AirXpanders AeroForm Tissue Expander System for Breast Reconstruction (XPAND-II)
Phase: NA
Conditions: Breast Cancer
Sponsor: AirXpanders, Inc.

Proprietary/Confidential 
 
 
 
 
 
 
Protocol CTP-0005 v 2.0 
June 30, 2015 
 
XPAND II 
AirXPanders AeroForm Tissue ExpaNDer System for Breast Reconstruction 
A  Prospective, Multi-Center, Single Arm, Open Label Continued Access Clinical Study 
Investigational Device Exemption (IDE) # G110022 
AirXpanders, Inc. 
1047 Elwell Court 
Palo Alto, CA 94303 
 
Author:  Kathryn Kelley, R.N., B.S.N., Director Clinical Affairs 
 
 
This document contains confidential and proprietary information.  It is intended for the use of AirXpanders, 
Inc., Clinical Investigators, Institutional Review Boards, U.S. Food and Drug Administration and others 
directly involved in the clinical investigation.  No unpublished information presented in this document may be 
disclosed, reproduced or referred to in any way without prior express written consent of AirXpanders, Inc.  
 
 

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Study Contacts 
 
AirXpanders Inc. 
 
 
1407 Elwell Court 
Palo Alto, CA  94303 
www.airxpanders.com 
 
650-390-9000 (Main) 
650-390-9007 (Fax) 
 
Daniel Jacobs, M.D. 
 
 
Chief Medical Officer 
jacobsdr@pacbell.net 
 
650-303-6140 (Cell) 
 
Kathryn Kelley, R.N., B.S.N. Director, Clinical Affairs 
AirXpanders, Inc. 
kkelley@airxpanders.com 
 
650-390-9003 (Office) 
650-390-9007 (Fax) 
925-360-5173 (Cell) 
 
SAE Hotline 
 
24 Hour FAX 
650-249-2200 
Emergency Contact 
 
AirXpanders (Main) 
650-390-9000 
 
 
 

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Protocol Signature Page – Sponsor 
 
Protocol: 
 
CTP-0005  
Study Title: 
AirXPanders AeroForm Tissue ExpaNDer System for Breast 
Reconstruction (XPAND II) 
Study Device: 
AeroForm® Tissue Expander System  
IDE #:   
 
G110022  
Protocol Version: 
2.0 
Device Version:   
Clinical Version 2.5 
Study Sponsor: 
AirXpanders, Inc. 
 
This protocol was written and will be conducted in compliance with FDA Investigational 
Device Exemption (IDE) regulations (21CFR, Part 812) as well as those regulations 
governing Institutional Review Boards (21 CFR, Part 56), Protection of Human Subjects 
(21 CFR, Part 50), Financial Disclosure by Clinical Investigators (21CFR, Part 54), ISO 
14155 for conduct of clinical investigations of medical devices including ICH Guidelines 
for Good Clinical Practice and any conditions of approval imposed by the FDA.  Any 
changes or modifications to this protocol will be submitted for approval to the appropriate 
regulatory authorities and/or IRBs prior to implementation of the proposed changes.  
 
Required Approval 
Name 
Signature 
Date 
Chief Medical Officer 
 
Daniel Jacobs, M.D. 
 
 
Director, Clinical Affairs 
 
Kathryn Kelley, R.N., B.S.N. 
 
 
Sr. Director, Quality & 
Regulatory  
 
Naghmeh Nouri 
 
 
President/CEO 
 
Scott Dodson 
 
 
Director, Research & 
Development 
Mark Payne 
 
 
 
 

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Statement of Agreement – Investigator 
Protocol: 
 
CTP-0005 
Study Title: 
AirXPanders AeroForm Tissue ExpaNDer System for Breast 
Reconstruction (XPAND II) 
Study Device: 
AeroForm® Tissue Expander System  
IDE #:  
G110022 
Protocol Version: 
2.0 
Study Sponsor: 
AirXpanders, Inc. 
I have read this protocol and agree to participate in the clinical investigation of the 
AeroForm® Tissue Expander System sponsored by AirXpanders, Inc.  I agree to 
conduct this investigation according to the requirements of the study protocol provided 
by the sponsor and in accordance with Good Clinical Practice guidelines and all 
applicable federal and state regulations as well as those conditions of approval imposed 
by the FDA and the governing Institutional Review Board. 
I agree to supervise all use of the investigational device at my institution and to ensure 
that appropriate written informed consent is obtained from all subjects prior to the 
performance of any study procedure.  I further agree to oversee all co-investigators and 
study personnel to whom I delegate responsibilities for the conduct of this study.  I will 
provide copies of this protocol and all pertinent information to the study personnel under 
my supervision.  I will discuss this material with them and ensure that they are properly 
trained regarding the use of this investigational device.  
I understand that this investigation will be monitored by the Study Sponsor and/or a 
designee of the Study Sponsor.  This monitoring will involve periodic inspection of my 
investigational site and ongoing review of the data that is submitted by me to the Study 
Sponsor. 
My current curriculum vitae are on file with the Study Sponsor along the curriculum vitae 
of those Physicians at my institution who will be participating in this study as co-
investigators under my supervision.  
______________________________________ 
 
____________________ 
Principal Investigator Signature 
 
 
 
 
Date 
______________________________________Printed Name 

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Table of Contents 
1 
Introduction ........................................................................................................................... 12 
1.1 
Background/Purpose ..................................................................................................... 12 
1.2 
Literature Review .......................................................................................................... 13 
1.3 
Pre-Clinical Testing ........................................................................................................ 14 
1.3.1 
Bench Testing ...................................................................................................... 14 
1.3.2 
Animal Testing ..................................................................................................... 14 
1.4 
Human Clinical Testing (PACE I/II, XPAND, ASPIRE) ....................................................... 15 
1.5 Marketing Authorizations .................................................................................................... 16 
2 
Study Rationale ...................................................................................................................... 16 
3 
Study Design .......................................................................................................................... 16 
4 
Study Objectives .................................................................................................................... 17 
4.1 
Primary Outcome Measure ........................................................................................... 17 
4.2 
Secondary Outcome Measures ..................................................................................... 17 
4.3 
Additional Outcome Measures ...................................................................................... 17 
5 
Statistical Considerations and Analysis Plan .......................................................................... 18 
5.1 
Introduction ................................................................................................................... 18 
6 
Study Population.................................................................................................................... 18 
7 
Subject Enrollment ................................................................................................................ 19 
7.1 
 Inclusion Criteria ........................................................................................................... 19 
7.2 
 Exclusion Criteria .......................................................................................................... 19 
8 
Study Duration ....................................................................................................................... 20 
9 
Subject Study Participation .................................................................................................... 20 
10 
Subject Withdrawal ............................................................................................................... 20 
11 
Study Visits ............................................................................................................................. 21 
11.1 
Pre-Screening ................................................................................................................. 21 
11.2 
Screening/Enrollment/Pre-Operative Visit (Pre Implant) ............................................. 21 
11.3 
Operative Visit (Implant) ............................................................................................... 23 
11.4 
Post-Operative Follow Up Visits (Post Implant) ............................................................ 24 
11.5 
Expansion Follow Up Visits (During Home Expansion) .................................................. 24 
11.6 
Operative Visit (Explant/Exchange to Permanent Implant) .......................................... 25 
11.7 
 Post-Operative (Post-Explant) Visit .............................................................................. 26 

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11.8 
Optional Visits/Additional Procedures .......................................................................... 26 
12 
Device Description/Intended Use .......................................................................................... 26 
12.1 
Device Description ......................................................................................................... 26 
12.1.1 
AeroForm™ Tissue Expander (Implant) .......................................................... 26 
12.1.2 
AeroForm Dosage Controller............................................................................. 27 
12.1.3 
AeroForm Physician Master Key ...................................................................... 28 
12.1.4 
Accessories .......................................................................................................... 29 
12.2 
Dosing ............................................................................................................................ 29 
12.2.1 
Physician Fill Mode ............................................................................................. 30 
12.3 
Intended Use ................................................................................................................. 30 
12.4 
Protocol/Device Training ............................................................................................... 30 
12.5 
Device Accountability .................................................................................................... 31 
12.6 
Device Disposition ......................................................................................................... 31 
12.7 
Device Malfunction/Damage/Loss ................................................................................ 31 
13 
Benefits/Risks ........................................................................................................................ 32 
13.1 
Benefits .......................................................................................................................... 32 
13.2 
 Clinical Risk Analysis ..................................................................................................... 32 
13.2.1 
Device Malfunctions ............................................................................................ 33 
13.2.1.1  Failure to Expand or Deflation ........................................................................... 33 
13.2.1.2 Over Expansion and/or Rupture ....................................................................... 33 
13.2.2 
Unknown Risks .................................................................................................... 34 
13.2.3 
Mitigations ............................................................................................................ 34 
13.2.3.1 Mitigations to prevent under expansion ........................................................... 34 
13.2.3.2 Mitigations to prevent over expansion ............................................................. 35 
13.2.3.3 Mitigations to prevent device rupture ............................................................... 35 
13.2.4 
Protection of Study Subjects ............................................................................. 36 
13.2.5 
Human Factors Considerations......................................................................... 37 
13.2.6 
Contraindications ................................................................................................. 37 
13.2.7 
Warnings ............................................................................................................... 37 
13.2.8     Precautions .......................................................................................................... 39 
13.2.9 
Other Considerations .......................................................................................... 41 
14 
Adverse Events ...................................................................................................................... 42 

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14.1 
Adverse Event (AE) ........................................................................................................ 42 
14.2 
Serious Adverse Event (SAE) .......................................................................................... 43 
14.3 
Device Related Adverse Event ....................................................................................... 43 
14.4 
Serious Device Related Adverse Event .......................................................................... 44 
14.5 
Unanticipated Adverse Device Event (UADE) ................................................................ 44 
14.6 
Reporting of Adverse Events ......................................................................................... 46 
14.7  
Additional Procedures, Pre-mature Explant, Device Replacement ............................... 46 
14.8  
Device Failures ............................................................................................................... 47 
15 
Investigator and Site Qualification ........................................................................................ 47 
16 
Investigator and Site Training ................................................................................................ 48 
17 
Monitoring of Investigational Sites ........................................................................................ 48 
18 
Protocol Compliance .............................................................................................................. 49 
18.1 
Protocol Violation .......................................................................................................... 49 
18.2 
Protocol Deviation ......................................................................................................... 49 
18.3 
Protocol Exemption ....................................................................................................... 50 
19 
Data Collection....................................................................................................................... 50 
19.1 
Electronic Case Report Forms (eCRFs) ........................................................................... 50 
19.2 
Subject Satisfaction and Usability Data ......................................................................... 50 
19.3 
Physician Satisfaction and Usability Data ...................................................................... 50 
19.4 
Photographs .................................................................................................................. 51 
19.5 
Device Data Logs ............................................................................................................ 51 
20 
Source Documentation .......................................................................................................... 51 
21 
Data Management ................................................................................................................. 52 
22 
Study Closeout ....................................................................................................................... 52 
23 
Record Retention ................................................................................................................... 53 
24 
Audits/Inspections ................................................................................................................. 53 
25 
Ethical and Regulatory Considerations .................................................................................. 53 
References: ................................................................................................................................ 54 
 
