Document text
Report Amendment 1 for Study 20GR142
PFIZER CONFIDENTIAL
Page 1Final Report Amendment 1
17-DAY INTRAMUSCULAR TOXICITY STUDY OF B NT162B2 (V9) AND
BNT162B3C IN WISTAR HAN RATS WITH A 3 -WEEK RECOVERY
Testing Facility Study Number: 20GR142
Alternative Test Article Identifier(s):
PF-07302048: Generic number for COVID -19 vaccine program
BNT162b2 (V9): BNT162b2 (Version 9); RBP020.2; PF -07305885
BNT162b3c: BNT162b3; RBP020.8; PF -07315256
TESTI NG FACILITY:
Pfizer Worldwide Research & De velopment
Drug Safet y Research & Development
Eastern Point Road
Groton, CT 06340 USA
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Report Amendment 1 for Study 20GR142
PFIZER CONFIDENTIAL
Page 2SIGNATURES
The final report has been amended to clarify and correct the data and/or interpretation of the
results following issuance on 13 Nov 2020.
Study Director
Quality Assurance Statement Signature
The signature for the following individual applies only to the Groton, CT Quality Assurance
Statement contained in this study report.
Regulatory Quality Assurance -Good Laboratory Practices, Pfizer, Groton CT.
For signatures see the Document Approval Record located on the last page of this report
amendment.
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Report Amendment 1 for Study 20GR142
PFIZER CONFIDENTIAL
Page 31. AMENDED TEXT
Section: GL P Compliance Statement
Justification for revision(s): Text is being revised based on feedback from regulatory
authorities to clarify that manufacturing of the test articles was conducted non -GMP but
characterization of the test articles was conducted under GMP conditions, and that serology
analysis was conducted under Good Clinical Laboratory Pract ice (GCLP).
Current:
This study was conducted in compliance with Good L aboratory Practice for Nonclinical
Laboratory Studies regulations as set forth in the Code of Federal Regulations (21 CFR
Part58) with the exceptions of the anal yses of alpha -1 acid g lycoprotein (A1AGP) and
alpha -2-macroglobulin (A2M), and testing performed on the test articles BNT162b2
(Version 9 [V9]) and BNT162b3c which were under non- GLP and non -GMP conditions,
respectivel y. These parameters were conducted under non -GLP and non -GMP conditions and
were performed according to fit- for-purpose methods. These exceptions did not have an
impact on the integrity or data interpretation of the study .
Amended To:
This study was conducted in compliance with Good L aboratory Practice for Nonclin ical
Laboratory Studies regulations as set forth in the Code of Federal Regulations (21 CFR
Part58) with the exceptions of the anal yses of alpha -1 acid gl ycoprotein (A1AGP) and
alpha -2-macroglobulin (A2M) which were under non -GLP conditions. Manufacturing of the
test articles BNT162b2 (Version 9 [V9]) and BNT162b3c was conducted under non -GMP
conditions, while characterization of the test articles was conducted under GMP conditions.
Serology anal ysis was performed in accordance with Good Clinical L aborator y Practice
(GCL P). All parameters that were conducted under non -GLP and non- GMP conditions were
performed according to fit -for-purpose methods. These exceptions did not have an impact on
the integrit y or data interpretation of the stud y.
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Regulatory Quality Assurance
Pfizer Confidential Quality Assurance Statement
Title : 17-DAY INTRAMUSCULAR TOXICITY STUDY OF BNT162B2 (V9) AND
BNT162B3C IN WISTAR HAN RATS WITH A 3 -WEEK RECOVERY
Study : 20GR142
In accordance with Pfizer policies and Regulatory Quality Assurance procedures for
Good Laboratory Practice (GLP), the conduct of this study has been inspected
and/or audited as follows. The Individual Quality Assurance Statement for study
phase(s) c onducted at other site(s) are contained within this report.
Phase Inspected Audit/Inspection Date GMT Reporting Date GMT
Report Amendment 1: 17-Dec-2020 to 17 -Dec-2020 17-Dec-2020
Nonclinical Study
In addition Routine Facility and Process audits are conducted in accordance with
RQA SOPs and Site Monitoring Plans.
