A Prospective, Multi-center, Randomized Clinical Study to Evaluate the Safety and Effectiveness of Biosure Regenesorb Interference Screw in Arthroscopic Reconstruction of Cruciate Ligaments in Chinese Patients
Phase: NA
Conditions: Cruciate Ligament Reconstruction, Knee
Sponsor: Smith & Nephew, Inc.

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 1 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
 
 
 
A Prospective, Multi-center, Randomized Clinical Study to Evaluate 
the Safety and Effectiveness of Biosure Regenesorb Interference 
Screw in Arthroscopic Reconstruction of Cruciate Ligaments in 
Chinese Patients 
 
Protocol No.: 
BIOSURE RG.SMD.PMA.2019.01 
Protocol version and date: 
V2.0/July 3rd, 2020 
Name of investigational medical 
device: 
Biosure Regenesorb Interference Screw 
Management category of 
investigational medical device: 
Class III medical device requiring clinical trial 
review and approval: Yes ☐ No☒ 
Similar product in China: Yes☒  No☐ 
Leading Site of Clinical Trial: 
Peking University Third Hospital 
Coordinating Investigator: 
Director Gong Xi 
Sponsor: 
Smith & Nephew Medical (Shanghai) Limited 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 2 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
1 
Signature 
1.1 
Signature Page of Protocol 
This page will be returned to Smith & Nephew Medical (Shanghai) Limited and a copy will be kept 
in the study site. 
I have read the protocol titled "A Prospective, Multi-center, Randomized Clinical Study to Evaluate 
the Safety and Effectiveness of Biosure Regenesorb Interference Screw in Arthroscopic 
Reconstruction of Cruciate Ligaments in Chinese Patients" (V2.0/July 3rd, 2020) and agree to 
follow all regulations described in this protocol. 
I agree to fulfill the duties and responsibilities of investigators regulated in Chapter 23 of the 
protocol. 
Without written approval of Smith & Nephew Medical (Shanghai) Limited, I agree to ensure that 
the confidential information contained herein won't be used for any other purpose other than the 
clinical study described herein. 
Responsibilities 
Name 
Signature* 
Date of Signature 
(DD-MMM-YYYY) 
 
Principal Investigator 
 
 
 
 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 3 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
1.2 
Coordinating investigator approval 
I have read the protocol titled "A Prospective, Multi-center, Randomized Clinical Study to Evaluate 
the Safety and Effectiveness of Biosure Regenesorb Interference Screw in Arthroscopic 
Reconstruction of Cruciate Ligaments in Chinese Patients" (V2.0/July 3rd, 2020) and agree to 
follow all regulations described in this protocol. 
Coordinating investigator approval - 
Name 
(Printed) 
Signature 
Date of Signature 
(DD-MMM-YYYY) 
 
Gong Xi 
 
 
 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 4 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
2 
Protocol synopsis 
Trial title 
A Prospective, Multi-center, Randomized Clinical Study to Evaluate the 
Safety and Effectiveness of Biosure Regenesorb Interference Screw in 
Arthroscopic Reconstruction of Cruciate Ligaments in Chinese Patients 
Sponsor 
Smith & Nephew Medical (Shanghai) Limited 
Investigational 
device 
Biosure Regenesorb Interference Screw 
Control device 
BIOSURE HA Interference Screw 
Trial objective 
The objective of this study is to compare the safety and effectiveness of 
Biosure Regenesorb Interference Screw versus BIOSURE HA Interference 
Screw (control device) in patients requiring reconstruction of cruciate 
ligaments of the knee. The trial results will be used for registration of Biosure 
Regenesorb Interference Screw in China. 
Trial design 
The clinical trial is designed to be a prospective, multi-center, randomized, 
evaluator-blinded, parallel-controlled, non-inferiority trial. 
Sample size 
It is planned to include 140 subjects, 70 in the trial group and control group, 
respectively. 
Target 
population 
The clinical trial is carried out in patients requiring knee cruciate ligaments 
reconstruction. 
Case selection 
1. 
Inclusion criteria 
1) 
Signing the Informed Consent Form (ICF) voluntarily; 
2) 
Patients aged 18-75 years; 
3) 
Patients clinically diagnosed with knee cruciate ligaments rupture or tear 
and suitable for cruciate ligaments reconstruction definitely; 
4) 
Normal contralateral knee joint. 
2. 
Exclusion criteria 
1) 
Patients fail to meet the diagnosis of cruciate ligaments rupture or tear; 
2) 
Patients with an unclosed epiphyseal plate shown on the X-ray film; 
3) 
Patients having underwent internal fixation or reconstruction due to a 
knee joint fracture; 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 5 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
4) 
Patients with obvious knee joint degeneration shown on the X-ray film; 
5) 
Patients who cannot make a knee flexion of more than 90° during 
operation; 
6) 
Patients undergoing autologous chondrocyte implantation; 
7) 
Patients with medial meniscus or lateral meniscus completely resected; 
8) 
Patients with significant anatomical abnormalities; 
9) 
Pregnant or breast-feeding females or those at a child-bearing age 
planning to become pregnant; 
10) Patients with serious osteoporosis that affects implantation of the screw; 
11) Patients with a malignant tumor that causes failure to effectively fix the 
implant; 
12) Known hypersensitivity to the implant materials; 
13) Patients not suitable for operation due to obvious local or systemic 
infection; 
14) Patients who cannot tolerate an operation due to severe malnutrition; 
15) Patients with severe coagulation disorder (judged by the investigator), 
e.g. the hemophiliac; 
16) Patients with immunodeficiency, including those who must receive 
immunosuppressant for a long time; 
17) Patients with extensive skin diseases; 
18) Obese patients having a Body Mass Index (BMI) > 35; 
19) Patients who cannot cooperate in postoperative rehabilitation due to a 
severe mental disease or those who cannot tolerate the operation due to a 
cardiopulmonary disease; 
20) Patients who received operation on the injured lower limb within the past 
year; 
21) Patients who participated in any other clinical trial within the past three 
months; 
22) Patients who cannot follow the requirements described in the study 
protocol; and 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 6 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
23) Other patients who are considered by the investigator not suitable for this 
clinical study. 
Exclusion criteria: 
During the operation, if the subject was not in accordance with the 
diagnosis of cruciate ligament rupture or tears, or meet any of the exclusion 
criteria, they will be excluded from the trial. 
Test duration 
Expected duration of participation of each subject is around 740 days. This 
trial includes a 10-d screening period and a 24-month follow-up period. 
Efficacy 
endpoints 
Primary efficacy endpoint: Lysholm score at 12 Months; 
Secondary efficacy endpoints: 
● 
Lysholm Score (6 Months, 24 Months) 
● 
IKDC Score (6 Months, 12 Months, 24 Months) 
● 
Drawer Test (6 Months, 12 Months, 24 Months) 
● 
Lachman Test (6 Months, 12 Months, 24 Months) 
● 
Radiological evaluation (6 Months, 12 Months, 24 Months) 
Safety evaluation 
indicators 
(1) Incidence (%) and frequency (number of events) of adverse events (AEs) 
related to device; 
(2) Incidence (%) and frequency (number of events) of adverse events; 
(3) Incidence (%) and frequency (number of events) of device deficiencies; 
(4) Reoperation rate. 
Number of study 
sites 
About 4 study sites. 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 7 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Study follow-up schedule 
Study 
procedures 
Pre-
operat
ion 
Intraopera
tive - 
postoperat
ive (Day 
0-5) 
6 weeks 
after 
operation 
(± 2 
weeks) 
3 months 
after 
operation 
(± 1 month) 
4.5 months after 
operation 
Telephone 
follow-up 
(± 2 weeks) 
6 months 
after 
operation 
(± 1 
month) 
9 months after 
operation 
Telephone 
follow-up 
(± 2 weeks) 
12 months 
after 
operation 
(± 2 months) 
24 months after 
operation 
(± 2 months) 
Days for study 
-30~-1 
0~5 
28-56 
61-121 
123-150 
153-213 
260-287 
305-426 
670-790 
Informed 
consent 
√ 
 
 
 
 
 
 
 
 
Inclusion/exclus
ion 
√ 
√ 
 
 
 
 
 
 
 
Demography/m
edical history 
√ 
 
 
 
 
 
 
 
 
Vital signs 
√ 
√ 
 
 
 
 
 
 
 
ECG 
√ 
 
 
 
 
 
 
 
 
Blood 
routine 
examination 
√(1) 
√(3) 
 
 
 
 
 
 
 
CRP 
√(1) 
 
 
 
 
 
 
 
 
Blood 
biochemistry 
√(1) 
√(3) 
 
 
 
 
 
 
 
Coagulation test 
√(1) 
 
 
 
 
 
 
 
 
Pregnancy test† 
√ 
 
 
 
 
 
 
 
 
Lysholm score 
√(1) 
 
 
 
 
√(8) 
 
√(8) 
√(8) 
IKDC score 
√(1) 
 
 
 
 
√(8) 
 
√(8) 
√(8) 
Drawer test 
√(1) 
 
 
 
 
√ 
 
√ 
√ 
Lachman test 
√(1) 
 
 
 
 
√ 
 
√ 
√ 
X-ray film 
√(2) 
√ 
 
√(5) 
 
√ 
 
√ 
√ 
CT 
√(2) 
√ 
 
√(5) 
 
√ 
 
√ 
√ 
MRI 
√2) 
 
 
√(5) 
 
√ 
 
√ 
√ 
Randomization 
√(7) 
 
 
 
 
 
 
 
 
Operation 
 
√ 
 
 
 
 
 
 
 
Telephone 
follow-up 
 
 
√ 
√(6) 
√ 
 
√ 
 
 
Concomitant 
drug (4) 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Adverse event 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Device 
Deficiency 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Reoperation 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Study 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 8 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
completion/with
drawal 
(1) For preoperative lab examinations and all scores, only those within Day 1~10 before the operation are acceptable. 
(2) If MRI, CT or X-ray film has been done within 30 days before the Informed Consent Form is signed, and the data are available, 
they can be used as the data for screening before operation. 
(3) It is tested before discharge. 
(4) All combination drugs associated with AEs or serious adverse events (SAEs) are reported. 
(5) Imaging examination 3 months after operation is optional. 
(6) Both telephone follow-up and follow-up visit to the hospital are acceptable. 
(7) Subjects are randomized after signing of ICF but before anesthesia begins. 
(†) If applicable, where, the pregnancy test is only suitable for females of child-bearing potential, neither premenstrual females nor 
sterilized or postmenopausal (i.e., 12-month amenorrhea without alternative medical reasons) females. 
(8) If the subject cannot return to the site due to any public incidents or other reasons, the subject may be changed to other ways of 
visit (eg. Remote visit, video visit, etc) after evaluation by the investigator. 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 9 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
3 
Contents 
1 
Signature .................................................................................................................................................................. 2 
1.1 Signature Page of Protocol ................................................................................................................................. 2 
1.2 Coordinating investigator approval .................................................................................................................... 3 
2 
Protocol synopsis ....................................................................................................................................................... 4 
Study follow-up schedule ................................................................................................................................................. 7 
3 
Contents ..................................................................................................................................................................... 9 
Abbreviations .................................................................................................................................................................. 12 
4 
Sponsor Information............................................................................................................................................... 13 
5 
List of study sites and investigators for the multi-center clinical trial: .............................................................. 14 
6 
Objective and contents of clinical trial .................................................................................................................. 15 
6.1 Trial objective ................................................................................................................................................... 15 
6.2 Study contents .................................................................................................................................................. 15 
7 
Background of Clinical Trial ................................................................................................................................. 15 
8 
Characteristics, structural composition, working principle, mechanism of action and study population of the 
investigation product .............................................................................................................................................. 18 
8.1 Product characteristics ...................................................................................................................................... 18 
8.2 Structural composition and mechanism of action of the product ..................................................................... 18 
8.3 Study population............................................................................................................................................... 20 
8.4 Control product................................................................................................................................................. 20 
9 
Indications, contraindications and precautions of the product .......................................................................... 21 
9.1 Indications ........................................................................................................................................................ 21 
9.2 Contraindications.............................................................................................................................................. 22 
9.3 Warnings and precautions ................................................................................................................................. 22 
9.4 Potential adverse reactions ............................................................................................................................... 23 
10 Overall design ......................................................................................................................................................... 24 
10.1 Trial design ....................................................................................................................................................... 24 
10.2 Study procedures .............................................................................................................................................. 33 
10.3 Monitoring plan ................................................................................................................................................ 40 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 10 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
11 
Data Management ................................................................................................................................................... 42 
12 Statistical considerations ........................................................................................................................................ 44 
12.1 Statistical design, method and analysis procedure............................................................................................ 44 
12.2 Calculation of sample size ................................................................................................................................ 46 
12.3 Significance level and power of the clinical trial ............................................................................................. 47 
12.4 Expected drop-out rate ..................................................................................................................................... 47 
12.5 Criteria for acceptability/unacceptability of clinical trial result ....................................................................... 48 
12.6 Criteria and reason for terminating the trial based on the statistical consideration .......................................... 48 
12.7 Statistical Method of All Data, Together with the Handling Method of Missing, Unused and Wrong Data 
(Including Discontinuation and Withdrawal) and Unreasonable Data ............................................................. 48 
12.8 Reporting Procedure of Deviation from Original Statistical Plan .................................................................... 48 
12.9 Selection criteria and justification of subjects included in the analysis ............................................................ 48 
13 Feasibility analysis .................................................................................................................................................. 49 
13.1 Possibility analysis on success ......................................................................................................................... 49 
13.2 Possibility analysis on failure ........................................................................................................................... 50 
14 Quality control of clinical trial............................................................................................................................... 50 
14.1 Study Monitoring ............................................................................................................................................. 50 
14.2 Audit of Sponsor .............................................................................................................................................. 51 
14.3 Laboratory Quality Control .............................................................................................................................. 52 
15 Ethical issues and informed consent of clinical trial ............................................................................................ 52 
15.1 Ethical Considerations and Ethical Approval ................................................................................................... 52 
15.2 Informed consent .............................................................................................................................................. 53 
16 Adverse Event Reporting and Complaint ............................................................................................................. 54 
16.1 Definition ......................................................................................................................................................... 54 
16.2 Treatment for Adverse Events .......................................................................................................................... 55 
16.3 Reporting of adverse events ............................................................................................................................. 55 
17 Protocol Amendment and Protocol Deviation ...................................................................................................... 59 
17.1 Protocol Amendment ........................................................................................................................................ 59 
17.2 Protocol Violation by Individual Subjects in Emergency ................................................................................. 59 
17.3 Protocol deviation ............................................................................................................................................. 60 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 11 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
18 Access to Source Data/Documents ......................................................................................................................... 60 
19 Finance and Insurance ........................................................................................................................................... 61 
19.1 Surgical instruments ......................................................................................................................................... 61 
19.2 Others ............................................................................................................................................................... 62 
20 Contents of the clinical trial report ....................................................................................................................... 62 
21 Confidentiality Principle ........................................................................................................................................ 63 
21.1 Disclosure ......................................................................................................................................................... 63 
21.2 Data Security and Confidentiality .................................................................................................................... 63 
22 Agreement on the Publication of Study results .................................................................................................... 64 
23 Responsibilities of each party ................................................................................................................................ 65 
23.1 Responsibilities of Sponsor .............................................................................................................................. 65 
23.2 Responsibilities of Study Sites and Investigators ............................................................................................. 67 
24 Bibliography ............................................................................................................................................................ 71 
 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 12 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Abbreviations 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
BMI 
Body Mass Index 
NMPA 
National Medical Products Administration 
CI 
Confidence Interval 
CRC 
Clinical Research Coordinator 
CRF 
Case Report Form 
CRP 
C-reactive Protein 
CTA 
Clinical Trial Agreement 
EC 
Ethics Committee 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IFU 
Instructions for Use 
ITT 
Intent-to-Treat Population 
NDA 
Non-Disclosure Agreement 
PI 
Principal Investigator 
PP 
Per-protocol Population 
QA 
Quality Assurance 
QC 
Quality Control 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 13 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
4 
Sponsor Information 
Sponsor name: 
Smith & Nephew Medical (Shanghai) Limited 
Address of sponsor: 
Section B, F4, General Workshop Building, No. 188, 
Aona Road, China (Shanghai) Pilot Free Trade Zone 
Contact information of sponsor: 
Brook Li 
Clinical Study Manager 
Address: No. B-E, F2, Building A, East Gate Plaza, No. 9 
Dong Zhong Street, Dongcheng district, Beijing, China 
Post code: 100027 
Tel.: 010- 6419-8395 
E-mail: Brook.Li@smith-nephew.com  
Project Coordinator: 
Astrid Yung 
Associate Director, Clinical Strategy and Operations 
Address: No. B-E, F2, Building A, East Gate Plaza, No. 9 
Dong Zhong Street, Dongcheng district, Beijing, China 
Post code: 100027 
Tel.: 010-6419-8200 
E-mail: Astrid.yung@smith-nephew.com  
Related qualification documents of 
sponsor: 
See the Qualification documents of sponsor. 
 