 
 

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List of Appendices 
Appendix A: 
Schedule of Study Procedures/Assessments 
Appendix B: 
Informed Consent Form Template (ICF) 
Appendix C: 
Case Report Forms (CRFs) 
Appendix D: 
Photography Protocol 
Appendix E:  Numeric Pain Scale 
 
List of Tables 
Table 1 AeroForm® Tissue Expander Models 
Table 2 Adverse Event Severity Rating 
Table 3 Adverse Event Device Relationship 
Table 4 Adverse Events 
Table 5 Potential AeroForm Device Malfunctions 
 
List of Figures 
Figure 1 AeroForm® Tissue Expander System 
Figure 2 AeroForm® Dosage Controller and AeroForm® Physician Master Key 
 
List of Product Labeling   
LS-0025 Recruitment Brochure  
LS-0003 Instructions For Use 
LS-0104 Patient Reference Card 
LS-0027 Patient Home Instructions  
LS-0128 Patient ID Card 
COL-0013 Patient Training  
 
 

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Protocol Synopsis 
 
Protocol 
CTP-0005, Version 2.0 
IDE # G110022 
Study Title 
AirXPanders  AeroForm Tissue ExpaNDer System for Breast Reconstruction 
(XPAND II) 
Sponsor 
AirXpanders Inc. 
Investigational Device 
AeroForm® Tissue Expander System v2.5 
Intended Use 
The AeroForm Tissue Expander System is intended for use in post-
mastectomy patients to develop tissue coverage prior to the placement of 
permanent breast implants.  The device is intended for temporary 
subcutaneous or submuscular implantation and is not intended for use 
beyond six months. 
Study Design 
This is a prospective, multi-center, single arm, open-label, continued access 
clinical study.  Subjects who meet the inclusion criteria and agree to 
participate in the study will be enrolled and implanted with the investigational 
AeroForm Tissue Expander.  If the subject is having a bilateral procedure, 
the AeroForm expander will be implanted in each side.  Subjects will be 
followed until the first post-operative visit after explant of the tissue 
expander(s) and exchange for permanent implant(s).  
Study Objective 
The objective of this study is to allow existing investigators continued access 
to the AeroForm Tissue Expander to treat patients while the company 
completes the marketing application and during the review process by FDA.  
Primary Outcome 
Measure 
The performance of the device will be evaluated by: 
Successful tissue expansion with exchange to a permanent breast implant 
unless exchange is precluded by a non-device related event. The primary 
endpoint will be analyzed per breast.  Breasts in which the expander is 
removed and/or replaced due to a device related adverse event or a device 
malfunction will be counted as failures. 
Secondary Outcome 
Measures 
The safety of the device will be evaluated by: 
 
Device related adverse events  
 
All adverse events, regardless of whether serious or there is a causal 
relationship to the device. 
 
Serious device related adverse events 
 
All serious adverse events, regardless of whether there is a causal 
relationship to the device. 
 
Device malfunctions leading to expander removal and/or 
replacement  
Additional Outcome 
Measures 
The usability of the device will be 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 implant to permanent implant). 
 
Subject reported pain ratings at the onset of active expansion and 
one week after beginning active expansion 

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Protocol 
CTP-0005, Version 2.0 
IDE # G110022 
Study Title 
AirXPanders  AeroForm Tissue ExpaNDer System for Breast Reconstruction 
(XPAND II) 
 
Overall subject satisfaction 
 
Overall physician satisfaction 
 
Reported device issues 
Study Population 
Women who are planning to undergo immediate or delayed breast 
reconstruction (unilateral or bilateral) post mastectomy and require tissue 
expansion to develop sufficient tissue coverage for placement of permanent 
implant(s). Up to 60 subjects will be enrolled in the study.  
Investigational Sites 
Up to 7 existing clinical sites will participate in the study. 
Investigators will be qualified board certified plastic and reconstructive 
surgeons with experience in breast reconstruction using tissue expanders 
and prior experience using the AeroForm Tissue Expander System. 
Recruitment/Enrollment 
Subjects will be recruited from current patient referrals at each site at the 
same rate of enrollment observed in the pivotal trial (XPAND). Investigators 
may enroll up to 4 subjects per month. The option of participating in the study 
will be discussed with the patients at their initial consultation visit and they 
will be given the informed consent.  Once the patient has had adequate time 
to read the informed consent and have all of their questions answered, they 
will be asked if they would like to participate in the study. Once an informed 
consent is signed, patients will be enrolled in the study and scheduled for 
surgery. 
Statistical Analysis 
Plan 
This study is a continued access study and the results of this study will be 
analyzed in accordance with the statistical analysis plan for the XPAND study 
(CTP-0003). 
Study Duration 
Approximately one year 
Subject Study Duration 
Expected subject participation will be up to 6 months.  Subjects will be 
followed from the time of implant to the first post-operative visit after explant 
of the tissue expander(s) 
Inclusion Criteria 
1. Subject is female between the ages of 18-70 
2. Subject requires tissue expansion as part of breast reconstruction 
3. Subject is able to provide written informed consent 
4. Subject is able and willing to comply with all of the study requirements 
5. Subject has the physical, perceptual and cognitive capacity to 
understand and manage the at home dosing regimen 
Exclusion Criteria 
1. Subject’s tissue integrity is unsuitable for tissue expansion 
2. Subject has residual gross malignancy at the intended expansion site  
3. Subject has current or prior infection at the intended expansion site 
4. Subject has a history of failed tissue expansion or breast 
reconstruction 
5. Subject has any co-morbid condition determined by the Investigator to 
place the subject at an increased risk of complications (e.g., severe 
collagen vascular disease, poorly managed diabetes) 
6. Subject is taking any concomitant medications determined by the 
Investigator to place the subject at an increased risk of complications 
(e.g., Prednisone, Coumadin). 

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Protocol 
CTP-0005, Version 2.0 
IDE # G110022 
Study Title 
AirXPanders  AeroForm Tissue ExpaNDer System for Breast Reconstruction 
(XPAND II) 
7. Subject is participating in a concurrent investigational drug or device 
study.  
8. Subject is current tobacco smoker. 
9. Subject is obese (BMI > 33). 
10. Subject is unwilling to comply with instructions to notify the investigator 
and discontinue dosing prior to air travel, travel to a higher altitude and 
during the travel period.  
11. Subject has an implanted electronic device such as a pacemaker, 
defibrillator, neurostimulator, or drug infusion device.  
12. Subject is pregnant or planning on becoming pregnant during the 
study period. 
13. Subject has a history of psychological condition, drug or alcohol 
misuse which may interfere with their ability to use the device safely. 
 
 
 

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1 
Introduction 
1.1 Background/Purpose 
According the American Society of Plastic Surgery statistics, 95,589 women 
underwent breast reconstruction in the United States in 2013. The majority of 
women chose implant based reconstruction (76,278), with most performed as a 
two stage procedure using tissue expanders followed by permanent implants 
(68,607). The current standard of care tissue expanders are filled with saline via 
needle injection on a periodic basis until expansion is complete.  Many women 
undergoing tissue expansion for breast reconstruction find this process 
uncomfortable and arduous requiring multiple office visits to complete the filling 
procedure. Physicians have long sought an alternative to the sterile procedure 
required to fill the current expanders.  
AirXpanders, Inc., located in Palo Alto, CA, has developed a novel remote-control 
breast tissue expander (AeroForm Tissue Expander System) which is filled from an 
internal source with carbon dioxide (CO2) eliminating the need for needle injections 
to fill the expander. This expander has the potential to make the process easier, 
faster and more comfortable while providing women with some degree of control 
over the expansion. The system is comprised of an implantable tissue expander 
which contains a reservoir filled with compressed carbon dioxide (CO2), and an 
external hand held remote control. The controller activates the opening of an 
internal valve housed within the CO2 reservoir to release carbon dioxide into the 
expander.   
Enrollment in a prospective, multicenter, randomized, controlled clinical trial to 
evaluate the safety and effectiveness of the AeroForm tissue expander was 
completed in the U.S. in 2015.  In this study, 150 women were randomized to 
either the investigational expander or saline expander control group using a 2:1 
randomization design.  Following mastectomy, subjects underwent a two stage 
procedure involving the placement of a tissue expander under the pectoralis major 
muscle and remaining skin of the absent breast.  The expanders were placed 
either at the same time as the mastectomy (immediate reconstruction) or at some 
point after the mastectomy (delayed reconstruction) in unilateral or bilateral 
procedures.    

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Once adequate wound healing was confirmed, the expanders were gradually 
inflated using the remote control in the investigational group, and by periodic 
injections of saline in the control group.  Once the overlying skin and muscle was 
stretched enough to provide adequate coverage, the expanders were removed and 
replaced by permanent breast implants.  
This study is a continued access study designed for experienced investigators for 
the purpose of retaining their skills and experience with the device while the 
company completes a marketing application and during FDA review.  The study is 
a single arm design with all subjects treated with AeroForm expanders.   
 