Report Amendment 1 for Study 20GR142
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17-DAY INTRAMUSCULAR TOXICITY STUDY OF B NT162B2 (V9) AND
BNT162B3C IN WISTAR HAN RATS WITH A 3 -WE EK RECOVERY
Testing Facility Study Number: 20GR142
Alternative Test Article Identifier(s):
PF-07302048: Generic number for COVID -19 vaccine program
BNT162b2 (V9): BNT162b2 (Version 9); RBP020.2; PF -07305885
BNT162b3c: BNT162b3; RBP020.8; PF -07315256
TESTI NG FACILITY:
Pfizer Worldwide Research & Development
Drug Safet y Research & Development
Eastern Point Road
Groton, CT 06340 USA
Report for Study 20GR142
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SIGNATURES
I approve the report and confirm that the study was conducted in compliance with GL P
regulations with the exceptions noted (see GLP Compliance Statement). My interpretation
and conclusion of the data accuratel y reflects the interpretation of the Contributing Scientists
and Principal Investigators.
Study Director
Quality Assurance Statement Signature
The signature for the following individual applies only to the Groton, CT Quality Assurance
Statement contained in this study report.
Regulatory Quality Assurance -Good Laboratory Practices, Pfizer, Groton CT.
For signatures see the Document Approval Record located on the last page of this report.Report for Study 20GR142
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OTHER STUDY PERSONNE L
The following personnel were involved in the conduct of this study :
Com parative Medicine Activities:
Ophthalmology Examinations:
Study Technician(s):
Study Scientist:
Study Toxicologist:
Test Formulations
Coordinator:
Form ulator:
Clinical Pathology Coordinator:
Necropsy/Histology Coordinator:
Biostatistician:
Safety Biomarkers and Translational Sciences
Scientist:
Principal Investigators:
Serum Antibody Sample Analysis:
Clinical Pathologist:
Anatomic Pathologist:
Peer Review PathologistReport for Study 20GR142
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GLP COMPLIANCE STATE MENT
This study was conducted in compliance with Good L aboratory Practice for Nonclinical
Laboratory Studies regulations as set forth in the Code of Federal Regulations (21 CFR
Part58) with the exceptions of the anal yses of alpha -1 acid gl ycoprotein (A1AGP) and
alpha -2-macroglobulin (A2M), and testing performed on the test articles BNT162b2 (Version
9 [V9]) and BNT162b3c which were under non- GLP and non- GMP conditions , respectivel y.
These parameters were conducted under non -GLP and non- GMP conditions and were
performed according to fit -for-purpose methods. These excep tions did not have an impact on
the integrit y or data interpretation of the stud y.
ANIMAL WELFARE COMPLIANCE
This study was conducted in accordance with the current guidelines for animal welfare
(National Research Council Guide for the Care and Use of Labo ratory Animals, 2011). The
procedures used in this study were reviewed and approved by the Institutional Animal Care
and Use Committee. Report for Study 20GR142
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TABLE OF CONTENTS
SIGNATURES .........................................................................................................................
OTHER STUDY PERSONNEL ..............................................................................................GLP COMPLIANCE STATEMENT ......................................................................................ABSTRACT .............................................................................................................................1. INTRODUCTION AND OBJECTIVE ...............................................................................2. STUDY RATIONALE ........................................................................................................3. MULTI-SITE INFORMATION ..........................................................................................
3.1. Communication Method ..........................................................................................................
3.2. Reporting Method ....................................................................................................................
4. CONTACT INFORMATION .............................................................................................
5. MATERIALS AND METHODS ........................................................................................
5.1. Study Schedule ........................................................................................................................
5.2. Test and Control Articles .........................................................................................................
5.2.1. Test Articles ...................................................................................................................
5.2.1.1. BNT162b2 (V9) ....................................................................................................
5.2.1.2. BNT162b3c ...........................................................................................................