In case of any change in the contact information of sponsor, it will be updated timely in the study. 
For the latest contact information, see the contact information of the sponsor in the investigator 
folder. 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 14 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
5 
List of study sites and investigators for the multi-center clinical trial: 
List of study sites and investigators should be provided in a separate document. 
The study sites may be adjusted during the trial. This is an administrative change. The 
Sponsor will submit a written document to each study site. 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 15 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
6 
Objective and contents of clinical trial 
6.1 
Trial objective 
The objective of this study is to compare the safety and effectiveness of Biosure Regenesorb 
Interference Screw versus the control device in patients requiring repair or reconstruction of 
cruciate ligaments (including anterior cruciate ligament (ACL) and posterior cruciate ligament 
(PCL)). The trial results will be used for registration of Biosure Regenesorb Interference Screw in 
China. 
 
6.2 
Study contents 
This clinical trial is designed to be a prospective, multi-center, randomized, evaluator-blinded, 
parallel-controlled, non-inferiority trial. The primary efficacy endpoints are not inferior to the 
control group. The Biosure Regenesorb Interference Screw and BIOSURE HA Interference Screw 
are used in the trial and control groups, respectively, to evaluate the safety and effectiveness of the 
investigational medical device Biosure Regenesorb Interference Screw in clinical repair or 
reconstruction of knee cruciate ligament rupture or tear. 
The subjects complying with the criteria for inclusion in this clinical trial will receive 24-month 
follow-up after being treated with the investigational product or the control product. The following 
endpoints will be recorded and evaluated: Lysholm score, IKDC score, Drawer test, Lachman test 
and imaging evaluation results at the follow-up visit at month 6, 12 and 24 after the operation, 
respectively, incidence and frequency of ADEs, AEs, and device deficiency throughout the trial and 
reoperation rate. 
 
7 
Background of Clinical Trial 
The knee becomes one of the most injured joints due to its anatomical structure and particular 
function in human body. According to the statistics, there are 200,000 ACL rupture cases per year in 
the United States, including 100,000 requiring ACL reconstruction. An epidemiological 
investigation in sport injury showed that the total incidence of ACL injury is 0.47% in China. PCL 
injury are relatively infrequent. As reported in foreign literature, PCL injury has an incidence of 3% 
in the common population and account for 20% of knee ligament injury. No similar reports are 
found in China. 
The ACL femoral attachment, located at the posterior part of the medial side of the lateral femoral 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 16 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
condyle, has an oval-shaped concavity, 18 mm long and 11 mm wide on average, and covers an area 
of 113-170 mm2. The distal end of ACL is fan-shaped and attached to the anterior intercondyloid 
spine of the tibial plateau, forming an anterior-wide posterior-narrow triangle or an oval region, 
with an average sagittal diameter of 17 mm and a coronal diameter of 11 mm. PCL begins at the 
medial side of the intercondylar fossa of femur (i.e., the lateral side of medial femoral condyle) and 
ends at the posterior of the tibial intercondylar eminence. The therapy selection for cruciate 
ligament injury is affected by the natural course of ligament injury. It has currently been 
demonstrated in literature that patients with cruciate ligament injury will experience meniscus tear 
and cartilage injury and finally osteoarthritis if they re-participate in sports activities and experience 
recurrent joint instability. A conservative treatment will be feasible if patients are willing to change 
their lifestyle and reduce joint activities. Plaster fixation is a common treatment method, but it 
cannot thoroughly cure knee joint instability. Therefore, at present, operation is still the main 
therapy for cruciate ligament injury. After twenty years of development, arthroscopic cruciate 
ligament reconstruction has become the main therapy for cruciate ligament injury. Bone avulsion 
can be repaired via arthroscopic reduction + screw-fixed suture. Early arthroscopic cruciate 
ligament reconstruction is able to relatively better restore stability of the knee joint, maintain 
functions of the knee joint and reduce the incidence of secondary injury of knee cartilage and 
meniscus, which is a currently better choice for cruciate ligament injury. 
Cruciate ligament reconstruction grafts include autografts and allotransplant. The common 
autografts of ligaments include ligamentum patellae, tendon of quadriceps femoris, hamstring 
tendon, semitendinosus tendon and gracilis tendon, etc. The most common ones are fixed bone-
patellar tendon-bone (B-PT-B) and hamstring tendon (HT). Via one or two years of follow-up, some 
investigators found that a reliable stability was achieved for both ligamentum patellae and 
semitendinosus tendon with no significant difference in postoperative knee stability and that no 
significant difference was found in the impact on myodynamia of quadriceps femoris and 
rehabilitation of knee functions. It is reported in many articles that allogeneic grafts and autografts 
will achieve similar efficacy in cruciate ligament reconstruction as long as appropriate operations 
are made, such as appropriate widening of allogeneic tendon grafts and pre-tension of autografts. 
Grafts can be fixed directly and indirectly. Direct fixation refers to directly squeezing the graft into 
the bone tunnel, while indirect fixation refers to hanging the graft into the bone tunnel. Direct 
fixation involves interference screws and Intrafix fixation system, etc.; while indirect fixation 
involves knotting on the bone bridge, Endobutton CL Ultra and Rigidfix cross pin systems, etc. 
Direct fixation with interference screws, the most clinically used fixation method, achieves a more 
stable reconstructed knee joint due to a shorter distance of the fixation point to the articular surface 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 17 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
as compared with indirect fixation. Interference screws can be used to fix multiple grafts mentioned 
above separately or in combination with other fixation methods. They can effectively fix grafts at 
both femoral and tibial attachments. Long-term follow-up shows that the efficacy in achieving knee 
joint stability doesn’t vary with neither different manufacturing materials nor a single or combined 
use of interference screws. 
Bone-tendon healing plays a critical role in surgery for repairing various injured tendons. Currently, 
interference screws have been widely used in clinical practice for operative fixation of the injured 
bone-tendon. Interference screws are often used to fix tendons in surgery for knee joint, shoulder 
joint and ankle joint, etc. In clinical practice, their application in knee joint ligament reconstruction 
is the most commonly reported and studied. 
Interference screws can be classified into absorbable ones and non-absorbable ones according to the 
material (e.g. metal interference screws). Metal interference screws were widely used due to their 
high fixation strength, but currently they have been less used because their deficiencies have been 
gradually recognized, e.g., cutting-induced damages to grafts. In a meta-analysis study carried out 
by Emond, no significant differences in the postoperative knee function score and postoperative 
complication rate were found between metal interference screws and absorbable screws when used 
to fix the reconstructed cruciate ligament. 
Absorbable screws have tended to replace the metal interference screws. They have the advantage 
of having no impact on MRI examination and providing more convenience for revision surgery 
while achieving similar fixation strength to metal interference screws. At present, polylactic acid is 
the most commonly used screw material and is degraded at different rates in different environment. 
Clinical effectiveness of absorbable screws has been demonstrated in many international articles. 
Christopher Kaeding, et al. reported that no differences in the range of motion, the level of motion 
and knee functions were found within 1-year follow-up between interference screws made of PPLA 
material (poly L-lactic acid) and those made of titanium. At the 2-year follow-up, no AEs caused by 
absorbable materials were found. Christian Fink, et al. reported that the absorbable screws was 
found in the CT scan at Month 12 to have been degraded in a 24-month study designed to compare 
interference screws made of polyglycolic acid/trimethylene carbonate (PGA/TMC) copolymer and 
those made of titanium. Yuval Arama, et al. reported PLLA-HA absorbable screws had not been 
completely ossified at the 5-year follow-up. Whether to be completely absorbed depends on the 
material of absorbable screws, bone tissue condition of patients and patient conditions in the 
rehabilitation period, instead of being generalized. The investigational device adopted in the study 
is made of PLGA, β-tricalcium phosphate and calcium sulfate, which are commonly used as the 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 18 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
absorbable screw material. 
This study is a registration study of the imported device Biosure Regenesorb Interference Screw. 
 
8 
Characteristics, structural composition, working principle, mechanism of 
action and study population of the investigation product 
8.1 
Product characteristics 
The Biosure Regenesorb Interference Screw, an absorbable screw designed with an open structure 
and made of biocomposite material, is used to fix ligaments, tendons, soft tissues or bone-tendon-
bone grafts in knee surgery. Its manufacturing material is made of PLGA, β-TCP (β-tricalcium 
phosphate) and calcium sulfate. As compared with other absorbable screws made of other 
absorbable materials, its open structural design enables rapid bone ingrowth to make the screw 
integrated with bone tissue so as to promote healing. It has the following characteristics: 
Bone ingrowth 
 
Its open structural design facilitates bone ingrowth. 
Advanced materials 
 
In the pre-clinical study, the Biosure REGENESORB Interference Screw was replaced with 
bone within 24 months, but the control product BIOSURE HA Interference Screw was 
absorbed in a relatively longer time and might not be completely absorbed within 3~5 years. 
Performance 
 
Excellent pullout resistance: Its fixation strength is similar to that of solid absorbable screws. 
 
BIOSURE Driver fully supports screws, maintains screw integrity and minimizes the 
possibility of breakage. 
 
8.2 
Structural composition and mechanism of action of the product 
The Biosure Regenesorb Interference Screw is composed of absorbable screws and relevant 
instruments. 
The specifications of absorbable screws are as follows: 
Product code 
Description 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 19 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
72204389 
BIOSURE REGENESORB Interference Screw, 5mm×20mm 
72204390 
BIOSURE REGENESORB Interference Screw, 5mm×25mm 
72204391 
BIOSURE REGENESORB Interference Screw, 6mm×20mm 
72204392 
BIOSURE REGENESORB Interference Screw, 6mm×25mm 
72204393 
BIOSURE REGENESORB Interference Screw, 6mm×25mm, Reverse Thread 
72204394 
BIOSURE REGENESORB Interference Screw, 7mm×20mm 
72204395 
BIOSURE REGENESORB Interference Screw, 7mm×25mm 
72204396 
BIOSURE REGENESORB Interference Screw, 7mm×25mm, Reverse Thread 
72204397 
BIOSURE REGENESORB Interference Screw, 7mm×30mm 
72204398 
BIOSURE REGENESORB Interference Screw, 8mm×20mm 
72204399 
BIOSURE REGENESORB Interference Screw, 8mm×25mm 
72204400 
BIOSURE REGENESORB Interference Screw, 8mm×25mm, Reverse Thread 
72204401 
BIOSURE REGENESORB Interference Screw, 8mm×30mm 
72204402 
BIOSURE REGENESORB Interference Screw, 8mm×35mm 
72204403 
BIOSURE REGENESORB Interference Screw, 9mm×20mm 
72204404 
BIOSURE REGENESORB Interference Screw, 9mm×25mm 
72204405 
BIOSURE REGENESORB Interference Screw, 9mm×30mm 
72204406 
BIOSURE REGENESORB Interference Screw, 9mm×35mm 
72204407 
BIOSURE REGENESORB Interference Screw, 10mm×20mm 
72204408 
BIOSURE REGENESORB Interference Screw, 10mm×25mm 
72204409 
BIOSURE REGENESORB Interference Screw, 10mm×30mm 
72204410 
BIOSURE REGENESORB Interference Screw, 10mm×35mm 
72204411 
BIOSURE REGENESORB Interference Screw, 11mm×25mm 
72204412 
BIOSURE REGENESORB Interference Screw, 11mm×30mm 
72204413 
BIOSURE REGENESORB Interference Screw, 11mm×35mm 
72204414 
BIOSURE REGENESORB Interference Screw, 12mm×35mm 
 
The supporting instruments are listed as follows: 
72204647 
BIOSURE Driver, 5mm 
72201887 
BIOSURE Driver 
72201201 
Guide Wire, 1.2mm×18" sterile 
72201889 
BIOSURE Tap, 6mm 
72201890 
BIOSURE Tap, 7mm 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 20 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
72201891 
BIOSURE Tap, 8mm 
72201892 
BIOSURE Tap, 9mm 
72201893 
BIOSURE Tap, 10mm 
 
Working principle/mechanism of action: 
The Biosure Regenesorb Interference Screw, an absorbable screw designed with an open structure 
and made of biocomposite material made of PLGA, β-TCP and calcium sulfate, is used to fix 
ligaments, tendons, soft tissues or bone-tendon-bone grafts in knee surgery. Its open structural 
design enables rapid bone ingrowth to make the screw integrated with bone tissues so as to promote 
healing. 
 
