A Prospective, Single-Arm Multi-Center Study of the HARMONIC® 1100 Shears and Generator G11 in Pediatric Surgical Procedures (General) and Adult Surgical Procedures (General, Gynecological, Urological, and Thoracic)
Phase: NA
Conditions: Pediatric Procedures, Adult Hepato-pancreato-biliary (HPB) Procedures, Adult Lower Gastrointestinal Procedures, Adult Gastric Procedures, Adult Gynecological Procedures, Adult Urological Procedures, Adult Thoracic Procedures
Sponsor: Ethicon Endo-Surgery

CONFIDENTIAL 
Trial Number: ENG_2020_06 
Version: Amendment 3 
Page 1 of 36 
17 MAY 2023 
A Prospective, Single-Arm Multi-Center Study of the HARMONIC® 1100 Shears and 
Generator G11 in Pediatric Surgical Procedures (General) and Adult Surgical Procedures 
(General, Gynecological, Urological, and Thoracic) 
Trial Number: ENG_2020_06 
Document 
Date
Original 
16 FEB 2021
Amendment 1 
23 SEP 2021
Amendment 2 
10 MAY 2022
Amendment 3 
17 MAY 2023
Sponsor: 
Ethicon Endo-Surgery, Inc. 
4545 Creek Road 
Cincinnati, Ohio 45242 
Name of Finished 
Product(s): 
HARMONIC® 1100 Shears 
Generator G11 (GEN11) 
Regulatory Classifications: 
HARMONIC 1100 Shears: Class II in the United States 
and Canada, Class IIb in the European Union and United 
Kingdom 
GEN11: Class II in the United States and Class III in 
Canada, Class IIb in the European Union and United 
Kingdom 
Sponsor’s Medical Monitor: 
Gustavo Scapini, M.D. 
Director, Medical Affairs 
4545 Creek Rd. 
Cincinnati, OH 45242 
This study will be performed in compliance with Good Clinical Practice (GCP), and in accordance 
with the Declaration of Helsinki, as well as any other applicable local and country regulatory 
requirements. 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by federal or state law or regulations. Subject to the foregoing, 
this information may be disclosed only to those persons involved in the study who have a need to know, but all such 
persons must be instructed not to further disseminate this information to others. These restrictions on disclosure will apply 
equally to all future information supplied to you which is indicated as privileged or confidential. 
NCT05039021

CONFIDENTIAL 
Trial Number: ENG_2020_06 
Version: Amendment 3 
Page 2 of 36 
17 MAY 2023 
 
 
 
 
 
PROTOCOL SIGNATURE PAGE 
 
A Prospective, Single-Arm Multi-Center Study of the HARMONIC® 1100 Shears and 
Generator G11 in Pediatric Surgical Procedures (General) and Adult Surgical Procedures 
(General, Gynecological, Urological, and Thoracic) 
 
 
 
Trial Number: ENG_2020_06 
 
 
Document 
Date
Original 
16 FEB 2021
Amendment 1 
23 SEP 2021
Amendment 2 
10 MAY 2022
Amendment 3 
17 MAY 2023
 
 
 
 
 
 
 
 
 
 
 
Approvals: 
 
KATHRINE LORENZ 
Digitally signed by KATHRINE LORENZ 
DN: c=US, o=JNJ, ou=Subscribers, 
0.9.2342.19200300.100.1.1=7354, cn=KATHRINE LORENZ 
Reason: I am approving this document. 
Date: 2023.06.16 11:07:38 -04'00' 
Adobe Acrobat version: 2020.013.20064 
 
 
Franchise Clinical Head 
Date 
Ethicon Endo-Surgery, Inc. 
 
This study will be performed in compliance with GCP, and in accordance with the Declaration of 
Helsinki, as well as any other applicable local and country regulatory requirements. 

CONFIDENTIAL 
Trial Number: ENG_2020_06 
Version: Amendment 3 
Page 3 of 36 
17 MAY 2023 
 
 
INVESTIGATOR SIGNATURE PAGE 
 
 
 
I have read, understood, and agree to: 
• 
Ensure that the requirements for obtaining informed consent are met; 
• 
Conduct the study in accordance with this protocol, including applicable local laws and 
regulations; 
• 
Maintain the confidentiality of all information received or developed in connection with this 
protocol; 
• 
Report all serious adverse events (SAEs) as soon as possible, but no later than 72 hours 
after becoming aware of the event; 
• 
Adhere to the publication policy, as stated in the Clinical Study Agreement, for data 
collected during this study; 
• 
Ensure that all associates, colleagues, and employees assisting in the conduct of the 
study are informed of their obligations in meeting the above commitments; and 
• 
Provide copies of the protocol and all pertinent information to all individuals responsible 
to me who assist in the conduct of this study. I will discuss this material with them to 
ensure they are fully informed regarding the conduct of the study. 
I will ensure that the Institutional Review Board (IRB) / Ethics Committee (EC) review complies 
with governmental requirements and will be responsible for the initial and continuing review and 
approval of the clinical investigation. I also agree to promptly report to the IRB/EC all changes in 
the research activity and all unanticipated problems involving risks to human subjects or others. 
Additionally, I will not make any changes in the research without Sponsor and IRB/EC approval 
of an amended protocol, except where necessary to eliminate apparent immediate hazards to 
human subjects. 
I agree to comply with all other requirements regarding the obligation of clinical Investigators and 
all other pertinent requirements of the Sponsor and government agencies. 
 
 
 
 
 
Signature of Principal Investigator (PI) 
Date 
 
 
 
Printed Name of Principal Investigator 
 
 
 
Site Identification Number 

CONFIDENTIAL 
Trial Number: ENG_2020_06 
Version: Amendment 3 
Page 4 of 36 
17 MAY 2023 
 
 
CLINICAL STUDY PROTOCOL SYNOPSIS 
Regulatory 
Classification: 
HARMONIC 1100 Shears: Class II in the United States and Canada, 
Class IIb in the European Union and United Kingdom 
GEN11: Class II in the United States and Class III in Canada, Class IIb in 
the European Union and United Kingdom 
Indication: 
HARMONIC® 1100 Shears 
The HARMONIC 1100 Shears are indicated for soft tissue incisions when 
bleeding control and minimal thermal injury are desired. The instruments 
can be used as an adjunct to or substitute for electrosurgery, lasers and 
steel scalpels in general, pediatric, gynecologic, urologic, thoracic 
procedures, and sealing and transection of lymphatic vessels. The 
instruments allow for the coagulation of vessels up to and including 7 mm 
in diameter, using the Energy button with Advanced Hemostasis. 
The instruments are not indicated for incising bone and are not intended 
for contraceptive tubal occlusion. 
Generator G11 (GEN11) 
The GEN11 provides radiofrequency power to drive ENSEAL 
electrosurgical instruments that are used during open or laparoscopic 
general and gynecological surgery to cut and seal vessels and to cut, 
grasp, and dissect tissues. In addition, the generator provides power to 
drive HARMONIC ultrasonic surgical instruments that are indicated for 
soft tissue incisions when bleeding control and minimal thermal injury are 
desired. 
ENSEAL and HARMONIC instruments, when used with the GEN11, have 
not been shown to be effective for sterilization procedures or tubal 
coagulation. 
Objective(s): 
The primary objective of this study is to demonstrate the acceptable 
performance and safety of the HARMONIC 1100 Shears and GEN11 
devices when used per the instructions for use (IFU) in pediatric surgical 
procedures (general) or adult surgical procedures (general, 
gynecological, urological, and thoracic) where at least one single vessel 
is planned to be transected by the HARMONIC 1100 Shears. 
The secondary objective of this study is to demonstrate the acceptable 
performance and safety of the HARMONIC 1100 Shears in the 
transection of > 5 to 7 mm diameter size vessels. 
Overview of 
Study Design: 
This prospective, single-arm, multi-center study will collect clinical data in 
a post-market setting for the pediatric population (general surgical 
procedures) and adult population (general, gynecological, urological, and 
thoracic surgical procedures). Investigators will perform each procedure 
using the device in compliance with their standard surgical approach and 
the HARMONIC 1100 Shears and GEN11 IFUs. 
Subjects will be consented and screened anytime during a period of 8 
weeks prior to the date of surgery. Subjects will be considered enrolled 

CONFIDENTIAL 
Trial Number: ENG_2020_06 
Version: Amendment 3 
Page 5 of 36 
17 MAY 2023 
 
 
 
when the HARMONIC 1100 Shears has been attempted to be used for at 
least one single vessel transection during pediatric surgical procedures 
(general) and adult surgical procedures (general, gynecological, 
urological, and thoracic). All enrolled subjects will be followed post- 
operatively through discharge and again at 28 days (± 14 days) post- 
surgery; therefore, from the surgery date to study exit, the duration will be 
approximately 6 weeks. 
Number of 
Subjects: 
A minimum of 165 subjects enrolled (maximum of 328 subjects enrolled) 
will be included in the study from up to 15 surgery centers globally with 
the following procedure targets: 
Procedure 
Procedures 
Estimated Initial 
Group 
Enrollment Range 
(minimum is 33 per 
procedure group) 
1 
Pediatric 
33 – 40 
2 
Adult General (contain the following subgroups) 
33 – 119 
2a 
Adult hepato-pancreato-biliary (HPB) (e.g. liver 
11 – 15 
resection) 
2b 
Adult lower gastrointestinal (GI) (e.g., large 
11 – 15 
intestine resection) 
2c 
Adult gastric (gastrectomy [e.g., subtotal, total], 
11 – 89 
esophagectomy, Roux-en-Y gastric bypass 
[RYGB], sleeve gastrectomy, or biliopancreatic 
diversion with duodenal switch [BPD/DS]) 
3 
Adult gynecological (e.g. hysterectomy, 
33 – 40 
oophorectomy, myomectomy or endometriosis 
resection) 
4 
Adult urological (e.g., nephrectomy, cystectomy 
33 – 40 
or prostatectomy) 
5 
Adult 
thoracic 
(lung 
resection 
[branches, 
33 – 89 
excluding main pulmonary artery {PA}/pulmonary 
vein {PV}]) 
Every subject enrolled in the study would count toward the primary 
enrollment goal of 165 subjects. In addition, a secondary enrollment goal 
for the study is to enroll a sufficient number of subjects to achieve a 
minimum of 165 vessels transected with a diameter size of > 5 to 7 mm 
based on surgeon determination. Every subject enrolled in the study that 
also had a > 5 to 7 mm vessel transected would count toward the 
secondary enrollment goal in addition to the primary enrollment goal. The 
initial assumption is that PA branches (thoracic procedure group) and left 
gastric veins (gastric procedure group) will have the greatest likelihood of 
having a vessel with a diameter size of > 5 to 7 mm. The number of 
vessels transected with a diameter of > 5 to 7 mm will be continuously 
monitored by the Sponsor throughout the course of the study. 

