relied upon and/or leveraged from prior marketing submissions to support the de novo request are summarized in Table 2.
| Test | Purpose | Methods | Acceptance Criteria | Results | ||
|---|---|---|---|---|---|---|
| Sterilization, Cleaning, and Disinfection – Sterilization validation was provided for the WallFlex Biliary RX Partially Covered stent and | ||||||
| delivery system that was previously cleared for marketing (K061231). The design and materials of this marketed device are nearly | ||||||
| identical to those of the subject device, and therefore it is acceptable to adopt the current device into the sterilization process. | ||||||
| Sterilization | Evaluate the sterility | |||||
| level of device | ||||||
| components | ANSI/AAMI/ISO | |||||
| 11135:1994: Medical | ||||||
| Devices - Validation and | ||||||
| Routine Control of Ethylene | ||||||
| Oxide Sterilization; | The sterility assurance level | |||||
| (SAL) shall be 10-6 | Passed: Sterilization was re- | |||||
| assessed in 2015 to ensure | ||||||
| compliance to most recent version | ||||||
| of ANSI/AAMI/ISO 10993-7. | ||||||
| Testing was conducted on the 10 | ||||||
| X 120 mm fully covered stent, | ||||||
| which was considered worst-case | ||||||
| for all the covered WallFlex | ||||||
| Biliary stents as it has the largest | ||||||
| surface area and greatest amount | ||||||
| of silicone covering. | ||||||
| Ethylene oxide | ||||||
| sterilization residuals | Ensure acceptable | |||||
| level of ethylene | ||||||
| oxide (EtOH) | ||||||
| residuals | ANSI/AAMI/ISO 10993-7: | |||||
| Biological Evaluation of | ||||||
| Medical Devices: Ethylene | ||||||
| Oxide Sterilization | ||||||
| Residuals | EtOH residual amounts are below | |||||
| the maximum amount allowed: | ||||||
| For the stent, the average daily | ||||||
| dose of EO to patient shall not | ||||||
| exceed 0.1 mg/day. In addition, | ||||||
| the maximum EO dose shall not | ||||||
| exceed 20 mg in the first 24 hr; 60 | ||||||
| mg in the first 30 days; 2.5 g in a | ||||||
| lifetime. For the delivery catheter, | ||||||
| the average daily dose shall not | ||||||
| exceed 4 mg. | ||||||
| Biocompatibility: All testing except that for nickel leaching and the toxicological risk assessment was provided for the WallFlex Biliary RX | ||||||
| Partially Covered stent and delivery system that was previously cleared for marketing (K061231). This device is identical to the subject | ||||||
| device with the exception that the stent has both covered and uncovered portions. This is acceptable as the surrogate stent represents the | ||||||
| materials found in the current stent design. | ||||||
| Cytotoxicity | Determine if polar | |||||
| and non-polar | ||||||
| extract of the stent | ||||||
| and delivery | ||||||
| catheter elicit a | ||||||
| cytotoxic response | ISO 10993-5 Biological | |||||
| Evaluation of Medical | ||||||
| Devices: Tests for | ||||||
| Cytotoxicity: in vitro; MEM | ||||||
| Elution method | - | Grade 0 (non-cytotoxic) | ||||
| Irritation | Determine if polar | |||||
| and non-polar | ||||||
| extracts of the stent | ||||||
| and delivery | ||||||
| catheter elicit a | ||||||
| hypersensitive | ||||||
| response | ISO 10993-10: Biological | |||||
| Evaluation of Medical | ||||||
| Devices: Tests for Irritation | ||||||
| and Sensitization: Rabbit | ||||||
| Intracutaneous method | - | Based on histopathologic | ||||
| evaluations, the stent with | ||||||
| delivery system is considered a | ||||||
| non-irritant | ||||||
| Sensitization | Determine if polar | |||||
| and non-polar | ||||||
| extracts of the stent | ||||||
| and delivery | ||||||
| catheter cause a | ||||||
| hypersensitive | ||||||
| response | ISO 10993-10: Biological | |||||
| Evaluation of Medical | ||||||
| Devices: Tests for Irritation | ||||||
| and Delayed Type | ||||||
| Hypersensitivity: Guinea Pig | ||||||
| Maximization Sensitization | ||||||
| method | - | No signs of sensitization from | ||||
| polar and non-polar extracts | ||||||
| Acute Systemic | ||||||
| Toxicity | Determine if polar | |||||
| and non-polar | ||||||
| extracts of the stent | ||||||
| cause adverse | ||||||
| effects | ISO 10993-11: Biological | |||||
