(280 days)
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.
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 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 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.
The provided text describes the WallFlex Biliary RX Fully Covered Stent System RMV, its design, nonclinical/bench studies, and a clinical study conducted to assess its safety and effectiveness.
Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria & Reported Device Performance
The acceptance criteria are primarily derived from the "Special Controls" section and the "Summary of Nonclinical Studies" (Table 2). The reported device performance is extracted from the "Summary of Nonclinical/Bench Studies" section and the "Results" section of the clinical study.
| Acceptance Criteria Category | Specific Acceptance Criteria | Reported Device Performance |
|---|---|---|
| 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 10x120mm fully covered stent, considered worst-case. |
| Ethylene Oxide 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, max EO dose of 20 mg in first 24 hr, 60 mg in first 30 days, 2.5 g in a lifetime. For the delivery catheter, the average daily dose shall not exceed 4 mg. | Passed: EtOH residual amounts are below the maximum amount allowed. |
| Biocompatibility | Cytotoxicity: Grade 0 (non-cytotoxic); Irritation: Non-irritant (based on histopathologic evaluations); Sensitization: No signs of sensitization from polar and non-polar extracts; Acute Systemic Toxicity: No evidence of mortality or systemic toxicity; Genotoxicity: Non-mutagenic; Implantation: Non-irritant (based on histopathologic evaluations); Subchronic Toxicity: No signs of systemic toxicity due to leachable components; Nickel leaching: Acceptable resistance to corrosion and acceptable nickel leach rates; Toxicological Risk: Not likely to lead to systemic toxicity. | Passed: Cytotoxicity Grade 0. Irritation non-irritant. No signs of sensitization. No evidence of mortality or systemic toxicity. Non-mutagenic. Non-irritant after implantation. No signs of systemic toxicity. Acceptable nickel leaching demonstrated. Exposure to the stent is not likely to lead to systemic toxicity. |
| Deployment Testing | 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. | Passed: Stent sizes tested represent the smallest and largest sizes available and can be used as surrogates. The stent was successfully placed in 100% (127/127) of patients in the clinical study. |
| Expansion/Compression Force Testing | Radial expansion forces must be at least 85% of specified N values for various stent diameters and compressions. Radial compression forces must be at least 85% of specified N values for various stent diameters and compressions. | Passed: The device met the specified radial expansion and compression forces. |
| Dimensional Testing | All dimensions should be within design tolerance ranges. | Passed: Dimensions of each stent size and delivery catheter were measured and verified to meet the acceptance criteria and labeled dimensions. |
| Tensile Strength Testing (Bond Integrity) | All bonded components of the delivery catheter should withstand forces that exceed those encountered during clinical use. | Passed: Bonded joints of delivery catheters were tested to failure and withstood forces exceeding those encountered clinically. |
| Stent Integrity | No crevice or pitting corrosion; No more than 2 weld breaks; No significant weight loss; Meet specification for radial compression and expansion forces; Wire must meet specification for tensile properties; Stent cover integrity must meet requirements for holes and delamination. | Passed: Stents tested represent worst-case scenario. No degradation observed. |
| MRI Compatibility | MRI compatibility labeling must be supported by testing. Displacement forces should not damage tissue, and localized temperature increases should not damage tissues when patients are scanned as outlined in the labeling. | Evaluated: Mean deflection angle of 3°. Worst case projected temperature rise of 5.5°C for whole body average SAR of 4 W/kg. Artifacts appeared as localized signal voids extending ~10 mm from stent wall perimeter and ~2mm beyond each end. This data supports the MRI Conditional labeling. |
| Shelf Life (Package Integrity) | Packaging must not be compromised below a minimum pressure threshold. No channels, pinholes, or other barrier breaches allowed. All samples must not have channels visible at 10X magnification. | Passed: Package integrity testing demonstrated maintenance of sterility. |
| Shelf Life (Functional Performance) | Deployment Testing: Delivery catheter should safely and reliably deliver the stent to the intended location without damage to the stent or patient after 25 months real time aging. Expansion/Compression Force Testing: Forces must not be impacted by aging. Flexural Rigidity: Stents must not become rigid after aging. Covering Material Integrity: Maximum of 6 diamonds containing compromised coating integrity. Weld Integrity: No more than two broken wire weld joints observed. Tensile Strength: Bonded components withstand forces after aging. | Passed: Deployment testing passed with largest stent size after aging. Expansion/compression forces passed after aging. Flexural rigidity passed after aging. Covering material integrity passed (maximum 6 diamonds with compromised coating). Weld integrity passed (no more than 2 broken welds). Tensile strength testing passed after aging. |