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Trial Number: ENG_2020_06 
Version: Amendment 3 
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17 MAY 2023 
 
 
 
The table above provides the minimum number of subjects to be enrolled 
per procedure group and the Sponsor will determine the maximum 
number of subjects to be enrolled per procedure group based on 
fulfillment of secondary endpoint. Once the minimum number has been 
met for a procedure group, enrollment for that group could be closed to 
further enrollment. 
Criteria for 
Inclusion: 
Subjects satisfying the following criteria will be considered eligible for 
enrollment in this study: 
Pediatric population: 
1. Non-emergent procedure (general) where at least one vessel is 
planned to be transected by the HARMONIC 1100 Shears per the 
IFU; 
2. Less than 18 years of age at the time of procedure; and 
3. The subject’s parent/legal guardian must be willing to give 
permission for the subject to participate in the study and provide 
written informed consent for the subject. In addition, assent must 
be obtained from pediatric subjects who possess the intellectual 
and emotional ability to comprehend the concepts involved in the 
study. If the pediatric subject is not able to provide assent (due to 
age, maturity and/or inability to intellectually and/or emotionally 
comprehend the study), the parent/legal guardian’s written 
informed consent for the subject will be acceptable for the subject 
to be included in the study. 
Adult population: 
1. Elective procedure (general, gynecological, urological, or 
thoracic) where at least one vessel is planned to be transected by 
the HARMONIC 1100 Shears per the IFU; 
2. Willingness to give consent and comply with all study-related 
evaluations and visit schedule; and 
3. At least 18 years of age. 
Criteria for 
Exclusion: 
Subjects meeting any of the following criteria will be considered ineligible 
for enrollment in this study: 
Preoperative 
1. Physical or psychological condition which would impair study 
participation; 
2. Female subjects, of childbearing age, who are pregnant; or 
3. Enrollment in a concurrent interventional clinical study that could 
impact the study endpoints. 
Intraoperative 
1. The HARMONIC 1100 Shears were not attempted to be used for 
at least one single vessel transection during the surgical 
procedure. 

CONFIDENTIAL 
Trial Number: ENG_2020_06 
Version: Amendment 3 
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17 MAY 2023 
 
 
 
Test Product: 
HARMONIC® 1100 Shears (Product Codes: HAR1120 or HAR1136) and 
Generator G11 (GEN11). 
Reference 
Therapy/Product: 
No comparator product is being used in this study. 
Duration of 
Treatment: 
Subjects will be exposed to the HARMONIC 1100 Shears and GEN11 
during the procedure and while the devices are used as indicated in the 
IFU. Neither the devices nor any device components will remain in the 
patient after use. 
Criteria for 
Evaluation: 
The primary performance endpoint will be: 
• 
Achievement of Grade 3 or lower hemostasis for each vessel 
transection (per the grading scale below): 
o Grade 1: no bleeding at transection site; 
o Grade 2: minor bleeding at transection site, no 
intervention needed; 
o Grade 3: minor bleeding at transection site, mild 
intervention needed, use of compression, basic energy 
devices (monopolar and/or bipolar) and/or touch-ups with 
HARMONIC 1100 Shears; or 
o Grade 4: significant bleeding (e.g., pulsatile blood flow, 
venous pooling) requiring intervention such as extensive 
coagulation or ligation with use of additional hemostatic 
measures (e.g., hemoclips, staples, sutures, fibrin 
sealants, other advanced energy products); 
The secondary performance endpoints will be: 
• 
Distribution of 5-point scale (very dissatisfied, dissatisfied, neither 
satisfied or dissatisfied, satisfied, or very satisfied) scores for 
sealing and transection of lymphatic vessels completed by the 
HARMONIC 1100 Shears; 
• 
Distribution of hemostasis grading scale (1-4) for each vessel 
transected; and 
• 
Type, name, and number of additional hemostasis measures 
required to achieve hemostasis for Grade 4 vessel transections. 
The primary safety endpoint will be: 
• 
Occurrence of device-related (possible, probable or causal) 
adverse events (AEs). 

CONFIDENTIAL 
Trial Number: ENG_2020_06 
Version: Amendment 3 
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17 MAY 2023 
 
 
 
Statistical 
Analysis: 
Analysis Sets 
The summary of all performance and safety endpoints will be performed 
on the set of subjects in whom the HARMONIC 1100 Shears is utilized 
during the surgical procedure. The summary of all performance and 
safety endpoints will be performed by surgical population (pediatric and 
adult), surgical procedure group, procedure subgroup, and on the entire 
pooled set of subjects. 
Sample Size Determination 
Primary performance analysis: A sample size of at least 165 subjects is 
required to have a minimum of 80% power for rejecting the null 
hypothesis that the rate of Grade 3 or lower transections is less than or 
equal to 87.5% when the expected rate of Grade 3 hemostatic 
transections is at least 94.0% using exact binomial test and a one-sided 
significance level of 0.025. The sample size estimation makes the 
assumption of one transection per subject which is likely very 
conservative as most subjects may have 2 or more transections during 
their procedure. At the time of study protocol amendment 3 it was found 
that on average there were 2 vessel transections per subject. A minimum 
of 33 subjects will be enrolled into each of the five individual procedure 
groups. 
Secondary performance analysis: A sample size of at least 165 vessels 
is required to have a minimum of 80% power for rejecting the null 
hypothesis that the rate of Grade 3 or lower transections is less than or 
equal to 87.5% when the expected rate of Grade 3 hemostatic 
transections is at least 94.0% for vessels with diameter size of > 5 to7 
mm. Sample size estimation considered an exact binomial test and a 
one-sided level of significance of 0.025. The number of vessels 
transected with a diameter size of > 5 to7 mm will be continuously 
monitored by the Sponsor throughout the course of the study to achieve 
the required number of vessels. 
Performance Analyses 
The number and percentage of vessels where hemostasis is achieved (≤ 
Grade 3) will be summarized and an exact 95% confidence interval 
based on Clopper-Pearson’s method will be estimated for each 
procedure group (pediatrics [general surgical procedures] and adult 
[general, gynecological, urological, and thoracic surgical procedures]), 
the three individual procedure subgroups, the > 5 to 7 mm diameter 
vessel population, and in total. The performance goal hypothesis will be 
evaluated on the total population and the > 5 to 7 mm diameter vessel 
population using the lower bound of the exact two-sided 95% confidence 
interval based on Clopper-Pearson’s method and a p-value from exact 
binomial test. Counts and percentages will be provided for type, size, and 
number of vessels transected, grading scale distribution for all vessels 
transected, number of times HARMONIC 1100 Shears touch-ups were 
required, and incidence of requirement for additional measures to obtain 
hemostasis on vessels (other advanced energy devices or hemostatic 
measures). 

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Version: Amendment 3 
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Safety Analyses 
All device-related and procedure-related AEs reported during the study 
will be coded to the Medical Dictionary for Regulatory Activities 
(MedDRA). All AEs will be summarized by MedDRA system organ class 
and preferred term by subject population (pediatric and adult), procedure 
group, procedure subgroup and in total. Separate summaries will be 
provided for device-related and procedure-related AEs. Serious AEs will 
be summarized in a similar manner. 

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Trial Number: ENG_2020_06 
Version: Amendment 3 
Page 10 of 36 
17 MAY 2023 
 
 
TABLE OF CONTENTS  
 
Page 
PROTOCOL SIGNATURE PAGE .......................................................................................... 2 
INVESTIGATOR SIGNATURE PAGE .................................................................................... 3 
CLINICAL STUDY PROTOCOL SYNOPSIS .......................................................................... 4 
PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS ............................................ 12 
ETHICS ............................................................................................................................... 13 
ADMINISTRATIVE REQUIREMENTS ................................................................................. 14 
1.0 
INTRODUCTION ........................................................................................................ 15 
2.0 
STUDY OBJECTIVES ................................................................................................ 15 
2.1 
Primary Performance Endpoint ............................................................................... 16 
2.2 
Secondary Performance Endpoints ......................................................................... 16 
2.3 
Safety Endpoint ...................................................................................................... 16 
2.4 
Additional Key Data Collected ................................................................................. 16 
3.0 
INVESTIGATIONAL PLAN ......................................................................................... 17 
3.1 
OVERALL STUDY DESIGN AND PLAN - DESCRIPTION ...................................... 17 
3.2 
STUDY POPULATION ........................................................................................... 17 
3.2.1 Enrollment .......................................................................................................... 17 
3.2.2 Screening Failures ............................................................................................. 18 
3.2.3 Inclusion Criteria................................................................................................. 18 
3.2.4 Exclusion Criteria ............................................................................................... 19 
3.2.5 Removal of Subjects from Study ......................................................................... 19 
3.2.6 Subject Replacement in Study ............................................................................ 20 
3.3 
STUDY PROCEDURES ......................................................................................... 20 
3.3.1 Procedure Description ........................................................................................ 20 
3.3.2 Identity of Study Products ................................................................................... 20 
3.3.2.1 
Device Description ...................................................................................... 21 
3.3.2.2 
Indications ................................................................................................... 21 
3.3.2.3 
Contraindications ........................................................................................ 21 
3.3.2.4 
Labeling of Study Products ......................................................................... 22 
3.3.2.5 
Accountability of Study Products ................................................................. 22 
3.3.3 Prior and Concomitant Therapy .......................................................................... 22 
3.4 
STUDY VARIABLES............................................................................................... 22 
3.4.1 Demographic and Baseline Characteristics ......................................................... 22 
3.4.2 Study Variables .................................................................................................. 23 
3.4.3 Questionnaires ................................................................................................... 24 
3.4.4 Safety Data Variables ......................................................................................... 25 
3.5 
SCHEDULE OF EVENTS ....................................................................................... 25 
3.6 
STUDY PROCEDURES ......................................................................................... 26 
3.6.1 Visit 1 – Screening (may occur over visits within 8 weeks of Visit 2 
including up to the day of the procedure) ............................................................ 26 
3.6.2 Visit 2 – Procedure Through Discharge .............................................................. 26 
3.6.3 Visit 3 – Post-procedure Follow-up ..................................................................... 26 
3.6.4 Unscheduled Visit(s) .......................................................................................... 26 
3.6.5 Vessel Image Capture ........................................................................................ 26 
4.0 
DATA MANAGEMENT AND INTEGRITY ................................................................... 27 
4.1 
DATA COMPLETION AND RECORD KEEPING .................................................... 27 
4.1.1 Source Documents ............................................................................................. 27 
4.1.2 Electronic Data Capture ..................................................................................... 27 
4.1.3 Data Collection ................................................................................................... 27 