| Evaluation of Medical | ||||||
| Devices: Tests for Systemic | ||||||
| Toxicity: b(4) | - | No evidence of mortality or | ||||
| systemic toxicity from test | ||||||
| material extracts | ||||||
| Genotoxicity | Determine if polar | |||||
| and non-polar | ||||||
| extracts of stent are | ||||||
| mutagenic | ISO 10993-3: Biological | |||||
| Evaluation of Medical | ||||||
| Devices: Tests for | ||||||
| Genotoxicity, | ||||||
| Carcinogenicity, and | ||||||
| Reproductive Toxicity: | ||||||
| Bacterial Mutagenicity | ||||||
| (Ames Assay) method | - | The stent is considered non- | ||||
| mutagenic in the Ames Bacterial | ||||||
| mutagenicity assay | ||||||
| Implantation | Determine if surgically implanted sections of the stent cause a hypersensitive response | ISO 10993-6: Biological Evaluation of Medical Devices: Tests for Local Effects After Implantation: Rabbit 28-Day Duration Intramuscular Implant method | Based on histopathologic evaluations, the stent with delivery system is considered a non-irritant | |||
| Subchronic Toxicity | Determine if polar and non-polar extracts of the stent cause prolonged exposure adverse effects | ISO 10993-11: Biological Evaluation of Medical Devices: Tests for Systemic Toxicity: b(4) Study method | There were no signs of systemic toxicity due to leachable components | |||
| Nickel leaching | Determine if the stent can leach toxic levels of nickel | ASTM F2129: Standard Test Method for Conducting b(4) the Corrosion Susceptibility of Small Implant Devices | Based on the manufacturing methods, acceptable ASTM F2129 results, the available literature on nickel leaching in similar systems, and considering the stent is coated, there is sufficient evidence that the device will exhibit adequate resistance to corrosion and the nickel leach rates will be acceptable |
Table 2 – Summary of Nonclinical Studies
5
6
7
| Toxicological risk | Determine if polar | A toxicological risk | Exposure to the stent is not likely | |
|---|---|---|---|---|
| assessment | and non-polar | assessment of the fully | to lead to systemic toxicity. | |
| extracts of the stent | covered stent was conducted | |||
| pose a chronic | per ISO 10993-18: Biological | |||
| systemic toxicity | Evaluation of Medical | |||
| risk | Devices: Chemical | |||
| Characterization of Materials, | ||||
| considering the tolerable | ||||
| intake of analytically | ||||
| identified leachables | ||||
| considering ISO 10993-17: | ||||
| Biological Evaluation of | ||||
| Medical Devices: Methods | ||||
| for the Establishment of | ||||
| Allowable Limits for | ||||
| Leachable Substances | ||||
| Beach Testing was provided for the WallFlex Biliary RX Covered stent and delivery system that was previously cleared for | ||||
| marketing (K083627) for a different intended use. This identical to the subject device. This is acceptable as the stent and delivery | ||||
| system are identical between the K083627 submission and this de novo request. MRI compatibility testing to support the current MRI | ||||
| safety labeling was previously reviewed (K112543) for the identical stents. | ||||
| Deployment Testing | The delivery | b(4) | The delivery catheter must safely | Pass: Stent sizes tested represent |
| Stent delivery | catheter should | b(4) | ||
| stents with the | and accurately deliver the stent to | the smallest and largest sizes | ||
| accuracy | safely and reliably | delivery system were | the intended anatomic location. | available. Therefore, they can be |
| Trackability | ||||
| ● | deliver the stent to | evaluated through simulated | No damage to the stent or | used as surrogates to represent the |
| Guidewire | the intended | use in a worst-case scenario | simulated stricture model should | spectrum of available stent sizes. |
| passage | location without | model | occur. | |
| Deployment and | damage to the stent | |||
| reconstrainment | or the patient. This | |||
| force | testing is used to | |||
| validate the | ||||
| accuracy and | ||||
| repeatability of the | ||||
8
| Expansion/
Compression Force
Testing | Excessive radial
force could injure
the surrounding
tissue, while a radial
force that is too low
can result in
incomplete
apposition of the
stent to the lumen.