1.2 Literature Review 
The formal concept of surgical tissue expansion was first reported by Neumann in 
1957, and further refined for breast reconstruction by Radovan and Argenta in the 
1980s.  Current standard of care using saline expanders requires months of weekly 
office visits for bolus injections and is associated with discomfort from high volume 
inflations, risk of infection and iatrogenic punctures of the expanders 
A system designed for gradual, continuous expansion was shown by Bergé and 
others to be more rapid and well tolerated reducing the time burden and patient 
discomfort.  In the Bergé study, investigators used an osmotic expander that 
continuously absorbed surrounding tissue fluid after deployment.  However, a 
remaining concern was the inability to control osmotic expanders after they are 
deployed in the body.  
Widgerow tested an expansion device using an external pump connected through 
tubing to the implanted expander which was controlled by the patient.  He showed 
rapid time courses and patient satisfaction.  However, the connector tubing 
imparted a cumbersome setup for the patient and the fear that prolonged 
connection to the external environment carries a high risk of contamination.  
Because the expanded pocket eventually receives a permanent implant, any level 
of contamination is unacceptable. 
Reported complications from tissue expansion are typically due to poor tissue 
perfusion due to the poor vascularity of thin tissue flaps remaining following the 

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removal of breast tissue. The major complications involve wound healing issues 
with tissue necrosis, flap failure and infections which can lead to expander removal 
and failed reconstruction.  Retrospective studies report an overall failure rate of 1.8 
to 18%.  Complications are exacerbated in this population in patients who undergo 
neo-adjuvant or adjuvant chemotherapy and radiation treatments for breast cancer.  
Published reports published on the use of the AeroForm Tissue Expander System 
indicate that tissue expansion and breast reconstruction can be accomplished 
faster using this device with a similar complication rate to that reported in the 
literature (Connell, Ascherman, Zeidler).  Connell and Zeidler also reported that 
radiation therapy can be delivered successfully with the expander in situ.   
1.3 Pre-Clinical Testing 
1.3.1 Bench Testing 
The AeroForm Tissue Expander System has undergone thorough verification and 
validation testing that included: 
 
Biocompatibility 
 
Performance and functionality 
 
Stress and wear 
 
Sterilization validation 
 
Transit  
 
Shelf-life 
 
Electrical safety 
 
EMC 
 
Software validation 
 
1.3.2 Animal Testing 
A pre-clinical study was conducted in February 2009 using two sheep to confirm 
that the AeroForm Tissue Expander System operated as designed.  Results of the 
in vivo sheep model study demonstrated that the device performed as intended 
(Jacobs).  All implants consistently responded to user input via the hand-held 
remote control, desired volume expansion was achieved and no clinical safety-
related issues were identified. 

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1.4 Human Clinical Testing (PACE I/II, XPAND, ASPIRE) 
The first human feasibility study (PACE 1, Connell) was conducted at one 
investigational site in Perth, Australia beginning in June 2009.  The study was a 
prospective, open-label, single arm feasibility study and established the safety of 
the AeroForm System for gradual, incremental breast tissue expansion prior to 
permanent breast reconstruction, paving the way for further clinical investigations.   
Seven subjects were enrolled in the study and 10 AeroForm expanders (Clinical 
Version 1.0) were implanted in combination with a latissimus dorsi flap procedure.  
All seven subjects were successful using the device to complete their expansion at 
home and completed their reconstructions.  The average length of active patient 
dosing was 15 days with a range of 5-22 days. The average time from expander 
implant to exchange for a permanent implant was 105 days with a range of 69-196 
days.  During the course of this study, some expanders had a higher than expected 
degree of permeation and required additional interim dosing.  This permeation was 
traced to a design issue (molding seam) that was eliminated in Clinical Version 2.0.  
Beginning in 2011, an additional 33 subjects were enrolled at the same site in the 
next phase of the study (PACE II, Connell). Sixty-one (61) AeroForm Tissue 
Expanders (Clinical Version 2.0) were implanted, and all 33 subjects successfully 
completed expansion and reconstruction. The average time to complete the 
expansion was 17 days and the average time to complete reconstruction was 90 
days.   
In a continued access study (ASPIRE) in Australia conducted in 2013 an additional 
21 subjects were enrolled with 34 expanders implanted. The average time to 
complete the expansion was 22 days and the average time to complete 
reconstruction was 96 days.  Two subjects in this study had prolonged courses due 
to complications related to poor tissue perfusion of dermal flaps that were used as 
an alternative to the investigators typical latissimus flap procedure.  
In parallel to PACE II and ASPIRE, a prospective, multi-center, randomized, 
controlled clinical trial was initiated in the United States in October 2011 with 
enrollment completed in December 2014.  A total of 150 subjects were treated after 
randomization (2:1 AeroForm to saline expander - 98 AeroForm, 52 Saline) at 17 
sites with 168 AeroForm expanders and 89 saline expanders implanted. The 

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bilateral rate was 71%.  The study was conducted with Clinical Version 2.0 (90 
expanders) and Clinical Version 2.5 (78 expanders).  Clinical version 2.5 was 
introduced during the trial to improve the barrier layer of the expander which 
contains the CO2 and to allow the physicians increased access to the available 
CO2 in the reservoir.   
1.5 Marketing Authorizations 
The AeroForm Tissue Expander has received CE marketing, but marketing and 
sales in Europe has not commenced.  Additionally, a license approval has been 
granted by the TGA (Australia), and a limited market release of the product began 
in September, 2014.  Limited data are available from the commercial experiences 
in Australia.  
2 
Study Rationale 
The creation of a stable formed pocket for placement of a permanent implant is the 
foundation of successful implant based breast reconstruction, which can significantly 
improve the quality of life for a woman following the devastating effects of breast cancer. 
The AeroForm System provides a needle free alternative to standard saline expanders 
and allows patients to participate in the expansion process with oversight by their 
physician.  Tissue expansion with the AeroForm System eliminates the need for periodic 
bolus injections and may be performed at the patient's convenience at home under the 
direction of the physician.  The incremental release of CO2 on a daily basis allows a 
more gradual method of tissue expansion than with saline expanders. 
Results of the previous clinical studies provides evidence that the AeroForm expander 
can be used safely and effectively to create the space needed to support permanent 
breast implants.  Continued access to this technology is necessary to confirm the 
performance, collect additional usability data and refine best practices for its use.   
3 
Study Design 
This is a prospective, multi-center, single arm, open-label, continued access study.  
Subjects who meet the inclusion criteria and agree to participate in the study will be 

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enrolled and implanted with the AeroForm Tissue Expander.  If the subject is having a 
bilateral procedure, the investigational expander will be implanted in each side. Subjects 
will be followed until the first post-operative visit after explant of the tissue expander(s) 
and exchange to permanent implant(s).  The study will be conducted according to IDE 
regulations. 
4 
Study Objectives 
The objective of this study is to allow existing investigators continued access to the 
AeroForm Tissue Expander to treat patients while the company completes the marketing 
application and during the review process by FDA.  
 
4.1 Primary Outcome Measure 
The performance of the device will be evaluated by: 
Successful tissue expansion with exchange to a permanent breast implant unless 
exchange is precluded by a non-device related event. The primary endpoint will be 
analyzed per breast. Breasts in which the expander is removed and/or replaced 
due to a device related adverse event or a device malfunction will be counted as 
failures.   
 
4.2 Secondary Outcome Measures 
The safety of the device will be evaluated by: 
 
Device related adverse events  
 
All adverse events, regardless of whether serious or there is a causal 
relationship to the device. 
 
Serious device related adverse events 
 
All serious adverse events, regardless of whether there is a causal 
relationship to the device. 
 
Device malfunctions leading to expander removal and/or replacement.  
 
4.3 Additional Outcome Measures 
The usability of the device will be evaluated by:  

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 
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 implant to permanent implant exchange). 
 
Subject reported pain ratings at the onset of expansion and one week after 
beginning active expansion 
 
Overall subject satisfaction 
 
Overall physician satisfaction 
 
Reported device issues  
5 
Statistical Considerations and Analysis Plan 
5.1 Introduction 
This is a prospective, multi-center, single arm, controlled, open-label continued 
access study.  The results will be analyzed in accordance with the statistical 
analysis plan for the XPAND study (CTP-0003, v 9.0).   
All subjects will be followed on an intent-to-treat basis.  The primary risk benefit 
analysis for the device will be assessed based on a per protocol analysis of the 
primary performance and safety endpoints. Modified Intent-to-Treat and Safety 
analyses, along with other secondary analyses, will also be completed and 
reported.   
6 
Study Population 
The study population will consist of women who are planning to undergo immediate or 
delayed breast reconstruction (unilateral or bilateral) post mastectomy and require tissue 
expansion to develop sufficient tissue coverage for placement of the permanent 
implant(s). Up to 60 subjects will be enrolled in the study.  

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7 
Subject Enrollment 
Subjects will be selected from current patient referrals at each site. Study participation 
will be open to subjects of all ethnicity and races.  The demographics are expected to 
reflect those of the current population of patients undergoing reconstructive surgery.  
The option of participating in the study will be discussed with the patients at their initial 
consultation visit and they will be given the informed consent to take home and read.  
Once the patient has had adequate time to read the informed consent and have all of 
their questions answered, they will be asked if they would like to participate in the study.  
Once an informed consent is signed, patients will be enrolled in the study and scheduled 
for surgery.  
7.1  Inclusion Criteria 
1. Subject is female between the ages of 18-70 
2. Subject requires tissue expansion as part of breast reconstruction 
3. Subject is able to provide written informed consent 
4. Subject is able and willing to comply with all of the study requirements 
5. Subject has the physical, perceptual and cognitive capacity to understand 
and manage the at home dosing regimen  
 
7.2  Exclusion Criteria 
1. Subject’s tissue integrity is unsuitable for tissue expansion 
2. Subject has residual gross malignancy at the intended expansion site 
3. Subject has current or prior infection at the intended expansion site 
4. Subject has a history of failed tissue expansion or breast reconstruction 
5. Subject has any co-morbid condition determined by the Investigator to place 
the subject at an increased risk of complications (e.g., severe collagen 
vascular disease, poorly managed diabetes) 
6. Subject is taking any concomitant medications determined by the Investigator 
to place the subject at an increased risk of complications (e.g. Prednisone, 
Coumadin) 
7. Subject is participating in a concurrent investigational drug or device study 
8. Subject is current tobacco smoker 
9. Subject is obese (BMI > 33) 

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10. Subject is unwilling to comply with instructions to notify the investigator and 
discontinue dosing prior to air travel, travel to a higher altitude and during the 
travel period. 
11. Subject has an implanted electronic device such as a pacemaker, 
defibrillator, neurostimulator or drug infusion device. 
12. Subject is pregnant or planning on becoming pregnant during the study 
period. 
13. Subject has a history of psychological condition, drug or alcohol misuse 
which may interfere with their ability to use the device safely. 
8 
Study Duration 
Subjects will be enrolled over a six month period.  Total study duration is expected to be 
up to one year. 
9 
Subject Study Participation 
Subject participation will be up to 6 months.  Subjects will be followed from the time of 
implant to the first post-operative visit following explant of the expander (s) and 
exchange to permanent implant (s).  It is expected that all subjects will have the 
expander(s) removed and permanent implant(s) placed within 6 months. 
10 Subject Withdrawal 
Participation in the XPAND II study is voluntary.  A subject may withdraw their consent at 
any time during the course of the study.  If the subject withdraws their consent prior to 
the expander implant procedure, the subject will be withdrawn from the study.  If the 
subject desires to withdraw their consent following the implant, the risks associated with 
withdrawal from the study will be discussed with the subject.  If the subject chooses to 
withdraw, the device must be explanted.  The Investigator may withdraw a subject from 
the study prior to the implant procedure if he/she determines that the subject is not an 
appropriate candidate.  Following implant, the Investigator should continue to follow the 
subject until the investigational device is explanted. 