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Version: Amendment 3 
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17 MAY 2023 
 
 
4.1.4 Data Correction .................................................................................................. 28 
4.1.5 Data Privacy ....................................................................................................... 28 
4.1.6 Record Retention, Inspection, and Custody ........................................................ 28 
4.2 
MEDICAL DICTIONARY CODING .......................................................................... 28 
4.3 
DATA QUALITY ASSURANCE ............................................................................... 28 
4.3.1 Site Personnel Training ...................................................................................... 28 
4.3.2 Monitoring .......................................................................................................... 28 
4.3.3 Quality Assurance .............................................................................................. 29 
4.4 
PROTOCOL DEVIATIONS ..................................................................................... 29 
5.0 
STATISTICAL METHODS PLANNED IN THE PROTOCOL AND DETERMINATION OF 
SAMPLE SIZE ........................................................................................................... 29 
5.1 
STUDY DESIGN .................................................................................................... 29 
5.2 
TREATMENT ASSIGNMENT ................................................................................. 29 
5.3 
INTERVAL WINDOWS ........................................................................................... 29 
5.4 
PRIMARY AND SECONDARY ENDPOINTS AND ASSOCIATED 
HYPOTHESES ....................................................................................................... 30 
5.5 
LEVELS OF SIGNIFICANCE .................................................................................. 30 
5.6 
ANALYSIS SETS .................................................................................................... 30 
5.7 
SAMPLE SIZE JUSTIFICATION ............................................................................. 30 
5.8 
DATA MONITORING COMMITTEE ........................................................................ 31 
5.9 
ANALYSES TO BE CONDUCTED ......................................................................... 31 
5.9.1 General Conventions .......................................................................................... 31 
5.9.2 Disposition of Study Subjects ............................................................................. 32 
5.9.3 Demographic, Baseline, and Surgical Characteristics ......................................... 32 
5.9.4 Primary and Secondary Endpoint Analyses ........................................................ 32 
5.9.5 Plans for Interim Analyses .................................................................................. 32 
5.9.6 Handling of Missing Data .................................................................................... 32 
5.9.7 Subgroup Analyses ............................................................................................ 32 
6.0 
ADVERSE EVENTS ................................................................................................... 33 
6.1 
DEFINITIONS ......................................................................................................... 33 
6.1.1 Adverse Event .................................................................................................... 33 
6.1.2 Serious Adverse Event ....................................................................................... 33 
6.1.3 Pre-existing Condition ........................................................................................ 33 
6.2 
SEVERITY OF ADVERSE EVENTS ....................................................................... 33 
6.3 
RELATIONSHIP OF ADVERSE EVENTS............................................................... 34 
6.4 
REPORTING PROCEDURES FOR ADVERSE EVENTS ....................................... 35 
6.4.1 Recording Adverse Events ................................................................................. 35 
6.4.2 Reporting Adverse Events .................................................................................. 35 
6.4.3 Reporting Serious Adverse Events ..................................................................... 35 
7.0 
PRODUCT COMPLAINTS .......................................................................................... 36 
7.1 
REPORTING PRODUCT COMPLAINTS FOR MARKETED DEVICES ................... 36 
7.1.1 Reporting of Approved EES Marketed Devices................................................... 36 
7.1.2 Reporting of Approved Marketed Devices and Commercially Available 
Devices (not Ethicon) ......................................................................................... 36 
8.0 
REFERENCES ........................................................................................................... 36 

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Version: Amendment 3 
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PROTOCOL-SPECIFIC ACRONYMS AND ABBREVIATIONS 
 
Acronyms/Abbreviations 
Terms 
AE 
Adverse event 
ASA 
American Society of Anesthesiologists Physical Status 
Classification System 
BPD/DS 
Biliopancreatic diversion with duodenal switch 
EC 
Ethics committee 
eCRF 
Electronic case report form 
EDC 
Electronic Data Capture 
EEPROM 
Electrically erasable programmable read-only memory 
EES 
Ethicon Endo-Surgery, Inc. 
GEN11 
Ethicon Endo-Surgery Generator G11 
FDA 
Food and Drug Administration 
GCP 
Good clinical practice 
GI 
Gastrointestinal 
HPB 
Hepato-pancreato-biliary 
ICD 
Informed consent document 
IFU 
Instructions for use 
IRB 
Institutional review board 
MedDRA 
Medical Dictionary for Regulatory Activities 
OR 
Operating room 
PA 
Pulmonary artery 
PI 
Principal Investigator 
PV 
Pulmonary vein 
PCF 
Product complaint form 
PHI 
Protected health information 
PMCF 
Post-market clinical follow-up 
RYGB 
Roux-en-Y gastric bypass 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOC 
Standard of care 

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Version: Amendment 3 
Page 13 of 36 
17 MAY 2023 
 
 
 
ETHICS 
 
Institutional Review Board/Ethics Committee 
Participating investigators will ensure that this protocol, Informed Consent Document (ICD), ICD 
or protocol amendments, and if applicable, any other written information provided to the 
subjects that assist in the decision to participate are reviewed by an Institutional Review Board 
(IRB) or Ethics Committee (EC) that complies with governmental requirements. The approving 
IRB/EC will be responsible for the initial and continuing review and approval of this clinical 
investigation. Participating investigators will be required to promptly report to the IRB/EC as 
required by the IRB/EC’s policies. Additionally, investigators will be required to refrain from 
making any changes in the clinical investigation plan without Sponsor and IRB/EC approval of 
an amended protocol, except where necessary to eliminate apparent immediate hazards to 
study subjects or others. 
Applicable Regulations 
This study will be conducted in compliance with GCP and in accordance with the Declaration of 
Helsinki, as well as any other applicable local and country regulatory requirements. 
Subject Information and Consent 
Regulations concerning the protection of subjects require that informed consent be obtained 
before a subject may participate in any clinical investigation. An IRB/EC approved informed 
consent must be sought from each subject and must be appropriately documented in the 
subject’s medical record prior to initiating the study. It is the Investigator’s responsibility to obtain 
written informed consent from the subject, the Investigator may delegate this responsibility if 
appropriately documented. In addition, assent must be obtained from pediatric subjects who 
possess the intellectual and emotional ability to comprehend the concepts involved in the study. 
If the pediatric subject is not able to provide assent (due to age, maturity and/or inability to 
intellectually and/or emotionally comprehend the trial), the parent/legal guardian’s written 
informed consent for the subject will be acceptable for the subject to be included in the study. 
The informed consent process involves the following: giving a subject adequate information 
concerning the study, providing adequate time for the subject to consider all available options, 
responding to the subject’s questions, ensuring that the subject has comprehended this 
information and finally, obtaining the subject’s written consent to participate in this study. All 
subjects in this study should be completely informed about the purpose, risks, benefits, and 
other pertinent details of this study. The informed consent process is careful to avoid the 
perception of any coercion or undue influence on, or inducement of, the subject to participate, 
and does not waive or appear to waive the subject's legal rights. The ICD is presented in native, 
non-technical language that is understandable to the subject. 
Prior to a subject’s participation in this study, an ICD will be signed and dated by the subject and 
person who conducted the consent discussion. The subject will be provided a copy of the 
signed ICD. The ICD and any other written materials provided to the subject to assist in the 
decision to participate must be revised whenever new information becomes available that may 
be relevant to their willingness to participate or continue participation in this study. Revision to 
the ICD and other written materials will receive IRB/EC approval before implementation. Each 
subject will be required to sign any amended ICD (as required by the IRB/EC) and will receive a 
copy of the signed ICD. 

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ADMINISTRATIVE REQUIREMENTS 
 
This study is sponsored by Ethicon Endo-Surgery, Inc. (EES, Cincinnati, OH, USA) and will be 
conducted in up to fifteen surgery centers globally under a single protocol approved by each 
participating site’s IRB/EC prior to implementation. The PI at each study site is a surgeon 
qualified by education, experience, and training to perform the study procedure and to assume 
responsibility for the conduct of this study. 
The Data Management and Biostatistics groups of the Sponsor will be responsible for the 
analysis of data from this protocol. An Electronic Data Capture (EDC) system will be utilized by 
study site personnel to transfer study data from source records (the first point of clinical data 
capture) onto common electronic case report forms (eCRFs). 
Protocol Modifications 
All protocol amendments must be issued by the Sponsor, signed and dated by the Investigator, 
and should not be implemented without prior IRB/EC approval, except where necessary to 
eliminate immediate hazards to the subjects or when the change(s) involves only logistical or 
administrative aspects of the study (e.g., change in monitor(s), change of telephone number(s)). 
The Investigator reports the protocol amendments to the IRB/EC as per their local requirements. 

CONFIDENTIAL 
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Version: Amendment 3 
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17 MAY 2023 
 
 
1.0 INTRODUCTION 
 
The HARMONIC 1100 Shears is a sterile, single-patient-use instrument used for dissection, 
grasping, coagulation, and cutting between the blade and clamp arm. It can be used in general, 
pediatric, gynecologic, urologic, thoracic, and sealing and transection of lymphatic vessels. The 
instruments allow for the coagulation of vessels up to and including 7 mm in diameter. 
The HARMONIC 1100 Shears differs primarily in two ways from the earlier version of the device, 
the HARMONIC HD 1000i Shears: 
1. An electrically erasable programmable read-only memory (EEPROM) with an improved 
algorithm that actively controls blade heat for lower maximum blade temperature 
compared to previous HARMONIC devices; and 
2. Branding updates to the device handle and distal shaft. 
The HARMONIC 1100 Shears have undergone extensive preclinical testing to ensure that they 
are capable of producing strong and durable seals for vessels up to 7mm in diameter. Figure 1 
shows a picture of the HARMONIC 1100 Shears. The device will be available in shaft lengths of 
20 and 36 cm. The instrument shaft can be rotated continuously to facilitate visualization and 
access to targeted tissue. 
 
