IMPAACT P1113/Aeras C-015-404
PHASE I/II, SAFETY AND IMMUNOGENICITY STUDY OF A RECOMBINANT
PROTEIN TUBERCULOSIS VACCINE (AERAS-404) IN BCG-PRIMED INFANTS
MANUAL OF PROCEDURES
A Limited Center, International Trial of the
International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT)
Sponsored by:
Aeras
In Collaboration with:
The National Institute of Allergy and Infectious Diseases (NIAID)
And
The Eunice Kennedy Shriver National Institute of Child Health and Human Development
(NICHD)
Pharmaceutical Support Provided by:
Sanofi Pasteur
And
Statens Serum Institut
Version 2.1 Final
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IMPAACT P1113/Aeras C-015-404
Manual of Procedures
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TABLE OF CONTENTS
Page
GLOSSARY ............................................................................................................................... 3
SECTION I:
RESOURCES ...................................................................................................... 6
STUDY MANAGEMENT ................................................................................................. 6
PROTOCOL SPECIFIC WEB PAGE (PSWP) ................................................................ 8
DOCUMENTATION REQUIREMENTS .......................................................................... 8
Essential Documents .......................................................................................... 8
Study-related Information Documents ................................................................. 8
Source Documentation ....................................................................................... 9
SECTION II: DATA MANAGEMENT PROCEDURES ............................................................... 9
INTERACTIVE VOICE RESPONSE SYSTEM (IVRS)/WEB RESPONSE SYSTEM
(IWRS) RANDOMIZATION AND TREATMENT ASSIGNMENT ...................................... 9
ELECTRONIC CASE REPORT FORM (eCRF) .............................................................. 9
SECTION III: STUDY VACCINE ................................................................................................ 9
AERAS-404 AND PLACEBO SHIPMENTS .................................................................... 9
RECEIVING AERAS-404 AND PLACEBO SHIPMENTS ...............................................10
TEMPERATURE DATA LOGGER .................................................................................11
STORAGE AND HANDLING OF AERAS-404 AND PLACEBO .....................................12
REQUIRED STUDY VACCINE ADMINISTRATION MATERIALS..................................13
PREPARATION OF INVESTIGATIONAL PRODUCT (AERAS-404) ............................13
PREPARATION OF CONTROL PRODUCT (PLACEBO) .............................................15
SYRINGE OVERLAY ....................................................................................................16
SYRINGE LABEL ..........................................................................................................18
Three-part syringe label .....................................................................................18
Labelling the syringe for dispensing ...................................................................19
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RECORDS MANAGEMENT ..........................................................................................19
Vaccine Request Form.......................................................................................20
Vaccine Dispensing Log.....................................................................................21
ACCIDENTS OR SPILLS ..............................................................................................21
CONTACT INFORMATION FOR STUDY VACCINE-RELATED ISSUES ......................21
SECTION IV: EXPANDED PROGRAM ON IMMUNIZATION (EPI) VACCINES ...................... 21
SECTION V: CLINICAL PROCEDURES ................................................................................. 22
HOME TEMPERATURE MEASUREMENT METHODOLOGY ......................................22
SUGGESTED ALGORITHM FOR TUBERCULOSIS (TB) CASE EVALUATION ...........23
Clinical evaluation ..............................................................................................23
Diagnostic tests .................................................................................................24
Categorization of Pulmonary TB (PTB) ..............................................................24
SECTION VI: LABORATORY PROCEDURES ........................................................................ 25
GENERAL OVERVIEW AND GUIDELINES ..................................................................25
LABORATORY DATA MANAGEMENT SYSTEM ..........................................................26
REQUIRED LABORATORY ASSAYS ...........................................................................27
SPECIMEN COLLECTION ............................................................................................27
Special Immunology...........................................................................................27
Ribonucleic Acid (RNA) Analysis .......................................................................29
Expanded Program on Immunization (EPI) Vaccine Antibody Titers ..................31
SECTION VII: APPENDICES .................................................................................................... 33
TEMPTALE 4 USB INSTRUCTIONS .............................................................................33
AERAS INVESTIGATIONAL PRODUCT TRANSFER FORM ........................................34
SSI CONTROL OF RECEIPT FORM FOR IMP SHIPPED FROM SSI TO SITE ............36
LOGGER DOCUMENTATION FORM ...........................................................................37
DELIVERY TO SITE COLD CHAIN FORM – PRODUCT RECEIPT VERIFICATION ....38
INVESTIGATIONAL PRODUCT ACCOUNTABILITY LOG ............................................39
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VACCINE REQUEST FORM – FOR STUDY DAY 0 .....................................................40
VACCINE REQUEST FORM – FOR SUCCEEDING STUDY VACCINATIONS .............41
VACCINE DISPENSING LOG .......................................................................................45
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GLOSSARY OF TERMS