5.2.2. Control Article(s) ...........................................................................................................
5.2.2.1. Vehicle ..................................................................................................................
5.2.3. Test Article Formulation and Analyses ..........................................................................
5.3. Test System ..............................................................................................................................
5.3.1. Acclimation ....................................................................................................................5.3.2. Identification ..................................................................................................................
5.3.3. Allocation and Randomization .....................................................................................
5.4. Housing and Environmental Conditions ................................................................................
5.5. Experimental Groups .............................................................................................................
5.6. Observations and Measurements ...........................................................................................
5.6.1. Clinical Observations/Measurements ...........................................................................5.6.2. Clinical Laboratory Measurements ..............................................................................
5.6.3. Antibody (Serology) Response to Vaccine Components .............................................
5.7. Postmortem Observations ......................................................................................................2
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5.8. Statistical Analysis .................................................................................................................
5.9. Data Acquisition ....................................................................................................................
5.10. Data Management and Archives ..........................................................................................
6. RESULTS ..........................................................................................................................
6.1. Clinical Observations/Measurements ....................................................................................
6.1.1. Mortality .......................................................................................................................6.1.2. Clinical Signs ...............................................................................................................
6.1.3. Body Weight .................................................................................................................
6.1.4. Food Consumption .......................................................................................................
6.1.5. Dermal Assessment ......................................................................................................
Text Table 1. BNT162b2 (V9) Animals with Injection Site Edema Score = 2 ....................
Text Table 2. BNT162b3c Animals with Injection Site Edema Score = 2 ...........................
Text Table 3. BNT162b2 (V9) Animals with Injection Site Edema Score = 2 ....................
Text Table 4. BNT162b3c Animals with Injection Site Edema Score = 2 ...........................
6.1.6. Body Temperature ........................................................................................................
6.1.7. Ophthalmology .............................................................................................................
6.2. Clinical Laboratory Measurements ........................................................................................
6.2.1. Bone Marrow Assessment ............................................................................................
6.3. Antibody (Serology) Analysis ...............................................................................................
6.4. Postmortem Observations ......................................................................................................
7. INTEGRATED SUMMARY AND DISCUSSION OF RESULTS ..................................
8. CONCLUSIONS ................................................................................................................9. REFERENCES ..................................................................................................................TABLES ................................................................................................................................
Table 1. Clinical Signs - Daily Summary Report by Interval .......................................................
Table 2. Ocular Exam Summary Report by Interval ....................................................................
Table 3. Body Weight ...................................................................................................................
Table 4. Body Weight Change During Interval ............................................................................
Table 5. Food Consumption - Empty Feeder During Interval ......................................................
Table 6. Hematology and Coagulation .........................................................................................
Table 7. Clinical Chemistry ..........................................................................................................17
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Table 8. Urinalysis ........................................................................................................................
Table 9. Organ Weights and Ratios Summary ..............................................................................
Table 10. Summary Report of Macroscopic Observations ...........................................................
Table 11. Summary Report of Microscopic Observations ............................................................
Table 12. Dermal Assessment - Dosing ......................................................................................
Table 12. Dermal Assessment - Recovery ..................................................................................
Table 13. Body Temperature ......................................................................................................
APPENDICES .....................................................................................................................
Appendix A. Individual Animal Data .........................................................................................
Appendix 1. Dead Animal Status Report .............................................................................Appendix 2. Clinical Signs - Daily ......................................................................................
Appendix 3. Ocular Exam ....................................................................................................
Appendix 4. Body Weight ....................................................................................................
Appendix 5. Body Weight Change During Interval .............................................................
Appendix 6. Food Consumption - Empty Feeder During Interval .......................................
Appendix 7. Hematology and Coagulation ..........................................................................
Appendix 8. Clinical Chemistry ...........................................................................................
Appendix 9. Urinalysis .........................................................................................................
Appendix 10. Organ Weights and Ratios .............................................................................
Appendix 11. Individual Macroscopic and Microscopic Observations With Correlations ..Appendix 12. Dermal Assessment .......................................................................................