 
 
Figure 1: Image of the HARMONIC 1100 Shears. 
The GEN11 supplies energy to the HARMONIC and ENSEAL surgical instruments. It also has a 
touchscreen for easy setup and operation, and a high-resolution display with wider viewing 
angles. Software updates to ensure that the system is operating optimally are available via USB 
memory stick. The generator uses a touchscreen display interface and has a unique receptable 
port that accepts either a HARMONIC or an ENSEAL instrument. Connectors (HGA11 for 
HARMONIC and EGA11 for ENSEAL) are used to enable the generator to power legacy 
instruments. 
This study is being conducted to evaluate the devices when used per their instructions for use 
(IFU) in the following types of procedures: pediatric surgical procedures (general) and adult 
surgical procedures (general, gynecological, urological, and thoracic). 
 
2.0 STUDY OBJECTIVES 
 
The primary objective of this study is to demonstrate the acceptable performance and safety of 
the HARMONIC 1100 Shears and GEN11 devices when used per the IFUs in pediatric surgical 

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procedures (general) or adult surgical procedures (general, gynecological, urological, and 
thoracic) where at least one single vessel is planned to be transected by the HARMONIC 1100 
Shears. 
The secondary objective of this study is to demonstrate the acceptable performance and safety 
of the HARMONIC 1100 Shears in the transection of > 5 to 7 mm diameter size vessels. 
2.1 PRIMARY PERFORMANCE ENDPOINT 
A hemostasis grading scale was adapted from Siegel et al.1 The primary performance 
endpoint will be: 
• 
Achievement of Grade 3 or lower hemostasis for each vessel transection (per the 
grading scale below): 
o Grade 1: no bleeding at transection site; 
o Grade 2: minor bleeding at transection site, no intervention needed; 
o Grade 3: minor bleeding at transection site, mild intervention needed, use of 
compression, basic energy devices (monopolar and/or bipolar) and/or touch- 
ups with HARMONIC 1100 Shears; or 
o Grade 4: significant bleeding (e.g., pulsatile blood flow, venous pooling) 
requiring intervention such as extensive coagulation or ligation with use of 
additional hemostatic measures (e.g., hemoclips, staples, sutures, fibrin 
sealants, other advanced energy products). 
2.2 SECONDARY PERFORMANCE ENDPOINTS 
The secondary performance endpoints will be: 
• 
Distribution of 5-point scale scores for sealing and transection of lymphatic vessels 
completed by the HARMOINC 1100 Shears. The scale will be a 5-point scale (very 
dissatisfied, dissatisfied, neither satisfied or dissatisfied, satisfied, or very satisfied) 
asking how satisfied the surgeon was with the use of the device for the task; 
• 
Distribution of hemostasis grading scale (1-4) for each vessel transected; and 
• 
Type, name, and number of additional hemostasis measures required to achieve 
hemostasis for Grade 4 vessel transections. 
2.3 SAFETY ENDPOINT 
The primary safety endpoint will be occurrence of device-related (possible, probable or 
causal) adverse events (AEs). 
2.4 ADDITIONAL KEY DATA COLLECTED 
Additional key data collected for evaluation in this study are: 
• 
Procedure duration; 
• 
Use of any other energy device (monopolar, traditional bipolar, advanced bipolar, 
ultrasonic) in primary procedure (type, name, and number of device and reason for 
use), if applicable; 
• 
Surgeon questionnaire administered once per investigator; 
• 
Generator questionnaire after each procedure for each GEN11 used; 
• 
Surgical procedure conducted; 
• 
Hospital stay duration; 

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• 
Name and number of vessels that were transected, surgeon determination of 
diameter size range (< 3 mm, 3 to 5 mm, and > 5 to 7 mm); 
• 
Occurrence and location of cancer and occurrence of pre-surgical 
radiation/chemotherapy within 90 days prior to surgery, if applicable; 
• 
Occurrence of vessel skeletonization; 
• 
Presence of inflamed tissue, calcified tissues/vessels, atherosclerotic tissue, fibrotic 
tissue, or presence of adhesions intraoperatively, if applicable; 
• 
Volume of estimated intra-operative blood loss; 
• 
Occurrence of blood transfusion, if applicable (record the total required units of blood 
and rationale); 
• 
Type of additional mild interventions (use of compression, monopolar device, bipolar 
device, and/or touch-ups with HARMONIC 1100 Shears) required to achieve 
hemostasis for Grade 3 vessel transections including number of times when 
HARMONIC 1100 touch-ups were used; and 
• 
Procedure-related AEs (possible, probable or causal). 
 
3.0 INVESTIGATIONAL PLAN 
 
3.1 OVERALL STUDY DESIGN AND PLAN - DESCRIPTION 
This prospective, single-arm, multi-center study will collect clinical data in a post-market 
setting for the pediatric population (general surgical procedures) and adult population 
(general, gynecological, urological, and thoracic surgical procedures). Investigators will 
perform each procedure using the device in compliance with their standard surgical approach 
and the HARMONIC 1100 Shears and GEN11 IFUs. 
Subjects will be consented and screened anytime during a period of 8 weeks prior to the date 
of surgery. Subjects will be considered enrolled when the HARMONIC 1100 Shears has been 
attempted to be used for at least one single vessel transection during pediatric surgical 
procedures (general) and adult surgical procedures (general, gynecological, urological, and 
thoracic). All subjects enrolled will be followed post-operatively through discharge and again 
at 28 days (± 14 days) post-surgery; therefore, from the surgery date to study exit, the 
duration will be approximately 6 weeks. 
3.2 STUDY POPULATION 
3.2.1 
Enrollment 
Subjects will be recruited from the investigators’ existing patient population who plan to 
have a procedure from the proposed procedure groups utilizing consecutive screening and 
enrollment in an effort to generate a random and representative patient population sample. 
All eligible subjects (Sections 3.2.3 and 3.2.4) will be considered enrolled at the time when 
the HARMONIC 1100 Shears has been attempted to be used for at least one single vessel 
transection during one of the proposed procedure groups. Up to 15 surgery centers 
globally will be selected as study sites. Each participating investigator is expected to 
perform a minimum of two procedures using the HARMONIC 1100 Shears. A minimum of 
165 subjects enrolled (maximum of 328 subjects enrolled) will be included in the study with 
the following procedure targets: 

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Version: Amendment 3 
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17 MAY 2023 
 
 
Table 1: Distribution of Targeted Procedures 
 
Procedure 
Group 
Procedures 
Estimated Initial Enrollment Range 
(minimum is 33 per procedure 
group) 
1 
Pediatric 
33 – 40 
2 
Adult General (contain the following subgroups) 
33 – 119 
2a 
Adult HPB (e.g. liver resection) 
11 – 15 
2b 
Adult lower GI (e.g., large intestine resection) 
11 – 15 
2c 
Adult gastric (gastrectomy [e.g., subtotal, total], 
esophagectomy, RYGB, sleeve gastrectomy, or BPD/DS) 
11 – 89 
3 
Adult gynecological (e.g., hysterectomy, oophorectomy, 
myomectomy or endometriosis resection) 
33 – 40 
4 
Adult urological (e.g., nephrectomy, cystectomy or 
prostatectomy) 
33 – 40 
5 
Adult thoracic (lung resection [branches, excluding main 
PA/PV]) 
33 – 89 
 
Every subject enrolled in the study would count toward the primary enrollment goal of 165 
subjects. In addition, a secondary enrollment goal for the study is to enroll a sufficient 
number of subjects to achieve a minimum of 165 vessels transected with a diameter size 
of > 5 to 7 mm based on surgeon determination. Each discreet vessel transected 
measuring > 5 to 7 mm in diameter (per surgeon assessment) would count toward the 
secondary enrollment goal in addition to the primary enrollment. The initial assumption is 
that PA branches (thoracic procedure group) and left gastric veins (gastric procedure 
group) will have the greatest likelihood of having a vessel with a diameter size of > 5 to 7 
mm. The number of vessels transected with a diameter of > 5 to 7 mm will be continuously 
checked throughout the course of the study by surgeon determination (see Section 3.4.2). 
The table above provides the minimum number of subjects to be enrolled per procedure 
group and the Sponsor will determine the maximum number of subjects to be enrolled per 
procedure group. Once the minimum number has been met for a procedure group, 
enrollment for that group could be closed to further enrollment. 
3.2.2 
Screening Failures 
All subjects signing consent who do not have at least one single vessel transection 
attempted by HARMONIC 1100 Shears during their procedures will be recorded as screen 
failures. For subjects who are determined to be screen failures, only the relevant eCRF 
pages (inclusion/exclusion criteria, demographics, AEs, subject 
completion/discontinuation) will be completed. 
3.2.3 
Inclusion Criteria 
Subjects satisfying the following criteria will be considered eligible for enrollment in this 
study: 
Pediatric population: 
1. Non-emergent procedure (general) where at least one vessel is planned to be 

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transected by the HARMONIC 1100 Shears per the IFU; 
2. Less than 18 years of age at the time of procedure; and 
3. The subject’s parent/legal guardian must be willing to give permission for the 
subject to participate in the study and provide written informed consent for the 
subject. In addition, assent must be obtained from pediatric subjects who possess 
the intellectual and emotional ability to comprehend the concepts involved in the 
study. If the pediatric subject is not able to provide assent (due to age, maturity 
and/or inability to intellectually and/or emotionally comprehend the study), the 
parent/legal guardian’s written informed consent for the subject will be acceptable 
for the subject to be included in the study. 
Adult population: 
1. Elective procedure (general, gynecological, urological, or thoracic) where at least 
one vessel is planned to be transected by the HARMONIC 1100 Shears per the 
IFU; 
2. Willingness to give consent and comply with all study-related evaluations and visit 
schedule; and 
3. At least 18 years of age. 
3.2.4 
Exclusion Criteria 
Subjects meeting the following criteria will be considered ineligible for enrollment in this 
study: 
Preoperative 
1. Physical or psychological condition which would impair study participation; or 
2. Female subjects, of childbearing age, who are pregnant; or 
3. Enrollment in a concurrent interventional clinical study that could impact the study 
endpoints. 
Intraoperative 
1. The HARMONIC 1100 Shears were not attempted to be used for at least one 
single vessel transection during the surgical procedure. 
3.2.5 
Removal of Subjects from Study 
A subject has the right to withdraw from the study at any time for any reason without 
prejudice to his/her future medical care by the physician or the institution. Should a subject 
(or subject’s legally authorized guardian/representative) decide to withdraw, 1) all data 
collected up to the point of withdrawal will be considered for analysis; and 2) all efforts will 
be made to collect and report the final visit observations as thoroughly and timely as 
possible. Participation may be terminated prior to completing the study for any of the 
reasons listed below (reasons that do not fit the categories below will be documented as 
“other”). 