Compression force
testing characterizes
the ability of the
stent to resist
collapse under
external loads | Expansion and compression
forces were measured for
b(4) | The radial expansion forces must
be at least 85% of b(4) N for 8
mm diameter stents compressed
to 4 mm.b(4)
for 8 mm
diameter stents compressed to 6
mm, b(4)
for 10 mm diameter
stents compressed to 6 mm, and
b(4)
for 10 mm diameter
stents compressed to 8 mm.
The radial compression forces
must be at least 85% of b(4)
for 8 mm diameter stents
compressed to 4 mm, b(4)
for
8 mm diameter stents compressed
to 6 mm.b(4)
for 10 mm
diameter stents compressed to 6
mm, and b(4)
for 10 mm
diameter stents compressed to 8
mm. | Passed |
|--------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------|
| Dimensional Testing
b | Accurate stent and
delivery catheter
dimensions help the
physician to achieve
proper stent sizing
and accurate
placement in the
body. They also
affect the functional
behavior of the
stent. | Dimensions of each stent size
and delivery catheter (b(4) 5
catheters) were measured
using an b(4)
and verified to meet the
acceptance criteria and that
the device complies with its
labeled dimensions. Stents
also were measured in the
unexpanded and expanded
states to generate
foreshortening information. | All dimensions should be within
design tolerance ranges. | Passed |
9
| Tensile Strength
Testing (bond
integrity) | Evaluate if failure of
bonds in the
delivery catheter
could lead to device
failure and clinical
complications | Bonded joints of the delivery
catheters loaded with 0(4)
b(4 fully covered stents were
tested to failure using a
tensile tester P(4) | All bonded components of the
delivery catheter should withstand
forces that exceed those
encountered during clinical use. | Pass |
|-------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Stent Integrity | Evaluate if stent
corrosion can cause
or contribute to
premature stent
failure | Stents were exposed to
simulated bile in an
accelerated fashion to
replicate an aging period of
one year:
b(4)
b(
AS | Stents:
No crevice or pitting
corrosion
No more than 2 weld breaks
No significant weight loss
Meet specification
requirements for radial
compression and expansion
forces
Wire must meet specification
requirements for tensile
properties
Stent cover integrity must meet
requirements for holes and
delamination | Pass: Stents tested represent the
worst-case scenario as they span
the size range of the stents offered
and are not all fully covered
which allows potentially more
degradation to occur. |
10
| MRI Compatibility
• Displacement
force
• RF induced
heating
• Artifact testing | Determine the
presence of
magnetic field
interactions,
localized tissue
heating, and image
artifacts in
association with the
use of an MR
system | Testing was conducted in
accordance with ASTM
F2052-02: Standard Test
Method for Measurement of
Magnetically Induced
Displacement Force on
Passive Implants in the
Magnetic Resonance
Environment, ASTM F2182-
02a: Standard Test Method
for Measurement of Radio
Frequency Induced Heating
Near Passive Implants During
Magnetic Resonance
Imaging, and ASTM F2119-
01: Standard Test Method for
Evaluation of MR Image
Artifacts from Passive
Implants | MRI compatibility labeling must
be supported by testing. To be
considered MRI conditional,
displacement forces should not
have the potential to damage the
tissue where the device is placed
and localized temperature
increases should not damage
tissues when patients are scanned
as outlined in the labeling | Evaluated b(4)
configurations as
worst-case scenario
configurations
Mean deflection angle of 3°
Worst case projected temperature
rise of 5.5°C for a whole body
average specific absorption rate
(SAR) of 4 W/kg
Artifacts appeared on the MR
images as localized signal voids
that extend ~10 mm from the
stent wall perimeter and ~2 mm
beyond each end of the length of
the stent |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Shelf Life: Package integrity testing was conducted for the Wallstent Enteral Stent (K000281). The packaging of the Wallstent