8.3 
Study population 
The clinical trial is carried out in patients requiring knee cruciate ligaments reconstruction. 
 
8.4 
Control product 
The already-marketed BIOSURE HA Interference Screw of Smith & Nephew Medical (Shanghai) 
Limited (hereinafter referred to as "Smith & Nephew") is selected as the control product. 
The specifications and description of product used in this study are as follows: 
72201768 
BIOSURE HA Screw, 6mm×20mm 
72201769 
BIOSURE HA Screw, 6mm×25mm 
72201770 
BIOSURE HA Screw, 6mm×25mm, Reverse Thread 
72201771 
BIOSURE HA Screw, 7mm×20mm 
72201772 
BIOSURE HA Screw, 7mm×25mm 
72201773 
BIOSURE HA Screw, 7mm×25mm, Reverse Thread 
72201774 
BIOSURE HA Screw, 7mm×30mm 
72201775 
BIOSURE HA Screw, 8mm×20mm 
72201776 
BIOSURE HA Screw, 8mm×25mm 
72201777 
BIOSURE HA Screw, 8mm×25mm, Reverse Thread 
72201778 
BIOSURE HA Screw, 8mm×30mm 
72201779 
BIOSURE HA Screw, 8mm×35mm 
72201780 
BIOSURE HA Screw, 9mm×20mm 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 21 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
72201781 
BIOSURE HA Screw, 9mm×25mm 
72201782 
BIOSURE HA Screw, 9mm×30mm 
72201783 
BIOSURE HA Screw, 9mm×35mm 
72201784 
BIOSURE HA Screw, 10mm×20mm 
72201785 
BIOSURE HA Screw, 10mm×25mm 
72201786 
BIOSURE HA Screw, 10mm×30mm 
72201787 
BIOSURE HA Screw, 10mm×35mm 
72201788 
BIOSURE HA Screw, 11mm×25mm 
72201789 
BIOSURE HA Screw, 11mm×30mm 
72201790 
BIOSURE HA Screw, 11mm×35mm 
72201791 
BIOSURE HA Screw, 12mm×35mm 
 
The supporting instruments are listed as follows: 
72201887 
BIOSURE Driver 
72201201 
Guide Wire, 1.2mm×18" sterile 
72201889 
BIOSURE Tap, 6mm 
72201890 
BIOSURE Tap, 7mm 
72201891 
BIOSURE Tap, 8mm 
72201892 
BIOSURE Tap, 9mm 
72201893 
BIOSURE Tap, 10mm 
 
9 
Indications, contraindications and precautions of the product 
9.1 
Indications 
The Biosure Regenesorb Interference Screw is suitable for re-attachment of ligaments, tendons, soft 
tissues or bone-tendon-bone grafts to treat the following indications: 
Knee 
● 
ACL repair 
● 
PCL repair 
● 
Extracapsular repair 
Medial collateral ligament 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 22 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Lateral collateral ligament 
Posterior oblique ligament 
● 
Patellar reconstruction and tendon repair 
Antedisplacement of vastus medialis oblique 
● 
Tendon fixation for iliotibial tract 
 
9.2 
Contraindications 
● 
Known hypersensitive response to graft materials. If it is suspected to be sensitive to materials, 
a relevant test should be carried out before implantation to exclude sensitivity to materials. 
● 
Possible reduction in the supporting force of screws and threads, e.g., insufficient number or 
quality of bones (including tumors and severe osteoporosis). 
● 
Presence of infection. 
● 
Possible limitations on activities, compliance ability or compliance willingness of patients in 
the healing period. 
● 
Contraindications may be relative or absolute and must be carefully evaluated based on overall 
evaluation results of patients. 
 
9.3 
Warnings and precautions 
● 
The content is sterile unless the package is opened or damaged. No re-sterilization is allowed. 
For single use only. Please discard any open, unused product. No use after the shelf life. 
● 
The physician is responsible for becoming familiar with related surgical techniques before 
using the device. 
● 
Please read all these instructions before use. 
● 
The product must be stored in its original sealing bag. 
● 
Insufficient screw insertion may cause poor screw performance. 
● 
Incorrect drilling of the insertion site may cause screw damage or fixation failure. 
● 
Prior to insertion, please check to ensure that the screw is completely seated onto the 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 23 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
BIOSURE Driver. Incorrect seating of the screw onto the BIOSURE Driver may cause screw 
damage. 
● 
Incomplete seating of the screw may cause screw damage. 
● 
The use of an unsuitable BIOSURE Driver may cause screw damage. The 5mm Biosure 
Regenesorb Interference Screw needs to be used with the 5mm BIOSURE Driver. All other 
Biosure Regenesorb Interference Screws need to be used with standard BIOSURE Driver. 
● 
Pathological changes in soft tissues may weaken the ability to firmly fix soft tissues onto the 
bone. 
● 
Do not try to implant the device into the epiphyseal plate or non-osseous tissue. 
● 
Pathological bones (e.g., tumors, severe osteoporosis and bone immaturity) may weaken the 
ability to firmly fix or anchor the device. 
● 
Hazards associated with the device reuse include, but not limited to, patient infection and/or 
device failure. 
● 
Check the device before use to ensure that it is undamaged. Do not use a damaged device. 
● 
Do not exert an excessive force onto the screws, skeletons or devices. 
● 
Light taps are recommended for insertion of absorbable screws for the bone-tendon-bone graft. 
● 
If the BIOSURE Driver is re-inserted into the implanted screw after being withdrawn, it shall 
be ensured that the BIOSURE Driver has been completely seated onto the screw before 
tightening the screw. Incomplete seating of the screw may cause screw damage. 
● 
Carefully carry out aseptic processing and avoid anatomical hazards. 
● 
Postoperative care is of great importance. The patients should be informed of limitations of the 
implant and precautions related to the load bearing and internal stress of the device prior to 
complete healing of the bone. 
● 
After use, potential biohazards of the device need to be handled in accordance with the 
recognized medical specifications and applicable local and national requirements. 
 
9.4 
Potential adverse reactions 
As with any surgery, this surgery will cause risks. Potential complications of such implantation 
surgery include, but not limited to, anesthetic complications, pain at the incision and surgical sites, 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 24 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
surface and deep infections, bone injury or fracture, damage to surrounding tissues or blood vessels, 
embolism or coagulation problems (e.g., pulmonary embolism and deep vein thrombosis), nerve 
injury or stroke, treatment or implantation failure and surgery or treatment related complications 
requiring secondary surgical intervention. The expected adverse reactions are mild inflammatory 
reaction, foreign body reaction, deep and superficial infections and anaphylactic reaction. 
 
10 Overall design 
10.1 Trial design 
10.1.1 Study objective 
This is a prospective, multi-center and randomized controlled clinical study to evaluate the safety 
and effectiveness of Biosure Regenesorb Interference Screw in arthroscopic repair and 
reconstruction of cruciate ligaments in Chinese patients. 
 
10.1.2 Study method selection and justification 
This is a prospective, randomized, multi-center clinical study designed to compare the safety and 
effectiveness of Biosure Regenesorb Interference Screw versus the BIOSURE HA Interference 
Screw in arthroscopic cruciate ligament reconstruction in Chinese subjects. 
This clinical trial is a clinical trial for registration of medical device, so it is required to follow the 
requirements of relevant regulations issued by National Medical Products Administration (NMPA). 
This study is designed as a prospective, multi-center, randomized, evaluator-blinded, parallel-
controlled study. 
The subjects meeting the inclusion/exclusion criteria specified in the protocol will be randomized to 
receive implantation with the investigational product or control product. A total of 140 subjects are 
planned to be included in about 4 study sites. The average number of subjects should be included in 
each study site as mean as possible. The number of subjects included in each study site should be no 
more than 70 cases. The clinical follow-up evaluation will be conducted at 6, 12 and 24 months 
respectively after operation. The telephone follow-up should also be conducted at 6 weeks, 3, 4.5 
and 9 months respectively after operation. In this study, 12-month follow-up data will be submitted 
for registration and 24-month follow-up will be made to observe the long-term performance and 
absorbability of the investigational device. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 25 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
10.1.3 Measures to Reduce and Avoid Bias 
10.1.3.1 Multi-center 
The samples from multi-center are more representative than those from single center, the latter may 
lead to deviation of test results due to its systematic errors. 
 
10.1.3.2 Blinding 
To avoid the bias occurring to the research design, we appoint an independent rator in each study 
site, who is blinded and responsible for completing scoring at each follow-up. 
 
10.1.3.3 Randomization/allocation 
The randomization allows the patients to be given equal opportunity to be assigned to the trial group 
or control group, independently of investigators and/or subjective views of subjects, so that the 
various influencing factors tend to be distributed in a similar way, avoiding the issues of selection 
bias and information bias. 
The subjects meeting all inclusion/exclusion criteria will be randomly allocated into any of two 
study groups (trial group or control group) in a ratio of 1:1 through network-based randomization 
system. The random number is allocated only when the subject has signed the Informed Consent 
Form and passes the screening test. 
 
10.1.3.4 Parallel-controlled 
This is a parallel controlled trial, in which treatment is conducted simultaneously for both the 
investigational group and the control group, so that potential differences influencing the outcome 
measures between both groups can be minimized. 
 
10.1.3.5 Consistency of score 
The training on the consistency of the scale should be provided to the scorer of primary endpoint 
and secondary endpoint evaluation (such as Lysholm score, IKDC score, drawer test and lachman 
score) in each site, ensuring that the scorer have consistent understanding and use of the scale, thus 
reducing the bias between scorers. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 26 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
 
10.1.3.6 Imaging evaluation 
The imaging observation indicators are reasonable and necessary indicators for the evaluation of 
arthroscopic repair of soft tissues, but not included in the Lysholm score. In order to reflect the 
importance of imaging, imaging evaluation will be performed pre-op, 6, 12 and 24 months post-op. 
 
10.1.3.7 Screening of subjects 
In order to eliminate selection bias, the investigators will continuously screen all subjects. Subject 
recruitment continues until the completion of recruitment of 140 subjects. File records and 
enrollment registration forms for screening work must be retained and submitted to the Sponsor as 
needed. 
 
10.1.3.8 Investigator training 
Prior to the clinical trial, the Clinical Research Associate, coordinating with the persons in charge of 
the study sites, will train the  investigators on the study protocol, making sure they are familiar with 
the use of investigational medical device, and implement patient enrollment strictly in accordance 
with the inclusion criteria and exclusion criteria, conduct relevant examinations according to the 
protocol requirements, also master all new device related information released during the clinical 
trial, thus to minimize the interferential factors. 
 
10.1.3.9 Clinical trial audit 
The monitoring plan is established. The Clinical Research Associate is selected and appointed by 
the sponsor to conduct a regular on-site monitoring visit of trial center, making sure that all contents 
in the trial protocol are strictly followed. The source data are verified to ensure it is consistent with 
the electronic case report form (eCRF). 
 
10.1.4 Selection of subjects 
10.1.4.1 Inclusion criteria 
Subjects must meet all of the inclusion criteria: 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 27 of 74 
 
Confidential and Proprietary 
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& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
(1) Signing the Informed Consent Form (ICF) voluntarily; 
(2) Patients aged 18-75 years; 
(3) Patients clinically diagnosed with knee cruciate ligaments rupture or tear and suitable for 
cruciate ligaments reconstruction definitely; 
(4) Normal contralateral knee joint. 
 
10.1.4.2 Exclusion criteria 
Subjects with any of the following characteristics must be excluded from participation in the study: 
(1) Patients not complying with the diagnosis criteria for cruciate ligaments rupture or tear; 
(2) Patients with an unclosed epiphyseal plate shown on the X-ray film; 
(3) Patients having underwent internal fixation or reconstruction due to a knee joint fracture; 
(4) Patients with obvious knee joint degeneration shown on the X-ray film; 
(5) Patients who cannot make a knee flexion of not less than 90° during operation; 
(6) Patients undergoing autologous chondrocyte implantation; 
(7) Patients with medial meniscus or lateral meniscus completely resected; 
(8) Patients with significant anatomical abnormalities; 
(9) Pregnant or breast-feeding females or those at a child-bearing age planning to become 
pregnant; 
(10) Patients with serious osteoporosis that affects screw implantation; 
(11) Patients with a malignant tumor that causes failure to effectively fix the implant; 
(12) Known hypersensitivity to the implant materials; 
(13) Patients not suitable for operation due to obvious local or systemic infection; 
(14) Patients who cannot tolerate an operation due to severe malnutrition; 
(15) Patients with severe coagulation disorder (judged by the investigator), e.g. the hemophiliac; 
(16) Patients with immunodeficiency, including those who must receive immunosuppressant for a 
long time; 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 28 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
(17) Patients with extensive skin diseases; 
(18) Obese patients having a Body Mass Index (BMI) > 35; 
(19) Patients who cannot cooperate in postoperative rehabilitation due to a severe mental disease or 
those who cannot tolerate the operation due to a cardiopulmonary disease; 
(20) Patients who received operation on the injured lower limb within the past 1 year; 
(21) Patients who participated in any other clinical trial within the past three months; 
(22) Patients who cannot follow the requirements described in the study protocol; and 
(23) Other patients who are considered by the investigator not suitable for this clinical study. 
 
10.1.4.3 Exclusion criteria 
During the operation, if subjects are found not to comply with the diagnosis criteria for cruciate 
ligaments rupture or tear or found to comply with the exclusion criteria, they will be excluded from 
the trial. 
 
10.1.4.4 Criteria and procedures for withdrawal/termination of study 
Participation in the study is voluntary and subjects may drop out at any time point in the study. Any 
subjects who have not completed the study should make every effort to complete the final 
evaluation. The reason for withdrawal must be recorded in the original document and the 
corresponding case report form (CRF). After the subject withdraws from the study, there is no need 
to replace him/her or continue follow-up. 
Investigators may also choose subjects to withdraw from the study for reasons including but not 
limited to: 
● 
Serious Adverse Event 
● 
Investigators decide subjects to withdraw for safety reasons. 
● 
The subjects do not accept the investigational device implantation during the operation 
● 
The subjects do not comply with follow-up 
● 
Subjects are lost to follow-up 
When investigators decide subjects to withdraw, the relevant reasons should be recorded in the 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 29 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
original document and the corresponding case report form (CRF). 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to other parties (investigator, Ethics Committee, 
Sponsor and regulatory authorities). If the study is prematurely terminated or suspended, the 
investigator will promptly inform the Ethics Committee and the GCP office and will provide the 
reason(s) for the termination or suspension. Circumstances that may need termination or suspension 
include, but are not limited to: 
● 
Determination of unexpected, significant, or unacceptable risk to participants 
● 
Demonstration of efficacy that would induce stopping 
● 
Insufficient compliance with protocol requirements 
● 
Data that are not sufficiently complete and/or evaluable 
● 
Determination of futility 
Study may resume once concerns about safety, protocol compliance, data quality are addressed and 
approved by the Sponsor and Ethics Committee. 
 