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11 Study Visits 
11.1 Pre-Screening 
At the initial consult with the plastic reconstructive surgeon, women who are 
planning on having two-stage breast reconstruction will be asked to consider 
participating in the XPAND II clinical study.  A standard HIPAA authorization will be 
placed in the medical record allowing access to their personal health information 
and pre-screening for eligibility may be done.  Patients will be given the written 
informed consent to read at home.  If after thoroughly reading the consent the 
patient is interested in study participation, a screening visit will be scheduled. 
11.2 Screening/Enrollment/Pre-Operative Visit (Pre Implant) 
Day (- 30) to Day (- 1) (Required) 
The initial screening visit will occur between 1-30 days prior to the planned surgery 
date.  This visit may be scheduled in conjunction with the standard pre-operative 
visit.  
At the screening visit the following procedures/assessments will be performed: 
HIPAA Authorization 
The subject will be asked to sign a study specific HIPAA authorization form 
acknowledging their consent to allow access to their personal health information by 
study staff, designated sponsor staff and required regulatory authorities during the 
course of their study involvement.  
Informed Consent  
The IRB approved informed consent form will be reviewed with the subject after 
they have had adequate time to read the form in its entirety.  The subject will be 
encouraged to ask questions and confirm their understanding of the study protocol 
and procedures.  The informed consent form will be signed by the subject, the 
designated study personnel delegated to administer the informed consent process 
and the subject will be given a fully executed copy.  No study procedures may be 
performed or data collected prior to the completion of the informed consent.  

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Inclusion/Exclusion Criteria 
The inclusion and exclusion criteria will be reviewed with the subject.  The subject 
may be enrolled in the study only if they meet all of the inclusion criteria and none 
of the exclusion criteria.  If any of the inclusion criteria are not met or if any of the 
exclusion criteria are met, the subject will not be enrolled in the study and will be 
considered a screen failure.  
Medical History 
The subject will be interviewed by delegated site personnel and all pertinent 
medical and surgical history will be recorded on the history and physical form.  
Physical Exam 
A brief physical exam will be performed by qualified site personnel.  Any abnormal 
findings will be recorded on the history and physical form.  
Concomitant Medications 
Prescription concomitant medications will be recorded at the screening visit.  Any 
changes to the concomitant medications will be recorded at each study visit. 
Subject’s will be asked to discontinue any medications such as blood thinners or 
platelet inhibitors (NSAIDs, Aspirin, Clopidogrel) that may place the subject at an 
increased risk of surgical complications prior to the operative procedure per the 
standard of care. It is not required to record vitamins, herbs, stool softeners, sleep 
medications or anesthetic agents given during the procedures.   
Laboratory Tests 
No study specific laboratory testing is required.  Routine pre-operative laboratory 
testing will be done per standard of care.  A urine pregnancy test will be performed 
at the screening visit for women of childbearing potential. If the test is positive, the 
subject cannot be enrolled in the study.  Study subjects will be counseled to use a 
medically acceptable form of birth control during the study period. 
 
 

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Pre-operative Photographs 
Photographs will be taken of the chest wall prior to surgery.  The photographs will 
be taken in accordance with AirXpanders Photography Protocol.  
Patient Teaching and Assessment 
All subjects will be provided the Patient Teaching presentation on the AeroForm 
System and shown teaching models of the AeroForm Tissue Expander and the 
AeroForm Dosage Controller.  The use of the dosage controller will be explained 
verbally and the patient will be given Patient Home Instructions to take home and 
review.  The subject will be given adequate time to review the material and ask 
questions.  The subject will verbally confirm their understanding, demonstrate their 
ability to operate the device and confirm their willingness to use the device for 
home tissue expansion. Note that patient teaching is an ongoing process and 
should be done at all visits.  
Enrollment 
The subject will be considered enrolled in the study once the written informed 
consent is signed, the inclusion/exclusion criteria have been confirmed and all 
screening procedures have been completed.  A subject specific identifier will be 
assigned at that time.  AirXpanders will be notified of patient enrollment and the 
scheduled implant date. 
11.3 Operative Visit (Implant) 
Day 0 (Required) 
At the operative visit the following procedures/assessments will be performed: 
 
Confirmation of Inclusion/Exclusion Criteria 
 
Surgical Procedure (Expander Implant) 
 
Intraoperative Dosing 
 
Device Accountability 
 
Operative Report (copy to subject study file) 
 
Physician Device Evaluation 
 
Concomitant Medications 
 
Adverse Events 

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 
Patient Teaching 
 
Subject will be given the Patient ID Card with emergency contact information 
prior to discharge 
11.4 Post-Operative Follow Up Visits (Post Implant)  
Day 7 +/- 3 days, Day 14 +/- 3 days, Day 21 (+/- 3 days) then every two weeks (+/- 
5 days) until expansion is started.(Required) 
After surgery, tissue perfusion and wound healing status will be assessed to 
determine readiness for active home expansion.  Once the subject is ready to 
begin active home expansion, she will be given the dosage controller (s) and 
instructed on daily dosing.  The Patient Home Instructions will be reviewed with the 
subject prior to starting home expansion. 
At the post-operative visits the following procedures/assessments will be 
performed: 
 
Surgical Site Assessment 
 
Concomitant Medications 
 
Adverse Events 
 
Patient Teaching 
 
MD Dosing (Optional) 
 
Record Date Home Expansion is Started  (start of home dosing is at the 
discretion of the investigator based on wound healing and subject comfort) 
 
Photographs (on the day that home expansion is started). Photographs 
should also be taken to document any adverse events related to the breast.  
 
Numeric Pain Scale (A standard 11 point numeric pain scale will be 
completed by the subjects on the day that home expansion is started) 
11.5 Expansion Follow Up Visits (During Home Expansion) 
1 week post home expansion start date (+/- 3), then every two weeks (+/-5) until 
expansion is complete, then monthly until the exchange procedure. 
After home expansion begins, subjects will be assessed for expansion progress.  
Once full expansion is reached, subjects will be instructed to dose once or twice 
per week to maintain the volume and visits may then occur monthly.  Once the 

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subject is ready for exchange, the procedure will be scheduled and AirXpanders 
will be notified of the scheduled explant date. 
At the expansion follow up visits the following procedures/assessments will be 
performed: 
 
Surgical Site Assessment 
 
Expansion Assessment 
 
Numeric Pain Scale (A standard 11 point numeric pain scale will be 
completed by the subjects one week after the start of home expansion, and 
on the day expansion is complete) 
 
Photographs (on the day that expansion is complete).  Photographs should 
also be taken to document any adverse events related to the breast. 
 
Concomitant Medications 
 
Adverse Events 
 
MD Dosing (Optional)  
 
Record Date Expansion is Complete (subjects to discontinue daily dosing and 
begin maintenance dosing at least once per week until explant)  
 
Patient Teaching 
11.6 Operative Visit (Explant/Exchange to Permanent Implant) 
Investigators Discretion (Not > 6 months post implant) 
The investigator will determine when the subject is ready to exchange to 
permanent implants. The expander(s) will be explanted and returned to 
AirXpanders for evaluation. Second stage breast reconstruction will be completed 
with placement of permanent implant(s).  
At the operative visit the following procedures/assessments will be performed: 
 
Tissue Expander Explant/Implant of Permanent Breast Prosthesis 
 
Device Accountability 
 
Operative Report (copy to subject study file) 
 
Concomitant Medications 
 
Adverse Events 
 
Physician Device Evaluation  

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11.7  Post-Operative (Post-Explant) Visit  
1-2 week post-operative (explant)  
Following the explant/exchange surgery the subject will be assessed and final 
reconstruction results documented.  
At the post-operative visit the following procedures/assessments will be performed: 
 
Surgical Site Assessment 
 
Concomitant Medications 
 
Adverse Events 
 
Photographs (Photographs of the final reconstruction results will be taken) 
 
Subject Satisfaction Survey 
 
Physician Satisfaction Survey 
11.8 Optional Visits/Additional Procedures 
Optional visits may be scheduled at the discretion of the investigator i.e., for 
follow up of adverse events or evaluation of expansion progress.  Any additional 
procedures performed during the course of the study such as needle aspirations, 
surgeries or radiation treatments will be recorded.    
12 Device Description/Intended Use 
12.1 Device Description 
The AeroForm Tissue Expander System (Figure 1) is comprised of the AeroForm 
Tissue Expander, the AeroForm Dosage Controller and AeroForm Physician 
Master Key.  For a full description and details of the components, please refer to 
the Instructions For Use (IFU).  
12.1.1 
AeroForm™ Tissue Expander (Implant) 
The AeroForm Tissue Expander is a sterile product and consists of a textured 
outer shell, an inner CO₂ gas barrier, a stainless steel CO2 reservoir and 
antenna/electronics for communication.  The CO₂ reservoir has an internal valve 

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that is activated by the remote control to release a small, 10cc dose of CO2.  The 
release of CO₂ results in gradual expansion of the implant.   
Following expansion, the expander is removed and exchanged for a permanent 
breast implant. 
 