| Clinical Performance (Removal) | The ability to safely place and subsequently remove the stent after the maximum labeled indwell period. | 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 indwell up to 613 days (~20 months). |
| Clinical Performance (Functionality) | The stent resolves strictures during the maximum labeled indwell period. | Stent Functionality During Stent Indwell: 77.2% (98/127) ITT, 83.1% (98/118) PP (lack of required reintervention). Stricture Resolution: 74.0% (94/127) ITT, 79.7% (94/118) PP (lack of stricture-related re-intervention). Biliary obstructive symptoms reduced from 51.2% (baseline) to 6.3% (Indwell month 6). Bilirubin and alkaline phosphatase levels decreased. |
| Clinical Performance (Recurrence) | Stricture resolution is maintained post-stent removal. | No Stricture Recurrence: 85.1% (80/94) ITT/PP patients who initially achieved stricture resolution did not experience recurrence over median 19.0 months follow-up. |
| Clinical Performance (Adverse Events) | All adverse event data including bile duct obstruction and trauma to the bile duct should be reported. | SAEs (patients with at least one SAE): 36.2% (46/127) ITT, 36.4% (43/118) PP. Common SAEs: Pancreatitis (16%), Cholangitis (9%). No stent or stent removal related deaths. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size for Clinical Study (Test Set): 127 patients for the Intent-to-Treat (ITT) cohort, and 118 patients for the Per-Protocol (PP) cohort.
- Data Provenance:
- Country of Origin: The clinical study was a "large prospective multinational study utilizing 13 centers in 11 countries outside of the US (OUS)." Specific countries are not listed, but it indicates a broad international representation.
- Retrospective/Prospective: The clinical study was explicitly prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of those Experts
The document does not specify the number or qualifications of experts establishing ground truth for the clinical study directly. The "ground truth" for clinical outcomes (e.g., stricture resolution, stent removability, adverse events) would have been established by the clinical investigators at the 13 centers based on patient follow-up, medical records, imaging, and endoscopic findings. These would be qualified medical professionals (e.g., gastroenterologists, interventional radiologists) involved in the care of the patients and the conduct of the trial. However, no specific details on their number or specific qualifications (e.g., "radiologist with 10 years of experience") are provided within this document.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (e.g., 2+1, 3+1) for establishing clinical outcomes. Clinical outcomes would likely have been determined based on predefined criteria in the study protocol and assessed by the attending clinicians at each site. Serious adverse events (SAEs) were reported and summarized, indicating a system for tracking and categorizing these events, but not explicitly an independent adjudication panel.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study involving human readers improving with AI vs. without AI assistance was not done. This device is a medical stent, not an AI diagnostic tool, so such a study would not be applicable. The clinical study assessed the device's performance directly in patients.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
No, a standalone (algorithm only) study was not done. This device is a physical medical device (stent system) that requires human intervention (endoscopic placement and removal). Its performance is inherently linked to human use in a clinical setting.
7. Type of Ground Truth Used
The ground truth for the clinical study was based on clinical outcomes data from patients, including:
- Endoscopic findings (stent placement, removability, removal success)
- Patient symptoms (biliary obstructive symptoms)
- Laboratory test results (bilirubin, alkaline phosphatase levels)
- Medical records (re-interventions, recurrence, adverse events, surgical outcomes)
For the non-clinical/bench studies, the ground truth was established through engineering and laboratory test standards, specifications, and physical measurements (e.g., ISO, ASTM standards, pre-defined tolerance ranges, visual inspections, mechanical testing).
8. Sample Size for the Training Set
The document describes a single prospective clinical study acting as the primary evidence for the device's clinical performance. It does not mention a separate "training set" in the context of machine learning or AI models. This is a traditional medical device submission, not an AI/ML device.
9. How the Ground Truth for the Training Set Was Established
As there is no "training set" in the context of an AI/ML model for this traditional medical device, this question is not applicable. The clinical study data was used to demonstrate the device's safety and effectiveness directly, not to train an algorithm.
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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.
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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.
