(380 days)
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Not Found
No
The device description and performance studies focus on mechanical, electronic, and software functionality for controlled CO2 release. There is no mention of AI, ML, or related concepts like image processing, training data, or complex algorithms for decision-making or pattern recognition. The software is described as having a 'MAJOR level of concern', which is typical for medical device software, but doesn't inherently indicate AI/ML.
Yes
The device aids in breast reconstruction and treatment of soft tissue deformities following mastectomy, which are therapeutic interventions.
No
Explanation: The device is a tissue expander used for breast reconstruction and soft tissue deformities, which is a therapeutic rather than a diagnostic purpose.
No
The device description clearly states the system is comprised of a sterile implant (AeroForm Tissue Expander) and a hand-held battery-powered device (Dosage Controller), in addition to the Physician Master Key. While software is mentioned as a component of the system with a 'MAJOR level of concern', the system includes significant hardware components.
Based on the provided information, this device is not an In Vitro Diagnostic (IVD).
Here's why:
- Intended Use: The intended use is for soft tissue expansion in breast reconstruction and treatment of breast deformities. This is a surgical/implantable device used directly on the patient's body.
- Device Description: The device is an implantable tissue expander that uses compressed CO2 to expand tissue. It interacts physically with the patient's body.
- Lack of In Vitro Activity: IVDs are used to examine specimens (like blood, urine, tissue samples) outside of the body to provide information about a person's health. This device does not perform any such analysis of biological samples.
- Performance Studies: The performance studies focus on the device's physical performance, biocompatibility, and clinical outcomes related to tissue expansion and reconstruction, not on diagnostic accuracy based on analyzing biological samples.
Therefore, the AeroForm Tissue Expander System is a medical device, but it falls under a different regulatory category than In Vitro Diagnostics.
N/A
Intended Use / Indications for Use
The AeroForm Tissue Expander System is used for soft tissue expansion in breast reconstruction following mastectomy, for the treatment of underdeveloped breasts, and for the treatment of soft tissue deformities in the breast.
The AeroForm Expander is intended for temporary subcutaneous or submuscular implantation and is not intended for use beyond six months.
Product codes
PQN
Device Description
The AeroForm® Tissue Expander System is comprised of the AeroForm Tissue Expander, the Dosage Controller, and the Physician Master Key.
AeroForm Tissue Expander: a sterile implant with an outer textured silicone shell and a non-distensible inner bag which are anatomically shaped to allow for directional expansion in the lower, anterior pole. It contains a reservoir of compressed carbon dioxide (CO2), which is released within the expander by using the Dosage Controller. The outer shell has suture tabs. A receiving antenna and electronics within the expander enable communication with the Dosage Controller. It has no intrinsic electrical power, batteries, or software, and can only be activated by the Dosage Controller. There are 3 different sizes: small (400cc), medium (600cc), and large (850cc).
Dosage Controller: a small, handheld, battery-powered, non-sterile device. It activates the AeroForm Tissue Expander to release the programmed amount of CO2 gas (10cc). It is configured to provide coded instructions to its bonded AeroForm Tissue Expander. It has a single push button and a bank of indicator lights (LEDs) and tones. Each dose administers 10cc of CO2. There is a patient dosing limit of 3 (10cc) doses per day and a 3-hour time period between doses.
Physician Master Key: used only by the physician in the operating room or in the physician office. With the Physician Master Key inserted into the Dosage Controller receptacle, the Dosage Controller can activate the Expander with no daily limit on the expansion volume. It allows the physician to inflate the Expander intra-operatively, add volume to the Expander at office visits, and add up to 25% of the labeled volume every 2 weeks. It is retained by the physician and not provided to the patient, overriding patient limits.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
breast tissue
Indicated Patient Age Range
18-70 years old
Intended User / Care Setting
Physician / operating room, physician office; Patient / home
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Animal Study:
Study Type: Sheep implant study
Sample Size: 12 implants in two male ovine subjects (each animal had 6 expanders placed)
Key Results: All twelve tissue expanders responded to and communicated with their corresponding dosage controllers throughout the expansion period. No adverse events were observed. The study showed that the device could be safely and effectively used in vivo.
Clinical Studies (Report of Prior Investigations):
-
PACE study (two-phase single center, prospective, open-label clinical study) conducted in Perth, Australia.
Sample Size: 40 subjects, 71 AeroForm Tissue Expanders implanted (7 subjects with 10 version 1.0 (V1.0) expanders in PACE 1; 33 subjects with 61 V2.0 expanders in PACE 2).
Key Results: All devices expanded as intended and 100% of the expanders were successfully exchanged to a permanent implant. Verified device performance and safety for breast tissue expansion for two-stage breast reconstruction. -
Second clinical study in Australia.
Sample Size: 21 subjects, 34 AeroForm Expanders.
Key Results: Overall success rate was 94%, with no device-related reconstruction failures.
Pivotal Study (XPAND trial - CPT-0003):
Study Type: prospective, multi-center, randomized, controlled, open-label, study comparing AeroForm to saline tissue expanders.
Sample Size: 158 subjects enrolled (106 randomized to investigational arm (AeroForm), 52 to control arm (Saline)). 151 patients were evaluated (99 AeroForm patients, 52 saline patients). (Subjects who received AeroForm device: 98, with 54 patients receiving V2.0 and 44 patients receiving V2.5. Total 168 breasts: 90 breasts received V2.0 and 78 breasts received V2.5).
Key Results:
- Primary Endpoint (Treatment Success Rate per breast, excluding non-device related failures): AeroForm was 96.1% (149/155). Saline was 98.8% (82/83). The difference (AeroForm - Saline) was -2.7% with a lower confidence limit of -7.3%, meeting the non-inferiority margin of > -10%.
- Secondary Effectiveness Endpoints:
- Median days to complete expansion: 21.0 days for AeroForm vs. 46.0 days for saline.
- Median days to complete breast reconstruction: 108.5 days for AeroForm vs. 136.5 days for saline.
- Pain assessment: No difference in reported pain intensity (Start of Expansion: 2.2 AeroForm, 1.9 saline; Worst Pain: 4.5 AeroForm, 4.6 saline).
- Overall subject satisfaction: 78% with AeroForm, 91% with Saline. For V2.5 only, 84% were mildly, moderately, or very satisfied.
- Overall physician satisfaction: 68% with AeroForm, 92% with Saline. For V2.5 only, 83% satisfied. (Lower satisfaction with V2.0 due to device malfunctions and gradual volume loss).
- Safety Endpoints (Adverse Events):
- Subjects with any adverse event: 63.3% for AeroForm, 63.5% for Saline.
- Subjects with any device-related adverse event: 21.2% for AeroForm, 19.2% for Saline.
- Subjects with any procedure-related adverse event: 46.5% for AeroForm, 46.2% for Saline.
- Proportion of subjects with AEs was similar between groups.
- Breast related adverse events (AEs): 53.5% in AeroForm arm, 44.2% in Saline arm.
- Device Malfunctions:
- Communication failures: 9 (5.4%) AeroForm expanders (all V2.0).
- Failure to reach or maintain volume / deflation: 42 (46.7%) V2.0 devices; reduced to 12 (15.4%) with V2.5.
- Over-expansion: 5 devices (4 V2.0, 1 V2.5).
Continued Access Study (XPAND II CAS):
Study Type: prospective, multi-center, single arm study of the V2.5 device.
Sample Size: 28 subjects (49 breasts) enrolled as of June 8, 2016. 11 subjects (21 breasts) completed final study visit.
Key Results:
- Primary Endpoint (Treatment Success): 100% (n=18 breasts where complete data available and 2 patients with 3 expanders were removed for non-device related reasons).
