Evaluation of the Aurora Xi New Nomogram Software 2.0
Phase: NA
Conditions: Apheresis Related Hypotension
Sponsor: Fenwal, Inc.

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Clinical Study Protocol 
PAND-004-CMD 
Evaluation of the Aurora Xi New Nomogram Software 2.0 
 
 
 
Sponsor: 
Fresenius Kabi 
Three Corporate Drive 
Lake Zurich, Illinois USA 60047 
 
 
Confidential Information 
The information contained in this protocol is confidential and is provided for the sole and 
exclusive use of Investigators in this clinical study. The information in this document may 
not be disclosed unless such disclosure is required by Federal, or applicable State Law or 
Regulations, or unless there is prior written consent from Fresenius Kabi. Subject to the 
foregoing, this information may be disclosed only to those persons involved in the clinical 
investigation who need it, and who share the obligation not to disseminate this information 
further. This document and its associated attachments and appendices are subject to United 
States Freedom of Information Act Exemption 4. 
 
 

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1 PROTOCOL SUMMARY 
Name of Sponsor: 
Fresenius Kabi 
Name of Investigational Product(s):  
Aurora Xi With Investigational 
Software 2.0 
Regulatory Identifier: 
IDE 29600 
CSP ID: PAND-004-CMD 
CSP Title: Evaluation of the Aurora Xi New Nomogram Software 2.0 
Estimated Duration: 6-9 Months 
Planned Number of Procedures: Approximately 51,720 procedures for the primary endpoint evaluation. 
Objective(s): 
Primary: 
• 
The primary objective of this study is to demonstrate that the overall rate of significant 
hypotensive adverse events (SHAEs, IQPP DAE Classification 1.2-1.6) in donors using the 
Aurora Xi New Nomogram algorithm is less than double the SHAE rate in donors using the 
Aurora Xi Optimized Nomogram algorithm. 
Secondary: 
• 
To determine if the incidence rate of SHAEs per donor status (first-time or repeat donor) 
observed with the New Nomogram (Test arm) is non-inferior to the incidence rate observed with 
the Optimized Nomogram (Control arm). 
• 
To determine if the incidence rate of SHAEs of female donors observed with the New Nomogram 
(Test arm) is non-inferior to the incidence rate observed with the Optimized Nomogram (Control 
arm). 
• 
To determine if the incidence rate of SHAEs for donors ≤20 years of age observed with the New 
Nomogram (Test arm) is non-inferior to the incidence rate observed with the Optimized 
Nomogram (Control arm). 
• 
To determine if the incidence rate of SHAEs for donors weighting ≤124 lbs observed with the 
New Nomogram (Test arm) is non-inferior to the incidence rate observed with the Optimized 
Nomogram (Control arm). 
• 
To determine if the incidence rate of hypotensive severe/injury adverse events (IQPP DAE 
Classification 1.5 or 1.6) observed with the New Nomogram (Test arm) is non-inferior to the 
incidence rate observed with the Optimized Nomogram (Control arm). 
• 
To determine if the time from start of plasmapheresis procedure to the first SHAE observed with 
the New Nomogram (Test arm) is non-inferior to the time observed with the Optimized 
Nomogram (Control arm). 
Exploratory: 
• 
To compare the plasma volume collected with the New Nomogram (Test arm) versus the 
Optimized Nomogram (Control arm) 
• 
To determine the collection time with the New Nomogram (Test arm) 
  

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Study Design: This is a multicenter, prospective randomized controlled clinical trial to evaluate the 
Aurora Xi New Nomogram for the collection of plasma.  The Test group will utilize the Aurora Xi 
Plasmapheresis system with New Nomogram (software version 2.0) and the Control group will utilize the 
Aurora Xi Plasmapheresis System with Optimized Nomogram (software version 1.3).  Subjects will be 
retained in the assigned study arm (Test/Control) throughout their participation in the study period. 
Participants will donate for up to 8 weeks for the primary endpoint analysis, resulting in at least 51,720 
plasmapheresis procedures. At that point, the primary endpoint analysis will take place. If noninferiority is 
demonstrated for the primary endpoint, but subgroup enrollment is not judged to be sufficient, an optional 
extension period will begin, during which collections and enrollment will continue from specific 
subpopulations (first-time donors, female donors, young donors, and low body weight donors). Collections 
performed during the optional extension period will not be included in the primary endpoint analysis but 
will be included for secondary endpoint analyses / subgroup analysis. 
 
 
 
 
   
 
It is anticipated that enrollment will take approximately 6-9 months.  Prior to enrollment, all subjects will 
be required to provide a signed informed consent for this research study and meet all standard 
requirements for the plasma collection center. Subjects will be considered enrolled at the time of 
venipuncture for the first on-study collection procedure. Plasmapheresis subject evaluations will be 
completed pre-procedure, during the procedure, and post-procedure between the date of the first on-study 
collection and up to 2 weeks after the last on-study collection. 
Inclusion/Exclusion Criteria: 
Inclusion: 
• 
All subjects must meet current safety guidelines for plasma donation as set forth by the FDA as 
well as those in the standard operating procedures established by the participating institution. 
• 
Enrolled subjects who do not meet inclusion criteria at a later donation attempt are eligible to 
remain in the clinical trial and to subsequently donate plasma once they meet eligibility criteria 
again. 
Exclusion: 
• 
Subjects not able or unwilling to give consent to participate. 
• 
Subjects withdrawn by a qualified healthcare provider due to safety concerns. 
• 
Subjects who are employed by the clinical site or Sponsor. 
Statistical Methods:  
The primary objective of the study is to demonstrate that the overall rate of significant hypotensive 
adverse events (SHAEs, IQPP DAE Classification 1.2-1.6) in donors using the Aurora Xi New Nomogram 
algorithm is less than double the SHAE rate in donors using the Aurora Xi Optimized Nomogram 
algorithm. A non-inferiority test will be carried out based on a confidence interval approach using a two-
sided 95% confidence interval for the relative rate of SHAE for the experimental versus control arms 
based on a log linear model. 
 
Secondary objectives of the study will be carried out by fitting a log linear model with the same 
specifications as the primary objective analysis with binary procedure-specific response, log-link, identity 
variance function, and working independence assumptions, Once the model is fitted, a point estimate and a 
95% confidence interval will be computed for the relative rate of SHAEs for the secondary endpoints. 
 
Summary statistics (N, mean, standard deviation, median, minimum, and maximum) will be reported on 
continuous (numeric) parameters for each Randomization Group for the Intent-to-Treat and Per-Protocol 
analyses unless otherwise indicated. Summary statistics (e.g., counts and percentages) will be reported on 
categorical (non-numeric) parameters for each Randomization Group for the Intent-to-Treat and Per-
Protocol analyses unless otherwise indicated. 

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TABLE OF CONTENTS 
1 PROTOCOL SUMMARY ............................................................................................ 2 
TABLE OF CONTENTS ................................................................................................. 4 
List of Tables .............................................................................................................. 6 
2 ABBREVIATIONS AND DEFINITIONS ................................................................... 7 
3 BACKGROUND ......................................................................................................... 10 
3.1 Primary Objective .............................................................................................. 11 
3.2 Secondary Objectives ......................................................................................... 11 
3.3 Exploratory Objectives ....................................................................................... 11 
4 SCOPE ........................................................................................................................ 11 
5 STUDY DESIGN ........................................................................................................ 12 
5.1 Overview of Study Design ................................................................................. 12 
5.2 Subject Selection ................................................................................................ 13 
5.2.1 Inclusion Criteria ....................................................................................... 13 
5.2.2 Exclusion Criteria ...................................................................................... 13 
5.2.3 Subject Enrollment .................................................................................... 13 
5.2.4 Subject Donation Status ............................................................................ 14 
5.2.5 Subject Withdrawal ................................................................................... 14 
6 STUDY PROCEDURES/METHODOLOGY ............................................................ 14 
6.1 Training .............................................................................................................. 14 
6.2 Lead-In Consenting Period................................................................................. 15 
6.3 Roll-in Procedures .............................................................................................. 15 
6.4 Study Procedures ................................................................................................ 15 
 
 
 
6.6 Study Evaluations ............................................................................................... 16 
6.6.1 Pre-Procedure ............................................................................................ 16 
6.6.2 During Procedure ...................................................................................... 17 
6.6.3 Post-Procedure .......................................................................................... 17 
6.6.4 Study Parameters ....................................................................................... 17 
6.7 Appropriateness of Measurements ..................................................................... 19 
6.8 Study Completion ............................................................................................... 19 
6.9 Site Closure ........................................................................................................ 19 
6.10 Discontinuation ................................................................................................ 19 
6.11 Study Termination ............................................................................................ 19 
6.12 Collected Plasma .............................................................................................. 19 
7 DESCRIPTION OF INVESTIGATIONAL PRODUCT ............................................ 19 