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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 | DeliverySystemWorkingLength(cm) | StentDiameter(mm) | StentLength(mm) |
|---|---|---|---|---|
| M00570340 | WallFlex Biliary Stent RXFully Covered System RMV | 194 | 8 | 60 |
| M00570350 | WallFlex Biliary Stent RXFully Covered System RMV | 194 | 8 | 80 |
| M00570360 | WallFlex Biliary Stent RXFully Covered System RMV | 194 | 10 | 40 |
| M00570370 | WallFlex Biliary Stent RXFully Covered System RMV | 194 | 10 | 60 |
| M00670380 | WallFlex Biliary Stent RXFully 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
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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
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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 anddelivery system that was previously cleared for marketing (K061231). The design and materials of this marketed device are nearlyidentical to those of the subject device, and therefore it is acceptable to adopt the current device into the sterilization process. | ||||||
| Sterilization | Evaluate the sterilitylevel of devicecomponents | ANSI/AAMI/ISO11135:1994: MedicalDevices - Validation andRoutine Control of EthyleneOxide Sterilization; | The sterility assurance level(SAL) shall be 10-6 | Passed: Sterilization was re-assessed in 2015 to ensurecompliance to most recent versionof ANSI/AAMI/ISO 10993-7.Testing was conducted on the 10X 120 mm fully covered stent,which was considered worst-casefor all the covered WallFlexBiliary stents as it has the largestsurface area and greatest amountof silicone covering. | ||
| Ethylene oxidesterilization residuals | Ensure acceptablelevel of ethyleneoxide (EtOH)residuals | ANSI/AAMI/ISO 10993-7:Biological Evaluation ofMedical Devices: EthyleneOxide SterilizationResiduals | EtOH residual amounts are belowthe maximum amount allowed:For the stent, the average dailydose of EO to patient shall notexceed 0.1 mg/day. In addition,the maximum EO dose shall notexceed 20 mg in the first 24 hr; 60mg in the first 30 days; 2.5 g in alifetime. For the delivery catheter,the average daily dose shall notexceed 4 mg. | |||
| Biocompatibility: All testing except that for nickel leaching and the toxicological risk assessment was provided for the WallFlex Biliary RXPartially Covered stent and delivery system that was previously cleared for marketing (K061231). This device is identical to the subjectdevice with the exception that the stent has both covered and uncovered portions. This is acceptable as the surrogate stent represents thematerials found in the current stent design. | ||||||
| Cytotoxicity | Determine if polarand non-polarextract of the stentand deliverycatheter elicit acytotoxic response | ISO 10993-5 BiologicalEvaluation of MedicalDevices: Tests forCytotoxicity: in vitro; MEMElution method | - | Grade 0 (non-cytotoxic) | ||
| Irritation | Determine if polarand non-polarextracts of the stentand deliverycatheter elicit ahypersensitiveresponse | ISO 10993-10: BiologicalEvaluation of MedicalDevices: Tests for Irritationand Sensitization: RabbitIntracutaneous method | - | Based on histopathologicevaluations, the stent withdelivery system is considered anon-irritant | ||
| Sensitization | Determine if polarand non-polarextracts of the stentand deliverycatheter cause ahypersensitiveresponse | ISO 10993-10: BiologicalEvaluation of MedicalDevices: Tests for Irritationand Delayed TypeHypersensitivity: Guinea PigMaximization Sensitizationmethod | - | No signs of sensitization frompolar and non-polar extracts | ||
| Acute SystemicToxicity | Determine if polarand non-polarextracts of the stentcause adverseeffects | ISO 10993-11: BiologicalEvaluation of MedicalDevices: Tests for SystemicToxicity: b(4) | - | No evidence of mortality orsystemic toxicity from testmaterial extracts | ||
| Genotoxicity | Determine if polarand non-polarextracts of stent aremutagenic | ISO 10993-3: BiologicalEvaluation of MedicalDevices: Tests forGenotoxicity,Carcinogenicity, andReproductive Toxicity:Bacterial Mutagenicity(Ames Assay) method | - | The stent is considered non-mutagenic in the Ames Bacterialmutagenicity 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
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| 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 | ||||