Enteral Stent is identical to that of the WallFlex Biliary RX Fully Covered Stent System RMV. Functional performance testing to
support a 2 year shelf life was conducted on the subject device of this de novo. | | | | |
| Package integrity
• heat seal peel test
• dye penetration | Evaluate the sterile
packaging integrity
to ensure that | ISTA 2A Partial Simulation
Performance Tests for
Packaged Products weighing | Packaging must not be able to be
compromised below a minimum
pressure threshold. | Pass |
| | devices remain
sterile throughout
the shelf-life | 150 lbs followed by heat seal
peel testing of packaging
(Tray/Lid and Pouch) b(4)
ISTA 2A Partial Simulation
Performance Tests for
Packaged Products weighing
150 lbs followed by dye
penetration testing of
packaging b(4) | No channels, pinholes, or other
barrier breaches allowed
All samples must not have
channels visible at 10X
magnification | |
11
| Deployment Testing
• Trackability
• Guidewire
passage
• Deployment and
reconstrainment
force
• System
withdrawal | The delivery
catheter should
safely and reliably
deliver the stent to
the intended
location without
damage to the stent
or the patient. This
testing is used to
validate the
accuracy and
repeatability of the
delivery system
upon 25 month real
time aging | Simulated use in a
trackability model consisting
of an endoscope working
channel configured in a
tortuous path b(4) | The delivery catheter must safely
and accurately deliver the stent to
the intended anatomic location.
No damage to the stent or
simulated stricture model should
occur. The stent should be able to
be removed with the delivery
catheter if the reconstrainment
point has not been exceeded. | Pass: Stent size tested represents
the largest size available. This is
acceptable for shelf life testing as
we do not expect stent size to
impact performance after aging. |
|------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Expansion/
Compression Force
Testing | Excessive radial
force could injure
the surrounding
tissue, while a radial
force that is too low
can result in
incomplete
apposition of the
stent to the lumen.
Compression force
testing characterizes
the ability of the
stent to resist
collapse under
external loads upon
25 month real time
aging | Expansion and compression
forces were measured for
b(4)
each) | Expansion and compression
forces must not be impacted by
aging | Passed |
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| Flexural Rigidity | Evaluate rigidity of stents to ensure stent integrity upon 25 month real time aging | Flexural rigidity b(4) | Stents must not become rigid after aging | Pass |
|---|---|---|---|---|
| Covering Material Integrity | Evaluate covering material for compromised surfaces upon 25 month real time aging | Covering b(4) were evaluated with the unaided eye after deploying and reconstraining the stent b(4) | Maximum of 6 diamonds (openings in the stent mesh) containing compromised coating integrity | Pass |
| Weld Integrity | Evaluate integrity of stent welded wires upon 25 month real time aging | Examined b(4) r broken wire weld joints after stent is deployed and reconstrained b(4) | No more than two broken wire weld joints observed | Pass |
| Tensile Strength Testing (bond integrity) | Evaluate if failure of delivery catheter could lead to device failure and clinical complications upon 25 month real time aging | Bonded joints were tested to failure using a tensile tester for delivery catheters with the b(4) | All bonded components of the delivery catheter should withstand forces that exceed those encountered during clinical use after aging. | Pass |
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SUMMARY OF CLINICAL INFORMATION
A prospective, nonrandomized clinical study (clinicaltrials.gov Identifier: NCT01014390) was conducted to determine the effectiveness and safety of WallFlex Biliary Fully Covered Stent System in the treatment of benign biliary stricture secondary to chronic pancreatitis (CP), post-liver transplant (OLT), and post-abdominal surgery (CCY).