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Adverse Event 
When the subject experiences an AE and the Investigator or Medical Monitor believes it is 
in the best interest of the subject to discontinue participation in the study, the subject will 
be withdrawn from the study. 
Lost to follow-up 
When contact with the subject has been lost without completing a final contact 
assessment, and every attempt to contact the subject has failed, the subject will be 
considered lost to follow-up. All attempts to contact the subject requesting his/her return 
for the final visit must be documented. 
Withdrawal of consent 
Any method of contact with the subject (or subject’s legally authorized 
guardian/representative) in which he/she state they no longer want to participate in the 
study specific activities constitutes withdrawal of consent for participation in the study. 
When possible, the reason for withdrawal will be documented. 
Site Termination or Study Termination 
A study site or the entire study may be terminated. When this occurs, all subjects currently 
enrolled at the site will be withdrawn and documented as early terminations. Reasons for 
site or study termination may include, but are not limited to the following: 
• 
Administrative concerns (e.g., inadequate subject enrollment, 
Investigator/institution non-compliance, change of business strategy, etc.); 
• 
Safety Issues, including those due to non-compliance, which substantially affect 
the risk to benefit ratio of the study subjects at a site or for the study as a whole; or 
• 
Regulatory Body Mandate(s). 
The Investigator has the right to terminate the subject’s participation at any time. Should 
this be necessary, procedures for termination will be provided by the Sponsor. 
Death 
• 
When possible, the cause of death will be documented. 
Other (which may include) 
• 
Investigator recommendation. 
3.2.6 
Subject Replacement in Study 
Subjects who withdraw or are terminated early from the study will not be replaced. 
3.3 STUDY PROCEDURES 
3.3.1 
Procedure Description 
Elective pediatric surgical procedures (general) or adult surgical procedures (general, 
gynecological, urological, and thoracic) where HARMONIC 1100 is indicated for use will be 
performed per the institution’s SOC. Only the PI or Sub-Investigator can use the device 
during the vessel transections. See Section 3.2.1 for a list of possible specific procedures. 
3.3.2 
Identity of Study Products 
The HARMONIC 1100 Shears and the GEN11 are the study devices for this study. 

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3.3.2.1 
Device Description 
HARMONIC 1100 Shears 
The HARMONIC 1100 Shears instrument is a sterile, single-patient-use instrument used 
for dissection, grasping, coagulation, and cutting between the blade and clamp arm. It 
consists of an ergonomic handle with an integrated hand piece and two energy delivery 
buttons. The instrument shaft can be rotated continuously to facilitate visualization and 
access to targeted tissue. The Energy button is indicated for vessels up to 5 mm in 
diameter. When the Energy button is used, cutting speed is the fastest. The Energy 
button with Advanced Hemostasis is designed for larger vessels and is indicated for 
vessels up to 7 mm in diameter. When the Energy button with Advanced Hemostasis is 
used, cutting speed is reduced and hemostasis is maximized. The instrument utilizes 
Adaptive Tissue Technology that is specific to the HARMONIC 1100 Shears. This 
provides the generator with the ability to identify and monitor the instrument during use, 
which enables the generator to modulate and adjust its power output as well as provide 
audible feedback to the user as appropriate. The HARMONIC 1100 Shears is designed 
for use exclusively with the GEN11 software version 2018-1 or later, packaged 
separately. 
GEN11 
The GEN11 device supplies energy to the HARMONIC and ENSEAL surgical 
instruments. The generator uses a touchscreen display interface and has a unique 
receptacle port that accepts either a HARMONIC or an ENSEAL instrument. Connectors 
(HGA11 for HARMONIC and EGA11 for ENSEAL) are used to enable the generator to 
power legacy instruments. 
3.3.2.2 
Indications 
HARMONIC 1100 Shears 
The HARMONIC 1100 Shears instrument is indicated for soft tissue incisions when 
bleeding control and minimal thermal injury are desired. The instruments can be used as 
an adjunct to or substitute for electrosurgery, lasers and steel scalpels in general, 
pediatric, gynecologic, urologic, thoracic, and sealing and transection of lymphatic 
vessels. The instruments allow for the coagulation of vessels up to and including 7 mm 
in diameter, using the Energy button with Advanced Hemostasis. 
GEN11 
The GEN11 provides radiofrequency power to drive ENSEAL electrosurgical instruments 
that are used during open or laparoscopic general and gynecological surgery to cut and 
seal vessels and to cut, grasp, and dissect tissues. In addition, the generator provides 
power to drive HARMONIC ultrasonic surgical instruments that are indicated for soft 
tissue incisions when bleeding control and minimal thermal injury are desired. 
ENSEAL and HARMONIC instruments, when used with the GEN11, have not been 
shown to be effective for sterilization procedures or tubal coagulation. 
3.3.2.3 
Contraindications 
HARMONIC 1100 Shears 
The HARMONIC 1100 Shears are not indicated for incising bone and are not intended 
for contraceptive tubal occlusion. 

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GEN11 
The use of the GEN11 and the attached instruments are contraindicated when, in the 
judgement of the physician, radiofrequency or ultrasonic surgery would be contrary to 
the best interest of the patient. The instruments are not indicated for incising bone. 
3.3.2.4 
Labeling of Study Products 
The HARMONIC 1100 Shears has received 510(k) clearance in the United States by the 
Food and Drug Administration (FDA), has clearance in Canada by Health Canada and 
has CE Mark in the European Union and United Kingdom. The GEN11 has received 
510(k) clearance in the United States by the FDA, has clearance in Canada by Health 
Canada and has CE Mark in the European Union and United Kingdom. The study 
devices will use the cleared labeling. The Sponsor requires no additional labeling in this 
study. 
3.3.2.5 
Accountability of Study Products 
The HARMONIC 1100 Shears may be provided to the participating institutions. The 
GEN11 (including footswitches) may be loaned to any institution in the study. Each 
institution not provided with HARMONIC 1100 Shears will use devices acquired through 
normal procurement process. If institutions are provided HARMONIC 1100 Shears, the 
devices will be tracked using shipping receipts and device accountability logs and all 
device returns will be managed by contacting the Sponsor study team. Devices provided 
for the study must be kept in a secure area and used only for treating subjects 
participating in the study, in accordance with the protocol. If applicable, the study device 
inventory/accountability logs must be available for routine monitoring purposes as part of 
required Sponsor oversight, or inspection. 
3.3.3 
Prior and Concomitant Therapy 
Subjects will be assessed for certain prior medication therapy used up to 30 days prior to 
surgery. These medications include aspirin, antiplatelet agents, nonsteroidal anti- 
inflammatory drugs, and anticoagulants. Review will occur during Visit 1 (Screening Visit) 
and Visit 2 (Procedure Visit). 
Subjects will be assessed for occurrence of pre-surgical radiation/chemotherapy used up 
to 90 days prior to surgery. Review will occur during Visit 1 (Screening Visit) and Visit 2 
(Procedure Visit). 
Subjects may continue with their current medical care while in the study and the following 
medications will be collected for this study: 
• 
Certain prior medication therapy used up to 30 days prior to surgery (listed above); 
and 
• 
Any medications administered during the study due to a device-related or 
procedure-related AE. 
3.4 STUDY VARIABLES 
Specific variables assessed in the study are provided in the following sections. Refer to 
Section 3.5 Schedule of Events for the time when the study variables will be collected 
throughout the course of the study. 
3.4.1 
Demographic and Baseline Characteristics 
The following will be collected preoperatively: 

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• 
Age (years); 
• 
Gender; 
• 
Race; 
• 
Ethnicity; 
• 
Administer pregnancy test as per standard of care; 
• 
Body weight (kg or lbs; no shoes); 
• 
Body height (cm or in; no shoes); 
• 
American Society of Anesthesiologists Physical Status Classification System 
(ASA) score; 
• 
Occurrence and location of cancer, if applicable; 
• 
Review and collection of relevant medical history and surgical history including the 
following: 
o For the gynecological procedure group, gravidity and parity; 
o Surgical procedure to be conducted, including primary indication for 
surgery; and 
o Smoking history (current smoking status, if stopped, length of time [months 
and years]). 
3.4.2 
Study Variables 
The following variables will be recorded preoperatively, intraoperatively, or postoperatively: 
• 
Date/time of hospital admission; 
• 
Procedure duration, defined as first skin incision to final skin closure; 
• 
Did vessel skeletonization occur (Yes/No; if Yes, describe vessel skeletonized and 
device used); 
• 
Was there presence of inflamed tissue, calcified tissues/vessels, atherosclerotic 
tissue, fibrotic tissue, or presence of adhesions intraoperatively, if applicable 
(Yes/No; if Yes, describe the tissue along with location)?; 
• 
Was there sealing and transection of lymphatic vessels by HARMONIC 1100 
Shears (Yes/No; if Yes, describe lymphatics and tissue bundles along with location 
and complete 5-point scale)?; 
• 
Conversion to open with reason, if applicable; 
• 
Volume of estimated intra-operative blood loss; 
• 
Use of any other energy device (monopolar, traditional bipolar, advanced bipolar, 
ultrasonic) in primary procedure (type, name, and number of device and reason for 
use), if applicable; 
• 
Name, product code, lot #, and number used of trocars used with HARMONIC 
1100 Shears, if applicable; 
• 
Was there prophylactic use of clips or sutures as standard of surgical care before 
vessel transection (Yes/No; if Yes, name vessel transected, and number of clips or 

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sutures prophylactically applied); 
• 
For each vessel transected with HARMONIC 1100 Shears: 
o Name of each vessel; 
o Hemostasis grading scale assessment (1-4); 
o Surgeon determination of diameter size range (< 3 mm, 3 to 5 mm, and > 5 
to 7 mm); 
o Image captured where the vessel is perpendicular and below the open jaw 
of the HARMONIC 1100 Shears; 
o For every Grade 3 vessel transection: 
 
Compression used as a mild intervention, if applicable (Yes/No); 
 
Touch-ups with a monopolar device, if applicable (Yes/No; if Yes, 
record number of touch-ups); 
 
Touch-ups with a bipolar device, if applicable (Yes/No; if Yes, record 
number of touch-ups); 
 
Touch-ups with HARMONIC 1100 (Yes/No; if Yes, record number of 
touch-ups); 
o For every Grade 4 vessel transection intervention: 
 
Type, name, and number of times used for each additional 
hemostatic measure used along with a description of why it was 
considered Grade 4; 
• 
For the gynecological procedure group, if applicable: 
o Estimated uterine size in grams; 
• 
Occurrence of blood transfusion, if applicable (record the total required units of 
blood and rationale); 
• 
Concomitant procedures, if applicable (defined as any medical or surgical 
procedure beyond those associated with primary study procedure). If a 
concomitant procedure requires vessel transection by HARMONIC 1100 Shears, 
each vessel transected will have the same information collected as stated above 
for vessel transections, but these will not be included as part of the primary 
endpoint; 
• 
Concomitant medication usage associated with device-related or procedure-related 
AEs and specific drugs used up to 30 days prior to surgery (aspirin, antiplatelet 
agents, nonsteroidal anti-inflammatory drugs, anticoagulants) and 90 days prior to 
surgery (pre-surgical radiation/chemotherapy); and 
• 
Date/time of hospital discharge. 
3.4.3 
Questionnaires 
Data related to the following study variables will be obtained from the Surgeon 
Questionnaire for every investigator after they have completed his/her second procedure 
and a GEN11 Questionnaire after every completed procedure. Both Surgeon and 
Generator Questionnaire responses will then be transcribed onto eCRFs, with the 
questionnaire serving as the source document. 