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| Expansion/Compression ForceTesting | Excessive radialforce could injurethe surroundingtissue, while a radialforce that is too lowcan result inincompleteapposition of thestent to the lumen.Compression forcetesting characterizesthe ability of thestent to resistcollapse underexternal loads | Expansion and compressionforces were measured forb(4) | The radial expansion forces mustbe at least 85% of b(4) N for 8mm diameter stents compressedto 4 mm.b(4)for 8 mmdiameter stents compressed to 6mm, b(4)for 10 mm diameterstents compressed to 6 mm, andb(4)for 10 mm diameterstents compressed to 8 mm.The radial compression forcesmust be at least 85% of b(4)for 8 mm diameter stentscompressed to 4 mm, b(4)for8 mm diameter stents compressedto 6 mm.b(4)for 10 mmdiameter stents compressed to 6mm, and b(4)for 10 mmdiameter stents compressed to 8mm. | Passed |
|---|---|---|---|---|
| Dimensional Testingb | Accurate stent anddelivery catheterdimensions help thephysician to achieveproper stent sizingand accurateplacement in thebody. They alsoaffect the functionalbehavior of thestent. | Dimensions of each stent sizeand delivery catheter (b(4) 5catheters) were measuredusing an b(4)and verified to meet theacceptance criteria and thatthe device complies with itslabeled dimensions. Stentsalso were measured in theunexpanded and expandedstates to generateforeshortening information. | All dimensions should be withindesign tolerance ranges. | Passed |
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| Tensile StrengthTesting (bondintegrity) | Evaluate if failure ofbonds in thedelivery cathetercould lead to devicefailure and clinicalcomplications | Bonded joints of the deliverycatheters loaded with 0(4)b(4 fully covered stents weretested to failure using atensile tester P(4) | All bonded components of thedelivery catheter should withstandforces that exceed thoseencountered during clinical use. | Pass |
|---|---|---|---|---|
| Stent Integrity | Evaluate if stentcorrosion can causeor contribute topremature stentfailure | Stents were exposed tosimulated bile in anaccelerated fashion toreplicate an aging period ofone year:b(4)b(AS | Stents:No crevice or pittingcorrosionNo more than 2 weld breaksNo significant weight lossMeet specificationrequirements for radialcompression and expansionforcesWire must meet specificationrequirements for tensilepropertiesStent cover integrity must meetrequirements for holes anddelamination | Pass: Stents tested represent theworst-case scenario as they spanthe size range of the stents offeredand are not all fully coveredwhich allows potentially moredegradation to occur. |
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| MRI Compatibility• Displacementforce• RF inducedheating• Artifact testing | Determine thepresence ofmagnetic fieldinteractions,localized tissueheating, and imageartifacts inassociation with theuse of an MRsystem | Testing was conducted inaccordance with ASTMF2052-02: Standard TestMethod for Measurement ofMagnetically InducedDisplacement Force onPassive Implants in theMagnetic ResonanceEnvironment, ASTM F2182-02a: Standard Test Methodfor Measurement of RadioFrequency Induced HeatingNear Passive Implants DuringMagnetic ResonanceImaging, and ASTM F2119-01: Standard Test Method forEvaluation of MR ImageArtifacts from PassiveImplants | MRI compatibility labeling mustbe supported by testing. To beconsidered MRI conditional,displacement forces should nothave the potential to damage thetissue where the device is placedand localized temperatureincreases should not damagetissues when patients are scannedas outlined in the labeling | Evaluated b(4)configurations asworst-case scenarioconfigurationsMean deflection angle of 3°Worst case projected temperaturerise of 5.5°C for a whole bodyaverage specific absorption rate(SAR) of 4 W/kgArtifacts appeared on the MRimages as localized signal voidsthat extend ~10 mm from thestent wall perimeter and ~2 mmbeyond each end of the length ofthe stent |
|---|---|---|---|---|
| Shelf Life: Package integrity testing was conducted for the Wallstent Enteral Stent (K000281). The packaging of the WallstentEnteral Stent is identical to that of the WallFlex Biliary RX Fully Covered Stent System RMV. Functional performance testing tosupport 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 sterilepackaging integrityto ensure that | ISTA 2A Partial SimulationPerformance Tests forPackaged Products weighing | Packaging must not be able to becompromised below a minimumpressure threshold. | Pass |
| devices remainsterile throughoutthe shelf-life | 150 lbs followed by heat sealpeel testing of packaging(Tray/Lid and Pouch) b(4)ISTA 2A Partial SimulationPerformance Tests forPackaged Products weighing150 lbs followed by dyepenetration testing ofpackaging b(4) | No channels, pinholes, or otherbarrier breaches allowedAll samples must not havechannels visible at 10Xmagnification |