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7.1 Intended Use ....................................................................................................... 19 
7.2 General Description............................................................................................ 20 
7.3 Materials and Supplies ....................................................................................... 20 
7.4 Labeling .............................................................................................................. 21 
7.5 Anticipated Changes to the Investigational Product During the Study .............. 21 
7.6 Method of Assignment to Investigational Product(s) ........................................ 21 
8 BIAS MITIGATION ................................................................................................... 22 
9 RISK ANALYSIS ....................................................................................................... 23 
9.1 Risks Associated with Blood Donation .............................................................. 23 
9.2 Risks Associated with an Apheresis Procedure ................................................. 23 
9.3 Risks Associated with Use of the Aurora Xi New Nomogram .......................... 23 
10 SAFETY EVALUATIONS....................................................................................... 24 
10.1 Adverse Events ................................................................................................. 24 
10.2 Serious Adverse Events .................................................................................... 26 
11 DATA QUALITY ASSURANCE ............................................................................ 27 
11.1 Data Capture System ........................................................................................ 27 
11.2 Data Flow ......................................................................................................... 27 
11.3 Data Recording ................................................................................................. 28 
11.4 Case Report Forms ........................................................................................... 28 
11.5 Monitoring Procedures ..................................................................................... 29 
11.6 Maintenance of Records ................................................................................... 29 
11.7 Record Retention .............................................................................................. 29 
11.8 Publications ...................................................................................................... 30 
12 STATISTICAL METHODS AND SAMPLE SIZE ................................................. 30 
12.1 General Overview ............................................................................................ 30 
12.2 Determination of Sample Size.......................................................................... 31 
12.3 Analysis Data Sets ............................................................................................ 32 
12.4 Analyses ........................................................................................................... 32 
12.4.1 Efficacy Analysis .................................................................................... 33 
12.4.2 Additional Analyses ................................................................................ 33 
12.5 Roll-in Procedures ............................................................................................ 33 
12.6 Data Safety Monitoring Board Review ............................................................ 33 
12.7 Subject Disposition .......................................................................................... 34 
12.8 Subject Demographics and Baseline Characteristics ....................................... 34 
12.9 Protocol Deviations .......................................................................................... 34 
12.10 Criteria for DSMB Review ............................................................................ 34 
12.11 Stopping Rules ............................................................................................... 35 
13 ADMINISTRATIVE RULES ................................................................................... 35 

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13.1 Investigators’ Responsibilities ......................................................................... 35 
13.1.1 Confidentiality ......................................................................................... 36 
13.1.2 Protocol Modifications ............................................................................ 36 
13.1.3 Protocol Deviations ................................................................................. 36 
13.1.4 On-Site Audits ......................................................................................... 36 
13.1.5 Institutional Review Board ..................................................................... 37 
13.1.6 Informed Consent .................................................................................... 37 
13.1.7 Investigational Product(s) ....................................................................... 38 
14 REFERENCES .......................................................................................................... 39 
15 APPENDICES ........................................................................................................... 41 
15.1 Investigator Signature ...................................................................................... 41 
15.2 IQPP Standard for Recording Donor Adverse Events ..................................... 42 
 
List of Tables 
Table 1. Summary of Study Parameters ................................................................... 17 
Table 2. IQPP Donor Adverse Event Hypotensive Classification Guide ................ 24 
Table 3 Required Reports from Investigator ............................................................ 26 
Table 44. Required Reports from Investigator ......................................................... 35 
 
 
 
 

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DOCUMENT CHANGE HISTORY 
Version 
Change 
Reason for Change 
2 
Updated number of donations required 
for subgroup analysis. 
The proportion of donors in the subgroups 
(female, young, low-weight) was not what was 
expected. 
 
 
 

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2 ABBREVIATIONS AND DEFINITIONS 
Abbreviation 
Definition 
AE 
adverse event 
ASAP 
as soon as possible 
bpm 
beats per minute 
CAP 
College of American Pathologists 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Act 
CRF 
case report form 
CSP 
Clinical Study Protocol 
CSP ID 
Fresenius Kabi Study Identifier 
CV 
curriculum vitae 
DIS 
Donor Information System 
DAE 
Donor Adverse Event 
DRS 
Donor Reaction System 
dL 
Deciliter 
DSMB 
Data Safety Monitoring Board 
 
 
 
 
EDC 
electronic data capture 
eDQ 
electronic donor questionnaire 
EU 
European Union 
F 
female 
°F 
degrees Fahrenheit 
FDA 
Food and Drug Administration 
FWA 
Federalwide Assurance 
g 
gram 
GCP 
Good Clinical Practice 
HIPAA 
Health Information Portability and Accountability Act 
ICH 
International Council for Harmonization 
ICF 
informed consent form 
IDE 
Investigational Device Exemption 
in 
inch 
IORG 
Institutional Review Board Organization 
IP 
investigational product 
IORG 
IRB Organization 
IQPP 
International Quality Plasma Program 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
lb 
pound 
IRT 
Interactive Response Technology 
LOC 
loss of consciousness 

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Abbreviation 
Definition 
M 
Male 
mL 
Milliliter 
mmHg 
millimeters of Mercury 
SAE 
serious adverse event 
SHAE 
Significant Hypotensive Adverse Event 
SOP 
standard operating procedure 
US 
United States 
 
 
 

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3 BACKGROUND 
The marketed Aurora Xi Plasmapheresis System, comprised of the Aurora Xi Instrument 
(hardware and software) and a Plasmacell Xi Disposable Set, is an automated 
plasmapheresis system intended for routine collection of plasma to be processed as Source 
Plasma. 
The collection of plasma by the Aurora Xi system is an automated procedure with the 
donor connected to the Plasmacell Xi Disposable Set via an apheresis needle set 
throughout the collection process. The collection procedure requires a single venipuncture, 
which means that one access site is used to draw whole blood and return concentrated 
cellular components. The procedure involves sequential cycles of alternating phases: one in 
which blood is drawn and plasma is separated and collected and the other in which residual 
cellular components are returned. Venous pressure is continuously monitored to avoid 
exceeding the flow capacity of the donor’s vein and to maintain comfortable pressures in 
the donor vein. 
The current, three-tiered, weight-based plasma nomogram in the US does not factor in the 
 
 
 
 
 
 
 
 A New Nomogram has been configured for the 
Aurora Xi software (Version 2.0) 
 
than the current Optimized Nomogram three-tier nomogram used with the Aurora Xi 
device. 
 
 
 
 
   
 
 
  
 
 
  
 
 
• 
 
 
 
 
 
 
 
  
 
 
 
 

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3 OBJECTIVE(S) 
 
3.1 Primary Objective 
The primary objective of this study is to demonstrate that the overall rate of significant 
hypotensive adverse events (SHAEs, IQPP DAE Classification 1.2-1.6) in donors using the 
Aurora Xi New Nomogram algorithm is less than double the SHAE rate in donors using 
the Aurora Xi Optimized Nomogram algorithm. 
3.2 Secondary Objectives 
To determine if the incidence rate of SHAEs per donor status (first-time or repeat 
donor) observed with the New Nomogram (Test arm) is non-inferior to the 
incidence rate observed with the Optimized Nomogram (Control arm). 
• 
To determine if the incidence rate of SHAEs for female donors observed with the 
New Nomogram (Test arm) is non-inferior to the incidence rate observed with the 
Optimized Nomogram (Control arm). 
• 
To determine if the incidence rate of SHAEs for donors ≤20 years of age observed 
with the New Nomogram (Test arm) is non-inferior to the incidence rate observed 
with the Optimized Nomogram (Control arm). 
• 
To determine if the incidence rate of SHAEs for donors weighting ≤124 lbs 
observed with the New Nomogram (Test arm) is non-inferior to the incidence rate 
observed with the Optimized Nomogram (Control arm). 
• 
To determine if the incidence rate of hypotensive severe/injury adverse events 
(IQPP DAE Classification 1.5 or 1.6) observed with the New Nomogram (Test 
arm) is non-inferior to the incidence rate observed with the Optimized Nomogram 
(Control arm). 
• 
To determine if the time from start of plasmapheresis procedure to the first SHAE 
observed with the New Nomogram (Test arm) is non-inferior to the time observed 
with the Optimized Nomogram (Control arm). 
 
3.3 Exploratory Objectives 
• 
To compare the plasma volume collected with the New Nomogram (Test arm) 
versus the Optimized Nomogram (Control arm) 
• 
To determine the collection time with the New Nomogram (Test arm) 
4 SCOPE 
This is a multicenter, randomized controlled prospective IDE clinical trial to evaluate the 
safety of the Aurora Xi Plasmapheresis System with New Nomogram compared to a 
Control group undergoing plasmapheresis on the Aurora Xi system using the currently 
marketed Optimized Nomogram. The trial will be conducted at a minimum of 3 BioLife 
plasma donation centers. 

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5 STUDY DESIGN 
5.1 Overview of Study Design 
This study will enroll human subjects in accordance with this protocol, the applicable 
sections of the FDA Code of Federal Regulations (21 CFR Parts 50, 54, 56, 640, and 812), 
the principles of the World Medical Association Declaration of Helsinki (2013 version), 
International Council for Harmonisation (ICH), protection of human subjects in research 
and the execution of good clinical trials, International Organization for Standardization 
(ISO) 14155:2020 Clinical investigation of medical devices for human subjects – Good 
clinical practice, and the privacy regulation of the Health Insurance Portability and 
Accountability Act of 1996 (HIPAA), as it pertains to this study. 
This multicenter, prospective randomized controlled clinical trial is designed to enroll 
donors from at least 3 BioLife plasma donation centers to reach a minimum of 51,720 total 
collection procedures for the primary analysis. Prior to the initiation of study collections, 
there will be a two-week period when individuals may be consented for the study, prior to 
commencing their first on-study procedure. Prior to enrollment, all subjects will be 
required to provide a signed informed consent. Each subject will be randomized prior to 
their first procedure and repeat donors will be retained in their randomized study group 
(Test/Control) throughout their trial participation. Subjects will not be informed to which 
group they have been randomized.   
For the primary endpoint analysis, individuals will be eligible to donate for a maximum of 
8 weeks, a time set to minimize the effect of the date of enrollment on the number of 
possible procedures per participant. It is estimated that the study will enroll approximately 
11,519 subjects, but fewer subjects may be enrolled if the number of procedures per subject 
is greater than the current estimate.  Upon collection of the target number of procedures 
and analyzing the primary endpoint, an optional extension period may commence, during 
which only donors who qualify for one or more high risk subgroup (female, weight ≤124 
lbs, ≤20 years of age and First-Time Donor) will be enrolled and undergo on-study 
collections. Individuals consented prior to the extension period may continue donating 
during this extension if they qualify for one or more of the relevant subgroups. The purpose 
of this extension period would be to generate additional data to support the secondary 
subgroup analysis. Collections during the extension period will not be included in the 
primary endpoint analysis since it represents a period of biased enrollment. After analyzing 
the primary endpoint, an optional extension period may commence, during which only 
donors who qualify for one or more high risk subgroup (female, weight ≤124 lbs, ≤20 
years of age and First-Time Donor) will be enrolled and undergo on-study collections. 
Individuals consented prior to the extension period may continue donating during this 
extension if they qualify for one or more of the relevant subgroups. The purpose of this 
extension period would be to generate additional data to support the secondary endpoint 
subgroup analysis. Collections during the extension period will not be included in the 
primary endpoint analysis since it represents a period of biased enrollment. 
Plasmapheresis subject evaluations will be completed pre-procedure.  Other parameters, 
including adverse events, will be collected during and/or post-procedure (See section 7 - 
Study Procedures/Methodology). 