Appendix 13. Body Temperature .........................................................................................
Appendix B. Contributing Scientist Reports ................................................................................
Ophthalmology Report .........................................................................................................
Serum Antibody Report ........................................................................................................
Clinical Pathology Report ....................................................................................................
Anatomic Pathology Report ................................................................................................
Appendix C. Other Supporting Documents ................................................................................
Certificate of Analysis - BNT162b2 ....................................................................................
Certificate of Analysis - BNT162b3c ...................................................................................
Quality Assurance Statement ...............................................................................................87
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ABSTRACT
BNT162b2 (Version 9 [V9]) and BNT162b3c are candidate COVID -19 vaccines, which are
based on a lipid nanopa rticle ( LNP )-RNA platform and express the SARS -CoV -2 spike
protein or its derivatives. The objective of this study was to determine the toxicity and
development of a specific immune response to the antigen in each of the vaccine candidates
following intra muscular (IM) administration once weekl y for a total of 3 doses to Wistar Han
(Crl:WI [Han]) rats. The reversibility of effects was evaluated following a 3 -week recovery
phase.
IM administration of BNT162b2 (V9) and BNT162b3c at 30 µg RNA /dose once weekl y for
a total of 3 doses to Wistar Han rats was tolerated without evidence of s ystemic toxicity and
produced nonadverse inflammatory changes consistent with expected immune responses to
vaccines .
At the conclusion of the dosing phase, test artic le-related immune responses to both vaccines
were evident as transient edema and ery thema at the injection site after each dose, transient
higher mean bod y temperatures compared with controls after each dose, higher white blood
cell count (primaril y involving neutrophils, monocytes and large unstained cells), and
changes in acute phase reactants (higher [alpha -1 acid gl ycoprotein and
alpha -2-macroglobulin and fibrinogen] and lower [lower albumin and albumin:globulin (AG)
ratios] acute phase proteins .These test article -related changes were full y reversed after the
recovery phase, with the exception of higher red cell distribution width, higher globulins, and
lower AG ratio.
Changes secondary to inflammation included lower mean bod y weight, lower mean food
consumption, transiently lower reticulocy te counts, and minor lower red cell mass at the
conclusion of the dosing phase. These changes fully resolved in the recovery phase.
At the conclusion of the dosing phase, nonadverse test article -related microscopic findings
consistent with immune activation and an inflammatory response included mixed cell
inflammation and edema of the injection sites (which correlated with macroscopic
observations of abnormal color, dark/pale and abnormal consistency , firm), increase d
cellularity of plasma cells and germinal centers of the draining and inguinal ly mph nodes
(which correlated with macroscopic observation of abnormal size, enlarged), increased
cellularity of hematopoietic cells and germinal centers of the spleen (which c orrelated with
macroscopic observation of abnormal size, enlarged and increased spleen weights), and
increased cellularit y of hematopoietic cells in the bone marrow were noted. These test
article -related changes fully recovered, except for partial recover y of enlarged draining and
inguinal l ymph nodes and microscopic findings of inflammation at the injection sites,
increased cellularit y of plasma cells and germinal centers in the draining and inguinal l ymph
nodes and increased cellularity of the germinal c enters in the spleen .
In addition, test article -related vacuolation of the periportal hepatocy tes in the liver was
observed, in the absence of biochemical evidence of liver injury, and may be related to
hepatic clearance of PEGylated lipids that are part of the LNP formulation. At the end of the
3-week recovery phase , this finding was completely recovered.Report for Study 20GR142
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Administration of 3 once weekl y doses of BNT162b2 (V9) or BNT162b3c elicited
SARS -CoV -2 neutralizing antibod y responses in both males and females at t he end of the
dosing and recovery phases of the study . SARS -CoV -2 neutralizing antibody responses were
not observed in animals prior to vaccine administration or in saline -administered control
animals.