10.1.4.5 Lost to Follow-up 
A subject will be considered lost to follow-up if he/she does not appear for the scheduled study visit 
for two (2) consecutive visits or does not return for a final visit, and study personnel is unable to 
contact the subject. 
Some actively enrolled subjects will not return for follow-up exams on time. Study personnel must 
make a reasonable effort to contact the subject and document the following contact attempts before 
declaring a subject to be lost to follow-up: the subject has been contacted according to the site's 
policies, but no fewer than two documented phone contacts and one certified letter without response. 
Copies of all attempts to reach the subjects by mail or email and/or the attempts to contact the 
subject via other means should be documented, and that documentation should be kept with the 
subject’s source documents. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 30 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
10.1.4.6 Time of enrollment 
The study enrollment can be started only after the Ethics Committee has approved and signed a 
clinical trial agreement at each site. Before the enrollment, the relevant procedures and 
requirements should be completed according to the regulations of relevant departments. The 
competitive enrollment is taken in the study with a preliminarily estimated time of 12 months. The 
enrollment time can be adjusted according to the actual situation. 
Subjects who have completed the informed consent form and have been assigned a random number 
are considered to be enrolled. 
 
10.1.4.7 Duration of the trial 
The enrollment of subjects is planned to last for about 12 months. The primary endpoint of study is 
Lysholm score at 12 months after operation. Considering the need of bone tissue ingrowth and 
patient functional recovery, the follow-up of this study should last throughout 12 months after 
operation. In this trial, a summary of 12-month follow-up data will be reported to NMPA, and 24-
month follow-up data will be observed. The specific duration will be adjusted according to the 
actual situation. 
 
10.1.4.8 Expected duration of participation of each subject 
The duration of participation of each subject in the clinical trial is about 12 months with long-term 
observation for 24 months, the data of which may be adjusted according to the visit window 
specified in the protocol due to the specific circumstances. 
 
10.1.4.9 Number of subjects 
Number of subjects required for the entire clinical trial is about 140. 70 subjects each in the 
investigational group and control group. For the number of subjects, see the chapter of sample size 
calculation. 
 
10.1.5 Efficacy evaluation method 
10.1.5.1 Primary efficacy endpoints 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 31 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
The primary study endpoint is the Lysholm score at Month 12 after operation. 
The Lysholm score, a knee scoring system created by Lysholm and Gillqui in 1982 and revised in 
1985, has been applied in many international literature articles, and its reliability, effectiveness and 
sensitivity have been demonstrated in international literature. The Lysholm score is a scoring scale 
the most commonly used before and after arthroscopic knee surgery. A preliminary assessment can 
be made for the level of motion of patients with different intensity. The scale evaluates functions of 
patients based on 8 items: limp, support, interlocking, pain, instability, swelling, stair climbing and 
squatting. The total Lysholm score is 0-100. Pain and instability account for a higher proportion in 
this score. The knee functions of patients are considered excellent when the score is 95-100, good 
when 84-94, fair when 65-83 and poor when less than 65. The measurement takes about 3-5 min. 
The Lysholm score emphasizes the patient's subjective perception of symptoms and grade 
dysfunction in combination with the score and the level of daily activity. Studies have shown that 
the scale is the most reliable for patients undergoing cruciate ligament reconstruction and the 
difference in score is more significant when it is used to evaluate patients who self-limit activities. 
10.1.5.2 Secondary efficacy endpoints 
● 
Lysholm Score (Month 6, Month 24) 
● 
International Knee Documentation Committee (IKDC) score (at months 6, 12 and 24) 
The scoring scale was proposed in 2000 after being repeatedly revised by major sports medicine 
and medical organizations in Europe and America. The scale is composed of a knee evaluation form 
(10 items) and a knee ligament examination form (8 items), involving joint pain, sport level and 
ability of daily activities. The total score is 0-100. The IKDC scale is for evaluating the symptoms, 
functions and physical activities of the knee joint, helping compare different knee diseases. 
● 
Drawer Test (Month 6, Month 12, Month 24) 
Anterior drawer test: It is used for ACL examination. The patient should be supine with the knees 
flexed to 90 degrees and the feet flat on table and keep relaxed. The examiner sits on the 
examination table against the patient feet for fixation, grasps the tibia of the knee and draws the 
shank forward. The patient will be diagnosed with forward straight instability if the tibia is forward 
displaced 5 mm more than the uninjured side. 
Posterior drawer test: It is used for PCL examination. The patient should be supine with the knees 
flexed to 90 degrees. The examiner places both hands behind the knee joint, with the thumbs on the 
extensor aspect. The proximal end of shank is repeatedly drawn backward. The posterior 
displacement of the tibia along the femur suggests partial or complete CL rupture. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 32 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
● 
Lachman Test (Month 6, Month 12, Month 24) 
The Lachman test is carried out at injured and uninjured sides simultaneously. The patient should be 
supine with the knees flexed to 20-30 degrees and the injured limb slightly rotated outward. The 
examiner stands beside the injured side, immobilizes the lower end of the femur with one hand, and 
presses the posterior side of the upper end of the tibia forward (Lachman test) or backward (reverse 
Lachman test). A positive test result is got. Positive results suggest ACL or PCL injury. 
● 
Imaging evaluation (Month 6, Month 12, Month 24) 
Take X-ray films, CT images and MRI images of the knee before operation, intraoperative - post-
operative (Day 0-5) (only X-ray films and CT images), 6, 12, 24 months after operation, 
respectively. Observe bone ingrowth and bone absorption, etc. All imaging observations are to be 
reported on the CRF. 
Other imaging films taken are at the discretion of the individual Investigator. 
Although imaging evaluation will be performed at each site by the investigator, all imaging 
examination data will be stored in electronic DICOM format at the site until they are no longer 
needed in case further evaluation by an independent centralized reviewer is requested by NMPA. 
All imaging examination data must be modified in order to protect subjects’ identity if they are sent 
to Smith & Nephew, or designee, for independent review. If independent review is required, it will 
be done by a board certified radiologist selected by the Sponsor based on experience in 
orthopaedics and joint replacement imaging. 
 
10.1.6 Safety evaluation method 
10.1.6.1 Description of safety parameters 
No formal hypothesis testing is performed for safety analysis. Descriptive statistics will be used to 
summarize safety events. 
 
10.1.6.2 Safety evaluation contents 
Safety evaluation includes the following contents: 
● 
Incidence (%) and frequency (number of events) of AEs related to device; 
● 
Incidence (%) and frequency (number of events) of adverse events; 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 33 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
● 
Incidence (%) and frequency (number of events) of device deficiencies; 
● 
Reoperation rate. 
 
10.2 Study procedures 
10.2.1 Study flowchart 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 34 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Figure 10.2.1Schematic diagram of study design 
 
 
10.2.2 Study procedures 
10.2.2.1 Evaluation before enrollment in the study 
Prior to initiating any study-related activities on a subject, sites must first perform the following 
pre-study activities: 
● 
Informed consent must be obtained from each subject entering the study using the EC-approved 
consent form. Informed consent must be obtained prior to any study activity. 
● 
Inclusion and exclusion criteria will be carefully reviewed to verify subject eligibility. 
● 
All combination drugs associated with AEs or SAEs are recorded after the subject signs the 
ICF. 
● 
The subject enrollment time is the moment when the device is implanted. 
 
10.2.2.2 Pre-operative study activities 
Prior to the operation, the following information must be collected: 
Pre-operation 
Intraoperative-
postoperative (Day 0-5) 
Postoperative follow-up 
Screening 
Day 0-5 
4.5 months 
6 months 
9 months 
12 months 
Signing the ICF, 
demographics, 
examination 
Meeting the 
inclusion/exclusion 
criteria 
Randomi
zation 
Investigational group 
Control group 
Follow-up visit 
Telephone visit 
24 months 
6 weeks 
3 months 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 35 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
● 
Demographics include: 
○ 
Age at surgery (calculated from date of birth) 
○ 
Gender (male/female) 
○ 
Occupation 
○ 
Height (in cm) and body weight (in kg) 
○ 
Body mass index (BMI) 
● 
Vital signs: pulse, blood pressure, respiration and body temperature 
● 
Physical examination status 
● 
Medical history will be obtained and will include: 
○ 
Previous medical history (HEENT, respiratory, gastrointestinal, hematological, 
cardiovascular, endocrine/metabolic, musculoskeletal, immunological, neurological, 
genitourinary, prior surgery, others) 
○ 
Tobacco use and alcohol intake (tobacco use: never used, past use, current use; alcohol 
intake) 
○ 
Closure of epiphyseal plate 
○ 
Current medical history of knee diseases: time of knee injury, cause of knee injury, 
conditions of the studied knee side (left/right) and the contralateral knee joint, cause of 
CL rupture or tear, other combined knee injury, knee degeneration and whether or not 
to totally excise the medial or lateral meniscus 
○ 
Previous surgeries on the affected knee joint (For surgery history, fracture fixation, 
arthroscopy, ligament surgery, autologous cell transplantation or other surgery, please 
specify) 
○ 
Safety events 
○ 
All combination drugs associated with AEs or SAEs are recorded. 
In addition, subjects will be evaluated clinically pre-operatively using: 
● 
Lysholm Score 
● 
IKDC Score 
● 
Drawer test 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 36 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
● 
Lachman test 
● 
Lab evaluation (blood routine, C-reactive protein (CRP), blood biochemistry and coagulation 
function) 
● 
Pregnancy test 
● 
ECG 
● 
Imaging evaluation 
○ 
X-ray film 
○ 
MRI 
○ 
CT 
 
10.2.2.3 Intraoperative-postoperative (Day 0-5) evaluation 
● 
Inclusion and exclusion criteria will be reviewed against to verify subject eligibility. 
● 
Vital signs 
● 
Collection of information on the operative procedure for each subject including: 
○ 
Surgical time (time from entering and leaving the operating room, from skin open to 
skin close) 
● 
Use of absorbable screws (specifications, number), femoral screws and tibial screws. 
○ 
Labels of the device components used are to be adhered to the Operative medical 
record page. 
○ 
Treatment of associated other injuries 
● 
Collection of information on discharge including: 
○ 
Admission date 
○ 
Discharge date 
● 
Lab evaluation (blood routine, blood biochemistry; and examination before discharge) 
● 
Imaging evaluation after the operation 
○ 
X-ray film 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 37 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
○ 
CT 
● 
Safety events 
● 
Device deficiency 
● 
All combination drugs associated with AEs or SAEs are recorded. 
 
10.2.2.4 Surgical operation training 
The investigators must make a professional judgment based on indications, surgical techniques and 
medical history of patients to select the appropriate size of screws, bone tunnels and BIOSURE 
Driver. 
Generally, arthroscopy is carried out via anteromedial and anterolateral incisions in the surgery. 
Remove residual ACL/PCL tissues and perform arthroplasty with a minimally invasive incision. 
The tibial and femoral tunnels are drilled and then fixed with or without absorbable screws for 
grafts. 
The patient is in supine position, and undergoes routine anesthesia and disinfection. Adopt the 
conventional approach. Prepare the graft: The investigator selects a homologous tissue as the graft 
based on conditions of the patient. Under the arthroscopic monitoring, find the femoral attachment 
of CL, select an appropriate BIOSURE Driver based on the graft diameter and complete the 
preparation of femoral tunnel. Find the tibial attachment of CL, select an appropriate BIOSURE 
Driver based on the graft diameter and complete the preparation of tibial tunnel. Insert the prepared 
graft into the bone tunnel at both ends, and insert the 1.2 mm Smith & Nephew guide wire when the 
graft is inserted at an appropriate position. Select appropriate absorbable screws based on bone 
tunnel length and graft diameter. 
Note: When BTB is used as a graft, it is recommended to prepare an insertion point using 
BIOSURE Driver of an appropriate size + 1.2 mm guide wire. The BIOSURE Driver 1 mm bigger 
than the screw is required when the bone is relatively rigid. Do not use the Biosure Regenesorb 
Interference Screw with reverse thread when BTB is used as a graft. 
Completely install the screw onto the BIOSURE Driver until the laser mark indicates that the screw 
is installed to the specified length. Tension the graft with a suitable force, and insert the absorbable 
screw to the appropriate depth to ensure that the graft has been sufficiently anchored in the bone 
tunnel. Ensure that the BIOSURE Driver is always parallel to the bone tunnel. Remove the 
BIOSURE Driver and the guide wire. The operation is completed. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 38 of 74 
 
Confidential and Proprietary 
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& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
If device replacement/repair is required in the initial operation, the investigators will need to 
replace/repair the device according to the conventional medical device replacement/repair method 
(e.g., other safe fixation methods). 
 
10.2.2.5 Study activities of follow-up visit post-op 
Subjects should return to hospital for follow-up visit at 6 weeks, 12 months and 24 months 
postoperatively and evaluated clinically using the following endpoints, and the follow-up 
information should be record in the medical record. Please refer to Study Visit Schedule for the 
acceptable follow-up windows. 
(1) 6, 12, 24 months after the operation 
● 
Lysholm Score 
● 
IKDC Score 
● 
Drawer test 
● 
Lachman test 
● 
Knee joint condition: whether to require a re-operation, whether to experience tear or rupture 
again. 
● 
Collect and record any AE since last visit. 
● 
Device Deficiency 
● 
All combination drugs associated with AEs or SAEs are recorded. 
● 
Imaging evaluation 
○ 
X-ray film 
○ 
MRI 
○ 
CT 
 
10.2.2.6 Telephone follow-up post-op 
Telephone follow-up will be performed at 6 weeks, 3, 4.5 and 9 months after the operation to ensure 
that the subject is not lost to follow-up between two visits, and to collect adverse events in time. 
The subject may choose to receive an imaging examination during his/her follow-up visit to the 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 39 of 74 
 
Confidential and Proprietary 
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& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
hospital 3 months after the operation. The follow-up information should be recorded in the medical 
record of the subject. Please refer to Study Visit Schedule for the acceptable follow-up windows. 
Collect and record any AE since last visit and necessity for re-operation. 
At one week prior to each follow up visit after the operation, the Clinical Research Coordinator will 
call the subject to confirm the appointment. During the contact with the subject, if any change of 
subject contact information is observed, e.g. address, phone number, then the corresponding contact 
information in the subject's medical file should be updated as well. 
 
10.2.2.7 Unscheduled Visits 
All information obtained during an unscheduled visit should be recorded in the source documents 
and on the appropriate CRF.、 
 
10.2.2.8 Laboratory examinations 
The laboratory examinations required to be performed include: 
● 
Blood routine examination: Haemoglobin, Platelet count, WBC count, neutrophil count, 
erythrocyte sedimentation rate 
● 
Coagulation examination: Prothrombin time (PT), activated partial thromboplastin time 
(APTT), thrombin time (TT), fibrinogen (FIB) 
● 
Biochemical examination: Urea or urea nitrogen, creatinine, AST (SGOT), ALT (SGPT), blood 
glucose 
● 
C-reactive Protein 
● 
Pregnancy test: females at a child-bearing age only 
 
10.2.2.9 Imaging examination 
Take X-ray films, CT images and MRI images of the knee joint pre-operation, intraoperative-
postoperative (Day 0-5) (X-ray film and CT image), 6- and 12- month follow-up after operation, 
respectively. All imaging observations are to be reported on the CRF. Postoperative device-related 
and surgical adverse events are to be reported. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 40 of 74 
 
Confidential and Proprietary 
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& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Mainly observe bone ingrowth into screw of the absorbable screw after implantation. 
X-ray films, CT images and MRI images are taken during the postoperative 24-month follow-up to 
mainly observe absorption of the absorbable screw after implantation. All imaging observations are 
reported in CRF. 
The specific imaging evaluation requirements will be provided in a separate document to 
radiologists for evaluation of examination results. 
10.2.2.10 Activity limitations 
The patients need to self-limit their activities and bear acceptable loads within 6 months after 
operation. Rehabilitation is recommended 2 weeks after operation until to 3 months. Moderate 
activities are allowed 4 months after operation. Vigorous exercise is only recommended 6 months 
after operation. 
 