- Secondary Endpoints (pain and satisfaction):
- Pain: Average pain reported as 1.8 (start of expansion), 2.3 (first visit after start of expansion).
- Subject satisfaction: 89% (8/9) subjects satisfied.
- Physician satisfaction: 90% (9/10) physicians satisfied with device performance, 80% (8/10) physicians satisfied with expansion results.
- Safety: 5 breast-related adverse events reported. One instance of loss of volume successfully managed with office dosing. No new failure modes identified, no over-expansion or sudden deflations.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Primary Endpoint (Treatment Success Rate per breast, excluding non-device related failures):
- AeroForm: 96.1% (149/155)
- Saline: 98.8% (82/83)
- Difference (AeroForm - Saline): -2.7%
- Lower confidence limit: -7.3%
- Meets non-inferiority margin of > -10%.
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
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Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 878.3510 Carbon dioxide gas controlled tissue expander.
(a)
Identification. A carbon dioxide gas controlled tissue expander is a prescription device intended for temporary subcutaneous or submuscular implantation to stretch the skin for surgical applications, specifically to develop surgical flaps and additional tissue coverage. The device is made of an inflatable elastomer shell and is filled with carbon dioxide gas. The device utilizes a remote controller to administer doses of carbon dioxide gas from an implanted canister inside the device.(b)
Classification. Class II (special controls). The special controls for this device are:(1) In-vivo performance testing must be conducted to obtain the adverse event profile associated with use, and demonstrate that the device performs as intended under anticipated conditions of use.
(2) The patient-contacting components of the device must be demonstrated to be biocompatible.
(3) Performance data must demonstrate the sterility of patient-contacting components of the device.
(4) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Cycle testing of expander showing that there are no leaks or tears after repeated cycling;
(ii) Mechanical assessment of implanted carbon dioxide (CO
2 ) canister including high impact testing;(iii) Leak testing of expander showing that device does not leak CO
2 ;(iv) Assessment of gas permeability during expansion and after full expansion; and
(v) Mechanical assessment of expander (tensile set, breaking force, shell joint test, and fused or adhered joint testing).
(5) Performance data must be provided to demonstrate the electromagnetic compatibility, electrical safety, and wireless compatibility of the device.
(6) Software verification, validation, and hazard analysis must be performed.
(7) Performance data must support shelf life by demonstrating continued sterility of the device or the sterile components, package integrity, and device functionality over the identified shelf life.
(8) Human factors testing and analysis must validate that the device design and labeling are sufficient for the end user.
(9) Physician labeling must include:
(i) The operating parameters, name, and model number of the indicated external dosage controller;
(ii) Information on how the device operates and the typical course of treatment;
(iii) Information on the population for which the device has been demonstrated to be effective;
(iv) A detailed summary of the device technical parameters; and
(v) Provisions for choosing an appropriate size implant that would be exchanged for the tissue expander.
(10) Patient labeling must include:
(i) Warnings, precautions, and contraindications, and adverse events/complications;
(ii) Information on how the device operates and the typical course of treatment;
(iii) The probable risks and benefits associated with the use of the device;
(iv) Post-operative care instructions; and
(v) Alternative treatments.
(11) Patient training must include instructions for device use, when it may be necessary to contact a physician, and cautionary measures to take when the device is implanted.
0
DE NOVO CLASSIFICATION REQUEST FOR AEROFORM® TISSUE EXPANDER SYSTEM
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Carbon dioxide gas controlled tissue expander. A carbon dioxide gas controlled tissue expander is a prescription device intended for temporary subcutaneous or submuscular implantation to stretch the skin for surgical applications, specifically to develop surgical flaps and additional tissue coverage. The device is made of an inflatable elastomer shell and is filled with carbon dioxide gas. The device utilizes a remote controller to administer doses of carbon dioxide gas from an implanted canister inside the device.
NEW REGULATION NUMBER: 21 CFR 878.3510
CLASSIFICATION: CLASS II
PRODUCT CODE: PQN
BACKGROUND
DEVICE NAME: AeroForm® Tissue Expander System
SUBMISSION NUMBER: DEN150055
DATE OF DE NOVO: December 8, 2015
CONTACT: AirXpanders, Inc. 1047 Elwell Court Palo Alto, CA 94303
INDICATIONS FOR USE
The AeroForm Tissue Expander System is used for soft tissue expansion in breast reconstruction following mastectomy, for the treatment of underdeveloped breasts, and for the treatment of soft tissue deformities in the breast.
The AeroForm Expander is intended for temporary subcutaneous or submuscular implantation and is not intended for use beyond six months.
LIMITATIONS
Prescription use only: Federal (USA) law restricts this device to sale by or on the order of a physician.
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Limitations on device use are also achieved through the following statements included in the instructions for use:
Contraindications:
The AeroForm Tissue Expander System MUST NOT be used when:
- · Magnetic Resonance Imaging (MRI) is required with the AeroForm Tissue Expander implanted. The AeroForm Tissue Expander is MR Unsafe. MRI equipment can cause movement of the expander and result in patient injury or expander displacement, requiring revision surgery.
- · Tissue at the intended expansion site is determined unsuitable by the surgeon. To a varying degree, radiation damage, ulceration, compromised vascularity, history of compromised wound healing, infection, or scar deformity may affect tissue suitability.
- · There is residual gross tumor at the intended expansion site.
- · The patient has another electronic implant (e.g., pacemaker, defibrillator, or neurostimulator device).
Warnings:
Altitude Changes: The patient should not travel by air in a non-pressurized cabin while the Expander is implanted. The surgeon must approve flight travel for the patient, based on physical examination to determine if the patient's wound is adequately healed and they would tolerate the volume increase. (Refer to the labeling for additional information.)
Infection: DO NOT expose the Expander to contaminants that could increase the risk of infection. DO NOT implant in patients who present with an active infection, as this will increase the risk of peri-prosthetic infection.
Other Therapies: Diagnostic x-rays and diagnostic ultrasounds may be performed without affecting the Expander. DO NOT use shortwave diathermy, microwave diathermy or therapeutic ultrasound diathermy on patients implanted with an Expander. Energy from diathermy can be transferred to the Expander and can cause damage to the device.
Overfilling: DO NOT overfill the Expander. Excess volume cannot be removed without intentional rupture of the Expander. Therefore, use caution when filling the Expander to avoid overfilling. Please see labeling for additional information on overfilling.
Radiation Therapy: The decision to use radiation therapy should be made with the consultation of the radiation oncologist. Please see labeling for additional information on radiation therapy.
Sterility: DO NOT re-sterilize or re-use the Expander. The Expander is intended for single use only. Re-sterilization or re-use may impact device functionality or lead to
2
serious infection.
Temporary Device: DO NOT use the Expander for permanent implantation. The Expander is a temporary device intended for up to 6 months of implantation. Implantation longer than 6 months may lead to volume loss and depletion of CO2 gas.
Precautions:
Avoid Contamination During Surgery: Surgeons must use aseptic technique to avoid contamination. DO NOT expose the tissue expander to lint, talc, sponge, towel and other contaminants. Contamination at the time of surgery increases the risk of peri-prosthetic infection, which could require premature removal of the tissue expander.
A void Damage During Surgery: Extreme care should be taken to avoid damage to the tissue expander during surgery. A sterile back-up Expander should be readily available at the time of surgery in case damage occurs. Expanders must be carefully inspected for nicks, tears, punctures or leaks prior to use. DO NOT alter the device. DO NOT attempt to repair damaged products.
Maintenance Dosing: Once the labeled volume is reached, a small amount of CO2 will permeate from the Expander. To offset this permeation, patients must be instructed to "Maintenance Dose" to maintain the volume of the Expander. Failure to maintain the volume of the Expander may result in deflation and other potential complications. Refer to the "Manage Dosing" section of the labeling for additional details.