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Enrollment for the primary endpoint evaluation is anticipated to take approximately 6-9 
months. The optional extension period may take up to an additional 3 months. 
5.2 Subject Selection 
Subjects will be recruited by the site investigator(s) or designee(s), who will discuss details 
of study participation with each potential subject. All recruitment material will be IRB 
approved. Each subject will provide signed informed consent, as approved by the IRB, 
before participating in the study.  In accordance with the clinical site’s SOPs, if a subject is 
unable to provide signed informed consent, his/her legally authorized representative may 
not sign on his or her behalf.  After providing written informed consent, subjects will be 
verbally asked if they consent to continued study participation prior to initiation of all 
subsequent study procedures. After choosing to participate, the subject can withdraw from 
the study at any time without prejudice, penalty or loss of benefits or care that he or she 
would otherwise be entitled.   
All subjects will be assessed for eligibility prior to any possible study procedure using the 
inclusion and exclusion criteria.  
All subject information will be kept confidential in compliance with all applicable state and 
federal laws and regulations.   
5.2.1 Inclusion Criteria 
Potential subjects must satisfy all the following criteria prior to enrollment in the study: 
• All subjects must meet current safety guidelines for frequent plasma donation as set 
forth by the FDA and the study sponsor, as well as those in the standard operating 
procedures established by the participating institution. 
• Currently enrolled subjects who do not meet inclusion criteria at a later donation 
attempt are eligible to remain in the clinical trial and to subsequently donate plasma 
once they meet eligibility criteria again. 
5.2.2 Exclusion Criteria 
Potential subjects must NOT satisfy any of the following criteria prior to enrollment or 
during the study: 
• Subjects not able or unwilling to give consent to participate. 
• Subjects withdrawn due to safety concerns by qualified healthcare provider. 
• Subjects who are employed by the clinical site or Sponsor. 
5.2.3 Subject Enrollment  
Subjects are enrolled/randomized at the time of consent. 
The 8-week donation period begins at the time a subject undergoes venipuncture for their 
first procedure. 

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5.2.4 Subject Donation Status 
First-time donors are defined as donors who have not donated plasma at BioLife within the 
past 6 months.  
Repeat donors are defined as donors who have donated plasma at BioLife within the past 6 
months.  
5.2.5 Subject Withdrawal 
Subjects who are withdrawn from the study, as well as the reason for withdrawal, will be 
recorded on a Subject Withdrawal Log located at the site.   
Possible reasons for withdrawal include but are not limited to: 
• Safety concerns of a qualified healthcare providerwhole blood or platelets outside 
of this clinical trial during the study participation period.If, after enrolling, the 
subject no longer satisfies Inclusion Criteria, meets any Exclusion Criteria, or 
otherwise withdraws from the study, any data from all previous procedures will 
remain in the database and be considered evaluable. However, a study procedure 
will be considered non-evaluable if the participant is found to have donated plasma, 
whole blood or platelet components outside of the study between the time of 
enrollment and that study procedure. 
 
If at any point during the study a subject undergoes a procedure on the incorrect group 
according to their initial assigned study arm, a protocol deviation will be documented, and 
the subject can donate on their assigned study arm for subsequent procedures.  
 
Subjects will not be asked prior to each visit if they want to continue to participate in the 
study. It will be the subject’s responsibility to inform the study staff prior to a study 
procedure if they want to be withdrawn from the study.STUDY 
PROCEDURES/METHODOLOGY 
6.1 Training 
Qualified healthcare professionals and site personnel will be trained before study start, 
including review the Clinical Study Protocol, any conditions imposed by the IRB, and any 
applicable regulatory requirements.  Training will be documented on training forms to 
verify training on the protocol, investigational software, use of case report form, and 
clinical trial conduct.  Duties of all site personnel will be documented on the Site Signature 
Delegation Key.   
Training will cover: 
• Clinical trial objectives 
• Clinical Study Protocol review 
• Personnel Responsibilities  
• Informed Consent requirements and process 
• Case Report Form procedures 

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• Enrollment procedures 
• Protocol deviation procedures 
• AE and SAE Reporting 
• Device Malfunction Reporting 
• Instructions for use (e.g., Operator’s Manual) 
• Device training 
• Good Clinical Practice (GCP) guidelines 
• Regulatory requirements 
 
Change to staff as documented on the Site Signature Delegation Key or addition of new 
personnel will require appropriate training and documentation. 
 
6.2 Lead-In Consenting Period 
Each site will be allowed to begin consenting subjects 2 weeks prior to the first planned 
study procedure at the site. During this lead-in period, plasma donors (first-time and 
repeat) can be presented with the opportunity to consent for this study. Any donors 
consented during this period will be able to continue donating whole blood, platelets, or 
plasma outside the study protocol, until the date that any study collection procedures begin 
at the site, without causing any exclusion criteria to be met. 
In order to minimize potential bias, the Lead-In Consenting Period will be capped at 1,152 
subjects across all study sites and 384 subjects at each of the three planned study sites 
(10% of the estimated total enrollment).  
6.3 Roll-in Procedures 
Roll-in procedures will follow all procedures/methodology detailed in this clinical study 
protocol and will consist of a safety evaluation by the Data Safety Monitoring Board 
(DSMB) after all sites have completed a minimum of 150 collection procedures. 
6.4 Study Procedures 
The Aurora Xi Plasmapheresis System will be operated by qualified operators who have 
been trained on the operation of the system.  The Test group will utilize the Aurora Xi 
Plasmapheresis System with New Nomogram (software version 2.0) and the Control group 
will utilize the Aurora Xi Plasmapheresis System with Optimized Nomogram (software 
version 1.3).  Instructions for apheresis disposable set installation, operation of the Aurora 
Xi system and troubleshooting procedures will be followed as described in the Aurora Xi 
Plasmapheresis System Operator’s Manual, Software Version 1.3 (47-19-16-307) or the 
investigational Aurora Xi Plasmapheresis System Operator’s Manual, Software Version 
2.0 (REC-024378).  
Prior to starting a collection procedure, each subject will be assessed for study eligibility 
(Inclusion and Exclusion Criteria), will be informed about the procedure and, if qualified, 
will be asked to sign an informed consent form (ICF).  Subject height will be measured 
using a stadiometer and a scale will be used to verify weight. Subjects will be randomized 
1:1 to the Test or Control group according to a pre-determined web-based randomization 

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schedule (See Section 7.6). Study arms will be coded as “Group A” or “Group B” within 
the collection center and within the donor information system of the site. Subjects will be 
assigned to the same study group (Test/Control) throughout their participation in the study.  
When a subject is sent to the instrument for donation, 
 
 
 
 
 
  
 
All subjects (Test and Control) will receive 500 mL of saline compensation as part of the 
plasmapheresis procedure as the primary form of re-hydration. (If, under exceptional 
circumstances, saline cannot be administered as part of the automated procedure, plasma 
center policies will be followed). 
Post-procedure, the instrument procedure data will be electronically transferred from the 
device itself into the center’s electronic DIS data capture system via the DXT system. 
Upon completion of the procedure, the subject will schedule their next visit(s).  This will 
ensure that the wait time prior to their next procedure is minimal and aligns with standard 
scheduling practices at BioLife.  The scheduling will account for Group A or Group B to 
manage equal donor flow/wait time). 
  
 
 
 
 
 
   
 
 
    
 
 
 
6.6 Study Evaluations 
6.6.1 Pre-Procedure 
 
 

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If the donor is deferred, based on BioLife standard deferral criteria, the 
date/time and reason will be collected.  
 
 
 
 
During the informed consent process, subjects will be asked to self-declare race and 
ethnicity and if they have donated whole blood, platelets or plasma at any collection center 
(i.e., even if not BioLife) in the past 6 months. Furthermore, prior to each potential study 
procedure, subjects will be asked, via the eDQ (Electronic Donor Questionnaire), if they 
donated whole blood, platelets, or plasma outside of the clinical trial since the last time 
they donated plasma. 
 
6.6.2 During Procedure 
During the procedure, the collection Date, Start and End times, procedure note ID and 
procedure notes will be recorded. All adverse event ID, adverse events, Start date/time, 
End date/time, signs and symptoms, adverse event notes and collected volume at time of 
AE will be collected during the procedure.  The adverse events will be categorized 
according to the definitions outlined in the International Quality Plasma Program (IQPP) 
Standard for Recording Donor Adverse Events. Categories 1.2 to 1.6 Hypotensive 
categorization will only be analyzed for primary objective. The Operator ID at 
Venipuncture, Re-Stick and Disconnect will also be collected. 
6.6.3 Post-Procedure 
 
 If the donor chooses to 
withdraw from the study, the date and reason will be collected.   
Adverse events (ID, category, sub-category, date, time) that occur within 72 hours post-
procedure will be subject-reported and recorded. Subjects may report post-procedure 
adverse events at any time during the study. For a period of 2 weeks after the last study 
collection, any adverse events related to study procedures that are reported to BioLife will 
be included in the study dataset. 
6.6.4 Study Parameters 
Table 1 provides a listing of all the study parameters that will be recorded pre-procedure to 
post-procedure. Additional information, such as the Instrument log files, DXT data files or 
Disposable Set Lot Number, may be reviewed as part of a quality or complaint 
investigation, per standard protocol. 