Ab / Abs
ACTG
CD4
CDC
CBER
CM
CPM
CRF / eCRF
CRS
CTS
CXR
DAIDS
DTL
EC
ELISA
EPI
EQA
GCP
GLP / GCLP
HANC
HiB
HIV
IATA
IB
ICH
ICL
ICS
ID
Ig
IL
IMPAACT
INF
IP
IRB
IVRS / IWRS
LDMS
LLOQ
LN
LOA
LPC
MOP
MSDS
M.tb. / Mtb
NIAID
NICHD
NIH
Antibody / Antibodies
AIDS Clinical Trials Group
Cluster of Differentiation 4
Centers for Disease Control and Prevention
Center for Biologics Evaluation and Research
Clarification Memo
Counts Per Minute
Case Report Form / Electronic Case Report Form
Clinical Research Site
Clinical Trials Specialist
Chest X-ray
Division of AIDS, NIAID
Data Team Lead (Quintiles)
Ethics Committee
Enzyme-linked Immunosorbent Assay
Expanded Program on Immunization
External Quality Assurance
Good Clinical Practice
Good Laboratory Practice / Good Clinical Laboratory Practice
HIV/AIDS Network Coordination
Haemophilus influenza B
Human Immunodeficiency Virus
International Air Transport Association
Investigator’s Brochure
International Conference on Harmonization
IMPAACT Central Laboratory
Intracellular Cytokine Staining
Identification
Immunoglobulin
Interleukin
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Interferon
Investigational Product
Institutional Review Board
Interactive Voice Response System / Web Response System
Laboratory Data Management System
Lower Limit of Quantitation
Liquid Nitrogen
Letter of Amendment
Laboratory Processing Chart
Manual of Operations
Material Safety Data Sheet
Mycobacterium tuberculosis
National Institute of Allergy and Infectious Diseases
National Institute of Child Health and Human Development
National Institutes of Health
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NL
NTF
PAL
PBMC
PDMC
PI
PRO
PRP
PSWP
PTB
QC
QFT-GIT
RIA
RNA
TNF
SIC
SID
SIP
SIV
SMILE
SOP
SP
SSI
SST
TB
US
WHO
ZN
Network Laboratory
Note-to-File
Protocol Analyte List
Peripheral Blood Mononuclear Cell
Protocol Development and Monitoring Committee
Principal Investigator
Protocol Registration Office
Polyribosylribitol Phosphate
Protocol-Specific Web Page
Pulmonary TB
Quality Control
QuantiFERON TB Gold In-Tube
Radioimmunoassay
Ribonucleic Acid
Tumor Necrosis Factor
Sample Informed Consent
Subject Identification Number
Site Implementation Plan
Site Initiation Visit
(Patient) Safety Monitoring in International Laboratories
Standard Operating Procedure
Sanofi Pasteur
Statens Serum Institut
Serum Separator Tube
Tuberculosis
United States
World Health Organization
Ziehl Neelson
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SECTION I:
RESOURCES
This section specifies the resources available to P1113/C-015-404 Clinical Research Site (CRS)
staff, including contact information, information resources and guidelines.
STUDY MANAGEMENT
All study procedures must be conducted in accordance with the protocol, this manual
and a separate Laboratory Processing Chart (LPC). In the event that this manual is
inconsistent with the protocol, the specifications of the protocol take precedence.
Please alert the P1113/C-015-404 Team (impaact.teamp1113@fstrf.org) of any such
inconsistencies.
For all questions sent to the team (impaact.teamp1113@fstrf.org), the appropriate
team member will respond via email with a “cc” to impaact.teamp1113@fstrf.org. A
response should generally be received within 24 hours (Monday – Friday).
General Questions: All general questions concerning this protocol should be sent via
e-mail to impaact.teamp1113@fstrf.org.
Email Groups: Contact the Clinical Trials Specialist (CTS) by email at
impaact.teamp1113@fstrf.org (include the protocol number in the subject line) to
have relevant personnel at your CRS added to the P1113/C-015-404 site e-mail
group. Inclusion in the site e-mail group will ensure that sites receive important
information throughout the course of the study.
Protocol Registration: Protocol Registration through the Division of AIDS (DAIDS)
Protocol Registration Office (PRO) will NOT be done for this study. Each CRS will
submit the local Ethics Committee (EC)/Institutional Review Board (IRB) approvals
and all essential regulatory documents directly to Aeras through Triclinium. All
regulatory documents will be submitted via email to Janine Strugo
(janine.strugo@triclinium.net) and Chenel Minadoo
(chenel.minadoo@triclinium.net).
Randomization: Randomization will be through an Interactive Voice Response
System/Web Response System (IVRS/IWRS). Refer to Section 2 of this manual for
the IVRS/IWRS instructions. For randomization questions or problems, refer to the
contact information in the IVRS/IWRS User Manual provided by Quintiles/Cenduit.
Treatment Assignment: Treatment will be assigned at the time of randomization
through the IVRS/IWRS. Only the CRS Pharmacist and Back-up Pharmacist
designated by the CRS Principal Investigator (PI) will be unblinded and will keep the
records of treatment assignment. For treatment assignment questions or problems,
refer to the contact information in the IVRS/IWRS User Manual provided by
Quintiles/Cenduit.
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Data Management: Data Management and the electronic case report forms (eCRFs)
will be managed by Quintiles, with oversight provided by the Aeras Manager,
Data Management. Refer to Section 2 of this manual for the eCRF completion
instructions. For non-clinical questions about transfers, inclusion/exclusion criteria,
eCRFs and other data management issues, refer to the contact information for the
Quintiles Data Team Lead (DTL) in the Case Report Form (CRF) Completion
Guidelines provided by Quintiles. Include the protocol number, subject identification
number (SID), and a detailed question when contacting the Quintiles DTL.
Clinical Management Questions: For questions concerning clinical management of
study subjects and adverse experiences contact the protocol team by sending an email message to impaact.teamp1113@fstrf.org. Include the SID in the subject line of
your e-mail and your site number and name in the message area. Also include a
brief relevant history.
Serious Adverse Event (SAE) Reporting/Questions: SAE reporting will be done
through the PPD World Wide Safety Center. Refer to Section 7.0, Appendix IV and
Appendix V of the protocol for more details.
Laboratory: Please refer to the P1113/C-015-404 LPC for detailed instructions
regarding specimen collection, processing, storage and shipment. Method
summaries of the special tests in this study and blood collection procedures are