10.2.3 Device operation specifications 
All study-related arthroscopic surgery procedures will be operated according to the surgical 
technique described in the specifications and IFU. 
The physicians participating in this study must skillfully master the arthroscopic surgery procedures 
for soft tissue repair. In addition, before the investigational device is implanted, all physicians 
participating in this study must be appropriately trained in the surgical technique and device use. 
 
10.3 Monitoring plan 
This study will be monitored by the Sponsor or qualified personnel designated by the Sponsor. The 
monitor can be employees of the Sponsor, can also come from the contract research organization 
(the Sponsor’s agent). The Sponsor or Sponsor’s agent will monitor according to the monitoring 
frequency and the monitoring contents specified in the monitoring plan. 
The Sponsor, Sponsor’s agent, EC and regulatory authorities can directly access the source 
documents, so as to verify and evaluate the clinical data submitted by the investigator to the 
Sponsor through the CRF. 
The investigator is responsible for obtaining and maintaining the integrity of the subject health 
information (original document) recorded in the medical record. The source data includes all 
original record information and certified copies of the original records (including clinical findings, 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 41 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
observations, or other activities used for study reconstruction and evaluation in clinical study). 
Prior to the implementation of the clinical agreement, the Sponsor performs qualification evaluation 
visits to each study site to ensure that all investigators have received the corresponding training and 
that their personnel, facilities and resources are sufficient to carry out this study. 
Before starting this study, the investigator must ensure that the following activities are completed 
and provide documentary records to the Sponsor. 
10.3.1 Non-Disclosure Agreement 
A Non-Disclosure Agreement (NDA) must be fully executed with the site and the Sponsor and any 
other appropriate parties. 
 
10.3.2 Clinical Trial Agreement 
A CTA must be fully executed by the site and the Sponsor and any other appropriate parties. Prior 
to initiation of the study, all investigators who will participate in the study need to be authorized by 
the principal investigator (PI), and the authorization outlines the responsibilities associated with the 
study. Unauthorized investigators are not allowed to participate in the study. 
 
10.3.3 Ethical Approval 
The protocol and informed consent materials must be approved by the EC at each institution. 
Copies of EC approval documents must be provided to the study Sponsor. 
 
10.3.4 Documentation of Qualifications 
A current, signed, dated CV and a current medical license for the principal Investigator and sub-
Investigators must be submitted to the Sponsor prior to the study and in case of any update. 
 
10.3.5 Monitoring visit by Sponsor 
A site initiation visit will be performed by the Sponsor following the completion of the CTA 
negotiation and documented EC approval to provide training to the site on the specifics of the study 
and its conduct. The site must have written approval from the Sponsor before beginning enrollment. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 42 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
The Sponsor may perform interim monitoring visits on a regular basis according to a schedule 
determined by the Sponsor. During these visits, the monitor will verify: 
● 
Signed and dated informed consent forms 
● 
Informed consent process occurred and is documented appropriately 
● 
All inclusion/exclusion criteria were met 
● 
Source documentation is complete and available 
● 
Data on CRFs is verified by the source documentation 
● 
Compliance with the protocol 
● 
The reporting of adverse events occurred as required 
● 
All required study documentation is complete and available 
A monitoring visit will be performed by the Sponsor after the study closed to retrieve and account 
for all remaining clinical data and to resolve outstanding queries. During study close-out, the 
monitor will review the investigator files to ensure required documentation and records are on file, 
confirm the disposition of any other ancillary items used for the study, and review regulatory 
requirements regarding records retention and EC reporting requirements. 
 
11 Data Management 
Investigators will be provided with eCRFs based on the electronic data acquisition and management 
system to collect the data obtained during this study. The eCRFs include fields to record from 
source documentation specific information relative to the schedule of events. The investigator will 
complete a complete eCRF after each subject is included. The investigator will submit the 
completed PDF version of eCRF to the Sponsor. 
Data quality procedures are designed to ensure that complete, accurate and timely data are 
submitted, that protocol requirements are followed, and that complications or adverse events are 
immediately identified and addressed until closure. 
The Sponsor and study sites will promptly review all faxed eCRFs and accompanying 
documentation to identify inconsistent or missing data and device-related complications. Problems 
with these data will be addressed via online data queries. Investigators will resolve the queries or 
provide the Sponsor with information regarding the reasons for not resolving the query and an 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 43 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
expected resolution date. 
To ensure the confidentiality of data, Smith & Nephew, Inc., the leading site and the authorizer will 
maintain a secure study database that maintains the confidentiality of study data. 
Data quality is the basis for evaluating the clinical study results. Standardized data management 
helps to obtain true, accurate, complete and reliable high-quality data. 
Clinical data management personnel should develop data management plan based on clinical trial 
protocol, specify and record data management tasks for the clinical trial, including personnel, roles, 
job contents, operation procedures, etc. in a detailed and comprehensive manner. The data 
management plan should be completed after the trial protocol is finalized and before the first 
subject is enrolled, which can be implemented only after the approval is obtained. Data 
management plans need to be updated and revised in time according to actual operations. 
Each step of data management needs to establish and follow the corresponding standard operating 
procedures. 
The design of the eCRF should guarantee the collection of all data which is specified in the trial 
protocol and meets the needs of statistical analysis. eCRF completion guidelines should be 
developed and training for investigators and CRC should be provided. 
In the data management plan, a clear data flow should be established. The investigators should 
cooperate with the CRC to complete all eCRFs after the end of visit and respond after receiving the 
online data query, or provide information to the Sponsor to indicate the reason why the query has 
not been resolved and expected resolved date. 
The data management department should formulate a detailed data verification plan before data 
verification, and define the data verification contents, methods and verification requirements. 
Medical coding is the process of matching the descriptions of adverse events, medical diagnoses, 
concomitant medication, previous medication, previous medical history, etc. collected from the 
CRF with the terms in the standard dictionary. If medical coding is used, the coding process, coding 
tools, coding dictionaries and versions, as well as the relevant standard documents for performing 
the coding should be detailedly described in the data management plan. 
The process of the database locking, the person in charge and the SOP file executed should be 
detailedly described in the data management plan. 
When the database is locked, the unlocking and re-locking of the database should be specified in 
advance and the conditions and processes should be described in detail. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 44 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
The trial data, the time of input/import into the database, the inputer, the data audit trail and the 
document formed in the data management process all need to be completely saved. The data formed 
in the data management process usually includes but is not limited to: clinical trial data, external 
data, database metadata information, laboratory test reference range, logical test and derived data 
change control list, electronic data query table, and program code, etc.. The files formed in the data 
management process usually includes but is not limited to: data management plan, blank eCRF, 
eCRF completion guide, PDF file of completed eCRF, annotated CRF, database design description, 
database entry description, data verification plan, data quality control verification report, etc. 
The trial data, management files, media, archiving methods and time limits that need to be archived 
should be specified in the data management plan. 
The data management department needs to determine the data as well as the quality control items, 
quality control methods (such as quality control frequency, sample selection method and sample 
size), quality requirements, qualification criteria and remedial measures for failure to meet the 
expected quality standards, etc. of data management operation process. 
For data management work during and after the study, data manager should write data management 
report, summarize data management process, and present data management implementation 
procedures,  SOP and management quality using qualitative and quantitative parameters. 
The contents related to the data management implementation process, SOP and management quality 
should be fully and detailedly described in the data management report, including participating 
institutions/departments and responsibilities, major time nodes, CRF and database design, data 
verification and clean-up, medical coding, external data management, data quality assurance, data 
transfer records at key nodes, version change records of key documents and deviations from data 
management plan. 
To ensure the confidentiality of data, the data management department will maintain the security of 
the study database and protect the confidentiality of study data. 
 
12 Statistical considerations 
12.1 Statistical design, method and analysis procedure 
12.1.1 Statistical analysis principles 
The statistical software SAS 9.4 or above is used for statistical analysis. The sample size is 
calculated using PASS 13. Adopt the trial results for endpoint analysis. FAS and PPS are used to 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 45 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
analyze primary and secondary outcomes while SS is used to analyze safety indicators. 
Unless otherwise specified, all significance tests and hypothesis tests use a two-sided test at a 
significance level of 5%. When appropriate, the obtained p value will be cited and the two-sided 95% 
confidence interval will be generated. All p values will be rounded to three decimal places. In all 
tables, the p values less than 0.001 will be expressed as "<0.001". 
Continuous variables will be summarized using summary statistics such as mean, standard deviation, 
median, minimum, maximum, lower quartile (Q1) and upper quartile (Q3), etc. Classified and 
ordinal variables are summarized using frequency and percentage. 
For comparison of general conditions in two groups, an appropriate method will be adopted based 
on the indicator type to carry out analysis. Continuous indicators in two groups will be evaluated 
using a two-sample t-test (if data is normally distributed) or the Wilcoxon rank-sum test (if data is 
non-normally distributed). Classified data will be analyzed using a chi-square test or the Fisher's 
Exact Test (if the chi-square test is not applicable), and ranked data using the Wilcoxon rank-sum 
test or CMH test. 
 
12.1.2 Completion and Demographic Analysis 
Baseline Data 
Demography and medical variables at baseline (including but not limited to, age, gender, race, 
medical history, medication history and disease diagnosis) will be used to describe subjects and 
summarize subject information. Summary statistics will be given based on the nature of variables 
(continuous or classified variables). For continuous variables, the number of observations, mean, 
standard deviation, median, minimum and maximum will be reported. For classified variables, the 
number of observations, frequency and percentage will be reported. 
A detailed list of different data set sizes in each group, case distribution of each site, total dropout 
rate comparison and reasons for not completing the study, should be provided. The demographic 
characteristics (age, height, vital signs, etc.), the medical history and the medication history of the 
patients are described, and comparison of the age, height, body weight, etc. between the two groups 
will be conducted to measure the comparability between the two groups. The outcome data can be 
accepted and reported only when the baseline of two groups is balanced; otherwise, the outcome 
data needs to be corrected and then can be reported. 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 46 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
12.1.3 Primary efficacy endpoints 
Primary efficacy evaluation will be based on Full Analysis Set (FAS) and Per-Protocol Set (PPS). 
For the statistical description and inference of the data, the applicable descriptive endpoints and 
hypothesis testing methods will be selected based on the characteristics of the data. 
The primary efficacy endpoint of this study is Lysholm score at 12 months after operation. The non-
inferiority testing is performed for efficiency of primary efficacy endpoint, and the test hypothesis 
is as follows: 
Invalid hypothesis: H0: μ1-μ2 ≤ -δ 
Alternative hypothesis: H1: μ1-μ2 > -δ, 
where, μ1 and μ2 are the Lysholm scores in the investigational group and control group, 
respectively. δ is a non-inferiority critical value. At α=0.025 (one-sided test), the hypothesis test is 
carried out using a two-sided t-test. A non-inferiority test is carried out on the Lysholm scores in the 
investigational group and control group. The 95% confidence interval between the two groups is 
calculated. 
 
12.1.4 Secondary efficacy endpoints 
The secondary efficacy evaluation is based on Full Analysis Set (FAS) and Per-Protocol Set (PPS). 
Summary statistics of all other secondary variables will be given based on the nature of variables 
(continuous or classified variables). For continuous variables, the number of observations, mean, 
standard deviation, median, minimum and maximum will be reported. For classified variables, the 
number of observations, frequency and percentage will be reported. 
 
12.2 Calculation of sample size 
12.2.1 Total Sample Size 
The primary efficacy endpoint of this study is the Lysholm score at 12 months after operation; the 
trial is designed as a non-inferiority trial. Accroding to references, the non-inferiority margin is set 
as 5 in this study. Assuming that the variance in both the investigational group and control group is 
9, the difference between two groups is 0, the significance level is set to α=0.025 (one-tailed), 
power 1-β=0.80, the calculation formula of sample size is analyzed by referring to the non-
inferiority of quantitative indicator: 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 47 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
𝑛𝑛𝑇𝑇= 𝑛𝑛𝐶𝐶= 2൫𝑍𝑍1−𝛼𝛼/2 + 𝑍𝑍1−𝛽𝛽൯
2𝜎𝜎2
(𝐷𝐷−∆)2
 
In which, σ is the standard deviation; D is the mean difference between two groups, which is 
expected to be detected, D=uT-uC; ∆ is the non-inferiority margin. At least 51 subjects should be 
included in each group in order to achieve 80% power, 102 in total. In consideration of 20% drop-
out rate, 64 subjects are planned to be included in each group, 128 subjects in total; 12 subjects are 
planned to be added to increase the success rate of trial, 140 subjects in total and 70 in each group. 
The estimation of sample size is completed by using PASS13. 
12.2.2 Number of Subjects with Each Disease in Clinical Trial and Reason for Determination 
In this trial protocol, it is strictly required that patients should be enrolled in compliance with the 
inclusion/exclusion criteria. It can be considered that all the patients have the same type of disease, 
and are not further divided. 
 
12.2.3 In multi-center clinical trial, minimum and maximum number of subjects in each 
clinical trial institution and justification 
This trial will be carried out at the same time in a number of clinical study sites. In principle, the 
number of subjects enrolled in each site will be distributed as evenly as possible to ensure adequate 
site representation. However, considering the feasibility and progress of the enrollment, the number 
of subjects enrolled will be adjusted according to the actual situation to ensure that the enrollment 
scale at each site is relatively balanced, and that the final enrollment scale for a specific site should 
not exceed 50% of the total number of cases. 
 
12.3 Significance level and power of the clinical trial 
The statistical significance level takes the one-tailed significance level of α=0.025, 80% power (1-
β). 
 
12.4 Expected drop-out rate 
Expected drop-out rate is not more than 20%. 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 48 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
12.5 Criteria for acceptability/unacceptability of clinical trial result 
Primary efficacy endpoint (the Lysholm score at 12 months after operation): If the lower limit of 95% 
CI for the efficacy difference between two groups is greater than the non-inferiority margin, it is 
considered that the investigational product is non-inferior to the control product, the statistical 
hypothesis is valid and the result of clinical trial is qualified; otherwise, the hypothesis is invalid, 
and the result of clinical trial is unacceptable. 
 
12.6 Criteria and reason for terminating the trial based on the statistical consideration 
This trial does not include interim analysis and does not terminate the trial according to statistical 
reasons. 
 