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6.7 Appropriateness of Measurements 
Employed test measurements are standard for the industry. 
6.8 Study Completion 
The Sponsor considers the study complete 2 weeks after the last procedure is completed at 
all clinical sites. 
6.9 Site Closure 
The Sponsor considers the site closed after the collection of the final data/data clarification 
forms, and the Sponsor has completed the Site Close-out Visit. 
6.10 Discontinuation 
Details of discontinuation of subjects or site(s) may include, but are not limited to: 
• Failure of the investigator to comply with the study protocol, regulatory 
requirements or other study provisions 
• Safety concerns 
• Inadequate study subject enrollment by the investigator 
 
6.11 Study Termination 
Study termination may be decided at any time by the sponsor or site investigator, provided 
there is reasonable cause and/or sufficient notice is given in advance of the intended 
withdrawal. Examples include, but are not limited to: 
• Safety concerns 
• Failure to demonstrate non-inferiority in the primary endpoint analysis 
 
6.12 Collected Plasma 
The plasma collected on both arms of this study will be considered equivalent and 
approved for use as source plasma. BioLife will release Source Plasma for further 
manufacture compliant with 21CFR Chapter I Subchapter F to a manufacturing facility for 
manufacture and distribution of US licensed plasma derived therapies. The plasma and 
downstream products will not be labeled as investigational. 
7 DESCRIPTION OF INVESTIGATIONAL PRODUCT 
7.1 Intended Use 
The intended use of Aurora Xi with the New Nomogram is the same as the currently 
cleared Aurora Xi system: 
The Aurora Xi Plasmapheresis System with investigational Software Version 2.0 is 
intended for the automated collection of plasma by membrane filtration to be processed as 
Source Plasma.  The Aurora Xi system is to be used with a single-use Plasmacell Xi 

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Disposable Set and 4% sodium citrate anticoagulant and allows for Saline and No Saline 
Protocol options.   
7.2 General Description 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 Subjects will be retained in the arm to 
which they were randomized for their first donation throughout the study.  
In order to accommodate the larger collection container, the Test and Control devices will 
include a bag hanger and container shroud specifically designed for the 2000 mL plasma 
collection container, in order to ensure that there is no interference between the larger 
container and the device (power column and/or protective shroud). Both the bag hanger 
and container shroud are cleared for use in the United States. 
 
 
 
 
7.3 Materials and Supplies 
The following investigational products are intended for use in this study: 
• Aurora Xi Plasmapheresis System Investigational Software Version 2.0 with New 
Nomogram Enable Key, FTX 4613 
• Aurora Xi Plasmapheresis System Operator’s Manual, Software Version 2.0, REC-
024378 
• Aurora Xi Plasmapheresis System Administrator’s Guide, Software Version 2.0, 
REC-024379 
Marketed materials may include, but are not limited to: 
• Aurora Xi Plasmapheresis System instrument, Code 6R4612 or 6R4612R 

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• Aurora Xi Plasmapheresis System, Software Version 1.3, Code 6R4612 
• Plasmacell Xi Disposable Set, Code 6R2600 
• Anticoagulant Sodium Citrate Solution, USP 500 mL, Code 4B7889Q or equivalent 
• Sodium Chloride Injection, USP 500 mL, 0.9% Sodium Chloride, Code 6B1275 or 
equivalent 
• Plasmalink Transfer Pack Container, 2000 mL, Code 6R2042 
• Apheresis Needle, with MasterGuard protector, 17 ga (Code 4R2441) 
• Rotated Plasma Collection Hanger (Code 6212599951) 
• Cutback Shroud (Code 61125999949) 
• Software Rev 1.2 Aurora Xi Optimized Nomogram Enable USB (Code 
6112598275) 
 
7.4 Labeling 
The Aurora Xi Plasmapheresis System with investigational software 2.0 will be labeled 
with the following information:  
CAUTION: This device is for Investigational Use Only with Clinical Study 
Protocol PAND-004-CMD. 
Even though the control arm is not investigational, to prevent bias, the Aurora Xi 
Plasmapheresis System with software 1.3 will also be labeled with the following 
information:  
CAUTION: This device is for Investigational Use Only with Clinical Study 
Protocol PAND-004-CMD. 
7.5 Anticipated Changes to the Investigational Product During the Study 
There are no changes anticipated to the investigation product during the study.  
7.6 Method of Assignment to Investigational Product(s) 
Subjects will be randomized 1:1 to the Test group (Aurora Xi Plasmapheresis System with 
New Nomogram) or the Control group (Aurora Xi Plasmapheresis System with Optimized 
Nomogram) by a qualified member of the study staff.  
 
 
 
  Upon completed 
entry of the required randomization parameters, the IRT system will assign the subject into 
either Group A or Group B.  All subjects must meet all eligibility criteria and sign an ICF 
prior to randomization.  Repeat donors will remain in the same study group (Group 
A/Group B) throughout their participation in the clinical trial. 
The block randomization (by subject) scheme will ensure a balanced allocation of subjects 
in each subgroup (Test/Control), and subjects will be randomized within blocks of variable 
size (2, 4, or 8) within strata defined within the site according to the following criteria:  

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Variable block sizes are used to ensure that investigators cannot predict what the next 
assignment will be. 
If at any point during the study a subject undergoes a procedure on the incorrect group 
according to their initial assigned study arm, a protocol deviation will be documented, and 
the subject can donate on their assigned study arm for subsequent procedures.  
If the optional extension period were to occur, previously randomized donors will keep 
their original randomization assignment. Donors who are consented and enrolled during the 
extension period will be randomized 1:1 to test and control, as described above. 
8 BIAS MITIGATION 
Subjects will not be made actively aware to which group they have been randomized.  To 
reduce potential bias, all study instruments will look visibly the same to the subject from 
their viewpoint, although the Test and Control instruments will be segregated from each 
other in each center.  Test and Control groups will be de-identified as either Group A or B 
on center documentation and the device itself.   
The following steps will be taken to help to reduce bias: all devices will be labeled for 
Investigational Use Only with Clinical Study Protocol PAND-004-CMD, and both groups’ 
devices will include a commercially available bag hanger and container shroud designed 
for the larger volumes of saline and storage bags, and collections will be completed using 
2000 mL containers and 500 mL bags of Sodium Citrate. All site documentation for the 
subject will be either Group A or B rather than Test or Control.  Group A or B will also be 
visible in DIS, so staff will be unaware of group type. 
 
 
 The way the operators interact and question regarding AE will 
remain the same for both groups. 
 
 
 
 
 Once all procedures are 
completed, Fresenius Kabi Clinical Affairs group will have access to all data.    
Fresenius Kabi Data Management will have access to all data during the study. Fresenius 
Kabi Data Management will create the Data Management Plan that will provide details 
about the hidden field processes. It will include details on how the hidden data will be 
restricted in the EDC system based on study roles, at what point the hidden data will be 
made available to Clinical Affairs and the Principal Investigator, and procedures if hidden 
fields are incidentally revealed to unauthorized personnel. 

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9 RISK ANALYSIS 
9.1 Risks Associated with Blood Donation  
The typical risks associated with venipuncture and routine blood donation may occur. 
These may include bruising/hematoma formation or skin irritation at the venipuncture site, 
rapid heart rate due to hypovolemia, tiredness, and vasovagal-associated symptoms, such 
as hyperventilation, sweating, weakness, pallor, dizziness/lightheadedness, loss of 
consciousness, nausea, vomiting or convulsions. Although the venipuncture needles are 
sterile and proper aseptic technique will be used, in rare cases infections or inflammation 
of the vein may occur. Rare complications include arterial puncture or peripheral nerve 
injury. 
9.2 Risks Associated with an Apheresis Procedure  
Risks and discomforts that are unique to apheresis procedures may occur. Mild symptoms 
of hypocalcemia, such as finger or perioral discomfort (e.g., tingling), unusual smell or 
taste sensation, vibrations, muscle discomfort and/or headache, or paresthesia (abnormal 
sensation of the skin) may occur temporarily and are caused by citrate in the anticoagulant 
that is returned to the subject more rapidly than the subject can metabolize. Study subjects 
will be monitored for sign/symptoms of hypocalcemia. Adjustments to the procedure or an 
over-the-counter calcium carbonate supplement such as Tums may be given, if any of these 
symptoms occur. Continued rapid administration of citrate anticoagulant may result in 
more severe evidence of citrate toxicity, including tetany, convulsions or, in extremely rare 
occasions, cardiac arrest and death. Other symptoms, although unlikely, may include skin 
redness, itching, hives, bronchospasm (difficulty breathing), and abdominal cramps. 
Other potential risks during apheresis include hemolysis, air embolus, blood loss, or blood 
clotting. Apheresis technology is designed to monitor for the presence of air, hemolysis, 
leaks, or blockage in the disposable kit during the procedure. 
9.3 Risks Associated with Use of the Aurora Xi New Nomogram 
Safety levels for all apheresis-related hazardous situations have been established in 
alignment with currently accepted industry practice and regulations, and these levels have 
been approved through a cross-functional review.  Fresenius Kabi’s documented design 
and development processes include risk management activities that assess the probability 
of these hazardous situations, and risk controls are established to maintain device safety.  
The device is verified to maintain performance within these established safety limits, with 
results of the verification and risk management activities reviewed through a formal cross-
functional design review prior to first human use release.  All changes to the device go 
through the same process of analysis, risk management, verification, and review prior to 
human use.  This process ensures that the original device and all subsequent modifications 
to the device, do not present unacceptable risks to the subject. 
Some subjects may donate more plasma than currently allowed under the established 
plasma volume limit, and the increase in absolute volume collected may increase the 
chance of adverse events. 