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Surgeon Questionnaire 
Investigators will be asked to answer a non-validated surgeon questionnaire related to 
his/her experience using the HARMONIC 1100 Shears. The survey will be completed by 
the Investigators as soon as possible after completion of his/her second procedure in any 
of the seven procedure groups. 
Generator Questionnaire 
Investigators will be asked to answer a non-validated generator questionnaire related to 
his/her experience using the GEN11 and any HARMONIC and/or ENSEAL device. The 
survey will be completed by the Investigators as soon as possible after each procedure, 
preferably on the same day for each GEN11 used. 
3.4.4 
Safety Data Variables 
All device-related and procedure-related AEs will be collected as outlined in Section 6.0. 
3.5 SCHEDULE OF EVENTS 
Table 2: Schedule of Events 
 
Activity 
Visit 1a 
Visit 2a 
Visit 3 
Unscheduled 
Visit, if 
applicableb 
Screening Visit 
(Day -56 to Day 
0) 
Procedure Day (0) 
Through Discharge 
Visit 
Post Procedure 
Follow Up Visit 
(Day 28 ± 14)b 
Informed consent/assent, as applicable 
X 
Demographics (age, gender, race, and 
ethnicity) 
X 
Administer pregnancy test as per 
standard of care 
X 
X 
Height and weight (both with no shoes) 
X 
Medical and surgical history (including 
diagnosis) 
X 
X 
Review of inclusion/exclusion criteria 
X 
X 
Concomitant medications 
X 
X 
X 
X 
Surgical data collected for evaluation 
X 
Collect vessel imagec 
X 
Collect generator questionnaired 
X 
Collect surgeon questionnairee 
X 
Concomitant procedures conducted 
besides primary procedure 
X 
Re-operation(s) associated with the 
primary procedure 
X 
X 
Assess for device-related and 
procedure-related AEs 
X 
X 
X 
Subject completion/discontinuation 
X 
X 
X 
a. Visit 1 and Visit 2 may be combined; 
b. This can be either an office visit or telephone follow-up; 
c. The image captured where the vessel is below the open jaw of the HARMONIC 1100 Shears perpendicular to the vessel during the 
primary procedure at Visit 2; 
d. The generator questionnaire will be completed after each Visit 2 procedure; 
e. The surgeon questionnaire will be completed after the investigator has completed his/her second procedure in any of the seven 
procedure groups. 
AE = adverse events. 

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3.6 STUDY PROCEDURES 
3.6.1 
Visit 1 – Screening (may occur over visits within 8 weeks of Visit 2 including 
up to the day of the procedure) 
Prospective subjects will be provided with the study information including the ICD. The 
subject must be given ample time to review and sign the ICD. The screening activities 
noted in Section 3.5 will occur prior to the study procedure. 
3.6.2 
Visit 2 – Procedure Through Discharge 
Pre-procedure 
The following must be obtained prior to the surgical procedure: 
• 
Pregnancy test as per standard of care; 
• 
Height and weight (both with no shoes); 
• 
Updates to concomitant medication and medical/surgical/smoking history; and 
• 
Confirm inclusion and exclusion criteria. 
Intra-operative and Post-operative 
Data collected during and after the procedure as defined in Section 3.4. 
3.6.3 
Visit 3 – Post-procedure Follow-up 
After the date of surgery, subjects will have a follow-up visit approximately 28 days (± 14 
days) later. This visit can be either an office visit or a telephone follow-up. Data to be 
collected is defined in Section 3.5. 
3.6.4 
Unscheduled Visit(s) 
Any unscheduled visit between Visit 2 and Visit 3 will be documented including the reason 
for the visit. This visit can be either an office visit or a telephone follow-up. Data to be 
collected is listed in Section 3.5. 
3.6.5 
Vessel Image Capture 
The preferred image should be captured during the primary procedure at Visit 2 where the 
vessel (or the tissue bundle containing the vessel) is below the open jaw of the 
HARMONIC 1100 Shears. The image should show the device perpendicular to the vessel. 
The image should have the entire length of the jaw of the HARMONIC 1100 Shears in 
view. The image will be uploaded to the electronic database capture (EDC) system as 
either a jpeg or pdf file. The Sponsor will determine if the image is analyzable and then 
each image will be reviewed and have a vessel size determined (if measurement is 
feasible) to the nearest quarter decimal (e.g., 5.0 mm, 5.25 mm, 5.50 mm, etc.) by the 
Sponsor utilizing computer software with the measurement captured in the EDC. No 
reconciliation will be performed between the surgeon determination of vessel size (see 
Section 3.4.2) and the vessel size determined by the image analysis. The primary vessel 
size determination will be by the surgeon determination. 

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4.0 DATA MANAGEMENT AND INTEGRITY 
 
4.1 DATA COMPLETION AND RECORD KEEPING 
4.1.1 
Source Documents 
Source documents are documents on which information regarding subjects is first 
recorded, including printed, optical, or electronic documents. Investigator subject files or 
hospital records generally are the basis of source document information. This includes but 
is not limited to, original subject files; hospital/clinic records; original recordings /tracing; 
radiographs; device accountability records; photographic negatives; and records kept at 
the investigation site, at the laboratories and at other departments involved in the clinical 
investigation. Source document worksheets may also be used to facilitate data collection 
and entry into eCRFs. 
Source documents must be retained by the Investigator as part of the subject’s study 
record. The information in the source documents is used to complete the eCRFs. All 
information captured on the eCRFs should be completely and accurately supported in 
source documentation. Any additional information relevant to the study should be included 
in the source documents. Any deviations from the study protocol or procedures should be 
recorded in the source documents. The Investigator will retain originals of all source 
documents, subject consent forms, and study data per site policy. 
4.1.2 
Electronic Data Capture 
An EDC system will be utilized by study site personnel to transfer study data from source 
records (medical records and/or source document worksheets) onto common eCRFs. This 
system is a web-based, secure electronic software application (Medidata® Rave, 350 
Hudson St. 9th Floor, NY, NY 10014). This system was designed and is developed and 
maintained by Medidata in a manner that is compliant with national and international GCP 
data protection/data privacy and electronic record/electronic signature (e.g., 21 Code of 
Federal Regulations Part 11) regulatory requirements. The EDC system will be used to 
facilitate the collection of all study data at the site. Designated site personnel will be 
responsible for entering subject data into the EDC system. All external and Sponsor 
internal users will be trained on the EDC application at a level dependent on their planned 
function. An EDC digital User Manual will be available under the help menu within the 
Medidata® Rave website to assist in the collection and entry of source data into the 
electronic casebook. 
A 24/7/365 Help Desk Support line (telephone: +001 973-659-6780; fax: 973-954-5621; 
toll free: +001 866-633-4328; Email: helpdesk@mdsol.com) staffed by the outsourced 
vendor will also be available to respond to site and monitor questions. 
4.1.3 
Data Collection 
Each EDC eCRF will be completed by the PI or PI’s designee. Every effort should be 
made to respond to all monitoring and/or data management questions on each eCRF as 
completion of the data is required by the protocol. A unique ID number will identify each 
subject and will be visible on each eCRF. At no time should the subject name or protected 
health information appear on the eCRFs. 
All data should be recorded accurately and completely. The PI is responsible for reviewing 
and approving each completed eCRF. Assurance of overall review and approval will be 
documented by the PI electronically signing each subject’s electronic casebook at the end 
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4.1.4 
Data Correction 
Required data corrections to eCRFs will be prompted via automated electronic edit checks 
and/or queries manually created by Sponsor reviewers. The change(s), individual making 
the change(s), and time the change(s) was made to the eCRFs will be automatically 
captured in the audit trail within Medidata® Rave. 
4.1.5 
Data Privacy 
The collection, use, and disclosure of all personal data, including subject health and 
medical information, are to be maintained in compliance with applicable personal data 
protection and security laws and regulations that govern protected health information and 
the informed consent given by each study subject. When collecting and processing such 
personal data, appropriate measures are to be taken to maintain the confidentiality of 
subject health and medical information and to prevent access by unauthorized persons. 
4.1.6 
Record Retention, Inspection, and Custody 
The PI must maintain all documentation related to the study until notified by the Sponsor. 
The PI will allow representatives of the Sponsor or other government regulatory agencies 
to inspect all study records, eCRFs, and corresponding portions of the subject’s office 
and/or hospital medical records at regular intervals during the study. These inspections 
are to verify adherence to the protocol, integrity of the data being captured on the eCRFs, 
and compliance with applicable regulations. 
Subject study records will be maintained in a confidential manner. Study reports will not 
identify subjects by name. These reports may be submitted to regulatory authorities. 
If custody of the records is transferred, notice of such a transfer should be given to the 
Sponsor no later than 10 working days before the transfer occurs. 
4.2 MEDICAL DICTIONARY CODING 
Medical dictionary coding of medical history and verbatim AEs captured on eCRFs will be 
performed using a coding thesaurus algorithm. The Medical Dictionary for Regulatory 
Activities (MedDRA) will be used after data entry and query resolution, via auto-encoding and 
interactive coding processes. 
4.3 DATA QUALITY ASSURANCE 
Steps to be taken to assure the accuracy and reliability of data include the selection of 
qualified investigators and appropriate sites, review of protocol procedures with the 
Investigator and associated personnel prior to the study, and periodic monitoring visits by the 
Sponsor. The Sponsor will review eCRFs for accuracy and completeness during either onsite 
or offsite monitoring visits; any discrepancies will be resolved with the Investigator or 
designees, as appropriate. 
4.3.1 
Site Personnel Training 
Prior to screening subjects for this study, any relevant study staff will be trained on study 
execution, data collection, and procedures specific to this clinical protocol, as applicable. 
4.3.2 
Monitoring 
This study will be monitored by the Sponsor or its representative to ensure: 
• 
The rights and well-being of the subjects are protected; 
• 
The reported study data is accurate, complete, and verifiable from source 
documents; and 

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• 
The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), applicable GCPs, and with applicable local/regional 
regulatory requirements. 
The extent and nature of monitoring will be predetermined and agreed to by the Sponsor 
and investigators. Monitors will comply with established written standard operating 
procedures as well as procedures specified by the Sponsor in the monitoring plan for this 
study. 
4.3.3 
Quality Assurance 
The extent and nature of quality assurance audits will be predetermined and based on 
considerations such as the regulatory classification, objective, and complexity of the study. 
Any audits performed will comply with established written standard operating procedures 
and the audit plan for this study. 
4.4 PROTOCOL DEVIATIONS 
A deviation (any activity conducted outside the parameters established by the protocol) can 
be identified from a number of sources. Potential sources for identification of deviations 
include, but are not limited to: a member of the Investigator’s staff, a Sponsor representative 
during monitoring visits, or a member of the data management or statistical groups when 
entering or analyzing data. Regardless of the source, it is crucial to document the deviation 
within source documentation. Protocol deviations will be captured in the eCRFs. The PI will 
report protocol deviations to the IRB/EC as required by the IRB/EC procedures. 
 