Surgical Planning: AirXpanders relies on the surgeon to know and follow proper surgical procedures specific to the expansion. Please see labeling for additional information on surgical planning.
PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
3
DEVICE DESCRIPTION
The AeroForm® Tissue Expander System is comprised of the AeroForm Tissue Expander, the Dosage Controller, and the Physician Master Key (see Figure 1). Each system component is further explained in subsections below.
Image /page/3/Figure/2 description: This image shows a medical device with several labeled components. On the left is a white, rounded device labeled as a "Tissue Expander" and "CO2 Gas Reservoir." An "Antenna" is positioned on the upper part of this device. To the right is a white and pink handheld device labeled as a "Dosage Controller," and a red component at the bottom is labeled as the "Physician Master Key."
Figure 1: Image of AeroForm Tissue Expander System
AeroForm Tissue Expander
The AeroForm Tissue Expander is a sterile implant with an outer textured silicone shell and a non-distensible inner bag which are anatomically shaped to allow for directional expansion in the lower, anterior pole. The AeroForm Tissue Expander contains a reservoir of compressed carbon dioxide (CO2), which is released within the AeroForm Tissue Expander by using the Dosage Controller. The outer shell has suture tabs to allow fixation of the device to the surrounding tissues to prevent rotation. A receiving antenna and electronics within the AeroForm Tissue Expander enable communication with the Dosage Controller. The AeroForm Tissue Expander has no intrinsic electrical power, batteries, or software, and can only be activated by the Dosage Controller. There are 3 different sizes of the expander, including small (400cc), medium (600cc), and large (850cc). The dimensions of the 3 different sizes of the AeroForm Tissue Expander are listed in Table 1 below:
| Table 1: Available Models and Sizes of AeroForm Tissue Expander | |
|---|---|
| ----------------------------------------------------------------- | -- |
| Model # | Surface | Shape | Size | Width (cm)
Un-inflated | Height (cm)
Inflated | Projection
(cm) | Volume
(cc) |
|-----------|----------|------------|--------|---------------------------|-------------------------|--------------------|----------------|
| LP105-400 | Textured | Anatomical | Small | 12.5 | 11.0 | 8.0 | 400 |
| LP120-650 | Textured | Anatomical | Medium | 14.0 | 12.5 | 9.5 | 600 |
| LP130-850 | Textured | Anatomical | Large | 15.5 | 14.0 | 10.5 | 800 |
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Dosage Controller
The Dosage Controller is a small, hand held battery-powered, non-sterile device. It activates the AeroForm Tissue Expander to release the programmed amount of CO2 gas (10cc). The Dosage Controller is configured to provide coded instructions to its bonded AeroForm Tissue Expander. It has a single push button for ease of use and a bank of indicator lights (LEDs) and tones. The LEDs are bi-color, with amber and green lights, where green indicates successful communication and dosing and amber indicates a notification regarding communication, dosing or power down. Each dose administers 10cc of CO2. There is a patient dosing limit of 3 (10cc) doses per day and a 3 hour time period between doses. A closer view of the Dosage Controller is provided in Figure 2 below.
Image /page/4/Figure/2 description: The image shows a medical device with several labels. The device has a "Lighting Bank" at the top and an "ON/OFF Indicator Button" in the middle. A "Patient Reference Card (Lanyard)" is attached to the device, labeled as the "Left/Right Controller ID".
Image /page/4/Figure/3 description: The image shows the title of a figure. The title is "Figure 2: Schematic of Dosage Controller". The title is written in a clear, bold font and is centered on the page. The text is black and the background is white.
Physician Master Key
The Physician Master Key is used only by the physician in the operating room or in the physician office. With the Physician Master Kev inserted into the Dosage Controller receptacle, the Dosage Controller can activate the Expander with no daily limit on the expansion volume. The Physician Master Key must remain plugged into the receptacle to continue functioning in this mode. Use of the Physician Master Key allows the physician to:
- · Inflate the Expander intra-operatively to the desired intra-operative fill volume
- · Add volume to the Expander at office visits, as therapeutically appropriate during the expansion process
- · Add up to 25% of the labeled volume every 2 weeks (to maintain volume and adjust the volume based on CO2 permeation).
The Physician Master Key is retained by the physician for use by the physician only, and is NOT provided to the patient. It will override the patient limits.
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Modifications to the AeroForm Tissue Expander
At the start of the clinical trial, an earlier version of the device was initially used. This initial version of the AeroForm Tissue Expander was called the version 2.0 or V2.0. Modifications were made to the AeroForm Tissue Expander V2.0 in response to device malfunctions that were seen during the clinical trial. These changes are as follows:
When the above listed changes were made to the device, it was called the AeroForm Tissue Expander 2.5 or V2.5. Both the V2.0 and V2.5 devices were used in the clinical study. A justification was provided explaining how the data from the V2.0 devices are applicable to the final V2.5 devices. The changes did not affect the intended use of the device: rather thev decreased malfunctions that were experienced with the previous version.
Please refer to the Instructions for Use, Patient Training Guide and Patient Home Instructions documents for additional details.
SUMMARY OF NONCLINICAL/BENCH STUDIES
BIOCOMPATIBILITY/MATERIALS
The AeroForm Dosage Controller, and Physician Master Key are expected to be limited superficial contact; therefore, they fall under the category of "surface devices", "skin", "limited" contact duration ( 30 days. It falls into the category of "Implant Devices. Tissue/Bone Communicating, permanent" contact duration (>30d) device according to ISO 10993-1:2009 Biological evaluation of medical devices -- Part 1: Evaluation and testing within a risk management process. Table 2 below summarizes the biocompatibility testing that was conducted on the AeroForm Tissue Expander.
| Biocompatibility Test | Acceptance Criteria | Results |
|---|---|---|
| Cytotoxicity | ||
| (ISO MEM Elution) | The biological response of the test samples extract must be grade 2 (mild or less) | Pass |
| Sensitization (Maximization) | The test samples must show a grade of 1 or less when compared to the control | Pass |
| Biocompatibility Test | Acceptance Criteria | Results |
| Irritation (ISO Intracutaneous) | The difference between the mean score of the test samples and control groups, in terms of erythema and edema, must be less than 1.0 | Pass |
| Acute Systemic Toxicity (USP Systemic Injection) | The test mice must not show a significantly greater reaction than the control mice | Pass |
| Acute Systemic Toxicity (USP Mediated Pyrogen) | The test rabbits must not show a temperature difference from the control of greater than or equal to 0.5°C | Pass |
| Sub-chronic toxicity | Evidence of irritation in the test animals will be scored and compared to the control animals | Pass |
| Chronic Toxicity | Evidence of irritation in the test animals will be scored and compared to the control animals | Pass |
| Genotoxicity (Bacterial Reverse Mutation) | The mean number of test revertants must be less than 2x the mean number of negative control revertants | Pass |
| Genotoxicity (Mouse Micronucleus) | The average % MN-RET for the test group must be less than 1.0% | Pass |
| Genotoxicity (Mouse Lymphoma) | The mutant frequency of the test sample must be 2X or less than that of the control | Pass |
| Implantation (2 week and 9 week) | The average macroscopic scores for test sample sites compared to control sites are correlated to a grade. The microscopic findings showing cellular changes will be graded according to severity (0-4) and any resulting irritant response indicated by a difference between test and control values will be graded as nonirritant, slight, moderate or severe. | Pass |
| Particulate Testing | Particle size [Redacted] (b) (4) particles per mL | |
| Particle size [Redacted] (b) (4) particles per mL | ||
| (per EN45502-1) | Pass | |
| LAL (Limulous Amoebocyte Lysate) Testing | Detected EU/device level is below (b) (4) EU/device | Pass |
| Carcinogenicity | Analysis of the biological test results, chemical characterization data and literature review | Pass by analysis and risk assessment |
Table 2: Biocompatibility testing conducted on AeroForm Tissue Expander
6
SHELF LIFE/STERILITY
The AeroForm Tissue Expander is provided sterile. The Dosage Controller and Physician Master Key are provided non-sterilization processes for the
7
AeroForm Tissue Expander include
and ethylene oxide per EN ISO 11135-1:2007. The AeroForm Tissue Expander is sterilized
The AeroForm Tissue Expander is provided in an inner polyester (PETG) tray sealed with a Tyvek® lid. The sealed inner tray is placed into an outer PETG tray, which is sealed with a second Tyvek® lid. The double-sealed product tray is then placed into a sealed chipboard box. Multiple sealed and labeled chipboard boxes are placed in a shipper box for shipping and distribution.