Figure 1:  AeroForm Tissue Expander System 
 
 
Table 1 lists the size options and corresponding model numbers for the AeroForm 
Tissue Expander.  All models have a textured surface and anatomical shape. 
Table 1 Available AeroForm Tissue Expander Models (Clinical Version 2.5) 
Model # 
Size 
Width (cm) 
Un-inflated 
Height 
(cm) 
Projection 
(cm) 
Inflated 
Volume 
(cc) 
LP105-400 
Small 
12.5 
11.0 
8.0 
400 
LP120-650 
Medium 
14.0 
12.5 
9.5 
600 
LP130-850 
Large 
15.5 
14.0 
10.5 
800 
 
12.1.2 
AeroForm Dosage Controller 
The AeroForm Dosage Controller (Figure 2) is a small, battery operated, hand held 
controller that remotely activates the expander to release CO2.  The controller is 
configured to provide temporary power and coded instructions to the paired 
expander.  It has a center button with a row of indicator lights and audible tones to 
provide position and CO2 delivery information to the user. The controller is 
permanently bonded to an expander at the time of implant and will not function with 

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other expanders.  The controller is programmed to deliver a dose of 10cc with each 
push of the button with a lockout period of 3 hours and a daily maximum of 30cc. 
The controller tracks the timing and volume of dosing and estimates the volume of 
CO2 in the expander. Once the controller estimates that the expander is at full 
volume, it is programmed to allow patient dosing in the amount required to 
maintain the labeled volume.   
12.1.3 
AeroForm Physician Master Key 
The AeroForm Physician Master Key is used by trained medical personnel only.  
When the key is inserted into the controller, consecutive doses can be given with 
no daily limit on the interval between doses or the number of doses (up to the 
labeled volume of the expander). The physician may provide volume above the 
programmed limits if needed using Physician Fill Mode.  Dosing beyond the 
labeled volume should only be done if there is a loss of volume.  
The Physician Master Key allows trained medical personnel to:  
 
Test the AeroForm expander in the operating room prior to implant 
 
Fill the expander to the desired intra-operative volume  
 
Add volume to the expander during office visits   
 
Add volume to the expander after labeled volume has been reached, if 
needed, due to a loss of volume 
The key is to be retained by the physician for their use only and is not to be 
provided to the subjects.  Figure 2 shows the controller and the key.   

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Figure 2: AeroForm Dosage Controller and AeroForm Physician Master Key 
12.1.4 
Accessories 
An Aseptic Transfer Pouch is provided with the Dosage Controller for use during 
the implant procedure to maintain the sterile field. 
12.2 Dosing 
A dose is defined as the amount of CO2 released within the expander each time 
the center button is pressed.  The controller is programmed to limit a single dose to 
10cc.  The subject will not be able to administer a dose more than once every three 
hours with a maximum of 30cc in a 24 hour period.  However, the surgeon may 
add volume if needed with the use of the Physician Master Key.  
Prior to implant, the expander is bonded to a controller by inserting the Physician 
Master Key that is packaged with the expander into the slot on the bottom of the 
controller.  A test dose is administered prior to implant to confirm that the controller 
is communicating with the expander.  Following implant, an initial series of 10cc 
doses are administered to fill the surgical pocket.  Post-operative, once the surgical 
site is adequately healed and the patient is comfortable, the first daily dose is 
administered in the physician’s office.  The subject is then instructed to administer 
daily doses (10cc) up to three times daily, dependent on their comfort level.  At 

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expansion follow up visits, the physician may administer additional doses in the 
office based on subject and tissue tolerance using the Physician Master Key.  
Once full expansion has been achieved, the patient should be instructed to 
administer weekly doses until explant to maintain the volume of the expander.   
12.2.1 Physician Fill Mode 
When the AeroForm expander reaches the programmed volume, the indicator 
lights will flash and the controller will shut off.  If the Physician Master Key is 
inserted and the controller is turned back on, the programming converts to 
Physician Fill Mode which allows the physician to administer up to 25% of the 
labeled volume every two weeks.   
This mode is intended to be used only when the physician assesses that the 
expander needs additional fill to maintain full volume. 
Dosing above the labeled volume may result in an increase in the relative pressure 
of the expander. Expander fill should be assessed by the physician based on 
tissue laxity, perfusion and firmness of the expander.  Care should be taken to 
ensure that overfilling does not occur. 
Once the controller has converted to Physician Fill Mode, no patient dosing will be 
possible, therefore, the controller will have no functional value to the patient and 
may be kept by the physician. Any further dosing will need to be done in the office.   
12.3 Intended Use 
Tissue expanders are intended for single patient use in post-mastectomy patients 
to develop adequate tissue coverage for the placement of permanent breast 
implants. The AeroForm expander is intended for temporary subcutaneous or 
submuscular implantation and is not intended for use beyond six months. 
12.4 Protocol/Device Training 
Training will be provided by the Sponsor to the Principal Investigator (PI), Co-
Investigators, and site study staff at the site initiation visit.  The training will include, 
at a minimum, the protocol requirements, device training, implant and explant 
procedures specific to the device, post-operative follow up, dosing, device 

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accountability, contraindications, warnings and precautions as stated in the 
Instructions For Use.  
The study staff will in turn, train the subjects on the protocol requirements, device 
function, dosing considerations, dosing limits, dosing steps, contraindications, 
warnings and precautions.  Written material will be provided to train the subjects on 
the AeroForm System and Patient Home Instructions will be provided.  
12.5 Device Accountability 
This AeroForm System is labeled for investigational use only in the United States.   
The investigator is responsible for ensuring that it is used only in subjects enrolled 
in the study as well as for maintaining accountability of all investigational devices in 
their possession.  Each expander is supplied with multiple patient record labels 
showing the model number and lot number for that expander.  One of these labels 
should be attached directly to the subject’s chart.  A second label should be 
attached to the bonded controller. Additional labels are provided to be used, as 
needed. 
12.6 Device Disposition 
The Investigator shall maintain records of the receipt and disposition of all 
investigational devices.  When enrollment is complete, the Investigator shall return 
any unused devices to the sponsor.  At the time of explant, the controller is to be 
returned to AirXpanders.  The explanted tissue expander should be returned to 
AirXpanders with the appropriate biohazard packaging supplied by the sponsor.   
12.7 Device Malfunction/Damage/Loss 
All device malfunctions should be reported to the Sponsor immediately and 
recorded on the device malfunction CRF.  If an expander malfunctions, explant and 
replacement may be necessary.  In the event of an expander malfunction requiring 
replacement, investigator and subject will have the option of replacement with the 
investigational expander or a standard saline expander.   
Dosage Controllers are intended for single patient use.  One controller will be 
bonded with one expander at the time of implant.  Subjects with bilateral implants 
will have two controllers, one for each expander.  The controllers will be labeled to 
indicate which expander/side it is bonded to.  The implanted expander can only be 

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activated by the bonded controller.  Subjects with bilateral expanders should be 
instructed to dose one implant at a time.  If a controller is lost or damaged a 
replacement controller will be provided and bonded with the respective expander. 
13 Benefits/Risks 
The device has the potential to make the expansion process faster, more comfortable 
and more convenient for both the patient and physician.  
13.1 Benefits 
Tissue expansion with saline tissue expanders is a lengthy and uncomfortable 
experience.  The AeroForm System is designed to allow for non-invasive, 
incremental expansion which can be controlled by the patient. Tissue expansion 
with the AeroForm System eliminates the need for weekly injections of saline and 
may be performed at the patient's convenience at home under the direction of their 
physician.  Incremental dosing on a daily basis provides a gradual method of 
expansion that can be adjusted according to a patient’s pain level, thus providing 
an easier, more comfortable method of expansion.  Results of the previous clinical 
studies indicate that the AeroForm System is safe and effective for breast tissue 
expansion and can expedite the expansion and reconstruction process.  
13.2  Clinical Risk Analysis 
Most risks associated with the use of the AeroForm System are similar to those 
associated with saline-filled tissue expanders.  Undergoing any surgical procedure 
may involve the risk of complications from the effects of anesthesia or the surgical 
procedure.  There are common side effects that may occur with any tissue 
expander implant such as inflammation, bruising, bleeding, hematoma, seroma, 
fever, infection, pain, paresthesia, scarring, stretch marks, skin breakdown, wound 
dehiscence, skin necrosis, extrusion, capsular contracture, chest wall deformity, 
displacement, or allergic reactions. 
There are also device malfunctions that may occur with either type of expander 
such failure to expand or deflation due to internal causes (valve failure) or due to 
external causes such as implant leak or inadvertent needle puncture.  Implant 

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rupture can occur from over-pressurization of the implant or from blunt force 
trauma.  If failure to expand, deflation, leaking, needle puncture, or rupture occurs, 
device removal and/or replacement will be necessary.   
13.2.1 
Device Malfunctions  
13.2.1.1  Failure to Expand or Deflation 
The expander will not be able to be fully inflated if: 
 
The expander antenna does not respond to the controller  
 
The controller fails to operate properly  
 
The valve of the CO2 reservoir fails to open  
 
The valve does not release the correct amount of CO₂  
 
There is not enough CO2 in the reservoir to achieve final volume  
 
There is a leak in the implant or excessive permeation through the CO₂ 
barrier  
 
If the expander fails to expand or becomes deflated, removal and/or replacement 
may be necessary.   
13.2.1.2 
Over Expansion and/or Rupture 
Over expansion of the expander may occur if:  
 
There is a change in altitude greater than approximately 3300 feet (1000 
meters) from baseline leading to CO₂ expansion  
 
The expander is filled beyond the tissue tolerance or patient comfort due to a 
device malfunction or operator error 
 
The valve fails and leaks or is stuck in the open position leading to a slow or 
rapid release of CO₂ 
Rupture of the expander may occur if:  
 
The volume of the inner gas barrier increases beyond the maximum labelled 
volume 
 
The expander is damaged either by a sharp instrument or by blunt force trauma 
 
An increase in volume could lead to pain and/or wound dehiscence (dependent on 
the healing stage of the surgical site).  Once the labeled volume is reached, the 

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pressure inside the non-distensible inner gas barrier will increase if additional 
volume is added up to the point at which the gas barrier will rupture.  The rupture 
will typically present as an opening in the anterior wall of the gas barrier through 
which CO₂ will be released into the space between the inner barrier and outer 
silicone shell.  The gas will permeate through the ventilation holes and the porous 
outer shell and dissipate in the surgical pocket (subcutaneous/subpectoral space) 
and surrounding tissue likely resulting in temporary subcutaneous emphysema. 
The CO₂ will be absorbed by the body via diffusion from the tissue into the 
bloodstream and eliminated through normal gas exchange in the lungs. If wound 
dehiscence occurs, CO₂ will be released via the separation of the wound.  If 
necessary, the expander may be deflated with a hypodermic needle.  The device 
may require removal and/or replacement (depending on the stage of expansion).   
13.2.2 
Unknown Risks 
As with any investigational device, there may be risks associated with the use of 
the AeroForm System that are unknown.  Any unexpected adverse device effect 
should be reported to the sponsor immediately. 
13.2.3 
Mitigations 
AirXpanders has designed, manufactured and thoroughly tested the AeroForm 
System to minimize the potential complications associated with its use.  This study 
protocol has been designed to protect the safety of the participants.  
A thorough biocompatibility study was performed on all materials used in the 
implant that are, or could come into patient contact. Additionally AirXpanders 
corporate quality control systems enforce that no unintended materials are used in 
the manufacture of the device.   
13.2.3.1 Mitigations to prevent under expansion 
The electronics and communication between the reservoir valve and the controller 
have been tested extensively as part of the quality assurance process, as well as 
during bench, animal and human studies. A replacement dosage controller can be 
provided and bonded with the implant if the expander stops communicating with 
the dosage controller or the dosage controller fails to operate. The CO2 reservoir 
valve had been tested extensively and the reservoir is filled with a sufficient 