In conclusion, BNT162b2 (V9) and BNT162b3c administer ed via intramuscular injection
once weekl y for a total of 3 doses to Wistar Han (Crl:WI [Han]) rats was tolerated without
evidence of s ystemic toxicity , generated a SARS -CoV -2 neutralizing antibody response, and
produced nonadverse changes consistent with a n immune or inflammatory response at the
conclusion of the dosing phase. At the end of the 3- week recovery phase, full or partial
recovery of all findings was observed . Other nonadverse findings included vacuolation in the
liver which may be related to h epatic clearance of PEGylated lipids and was noted at the
conclusion of the dosing phase and completely recovered. The findings in this study are
consistent with those ty pically associated with the intramuscular administration of
LNP -encapsulated mRNA vac cines. Animals administered BNT162b2 (V9) or BNT162b3c
elicited SARS -CoV -2 neutralizing antibody responses at the end of the dosing and recovery
phases of the stud y.Report for Study 20GR142
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1.INTRODUCTION AND OBJ ECTIVE
BNT162b2 (Version 9 [V9]) and BNT162b3c are candidate COVID -19 vaccines, which
consist of an LNP -encapsulated RNA encoding the SARS -CoV -2 spike protein or its
derivatives. The objective of this study was to determine the toxicity and development of a
specific immune response to the antigens in each of the vaccine candidates following
administration of intramuscular (IM) doses once weekl y for a total of 3 doses to Wistar Han
(Crl:WI [Han]) rats. The reversibility of effects was evaluated following a 3 -week recovery
phase.
2. STUDY RATIONALE
BNT162b2 (V9) and BNT162b3c were evaluated at the highest intended dose (doses up to
30µg of RNA administered twice) in clinical trials. Therefore, 3 IM administrations of each
vaccine at 30 µg RNA for a total of 3 doses were evaluated in the current study in rats on a
more accelerated schedule (once weekl y) compared to the clinic. The IM route is the clinical
route of administration. The rat is a standard rodent test species for use in toxicity studies
and has been shown to generate an immune response to very similar ty pes of RNA -based
vaccines .
3. MULTI- SITE INFORMATI ON
Microscopic examination was conducted at Pfizer, Pearl River. Evaluation of Clinical
Laboratory parameters was conducted at Pfizer, Pearl River. The anal ysis for detection of
neutralizing antibod y titers (serology ) to wild t ype live SARS -CoV -2 virus was conducted at
VisMederi, Srl (Siena, Italy ).
3.1.Communication Method
The Principal Investigator was responsible for informing the Study Director of any deviations
to the protocol or Standard Operating Procedures (SOPs) and unexpected events as they
occurred during the respective study phase. Other issues were communicated at the end of
the respective study phase prior to the issuance of the report.
3.2.Reporting Method
Clinical Pathology and Anatomic Pathology Principal I nvestigator’s reports are appended to
the final study report. Data and interpretation areintegrated into the final study report. The
Serology Principal Investigator’s report isintegrated and appended to the final study report.
Methods for each phase are described in the SOP of the respective test site.Report for Study 20GR142
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4.CONTACT INFORMATION
Pfizer Lead Quality
Assurance ( QA)a
Pfizer
Regulatory Quality Assurance -Good Laboratory Practices (RQA -GLP)
Eastern Point Road,
Groton CT 06340
Pfizer Test Site QAa
Pfizer
Regulatory Quality Assurance -Good Laboratory Practices (RQA -GLP)
401 N. Middletown Road
Pearl River NY 10965
CRO Test Siteb
CRO = Contract Research Or
a. The Pfizer lead and test site QA monitor edapplicable study phases, audit edthe final study or Principal
Investigator (PI) report(s), and issue dQA statement(s) for work conducted at their respective test sites
according to RQA -GLP SOPs. Lead QA was responsible for coordination to ensure appropriate overall
study monitoring.
b. The CRO test site QA monitor edthe phase, audit edthe CRO Principal Investigator’s report, and issue da
QA Statement according to CRO test site QA SOPs.