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The risk management process has been reviewed and concluded that there are no 
unacceptable risks, and that the benefits of this device outweigh the risks. 
Stated special controls, when combined with general controls (e.g., Good Manufacturing 
Practice), should mitigate any risks associated with the use of Aurora Xi with New 
Nomogram. 
10 SAFETY EVALUATIONS 
10.1 Adverse Events 
Adverse events that occur from venipuncture through 72 hours post-donation will be 
handled initially by the BioLife site’s standard operating procedures. All Adverse Events 
(AEs) will be defined and categorized in accordance with plasma center operating 
procedures, which follow IQPP standards (refer to Appendix 15.2 – IQPP Standard for 
Recording Donor Adverse Events). Initial review and classification of adverse events will 
be done by the BioLife site Center Physician, using their standard procedures. Note that the 
collection volume at the time of an adverse event will be visible to those medical 
reviewers, who may indicate which arm of the study an individual was participating on. 
Therefore, a second, blinded Medical Review will be conducted for all SHAE Events. This 
medical reviewer will be blinded to study arm assignment and volume of plasma collected. 
If there is a discrepancy between the independent Medical Reviewer and the site’s routine 
medical classification, the independent medical review categorization will used for the 
endpoint analysis. 
All AEs that occur and are self-reported by the subject during or after the start of any 
apheresis donation through 72 hours post-donation will be recorded.  The subject will have 
up to 2 weeks post-donation to self-report any AEs that occur through 72 hours post-
donation. 
For the purposes of this study only SHAE Classifications 1.2-1.6, considered significant 
hypertensive adverse events (SHAEs), will be analyzed for the primary objective.  A 
blinded independent Medical Review will be conducted of the SHAE Events categorization 
and sub-categorization. 
Table 2. IQPP Donor Adverse Event Hypotensive Classification Guide 
DAE Classification 
Description 
Signs/Symptoms/Findings 
1.  
Hypotensive (Vasovagal/Hypovolemia) 
Hypotensive reaction (vasovagal/hypovolemia) that falls into any of the following categories. 
 
Note: For the purposes of this IQPP Standard, “medical staff intervention” means the use of expertise from 
the physician or physician substitute to make decisions regarding management of the DAE. 
1.1 Hypotensive: Prefaint, No 
LOC (Minor) 
This reaction: 
- 
Must resolve without 
medical staff (e.g., 
physician substitute) 
intervention, AND 
Involves signs and symptoms that 
resolved quickly (e.g. within 
approximately 10 minutes). 
May include one or more of the 
following: 
a. 
Abdominal cramps; 
b. Auditory disturbance 
(e.g. sounds coming 
from a distance or 
“buzzing” in the ears); 
c. 
Chills or Shivering; 

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DAE Classification 
Description 
Signs/Symptoms/Findings 
d. Clammy; 
e. 
Cold extremities; 
f. 
Dizziness; 
g. Epigastric discomfort; 
h. Facial pallor (e.g. pale 
skin or lips) 
i. 
Feeling of Warmth; 
j. 
Headache or neck ache; 
k. Hypotension; 
l. 
Lightheadedness; 
m. Nausea; 
n. Palpitations; 
o. Sweating; 
p. Visual Disturbance (e.g. 
blurred or faded vision); 
or 
q. Weakness 
1.2 Hypotensive: Prefaint, No 
LOC (Moderate): 
This reaction: 
a. 
Requires medical staff 
(physician substitute) 
intervention, OR 
b. Involves 
signs/symptoms that did 
not resolve quickly (e.g. 
within 10 minutes) OR  
Additional signs/symptoms may 
be present. 
May include any in 1.1 AND 
a. 
Vomiting 
1.3 Hypotensive: LOC (brief) 
In this reaction, LOC lasts 
approximately less than sixty 
seconds. 
May include any in 1.1 or 1.2 
1.4 Hypotensive: LOC 
(prolonged) 
In this reaction, LOC lasts 
approximately sixty seconds or 
longer. 
May include any in 1.1 or 1.2 
1.5 Hypotensive; Severe (With 
or Without LOC) 
This reaction may or may not 
include LOC. 
May include any in 1.1 through 
1.4 AND any of the following: 
a. 
Chest Pain; 
b. Convulsions/Seizures 
c. 
Loss of Bladder/Bowel 
Control; or  
d. Prolonged signs or 
symptoms that do not 
resolve. 
1.6 Hypotensive; Injury 
A hypotensive event that results 
in ANY type of injury such as: 
a. 
Closed Head Injury; 
b. Dental Injury; 
c. 
Fracture; 
d. Laceration; 
e. 
Soft Tissue Injury (not 
phlebotomy-related); or 
f. 
Other 
May include any of 1.1 – 1.5 as 
well as any signs/symptoms 
related to the injury itself. 
NOTE: If the donor exhibits symptoms of a hypotensive event (1.1 through 1.6), in addition to “anxiety,” 
then the event should be classified according to “1.1-1.6 Hypotensive.” 
 

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10.2 Serious Adverse Events 
21 CFR312.32 defines a serious adverse event (SAE) as any AE that results in any of the 
following outcomes: 
• Death 
• Life-Threatening 
• Hospitalization (initial or prolonged) 
• Disability or Permanent Damage 
• Congenital Anomaly/Birth Defect 
• Required Intervention to Prevent Permanent Impairment or Damage (Devices) 
• Other Serious (Important Medical Events) 
 
All SAEs shall be investigated, documented, managed, and reported according to this 
procedure and in compliance with the appropriate regulations and local authorities. 
Prior to the start of the study, the monitor shall: 
• Inform the investigator(s) of the definition of a serious adverse event, and 
• Advise the investigator(s) of the time frame for reporting SAEs to the sponsor and 
their IRB and the regulatory requirements for reporting serious adverse events. 
 
It is expected that the investigator(s) shall report all serious adverse events to the sponsor 
within 24 hours of onset or identification of an event. All UADEs must be reported to the 
IRB within ten working days. All SAEs must be recorded per the Sponsor Serious Adverse 
Event reporting process.  
According to ISO 14155:2020, an Adverse Device Effect (ADE) is an adverse event 
related to the use of an investigational medical device resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation of the 
investigational medical device.  This includes any malfunction of the investigational 
medical device, or any event resulting from user error or intentional misuse of the 
investigational medical device. 
21CFR812.3(s) defines an Unanticipated Adverse Device Effect (UADE) is any serious 
adverse effect on health or safety or any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or death was not previously identified in 
nature, severity, or degree of incidence in the investigational plan or application (including 
a supplementary plan or application), or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects.  
Table 3 Required Reports from Investigator 
Report 
Submit To 
Time 
Withdrawal of IRB approval 
21 CFR 812.150(a)(2) 
Sponsor 
Within 5 working days 
Progress Report(s) 
21 CFR 812.150(a)(3) 
Sponsor, Monitor, IRB 
Regular intervals (at least yearly) 

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Report 
Submit To 
Time 
Deviation from protocol 
21 CFR 812.150(a)(4) 
Sponsor, IRB 
ASAP but no later than 5 working days 
Failure to obtain informed 
consent 
21 CFR 812.105(a)(5) 
Sponsor, IRB 
Within 5 working days 
Final Report 
(Completed Case Report Forms 
constitute a Final Report from 
Investigator) 
21 CFR 812.150(a)(6) 
Sponsor, IRB 
Within 3 months after termination 
Both Serious and Unanticipated 
Adverse Device Effects 
21CFR 812.150(a)(1) 
Sponsor 
ASAP (within 24 hours) by telephone, 
facsimile or email 
IRB 
ASAP, but in no event later than 
10 working days after the investigator 
first learns of the effect. 
 
11 DATA QUALITY ASSURANCE 
11.1 Data Capture System 
The 21 CFR Part 11 compliant Zelta electronic data capture (EDC) system will be utilized 
for this study. Appropriate controls will be in place at each step at which a computerized 
system will be used to create, modify, maintain, archive, retrieve, or transmit source data. 
Technical and procedural controls will be implemented to protect information and personal 
data processed against unauthorized or unlawful access, disclosure, dissemination, 
alteration, or destruction or accidental loss, especially where the processing involves 
transmission over a network.  
11.2 Data Flow 
Fresenius Kabi Data Management will create the Data Management Plan document that 
will specify the procedures and controls followed at every step of the data flow from the 
subject to the study EDC system, including source documentation retention, file type and 
mode of transfer, system requirements, account and access credentials, file protection, 
transfer security, change controls, frequency, data storage and archiving, and reconciliation 
processes.  
Data generated from the Advarra eConsent System, endpoint PULSE IRT System, 
electronic Donor Questionnaire (eDQ) System, Donor Reaction System, Donor 
Information System, and TrackWise System will serve as the primary data sources for the 
clinical trial record; all are 21 CFR Part 11 compliant. Only individuals with documented 
training and authorization will have access to study data.  
The DXT Data Management System will send instrument data to the site’s Donor 
Information System. Information may also be manually entered into the Donor Information 
System by designated and qualified site staff. Information from the Advarra eConsent 
System will be manually entered into the endpoint PULSE IRT System by designated and 
qualified site staff. Designated site staff will export data from the Donor Information 
System, Donor Reaction System, electronic Donor Questionnaire (eDQ) System, and 

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TrackWise System to a secure File Transfer Protocol site. Only Fresenius Kabi Data 
Management and designated and qualified site staff will have access to the secure File 
Transfer Protocol site. Fresenius Kabi Data Management will download the files from the 
secure File Transfer Protocol site onto a Fresenius Kabi closed network location protected 
by password access and appropriate system controls. Only Fresenius Kabi Data 
Management will have access to the network location. Fresenius Kabi Data Management 
will then import the electronic Donor Questionnaire (eDQ), Donor Information System, 
and Donor Reaction System data files directly into the 21 CFR Part 11 compliant Zelta 
EDC System. The TrackWise System data files may be directly imported into the Zelta 
EDC System by Fresenius Kabi Data Management, or manually entered into the Zelta EDC 
System by trained and authorized site personnel. 
Fresenius Kabi Data Management will download data files directly from the endpoint 
PULSE IRT System to a closed network location protected by password access and 
appropriate system controls. Only Fresenius Kabi Data Management will have access to 
the network location. Fresenius Kabi Data Management will then send the endpoint 
PULSE IRT System data files over a closed password-protected network   to designated 
site staff. Fresenius Kabi Data Management will then import the endpoint PULSE IRT 
System data directly into the Zelta EDC system. 
 