provided in Section V of this manual. For any laboratory questions, send an e-mail
message to impaact.teamp1113@fstrf.org. Include the SID, when applicable, and a
detailed question.
Protocol Documents: Please refer to the IMPAACT website https://impaactgroup.org/
and the P1113/C-015-404 Protocol Specific Web Page (PSWP) tab for all studyrelated documents and materials.
Investigator Brochure (IB): The IB for the investigational product used for this study
will be provided to each CRS by Aeras. For any questions regarding the IB or
problems receiving it, contact the CTS for this study by email at
impaact.teamp1113@fstrf.org.
Study Drug Orders: The H4 antigen component of AERAS-404 (investigational
product) and the placebo will be provided to each CRS by Sanofi Pasteur (SP). The
IC31 adjuvant component of AERAS-404 will be provided to each CRS by Statens
Serum Institut (SSI). Contact the designated unblinded study monitor and Aeras
Investigational Product (IP) Manager (CSSM@aeras.org) if additional shipment of
the study vaccine (AERAS-404 or placebo) is needed. Refer to Section III of this
manual for study vaccine details, including shipment and contact information for any
issues.
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PROTOCOL SPECIFIC WEB PAGE (PSWP)
A variety of P1113/C-015-404 study-related materials and information can be found
on the PSWP tab in the Member/MIS area of the IMPAACT website:
https://impaactgroup.org/.
Use your individual username and password to enter the Member/MIS area of the
website. Search for the study number. From the protocol [P1113] web page you will
have the option to click the PSWP tab.
Resources available on this site include:
 Protocol summary
 Current version of the protocol, including the Sample Informed Consent (SIC)
form, Notification Memorandum, Note-to-File (NTF) and other official
notifications
 Current study implementation materials, including the Site Implementation Plan
(SIP), Manual of Procedures (MOP) and a Subject Visit and Age Calculator
 Laboratory information, including the Laboratory Processing Chart (LPC)
 Study start-up materials, including slides from the Site Initiation Visit (SIV)
 Expedited Adverse Event Reporting information
 Study Monitoring Reviews/DAIDS Safety Letters
 Other resources
 Training and Quality Management resources and tools
 Protocol historical documents
DOCUMENTATION REQUIREMENTS
Essential Documents
Each CRS must comply with Aeras’ requirements for Essential Regulatory
Documents per the International Conference on Harmonization (ICH) Good
Clinical Practice (GCP) guidelines. In addition to the Essential Regulatory
Documents, modifications made by the investigator to the informed consent
template provided must be reviewed and approved by Aeras before it is
submitted to the local EC/IRB.
Approval for a CRS to begin screening and enrollment into the study will be
issued by Aeras after all Essential Regulatory Documents requirements have
been met. The official notification that a site has been approved for the study will
be sent to the site by the IMPAACT Operations Center.
Study-related Information Documents
Any documents or forms to be provided to the parent or legal guardian of the
subject, and all forms of study advertising, must be reviewed and approved by
Aeras before they are submitted to the local EC/IRB. Approval of the EC/IRB
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must be obtained before the documents are provided to the parent or legal
guardian.
Source Documentation
All sites must comply with the DAIDS policy on Requirements for Source
Documentation in DAIDS Funded and/or Sponsored Clinical Trials. Refer to the
detailed operational guidance provided in Appendix I of this policy, entitled
DAIDS Source Documentation Requirements. Both the policy and the appendix
are located in the Clinical Site section of the DAIDS Policies and Standard
Operating Procedures website:
http://www.niaid.nih.gov/labsandresources/resources/daidsclinrsrch/
SECTION II: DATA MANAGEMENT PROCEDURES
INTERACTIVE VOICE RESPONSE SYSTEM (IVRS)/WEB RESPONSE SYSTEM
(IWRS) RANDOMIZATION AND TREATMENT ASSIGNMENT
Refer to the IVRS/IWRS User Manual provided by Quintiles/Cenduit.
ELECTRONIC CASE REPORT FORM (eCRF)
Refer to the CRF Completion Guidelines provided by Quintiles.
SECTION III: STUDY VACCINE
The investigational product (IP) for this study is AERAS-404. Refer to Section 1.11 of the
protocol for the description of the AERAS-404 vaccine.
AERAS-404 AND PLACEBO SHIPMENTS
Adequate quantities of AERAS-404 (H4 antigen and IC31 adjuvant) and placebo will
be provided by Sanofi Pasteur (SP; in Toronto, Canada) and Statens Serum Institut
(SSI; in Copenhagen, Denmark).
Sanofi Pasteur will provide the AERAS-404 H4 antigen and placebo. SSI will provide
the AERAS-404 IC31 adjuvant.
AERAS-404 will be shipped on dry ice (-65°C or colder) with a temperature
monitoring device. Placebo will be shipped cold (2 to 8°C) with a temperature
monitoring device.
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The Aeras IP Manager will contact the Investigator or a designee in order to
determine the dates and times of delivery of the H4 antigen, IC31 adjuvant and
placebo.
Each vaccine shipment will include a temperature-monitoring device to verify
maintenance of the cold chain during transit (see Section III-C of this manual). On
delivery of the product to the CRS, the CRS pharmacist must follow the instructions
provided in Section III-B, including immediately inspecting all study vaccine for
damage, checking that the cold chain was maintained during shipment (i.e.,
verification of the temperature recorders), and inventory compared to the packing list.
RECEIVING AERAS-404 AND PLACEBO SHIPMENTS
Each CRS will initially receive sufficient supplies of AERAS-404 and placebo to
initiate enrollment. The H4 antigen, IC31 adjuvant and placebo (buffer) will all be
supplied in individual cartons containing 10 vials each. Additional supplies will be
shipped later as they are needed for the study.
AERAS-404 vaccine is shipped frozen on dry ice. Proper precautions must be taken
when handling dry ice.
All shipments must be inspected immediately upon receipt by the CRS Pharmacist
(or designated backup). Please note the exact time that the shipper is opened. This
information will need to be recorded on the confirmation of receipt documentation.