12.7 Statistical Method of All Data, Together with the Handling Method of Missing, Unused 
and Wrong Data (Including Discontinuation and Withdrawal) and Unreasonable Data 
The statistical analysis plan is developed before the trial. The statistical analysis programming and 
logic test programming are conducted according to the statistical analysis plan after database 
locking, then the simulation database test is conducted and the statistical analysis plan is issued 
according to the results. 
The Last Observation Carried Forward (LOCF) is used for imputation for missing data of primary 
efficacy endpoint. The handling of the outliers is to inquire the investigator about the unreasonable 
data and determine how to resolve the queries which are given by the data manager. 
 
12.8 Reporting Procedure of Deviation from Original Statistical Plan 
In the event of an "incomplete implementation of the statistical analysis plan", the change procedure 
should be applied in advance, such as changes in the statistical plan should be truthfully recorded in 
the statistical analysis plan, including changed position, change reasons, change time and other 
revision records. 
 
12.9 Selection criteria and justification of subjects included in the analysis 
12.9.1 Full Analysis Set (FAS) 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 49 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Full Analysis Set (FAS): According to the basic principle of Intention To Treat (ITT), all subjects 
who are randomized in the trial and have at least one effectiveness evaluation are included in the 
Full Analysis Set. The Last Observation Carried Forward (LOCF) is used for analysis when the 
primary efficacy endpoint is missing. 
 
12.9.2 Per-protocol Set (PPS) 
Per Protocol Set (PPS): it refers to a set of subjects that complete the trial, excluding those with 
serious protocol violation. 
12.9.3 Safety Data Set (SAS) 
Safety Analysis Set (SS): Refers to all subjects who are randomly assigned to use the 
investigational device and have at least one baseline safety evaluation. 
 
13 Feasibility analysis 
13.1 Possibility analysis on success 
Smith & Nephew is a leading enterprise in the domestic arthroscope industry and has a complete 
R&D, production and quality control (QC) system. The Biosure Regenesorb Interference Screw and 
similar products developed by Smith & Nephew have been marketed and used in foreign countries. 
Post-marketing supervision results show that no unexpected AEs and SAEs have been reported, 
demonstrating their safety and effectiveness. 
The material and design of the investigational product in this trail meet the technical requirements 
of national registration and testing, the product has passed the testing of Quality Supervision and 
Inspection Center for Medical Devices successfully, and all the performance indicators are qualified. 
The design of this clinical study protocol is in accordance with Guidance for Clinical Trial Design 
of Medical Devices, and is repeatedly discussed and demonstrated by clinical experts, clinical study 
sites, statisticians and internal experts of Smith & Nephew. 
The clinical sites that undertake this trial have complete instruments, equipment and technical 
resources, and have passed the national certification for qualifications of clinical study sites. The 
investigators are outstanding academic leaders in the field of domestic sports medicine, with rich 
experience in clinical study, and can guarantee the smooth progress of clinical study. 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 50 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
13.2 Possibility analysis on failure 
In the previous studies, most of the subjects were older patients. During the early follow-up of the 
trial, due to the limitation of functional recovery of patients after surgery, there was a phenomenon 
of loss to follow-up. In view of this problem, according to the Guidance for Clinical Trial Design of 
Medical Devices, the follow-up time is arranged scientifically, which not only ensures that the early 
recovery data of patients can be collected completely in the study, but also fully considers the 
convenience of patients' actions. In order to avoid the loss to follow-up of patients, in the informed 
process, the study team will fully emphasize the necessity for follow-up and the importance of 
protocol compliance with the patient, allowing the patient to fully understand the study procedures, 
arrange telephone follow-up at 4.5 months and 9 months, and ensure the integrity of the adverse 
event collection of patients during the trial, at the same time repeatedly confirm and remind the 
follow-up arrangements of patients in advance, and give compensation for the transportation cost 
from an ethical perspective. 
Rating scale is a subjective evaluation index; in order to ensure consistency, each site should 
specify the fixed raters, who are given consistency training according to scoring criteria. 
The grasp of inclusion and exclusion criteria is the key to the success of the trial. The sites and the 
Sponsor will provide sufficient training and the portable reminder cards for the investigators at the 
start of the trial. After the first patient is enrolled in each site, the inspector of Sponsor will arrange 
a visit to the study site to ensure that the understanding of the study sites for the inclusion and 
exclusion criteria as well as the grasp of the study sites for the process are in line with the protocol 
requirements. 
 
14 Quality control of clinical trial 
The quality assurance (QA) process is designed in each link of this study to ensure that the study is 
carried out according to the protocol, ensure that the complete and accurate data is submitted to the 
Sponsor in time, and ensure that complications or adverse events are immediately discovered and 
handled until the end of the trial. The investigators and study sites will provide direct access right to 
the original documents and study records for the audit of the Sponsor, the representative of Sponsor, 
EC and other regulatory authorities. 
 
14.1 Study Monitoring 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 51 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Clinical study monitoring is an important means to ensure the quality of clinical study. 
This study will be monitored by the Sponsor or by qualified personnel designated by the Sponsor. 
Qualified personnel may be employees of the Sponsor, or may be from a contract research 
organization (the agent of Sponsor). The Sponsor will monitor according to the monitoring 
frequency and the monitoring contents specified in the monitoring plan. The monitoring contents 
include and are not limited to the following aspects. 
The Sponsor, the agent of Sponsor, EC and regulatory authorities can directly access the source 
documents, so as to verify and evaluate the clinical data submitted by the investigator to the 
Sponsor through the CRF. 
The investigator is responsible for obtaining and maintaining complete health information of 
subjects recorded in the medical records (original documents). The raw data includes all original 
record information and certified copies of the original records (including clinical findings, 
observations, or other activities used for study reconstruction and evaluation in clinical study). 
Prior to the implementation of the clinical agreement, the Sponsor performs qualification evaluation 
visits to each study site to ensure that all investigators have received the corresponding training and 
that their personnel, facilities and resources are sufficient to carry out this study. 
Details can be found in the section of "Monitoring Plan" of this trial. 
 
14.2 Audit of Sponsor 
The objective of audit is to ensure the quality of the clinical trial project, ensure that the risk of the 
trial is controllable and evaluate whether the implementation of the trial is strictly in accordance 
with the trial protocol and the standard operating procedure of the Sponsor; audit also check 
whether all study guidelines and quality standards are implemented, promptly discover any careless 
mistake and errors, ensure the authenticity and reliability of clinical data, and data traceability, and 
promote the investigators, monitors, CRC to perform their work better, put forward meaningful 
suggestions for the trial, and guide the project to carry out better. 
Participation in the study means acceptance of an audit to the study site, and is independent of the 
monitoring follow-up, so as to assess the compliance with the protocol, guidelines and regulations. 
The auditor designated by the quality control department or his/her representative will be 
responsible for such visits. The Sponsor has the right to require the sites with poor trial quality to 
perform rectification. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 52 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
 
14.3 Laboratory Quality Control 
The laboratories of each study site should establish a unified standard for laboratory test indicators, 
standard operating procedures and quality control procedures. For the laboratory test items, the 
national legal measurement units must be adopted, the items of the test reports must be complete 
(including date, test items, test results and their normal ranges). Special test item(s) must be tested 
by a special person. 
 
15 Ethical issues and informed consent of clinical trial 
15.1 Ethical Considerations and Ethical Approval 
This clinical study must follow the Declaration of Helsinki, and should be carried out according to 
the clinical study standards and regulations related to medical devices issued by International 
conference on Harmonization (ICH) and China. 
Investigators are responsible for obtaining written and dated approval from an Ethics Committee 
(EC) prior to enrolling subjects. This approval should include the protocol, the informed consent 
form, subject recruitment materials, advertising or any written information that will be provided to 
subjects. 
Investigators are responsible for maintaining EC approval throughout the study by submitting 
progress reports (continuing review reports) at least annually and more often if requested by the EC. 
Withdrawal of EC Approval: The Investigator shall report to the Sponsor within 5 working days 
if, for any reason, the EC withdraws approval to conduct the investigation. The report will include a 
complete description of the reason(s) for which approval was withdrawn. 
Progress Reports: The Investigator is required to submit annual progress reports to the study 
Sponsor and to the reviewing EC. Reports must include the number of subjects, a summary of all 
follow-up evaluations, a summary of all adverse events, protocol deviations and a general 
description of the study progress. 
Final Report: The Investigator will submit a final report to the Sponsor and to the EC within 3 
months of completion of the study, termination of the study or termination of that Investigator’s 
participation in the study. 
Other Reports: Upon request of the Sponsor, NMPA or the EC, the Investigator shall provide 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 53 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
accurate, complete and current information. 
Additional documents that require the Investigator obtain written and dated EC approval during the 
course of the study include: 
● 
Protocol amendments (should not be implemented prior to EC approval) 
● 
Informed consent form revisions (Sponsor reserves the right to review all revised informed 
consent forms prior to submission as they relate to the Sponsor’s obligations) 
● 
Protocol deviation report 
● 
Adverse events described in Section 16 of this protocol 
● 
All other documents as required by the EC 
 
15.2 Informed consent 
Investigators are responsible for obtaining and documenting the voluntary informed consent of the 
study subjects prior to conducting any study-related assessments per International Conference on 
Harmonization (ICH) and Good Clinical Practice (GCP) guidelines. 
In obtaining informed consent, Investigators must adhere to GCP guidelines and to the ethical 
principles that have their origin in the Declaration of Helsinki. 
Prior to beginning the study, the Investigator must obtain written and dated EC approval of the 
informed consent form. The informed consent form and any other written information provided to 
subjects should be revised whenever important new information becomes available that may be 
relevant to the subject’s continued consent. All revised informed consent forms must have written 
and dated EC approval in advance of use. 
The communications with the subject regarding informed consent process (initial and subsequent) 
will be documented in the medical record. Subjects should receive a copy of the initial signed and 
dated informed consent form (in the local language) prior to the subjects’ participation in the study 
and any revised informed consent forms during the duration of the study. 
Use of device without Informed Consent: No subject may be treated with a study device without 
prior Informed Consent. Such treatment constitutes a violation of NMPA regulations. The 
Investigator shall submit a report indicating the circumstances for the occurrence to Smith & 
Nephew and to the reviewing EC within five working days after the use occurs. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 54 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
 
16 Adverse Event Reporting and Complaint 
16.1 Definition 
An adverse event is defined as any untoward medical occurrence in a clinical investigation in which 
a subject is administered a study device and which does not necessarily have a causal relationship 
with the device. An adverse event can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of study 
device, whether or not related to the study device. 
Any events that occur newly or deteriorate in severity and frequency as compared with baseline 
conditions, or abnormal results found in the process of diagnosis, including abnormal laboratory 
findings, are included herein. 
Note: The Sponsor collects the information on adverse events when the subjects sign the informed 
consent form. 
The following are specific definitions of adverse events: 
AE Adverse event - any untoward medical occurrence in a subject, regardless if there is a 
relationship between the AE and the device. 
SAE Serious Adverse Event - an adverse event that: 
A Serious Adverse Event is any AE that results in a death or a serious deterioration in the health of 
the subject during the clinical trial, including a life-threatening illness or injury, a permanent 
impairment of a body structure or a body function, in-patient hospitalization or prolongation of 
existing hospitalization, medical or surgical intervention to prevent permanent impairment of a 
body structure or a body function; or results in fetal distress, foetal death or congenital abnormality, 
congenital anomaly, etc. 
ADE Adverse Device Effect – any untoward and unintended response to a medical device (This 
definition includes any event that is a result of a user error). 
SADE Serious Adverse Device Effect – An adverse effect that has resulted in any of the 
consequences characteristic of a serious adverse event 
UADE Unanticipated Adverse Device Effect - An “unanticipated adverse device effect” (UADE) 
is defined as any serious adverse effect on health or safety or any life-threatening problem or death 
caused by or associated with this device which was not previously identified in nature, severity, or 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 55 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
degree of incidence in the application of the device. 
USADE Unanticipated Serious Adverse Device Effect - Serious adverse device effect which by 
its nature, incidence, severity or outcome has not been identified in the current version of the risk 
analysis report. 
ASADE Anticipated Serious Adverse Device Effect - A serious adverse device effect which by its 
nature, incidence, severity or outcome has been previously identified in the risk analysis report. 
DD Device Deficiency - An inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, safety or performance; Device deficiencies include malfunctions, use errors, 
and inadequate labeling. 
16.2 Treatment for Adverse Events 
In the event of an adverse event, the Investigator and/or other professional personnel in attendance 
will provide whatever appropriate therapy for the event. Under all circumstances, a suspected 
adverse event relating to the study device should be provided the adequate medical treatment. 
 
16.3 Reporting of adverse events 
16.3.1 Investigator Adverse Event Reporting 
All AEs will be categorized according to the investigator’s clinical judgment as mild, moderate or 
serious based on the following definitions: 
Mild: The subject is aware of the sign or symptom, but finds it easily tolerated. The event is of little 
concern to the subject and/or little clinical significance. The event is not expected to have any effect 
on the subject’s overall health or well-being. 
Moderate: The subject has discomfort enough to cause interference with or change in usual 
activities. The event is of some concern to the subject’s health or well-being and may require 
medical intervention and/or close follow-up. 
Serious: The adverse event interferes considerably with the subject’s usual activities. The event is 
of definite concern to the subject and/or poses substantial risk to the subject’s health or well-being. 
The event is likely to require medical intervention and/or close follow-up and may be incapacitating 
or life threatening. Hospitalization and treatment may be required. 
Reporting of adverse events to regulatory authorities will be undertaken according to the provisions 
of NMPA and guidances. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 56 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
For all UADEs, SAEs, USADEs, SADEs and device deficiencies which may lead to a SAE, that 
occur during the course of the clinical study, once the investigator knows, he/she must take 
appropriate treatment measures for the subjects and report to the Sponsor and the study site of 
hospital immediately. 
The administrative department of medical device clinical trials shall send written reports to 
corresponding EC, the food and drug administration of the concerned province or autonomous 
region or municipality directly under the central government, and the competent authority of health 
and family planning within 24h. Regarding adverse events of death, study sites and investigators 
should provide all required data to the corresponding Ethics Committees and Sponsor. 
Details of all adverse events or device deficiency must be recorded on the adverse event/device 
deficiency forms provided and faxed/e-mailed to the contact of Sponsor where possible at the time 
of reporting. Please keep the fax report or print an email as a record of the time limit. The contact 
details are shown in the Section “1. Sponsor Information” of the protocol. 
The Investigator must submit a detailed report that will identify the description of symptoms, 
classification of the event, date of onset, severity, treatment, and outcome. Supporting medical 
records may be obtained as an adjunct to an adverse event report and placed in the subject’s study 
file. 
During the clinical study, all serious and non-serious adverse events should be followed up to 
determine the final outcome. 
All SAEs, which haven’t been resolved at the end of the study or when the subjects withdraw 
prematurely from the study, must be followed up until one of the followings is achieved: 
● 
The event is resolved 
● 
Achieve stable state 
● 
Reasonable explanation is provided 
● 
Lost to follow-up or death 
● 
The event restores to the baseline level (if the baseline value is available) 
● 
When it is impossible to obtain more information (the patient or medical staff refuses to 
provide more information, and there is evidence showing that the patient is still lost to follow-
up after the medical staff tries his/her best) 
Once a subject has completed the study, the investigator should follow up for outcomes on all AEs 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 57 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
classified as possibly/definitely related to the investigational product and all serious adverse events 
until a final outcome can be determined or the end of the whole study (last subject last visit), 
whichever comes first. 
During the subject's participation in the trial, any event that caused hospitalization or prolonged 
hospitalization must be reported as a serious adverse event, unless because of: 
● 
Hospitalization for social reasons rather than adverse events 
● 
Surgery or operation that has been planned prior to participation in the trial (must be recorded 
in the original medical record and CRF) 
 
16.3.2 Sponsor Adverse Event Reporting 
For the serious adverse events and the device deficiencies that may cause serious adverse events, 
Smith & Nephew should report to the food and drug administration and the competent authority of 
health and family planning at the same level where the device is registered within 5 workdays after 
being informed. Smith & Nephew should also inform other study sites and investigators that 
participate in the trial, and timely inform the Ethics Committee of such study site through its 
administrative department for clinical trial of medical device. 
 