5.0 STATISTICAL METHODS PLANNED IN THE PROTOCOL AND 
DETERMINATION OF SAMPLE SIZE 
 
The Sponsor will be responsible for the analysis of data from this protocol. A detailed Statistical 
Analysis Plan (SAP) will be written and approved prior to final database lock. The SAP will 
describe all planned analyses based on the statistical design of this study and the subsequent 
data collected. A brief overview of key statistical analyses is provided below. 
5.1 STUDY DESIGN 
Study design is described in Section 3.1. 
5.2 TREATMENT ASSIGNMENT 
This is a single-arm study where all enrolled subjects will have the HARMONIC 1100 Shears 
utilized for transection of at least one single vessel. 
5.3 INTERVAL WINDOWS 
Interval windows for the purpose of analysis in this study will not be defined outside of those 
already specified in the protocol for visit scheduling as the collection of data for the primary 
and secondary performance endpoints occurs intra-operatively. The final visit occurs 
approximately 4 weeks after surgery, thus no interval windows need to be defined given the 
absence of long-term follow-up in this study. The Schedule of Events specifies a window of 
14 days around the scheduling of the 4-week follow-up visit, and any information entered in 
the eCRFs at this visit will correspond to the 4-week visit. There will be no assigning of 
observations to time points outside of the visit to which they are recorded in the eCRFs. 

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5.4 PRIMARY AND SECONDARY ENDPOINTS AND ASSOCIATED HYPOTHESES 
All study endpoints are described in Section 2.1 through Section 2.4. The following 
hypothesis will be evaluated for the primary endpoint: 
H0: p ≤ 87.5% 
H1: p > 87.5% 
Where p is the percentage of transections achieving a Grade 3 or lower hemostasis rating 
and 87.5% is set as a performance goal for the lower bound of acceptable hemostasis. A 
two-sided 95% confidence interval will be calculated for p based on the sample proportion of 
transections where Grade 3 or lower hemostasis was achieved using exact Binomial 
methods proposed by Clopper-Pearson and the lower limit of this confidence interval will be 
compared to 87.5% to evaluate the above hypotheses. A p-value will be determined based 
on an exact binomial test. The null hypothesis will be rejected if the lower limit of the 
confidence interval is greater than 87.5%. 
Given that multiple transections per subject may occur, a sensitivity analysis will be 
performed using an appropriate method to account for the potential correlation among the 
outcomes of multiple transections within the same subject. Complete details of this approach 
will be provided in the SAP. 
The hypothesis and evaluation of hypothesis for the secondary endpoint for the proportion of 
vessels transected of diameter size > 5 to 7 mm with hemostasis grade 3 or lower will be 
similar to the primary endpoint as described above. 
5.5 LEVELS OF SIGNIFICANCE 
The hypotheses above will be evaluated using a one-sided significance level of 0.025. 
Estimation of all additional endpoints will be performed using two-sided 95% confidence 
intervals. 
5.6 ANALYSIS SETS 
The summary of all performance and safety endpoints will be performed on the set of 
subjects in whom the HARMONIC 1100 Shears is utilized during the surgical procedure to 
transect at least one vessel. The summary of all primary and secondary performance and 
safety endpoints will be performed by surgical population (pediatric and adult), surgical 
procedure group, procedure subgroup, and on the entire pooled set of subjects. The 
hypotheses described in Section 5.4 will be evaluated on the pooled set of subjects and the > 
5 to 7 mm diameter vessel population. The > 5 to 7 mm diameter vessel population will be 
based off the surgeon determination of the vessel size. 
5.7 SAMPLE SIZE JUSTIFICATION 
Primary performance analysis: A sample size of at least 165 subjects is required to have a 
minimum of 80% power for rejecting the null hypothesis that the rate of Grade 3 or lower 
transections is less than or equal to 87.5% when the expected rate of Grade 3 hemostatic 
transections is at least 94.0% using an exact binomial test and an one-sided significance 
level of 0.025. This sample size estimation makes the assumption of one transection per 
subject which is likely very conservative as most subjects may have 2 or more transections 
during their procedure. Therefore, it is expected that greater than 165 transections will be 
observed and thus the study will be well powered for evaluating the performance goal 
hypothesis under the assumption of independence of observations. At the time of study 
protocol amendment 3 it was found that on average there were 2 vessel transections per 
subject. 

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The assumption of independence and its impact on the overall study conclusion will be 
evaluated through sensitivity analyses. Given that the primary endpoint is being evaluated 
intra-operatively, it is not anticipated that there will be subject dropout prior to evaluating this 
endpoint, thus no adjustment or increase in subject enrollment is planned to account for 
dropout. A minimum of 33 subjects will be enrolled into each of the five individual procedure 
subgroups. 
The performance goal of 87.5% was selected to represent a minimum acceptable level of 
clinical performance across all procedure groups. A recent energy study2 with the same 
hemostasis endpoint in similar procedure groups showed point estimates of the primary 
endpoint ranging from 94.2% to 100.0%. The 95% confidence interval for the lowest 
performing group had a lower bound of 89.3%, thus selection of 87.5% represents a less 
than 2% region of indifference for maintaining average acceptable performance. In the recent 
study, average performance across all groups was 96.2% and selection of 87.5% as the 
performance goal corresponds to a noninferiority margin of 8.7% which is less than the 
commonly chosen value of 10%. Finally, consideration of the performance goal of 87.5% in 
the context of the relative reduction from the overall average performance of 96.2%, this can 
be interpreted as preserving at least 91.0% of the original average treatment effect 
(87.5/96.2*100% = 91.0%). Maintaining at least 91.0% of the expected effect of similar 
therapies represents a clinically meaningful metric for maintaining minimum acceptable 
performance and is actually considerably larger than the standard limits used for 
bioequivalence where the lower bound for relative therapeutic efficacy is set at 80%, 
considerably lower than the 91.0% of therapeutic efficacy that is represented by a 
performance goal of 87.5% chosen for this trial. 
Secondary performance analysis: A sample size of at least 165 vessels is required to have a 
minimum of 80% power for rejecting the null hypothesis that the rate of Grade 3 or lower 
transections is less than or equal to 87.5% when the expected rate of Grade 3 hemostatic 
transections is at least 94.0% for vessels with diameter size of > 5 to 7 mm. Sample size 
estimation considered an exact binomial test and a one-sided level of significance of 0.025. 
The number of vessels transected with a diameter size of > 5 to 7 mm will be continuously 
checked throughout the course of the study to achieve the required number of vessels. 
Safety analysis: From a safety perspective on the pooled analysis of 165 subjects and in 
consideration of rare AEs that may occur (e.g., bleeding requiring blood product transfusion), 
for an event that has an incidence rate of, for example, 1%, then in a sample of 165 subjects, 
the probability of observing at least 1 event is 81.0% under a binomial probability model. 
Thus, this sample size provides a high probability of observing rare events if they do occur, 
and provides reasonable assurance to conclude that the likelihood of such AEs is less than 
2.3% if they do not occur based on the upper limit of an exact 95% confidence interval when 
0 events out of 165 subjects are observed. 
5.8 DATA MONITORING COMMITTEE 
There are no plans to utilize a data monitoring committee during this study. 
5.9 ANALYSES TO BE CONDUCTED 
5.9.1 
General Conventions 
Categorical variables will be summarized descriptively by frequencies and associated 
percentages. Continuous variables will be summarized descriptively by number of 
subjects, mean, standard deviation, median, minimum, and maximum. Confidence 
intervals will also be provided for procedure-related variables. 

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5.9.2 
Disposition of Study Subjects 
Subject disposition will be summarized in total, by surgical population (pediatric and adult), 
surgical procedure group, and procedure subgroups using counts and percentages. The 
number and percentage of subjects completed and discontinued will be tabulated along 
with the specific reasons for discontinuation. 
5.9.3 
Demographic, Baseline, and Surgical Characteristics 
Summary statistics of subject demographics (age, gender, and race) will be presented in 
total, and by surgical population (pediatric and adult), surgical procedure group, and 
procedure subgroups. Surgical characteristics including, at minimum, estimated blood 
loss, requirement for blood transfusion, and procedure duration will be summarized by 
surgical population (pediatric and adult), surgical procedure group, and procedure 
subgroups and in total. 
5.9.4 
Primary and Secondary Endpoint Analyses 
The number and percentage of vessels where hemostasis is achieved (≤ Grade 3) will be 
summarized and an exact two-sided 95% confidence interval based on Clopper-Pearson’s 
method will be estimated for each surgical population (pediatric and adult), surgical 
procedure group, procedure subgroup, the > 5 to 7 mm diameter vessel population, and in 
total. The performance goal hypothesis will be tested as described in Section 5.4 on the 
total population and the > 5 to 7 mm diameter vessel population. 
Summary statistics appropriated for categorical or continuous variable will be provided for 
type, size, and number of vessels transected, as well as for the grading scale distribution 
for all vessels transected, number of times HARMONIC 1100 Shears touch-ups were 
required, incidence of requirement for additional measures to obtain hemostasis on 
vessels (other advanced energy devices or hemostatic measures), and 5-point scale 
scores for sealing and transection of lymphatic vessels completed by the HARMONIC 
1100 Shears. In addition, these analyses will also be completed for the vessels in the > 5 
to 7 mm diameter size vessel range. 
All device-related and procedure-related AEs reported during the study will be coded to 
MedDRA. All AEs will be summarized by MedDRA system organ class and preferred term 
by surgical population (pediatric and adult), surgical procedure group, procedure 
subgroup, and in total. Separate summaries will be provided for device-related and 
procedure-related AEs. Serious AEs will be summarized in a similar manner. In addition, 
these analyses will also be completed for the vessels in the > 5 to 7 mm diameter size 
vessel range. 
5.9.5 
Plans for Interim Analyses 
No interim analysis is planned for this study. 
5.9.6 
Handling of Missing Data 
All summaries will be performed only on subjects undergoing the scheduled procedure 
and only observed data will be summarized. There will be no imputation of data for early 
terminated subjects or for missing data within the database. 
5.9.7 
Subgroup Analyses 
Subgroup analyses are planned to be performed for the subgroup of subjects who have a 
medical history of treatment for cancer (e.g. chemotherapy or radiation) and may be 
performed for additional groups pending the distributions of baseline demographic or 
clinical characteristics. These analyses will be exploratory and summary statistics for the 

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procedure-related parameters will be provided for each subgroup. 
 