The Dosage Controller package includes a sterile Aseptic Transfer pouch and the nonsterile Dosage Controller. Using standard sterility techniques, the Dosage Controller must be transferred to the Aseptic Transfer pouch in order to maintain sterility of the surgical field during the surgical procedure.
The shelf-life for the sterile AeroForm Tissue Expander is 12 months, based on accelerated and real time shelf-life studies. The test articles were environmentally conditioned based on ASTM D4332-2014 Standard Practice for Conditioning Containers. Packages, or Packaging Components for Testing, and EN 45502-1:1998, Clause 10.2 Active implantable medical devices: General requirements for safety, marking and information to be provided by the manufacturer. Following climatic conditioning, test articles were subjected to transit shipping and handling tests, as described in ASTM D4169-2014 Standard Practice for Performance Testing of Shipping Containers and Systems for packages up to 150 lbs. Test articles were then sealed in a pressure vessel and subjected to high pressure conditions, 150 kPa ± 5% for 1 hour (pressure is absolute) per EN 45502-1:1998. Clause 25.1. Package integrity and seal integrity were evaluated to ensure transportation and climactic conditioning did not impact the sterile barrier seal. Following testing and inspection of the product package and labeling, the product was then tested according to protocol to confirm performance and functionality after one year of real time storage. Performance testing included simulated use testing, functional testing, and shell integrity evaluation. After one year of both accelerated and real time aging, testing of the AeroForm Tissue Expander and its package met the requirements specified in the protocol, including packaging integrity and functional specifications. The testing supports the expiration date of 12 months and the AeroForm Tissue Expander is labeled with a 12 month shelf life.
The Dosage Controller has no expiration date. All Dosage Controller materials are rated for a shelf life of more than 10 years. The batteries have a minimum 10 year shelf life
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based on analysis of the battery drain and the battery capacity.
ELECTROMAGNETIC COMPATIBILITY AND WIRELESS COEXISTENCE TESTING
Electromagnetic compatibility (EMC) testing was conducted on the device. The testing is summarized in Table 3 below:
| Table 3: EMC and wireless coexistence testing conducted on the AeroForm Tissue |
|---|
| Expander System |
| Test | Description | Standard | Result |
|---|---|---|---|
| Radiated emissions; | |||
| transmitter spurious | |||
| high | Place test article on 1m | ||
| table in transmit mode, | |||
| measure emission within | |||
| 30MHz to 1000MHz range | EN 300 330-2: 2010- | ||
| 02 4.2.1.4 | |||
| IEC 60601-1-2:2007 | Pass | ||
| Limits for transmitters; | |||
| transmitter spurious | Place test article on 1m | ||
| table in transmit mode, | |||
| measure emission in 9k to | |||
| 30MHz range | EN 300 330-2: 2010- | ||
| 02 4.2.1.2 | |||
| EN 300 330-2: 2010- | |||
| 02 4.2.1.4 | Pass | ||
| Permitted frequency | |||
| range of modulation | |||
| bandwidth | Place test article on 1m | ||
| table in transmit mode, | |||
| measure emission within | |||
| $13.56MHz \pm 7kHz$ range | EN 300 330-2: 2010- | ||
| 02 4.2.1.1 | |||
| EN 300 330-2:2010-02 | |||
| 4.2.1.4 | Pass | ||
| Radiated immunity | Place test article in 3m | ||
| chamber and subject to | |||
| 3V/m radiation in 80-2500 | |||
| MHz range | IEC 60601-1:2007 | Pass | |
| Magnetic immunity | Place test article inside coil | ||
| and subject to 3A/m | |||
| magnetic field, 3-axis | IEC 60601-1-2:2007 | Pass | |
| ESD | Hold ESD gun to target, | ||
| apply 6kV contact | |||
| discharge, 8kV air | |||
| discharge. Repeat for 8kV | |||
| contact discharge, 15kV air | |||
| discharge | IEC 60601-1-2:2007 | Pass | |
| Immunity from hand | |||
| held transmitters | Exposure of test articles to | ||
| simulated handheld | |||
| transmitter held in very | |||
| close proximity to the | |||
| device, to expose the device | |||
| to very large | |||
| electromagnetic fields | ANSI/AAMI PC69: | ||
| 2007 | Pass | ||
| Immunity from security | |||
| and logistical systems | Exposure of test articles to | ||
| devices intended to radiate | |||
| large magnetic fields at or | |||
| near the operating | |||
| frequency of the AeroForm | |||
| System | N/A | Pass |
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MAGNETIC RESONANCE (MR) COMPATIBILITY
The AeroForm Tissue Expander System is MR Unsafe. MRI equipment can cause movement of the Expander and result in patient injury or Expander displacement, requiring revision surgery.
SOFTWARE
Software for the device is consistent with a 'MAJOR level of concern', as discussed in the FDA document, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices," issued May 11, 2005.
Adequate documentation describing the software development program as required per the guidance document was provided and deemed adequate. Verification and validation (V & V) testing was conducted to address the potential hazards with satisfactory results. The software development procedures provide the foundation that the software will operate in a manner as described in the specifications.
An assessment of cybersecurity risks and mitigations was provided. The risks were identified as eavesdropping, man-in-the-middle attacks or data manipulation, communication data disruption, communication data corruption, and loss of information confidentiality, integrity, and availability. The mitigations included very near field communication, an active-passive communication mode, proprietary communication protocol between the controller and expander, serial number verification, and proprietary data key and data port.
The software documentation is in sufficient detail to provide reasonable assurance that the software performs as intended and all software-related risks have been adequately mitigated.
PERFORMANCE TESTING - BENCH
Additional bench testing is summarized in Table 4 below.