16.3.3 Causal relationship between AEs and the device and its evaluation criteria 
The AE is set to be related to the device in case of being "extremely probably related", "definitely 
related" and "probably related"; in case of other classification, the AE is set to unrelated to the 
device. 
Classification 
Description 
Definitely un-related The AE is identified as a result of a concomitant disease or the effects of 
another device/drug and is not related to the investigational product. 
Probably un-related 
The AE is more probably caused by other reasons and will not be improved 
or its prognosis is difficult to be judged after device withdrawal. Its 
recurrence is not found or difficult to be judged after device reuse. 
Probably related 
The occurrence of the AE meets the reasonable time sequence upon device 
use. The AE may be caused by the device or other reasons. It is improved 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 58 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
after device withdrawal. 
Extremely probably 
related 
The occurrence of the AE meets the reasonable time sequence upon device 
use. The AE is more reasonably attributed to the used device than other 
reasons. It is improved after device withdrawal. 
Definitely related 
The occurrence of the AE meets the reasonable time sequence upon device 
use. The AE is more reasonably attributed to the used device than other 
reasons. The AE mode is consistent with the previously known mode caused 
by the device. The AE is improved after device withdrawal but appears after 
device reuse. 
 
16.3.4 Causal relationship between AEs and surgery and its evaluation criteria 
The AE is set to be related to the operation in case of being "extremely probably related", 
"definitely related" and "probably related"; in case of other classification, the AE is set to unrelated 
to the operation. 
Classification 
Description 
Definitely un-related 
The AE is identified as a result of a concomitant disease or the effects of 
another device/drug and is not related to the operation. 
Probably un-related 
The AE is more probably caused by other reasons and will not be 
improved or its prognosis is difficult to be judged in case of no 
operation/upon operation. Its recurrence is not found or difficult to be 
judged in case of operation. 
Probably related 
The occurrence of the AE meets the reasonable time sequence of 
operation. The AE may be caused by the operation or other reasons. It is 
improved upon operation completion. 
Extremely 
probably 
related 
The occurrence of the AE meets the reasonable time sequence of 
operation. The AE is more reasonably attributed to the operation than 
other reasons. It is improved upon operation completion. 
Definitely related 
The occurrence of the AE meets the reasonable time sequence of 
operation. The AE is more reasonably attributed to the operation than 
other reasons. The AE mode is consistent with the previously known mode 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 59 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
generated in the operation. The AE is improved upon operation 
completion but appears in case of re-operation. 
 
16.3.5 Device Deficiency 
The device deficiency is defined as unreasonable risk occurred under normal use of medical device 
during the clinical trial, which may do harm to the human health and life safety, such as label error, 
quality problem and fault. 
The investigators should timely report the device deficiency to the Sponsor and evaluate results of 
device deficiencies. The device deficiencies that may cause severe adverse events need to be 
reported as required by the GCP. 
Device deficiencies must be observed intra-operatively and post-operatively, e.g. screw breakage. 
 
17 Protocol Amendment and Protocol Deviation 
17.1 Protocol Amendment 
If neither the investigator nor the Sponsor has reached an agreement, either party is prohibited from 
modifying the protocol. Only after consulting and agreeing to amend, the protocol can be revised. 
Protocol amendment may affect the scientificity, or infringe the rights, safety or health of subjects, 
which should be submitted to the regulatory authorities and EC for approval before the 
implementation of the protocol amendment. 
 
17.2 Protocol Violation by Individual Subjects in Emergency 
An individual subject is allowed to violate the protocol only if measures are required to be taken to 
protect the life or physical health of the subject in an emergency, and such violation is limited to 
this subject. The investigator or other attending physician handling the situation should inform the 
EC and call the clinical study manager of Smith & Nephew (within 48 hours) (see study contact on 
page 13). If the study manager cannot be contacted, the investigator should contact the second 
contact of the Sponsor; see page 13 for details. 
The investigator and Smith & Nephew should decide whether the subject who violates the study 
protocol can continue to participate in the study. Any protocol violations will be recorded in the 
written report of the investigator. The investigator should send the report and the reasons for the 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 60 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
violation (including the relationship with the therapeutic use of the device) to EC and Smith & 
Nephew. The EC can also determine that the subject should not continue to participate in this study. 
 
17.3 Protocol deviation 
Protocol deviation is defined as any case of non-compliance with the study protocol. Once the study 
site finds a protocol deviation, it should be reported to Smith & Nephew. According to the 
requirements, the investigator must also report the protocol deviation to the EC. 
For protocol deviations, it is minimally required to report major protocol deviations, including GCP 
deviations, events affecting safety of subjects (inclusion/exclusion criteria), impact of examination 
or operation on study results, and the process of obtaining informed consent. A protocol deviation is 
judged as a major or minor one based on the information whether to affect the safety of subjects, 
whether to affect the study results and whether to affect obtainment of informed consent. 
 
18 Access to Source Data/Documents 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with the Good Clinical Practice for Medical Device Clinical Trials and regulatory and 
institutional requirements. In order to protect the safety and rights and interests of the subjects, to 
ensure the authenticity, accuracy and integrity of the study progress and data, each study site should 
allow and cooperate with the Sponsor's monitors, quality assurance personnel, regulatory authorities 
and authorized representatives to perform quality review and audit. In order to complete the above 
activities, the above personnel should have the right to access, review or verify source data or 
source files. 
Source data is all information, original records of clinical findings, observations, or other activities 
in a specific clinical trial necessary for the reconstruction and evaluation of the trial. These original 
documents and data records include, but are not limited to, inpatient or outpatient medical records, 
clinical and office charts, laboratory notes, memoranda, participants’ memory aids or evaluation 
checklists, transportation, delivery, use and recovery records of the device, recorded audio tapes of 
counseling sessions, recorded data from automated instruments, copies certified after verification as 
being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-
rays, and participant files and records kept at the pharmacy, at the laboratories, and ancillary 
departments involved in the clinical trial. The CRF for recording scales is saved as a source 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 61 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
document. The Adverse Event and Serious Adverse Event Report Form contains more information 
than medical records and should be considered as the source document. In the inpatient and 
outpatient medical record system of the hospital, the severity of adverse events and the causality 
judgments are usually not recorded, and there is a lack of records of correlation between the 
concomitant medication and adverse events. Therefore, the Sponsor will provide corresponding 
forms as source documents to save and record relevant information. 
 
19 Finance and Insurance 
19.1 Surgical instruments 
After the Ethics Committee of the hospital approves the start of the clinical study, the Sponsor 
sends the investigational device to each study site. Only qualified personnel participating in this 
study is allowed to receive the investigational product. When the investigational device is delivered 
to each site, the complete inventory list should be provided. When there are any discrepancies 
between the contents recorded in the device transport form and the objects provided, they should be 
indicated on the transport form and immediately informed to the Smith & Nephew company. The 
device transport forms need to be kept in the folders of the study site. For any devices received, 
their quantity and size should be recorded in the device inventory log. 
During the study process, the investigator must fully record the receipt, use, loss and disposal of the 
investigational product in the device study log to ensure that the storage and distribution of the 
investigational device is always under supervision. All device supplies must be stored in accordance 
with the conditions specified by the manufacturer, while complying with applicable regulatory 
requirements. The investigational device must be stored separately from the usual 
facilities/conventional items in the hospital. Until distribution prior to operation, all investigational 
devices must be stored in a safe locked area according to the conditions required in the instructions 
for use and only authorized personnel is allowed to enter. 
It is the responsibility of the investigator to ensure that the investigational device inventory is 
sufficient and is only used for the subjects enrolled in this study. When the inventory is insufficient, 
the Sponsor should be contacted in advance. In addition, the Sponsor will coordinate as necessary to 
ensure supervision. 
According to the instructions of the Sponsor, the investigator should return all remaining devices 
after completing the recruitment of subjects in this study. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 62 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
 
19.2 Others 
Clinical study sites and principal investigators should properly manage the surgical tools, 
investigational devices and test equipment in accordance with regulations of applicable guidelines 
and trial protocol. The clinical study sites and the principal investigators cannot use and permit the 
use of the investigational devices and test equipment for any purpose other than the implementation 
of this trial, and will follow applicable guidelines, trial protocol and any instructions given by the 
Sponsor regarding any operation, maintenance or storage of the investigational devices and test 
equipment. Upon termination or expiration of this Agreement, according to the Sponsor's choice, all 
unused investigational devices and test equipment should be returned to the Sponsor or be disposed 
according to the written instructions of the Sponsor. 
The Sponsor purchases insurance for this study. 
 
20 Contents of the clinical trial report 
A clinical study summary is issued after each sub-site completes the clinical study. The clinical trial 
report is also issued. All sub-sites confirm the contents of the summary report and submit it after 
signing and stamping. The clinical trial report should be consistent with the clinical trial protocol, 
mainly including: 
● 
General information; 
● 
Synopsis; 
● 
Introduction; 
● 
Clinical trial objective; 
● 
Clinical trial method; 
● 
Contents of clinical trial; 
● 
General clinical information; 
● 
Investigational medical device; 
● 
Statistical analysis methods and evaluation methods adopted; 
● 
Clinical evaluation criteria; 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 63 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
● 
Organizational structure of clinical trial; 
● 
Ethical compliance statement; 
● 
Clinical trial results; 
● 
Adverse events found in the clinical trial and their handling; 
● 
Analysis and discussion of clinical trial results, especially the indications, scope of application, 
contraindications and precautions; 
● 
Conclusion of clinical trial; 
● 
Existing problems and improvement suggestion; 
● 
List of investigators; 
● 
Other conditions that need to be described. 
21 Confidentiality Principle 
21.1 Disclosure 
Clinical data obtained in this study will not be disclosed by the Sponsor other than for the purposes 
outlined in the protocol. Anonymized personal information may be used by the Sponsor within 
China or elsewhere in the world. 
Personal data will be collected and processed to: 
● 
Check subject suitability to take part in the study 
● 
Monitor treatment with the investigational device 
● 
Compare and incorporate treatment results with those of other subjects in clinical studies 
● 
Support the development of the investigational device 
● 
Support the licensing application for regulatory approval of the investigational device in the 
world 
● 
Support the marketing, distribution, sale and use of the investigational device anywhere in the 
world. 
 
21.2 Data Security and Confidentiality 
Clinical study sites and principal investigators should truthfully, accurately, completely and timely 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 64 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
collect, record and submit data specified in the trial protocol to Smith & Nephew (or the related 
party of Smith & Nephew according to the instructions of Smith & Nephew) in accordance with the 
regulations of applicable guidelines and the trial protocol, including CRF (whether in paper or 
electronic form) and any other documents or materials which are developed for this trial and should 
be submitted to Smith & Nephew (hereinafter collectively referred to as "trial data"). Clinical study 
sites, principal investigators and Smith & Nephew should properly handle and save trial data in 
accordance with the regulations of applicable guidelines and trial protocol. It is agreed by each 
party that the trial data is exclusively owned by Smith & Nephew, but Smith & Nephew does not 
claim ownership of such medical records of subjects that may contain some trial data. 
All parties should follow the principles of medical confidentiality related to the subjects involved in 
this trial. The principal investigator and clinical study sited may disclose the personal data specified 
in the relevant data protection laws applicable to the clinical study site (the "relevant data protection 
regulations") to Smith & Nephew (or the related party of Smith & Nephew according to instructions 
of Smith & Nephew) only if disclosure is necessary to meet the requirements of the trial protocol or 
for the purposes of monitoring, adverse event reporting or investigation, or claims or proceedings 
brought by subjects in respect of this trial. Except in accordance with the relevant data protection 
regulations, neither party can disclose the identity information of subjects to any third party other 
than Smith & Nephew and its related party without the prior written consent of subjects, unless such 
disclosure is related to the claims or proceedings brought by subjects in respect of this trial. 
Each party should ensure that any confidential information disclosed to the other party is only 
disclosed to the managers and employees (in terms of Smith & Nephew, related party of Smith & 
Nephew and their respective managers and employees are also included) directly involved in the 
implementation of this agreement. In addition, all parties should keep strictly confidential and 
cannot disclose any such confidential information of the other party to any third party, except as 
required by the regulatory authorities or the law. The party requiring disclosure should notify the 
other party in advance on the disclosure requirements and the information to be disclosed within a 
reasonable time before the disclosure is required. Each party undertakes not to use any such 
confidential information of the other party for the purposes other than this agreement without the 
prior written consent of the other party. 
 
22 Agreement on the Publication of Study results 
The main objective of this study is to support the registration of investigational device in China 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 65 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
researched and developed by Smith & Nephew. However, after the study is completed, the study 
results may be submitted and announced. The publication policy is detailed in the Clinical Trial 
Agreement (CTA). If the investigator wishes to publish the clinical study results or the results of the 
activities in the clinical study, the manuscript should be submitted to Smith & Nephew for review 
before the manuscript for publication is submitted. Before publication of the total study or at 2 years 
after the end of the study (based on the earliest time), any sites may not publish this study. 
After completion of this trial, the principal investigator should collate the data generated from this 
trial for publication. The principal investigator should submit the data and materials to be publicly 
disseminated to Smith & Nephew at least sixty (60) days in advance, and can submit them for 
publication, public dissemination or review by the publication committee after obtaining the written 
consent of Smith & Nephew; and the principal investigator should write the reasonable revision 
comments proposed by Smith & Nephew into the contents to be published. If Smith & Nephew 
considers that any contents to be published contain any information related to applicable patent 
matters, disclosure of the contents to be published by the clinical study site and/or principal 
investigator to any third party may be delayed by up to six (6) months in order to allow Smith & 
Nephew to submit the relevant patent application. 
The principal investigator has the right to introduce the methods and results of this trial at seminars 
and academic conferences, or to publish them in journals or academic dissertations, or though other 
ways. Such rights may be exercised before or after the methods and results of the trial are disclosed 
in any other manner, but the specific contents should have been previously reviewed and approved 
by Smith & Nephew. 
 