6.0 ADVERSE EVENTS 
 
Only AEs that have a relationship considered possible, probable, or causal to the devices or the 
procedure will be collected during this study. 
6.1 DEFINITIONS 
6.1.1 
Adverse Event 
An AE is defined as any untoward medical occurrence, regardless of its relationship to the 
study device or the study procedure. An untoward medical occurrence includes any new, 
undesirable medical experience or worsening of a pre-existing condition, which occurs 
throughout the duration of the clinical study. 
6.1.2 
Serious Adverse Event 
It is the Investigator’s responsibility to determine the “seriousness” of a reportable AE. 
A SAE is defined as an AE (as defined in Section 6.1.1) that results in any of the following: 
• 
Death; 
• 
A life-threatening illness or injury; 
• 
A permanent impairment of a body structure or a body function; 
• 
Required in-patient hospitalization or prolongation of existing hospitalization; 
• 
Resulted in medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function; 
• 
Led to a fetal distress, fetal death, or a congenital abnormality or birth defect. 
Note: “Death” should not be reported as an AE. The cause of death should be reported as 
the AE. The only exception is “Sudden Death” when the cause is unknown. 
Note: Planned hospitalization for a pre-existing condition, or a procedure required by the 
protocol, without serious deterioration in health, is not considered a SAE. 
6.1.3 
Pre-existing Condition 
A pre-existing condition is defined as a medical condition that is present at the initiation of 
the study and is to be reported as part of the subject’s medical history with a listed start 
date. Any pre-existing condition that has worsened in intensity, frequency, or the character 
of the condition, if related to the devices or the procedure, should be recorded as a new 
AE on the AE eCRF, as an exacerbation of the pre-existing condition and the start date 
will be recorded as the time when the exacerbation occurred. 
6.2 SEVERITY OF ADVERSE EVENTS 
It is the Investigator’s responsibility to assess the severity of an AE. A change in severity may 
constitute a new reportable AE. 
The following guideline should be used to determine the severity of each AE: 
• 
MILD: A type of AE that is usually transient and may require only minimal 
treatment or therapeutic intervention. The event does not generally interfere with 
usual activities of daily living. 
• 
MODERATE: A type of AE that is usually alleviated with additional specific 
therapeutic intervention. The event interferes with usual activities of daily living, 
causing discomfort but poses no significant or permanent risk of harm to the 

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research participant. 
• 
SEVERE: A type of AE that interrupts usual activities of daily living, or significantly 
affects clinical status, or may require intensive therapeutic intervention. 
6.3 RELATIONSHIP OF ADVERSE EVENTS 
It is the Investigator’s responsibility to assess the relationship of a reportable AE (as defined 
in Section 6.1.1). Only AEs that have a relationship considered possible, probable, or causal 
to the study procedures or either of the HARMONIC 1100 Shears or GEN11 devices are to 
be recorded in the eCRF and reported to the Sponsor. 
The following guidelines should be used in determining the relationship of an AE in the study: 
• 
Not related – Relationship to the procedures or device can be excluded when: 
o The event is not a known side effect of the product category the device 
belongs to or of similar devices and procedures; 
o The event has no temporal relationship with the use of the device or the 
procedures; 
o The event does not follow a known response pattern to the device (if the 
response pattern is previously known) and is biologically implausible; 
o The discontinuation of the device application or the reduction of the level 
activation/exposure (when clinically feasible) and reintroduction of its use 
(or increase of the level of activation/exposure), does not impact on the 
event; 
o The event involves a body-site or an organ not expected to be affected by 
the device or the procedure; 
o The event can be attributed to another cause (e.g. an underlying or 
concurrent illness/clinical condition, an effect of another device, drug, 
treatment, or other risk factors); 
o Harms to the subject are not clearly due to use error; or 
o To establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedure and the 
event. 
• 
Possible – The relationship with the use of the device is weak but cannot be ruled 
out completely. Alternative causes are also possible (e.g. an underlying or 
concurrent illness/condition and/or an effect of another device, drug, or treatment). 
Cases where relatedness cannot be assessed or no information has been obtained 
should also be classified as possible. 
• 
Probable – The relationship with the use of the device seems relevant and/or the 
event cannot reasonably be explained by another cause, but additional information 
may be obtained. 
• 
Causal relationship – The event is associated with the device or with procedures 
beyond reasonable doubt when: 
o The event is a known side effect of the product category the device belongs 
to or of similar devices and procedures; 
o The event has a temporal relationship with the device uses/application or 

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procedures; 
o The event involves a body-site or organ that: 
 
The device or procedures are applied to; 
 
The device or procedures have an effect on; 
o The event follows a known response pattern to the medical device (if the 
response pattern is previously known); 
o The discontinuation of medical device application (or reduction of the level 
of activation/exposure) and reintroduction of its use (or increase of the level 
of activation/exposure), impact on the event (when clinically feasible); 
o Other possible causes (e.g. an underlying or concurrent illness/clinical 
condition and/or an effect of another device, drug, or treatment) have been 
adequately ruled out; 
o Harm to the subject is due to error in use; or 
o To establish the relatedness, not all the criteria listed above might be met at 
the same time, depending on the type of device/procedure and the event. 
6.4 REPORTING PROCEDURES FOR ADVERSE EVENTS 
6.4.1 
Recording Adverse Events 
The Investigator will record all AEs (both AEs and SAEs) considered attributable 
(relationship of possible, probable, causal relationship) to the study procedure or either of 
the HARMONIC 1100 Shears or GEN11 devices in the source documents and eCRF. 
Standard medical terminology should be used when recording AEs. In addition, the 
following information should be recorded: 
• 
Onset date; 
• 
Resolution date or date of death; 
• 
Severity of the event; 
• 
Indication of whether the event is serious; 
• 
Relationship of AE to the study devices; 
• 
Relationship of AE to the study procedure; 
• 
Action taken; 
• 
Event status; and 
• 
Was AE anticipated or not (only for SAEs). 
Data related to AEs will be collected until the event resolution, or until the event is 
considered stable, or until all attempts to determine the resolution of the event are 
exhausted. All AEs that are unresolved at study completion (or at the last visit completed 
for early withdrawal subjects) will be recorded as ongoing at study end. 
6.4.2 
Reporting Adverse Events 
The Investigator is required to report AEs to the Sponsor within 2 weeks from when the 
study site becomes aware of the event. All AEs must be reported on the AE eCRF and be 
documented in a timely manner throughout the study duration, with reporting of AEs 
starting from the time the subject is enrolled. 
6.4.3 
Reporting Serious Adverse Events 
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within 72 hours of becoming aware of the event to the Sponsor by completing the AE 
eCRF. A notification containing the pertinent data will be automatically generated by the 
EDC system and forwarded to the Sponsor. If applicable, supporting SAE documentation 
should be de-identified and provided to the Clinical Trial Leader. The report of an SAE by 
a study site does not constitute an admission that study personnel or the user facility 
(hospital/clinic) caused or contributed to the event. The study site is also responsible for 
submitting SAEs to the reviewing IRB/EC per their IRB/EC procedures. 
 
7.0 PRODUCT COMPLAINTS 
 
A product complaint is any written, electronic, or oral communication that alleges deficiencies 
related to the identity, labeling, quality, durability, reliability, safety, effectiveness, or 
performance of a device after it is released for distribution. A product complaint may or may not 
be associated with an AE/SAE. 
7.1 REPORTING PRODUCT COMPLAINTS FOR MARKETED DEVICES 
7.1.1 
Reporting of Approved EES Marketed Devices 
All product complaints related to devices in the procedure shall be documented throughout 
the clinical investigation. Product complaints related to Ethicon-manufactured HARMONIC 
1100 Shears or GEN11 devices must be reported to the Sponsor in a timely manner and 
no later than 24 hours after becoming aware of the event. When a sponsor representative 
becomes aware of a product complaint, the Product Complaint Team must be notified 
within 24 hours after becoming aware of the event. The Product Complaint Form must be 
emailed to the Sponsor Customer Complaint team at the following email address: 
Productcomplaint1@its.jnj.com 
The sites will report Product Complaints by completing the Product Complaint Form. If a 
product complaint is related to a safety event, the site must complete an AE eCRF as well. 
One copy of the processed form should be kept on-site, and the device should be 
retained. Sponsor representatives will organize collection of the device for evaluation as 
needed. 
7.1.2 
Reporting of Approved Marketed Devices and Commercially Available 
Devices (not Ethicon) 
The site should report Product Complaints of non-Ethicon devices that are approved 
marketed devices or commercially available medical devices according to the specific 
product’s manufacturer specifications/guidelines. 
 
 
8.0 REFERENCES 
 
1. Siegel JM, Cummings JF, Clymer JW. Reproducible, repeatable and clinically-relevant 
hemostasis scoring. J Adv Med Pharm Sci 2014;1:30-39. 
2. Schilder J, Anderson D, Shah F. et al. Hemostatic efficacy of an advanced bipolar sealer 
in open gynecologic, thoracic, and colectomy procedure: a prospective cohort study. Int 
J Surg Open 2020;24:57-63.