Upon opening the shipper, locate the temperature logger and stop it from
recording by pressing the “Stop” button for 3 to 5 seconds. The temperature
logger can be set aside but will need to be downloaded following the
instructions provided in Appendix A.

Check for damage to the vials and the secondary packaging.

Check the packing slip against the contents of the shipment. Record any
discrepancies and promptly notify the Aeras IP Manager and the unblinded
study monitor.

If there is an indication that the cold chain was broken, the CRS pharmacist
should immediately quarantine the product, alert the Aeras IP Manager and the
designated unblinded study monitor, and request authorization to use the
product.
Immediately transfer the AERAS-404 to a secure, temperature-monitored freezer at
≤ -15C and the Placebo to a secure, temperature-monitored refrigerator at 2 to 8°C.
Complete Section III of the “Aeras Investigational Product Transfer Form” (Appendix
B), the “SSI Control of Receipt Form for IMP Shipped from SSI to Site” form
(Appendix C), the “Logger Received at Site” section of the Logger Documentation
Form (Appendix D) and the Sanofi Pasteur “Delivery to Site Cold Chain Form –
Product Receipt Verification” (Appendix E) to acknowledge receipt of the
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investigational product. Copies of these forms should be returned to the Aeras IP
Manager via e-mail at CSSM@aeras.org upon completion. The originals should be
filed in the Pharmacy Binder.
Complete the Investigational Product Accountability Log (Appendix F) and maintain
this log in the Pharmacy Binder.
NOTE: A separate IP Accountability Log must be completed for each batch/lot of
material received.
TEMPERATURE DATA LOGGER
Each shipment from SP and SSI will contain one TempTale 4 USB monitor. Refer to
Section VI Appendix A for the TempTale 4 USB download instructions.
It is important to note the exact time the shipper was opened and the IP transferred
to the freezer/refrigerator on the appropriate forms. The TempTale 4 ID must also be
recorded on the Aeras IP Transfer form.
The Aeras IP Manager will provide documentation (Section IV of the IP Transfer form
[Appendix B]) notifying you whether the IP is acceptable for use and can be released
from quarantine.
IMPORTANT: Do NOT use the AERAS-404/Placebo until you have received
notification that the IP is acceptable for use.
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STORAGE AND HANDLING OF AERAS-404 AND PLACEBO
All AERAS-404 and Placebo vaccine supplies must be stored in a secure location
with no access for unauthorized personnel. The refrigerators and freezers used to
store study vaccines (AERAS-404 and Placebo) must be equipped with a continuous
temperature monitor (e.g. wheel device) and should be alarmed in case the
temperature deviates from the specified range. Continuous monitoring with the
capacity for data download is preferred. The refrigerator and freezer should be
equipped with back-up power systems.
Any and all deviations from the allowable temperature range must be reported to the
unblinded study monitor immediately. Any product experiencing a temperature
excursion must be held in quarantine and not used until Aeras provides written
notification that the material is acceptable for use. Information about the affected IP
(concentration, lot number, # of vials affected, etc.); the extent of the temperature
excursion (temperature range of excursion, timeframe of excursion, etc.); the
probable cause of the excursion/ any actions taken to correct the temperature
excursion and any actions taken to prevent a similar occurrence in the future should
be provided to your monitor at the time of reporting the incident.
NOTE: Reporting of temperature excursions to your monitor should be done in
addition to your normal site procedures for recording and reporting temperature
excursions.
1. AERAS-404 and Placebo Storage
AERAS-404 (H4 Antigen & IC31 Adjuvant) and Placebo vials must be stored in
the following manner:
a. Store all vials in their original secondary packaging cartons in order to
protect them from exposure to light.
b. Store H4 Antigen and IC31 Adjuvant vials in a freezer at ≤ -15C (≤ 5F).
c. Store Placebo vials in a refrigerator at 2 to 8°C (36 to 46°F).
2. Handling
AERAS-404 should be prepared using aseptic technique in a location separate
from where other parenteral drugs are prepared. Precautions should be taken to
avoid inadvertent inhalation or contact with broken skin or mucosal surfaces.
Gloves and eye protection (safety goggles) should be worn. Reconstitution
under a hood is NOT required. Refer to Sections F and G for the detailed
instructions for the Investigational Product (AERAS-404) and Control Product
(Placebo) preparation.
Clinic staff should wear gloves during administration of the vaccine.
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All equipment and supplies coming in contact with the vaccine, as well as any
unused prepared study vaccine, should be handled and disposed of as
biohazardous waste. Used needles/syringes should be discarded as
biohazardous waste in puncture-proof containers.
REQUIRED STUDY VACCINE ADMINISTRATION MATERIALS
The syringe and needle that will be used for AERAS-404 and placebo administration
is a 1 mL polypropylene Luer-SlipTM syringe and a 25 gauge 16 mm needle.
These materials will not be included with the AERAS-404 and placebo shipments.
The CRS must procure these materials locally.
PREPARATION OF INVESTIGATIONAL PRODUCT (AERAS-404)
Table 1. AERAS-404 Dose Preparation
Cohort
1
2
3A
3B
4
5
6
Dose
Combination
H4/IC31
5 µg H4/
100nmol IC31
5 µg H4/
500nmol IC31
5 µg H4/
500nmol IC31
15 µg H4/
500nmol IC31
15 µg H4/
500nmol IC31
50 µg H4/
500nmol IC31
H4 antigen H4 antigen H4 antigen
50 µg/mL 150 µg/mL 500 µg/mL
0.2 mL
IC31
adjuvant
200nmol
KLK/0.8mL
IC31
adjuvant
1000nmol
KLK/0.8mL
0.8 mL
0.2 mL
0.8 mL
0.2 mL
0.8 mL
0.2 mL
0.8 mL
0.2 mL
0.8 mL
0.2 mL
0.8 mL
Pending
A maximum 2-hour time period is allowed between the time the study vaccine
is reconstituted and the vaccine is administered.
To ensure that the study vaccine has been administered within the 2 hour
timeframe, the CRS Pharmacist (or designee, if appointed) and the CRS
Principal Investigator (or authorized designee) will need to coordinate their
efforts to administer the vaccine soon after it has been drawn into the syringe
and within the 2 hour period.
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Please review the timetable below for the preparation and administration of the
AERAS-404 vaccine.
Time
Vaccine vials
will need 45
minutes to
thaw at room
temperature
Steps
Using aseptic technique, the CRS Pharmacist will prepare
AERAS-404 dose required for the cohort as described below
combining the vials of H4 antigen and IC31 adjuvant as
outlined in Table 1 above. Document the preparation on the
Vaccine Dispensing Log (see Section J).
Remove the appropriate AERAS-404 H4 Antigen vial from the
freezer and the appropriate IC31 vial from the freezer and
allow the vials to thaw at room temperature for 45 minutes
prior to preparation.
The 2 hour
clock starts
when H4 and
IC31 are
mixed
Remove the plastic caps, wipe the tops of the vials with an
alcohol swab and allow to air dry completely.
There is 1.5
hours left to
administer
vaccine
To ensure proper combining of the antigen and adjuvant, the
study vaccine must remain reconstituted in the vial for a
minimum of 30 minutes at room temperature.
Vaccine
administrator
should be
aware that
the vaccine
will soon be
delivered to
clinic to be
administered
Withdraw more than 0.5 mL of the antigen/adjuvant solution
into the appropriate administration syringe (see Section E).
Replace the needle used to withdraw the product from the
vial with a new needle and adjust the volume to 0.5 mL.
Document the time drawn into syringe.
Using a 1 mL syringe, withdraw 0.2 mL of the H4 antigen
solution from the vial and add to the IC31 adjuvant vial. The
adjuvant vial will now contain 1.0 mL of solution. Document
the time of reconstitution.
Place a syringe overlay and label on the syringe (for syringe
overlay and labeling instructions, refer to Section H) and
send the syringe (along with a completed copy of the
appropriate Vaccine Request Form) to the clinic immediately
so it can be administered.
The AERAS-404 vaccine must be maintained at room
temperature during transport from the pharmacy to the clinic.
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The CRS Pharmacist (or designee, if appointed) will:

Ensure the Vaccine Request Form is complete and file the original in
the Pharmacy Binder.

Enter the appropriate information into the Vaccine Dispensing and IP
Accountability Logs maintained in the Pharmacy Binder.
The CRS Principal Investigator or authorized designee will:

Ensure that the date, time and location the vaccine was administered is
documented in the subject’s source document.
PREPARATION OF CONTROL PRODUCT (PLACEBO)
The CRS pharmacist (or designee, if appointed) will prepare the Placebo/buffer
solution as described below and document the preparation on the Vaccine
Dispensing Log (see Section J).
To ensure the study blind, the same 2 hour window for vaccine administration
should be used as noted in the instructions for preparation of AERAS-404 (see
Section F).

Remove one Placebo vial from the refrigerator and allow vial to come to
room temperature for 75 minutes prior to preparation (to maintain blind
it is important to account for the 45 minutes thawing time plus the 30
minutes that the antigen + adjuvant mixture must remain in the vial).

Remove the plastic cap, wipe the top of the vial with an alcohol swab
and allow to air dry completely.

Withdraw more than 0.5 mL of the Placebo solution into the appropriate
administration syringe (see Section E). Replace the needle used to
withdraw the product from the vial with a new needle and adjust the
volume to 0.5 mL. Document the time drawn into syringe.