| Test | Purpose | Acceptance Criteria | Results |
|---|---|---|---|
| Cycle Rub Test | The Cycle Rub Test | ||
| simulates repeated | |||
| severe flexing and | |||
| delamination of the film | |||
| barrier, representing the | |||
| pectoral and serratus | |||
| anterior muscles in the | |||
| chest exerting | |||
| compressive and shear | |||
| forces on the Expander. | There are no major leaks or tears | ||
| in the film or the seals, after | |||
| 25,000 cycles. | The Expander | ||
| successfully met the | |||
| no leak and tear | |||
| requirements after | |||
| 25,000 cycles. | |||
| Impact Test | This test confirms the | ||
| gas barrier and seal | |||
| integrity by exerting a | |||
| load resulting in 3.3 psi | |||
| of internal pressure. | There are no ruptures after the | ||
| impact test. | No ruptures were | ||
| reported after the | |||
| impact test. | |||
| Test | Purpose | Acceptance Criteria | Results |
| Impact Force Test | The purpose of this test | ||
| is to characterize the | |||
| effects of high impact | |||
| loading on the CO2 | |||
| reservoir and valve sub- | |||
| assembly, and to assess | |||
| the anticipated force that | |||
| could damage the valve | |||
| and/or forcefully | |||
| dislodge the valve. | The device shall not fail or leak | ||
| when experiencing forces less | |||
| than 1700 lbs. | All acceptance | ||
| criteria were met. | |||
| The reservoir and | |||
| valve assembly | |||
| withstood an impact | |||
| load of ~4X the | |||
| human tolerance | |||
| levels of 1700lbs | |||
| without leakage. | |||
| Impact loads to ~7X | |||
| the human tolerance | |||
| level resulted in | |||
| slow leaks. | |||
| Leak Test | This test confirms that | ||
| the tissue expander does | |||
| not leak CO2 after all | |||
| the simulated use tests | |||
| have been completed. | The CO2 concentration shall not | ||
| increase more than 100 PPM. | The Expander | ||
| successfully met the | |||
| leak test | |||
| requirements | |||
| following functional | |||
| testing. | |||
| Permeability Test | This test records the | ||
| permeation rate after at | |||
| least 10 days of a fully | |||
| expanded Expander. | Small & Medium Size: | ||
| Each test article shall have a daily | |||
| average permeation rate of 0-4.1 | |||
| mL CO2 per day. |
Large Size:
Each test article shall have a daily
average permeation rate of 0-6.0
mL CO2 per day. | The small and
medium test articles
met the daily
average permeation
rate of 33).
- 12. Subject is unwilling to comply with air travel or altitude restriction of not > 3300 feet (1000 meters) from baseline during the time the AeroForm Expander is implanted
-
- Subject has currently implanted electronic device such as a pacemaker, defibrillator, neurostimulator device, or drug infusion device
-
- Subject is pregnant or planning on becoming pregnant during the study period
-
- Subject has a history of psychological condition, drug or alcohol misuse which may interfere with their ability to use the device safely
All subjects were followed by the investigator in the post-operative period. When their incisions were healed, they were ready to begin active expansion. Subjects in the investigational arm were
13
given the Dosage Controller to expand at home with up to three (10cc) doses per day based on their comfort level. Subjects in the saline expander arm were injected with a bolus of saline through the magnetic port on the outer surface of the expander. These subjects received periodic bolus saline injections during their follow up visits to fill their expanders. The investigator determined the amount of saline to be added to the saline expander arm based on patient tolerance and need. All subjects were followed weekly until expansion was complete and monthly thereafter, until their procedure was scheduled to remove the expander(s) and to place permanent breast implant(s).
The timing of the exchange procedure was at the discretion of the investigator and needs of the subject. The subject's participation in the study was complete when their expander(s) were removed. Follow-up was discontinued if the subject was terminated or voluntarily withdrew from the study.
Primary Endpoint
The performance of the device was evaluated by successful tissue expansion and exchange to a permanent breast implant unless precluded by a non-device related event. The primary endpoint was analyzed per breast. Breasts in which the expander was removed and/or replaced due to a device related adverse event or a device malfunction were counted as failures.
The overall study success was based on an expected treatment success rate of 95%, with a -10% margin of non-inferiority when compared to the saline control group.
Secondary Effectiveness Endpoints
The usability of the device was evaluated by:
-
- The average number of days to achieve the desired expansion (onset of active expansion to completion of expansion)
-
- The average number of days for completion of stage 1 reconstruction (expander implantation to permanent implant exchange).
-
- Subject reported pain ratings during active expansion
-
- Overall subject satisfaction
-
- Overall physician satisfaction
Safety Endpoints
The safety of the device was evaluated by:
-
- Device related adverse events
-
- Serious device related adverse events
-
- All adverse events, regardless of whether serious or there is a causal relationship to the device.
-
- All serious adverse events, regardless of whether there is a causal relationship to the device.
-
- Device failures leading to expander removal and/or replacement.
Randomization
Subjects were randomized to either the investigational arm (AeroForm Tissue Expander System), or the control arm (standard saline tissue expander) using a 2:1 (AeroForm Tissue Expander System to saline) permuted block randomization process, stratified by investigational center and
14
procedure (unilateral or bilateral). A computerized system was used to generate the randomization scheme to assign the subject to the control arm or the investigational arm. The randomization was stratified per investigational site and procedure (unilateral) to ensure the same number of saline and AeroForm tissue expanders per site. The same type of expander was placed on each side in subject's having a bilateral procedure.
Subject Enrollment
One hundred and fifty-eight (158) subjects were enrolled from 11/11/2011 through 12/23/2014 at 17 U.S. investigational sites. Subjects were randomized (2:1) to the investigational arm (AeroForm) (n=106) or the control arm (Saline) (n=52). All enrolled subjects were assigned to analysis cohorts as defined in the statistical analysis plan. There were 7 investigational subjects who were randomized to treatment, but did not receive the device. One investigational subject was randomized to treatment and a procedure was attempted, however no device was implanted due to positive lymph nodes and radiation therapy was required. This patient was included in the evaluable numbers for the safety analysis, but not for the effectiveness analysis. A total of 151 patients (99 AeroForm patients and 52 saline patients) were evaluated. The patient disposition is shown in Figure 3 below:
Figure 3: Patient Disposition
Image /page/14/Figure/4 description: This image is a flowchart that shows the enrollment and randomization of participants in a study. 158 participants were enrolled and randomized. The participants were then divided into two groups: AeroForm (n=106) and Saline (n=52). The flowchart also shows the number of participants who were randomized but no procedure was attempted (n=7), randomized procedure attempted, no AeroForm implanted (n=1), and the number of participants in the safety population and per protocol population for each group.
There were 98 subjects who received the AeroForm device in the investigational arm. Of the 98 AeroForm subjects, 54 patients received the V2.0 Expander and 44 patients received the V2.5 Expander (90 breasts received V2.0 and 78 breasts received V2.5).
No subjects were lost to follow up. Ninety-eight (98%, 147/150) of the implanted subjects completed the study. Three implanted subjects did not complete the study and were considered failures. This includes 2 subjects in the AeroForm arm and 1 subject in the saline arm. The first subject in the AeroForm arm who did not complete the study had bilateral expanders and experienced unilateral under-expansion. The subject elected to have only fat grafting, not to complete reconstruction and had both expanders removed, with no permanent implants placed. The second subject in the AeroForm arm who did not complete the study had bilateral expanders and experienced unilateral deflation. The subject elected to have both expanders removed and replaced with saline expanders and complete reconstruction at a later time. The subject in the
15
control arm who did not complete the study had bilateral expanders and experienced unilateral exposure. The subject elected to have both saline expanders removed, not to complete reconstruction, and had no permanent implants placed.
Primary Endnoint Data
The Treatment Success Rate per breast (excluding non-device related failures) for AeroForm is 96.1% (149/155). The Treatment Success Rate per breast for Saline is 98.8% (82/83). The difference in the treatment success rate (AeroForm - Saline) is -2.7% with a lower confidence limit of -7.3%, meeting the non-inferiority margin of > -10%.
Secondary Endpoints Data
The median number of days to complete expansion, and similarly, the median number of days for completion of reconstruction were reduced in the AeroForm group compared to the saline group. The median days to complete expansion was 21.0 (95% CI 15.0, 24.0) days for AeroForm and 46.0 (95% CI 38.0. 55.0) days for saline. The median days to complete breast reconstruction was 108.5 (95% CI 99.0, 117.0) days for AeroForm and 136.5 (95% CI 119.0, 147.0) days for saline.
Pain assessment is a patient reported outcome score and was judged using an 11-point visual analog scale with higher numbers representing higher levels of pain. The results show no difference in the intensity of the pain reported by patients implanted with the AeroForm device or the saline expander at the first visit after Start of Expansion (Average = 2.2 AeroForm, 1.9 saline) or for the worst pain experienced overall (Average = 4.5 AeroForm, 4.6 saline).