23 Responsibilities of each party 
23.1 Responsibilities of Sponsor 
The Sponsor is responsible for the initiation, application, organization and monitoring of a clinical 
trial and is responsible for the truthfulness and reliability of the clinical trial. 
The Sponsor is responsible for the organization to establish and modify the investigator’s brochure, 
clinical trial protocol, informed consent form, CRF, relevant standard operating procedures and 
other relevant documents, and carry out the training required for the clinical trial. 
The Sponsor should, according to the characteristics of the investigational medical device, select the 
study sites and the investigators with qualifications. Before signing the clinical trial protocol with 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 66 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
the study site, the Sponsor should provide the latest investigator's brochure and other relevant 
documents for the study site and investigators, for their decision whether they can undertake this 
clinical trial. 
During the clinical trial, in case of important information affecting the study process, the Sponsor 
should accordingly revise the investigator's brochure and related documents in a timely manner, 
submit through the study site's administrative department for clinical trial of medical device to the 
Ethics Committee for review and approval. 
The Sponsor is responsible for the safety of investigational medical device in clinical trial. When 
the trial is found to affect the safety of the subjects or the trial implementation may change the 
approval of the Ethics Committee to continue the trial, the Sponsor should immediately notify all 
study sites and investigators and deal with them accordingly. 
Where suspension or termination of the study is decided, the Sponsor should notify all the 
administrative departments for clinical trial of medical device of all the study sites within 5 days, 
and give reasons in writing. The administrative department for clinical trial of medical device of all 
the study sites should notify promptly corresponding investigators and Ethics Committees. The 
suspended clinical trial should not be resumed without the consent of the Ethics Committee. Upon 
end of clinical trial, the Sponsor should report in writing form to the local food and drug 
administration at the provincial, autonomous regional and municipal level. 
Ensure that all investigators who implement clinical trials strictly follow the clinical trial protocol 
and correct any incompliance of the study sites and investigators with the relevant laws and 
regulations, the GCP of medical devices and the clinical trial protocols; in case of serious violation 
or absence of rectification, the trial should be terminated and the report should be reported to the 
food and drug administrations of province, autonomous region and municipalities directly under the 
Central Government where the study site is located and to the China Food and Drug Administration. 
The Sponsor should bear the treatment cost and relevant economic compensation for the clinical 
trial-related injury or death of subjects, with the exception of damages due to the fault of medical 
institution and medical staff in the diagnosis and treatment. 
The Sponsor should be responsible for monitoring the clinical trial and selecting qualified CRA to 
perform monitoring duties. 
For the multi-center clinical trial, the Sponsor should ensure that the protocol document has been 
established before the clinical trial, giving clear assignment of responsibility of the coordinating 
investigator and other investigators. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 67 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
 
23.2 Responsibilities of Study Sites and Investigators 
The study sites should evaluate the relevant resources according to the features of investigational 
medical device prior to the clinical trial, so as to decide whether to perform this clinical trial. 
It is the responsibility of the investigators to ensure that the study is carried out in accordance with 
the clinical study agreement, this protocol and applicable local laws and regulations. About the 
definition of responsibilities of the investigator, please refer to the Good Clinical Practice for 
Medical Devices. 
The administrative department for clinical trial of medical device of study site should cooperate 
with the Sponsor to apply to the Ethics Committee and submit the relevant documents prior to the 
clinical trial according to requirements. 
The investigators should ensure that the relevant staff involved in the trial are familiar with the 
principles, scope of application, product performance, method of operation, installation 
requirements and technical specifications of the investigational medical device, understand the pre-
clinical study data and safety data of the investigational medical device, and grasp the prevention 
and emergency treatment methods of possible risk in clinical trial. 
The investigators should ensure that all clinical trial participants are fully aware of the clinical trial 
protocol, the relevant regulations, the characteristics of the investigational medical device, and the 
responsibilities associated with clinical trials, and ensure that a sufficient number of subjects who 
meet the criteria for inclusion in clinical trials are admitted to clinical trials, and ensure that there is 
sufficient time to securely implement and complete the clinical trial within the agreed study period 
of the agreement according to the relevant provisions. 
The investigators should ensure to use the investigational medical device only for the subjects of 
this clinical trial, and may not charge any fee. 
The investigators should strictly follow the clinical trial protocol, and should not deviate from the 
protocol or substantially change protocol without the consent of the Sponsor and the Ethics 
Committee or without approval from the China Food and Drug Administration as required. Where 
there is emergency in which the subject faces the direct risk and which needs to be immediately 
tackled, report can be submitted in writing afterwards. 
The investigators are responsible for recruiting the subjects, communicating with the subjects or 
their legal guardians. The investigators have a responsibility to explain to the subject the related 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 68 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
details of the investigational medical device and the clinical trial, inform the subject of possible 
benefit and known, foreseeable risk, and obtain the signature and informed consent dated of the 
subject or his/her guardian. 
The investigators or other personnel participating in the trial should not compel or induce the 
subject to participate in the trial in any other improper manner. 
In clinical trials, when investigators found unexpected adverse events of the investigational medical 
device, they should modify the relevant contents of the informed consent form together with the 
Sponsor. After reporting to the Ethics Committee for review and approval in accordance with the 
relevant work procedures, the affected subjects or their guardians resign and confirm the amended 
informed consent form. 
The investigators are responsible for making medical decisions related to clinical trials. In the event 
of adverse events associated with clinical trials, the study site and the investigator should ensure 
that the subject is provided with adequate and timely treatment and management. The investigators 
should inform the subjects in time when the subjects suffer from concurrent diseases requiring 
therapy and treatment. 
In case of any SAE during the clinical trial, the investigators should immediately take appropriate 
therapeutic measures for subjects, report the event in written to the administrative department for 
medical device clinical trial of the study sites, and then the study site reports the event to the 
Sponsor in writing. The administrative department of medical device clinical trials shall send 
written reports to corresponding EC, the food and drug administration of the concerned province or 
autonomous region or municipality directly under the central government, and the competent 
authority of health and family planning within 24h. Regarding adverse events of death, study sites 
and investigators should provide all required data to the corresponding Ethics Committees and 
Sponsor. 
The investigators should record all adverse events occurred and device defects found during the 
clinical trial, work with the Sponsor to analyze the causes of the events, prepare the written analysis 
report, make decision on whether to continue, suspend or terminate the trial. The decision will be 
reported to the Ethics Committee for review by the administrative department for clinical trial of 
medical device in the study site. 
The study site and investigator should accept the monitoring and audit of the sponsor, and the 
supervision of the Ethics Committee, and provide all required records related to the trial. When the 
food and drug regulatory authorities and competent departments of health and family planning send 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 69 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
the inspection personnel to carry out the inspection, the study site and investigator shall cooperate 
with them. 
When the study site and investigator conclude that the risk outweighs the possible benefit or that the 
safety and efficacy of the investigational medical device have been validated, and suspension or 
termination of the trial may be necessary, the subjects should be informed and it should be ensured 
that the subjects can receive the proper care and follow-up. The study site and investigator should 
also report in accordance with the provisions, and provide the detailed written explanation. Relevant 
report should be submitted to the local food and drug administration at the provincial, autonomous 
regional and municipal level if necessary. 
When investigator is notified by the Sponsor or the Ethics Committee to suspend or terminate the 
clinical trial, the subjects should be informed, and it should be ensured that the subjects can receive 
the proper care and follow-up. 
When the sponsor alters the trial data and conclusions in violation of the relevant provisions or 
requirements, study sites and investigators should report to the food and drug administration of the 
province or autonomous region or municipality directly under the Central Government where the 
sponsor is located or CFDA. 
The investigators should ensure to complete all records and reports at the end of clinical trial. At the 
same time, the investigators should also ensure that the investigational medical device received is 
consistent with the amount used, discarded and returned, ensuring that the remaining investigational 
medical device is properly processed and documented. 
Investigators may, based on the need of clinical trial, authorize the relevant staff to undertake the 
subject recruitment, communication with subjects, recording of clinical trial data and management 
of investigational medical device. The investigator shall provide training for the authorized persons 
and form the corresponding document. 
The investigator should make sure that the clinical trial data are accurately, completely, clearly and 
timely recorded into the CRF. CRF is signed by the investigator, and any data changes should be 
signed and dated by the investigator; meanwhile, the original record should be retained and should 
be legible. The study sites and investigators should make sure that the data, documents and records 
generated in the clinical trial are true, accurate, clear and safe, including but not limited to the 
following data: 
● 
Communications with the Sponsor, clinical monitors, other investigators, EC or 
NMPA/regulatory authorities. 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 70 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
● 
Signed investigator agreement as well as resumes of the principal investigator and any 
important investigators. 
● 
The records of subjects in the study include: informed consent form with signature and date, all 
original documents, CRFs of subjects, data query and the use record of devices by each subject; 
● 
All relevant observations, including records and reports of adverse reactions (whether expected 
or unexpected); 
● 
The date and detailed reasons for all versions of the study protocol and any protocol deviations 
(which may affect the scientific quality of the study or rights, safety or health of subjects); 
● 
Approved blank informed consent form and blank case report form of subjects; 
● 
All necessary study documents 
The study sites should properly keep the records and documents of clinical trial according to the 
agreement with the Sponsor until 10 years after the end of the clinical trial. Prior to the transfer or 
destruction of the study documents, the investigators must obtain the written consent of the Sponsor. 
If the investigators are unable to save these records in their file, the investigators must obtain 
permission from the Sponsor to make other arrangements. If the investigator leaves the study site, 
another responsible person must be appointed to keep these records. The specific arrangements need 
to be recorded in a written form, and then submitted to the Sponsor and the EC. 
The responsibilities of each party are detailed in the Clinical Trial Agreement. 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 71 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
24 Bibliography 
1. 
Rocco Papalia, Sebastiano Vasta, et al. Metallic or bioabsorbable interference screw for graft 
fixation in anterior cruciate ligament (ACL) reconstruction J British Medical Bulletin, 2014, 
Vol.109 19-29. 
2. 
Christopher Kaeding, Jack Farr et al. A Prospective Randomized Comparison of Bioabsorbable 
and Titanium Anterior Cruciate Ligament Interference Screws J Arthroscopy: The Journal of 
Arthroscopic and Related Surgery, Vol 21, No 2 (February), 2005:pp 147-151. 
3. 
Christian Fink, Karl P. Benedetto et al. Bioabsorbable Polyglyconate Interference Screw 
Fixation in Anterior Cruciate Ligament Reconstruction: A Prospective Computed Tomography- 
Controlled Study J Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 16, No 
5 (July-August), 2000:pp 491-498. 
4. 
Yuval Arama, Lucy J. Salmon et al. Bioabsorbable Verus Titanium Screws in Anterior Cruciate 
Ligament Reconstruction Using Hamstring Autograft J The American Journal of Sports 
Medicine, Vol.43, No.8 1893-1901. 
5. 
Ao Yingfang, and Shi Hefu. Epidemiological Investigation of Anterior Cruciate Ligament 
Injury in Athletes [J]. Sport Science, 2000, 20(4):47-48. 
6. 
Li Huan, Wang Kejie and Yan Weihong. Current Research on ACL Reconstruction for Knee 
Joint [J]. Chinese Orthopaedic Journal of Clinical and Basic Research, 2013(3):184-189. 
7. 
Feng Shiqing, Guo Shifu, Wang Pei and et al. Reconstruction of the anterior cruciate ligament 
with bone-patellar tendon-bone transplantation and absorbable screws fixation under knee 
arthroscopy [J]. Chinese Journal of Orthopaedics, 2004, 24(3):137-140. 
8. 
Iorio R, Ciardini R, Russo A, et al. Reconstruction of the anterior cruciate ligament with the 
tendons of the semitendinosus and gracilis doubled: a comparison with reconstruction using 
the patellar tendon.[J]. La Chirurgia Degli Organi Di Movimento, 2005, 90(4):379-86. 
9. 
Kivanc A, Fu F H, Wolf M R, et al. Augmentation of tendon-to-bone healing.[J]. Journal of 
Bone & Joint Surgery, 2014, 96(6):513-21. 
10. Brady P C, Pablo N, Adams C R, et al. Arthroscopic proximal biceps tenodesis at the articular 
margin: evaluation of outcomes, complications, and revision?rate.[J]. Arthroscopy the Journal 
of Arthroscopic & Related Surgery, 2015, 31(3):470–476. 
11. Shen Yuhui, Liu Jinhao and Xu Xiangyang. Treatment of degenerative Achilles'tendon rupture 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 72 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
using V-Y tendinous flap and transfer of flexor hallucis longus tendon [J]. Chinese Journal of 
Orthopaedic Trauma, 2008(3):238-241. 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 73 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Investigator’s Statement 
I agree: 
1. 
To conduct this clinical trial in strict compliance with Declaration of Helsinki, current laws and 
regulations of China, and the requirements of the protocol. 
2. 
To accurately record all data required into the Case Report Form (CRF) and complete the 
report of the clinical trial on time. 
3. 
The investigational medical device will be used only for this clinical trial and the receipt and 
use of the investigational medical device will be recorded completely and accurately and the 
records will be retained throughout the clinical trial. 
4. 
To allow CRA and auditor authorized by the Sponsor as well as regulatory authorities to 
conduct monitoring, verification and inspection on the clinical trial. 
5. 
To strictly perform the articles of clinical trial contract/agreement signed among parties. 
I have already read the clinical trial protocol entirely, including the above statement and I fully 
agree all the above contents. 
 
Comments of investigator 
 
 
 
Signature: 
 
 
MM/DD/YYYY 
 
 
 

Study Protocol - Device 
 
A Prospective, Multi-center, Randomized Clinical Study to 
Evaluate the Safety and Effectiveness of Biosure Regenesorb 
Interference Screw in Arthroscopic Reconstruction of Cruciate 
Ligaments in Chinese Patients 
Study No.: BIOSURE 
RG.SMD.PMA.2019.01 
Version: V2.0/July 3rd, 2020 
Page 74 of 74 
 
Confidential and Proprietary 
This document contains confidential and proprietary information on Smith & Nephew PLC and Smith & Nephew, Inc. and is only available to Smith 
& Nephew and its manufacturers. Without prior written approval of Smith & Nephew, the content cannot be replicated, printed totally/partially or 
disclosed in any other way, and anyone must use it as per the requirements, either expressed or implied by Smith & Nephew. 
Comments of sponsor 
 
 
 
Signature (stamp) 
 
 
MM/DD/YYYY 
 
 
Comments of medical device study site GCP office 
 
 
 
Signature (stamp) 
 
 
MM/DD/YYYY