Only the CP cohort consisting of 127 subjects was evaluated for the de novo request. Neither the de novo request nor the labeling include indications for the OLT and CCY patient populations with the exception of a Warning included within the labeling that states the following:
Warning: The safety and effectiveness of the WallFlex Biliary RX Fully Covered Stent System RMV has not been established in the treatment of benign biliary anastomotic strictures in liver transplant patients and benign biliary post abdominal surgery strictures.
Objective of the study
To assess the safety and performance of temporary placement of the WallFlex Biliary RX Fully Covered Stent as a treatment of biliary obstruction resulting from benign bile duct strictures.
Methods
The study was a large prospective multinational study utilizing 13 centers in 11 countries outside of the US (OUS). The results of this study were published in the journal Gastroenterology (Deviere, Nageshwar Reddy et al. 2014).
Primary Endpoint:
Stent removability, defined as ability to remove the stent endoscopically without serious stent removal related adverse events as assessed from the time of stent removal to 1 month post-stent removal. Per-protocol stent removal occurred at 11 ± 1 month for CP patients.
Secondary Endpoints:
-
- Stricture resolution during stent indwell, defined by lack of stent-related re-interventions
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- Stricture resolution after stent removal, defined by lack of stricture related re-intervention
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- Occurrence and severity of adverse events related to the stent and/or the procedure
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- Ability to deploy the stent in satisfactory position across the stricture (technical success at placement)
-
- Length of stent placement procedure, length of stent removal procedure and methods of removal (to include video recording if available)
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- Biliary obstructive symptom assessment at all visits
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- Liver Function Tests (LFT's) at baseline, at month 1 post-stent placement, at stent removal and at months 6, 12 and 24 post-stent removal
Inclusion Criteria:
- Age 18 or older .
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- . Willing and able to comply with the study procedures and provide written informed consent to participate in the study
- . Chronic pancreatitis or prior liver transplantation or prior other abdominal surgery (to include cholecystectomy )
- Indicated for endoscopic retrograde cholangiopancreatography (ERCP) procedure with stent ● placement for:
- . Symptomatic bile duct stricture (i.e. obstructive jaundice, persistent cholestasis, acute cholangitis) confirmed by cholangiogram and/or
- Bile duct stricture confirmed by cholangiogram and/or
- . Exchange of prior plastic stent(s) for management of benign stricture
Exclusion Criteria:
- . General:
- Placement of the stent in strictures that cannot be dilated enough to pass the delivery . system
- I Placement of the stent in a perforated duct
- Placement of the stent in very small intrahepatic ducts l
- 트 Patients for whom endoscopic techniques are contraindicated
- I Biliary stricture of malignant etiology
- I Biliary stricture of benign etiology other than chronic pancreatitis or liver transplant anastomosis or other abdominal surgery
- I Stricture within 2 cm of duct bifurcation
- I Symptomatic duodenal stenosis (with gastric stasis)
- 트 Prior biliary self-expanding metal stent
- I Suspected stricture ischemia based on imaging of hepatic artery occlusion or endoscopic evidence of biliary cast syndrome
- 트 Known bile duct fistula
- 트 Known sensitivity to any components of the stent or delivery system
- . Participation in another investigational study within 90 days prior to consent or during the study
- Additional Exclusion Criteria Specific to Chronic Pancreatitis Patients: ●
- . Developing obstructive biliary symptoms associated with an attack of acute pancreatitis
- · Additional Exclusion Criteria Specific to Post-Abdominal Surgery Patients:
- History of hepatectomy
- . History of liver transplant
- · Additional Exclusion Criteria Specific to Liver Transplant Patients:
- Live donor transplantation
Results
Chronic Pancreatitis Study Cohort Information
Patients:
One hundred and twenty-seven (127) patients with a benign biliary stricture secondary to chronic pancreatitis with either ongoing biliary obstructive symptoms or being managed for biliary obstructive symptoms were enrolled.