Place a syringe overlay and label on the syringe (for syringe overlay
and labeling instructions, refer to Section H) and send the syringe
(along with a completed copy of the appropriate Vaccine Request Form)
to the clinic immediately so it can be administered within 2 hours of the
time of preparation (to maintain the blind).

Ensure the appropriate Vaccine Request Form is complete and file the
original in the Pharmacy Binder.

Enter the appropriate information into the Vaccine Dispensing and IP
Accountability Logs maintained in the Pharmacy Binder.
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The CRS Principal Investigator or authorized designee will:

Ensure that the date, time and location the vaccine was administered is
documented in the subject’s source document.
SYRINGE OVERLAY
Each CRS will be provided with an adequate number of clear adhesive labels with
each shipment of AERAS-404 and Placebo. The labels will be used as a syringe
overlay to mask the color of the active vaccine and placebo in the syringe.
The syringe overlay will be applied to the syringe following the instructions outlined
below.
a. Prepare the study vaccine (AERAS-404 or Placebo) and syringe overlay.
b. Peel the overlay from the backing.
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c. Put one edge of the overlay on the syringe.
d. Roll the syringe until the overlay is wrapped completely around the syringe.
e. Masked study vaccine.
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SYRINGE LABEL
Three-part syringe label
The CRS Pharmacist (or designated back-up) must complete a pre-printed
syringe label with the following information at the time of AERAS-404/Placebo
preparation:
a. Subject ID (“SID”)
b. Subject Initials (“Init.”)
c. Date of dose preparation (“Date prepared”)
d. Time when vaccine was drawn into the syringe (“Time in syringe”)
The same information should be recorded on all three portions of the label.
IMPORTANT: Be sure to write legibly using a smudge-resistant, permanent
pen/marker.
Example:
The three portions of the label will be affixed to the following locations:
a. Syringe
b. Vaccine Request Form (Vaccine Request – for Study Day 0 [Appendix G]
OR Vaccine Request – for succeeding study vaccinations in Cohorts 3 to
7 [Appendix H])
c. Vaccine Dispensing Log (Appendix I)
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Labelling the syringe for dispensing
After properly completing the three-part labels, peel and wrap ONLY one part of
the label around the syringe.
Place one label near the plunger end of the barrel, so as not to obscure the fill
line on the syringe. Syringe contents should be visible and should not be hidden
behind the syringe label.
Carefully fold the label around the barrel, so that the ends of the label meet and
the label forms a ‘flag’ surrounding the barrel.
RECORDS MANAGEMENT
All forms pertaining to the study vaccines for protocol IMPAACT P1113/Aeras C-015404 must be retained in the Pharmacy Binder (unless otherwise noted). All records
must be kept current. At the end of the study, the study monitor will provide
instructions pertaining to record retention. A list of the records and completed forms
to be retained include the following:

Investigational Product Accountability Logs (AERAS-404 and Placebo)

Vaccine Request Forms
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
Vaccine Dispensing Logs (AERAS-404 and Placebo)

Shipping records (including shipment receipts, packing slips, IP Transfer forms,
etc.)

Investigational Product End of Study Reconciliation Log

Correspondence related to study vaccine management for IMPAACT P1113 /
Aeras C-015-404
Vaccine Request Form
The second portion of the 3-part label will be affixed to the bottom section of the
Vaccine Request form (Vaccine Request Form – for Study Day 0 [Appendix G] or
the Vaccine Request Form – for succeeding vaccinations in Cohorts 3A to 6
[Appendix H]). A copy of this completed form (with the label attached) must be
returned to the clinic with the vaccine dose. The originals of these documents
should be retained in the Pharmacy Binder.
Example of Vaccine Request Form: (Vaccine Request Form for Study Day 0
sample provided below; please see Appendix H for the samples of the form to be
used for succeeding vaccinations.)
Label #2
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Vaccine Dispensing Log
The final portion of the 3-part label will be affixed to the Vaccine Dispensing Log
(Appendix I). This form should be maintained in the Pharmacy Binder.
Example of Vaccine Dispensing Log:
Label #3
ACCIDENTS OR SPILLS
All equipment and supplies that come in contact with AERAS-404 should be handled
and disposed of as biohazardous waste according to local procedures. In the event
of an accidental exposure to or spill of AERAS-404, refer also to the AERAS-404
Investigator’s Brochure (IB) or the Material Safety Data Sheet (MSDS) included in
the Pharmacy Binder.
CONTACT INFORMATION FOR STUDY VACCINE-RELATED ISSUES
The communication flow instruction for cold-chain disruption during shipment
is provided in Section III-B of this manual. Refer to Protocol Section 5.3 for the
communication flow instructions in the event of accidental thawing and expected or
potential shortage.
For all other study vaccine-related issues, the CRS should contact their designated
unblinded study monitor and the Aeras IP Manager.
SECTION IV: EXPANDED PROGRAM ON IMMUNIZATION (EPI) VACCINES
The EPI vaccines will be handled and administered according to the manufacturer’s
instructions. Refer to Protocol Section 5.0 for protocol specific guidance for the
administration of the EPI vaccines.
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SECTION V: CLINICAL PROCEDURES
This section contains instructions related to clinical evaluation procedures required for the
P1113/C-015-404 study.
HOME TEMPERATURE MEASUREMENT METHODOLOGY
The parent/legal guardian of participants will receive the diary card as well as a
digital thermometer during the first study visit. A good time to instruct the mother on
how to use the thermometer and diary would be during the 60 minutes after the
participant has received the first injection and while the participant is being observed
post vaccination.
The clinical staff member can explain to the parent/legal guardian that the
temperature will be taken under the baby’s armpit and that it is called the axillary
temperature.
The following instruction can be given to the caregiver for an axillary reading:

Turn on the thermometer and make sure the screen is clear of old readings.

Undress the baby from the waist up.

Make sure the baby’s underarm area is dry.

Hold the baby on your lap or next to you, whatever makes you both most
comfortable. Showing the baby a book or toy might help to relax or occupy
him/her.

Slip the bulb of the thermometer into his/her armpit and make sure the tip of the
thermometer is in the middle of the armpit against the bare skin.
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
Hold the thermometer in place with one hand, and keep your baby’s arm
pressed firmly against his/her side or bent and fold across his/her chest.

Remove the thermometer when it beeps or when the time has elapsed as
indicated on the thermometer instruction pamphlet.

Read the temperature as displayed on the screen and write it down on the
diary card.

Dress the child.

Clean the thermometer with soap and cold water, dry and store in container.

Repeat this process for 7 days, starting today.