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amount of compressed CO2 to inflate the tissue expander to the labelled volume 
and account for expected loss due to permeation.  The inner gas barrier of the 
expander was specifically designed to minimize the loss of CO2.  The seals of the 
expander have been reinforced and tested to minimize the chance of leaks.  
Once the desired volume is reached, if more than expected loss of volume occurs, 
intermittent dosing (up to 25% of the labelled volume every two weeks) using 
Physician Fill Mode can be done to maintain the volume of the expander.  
13.2.3.2 Mitigations to prevent over expansion 
Once the CO2 is released into the implant, it may expand if there is a significant 
change in altitude.  This is due to the fact that CO₂ expands at higher altitudes 
such as during air travel.  The instructions for use and device labelling contain 
warnings and precautions for patients planning air and mountain travel.  Subjects 
will be required to inform their physician prior to travel and discontinue dosing for a 
period of at least two weeks prior to travel until their return.  Care should be taken 
not to over fill the expander beyond tissue tolerance or patient comfort since there 
is no way to remove CO₂. 
The possibility of over filling the expander is reduced through the programmed 
limits of a maximum daily dose of 30cc and the interval lock out period of 3 hours.  
Only the investigator may add volume above these limits with the use of the 
Physician Master Key.  The limits are intended as a patient safety feature only and 
are not meant to be prescriptive.  The physician should exercise his/her clinical 
judgement to fill the expander to the desired volume according to tissue tolerance 
and subject comfort as noted in the Instructions For Use (IFU).  
The AeroForm System has been designed and tested to address potential failures 
of the device that may lead to over expansion.  The reservoir valve is 
manufactured with a non-reactive material and has been designed to fail in the 
closed position, thus minimizing the risk of over expansion. 
13.2.3.3 
Mitigations to prevent device rupture  
As noted above, the AeroForm System has been designed to mitigate against 
over-expansion which may lead to excessive pressure and potential device 

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rupture.  Labeling and training are in place to take precautions when traveling to 
higher altitudes or over-filling the expander.  The valve is designed to fail in the 
closed position minimizing the possibility of a rapid release of CO₂.  Injury by blunt 
trauma or sharp objects may result in damage to the expander, resulting in rupture 
which may occur with any implant.  In the event of a sudden rupture of the 
AeroForm expander, an accumulation of CO₂ under the skin (subcutaneous 
emphysema) could occur.  CO2 is a natural product of cellular activity and is highly 
soluble in tissue and was chosen specifically because of its demonstrated safety 
when used in the body for other medical purposes.  Any risks associated with 
tissue contact with the CO2 and the inner components of the device are negligible 
as both are composed of common materials used for medical purposes and are 
sterilized.   
Rupture of the device will disable the device and will require immediate medical 
attention and removal of the expander.  
13.2.4 
Protection of Study Subjects  
 
AirXpanders has incorporated several procedures into the investigational plan and 
system labelling to protect study patients from any potential adverse device effects.  
There are stringent inclusion/exclusion criteria in the investigational protocol that 
will exclude any study subject who may be at increased risk of complications.  The 
investigational protocol requires routine office visits to assure that any acute 
adverse effects are detected in a timely manner and proper medical treatment can 
be initiated.  Subjects will be instructed to call their doctor immediately if they 
encounter any problems with the device or experience signs of complications.  The 
Instructions for Use (IFU) describes the proper technique for the implantation 
procedure and expansion process in detail and training will be provided to both 
Investigators and study subjects on the proper use of the device.  Device Training, 
Investigator and Patient Reference Cards along with Patient Home Instructions are 
provided to reinforce this training.  Only Investigators who are experienced and 
skilled in using breast tissue expansion devices for breast reconstruction and who 
are trained to the protocol and the AeroForm Tissue Expander System will be 
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13.2.5 
Human Factors Considerations 
AirXpanders has designed this device with consideration of human factors to 
minimize misuse of this device.  Features incorporated into the device include 
software controls such as limiting the dosing to 10cc, 3 hour lock out intervals for 
repeat dosing and a maximum daily dose of three doses or 30cc.  A Physician 
Master Key is required to dose beyond the pre-set maximum dose and dosing 
intervals.  Labeling mitigations include Instructions for Use (IFU), Physician and 
Patient Reference Cards and Patient Home Instructions.  Physician and patient 
training materials are provided prior to use of the device.  Subjects will be given a 
Patient ID card with information for 24 hour emergency contact in the event of any 
device problems. 
13.2.6 
Contraindications 
The AeroForm Tissue Expander is contraindicated when: 
 
Tissue at the intended expansion site is determined unsuitable by the 
physician. 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. 
 
There is a pre-existing physiological condition, determined by the physician, 
which pose a high risk of surgical or postoperative complications. To a varying 
degree, sensitive overlying or underlying anatomy, obesity, smoking, diabetes, 
autoimmune disease, hypertension, chronic lung or severe cardiovascular 
disease, or osteogenesis imperfecta may affect patient suitability for surgery. 
 
The patient has another electronic implant (e.g., pacemaker, defibrillator, or 
neurostimulator device)  
13.2.7 
Warnings 
Radiation Therapy 
Functional testing of the AeroForm Tissue Expander at radiation levels exceeding 
standard clinical practice has been performed, demonstrating no degradation in 
functionality.  However, AirXpanders does not provide recommendations regarding 
the use of radiation therapy. As with any implant, the decision to use radiation 

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therapy should be made with the consultation of the radiation oncologist using 
standard radiation treatment planning.   
If radiation therapy is planned, the risks of radiation therapy and alternative 
treatment options should be discussed with the patient. In the event that radiation 
therapy is administered, there should be no active expansion during radiation 
therapy.  
Overfilling 
The reservoir inside the AeroForm Tissue Expander releases a controlled amount 
of CO2 when the button on the hand-held controller is activated.  AirXpanders 
recommends that the physician and the patient expand gradually. Expansion 
progress should be assessed by the physician based on tissue laxity, perfusion 
and firmness of the expander. 
Note that the AeroForm Tissue Expander has a non-distensible inner liner which 
cannot be inflated beyond the labeled volume. Dosing beyond the labeled volume 
or too rapid tissue expansion may lead to increases in the relative expander 
pressures, possibly leading to discomfort, wound dehiscence, tissue damage or 
rupture of the expander.  If that occurs, stop expansion immediately. 
Altitude Change 
Patients with an implanted tissue expander considering travel to a higher altitude  
should consult with their physician prior to their travel. They should be instructed to 
discontinue dosing for at least two weeks prior to their travel and resume dosing 
after their travel is complete.  
An increase in altitude will lead to an increase in the expander volume and the 
relative internal pressure, which may cause discomfort, wound dehiscence, or 
damage to the expander.  The volume increase will be reversed upon descent.   
MRI 
Do not undergo diagnostic testing with Magnetic Resonance Imaging (MRI) with 
the AeroForm Tissue Expander in place. MRI equipment can cause movement of 
the expander and result in patient injury, or expander displacement requiring 
revision surgery. In addition, the metal CO2 reservoir could interfere with MRI 
detection capabilities. 
Infection 
Patients who present with any active infection may need to be treated and the 
infection resolved before placement of the expander.  Do not expose the expander 
to contaminants that could increase the risk of infection. Patients who present with 
active infection, wound dehiscence, tissue erosion, ischemia, or necrosis run an 
increased risk of periprosthetic infection.  

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Temporary Device 
The AeroForm Tissue Expander is a temporary device intended for up to six 
months of implantation, and is not to be used for permanent implantation. 
Expanders should be removed once adequate tissue has developed. The total 
expansion period will vary depending on patient tolerance, tissue tolerance, and 
planned permanent implant size. 
13.2.8     Precautions 
Surgical Planning 
The physician should follow proper surgical procedures to minimize the occurrence 
of adverse reactions. A qualified physician must carefully evaluate patient 
suitability for expansion and desired physical outcome, expander dimensions, 
incision placement, pocket dissection, expander filling, and final flap dimensions 
using current, accepted techniques and individual experience.  
Contamination at Surgery 
To avoid contamination, aseptic technique is essential. Do not expose the 
expander to lint, talc, sponge, towel, and other contaminants. Contamination at the 
time of surgery increases the risk of periprosthetic infection which could require 
premature explantation of the expander.  
Damage During Surgery 
Take extreme care to avoid damage to the expander during surgery; for example: 
 Excessive manipulation by forcing the expander through too small an access 
incision or into a small surgical pocket.  
 Sharp surgical instruments, such as scalpels and needles used during the initial 
surgery, or hematoma/fluid evacuation. During surgery, have a sterile back-up 
expander readily available in case damage occurs. Products must be carefully 
inspected for leaks or nicks prior to use. Do not attempt to repair damaged 
products.  
Hemostasis and Avoiding Fluid Accumulation 
Minimize post-operative hematoma and seroma by meticulous attention to 
hemostasis during surgery, and possibly by postoperative use of closed drains. 