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| Deployment Testing• Trackability• Guidewirepassage• Deployment andreconstrainmentforce• Systemwithdrawal | The deliverycatheter shouldsafely and reliablydeliver the stent tothe intendedlocation withoutdamage to the stentor the patient. Thistesting is used tovalidate theaccuracy andrepeatability of thedelivery systemupon 25 month realtime aging | Simulated use in atrackability model consistingof an endoscope workingchannel configured in atortuous path b(4) | The delivery catheter must safelyand accurately deliver the stent tothe intended anatomic location.No damage to the stent orsimulated stricture model shouldoccur. The stent should be able tobe removed with the deliverycatheter if the reconstrainmentpoint has not been exceeded. | Pass: Stent size tested representsthe largest size available. This isacceptable for shelf life testing aswe do not expect stent size toimpact performance after aging. |
|---|---|---|---|---|
| Expansion/Compression ForceTesting | Excessive radialforce could injurethe surroundingtissue, while a radialforce that is too lowcan result inincompleteapposition of thestent to the lumen.Compression forcetesting characterizesthe ability of thestent to resistcollapse underexternal loads upon25 month real timeaging | Expansion and compressionforces were measured forb(4)each) | Expansion and compressionforces must not be impacted byaging | 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)
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- 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 (<1 month to ~20 months). Key outcomes are summarized in Table 3 below for all patients and for the subset of patients with stent indwelling for the intended duration.
| Metric | Intent-to-treatPatients (ITT) | Per ProtocolPatients (PP) | PP Patients withEndoscopic StentRemoval asScheduled |
|---|---|---|---|
| Stent functionalityduring stent indwell | 77.2% (98/127) | 83.1% (98/118) | 100% (95/95) |
| Stent removability | 72.4% (92/127) | 78.0% (92/118) | 96.8% (92/95) |
| Removal success | 84.3% (107/127) | 90.7% (107/118) | 96.8% (92/95) |
| Stricture resolution | 74.0% (94/127) | 79.7% (94/118) | 90.5% (86/95) |
| No stricturerecurrence | 85.1% (80/94) | 85.1% (80/94) | 87.2% (75/86) |
| SAEs (patients withat least one SAE) | 36.2% (46/127) | 36.4% (43/118) | 29.5% (28/95) |
Table 3 - Summarv of Kev Clinical Outcomes
Adverse Events
Serious adverse events (SAEs) that have the potential to be device/procedure related occurred in 27.6% (35/127) of patients during stent placement, indwell, removal or biliary reintervention. SAEs that have the potential to be device/procedure related occurred in 14.2% (18/127) of patients during the post stent removal follow-up period. In total, 36.2% (46/127) ITT patients and 36.4% (43/118) PP patients experienced 86 events as detailed below. There were no stent or stent removal related deaths; however, 7 patients died during the stent indwell period and an additional 3 patients died during the follow-up period due to non-device/procedure related causes. A summary of the potentially device/procedure related SAEs is provided in Tables 4-6.
| SAE Term | Number ofEvents | Patient Incidence |
|---|---|---|
| Biliary leak | 1 | 0.8% (1/127) |
| Gas embolism | 1 | 0.8% (1/127) |
| Abdominal pain | 12 | 5.5% (7/127) |
| Pancreatitis | 14 | 10.2% (13/127) |
| Cholecystitis | 3 | 2.4% (3/127) |
| Chest pain | 1 | 0.8% (1/127) |
| Cholangitis | 12 | 7.1% (9/127) |
| Cholelithiasis | 1 | 0.8% (1/127) |
Table 4 - Stent Placement. Stent Indwell, and Biliary Reintervention SAEs
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| Cholestasis | 2 | 1.6% (2/127) |
|---|---|---|
| Peripancreaticabscess | 1 | 0.8% (1/127) |
| Insufficientpancreatic drainage | 1 | 0.8% (1/127) |
| Hepatic abscess | 2 | 1.6% (2/127) |
| Peripancreaticcyst/pseudocyst | 3 | 2.4% (3/127) |
| Sepsis | 2 | 1.6% (2/127) |
| Bacterial infection | 1 | 0.8% (1/127) |
Table 5 – Stent Removal SAEs
| SAE Term | Number ofEvents | Patient Incidence |
|---|---|---|
| Cholangitis | 3 | 2.4% (3/127) |
| Abdominal pain | 1 | 0.8% (1/127) |
Table 6 – Post Stent Removal Follow-Up SAEs
| SAE Term | Number ofEvents | Patient Incidence |
|---|---|---|
| Biliary leak | 1 | 0.8% (1/127) |
| Abdominal pain | 4 | 3.1% (4/127) |
| Pancreatitis | 10 | 7.1% (9/127) |
| Cholangitis | 8 | 4.7% (6/127) |
| Hepatic abscess | 1 | 0.8% (1/127) |
| Peripancreaticpseudocyst | 1 | 0.8% (1/127) |
LABELING
The labeling comprises physician labeling that includes the device indications for use, a description of the device, warnings and precautions, clinical data on the device, and instructions for the safe and effective use of the device. The labeling satisfies the requirements of 21 CFR 801.109 Prescription devices.