 
 
Fresenius Kabi Data Management will have access to all data during the study. Fresenius 
Kabi Data Management will create the Data Management Plan that will provide details 
about the hidden field processes, including how the hidden data will be restricted in the 
Zelta EDC System based on study roles, at what point the hidden data will be made 
available to Fresenius Kabi Clinical Affairs and the Principal Investigator, and procedures 
if hidden fields are incidentally revealed to unauthorized personnel. 
11.3 Data Recording 
All data provided to the study sponsor will be encoded to maintain study subject 
confidentiality. Each data element will be associated with an authorized data originator. 
When data is automatically populated a data element identifier will automatically be 
created to identify and record the originator of the data element. Corrections to data will be 
tracked via an audit trail, and each correction will be identified by the person making the 
change. The time, date, and reason for change will all be recorded. Only those individuals 
who have documented training and authorization will have access to the data. Processes 
and procedures will be established to ensure that backup copies of data are maintained and 
retained for a defined period within a safe and secure location only accessible to authorized 
personnel. 
11.4 Case Report Forms 
All study data will be imported or manually entered into the EDC system by trained and 
authorized personnel. The data import into EDC will be a controlled, validated, secure 
process with supporting documentation created and implemented by Fresenius Kabi Data 
Management. The EDC system will record who entered or generated the data and when it 

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was entered or generated. Modifications and corrections to the data will include who made 
the change, when, and why. Authorized, trained study site personnel will receive a secure 
login and password from the sponsor to manually update study data if needed. Controls 
will be employed to ensure the security and integrity of all authorized users. 
The EDC system will automatically generate data quality queries as data is added. 
Fresenius Kabi clinical monitors, Data Management, or Statistics personnel may also 
generate manual queries as necessary. The study site will need to address each query in a 
timely matter. 
11.5 Monitoring Procedures 
Details will be outlined in the Study Monitoring Plan.  Key risk indicators may include, but 
are not limited to, adverse event reporting, compliance to the protocol, enrollment, and the 
Investigator Site File.  In the event where a particular site is not performing as expected, 
appropriate intervention may be made.  Interventions may include, but are not limited to, 
retraining, site audits, enrollment suspension or site termination.   
Safety monitoring on a real-time basis will be implemented, such that the sponsor, and 
independently the Principal Investigator, will be able to take appropriate steps to manage 
emergent safety signals, e.g., to put on hold or stop the clinical trial in case a safety signal 
is observed. In addition, an external Data Safety Monitoring Board will perform a review 
of the safety data after the roll-in procedures and if a safety event is triggered.  
11.6 Maintenance of Records 
Documents that must be provided to the Sponsor prior to any study Site Initiation include: 
• Medical Device Agreement 
• Financial Disclosure and Arrangements of Clinical Investigator 
• Investigator’s Signed Protocol Signature Sheet 
• Study Site Personnel CVs and Medical Licenses 
• A copy of the IRB-approved informed consent form (ICF) and other adjunctive 
material (e.g., marketing flyers) to be used in the study, including written 
documentation of IRB approval for these materials 
• Name and address of the IRB and a statement/document that attests that it is 
organized and operates according to GCPs and applicable laws and regulations (i.e., 
the FWA number and/or IORG number and/or a list of the IRB's current members) 
11.7 Record Retention 
During or after the study, the appropriate regulatory agency may inspect study records at 
the investigational site. Since inspection may arise at any time, records should be kept 
current at all times. The Sponsor must be advised of any request by a regulatory agency to 
visit or inspect the laboratory. 
Records must be maintained for: 

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• A period of at least 2 years after the last approval of a marketing application in an 
ICH region when there are no pending or contemplated marketing applications in an 
ICH region. 
• A period of at least 2 years after the formal discontinuation of development of the 
investigational product(s). 
 
These documents should be retained for a longer period of time if required by the 
applicable regulatory requirement(s) or if required by the Sponsor. 
11.8 Publications 
The protocol, procedures, and data pertaining to this study will be treated as confidential 
information. Publication of data and/or information derived from these studies must be 
done with the prior review and approval of the Sponsor. Scientific personnel may share 
authorship with investigators on abstracts, oral presentations and manuscripts. The first 
author will be the person assuming primary responsibility for the abstract or manuscript. 
12 STATISTICAL METHODS AND SAMPLE SIZE 
12.1 General Overview 
All of the data will be verified and archived by Fresenius Kabi, USA, Lake Zurich, IL. Any 
change to the data analysis methods described in this protocol will require an amendment 
ONLY if it changes a principal feature of the protocol. Any change to the data analysis 
methods described in the protocol, and the justification for making the change will be 
described in the final study report. 
The primary objective of this study is to demonstrate that the per procedure rate of 
significant hypotensive adverse events (SHAEs) using the Aurora Xi New Nomogram 
algorithm is less than double the SHAE rate under the Aurora Xi Optimized Nomogram 
algorithm.  This is a multi-center randomized controlled trial in which plasma donors at 
three centers will be recruited and randomized in a 1:1 ratio to use the Aurora Xi New 
Nomogram algorithm or the Aurora Xi Optimized Nomogram algorithm. 
Standard summary statistics (e.g., count, mean, standard deviation, minimum, median, and 
maximum values) will be reported for subject and procedure parameters.  
 
One secondary objective is to demonstrate that the per procedure rate of severe 
hypotensive adverse events (IQPP DAE Classification 1.5 or 1.6) under the Aurora Xi New 
Nomogram algorithm is non-inferior to the per procedure severe hypotensive adverse event 
rate using the Aurora Xi Optimized Nomogram algorithm. Analyses will be carried out as 
in the primary analysis with this binary donation-specific response, log-link, identity 
variance function, and working independence assumption. A robust variance estimate will 
be used for inference to provide protection against a within-donor association in responses 
of successive procedures within clusters defined by donor identifying numbers.  
 
The Statistical Analysis Plan will expand on the data analysis to be conducted for the 
remaining endpoints. 

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12.2 Determination of Sample Size 
The sample size requirement is calculated based on a model for correlated binary data in 
which the marginal mean is modelled with a log-link function and set by 
𝑙𝑜𝑔 𝜇𝑖𝑗= 𝛽0 + 𝛽1𝑋𝑖 
where 𝑋𝑖= 1 for an individual assigned to the experimental arm and 𝑋𝑖= 0 otherwise. Note 
that center is not controlled for in the sample size calculation. Controlling for center is 
anticipated to improve power by explaining variation in the response, so this is a 
conservative approach to estimating the sample size since the power is anticipated to be at 
least the desired power. For the sample size derivation, the fitted model uses the identity 
variance function and a working independence assumption with a robust variance derived 
from a joint model to account for the association in the responses from serial donations 
from the same donor. The calculations require specification of the mean µx = E(Yij|Xi = x) 
and the variance Vx = var(Yij|Xi = x) of the response Yij to procedure j from donor i as well 
as the within-donor correlation. If κx and µx is the mean and variance for the number of 
procedures for a donor in arm x and n is the total number of donors to be recruited, then the 
asymptotic (large sample) variance (asvar) of the estimator of the log relative rate satisfies 
𝑎𝑠𝑣𝑎𝑟{√𝑛(𝛽
^
1 −𝛽1)} ≃2𝑉0
𝜅0𝜇0
2 (1 + 𝛿0𝜌
𝜅0
) + 2𝑉1
𝜅1𝜇1
2 (1 + 𝛿1𝜌
𝜅1
) 
where δx = νx + κx2 − κx and ρ is the within-donor correlation in the responses over 
successive procedures from the same donor. The sample size involves computation of an 
asymptotic robust variance estimate for the estimator based on a multivariate binary 
probability mass function with specified marginal event rates of SHAE for the Test and 
Control arms and a specified exchangeable correlation for responses over successive 
procedures within the same donor, using the conditional linear family (Preisser and Qaqish, 
2014) of multivariate binary models. In addition to the response model, a zero-truncated 
negative binomial model is used for the number of donation procedures over time from 
each donor which accommodates between-donor heterogeneity in the procedure rate. The 
number of required donors is computed based on the constraint 
𝑃(𝛽
^
1 + 1.96√𝑎𝑠𝑣𝑎𝑟𝐴(𝛽
^
1) < 𝛽1𝑀|𝛽1 = 𝛽1𝐴) = 0.80 
which ensures that the probability that the upper limit of a two-sided 95% confidence 
interval for the relative risk is below RRM = exp(β1M) = 2 with 80% power if the true log 
relative rate is determined by β1A. Based on historical data, the event rate in the control arm 
is expected to be 0.221% thus setting pC = 0.00221 or equivalently log µ0 = β0 = 
log(0.00221). The margin of non-inferiority is specified as exp(β1M) = 2. To accommodate 
a slight elevation in the SHAE rate under the alternative hypothesis of non-inferiority, the 
sample size calculations will be carried out with exp(β1A) = 1.2, corresponding to a 20% 
relative increase in the SHAE rate (still within the region of non-inferiority). 
Accommodating a slight increase helps ensure that the power objectives are met to 
demonstrate non-inferiority even if there is a 20% relative increase in the SHAE rate using 
the Aurora Xi New Nomogram. In order to achieve 80% power when exp(β1A) equals 1.2, 

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when donations are taken over an 8-week follow-up period, a sample size of n = 11,519 
donors may be required. The total number of procedures across all trial participants of n×κ 
will target 51,720 for the primary endpoint evaluation. 
 