You must contact the study staff if your baby has a fever during the 7 days after
the injection.
SUGGESTED ALGORITHM FOR TUBERCULOSIS (TB) CASE EVALUATION
The diagnosis of TB presents a challenge in many settings especially in young
children. To standardize the approach to the diagnosis and clinical case definitions
of pulmonary TB between the study sites, the study team recommends the following
algorithm when investigating TB in study participants.
TST should not be used for the evaluation of children who received AERAS-404. The
QuantiFERON TB Gold In-Tube (QFT-GIT) test should be used instead. The
investigational vaccine (AERAS-404) does not interfere with QFT-GIT testing.
TB treatment should follow the local TB program guidelines.
Clinical evaluation
The following history and clinical findings should be elicited. If one or more of the
clinical findings listed here are present the study participant should be evaluated
for TB.
a. History of exposure to a household or non-household contact. A contact
is a person with smear or culture positive TB or a person who is receiving
anti-TB treatment and has not yet completed the course of treatment.
b. Persistent cough for > 2 weeks not responding to treatment.
c. Loss of weight or inability to maintain weight above the 3rd percentile for
age (80% of expected weight for age) using the World Health
Organization (WHO) growth charts.
d. Fever not responding to treatment.
e. Recurrent pneumonia or bronchopneumonia.
f.
General malaise, i.e. lethargy, reduced activity.
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Diagnostic tests
The following evaluations should be performed if one or more symptoms are
present:
a. Chest X-ray (CXR) – AP and lateral
A CXR is suggestive of TB if at least one of the following is present:
 hilar lymphadenopathy,
 paratracheal lymphadenopathy,
 alveolar consolidation,
 miliary pattern,
 lung parenchymal breakdown or cavitation,
 Ghon focus.
b. QFT-GIT test
c. Gastric aspirates or induced sputum on three separate samples should
be sent for TB smear and culture
Categorization of Pulmonary TB (PTB)
a. Option 1

Definite intrathoracic or culture confirmed TB:
Mycobacterium tuberculosis (Mtb) isolated from gastric aspirates,
nasopharyngeal aspirates, sputum, induced sputum or lung tissue.

Probable intrathoracic TB or smear positive TB:
Positive AFB (auramine fluorochrome, most commonly used in
South Africa, or Ziehl Neelson [ZN]) stain on a specimen obtained
by gastric washings or induced sputum in a child who fulfills at least
one of the clinical criteria listed under sub-section 1 (Clinical
Evaluation) above.

Possible pulmonary TB:
An abnormal CXR suggestive of PTB as defined above and at least
one of the clinical criteria listed under sub-section 1 (Clinical
Evaluation) above.

Suspected or clinical TB:
Not fulfilling any of the above criteria but prescribed TB treatment on
clinical suspicion.
b. Option 2
Based on the definitions presented in the article “Evaluation of
Tuberculosis Diagnostics in Children: 1. Proposed Clinical Case
Definitions for Classification of Intrathoracic Tuberculosis Disease.
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Consensus From an Expert Panel”, The Journal of Infectious Diseases
2012, 205:S199-208. The article is intended to provide definitions for use
in research to evaluate diagnostic assays and not assist clinical decision
making.
Table 2
(Adjusted from Intrathoracic Tuberculosis Definitions for Diagnostic Research in Children, JID
2012)
Clinical definition
Confirmed TB
One positive culture with MTB speciation
PLUS
One of the signs and symptoms suggestive of TB
Probable TB
Suggestive CXR
PLUS
One of the signs and symptoms suggestive of TB
PLUS
Clinical response to treatment or documented exposure or
immunological evidence of infection
Possible TB
One of the signs and symptoms suggestive of TB
AND EITHER
Clinical response to treatment or documented exposure or
immunological evidence of infection
OR
Suggestive CXR
TB unlikely
Symptomatic but not fitting the above definitions
SECTION VI: LABORATORY PROCEDURES
This section contains instructions related to laboratory procedures required for the P1113/C015-404 study. Some laboratory procedures will be performed at local laboratories while, for
others, specimens will be shipped to specialty regional or US laboratories.
GENERAL OVERVIEW AND GUIDELINES
Regardless of whether tests are performed in clinic or laboratory settings, study staff
members who collect specimens and perform assays must be trained in proper
testing and associated quality control (QC) procedures prior to performing the tests
for study purposes; training documentation should be available for inspection at any
time.
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Each study site must adhere to standards of good clinical laboratory practice
(GCLP), the IMPAACT and AIDS Clinical Trials Group (ACTG) Network Laboratory
Joint Laboratory Manual and their site-specific Standard Operating Procedures for
proper collection, processing, labeling, and transport of specimens. Transportation
of all specimens must comply with country, federal, state, local and International Air
Transport Association (IATA) specimen shipping regulations.
As transmission of the Human Immunodeficiency Virus (HIV) and other infectious
agents can occur through contact with contaminated needles, blood, blood products,
and genital secretions, all study staff must take appropriate precautions when
collecting and handling biological specimens. Guidance on universal precautions is
available from the US Centers for Disease Control and Prevention (CDC):
http://www.cdc.gov/niosh/topics/bbp/universal.html
Additional laboratory reference information can be found in the joint ACTG-IMPAACT
Laboratory Manual, which is available at:
http://www.hanc.info/labs/labresources/Pages/default.aspx
Storage and shipping must be documented using the Laboratory Data Management
System (LDMS). Ideally one method, test kit, and or combination of test kits will be
used for protocol specified testing throughout the duration of the study. If for any
reason a new or alternative method, kit, or instrument must be used after study
initiation, the site laboratory staff must perform a validation study of the new method
or instrument prior to changing methods. Contact the IMPAACT Central Laboratory
(ICL) at impaact.qaqc@fstrg.org for further guidance on validation requirements.
Similarly, contact the ICL in the event that the local normal range for any protocolspecified test is updated after study initiation.
All laboratories participating in P1113/C-015-404 are required to complete the
Protocol Analyte List (PAL) before study activation. The PAL will be used by the
IMPAACT Network Laboratory (NL), Patient Safety Monitoring in International
Laboratories (SMILE), and DAIDS to assess the laboratory’s capability to: perform
required analytes, identify backup methods/ instruments or laboratories, and ensure
that the laboratory is enrolled in proper External Quality Assurance (EQA) programs.
LABORATORY DATA MANAGEMENT SYSTEM
The LDMS must be used at all sites to track the collection, storage, and shipment of
the various types of laboratory specimens tested at remote laboratories (the
IMPAACT NL or a laboratory off-site). Detailed instructions for use of the LDMS are
available at:
https://www.fstrf.org/apps/cfmx/apps/ldms/manual/manual.html
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REQUIRED LABORATORY ASSAYS
For complete details on the collection, processing and testing of samples refer to the
P1113/C-015-404 LPC.
The P1113/C-015-404 Team has adopted the National Institutes of Health (NIH)
guidelines for infant blood collection limits of 5 mL/kg in a single day and a limit of 9.5
mL/kg in any 8-week period. Refer to the P1113/C-015-404 LPC for the priorities for
the laboratory assays. If the blood volume to be drawn in a small baby will exceed
these limits, contact the P1113/C-015-404 team for specific approaches to prioritizing
the sample collection.
SPECIMEN COLLECTION
Special Immunology
Immunologic evaluation will be conducted to assess both cellular and humoral
immune responses induced by the AERAS-404 vaccine. Blood for Peripheral
Blood Mononuclear Cell (PBMC) and plasma will be collected using the site’s
phlebotomy procedures and processed, stored and shipped as per the P1113/C015-404 LPC.
a. Special Immunology Tests