Overall, subjects were satisfied with the expansion process in 78% of the reconstructions with AeroForm and 91% with Saline. Analyzing the data for v2.5 only (n=69), 84% of the responses were mildly, moderately, or very satisfied.
Physician satisfaction with the results of expansion was 68% with AeroForm, and 92% with Saline. The lower satisfaction scores observed with the AeroForm were a direct reflection of the device malfunctions and gradual loss of volume that were experienced with the V2.0 device. which was used at the beginning of the clinical trial. Dissatisfaction comments were primarily related to permeation (loss of volume), bulkiness of the device, and physician modes. The satisfaction scores improved with V2.5 after the introduction of the enhanced inner liner which reduced permeation, as well as the software reprogramming to increase the capability of the physician to adjust the volume. Analysis of device V2.5 data alone resulted in physician satisfaction of 83% with the expansion results.
Safety
The number of subjects with any adverse event was 63 (63.3%) for the AeroForm arm and 33 (63.5%) for the Saline arm. The number of subjects with any adverse event related to the study device was 21 (21.2%) for the AeroForm Arm and 10 (19.2%) for the Saline arm. The number of subjects with any adverse event related to the study procedure was 46 (46.5%) for the AeroForm arm and 24 (46.2%) for the Saline arm. The proportion of subjects with any adverse event, any device-related adverse event and any procedure-related adverse event was similar between treatment groups. In addition, the treatment groups were, in general, similar in the
16
incidence of specific breast-related adverse events. There were 53 subjects (53.5%) in the AeroForm arm and 23 subjects (44.2%) subjects in the Saline arm who experienced breast related adverse events. The breast related adverse events that are most relevant to the study and device are listed in Table 5 below:
| AeroForm | Saline | |||
|---|---|---|---|---|
| Breasts | ||||
| (n=169) | ||||
| Quantity (%) | Subjects | |||
| (n=99) | ||||
| Quantity (%) | Breasts | |||
| (n=88) | ||||
| Quantity (%) | Subjects | |||
| (n=52) | ||||
| Quantity (%) | ||||
| Breast Related AEs* | 74 (43.8%) | 53 (53.5%) | 35 (39.8%) | 23 (44.2%) |
| Allergic/Foreign Body Reaction | 0 (0%) | 0 (0%) | 2 (2.3%) | 1 (1.9%) |
| Bleeding, Post Procedure | 1 (0.6%) | 1 (1.0%) | 0 (0%) | 0 (0%) |
| Capsular Contracture | 1 (0.6%) | 1 (1.0) | 0 (0%) | 0 (0%) |
| Device Displacement | 0 (0%) | 0 (0%) | 3 (3.4%) | 2 (3.8%) |
| Device Malfunction | 7 (4.1%) | 6 (6.1%) | 1 (1.1%) | 1 (1.9%) |
| Extrusion | 2 (1.2%) | 1 (1.2%) | 1 (1.1%) | 1 (1.9%) |
| Hematoma | 2 (1.2%) | 2 (2.0%) | 3 (3.4%) | 3 (5.8%) |
| Infection | 9 (5.3%) | 8 (8.1%) | 6 (6.8%) | 5 (9.6%) |
| Inflammation | 15 (8.9%) | 12 (12.1%) | 5 (5.7%) | 4 (7.7%) |
| Delayed Wound Healing, | ||||
| Tissue Necrosis | 16 (9.5%) | 11 (11.1%) | 4 (4.5%) | 3 (5.8%) |
| Procedural Pain | 10 (5.9%) | 7 (7.1%) | 10 (11.4%) | 7 (13.5%) |
| Seroma | 15 (8.9%) | 11 (11.1%) | 5 (5.7%) | 4 (7.7%) |
| Wound Dehiscence | 2 (1.2%) | 2 (2.0%) | 1 (1.1%) | 1 (1.9%) |
| Table 5: Breast Related Adverse Events Observed in Pivotal Study | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| -- | -- | -- | -- | -- | -- | ------------------------------------------------------------------ | -- | -- | -- | -- |
*Adverse events coded using the MedDRA dictionary v18.0. The tables include counts and percentages. At each level of summation, breasts are counted only once.
17
Table 6 below lists the adverse events for the AeroForm investigational arm divided by the different versions of the device (Version 2.0 and Version 2.5).
| | Breasts Receiving
AeroForm Expander Version 2.0
N=90
n (n/N%) | Breasts Receiving
AeroForm Expander Version 2.5
N=78
n (n/N%) |
|-------------------------------------------------|------------------------------------------------------------------------|------------------------------------------------------------------------|
| Breast Related AEs* | 52 (57.8%) | 22 (28.2%) |
| Post-Operative Wound
Complication (Necrosis) | 13 (14.4%) | 3 (3.8%) |
| Seroma | 4 (4.4%) | 11 (14.1%) |
| Hematoma | 1 (1.1%) | 1 (1.3%) |
| Post-Operative Wound Infection | 8 (8.9%) | 1 (1.3%) |
| Wound Dehiscence | 2 (2.2%) | 0 (0.0%) |
| Extrusion | 1 (1.1%) | 1 (1.3%) |
| Capsular Contracture | 1 (0.6%) | 0 (0%) |
| Procedural Pain | 8 (8.9%) | 2 (2.6%) |
| Device Malfunction | 5 (5.6%) | 2 (2.6%) |
| Device Dislocation | 0 (0%) | 0 (0.0%) |
| Foreign Body Reaction | 0 (0%) | 2 (0.0%) |
Table 6: Breast Related Adverse Events Observed in Version 2.0 and Version 2.5 of AeroForm Expanders
- Adverse events coded using the MedDRA dictionary v18.0. The tables include counts and percentages. At each level of summation, breasts are counted only once.
Device Malfunctions
Communication failures were reported for 9 (5.4%) AeroForm expanders used in the study; all failures were observed with V2.0 devices. Failure to reach or maintain volume, or the incidence of deflation of the device, was reported for 42 (46.7%) V2.0 devices. The device was modified
18
to mitigate this issue. The design changes of the V2.5 devices reduced this mode of device failure to 12 incidences, or from 46.7% to 15.4%.
Five (5) devices over-expanded due to failure of the micro valve to seal properly and required deflation of the expanders using a hypodermic needle. A needle puncture compromises the integrity of the device and device explantation is necessary.
All device malfunctions are listed in Table 7 below:
| Event Description | AeroForm V2.0
n=90 | AeroForm V 2.5
n=78 | All AeroForm
n=168 |
|---------------------------------------------------|-----------------------|------------------------|-----------------------|
| Loss of Communication | 9 (10%) | 0 (0%) | 9 (5.4%) |
| Under Expansion/Deflation (Total) | 42 (46.7%) | 12 (15.4%) | 54 (32.1%) |
| Under-Expansion - Failure to Reach Full
Volume | 1 (1.1%) | 2 (2.6%) | 3 (1.8%) |
| Deflation - Failure to Maintain Volume | 16 (17.8%) | 1 (1.3%) | 17 (10.1%) |
| Deflation - Gradual | 23 (25.6%) | 8 (10.3%) | 31 (18.5%) |
| Deflation - Sudden | 2 (2.2%) | 1 (1.3%) | 3 (1.8%) |
| Over-Expansion | 4 (4.4%) | 1 (1.3%) | 5 (3.0%) |
| Rupture | 0 (0%) | 0 (0%) | 0 (0%) |
Table 7: Device Malfunctions Experienced in AeroForm Expanders
As shown in Table 6. there were 7 AeroForm device malfunctions that led to breast related adverse events, or more specifically those patients that had a failed reconstruction due to the device related failure. This includes 5 cases of over-expansion, 1 case of deflation and 1 case of under expansion.