12.3 Analysis Data Sets 
The study endpoints include the primary and secondary objectives. The Intent-to-Treat 
Analysis (All Subjects Enrolled) will consist of individuals who signed an informed 
consent form, were randomized, and had at least one procedure initiated during the study. 
Outcomes for all procedures will be analyzed and responses attributed to the arm to which 
donors were randomized. The Per-Protocol Analysis will restrict attention to procedures in 
which the device used (Test or Control) matched the arm to which the donor was 
randomized. 
The hypothesis for the primary endpoint for the Intent-to-Treat and Per Protocol analyses is 
shown as  
H0 : RR ≥ RRM (inferiority) vs. 
HA : RR < RRM (non-inferiority) 
Summary statistics (mean, standard deviation, median, minimum, maximum and count) 
will be presented for continuous parameters with their 95% confidence limits as applicable. 
Discrete parameters will be presented by total number and percentage.  Summary statistics 
will be presented for continuous parameters or descriptive statistics for discrete parameters. 
12.4 Analyses 
Standard summary statistics (e.g., number, mean, standard deviation, minimum, median, 
and maximum values) will be reported for subject and procedure parameters. Analyses will 
be performed to evaluate the primary objective to demonstrate that the per procedure rate 
of significant hypotensive adverse events (SHAEs) using the Aurora Xi New Nomogram 
algorithm is less than double the rate of SHAE rate under the Aurora Xi Optimized 
Nomogram algorithm in Section 12.2. 
Additional analysis will be performed to demonstrate that the per procedure rate of severe 
hypotensive adverse events (IQPP DAE Classification 1.5 or 1.6) under the Aurora Xi New 
Nomogram algorithm is non-inferior to the per procedure severe hypotensive adverse event 
rate using the Aurora Xi Optimized Nomogram algorithm. Analyses will be carried out as 
in the primary analysis with this binary procedure-specific response, log-link, identity 
variance function, and working independence assumption. A robust variance estimate will 
be used for inference to provide protection against a within-donor association in responses 
of successive procedures with clusters defined by donor identifying numbers. The same 
non-inferiority margin will be used as for the primary response. 
A detailed statistical procedure will be outlined in the Statistical Analysis Plan for the other 
secondary endpoints. 

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12.4.1 Efficacy Analysis 
There are no Efficacy Analysis planned as the purpose of this study is to demonstrate 
safety.  A variety of secondary analyses (described in Section 3.2) will be carried out to 
assess the effectiveness of the Test procedure for the collection of greater volume, etc. 
12.4.2 Additional Analyses 
Once the minimum number of procedures has been achieved for the primary endpoint 
analysis, a review of the data will occur. The primary endpoint will be evaluated based on 
the population/procedures up to this point. If this analysis demonstrates non-inferiority of 
the Test arm relative to the Control (i.e., the primary objective), then a specific analysis of 
subgroup sample sizes will be conducted. If any subgroup targets have not been achieved, 
the sites will be asked to specifically enroll and collect procedures from the target 
subgroup(s) only, until the subgroups in question meet their target minimum number of 
procedures. Each participant can donate for up to 8 weeks. The subgroup analysis will be 
conducted once a sufficient number of procedures for each subgroup is recorded. The 
primary endpoint will not be re-evaluated with the additional collections performed during 
this target enrollment and donation period to ensure that the primary analyses are based on 
a representative sample of donors and procedures. 
12.5 Roll-in Procedures 
Upon completion of the Roll-in procedures at each site (minimum of 150 procedures at 
each clinical site), summary statistics of Adverse Events (category and sub-category) will 
be evaluated by the DSMB.  The summary statistics listing will have the randomization 
category, device serial number, device software version, collection volume at time of 
adverse event, total plasma volume and total collection volume fields hidden from 
reviewers.  If deemed acceptable, the study enrollment will remain unaffected and will 
continue.  Roll-in procedures will be included in the evaluable population. Enrollment will 
not be paused during the safety evaluation.   
12.6 Data Safety Monitoring Board Review 
A Data Safety Monitoring Board (DSMB) may conduct one or more safety analyses based 
on the Criteria for DSMB Review (Section 12.10) to review safety-related data. All 
members of the DSMB will be external to Fresenius Kabi. The DSMB will meet as 
required and will monitor the safety of the trial, according to the DSMB charter. 
The Criteria for DSMB Review will be shared with the DSMB, which will determine, 
based on these or alternative criteria that they may independently develop, the safety of 
continuing with the study. This evaluation will be based on a comprehensive review of the 
available safety information as the clinical trial progresses. The DSMB may have access to 
additional information in its review, e.g., from a requested unblinded data review, that may 
allow them to come to a more informed decision. Their independent assessment will be 
shared with the sponsor team.  

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The DSMB will also review data related to the Criteria for DSMB Review, as defined in 
section 12.10. The DSMB will determine if it is safe to continue the trial or will decide to 
terminate the study. This decision is binding for the sponsor. 
12.7 Subject Disposition 
Subject disposition and reasons for study procedure/drug discontinuation will be 
summarized for inclusion in the final report. 
12.8 Subject Demographics and Baseline Characteristics 
Subject demographics and baseline characteristics will be collected and summarized for 
inclusion in the final report. 
12.9 Protocol Deviations 
A protocol deviation is defined as any change or alteration from the procedure stated in the 
study plan, consent form or clinical trial materials that were originally provided by the 
sponsor and approved by the IRB.  
 
All protocol deviations must be reported to Fresenius Kabi through the TrackWise System 
data files. All deviations, regardless of whether medically justifiable (e.g., the subject’s 
safety), shall be reported. In addition, the qualified healthcare professional is required to 
adhere to the IRB’s reporting requirements for protocol deviations. 
 
Qualified healthcare professionals are required to maintain accurate, complete and current 
records, including documentation showing the dates of, and reasons for, each deviation 
from the protocol. Failure to comply with the protocol may result in qualified healthcare 
professional termination of participation in the clinical trial. 
 
12.10 Criteria for DSMB Review 
In addition to safety monitoring after the roll-in procedures, the following criteria for 
DSMB review will apply for possible study termination due to safety concerns: 
Rule 1: Subject Death 
If at any time during the study there are: 
• One or more subject deaths reported. 
 
Rule 2: Occurrence of Severe Hypotensive Events 
If at any point in the first 50% of planned procedures, there are: 
• 6 or more severe hypotensive events [1.5 (Hypotensive; Severe (With or Without 
LOC)) or 1.6 (Hypotensive; Injury)] of the IQPP definition. 
 
Within 24 hours of sponsor notification, the DSMB will be notified of the event(s) and 
perform an unblinded review of the event(s).  If the event(s) is determined to be related to 

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the Investigational Product and affects the safety profile, the study will be put on hold and 
the information will be transmitted to the FDA immediately.   
If the event(s) is determined not to be related to the Investigational Product and has no 
effect on the safety profile, the study may continue and all DSMB documentation of the 
event(s) and decision will be immediately transmitted to the FDA for further review. 
12.11 Stopping Rules 
After the primary endpoint evaluation period, the extension period, if needed, will end at 
the discretion of the sponsor, when a sufficient sampling of each high-risk subgroup has 
been achieved. Due to potential difficulty recruiting participants from each high-risk 
subgroup, the sponsor reserves the option to stop the study prior to or at any time during 
this optional extension period. 
• If the primary endpoint fails, then the extension phase will not occur. 
• If enrollment during the extension period for any of the subgroups is not sufficient 
to complete the study in a reasonable time period (up to 3 months), then the 
extension period could be stopped at the discretion of the sponsor.  
13 ADMINISTRATIVE RULES 
13.1 Investigators’ Responsibilities 
The study will be conducted in a manner designed to assure the acceptability of the data by 
regulatory authorities. All Investigators, Sub-investigators, and DSMB members are 
required to complete a Disclosure of Financial Interest supplied by the Sponsor. This 
section contains a summary of Investigator responsibilities that will help ensure the study 
is performed in compliance with regulations. Specific mechanisms and procedures are 
described to maintain the compliance of both the Investigator and the Sponsor. 
The PI may delegate tasks to qualified members of the investigation site team but retains 
responsibility for the clinical investigation. This also applies when activities are outsourced 
to an external organization by the Principal Investigator, in which case he/she shall 
implement procedures to ensure the integrity of all tasks performed and any data generated 
by this external organization. 
Certain events in the performance of the study require particular reports from the 
Investigator within prescribed time frames. A summary of the required Investigators' 
reports follows: 
Table 44. Required Reports from Investigator 
Report 
Submit To 
Time 
Withdrawal of IRB approval 
21 CFR 812.150(a)(2) 
Sponsor 
Within 5 working days 
Progress Report(s) 
21 CFR 812.150(a)(3) 
Sponsor, Monitor, IRB 
Regular intervals (at least yearly) 

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Report 
Submit To 
Time 
Deviation from protocol 
21 CFR 812.150(a)(4) 
Sponsor, IRB 
ASAP but no later than 5 working days 
Failure to obtain informed 
consent 
21 CFR 812.105(a)(5) 
Sponsor, IRB 
Within 5 working days 
Final Report 
(Completed Case Report Forms 
constitute a Final Report from 
Investigator) 
21 CFR 812.150(a)(6) 
Sponsor, IRB 
Within 3 months after termination 
Both Serious and Unanticipated 
Adverse Device Effects 
21 CFR 812.150(a)(1) 
Sponsor 
ASAP (within 24 hours) by telephone, 
facsimile or email 
IRB 
ASAP, but in no event later than 
10 working days after the investigator 
first learns of the effect. 
Note: Requirements for Investigator-required reports may vary, depending on local regulatory requirements. 
 