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Demographics:
The mean age was 52.5 years (sd 10.3 years) and 104 (82%) of the 127 enrolled were male. The median time since CP diagnosis was 28 months. At baseline median total bilirubin level was 0.6 mg/dl (range 0.1-22.0 mg/dl) and median alkaline phosphatase level was 201 IU/1 (range 27-2371 IU/I).
The benign biliary stricture location was mostly distal, notably 115 (90.6%) were in the distal common bile duct (CBD), 2 (1.6%) in the mid CBD, 8 (6.3%) in the proximal CBD, and 2 (1.6%) were papillary. The majority of patients had received a prior sphincterotomy (124; 97.6%) and had previously received endotherapy using plastic biliary stents (105; 82.7%). The gallbladder was in situ in 101 (79.5%) of patients.
Patient Disposition:
The intent-to-treat (ITT) patient cohort includes all 127 enrolled patients. The per-protocol (PP) patient cohort has 118 patients. Nine (9) patients were excluded from the PP cohort due to death due to unrelated causes (7), transition to palliative care in setting of pancreatic cancer (1) and withdrawal of consent (1).
Stent removability, stricture resolution and rates of SAEs were assessed for the ITT cohort (127) and PP cohort (118).
Stricture recurrence after stent removal or complete distal migration was assessed on 94 patients who reached stricture resolution.
Clinical indwell performance and removal success were assessed as post-hoc analyses in the ITT and PP cohorts.
Stent Placement:
Five WallFlex stent sizes (diameter x length) were available and stent selection was as follows: 8 x 60 mm (4; 3.1%), 8 x 80 mm (0; 0%), 10 x 40 mm (78; 61.4%), 10 x 60 mm (43; 33.9%), and 10 x 80 mm (2; 1.6%). The stent was successfully placed in 100% (127/127) of patients. Mean procedure duration was 26.6 min (sd 21.0 min).
Stent Migration
Stent migration in the course of the study was reported in 19 of 127 patients. The migration was proximal - in the direction of the liver - in 7 cases (37%), was partial distal - in the direction of the duodenum but still inside of the common bile duct - in 7 cases (37%), and was complete distal - completely out of the common bile duct - in 5 cases (26%). The 19 migrations were observed a median of 318 days (range 60-1140 days) after stent placement.
Stent Removability
Stent removability is defined as the ability to remove the stent endoscopically without serious stent removal related adverse events as assessed from the time of stent removal to one (1) month post-stent removal. Stent removability was successful in 72.4% (92/127) ITT patients and 78.0% (92/118) PP patients. A summary of the subjects classified as failures is given below:
- . Seven (7) deaths due to unrelated causes (ITT only)
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- One (1) transition to palliative care in setting of pancreatic cancer (ITT only)
- One (1) withdrew consent (ITT only)
- Thirteen (13) early endoscopic removal ●
- Four (4) loss to follow-up
- One (1) surgery for progression of CP
- Three (3) stent removal related SAEs
- Three (3) spontaneous stent migration without restenting
- Two (2) spontaneous stent passage with immediate restenting ●
Removal Success
Removal success is defined as either scheduled endoscopic stent removal with no removalrelated serious adverse events (SAEs), or spontaneous stent passage without the need for immediate restenting. Removal success was achieved in 84.3% (107/127) ITT patients and 90.7% (107/118) PP patients after stent indwell ranging from 8 to 613 days. Forceps/graspers and/or a snare were used in all but one case in which a stent-in-stent technique was used for endoscopic removal of the WallFlex stents.
A summary of the subjects classified as failures is given below:
- Four (4) patients experienced removal-related serious adverse events including three (3) . cases of cholangitis and one (1) case of abdominal pain.
- Stent removal was not indicated in nine patients (9) due to death (7), transition to palliative care in setting of pancreatic cancer (1) and withdrawal of consent (1) (ITT only).
- . Attempts were not made in five (5) patients due to loss to follow up (4) and surgery for CP progression (1).
- . Two (2) patients experienced complete distal stent migration that required immediate restenting.