19
Carbon Dioxide Permeation
At the start of the clinical trial, a different version of the device was used, V2.0. With the V2.0, there were many reports of carbon dioxide permeating or leaking through the shell. This reported leakage did not result in abnormal tissue responses or clinical chemistry responses. There were, however, noticeable volume losses noted in the expanders. In the device malfunctions data (Table 7), this is categorized as either under expansion or deflation. With the original version V2.0, there were 42 instances of under expansion/deflation. The sponsor modified the design on their device, as described in the "Modifications to the AeroForm Tissue Expander' section of this document. As explained, an additional layer was added to the inner bag to increase durability and decrease permeation of carbon dioxide. In addition, a physician mode was added to allow the capability of adding 25% of full volume every two weeks. Once all the device modifications were implemented. the device (known as V2.5) showed a reduced number of 12 instances under expansion/deflation.
When expansion is complete and the labeled volume is reached, a small amount of CO2 may permeate from the Expander. To offset this permeation, subjects will need to administer a maintenance dose. The maintenance dosing allows subjects to administer enough doses to account for the small amount of carbon dioxide that can permeate from the expander. Maintenance dosing is required to maintain the volume and prevent deflation.
Continued Access Study
When enrollment was complete for the pivotal study, patients continued to be enrolled under the Continued Access Study (CAS) IDE provision. XPAND II CAS is a prospective, multi-center, single arm study of the V2.5 device. As of June 8, 2016, a total of 28 subjects (49 breasts) have been treated at 6 clinical sites. Eleven (11) subjects (21 breasts) have completed the final study visit and complete data are available. An additional 4 subjects (6 breasts) have undergone the explant procedure but only have partial data available as they have not completed their final study visits.
The primary endpoint of Treatment Success in the XPAND II CAS was 100% (n=18 breasts). Two patients had their devices (3 expanders) removed for non-device related reasons. The first subject elected to have both expanders removed due to severe reactions to multiple antibiotics and withdrew from the study. The second subject had an incision which failed to heal properly and led to an open wound, requiring removal of her left expander and replacement with a saline expander. Expansion was completed and both tissue expanders were exchanged to breast implants.
The secondary endpoints, pain and satisfaction, were assessed. Pain was assessed at two time points: at the start of expansion and at the first visit after start of expansion. At the start of expansion, average pain was reported as 1.8 in 24 subjects with data available, and 2.3 in 26 subjects with data available for the first visit after the start of expansion. Satisfaction data from both subject and physician surveys in XPAND II are available for subjects who have completed their final study visit (n=11). Two patients and one physician did not complete the XPAND II survey. Overall, 89% (8/9) subjects and 90% (9/10) physicians were satisfied with the device performance and 80% (8/10) physicians were satisfied with the results of expansion.
20
Dissatisfaction comments were primarily related to permeation and bulkiness of the device. One physician was neither satisfied nor dissatisfied and one patient and their physician were moderately dissatisfied due to gradual volume loss, requiring office dosing.
There were 5 breast-related adverse events revorted in the CAS. Those events most relevant to the study are summarized in Table 8 below.
| | Breasts
(n=21)
Quantity (%) | Subjects
(n=11)
Quantity (%) |
|--------------------------------|-----------------------------------|------------------------------------|
| Breast Related AEs* | 5 (23.8%) | 4 (36.4%) |
| Inflammation | 1 (4.8%) | 1 (9.1%) |
| Post-Operative Wound Infection | 1 (4.8%) | 1 (9.1%) |
| Wound Dehiscence | 1 (4.8%) | 1 (9.1%) |
Table 8: Breast Related Adverse Events Observed in XPAND II CAS
- Adverse events coded using the MedDRA dictionary v18.0. The tables include counts and percentages. At each level of summation, breasts are counted only once.
There was one instance of loss of volume which was managed by the surgeon with office dosing, leading to a successful exchange procedure. There were no new failure modes identified and no over-expansion or sudden deflations occurred in the XPAND II study.
HUMAN FACTORS
Human factors evaluation and validation was performed in compliance with ANSI/AAMI HE 75:2009. Human factors engineering—Design of medical devices, and EN 62366-2008 Medical devices - Application of usability engineering to medical devices. A Formative Human Factors Usability study was performed to optimize the design of the Dosage Controller, followed by a Summative Human Factors Validation study. These studies were performed to assure that design of the Dosage Controller and patient instructions are easily understood by the intended user population.
The study results, analyses and conclusions established that the AeroForm Tissue Expander System is safe and effective for the intended users, its intended uses, and use environments.
LABELING
Labeling has been provided which includes the instructions for use and an appropriate prescription statement as required by 21 CFR 801.109.
21
Device-specific risks addressed in the labeling include:
- . Patients must not undergo Magnetic Resonance Imaging (MRI) while the AeroForm Tissue Expander is in place. MRI equipment can cause damage to the electronics and/or result in movement or displacement of the Expander that could lead to patient injury or revision surgery.
- . During the ascent on commercial flights, the AeroForm Tissue Expander will increase in volume. An increase in volume may cause the patient discomfort and the possibility of pressure related wound complications. The Expander volume will return to its original state and the filling sensation that the patient may experience will subside when the plane descends and lands. The surgeon must approve flight travel for the patient, based on physical examination to determine if the patient's wound is adequately healed and if the patient would tolerate the volume increase. Depending on the size and how full the AeroForm Tissue Expander is, the patient will experience an average volume increase during air travel as follows:
| Percent Full* | 20% | 40% | 60% | 80% | 100% |
|---|---|---|---|---|---|
| Small (400cc) | 44cc | 59cc | 75cc | 87cc | 96cc |
| Medium (600cc) | 61cc | 88cc | 115cc | 131cc | 141cc |
| Large (800cc) | 83cc | 122cc | 160cc | 164cc | 143cc |
*Percent full as indicated by lighting bank on Controller
For moderate altitude change, such as during car travel, if increasing pressure and discomfort in the breast is experienced, the patient should stop the ascent and wait for the discomfort to pass. If the discomfort does not pass, the patient should return to lower altitude. The AeroForm Tissue Expander has not been evaluated in other pressurized environments (i.e., scuba diving, or hyperbaric chambers). The patient should not travel by air in a non-pressurized cabin while the Expander is implanted.
-
The ability to establish communication between the Expander and the Controller may be . impaired by electromagnetic interference from other RF wireless devices operating nearby. Interference from other RF wireless devices may be resolved by simply moving away from the other RF wireless device.
Physician labeling includes instructions for use by the physician and includes the following information: -
. Device description and indications for use.
-
Instructions for use including information that should be provided to the patient. ●
-
Contraindications, warnings, precautions, and limitations for safe use of the device and . adverse events associated with device use.
-
. Information on how the device operates including dosing instructions, dosing limits and the physician fill mode.
-
A description of the verified temperature controls and safety features included in the . device.
-
A summary of the pivotal clinical investigation information. ●
22
Additional labeling information for the physician includes a Physician Ouick Reference Card.
Patient labeling (patient guide) includes instructions for the patient and includes the following information:
- . Contraindications, warnings, and precautions.
- Description of the device and device care. ●
- . Risks associated with device use.
- Explanation of breast reconstruction and breast reconstruction with the device, including ● alternative treatments.
- Instructions for dosing and an explanation of dosage controller notifications.
- Summary of clinical investigational information. ●
- . Glossary of terms.
Additional patient labeling information includes a patient reference card and a patient ID card, which includes information on metal detectors.
Presentations to guide the physician and patient in the proper use of the device have been prepared. The "physician training presentation for medical professionals" is used to explain the device to medical personnel. The "patient training presentation" is a presentation that is to be used by the physician to explain the device to the patients.
After the patient receives training, they must demonstrate comprehension of the device or they should be re-trained.