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Persistent, excessive bleeding must be controlled before the expander is placed. 
The expander may be filled to tissue tolerance at the time of surgery to help 
minimize serous fluid accumulation in the surrounding pocket. Any postoperative 
evacuation of hematoma or other fluid accumulation must be carefully conducted to 
avoid introduction of contaminants or damage to the expander from needles or 
other sharp instruments. 
Physician Expansion 
 DO NOT over inflate the expander, as there is no method to remove volume. 
For patient safety, the expander has a default maximum dose of 30cc per day. 
However, actual volume delivery should be guided by patient comfort and 
wound status.  
 Excessive pressure from over expansion can lead to discomfort, wound 
dehiscence, tissue damage or rupture of the expander. In an emergency, the 
device can be deflated with a standard hypodermic needle. 
 DO NOT give the Physician Master Key to the patient at any time. It is to be 
used exclusively by the physician to administer doses during patient office visits 
when therapeutically appropriate. 
 If the patient has bilateral implanted expanders, she should be instructed to 
expand one at a time, using the controller labeled for that expander. She should 
not attempt to expand both expanders simultaneously using both controllers. 
 During dosing, if the expander appears to be filling excessively with 
accompanying patient pain and/or discomfort, remove the controller from the 
proximity of the expander.  Contact AirXpanders for technical support. 
Electromagnetic Interference 
The ability to establish communication between the AeroForm Tissue Expander 
and the Dosage 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 
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Subjects who work in areas of high radiation, magnetic or electrical fields should 
discuss this with their physician prior to implantation. 
Over-expansion/Rupture 
 Over-expansion of the expander due to device malfunction or excessive filling 
by the physician, can lead to extreme pain and/or wound dehiscence or may 
compromise the tissue integrity and require device deflation. If the subject 
experiences severe discomfort due to over inflation, the tissue integrity should 
be assessed and the subject should be treated as necessary.  The expander 
can be deflated with a small gauge needle however; this will permanently 
disable the expander necessitating removal. 
 The expander could rupture if the pressure inside becomes excessive due to 
over expansion, a rapid release of CO2 into the expander, a significant change in 
altitude, or sharp or blunt force injury to the chest.  Damaged, leaking, or broken 
expanders cannot be repaired and may require replacement surgery. 
No-expansion/Under-expansion 
 Under-expansion of the expander due to device malfunction or excessive 
permeation of CO2 through the inner liner could occur. Advise patients that the 
expanders may deflate, and require replacement surgery. 
13.2.9 
Other Considerations 
Chemotherapy 
During the course of the study, some subjects may have to undergo adjuvant 
chemotherapy treatment.  This may delay the explant of the expander to allow for 
the immune system to recover prior to surgery. In the event of a delayed exchange 
due to chemotherapy, the subject should continue to be followed per the study 
protocol.  If the subject is unable to maintain the study schedule due to 
chemotherapy, this should be documented and the sponsor should be notified. 

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14 Adverse Events 
During the course of the study, adverse event data will be collected according to the 
definitions below:  
14.1 Adverse Event (AE) 
An adverse event is defined as any untoward medical occurrence in a subject, 
regardless of whether the event is related to the device.  All adverse events 
occurring during the subject’s participation from the time of implant to the time of 
explant of the expander(s) will be recorded on the AE Case Report Form.  Data 
collected will include a description of the event, onset date, management or 
treatment/intervention required, outcome, and resolution date (or whether the AE is 
ongoing).  Subjects with adverse events that are ongoing should be followed until 
resolution of a serious AE and/or if they may be device related.  All AEs will be 
reviewed and assessed by the investigator for severity (Table 2) and causal 
relationship to the device (Table 3).  The investigator will also determine whether 
the AE meets the definition of serious as described in Section 14.2. 
 
 

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The investigator will use the following definitions to rate the severity of each AE:  
 
Table 2 Adverse Event Severity Rating 
Severity 
Description 
Mild 
 
Awareness of a sign or symptom that does not interfere with the 
subject’s usual activity or is transient, resolved without treatment 
and 
 
no sequelae 
Moderate  
Interferes with the subject’s usual activity and/or 
 
requires symptomatic treatment 
Severe 
 
Symptom(s) causing severe discomfort and  
 
significant impact on the subject’s usual activity and  
 
requires treatment 
Note:  Adverse events that are rated as severe are not the same as serious adverse 
events.  For example a subject may have severe pain may require treatment but not 
lead to a ‘serious’ event as defined below.  
 
14.2 Serious Adverse Event (SAE) 
Any untoward medical occurrence in a subject, regardless of whether the event is 
related to the device that: 
a. results in death; 
b. results in a life threatening illness or injury; 
c. results in a permanent impairment of a body structure or body function;  
d. requires in-patient hospitalization or prolongation of existing hospitalization 
e. results in medical or surgical intervention to prevent permanent impairment to 
body structure or function; 
f. results in fetal distress, fetal death, or a congenital abnormality/birth defect. 
 
14.3 Device Related Adverse Event 
Any sign, symptom, or disease in a study subject that occurs during the course of a 
clinical study that is determined by the investigator to have a causal relationship or 
possible causal relationship with the investigational device. 

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Table 3 Adverse Event Device Relationship 
Relationship 
Description 
Not Related 
 
Not associated with the device 
 
due to an underlying or concurrent illness or effect of another 
device or drug 
Unlikely 
 
Little or no temporal relationship to the study device and/or 
 
a more likely alternative etiology exists 
Possible 
 
Temporal sequence between device application and event is 
such that the relationship is not unlikely or  
 
subject’s condition or concomitant therapy could have caused 
the AE 
Probable 
 
Temporal sequence is relevant or 
 
Event abates upon device removal or  
 
event cannot be reasonable explained by the subject’s 
condition 
Highly Probable 
 
temporal sequence is relevant and 
 
event abates upon device removal or  
 
reappearance of the event on repeat device application 
 
14.4 Serious Device Related Adverse Event 
Any sign, symptom, or disease in a study subject that occurs during the course of a 
clinical study that is determined by the investigator to have a causal relationship or 
possible causal relationship with the investigational device and meets the definition 
of serious as described above. 
14.5 Unanticipated Adverse Device Event (UADE) 
Any serious adverse effect on health and safety or any life-threatening problem or 
death caused by, or associated with a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the 
investigational plan, or any other unanticipated serious problem associated with a 
device that relates to the rights, safety, or welfare of subjects. 

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As with any investigational device, there may be risks associated with the use of 
the AeroForm System that are unknown.  If any serious unanticipated device 
related adverse events occur during this study, they will be immediately (24 hours 
from knowledge of event) reported to the IRB and Sponsor in accordance with 
applicable regulations. 
The following table summarizes the potential adverse events in this study:  
Table 4  Adverse Events 
Event 
Definitions/Criteria 
Surgical Site 
Inflammation 
Severe erythema (redness), edema (swelling), and tenderness at 
the surgical site. 
Bruising 
Severe bruising (purple discoloration) at the surgical site 
Bleeding 
Significant bleeding at the surgical site requiring medical 
intervention or return to the operating room.  
Hematoma 
Collection of blood under the skin at the surgical site requiring 
medical intervention or return to the operating room for evacuation 
Seroma 
Collection of serous fluid under the skin at the surgical site 
requiring medical intervention or return to the operating room for 
drainage. 
Fever 
Post-operative fever of > 38.5◦ C (101.3◦ F) 
Surgical Site Infection 
Infection at the surgical site requiring medical treatment 
Systemic Infection or 
Sepsis 
Positive blood cultures and clinical diagnosis of sepsis 
Pain 
Severe pain requiring additional medical intervention or follow up 
Sensory Loss 
Significant numbness (paresthesia) at the surgical site 
Tissue damage 
Tissue thinning, necrosis, sloughing, (due to due to poor 
vascularization) 
Wound dehiscence 
Open wound at the expansion site 
Extrusion 
Extrusion at intended pressure, not wrinkle edge 
Erosion 
Exposure of the implant despite a lack of excessive pressure 
Capsular contracture 
Contracture of the pocket preventing adequate expansion 
Malposition 
Displacement of the implant due to migration 
Reoperation 
Any unplanned return to the operating room including device 
removal and/or replacement.  
Other 
Any other new sign or symptom that is reported by the subject 
during their enrollment in the study. Record by body system/event, 
i.e., Cardiac/Chest Pain, Pulmonary/Pneumonia that in the opinion 
of the investigator constitutes an adverse event.  
 

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14.6 Reporting of Adverse Events 
For the purposes of this study, adverse events will be categorized based on their 
relationship to the device.  The Investigator at each site is responsible for 
monitoring the safety of the subjects enrolled at that site and for determination of 
the causal relationship of all adverse events to the device.  All adverse events 
determined by the investigator to be unanticipated, serious and/or possibly, 
probably or highly probably related to the device must be reported to the sponsor 
within 24 hours after the investigator first learns of the event and to the reviewing 
IRB per their written policy.   
An investigator shall submit to the sponsor and to the reviewing IRB a report of any 
unanticipated non-serious adverse device event occurring during the investigation 
as soon as possible, but in no event later than 10 working days after the 
investigator first learns of the effect. 
The Sponsor is responsible for the ongoing safety evaluation of the investigational 
product.  The Sponsor shall be responsible for immediate adjudication of all 
reported serious and/or device related adverse events to determine whether the 
event is reportable under federal regulations.  The sponsor will select a safety 
committee comprised of at least one physician who is neither an investigator in the 
study or employed by the sponsor to adjudicate all adverse events to determine if 
the event is related to the investigational device.   
The Sponsor will promptly, within 10 working days after the sponsor first receives 
notice of the effect, notify all participating investigators and regulatory authorities, 
as appropriate, of findings that could affect adversely the safety of subjects, impact 
the conduct of the study or alter the IRB’s approval opinion to continue the study. 
If the Sponsor determines that an unanticipated adverse device effect presents an 
unreasonable risk to subjects, the Sponsor shall terminate all investigations or 
parts of investigations presenting that risk as soon as possible. 
14.7  Additional Procedures, Pre-mature Explant, Device Replacement 
As with any surgical procedure, additional procedures may be required in the event 
of an adverse event. The occurrence of complications may result in premature 
explant and/or replacement.  Device replacement may be required if desired 

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volume is not achieved or if over-expansion leads to complications.  Excess 
pressure may cause pain, ischemia, tissue injury or dehiscence of the wound if the 
pressure is not relieved.   
14.8  Device Failures 
Device Failures are defined as a malfunction of the device which leads device 
removal and/or replacement.  Device malfunctions that occur but do not lead to an 
adverse event or removal and/or replacement will be reported as malfunctions but 
not be counted as failures.  The table below lists potential device malfunctions. In 
the event of an adverse event requiring replacement of the AeroForm expander, 
this will be considered a treatment failure and the patient and surgeon will have the 
option of replacing the AeroForm with a replacement AeroForm expander or a 
standard saline expander.  
Table 5 
Potential AeroForm Device Failures 
Event 
Potential Causes 
Failure to Expand 
Leaking implant or Excessive Permeation leading to loss of CO₂ 
volume 
Inadequate CO₂ in the reservoir to achieve final volume 
Electronic Failure: Non-response of the reservoir valve to signal 
from hand held controller 
Valve Failure – Stuck in closed position  
Device Deflation 
Loss of CO2 sufficient to cause complete deflation of the expander 
without adequate tissue expansion  
Over-expansion 
 