The Instructions for Use address the known hazards and risks of the intended use and incorporate safety statements to mitigate these risks. The labeling includes:
- Safety instructions intended to minimize the risk of improper placement of the stent .
- . A detailed summary of the clinical testing including device effectiveness, and device- and procedure-related adverse events
- Contraindications and warnings to ensure usage of the device for the intended patient . population
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- . A shelf life
- Compatibility information for use in the magnetic resonance environment
RISKS TO HEALTH
Table 7 below identifies the risks to health that may be associated with use of a Metallic Biliary Stent System for Benign Strictures and the measures necessary to mitigate these risks.
| Identified Risk | Mitigation Measure |
|---|---|
| Adverse tissue reaction | Biocompatibility EvaluationLabeling |
| Infection | Sterilization ValidationShelf Life ValidationLabeling |
| Bile duct obstruction● Stent migration● Stent does not resolve obstruction● Stent cannot be placed● Expansion/compression forces● Foreshortening | Clinical Performance TestingNon-clinical Performance TestingShelf Life ValidationLabeling |
| Trauma to bile ducts● During stent deployment● During removal● Due to stent migration● During stent indwell● Inability to safely remove stent● Expansion/compression forces | Clinical Performance TestingNon-clinical Performance TestingShelf Life ValidationLabeling |
Table 7 - Identified Risks to Health and Mitigation Measures
SPECIAL CONTROLS:
In combination with the general controls of the FD&C Act, the Metallic Biliary Stent System for Benign Strictures is subject to the following special controls:
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- Clinical performance testing must demonstrate or provide the following:
- The ability to safely place and subsequently remove the stent after the maximum labeled a. indwell period
- b. All adverse event data including bile duct obstruction and trauma to the bile duct
- c. The stent resolves strictures during the maximum labeled indwell period
- d. Stricture resolution is maintained post-stent removal
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- Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be demonstrated:
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- Corrosion testing to demonstrate that the stent maintains its integrity during indwell and a. does not release potentially toxic levels of leachables
- b. Stent dimensional testing supports the intended use
- c. Compression and expansion forces must be characterized
- d. 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.
- e. The delivery system must withstand clinically anticipated forces.
- Compatibility in a magnetic resonance environment. f.
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- All patient contacting components of the device must be demonstrated to be biocompatible.
-
- Performance data must demonstrate the sterility of the device components intended to be provided sterile.
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- 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.
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- Labeling for the device must include:
- a. A detailed summary of the clinical testing including device effectiveness, and device- and procedure-related adverse events
- b. Appropriate warning(s) to accurately ensure usage of the device for the intended patient population
- c. Shelf life
- d. Compatibility information for use in the magnetic resonance environment
- e. Stent foreshortening information supported by dimensional testing
BENEFIT/RISK DETERMINATION
Summary of Benefits
Among a population of 127 patients with benign biliary strictures (BBS) related to CP, 94 (74%) patients had stricture resolution although 10 patients developed recurrent strictures. Stent removability was successful in 92/118 (78%) patients (PP population). In addition, 98/118 (83%) of the patients did not require reintervention during the intended indwell period or immediate restenting in the event of spontaneous stent passage.