Cellular assay – Flow cytometry, intracellular cytokine staining (ICS)
Cellular responses will be assessed using multiparameter flow cytometry
on PBMCs collected at multiple time points during the trial. The staining
panel for these assays will likely include IFN-g, IL-2, TNF-a, IL-4, IL-17a,
IL-22 and CD40L; however, the panel may be adjusted to meet current
scientific knowledge at the time assays are conducted. A detailed study
plan will be provided prior to the initiation of assays. Briefly,
cryopreserved PBMC samples will be stimulated for 6 hours with peptide
pools at a final concentration of 1µg/ml. Peptide pools will consist of
15mer peptides overlapping by 11 amino acids covering the protein
sequences in the vaccine immunogen. Primary level positivity will be
assessed based on comparison of sample wells to the negative control
wells. Secondary level positivity will be assessed based on comparison
of pre-vaccination responses to post vaccination responses for each
participant.

Antibody assay – Multiplex binding antibody
Custom multiplex bead arrays (Luminex) will be performed to examine
total binding IgG (IgG1, IgG2, IgG3, IgG4) and IgA antibodies to the
vaccine antigens that will be coupled to carboxylated fluorescent beads.
Plasma samples will be assessed from all study participants taken at
baseline and the primary immunogenicity time points. Specimens from
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the other time points as well as other antigens may also be assayed
based on the results of the initial assay. Antibody measurements will be
acquired on a Bio-Plex instrument (Bio-Rad) and the data will be reported
in mean fluorescence intensity or μg/ml equivalents based on a standard
curve for each detection antibody and/or midpoint titer (5 PL curve fitting).
b. Viable PBMCs
(LDMS Specimen Code = BLD/EDT/CEL/DMS)
Viable cryopreserved PBMCs will be collected, processed and stored
according to the Cross-Network PBMC Processing Standard Operating
Procedure for the isolation and cryopreservation of peripheral blood
mononuclear cells from whole blood at the HIV/AIDS Network Coordination
(HANC) public website and use the specific instructions for IMPAACT labs:
http://www.hanc.info/labs/labresources/Pages/default.aspx

If both cells and plasma are to be retrieved, centrifuge tubes at 400 x g for
10 minutes to separate cells and plasma.

Remove plasma carefully to avoid disturbing the cell layer. Transfer
plasma to a sterile centrifuge tube.
NOTE: If multiple tubes of the same anticoagulant were drawn at the
same time point, plasma should be pooled before storage aliquots are
prepared.
Centrifuge plasma again at ~800 x g for 10 minutes to remove any
contaminating debris, cells and platelets, as described above and store
PL2 aliquots at -70°C or lower.
Viable PBMC Preparation (LDMS Specimen Code: BLD/EDT/CEL/DMS)
1) Only EDTA blood will be used for the preparation of viably preserved
PBMC.
2) Proceed for PBMC retrieval from the original tube using Cross-Network
PBMC Standard Operating Procedure (SOP) on HANC:
https://www.hanc.info/labs/labresources/procedures/Pages/pbmcSop.aspx
3) Viable PBMCs: Store 2 aliquots of viable PBMCs with equal volume
and cell counts in both aliquots. Processing should be completed
as soon as possible (within 8 hours of collection). Consult the
P1113/C-015-404 LPC for processing requirements.
4) Label cryovials with LDMS-derived specimen number, SID, Global Spec
ID, protocol, date of collection, visit code, cell count, and LDMS code
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(BLD/EDT/CEL/DMS). The label should be placed on the tube so that
the contents are visible.
5) Make sure that following are logged in the Specimen Management
Module of LDMS for PBMCs:
 Processing Date
 Processing Time
 Processed by (Tech initials)
 Total Cell Count
 Frozen Time
6) Once processed, place the PBMC vials in a step down freezer, Mr.
Frosty, CoolCell or Stratogene cooler overnight. The next day, transfer
the viable PBMC aliquots to the vapor phase of liquid nitrogen (LN2) or a
-150°C freezer for long-term storage.
Ribonucleic Acid (RNA) Analysis
a. Required blood collection accessories
NOTE: These are NOT included with the PAXgene® Blood RNA Tube.
1) Blood collection set such as the BD Vacutainer® Push Button Blood
Collection Set or the BD Vacutainer®
2) Safety-Lok™ Blood Collection Set
3) A BD Vacutainer® Needle Holder must be used to ensure proper function
4) A "Discard Tube" if the PAXgene® Blood RNA Tube is the only tube
being drawn
5) Labels for positive donor identification of samples
6) Alcohol swab
7) Dry sterile gauze
8) Tourniquet
9) Needle disposal container for used needle or needle/holder combination
b. Blood collection procedure
1) Ensure PAXgene® Blood RNA Tube is at 18oC to 25oC prior to use and
properly labeled with identification.
2) Check the expiration date listed on the label. DO NOT USE IF EXPIRED.
3) The PAXgene® Blood RNA Tube should be the last tube drawn in the
phlebotomy procedure. Blood for safety or other immunology tests
should be drawn prior to blood for PAXgene® RNA. If the PAXgene®
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Blood RNA Tube is the only tube to be drawn, a small amount of blood
should be drawn into a “Discard Tube” prior to drawing blood into the
PAXgene® Blood RNA Tube.
4) Using a blood collection set and a holder, collect blood into the
PAXgene® Blood RNA Tube using your institution’s recommended
phlebotomy procedure. Make sure tube additives do not touch stopper or
end of the needle during venipuncture.
5) Completely fill 2.5mL PAXgene® Blood RNA Tube with blood as shown
below, allowing at least 10 seconds for a complete blood draw to take
place. Ensure that the blood has stopped flowing into the tube before
removing it from the tube holder.
6) Immediately after blood collection, gently invert the PAXgene® Blood
RNA Tube 8-10 times.
7) Store the PAXgene® Blood RNA Tube upright at room temperature (18oC
to 25oC) for a minimum of 2 hours and a maximum of 72 hours before
freezing. Send to your site laboratory for storage.
8) The lab will log this collection in the LDMS. LDMS Specimen code:
BLD/PAX/BLD/NON
NOTE: Refer to the P1113/C-015-404 LPC for the processing/freezing,
storage and shipping procedures.
c. PAXgene® Blood RNA Tube product circular and video clips for collecting
and freezing samples
PAXgene_Blood_RNA
_Tube_Product_Circular v02.pdf
http://www.preanalytix.com/videos/rna-tube-collection-video/
http://www.preanalytix.com/videos/rna-tube-freezing-video/
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Expanded Program on Immunization (EPI) Vaccine Antibody Titers
Antibody titers to Haemophilus influenza B (Hib) conjugate and Tetanus toxoid
vaccines will be assessed from the stored serum. Responses to other EPI
vaccines including measles vaccine may also be assessed.
a. EPI Antibody titers method summary
1) Hib
Anti- Polyribosylribitol Phosphate (PRP) antibodies are measured using a
Farr-type radioimmunoassay (RIA) in which serum samples are incubated
with radiolabeled PRP (3H-PRP) in the presence of 36Cl (volume
marker). Specific antibodies are bound to tritiated capsular
polysaccharide to form antigen-antibody (Ab) complexes. These
complexes are precipitated with ammonium sulfate and collected by
centrifugation. The radioactivity is measured in the precipitated pellet, in
counts per minute (CPM) and is proportional to the amount of anti-PRP
Ab present in the serum sample. The concentration of anti-Hib capsular
polysaccharide Ab in the serum sample is determined from the
concentration response curve generated by the titration results of
dilutions of the reference standard analyzed in the assay. Results are
reported in μg/mL by comparison to the Center for Biologics Evaluation
and Research (CBER), Lot No. 1983 reference standard. The Lower Limit
of Quantitation (LLOQ) of the anti-PRP RIA is 0.06 μg/mL.
2) Tetanus toxoid
Anti-tetanus Abs are measured by Enzyme-linked Immunosorbent Assay
(ELISA). Purified tetanus antigen is adsorbed to the wells of a microtiter
plate. Diluted serum samples (test samples, reference standard, and
quality control) are incubated in the wells. Specific Abs in the serum
samples bind to the immobilized antigen. Unbound antibodies are
washed from the wells, and enzyme-conjugated anti-human Ig (IgG) is
added. The enzyme conjugate binds to the antigen-Ab complex. Excess
conjugate is washed away and a specific colorimetric substrate added.
Bound enzyme catalyzes a hydrolytic reaction, which causes color
development. The intensity of the generated color is proportional to the
amount of specific Ab bound to the wells. The results are read on a
spectrophotometer (ELISA plate reader). A reference standard assayed
on each plate, WHO human standard lot TE3, is used to calculate the
amount of specific anti-tetanus Ab in the unitage assigned by the
reference standard (IU/mL of serum). The LLOQ for the anti-tetanus
ELISA is 0.01 IU/mL.
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b. Blood collection procedure
1) Prior to blood collection, ensure tube and cryovials are properly labeled
with identification.
2) Draw blood for visits as follows:

All blood samples will be collected using your institution’s
recommended procedure. Study personnel must wear protective
gloves while performing blood collection, and respect all safety
precautions.

Use a red top tube with no additives.

Allow the tube to clot by standing it vertically at room temperature for
60 to 120 minutes (no more and no less) prior to centrifuging. DO
NOT SHAKE.

The maximum amount of time the blood should stand at room
temperature in the upright position is 2 hours. If the time between
blood sampling and centrifugation is longer than 2 hours, the
vacutainer should be refrigerated at 2° to 8°C for up to 24 hours from
the initial blood draw time.
NOTE: Refer to the P1113/C-015-404 LPC for the processing, storage
and shipment procedures.
3) All procedures and times must be documented on the source documents.
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SECTION VII: APPENDICES
TEMPTALE 4 USB INSTRUCTIONS
ATTENTION: IMMEDIATE ACTION REQUIRED


Remove TempTale 4 USB monitor from box
Press and hold the red “Stop” button for 3+ seconds until the
STOP icon appears.
o
o



Please store this TempTale 4 USB
temperature logger until you have
received notification that the IP is
acceptable for use from the Aeras IP
Manager.


Icons may not be visible on the face of the dry ice logger. To
ensure the dry ice logger has been stopped, press and hold the
stop button for 5-10 seconds, release then press and hold for
another 5-10 seconds. No change will be visible on the
display.
Set monitor aside and inspect after 3 – 5 minutes. STOP icon
should now be visible.
Place product shipment into cold storage at appropriate
temperature
Pull out the USB connector cable from the side of the logger and
insert the plug into a USB port on the computer. The logger will
automatically begin creating the PDF & TTX data files.
When the LED on the face of the logger glows solid green, the
logger has completed the report and data file generation. The
data is now accessible as a file on a “removable drive”. NOTE:
Do not remove the plug from the USB port on the computer until
the LED on the face of the unit glows solid green.
Drag and drop BOTH the PDF and TTX files into an e-mail
addressed to the Aeras IP Manager (CSSM@aeras.org). Be
sure to attach all the other confirmation of receipt documentation
referenced in SECTION III of the MOP.
Product should NOT be used until you have received notification
that the IP is acceptable for use.
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AERAS INVESTIGATIONAL PRODUCT TRANSFER FORM
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SSI CONTROL OF RECEIPT FORM FOR IMP SHIPPED FROM SSI TO SITE
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LOGGER DOCUMENTATION FORM
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DELIVERY TO SITE COLD CHAIN FORM – PRODUCT RECEIPT VERIFICATION
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INVESTIGATIONAL PRODUCT ACCOUNTABILITY LOG
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VACCINE REQUEST FORM – FOR STUDY DAY 0
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VACCINE REQUEST FORM – FOR SUCCEEDING STUDY VACCINATIONS
41
IMPAACT P1113/Aeras C-015-404
Manual of Procedures
Version 2.1 Final
23 June 2014
42
IMPAACT P1113/Aeras C-015-404
Manual of Procedures
Version 2.1 Final
23 June 2014
43
IMPAACT P1113/Aeras C-015-404
Manual of Procedures
Version 2.1 Final
23 June 2014
44
IMPAACT P1113/Aeras C-015-404
Manual of Procedures
Version 2.1 Final
23 June 2014
VACCINE DISPENSING LOG
45