NOTE: Stent-in-Stent removal as a technique for removal of biliary self-expanding metal stents was described in peer-reviewed publications (Tan, Lillemoe et al. 2012, Menon 2013, Tringali, Blero et al. 2014). In total, the three references report on 7 cases. The authors concluded that the stent-in-stent technique is effective when difficulties are encountered during self-expanding metal stent removal due to stent migration or hyperplastic stent ingrowth or overgrowth.
Stent Functionalitv During Stent Indwell
Stent functionality during stent indwell is defined as lack of required reintervention during intended indwell or spontaneous stent passage without the need for immediate restenting within 6 days. Stent functionality during stent indwell was obtained in 77.2% (98/127) ITT patients and in 83.1% (98/118) PP patients.
A summary of the subjects classified as failures is given below:
- Seven (7) deaths due to unrelated causes (ITT only) ●
- One (1) transition to palliative care in setting of pancreatic cancer (ITT only) .
- One (1) withdrew consent (ITT only) ●
- . Thirteen (13) early endoscopic removal
- Four (4) loss to follow-up ●
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- . Two (2) spontaneous stent passage with immediate restenting
- One (1) surgery for progression of CP .
Stricture Resolution
Stricture resolution is defined by the lack of stricture-related re-intervention. At the end of indwell, stricture resolution without the need for restenting was achieved in 74.0% (94/127) ITT patients and in 79.7% (94/118) PP patients.
A summary of the subjects classified as failures is given below:
- . Nine (9) not indicated for removal due to death (7), transition to palliative care in setting of pancreatic cancer (1) and withdrawal of consent (1) (ITT only)
- Nine (9) immediate restenting after scheduled removal ●
- Eight (8) immediate restenting after early removal ●
- Four (4) loss to follow-up ●
- Two (2) spontaneous stent passage with immediate restenting ●
- One (1) surgery for progression of CP ●
Stricture Recurrence
Stricture recurrence is defined by the need for stricture related re-intervention post-stent removal. Over a median follow-up period of 19.0 months (range 0.9-29.7 months) after stent removal, 85.1% (80/94) ITT patients and 85.1% (80/94) PP patients with stricture resolution at time of removal did not experience stricture recurrence.
A summary of the subjects classified as failures is given below:
- Ten (10) patients had strictures re-occur ●
- . Four (4) patients were lost to follow-up
Liver Function Tests
Bilirubin levels and alkaline phosphate levels were measured at visits from baseline to 24 months post-removal. Reported are the mean ± standard deviation (number of patients) bilirubin level in mg/dL and alkaline phosphatase level in U/L.
Bilirubin: Baseline: 1.6 ± 3.1 (126), Indwell month 1: 0.6 ± 0.4 (109), Stent removal: 0.8 ± 1.3 (106), Post-removal month 6: 0.8 ± 1.2 (66), Post-removal month 12: 0.6 ± 0.3 (57), Postremoval month 24: 1.0 ± 2.1 (24)
Alkaline phosphatase: Baseline: 332 ± 363 (125), Indwell month 1: 166 ± 130 (113), Stent removal: 166 ± 198 (105), Post-removal month 6: 142 ± 151 (67), Post-removal month 12: 127 ± 139 (59), Post-removal month 24: 136 ± 115 (25)
Biliary Obstructive Symptoms
Biliary obstructive symptoms were right upper quadrant pain, fever, jaundice, itching, dark urine, pale stool, and nausea. The number of patients with any symptom was normalized by the number of patients for which visit data were available.
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Baseline: 51.2% (65/127), Indwell month 1: 16.3% (20/123), Indwell month 3: 8.6% (10/116), Indwell month 6: 6.3% (7/112), Indwell month 9: 7.8% (8/102), Stent removal: 12.8% (14/109), Post-removal month 3: 7.0% (6/86), Post-removal month 6: 16.1% (14/87), Post-removal month 12: 9.7% (7/72), Post-removal month 24: 6.2% (2/33)
Summary of Clinical Findings
Stent removability was possible after stent indwell ranging from 8 to 613 days (