 Increased volume as a result of significant altitude change 
Inadvertent overdose due to operator error  
Valve Failure – Failure to close or seal or stuck in open position  
Device rupture 
Sudden deflation of the expander due to device damage 
(puncture or blunt force trauma) or excessive pressure 
15 Investigator and Site Qualification 
Investigator sites will be selected per established AirXpanders standard operating 
procedure to ensure that Investigators and research staff are qualified with 
appropriate training and experience to investigate the device.  At a minimum, 
Investigators will be qualified to practice, board certified and experienced in the field 

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of breast reconstructive surgery using tissue expanders.  Investigators with previous 
experience using the AeroForm System will be selected for this study based on 
previous performance. The Investigator and research staff will be familiar with the 
regulatory and good clinical practice requirements necessary to conduct a clinical 
study and agree to conduct the study in accordance with their institutional review 
board policies and procedures and conditions of approval imposed by the FDA and 
reviewing IRB.  The facility in which the research will be conducted must have the 
available resources and physical space to conduct the study. 
16 Investigator and Site Training 
Investigator and study personnel training will be the conducted by the Sponsor or 
designee at the site initiation visit prior to the enrollment of any study subjects per 
established AirXpanders standard operating procedure.  To ensure proper device usage, 
uniform data collection, and protocol compliance, the Sponsor or designee will present a 
formal training session to the Investigator and all study site personnel which will review 
the instructions for use of the device, the investigational plan, instructions on data 
collection, methods for soliciting data from alternative sources, completion of case report 
forms, schedules for follow-up, and regulatory requirements.  Detailed feedback 
regarding completion of forms will be provided by the Sponsor or designee through the 
regular site monitoring.   
17 Monitoring of Investigational Sites 
A properly trained and qualified representative of the Sponsor or designee shall monitor 
the progress of this study to assure adequate protection of the rights and safety of the 
subjects and the quality and integrity of the resulting data.  The monitoring shall be 
performed in accordance with the FDA Guideline for Monitoring of Clinical Investigations 
and established AirXpanders Standard Operating Procedures.  Sites will be previously 
qualified, to assure that the investigator has the appropriate facilities and sufficient time 
and experience to conduct the investigation. Site initiation visits will be completed prior 
to subject enrollment to ensure that all study personnel are properly trained and 
understand their obligations to conduct the study in accordance with the investigational 
plan and all applicable regulations. Initial monitoring visits will be scheduled following the 

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first subject enrollment and periodic monitoring visits will be scheduled at all active 
investigational sites throughout the clinical study.  Additional review will be performed on 
a site-by-site basis, as warranted by the findings of previous monitoring visits.  The 
monitoring is designed to assure that the clinical investigation is being conducted 
according to the protocol requirements, all applicable state and federal regulations, 
conditions imposed by the FDA, IRB policies and procedures and GCP guidelines.  
These visits will assure that all enrolled subjects meet inclusion/exclusion criteria and 
that proper informed consent procedures are being followed.  In addition, the monitor will 
ensure that CRFs are complete and accurate, regulatory records are maintained, all 
reports of device malfunction and/or device or procedure related adverse events are 
reported as required and device accountability and device inventory are controlled.  The 
site shall provide working space and access to the subject’s medical records to the 
monitor for source verification. 
18 Protocol Compliance 
The study investigators are responsible for performing the study in compliance with the 
protocol.  Non-adherence to the protocol is to be classified as a protocol violation, 
protocol deviation, or protocol exemption, as defined below: 
18.1 Protocol Violation 
 A protocol violation is any non-adherence to the protocol that may result in 
significant additional risk to the subject (e.g., enrollment of a subject who does not 
meet the study criteria) or non-adherence to Good Clinical Practices (GCP) that 
may impact patient safety (e.g., failure to obtain proper consent prior to performing 
study procedures).  Violations should be reported to the study Sponsor and the IRB 
within 5 working days if they occur. 
18.2 
Protocol Deviation 
Protocol deviations are non-adherence to study procedures which does not result 
in additional risk to the subject (e.g., subject missed visit).  Protocol deviations 
must be reported to the sponsor on the deviation log by the study monitors and to 
be reported to the IRB per local policy.    

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18.3 Protocol Exemption 
The Sponsor may decide to provide a protocol exemption in cases in which it is 
determined that the subject does not meet specific criteria for entering or 
continuing in the study as defined by the protocol; however, in the opinion of the 
Investigator and the Sponsor, the subject would possibly benefit from participation, 
and participation would not impact the safety of the subject, the ability to interpret 
the data, nor the rights and well-being of the subject.  Exemptions should be 
reported promptly to the IRB given the severity and circumstances of the incident; 
per local IRB policy.  
19 Data Collection 
19.1 Electronic Case Report Forms (eCRFs) 
All study-related data collection will be recorded on Sponsor provided source 
worksheets and entered into electronic Case Report Forms (eCRFs) by designated 
site personnel within 7 days of the subject visit.  Data entered in the eCRFs must 
be supported by source documentation and will be reviewed by the monitors.  Any 
discrepancies will be noted by the monitor and resolved by the delegated site 
personnel.  The original source documents will be filed at the investigational sites.   
19.2 Subject Satisfaction and Usability Data 
Subjects will complete a satisfaction and usability questionnaire at the post-explant 
visit.   Subject satisfaction data will be collected via a standard 7 point Likert Scale.  
Subjects will be asked to determine overall satisfaction with the treatment and 
study, and will be asked a series of questions aimed at identifying any user issues 
with the AeroForm device.  
19.3 Physician Satisfaction and Usability Data 
Physicians will complete a satisfaction and usability questionnaire at the post-
explant visit.  Physician satisfaction data will be collected via a standard 7 point 
Likert Scale.  Physicians will be asked to determine overall satisfaction with the 
treatment and study, and will be asked a series of questions aimed at identifying 
any user identified issues with the AeroForm device.  

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19.4 Photographs 
A series of baseline and follow-up photographs of the treatment area will be taken 
by qualified study personnel using the AirXpanders Photography Protocol.  The 
subject’s faces will not be photographed and no identifiable subject information will 
be recorded on the photographs. The photographs may be cropped or re-sized for 
comparison purposes but otherwise will not be re-touched or altered in any way.  
Image files will be stored electronically by AirXpanders and indexed by subject 
identifier.  Copies of subject photographic data will be filed electronically at the 
clinical sites. 
19.5 Device Data Logs 
Dosage Controllers will be returned to AirXpanders at the time of explant and the 
device logs will be downloaded from the controllers by AirXpanders personnel for 
data analysis.  Data from the logs includes dosing, volume, and the calculated CO₂ 
permeation rate.  Interim data may be downloaded from the Dosage Controllers 
during the course of the study, as necessary to assess subject usage or 
troubleshoot any device issues. 
20 Source Documentation 
Source documentation includes subject medical records, results of laboratory or 
radiographic testing, operative reports, photographs, and any records pertinent to the 
care of the subjects while participating in the study.  Regulations require that 
Investigators maintain information in the study patient’s medical records which 
corroborate the data entered on the eCRFs.  Source data and worksheets must be 
maintained and made available as required by monitors and/or regulatory inspectors for 
source verification.  Examples of source documentation include: 
1. 
Medical history/physical condition of the study subject before involvement in 
the study sufficient to verify protocol entry criteria. 
2. 
Medical record documenting that informed consent was obtained for the 
subject’s participation in the study. 
3. 
Description of device implantation procedure (material used, drugs 
administered during the procedure, date, time, clinical findings, including 

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supporting data, if needed. 
4. 
Dated and signed notes for each study patient visit including results of 
examinations. 
5. 
Description of adverse events and follow-up of the adverse events (minimally 
event description, severity, onset date, duration, relation to study device, 
outcome and treatment for adverse event). 
6. 
Notes regarding relevant concomitant medications taken during the study 
(including start and stop dates). 
7. 
Study patient’s condition upon completion of or withdrawal from the study. 
21 Data Management 
The original source data will be maintained at the study site.  The source data will be 
entered into a designated study database and be monitored by in-house sponsor and/or 
contracted data management personnel.  The eCRF entries for each subject will be 
compared against the original source documents.  Data queries will be issued to the site 
for resolution, as necessary to clarify discrepancies in the data.  Queries will be verified 
by monitors and data management. Final validation of the data will be complete and the 
database locked prior to analysis of the data in accordance with AirXpanders Standard 
Operating Procedures to ensure the quality and integrity of the data. 
22 Study Closeout 
Upon completion of the clinical study (when all patients enrolled have completed the 
follow-up visits, data has been monitored and queries have been completed), the 
Sponsor or designee will notify the site of closeout and a study closeout visit will be 
performed.  Site close out will be done per established AirXpanders standard operating 
procedures.  All unused study devices and any unused study materials will be collected 
and returned to the Sponsor.  The Monitor will ensure that the Investigator’s regulatory 
files are up to date and complete and that any outstanding issues from previous visits 
have been resolved.  Other issues which will be reviewed at this visit include: discussion 
regarding retention of study files, possibility of site audits, publication policy, and 
notifying the IRB of study closure. 

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23 Record Retention 
All study records and reports will remain on file at the investigational sites for a minimum 
of 2 years after completion of the study and/or marketing clearance of the device.  The 
Investigator must contact AirXpanders before the destruction of any records and reports 
pertaining to the study to ensure they no longer need to be retained.  In addition, the Site 
Monitor should be contacted if the Investigator plans to leave the investigational site. 
24 Audits/Inspections 
In the event that audits are initiated by the Sponsor (or its designee), FDA or other 
regulatory authorities, the Investigator shall allow access to the original medical records 
and study records, and provide all requested information.  In the event of FDA audit, the 
site should notify the Sponsor promptly. 
25 Ethical and Regulatory Considerations 
This study shall be performed in accordance with all applicable federal, state and local 
laws and regulations, including without limitation 21 CFR Parts 11, 50, 54, 56, and 812, 
the requirements of the Food, Drug and Cosmetics Act (the “FDCA”) and similar or 
successor legislation, any policies issued or conditions imposed by the U.S. Food and 
Drug Administration (the “FDA”), the ICH Guidelines for Good Clinical Practice (the 
“GCP Guidelines”) and the Health Insurance Portability and Accountability Act of 1996 
(“HIPAA”) and any regulations and official guidance promulgated thereunder.  Patient 
confidentiality will be maintained throughout the clinical study in a way that ensures the 
information can always be tracked back to the source data.  For this purpose, a unique 
patient identification code (ID number and patient name code) will be used that allows 
identification of all data reported for each patient. Data relating to the study might be 
made available to third parties (for example in case of an audit performed by regulatory 
authorities) provided the data are treated confidentially and that the patient’s privacy is 
guaranteed. 
 
 

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