13.1.1 Confidentiality 
The Investigator and his/her staff will agree to treat all aspects of the study in a confidential 
manner. All documents and data pertaining to the study can only be released with the 
consent of the Sponsor or as required by federal or state law or authorized regulatory 
agencies. Each Investigator agrees to permit review of all pertinent data by the Sponsor or 
its agents as well as representatives of the US FDA or other appropriate regulatory 
agencies during and/or following performance of the study. 
13.1.2 Protocol Modifications 
All protocol revisions must be issued by the Sponsor. The investigator will acknowledge 
the change by signing and dating the Investigator Signature Page. Protocol modifications 
should not be implemented prior to any required IRB approval, except where necessary to 
eliminate hazards to subjects when the change(s) involve only logistical or administrative 
details (example: address or telephone change). 
13.1.3 Protocol Deviations 
In situations regarding a departure from the protocol, the investigator will contact the 
appropriate Sponsor representative as soon as possible but no later than 5 working days. 
Notification to the Sponsor should be made prior to implementing a departure from the 
protocol, if at all feasible. In all cases, contact with the Sponsor should be made as soon as 
possible in order to discuss the situation and agree on an appropriate course of action. 
Protocol deviation(s) will be documented and describe any departure from the protocol and 
the circumstances that necessitated the departure. 
13.1.4 On-Site Audits 
The investigator agrees to allow representatives of the sponsor to visit the investigational 
site to carry out an audit of the study in compliance with regulatory guidelines and 
company policy. Such audits will require access to all study records, including source 

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documents, for inspection and comparison with CRFs. Subject privacy will be respected at 
all times and will be in accordance with any local or country-specific requirements. 
Sufficient prior notice will be provided by the sponsor to allow the investigator time to 
prepare for the audit. 
The governing IRB may conduct an on-site audit during the course of the study. The 
investigator should notify the Sponsor if he has been contacted by the IRB regarding an 
audit. 
Similar auditing procedures may be conducted by agents of any regulatory body reviewing 
the results or procedures of this study. The investigator should immediately notify the 
Sponsor if they are contacted by a regulatory agency concerning an inspection. 
13.1.5 Institutional Review Board 
The Investigator will be responsible for obtaining IRB approval for the study and for 
providing the Federalwide Assurance (FWA) and/or Institutional Review Board 
Organization (IORG) number(s) to the Sponsor, as appropriate. All study-related plasma 
facility SOPs and work aids will be submitted to the IRB, as required. After approval of the 
protocol, informed consent form, and any other adjunctive material (e.g., marketing flyers) 
by the IRB, the investigator must provide a copy of the IRB approval document to the 
Sponsor. Copies of these documents are to be maintained at the study site. 
The written notification must be signed by the Chairman of the IRB, or his/her designee, 
and must identify the specific protocol. In cases where an IRB member has a specific 
conflict of interest, abstention of the individual from the vote should be documented. An 
investigator or sub-investigator may be a member of the IRB but may not participate in the 
deliberation or vote on any research in which he/she is involved. 
13.1.6 Informed Consent 
The ICF will be in accordance with the Declaration of Helsinki, principles of GCP, 
applicable regulatory requirements, subject privacy requirements and the Sponsor's 
policies. The ICF must be reviewed by the Sponsor and approved by the IRB.  
Each subject must provide signed informed consent according to local requirements, after 
the nature of the study has been fully explained, in order to participate in the study. The 
ICF must be signed prior to performance of any study-related activity.  
The investigator, or designee, must explain to potential subjects the aims, methods, 
reasonably anticipated benefits, potential hazards and risks of the study, right to refuse 
participation and right to withdraw without affecting the subject's medical care. The other 
elements of the informed consent will be explained, and subjects will be given the 
opportunity to ask questions. After this explanation, but before entry into the study, consent 
should be appropriately documented by the subject's dated signature. If a subject is unable 
to read or requires a translator, an impartial witness must be present during the entire 
informed consent discussion and process. The signature of the impartial witness will certify 

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the subject's consent. The subject will be given a signed and dated copy of the informed 
consent form. 
Subjects will not be asked prior to each visit if they want to continue to participate in the 
study. It will be the subject’s responsibility to inform the study staff prior to a procedure if 
they want to be withdrawn from the study. 
13.1.7 Investigational Product(s) 
Any investigational product (IP) under evaluation must be kept under strict control and 
used only as described in the protocol. The Investigator will be asked to ensure that IP(s) is 
stored and returned/destroyed appropriately and to provide documentation in support of 
this. 
All IP(s) will be labeled according to regulatory requirements. IP(s) must be stored under 
conditions set forth by the Sponsor in this protocol, on the product label, and/or 
communicated in writing. The IP(s) must be installed in a segregated area of the BioLife 
collection centers, which are expected to maintain their standard security protocols and 
access restrictions throughout the duration of the study. BioLife shall establish site-specific 
standard operating procedures that instruct staff to only use study devices (Test and 
Control) for on-study collections.  
If an IP(s) fails to perform in the expected manner, the Investigator will notify the Sponsor 
immediately. 
 
 

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14 REFERENCES 
 Crocco A. and D’Elia D. “Adverse reactions during voluntary donation of blood and/or 
blood components. A statistical-epidemiological study”. Blood Transfusion. 2007 Jul; 
5(3): 143-152. 
 McLeod B.C., et al, “Frequency of Immediate Adverse Effects Associated with 
Apheresis Donation”. Transfusion 38:938-943, 1998. 
 IQPP Qualified Donor Standard, Version 4.0, Plasma Protein Therapeutics Association, 
2014. 
 IQPP Standard for Recording Donor Adverse Events, Version 2.0, Plasma Protein 
Therapeutics Association, 2018. 
 Aurora Xi Plasmapheresis System Operator’s Manual, Software Version 1.3 (47-19-16-
307) 
 Aurora Xi Plasmapheresis System Operator’s Manual, Software Version 2.0, REC-
024378. 
 Aurora Xi Plasmapheresis System Administrator’s Guide, Software Version 2.0, REC-
024379. 
 Effect of the Aurora Xi Maximum Extracorporeal Red Cell Volume Setting on the 
Frequency of Hypotensive Adverse Events, 123-ANA-080291, 2/16/23. 
 Zhu H. Sample size calculation for comparing two Poisson or Negative Binomial rates 
in noninferiority or equivalence trials. Statistics in Biopharmaceutical Research 9:107-
115, 2017. 
 Ahn C, Heo M and Zhang S. Sample Size Calculations for Clustered and Longitudinal 
Outcomes in Clinical Research. New York, NY: Chapman and Hall/CRC, 2014. 
 Lumley T, Kronmal R and Ma S. Relative risk regression in medical research: models, 
contrasts, estimators, and algorithms. University of Washington Biostatistics Working 
Paper Series, 7-19-2006. 
 McCullagh P and Nelder JA. Generalized Linear Models. Routledge, 2019. 
 Preisser JS and Qaqish BF. A comparison of methods for simulating correlated binary 
variables with specified marginal means and correlations. Journal of Statistical 
Computation and Simulation, 84(11), 2441-2452, 2014. 

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 Seaman S, Pavlou M and Copas A. Review of methods for handling confounding by 
cluster and informative cluster size in clustered data. Statistics in Medicine, 33(30), 
5371-5387, 2014. 
 
 
 

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15 APPENDICES 
15.1 Investigator Signature 
INVESTIGATOR SIGNATURE PAGE 
I have reviewed the Clinical Study Protocol PAND-004-CMD, Evaluation of the Aurora Xi 
New Nomogram Software 2.0, Version 2. 
I have fully discussed the objective of this study and the contents of this protocol with the 
Sponsor's representatives. 
I confirm that I have read and understand this protocol. I agree to conduct this study in 
accordance with this protocol, the applicable FDA Code of Federal Regulations (21 CFR 
Parts 50, 54, 56, 640, and 812) and the principles of the World Medical Association 
Declaration of Helsinki (2013 Version), protection of human subjects in research and the 
execution of good clinical trials, the privacy regulation of the Health Insurance Portability 
and Accountability Act of 1996 (45 CFR Parts 160 and 164), any local regulations and 
with the terms outlined in the Study Agreement. 
I will accept the Sponsor's oversight of the study. I have read and understand all related 
information and guides provided by the Sponsor, as applicable. I will abide by the 
publication plan set forth in my agreement with Fresenius Kabi and will promptly submit 
the protocol to the applicable IRB. 
 
 
 
 
 
Principal Investigator (Print Name) 
 
Signature 
 
Date 
 
 
Institution 
 
 
 

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15.2 IQPP Standard for Recording Donor Adverse Events 
 
Embedded PDF 
IQPP_DAERS_V2.pdf
URL 
IQPP Standard for Recording Donor Adverse Events