RISKS TO HEALTH
Table 9 below identifies the risks to health that may be associated with use of a carbon dioxide gas controlled tissue expander and the measures that have been used to mitigate these risks.
| Identified Risk | Mitigation Measure |
|---|---|
| Pain From Overexpansion with Carbon Dioxide | Labeling Software verification, validation and hazard analysis |
| Tissue Damage From Overexpansion with Carbon Dioxide | In-vivo performance testing Labeling Software verification, validation and hazard analysis |
| Prolonged Treatment Time Due To Under Expansion Because of Carbon Dioxide Permeation Due to Overexpansion with Carbon Dioxide | In-vivo performance testing Non-clinical performance testing Labeling Software verification, validation and hazard analysis |
Table 9: Identified Risks and Mitigation Measures
23
| Re-operation | In-vivo performance testing |
|---|---|
| Due to No Expansion Because of Device Failure Due to Overexpansion with Carbon Dioxide | Non-clinical performance testing |
| Underexpansion, Overexpansion, or No Expansion | |
| Due To Interference With Other Devices Due to Use Error | Electromagnetic compatibility, electrical safety, and wireless compatibility testing Labeling Software verification, validation and hazard analysis Human factors testing Patient training |
| Adverse Tissue Reaction | Biocompatibility evaluation |
| Infection | Sterilization validation Shelf life testing |
SPECIAL CONTROLS:
In combination with the general controls of the FD&C Act, the carbon dioxide gas controlled tissue expander is subject to the following special controls:
-
- In-vivo performance testing must be conducted to obtain the adverse event profile associated with use, and demonstrate that the device performs as intended under anticipated conditions of use
-
- The patient-contacting components of the device must be demonstrated to be biocompatible
- Performance data must demonstrate the sterility of patient-contacting components of the 3. device
-
- Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
- a. Cycle testing of expander showing that there are no leaks or tears after repeated cycling
- b. Mechanical assessment of implanted CO2 canister including high impact testing
- c. Leak testing of expander showing that device does not leak CO2
- d. Assessment of gas permeability during expansion and after full expansion
- e. Mechanical assessment of expander (tensile set, breaking force, shell joint test, and fused or adhered joint testing)
-
- Performance data must be provided to demonstrate the electromagnetic compatibility, electrical safety, and wireless compatibility of the device
-
- Software verification, validation and hazard analysis must be performed
24
-
- Performance data must support shelf life by demonstrating continued sterility of the device or the sterile components, package integrity, and device functionality over the identified shelf life
-
- Human factors testing and analysis must validate that the device design and labeling are sufficient for the end user
-
- Physician labeling must include:
- The operating parameters, name, and model number of the indicated external a. dosage controller
- b. Information on how the device operates and the typical course of treatment
- Information on the population for which the device has been demonstrated to be C. effective
- d. A detailed summary of the device technical parameters
- e. Provisions for choosing an appropriate size implant that would be exchanged for the tissue expander
-
- Patient labeling must include:
- Warnings, precautions, and contraindications, and adverse events/complications a.
- b. Information on how the device operates and the typical course of treatment
- c. The probable risks and benefits associated with the use of the device
- d. Post-operative care instructions
- e. Alternative treatments
-
- Patient training must include instructions for device use, when it may be necessary to contact a physician, and cautionary measures to take when the device is implanted.
BENEFIT/RISK DETERMINATION
The risks of the AeroForm Tissue Expander System are based on nonclinical laboratory and/or animal studies as well as data collected in a clinical study described above. In summary, the risks associated with use of the device include pain from overexpansion with carbon dioxide, tissue damage from overexpansion with carbon dioxide, prolonged treatment time due to under expansion because of carbon dioxide permeation, re-operation due to no expansion because of device failure, under or no expansion due to interference with other devices, adverse tissue reaction, infection, allergic/foreign body reaction, under or overexpansion of device from user error, capsular contracture, device displacement, extrusion, hematoma, delated wound healing/ tissue necrosis, seroma, wound dehiscence, premature expander removal, rupture, device malfunction, and deflation. There were 53 subjects (53.5%) in the AeroForm arm and 23 subjects (44.2%) subjects in the Saline arm who experienced breast related adverse events. The breast related adverse events that are most relevant to the study and device are listed in Table 10.
| Event | Incidence |
|---|---|
| Post-Operative Wound Complication | |
| (Necrosis) | 9.5% |
| Seroma | 8.9% |
| Hematoma | 1.2% |
| Post-Operative Wound Infection | 5.3% |
Table 10: Breast Related Adverse Events (most relevant to the study)
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| Event | Incidence |
|---|---|
| Wound Dehiscence | 1.2% |
| Extrusion | 1.2% |
| Capsular Contracture | 0.6% |
| Procedural Pain | 5.9% |
| Device Malfunction | 4.1% |
Device malfunctions seen in the AeroForm breasts are listed in Table 11:
| Table 11: Device Malfunctions | ||||
|---|---|---|---|---|
| -- | -- | -- | -- | ------------------------------- |
| Malfunction | Incidence |
|---|---|
| Loss of Communication | 5.4% |
| Under Expansion/Deflation (Total) | 32% |
| Under-Expansion – Failure to Reach Full Volume | 1.8% |
| Deflation - Failure to Maintain Volume | 10.1% |
| Deflation - Gradual | 18.5% |
| Deflation - Sudden | 1.8% |
| Over-Expansion | 3% |
The probable benefits of the AeroForm Tissue Expander System are also based on nonclinical laboratory and animal studies as well as on data collected in the clinical studies as described above. The benefits of the study included a reduction in the median number of days to complete expansion, and the median number of days for completion of reconstruction. Patients can benefit from the device by the need for fewer office visits to the surgeon for expansion, avoidance of needle puncture for expansion, and faster time to completion of expansion and reconstruction. Overall, subjects were satisfied with the expansion process in 78% of the reconstructions with AeroForm and 91% with Saline. Analyzing the data for V2.5 only (n=69), 84% of the responses were satisfied.
Additional factors to be considered in determining probable risks and benefits for the AeroForm Tissue Expander System include noting that the clinical study design was robust. The study was prospective. randomized and controlled. There was no loss to follow-up and low missing data. There were no major deviations from the study protocol. There is a Continued Access Study that has data that supports the study robustness. There were limitations to the study, including a modification of the device made during the study resulted in a smaller number of subjects that received the final device (44/98); the evaluators were non-blinded and therefore aware of which device was placed: and the largest size of the expander was under represented in its utilization in the study, however, this limitation was observed in both the saline and AeroForm arms. Despite the limitations, the study design remains robust. In addition, 3 OUS clinical studies were performed to demonstrate the safety and effectiveness of the AeroForm System.
Patient Perspectives
Patient perspectives considered for the AeroForm® Tissue Expander System included:
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- Subject reported pain ratings during active expansion. ●
- . Overall subject satisfaction.
- A human factors evaluation whereby the patients assessed the patient instructions to ● assure that they were easily understood.
- . A patient training process, whereby after receiving training, the patient will be assessed regarding their understanding.
- Patient has control over expansion process. .
Benefit/Risk Conclusion
In conclusion, given the available information above, the data support that for soft tissue expansion in breast reconstruction following mastectomy, treatment of underdeveloped breasts, and treatment of soft tissue deformities for a time period not extending beyond six months, the probable benefits outweigh the probable risks for the AeroForm Tissue Expander System. The device provides substantial benefits and the risks can be mitigated by the use of general and the identified special controls.
CONCLUSION
The De Novo request for the AeroForm® Tissue Expander System is granted and the device is classified under the following:
Product Code: PQN Device Type: Carbon dioxide gas controlled tissue expander Class: II Regulation: 21 CFR 878.3510