At baseline, 51% of the ITT population patients complained of biliary obstructive symptoms which were right upper quadrant pain, fever, iaundice, itching, dark urine, pale stool, and nausea. This value was reduced to 16% after one month, 9% after 3 months, 6% after 6 months, 8% after 9 months, and 13% at stent removal. The value was maintained at 7% after 3 months post-stent removal, 16% after 6 months post-stent removal, 10% after 12 months post-stent removal, and 6% after 24 months post-stent removal.
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. The bilirubin and alkaline phosphatase levels decreased during the conduct of the study.
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)
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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)
Summary of Risks
There were 57 SAEs among 35 (30%) patients related to stent placement, stent indwell or biliary intervention, 4 SAEs among 4 (3%) patients related to stent removal and 25 SAEs among 18 (14%) patients with post-stent removal follow-up SAEs.
Overall, there were 24 SAEs of pancreatitis among 20 (16%) and 20 SAEs among 12 (9%) of cholangitis.
Additional SAEs included biliary leaks, peripancreatic abscess, hepatic abscess and sepsis.
Study related SAEs are in accordance with those found in the literature. In a recent study of Covered self-expanding metallic stents (CSEMS) for the treatment of benign biliary strictures (BBS) of any etiology, stent migration (9.7%) was the most common complication, followed by stent occlusion (4.9%), cholangitis (4.1%), and pancreatitis (3.3%) (Saxena, Diehl et al. 2015). In another study, 11 serious adverse events occurred in 10 patients (29%), with cholangitis (n = 5) being most common (Walter, Laleman et al. 2015).
Patient Perspectives
This submission did not include specific information on patient perspectives for this device.
Benefit/Risk Conclusion
Given the available information, the data support that when the WallFlex Biliary RX Fully Covered Stent System RMV is used as intended for the population identified in the labeling, the probable benefits outweigh the probable risks. The device provides clinical benefit and the risks can be mitigated by the use of general and the identified special controls.
REFERENCES
Deviere, J., D. Nageshwar Reddy, A. Puspok, T. Ponchon, M. J. Bruno, M. J. Bourke, H. Neuhaus, A. Roy, F. Gonzalez-Huix Llado, A. N. Barkun, P. P. Kortan, C. Navarrete, J. Peetermans, D. Blero, S. Lakhtakia, W. Dolak, V. Lepilliez, J. W. Poley, A. Tringali, G. Costamagna and G. Benign Biliary Stenoses Working (2014). "Successful management of benign biliary strictures with fully covered selfexpanding metal stents." Gastroenterology 147(2): 385-395; quiz e315.
Menon, S. (2013). "Removal of an embedded "covered" biliary stent by the "stent" technique." World J Gastroenterol 19(36): 6108-6109.
Saxena, P., D. L. Diehl, V. Kumbhari, F. Shieh, J. M. Buscaglia, W. Sze, S. Kapoor, S. Komanduri, J. Nasr, E. J. Shin, V. Singh, A. M. Kalloo and M. A. Khashab (2015). "A US Multicenter Study of Safety and Efficacy of Fully Covered Self-Expandable Metallic Stents in Benign Extrahepatic Biliary Strictures." Dig Dis Sci 60(11): 3442-3448.
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Tan, D. M., K. D. Lillemoe and E. L. Fogel (2012). "A new technique for endoscopic removal of uncovered biliary self-expandable metal stents: stent technique with a fully covered biliary stent." Gastrointest Endosc 75(4): 923-925.
Tringali, A., D. Blero, I. Boskoski, P. Familiari, V. Perri, J. Deviere and G. Costamagna (2014). "Difficult removal of fully covered self expandable metal stents (SEMS) for benign biliary strictures: the "SEMS in SEMS" technique." Dig Liver Dis 46(6): 568-571.
Walter. D., W. Laleman, J. M. Jansen, A. W. van Milligen de Wit, B. L. Weusten, P. G. van Boeckel, M. M. Hirdes, F. P. Vleggaar and P. D. Siersema (2015). "A fully covered self-expandable metal stent with antimigration features for benign biliary strictures: a prospective, multicenter cohort study." Gastrointest Endosc 81(5): 1197-1203.
CONCLUSION
The de novo request for the WallFlex Biliary RX Fully Covered Stent System RMV is granted and the device is classified under the following:
Product Code: PNB Device Type: Metallic Biliary Stent System for Benign Strictures Class: Class II Regulation: 21 CFR 876.5011
§ 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.