5.MATERIALS AND METHOD S
For phases of the stud y conducted at Pfizer Worldwide Research & Development ( Pfizer
WRD), Groton, CT, details of methods described below are included in the Standard
Operating Procedures of P fizer WRD, Groton, CT and in the SOPs of the respective Pfizer
WRD facility conducting those activities.
Minor deviations from the protocol a nd/or current standard operating procedures occurred
and did not affect the quality , integrity or interpretations of the data or the conclusions of the
study . The deviations are documented in the study records and are discussed in the
appropriate section of the report.
5.1.Study Schedule
Study Initiation Date (date protocol signed): 23 Jun 2020
Experimental Start Date (first day of study -speci fic data collection): 24 Jun 2020
First Day of Dosing (Day 1): 06 Jul 2020
First Day of Recovery Phase: 23 Jul 2020
Dosing Phase Necropsy (first 10 animals/sex/group): 22 Jul 2020
Recovery Phase Necropsy (remaining animals): 13 Aug 2020
Experimental Completion Date (last day of study -specific data collection): 13 Aug 2020Report for Study 20GR142
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5.2. Test and Control Articles
5.2.1. Test Articles
5.2.1.1. BNT162b2 (V9)
Test Article Number: BNT162b2 (V9)
Lot Number: COVVAC/270320
Manufacturer: Polymun
Com position 0.5 mg/mL RNA encoding the full SARS -CoV -2 Spike (S) P2 variant protein
Expiration Date: 27 Sep 2020
Storage Conditions: Frozen at -80°C, protected from light
Com position: See Certificate of Analysis in Appendix C .
5.2.1.2. BNT162b3c
Test Article Number: BNT162b3c
Lot Number: BCV/040620
Manufacturer: Polymun
Com position 0.5 mg/mL RNA encoding Membrane -anchored, trimerized variant of the
RBD of the SARS -CoV -2 S protein
Expiration Date: 04 Dec 2020
Storage Conditions: Frozen at -80°C, protected from light
Com position: See Certificate of Analysis in Appendix C .
5.2.2. Control Article(s)
5.2.2.1. Vehicle
A solution of 0.9% sterile saline was used to dose the control animals (Group 1).
Excipient: 0.9% sterile saline
Lot Number: J8L247
Expiration Date: 31 Mar 2021Report for Study 20GR142
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5.2.3. Test Article Formulation and Analyses
Test Article Numbers: BNT162b2 (V9) and BNT162b3c
Type of Formulation: Suspension
Method of Preparation: Thaw ing of frozen formulation
Frequency of Preparation: 06 Jul 2020, 13 Jul 2020, and 20 Jul 2020
Storage: Room temperature, protected from light
Form ulation Handling at Time of Dispensing
for Dosing:Form ulations were gently inverted to mix to ensure
uniformity prior to dose administration
Stability: 2 hours from the time thaw was completeda
Concentration Analyses: Not applicable; material was utilized as supplied
a. Reference: DOSAGE AND ADMINISTRATION INSTRUCTIONS FOR BNT162 (PF -07302048)
VACCINE, 0.5 MG/ML (C459 -INX100407124 -V4.0). NOTE: Although the information in this reference
document is not specific to the test articles utilized in this study, it was for the same platform of vaccines and
was deemed appropriate for use.
5.3.Test System
Species: Rat
Strain/Breed/Origin: Wistar Han (Crl:WI[Han])
Animal Use Protocol (AUP) Number: GTN -2011 -00314
Source: Charles River Laboratories
Raleigh, NC
Age at Dose Initiation: 9 weeks
Weight at Dose Initiation: Males: 243.1 grams -291.6 grams
Females: 172.9 grams -209.5 grams
5.3.1. Acclimation
Animals were acclimated to the laboratory environment for a minimum of 13 day s prior to
initiation of dosing.
5.3.2. Identi fication
Animals were identified by a radio frequency identification device (RFID) implanted by the
vendor (subscapular region) that was associated with a unique identification number for each
animal. Each cage was labeled with a cage card for each animal in the cage.Report for Study 20GR142
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5.3.3. Allocation and Randomization
Clinically acceptable animals were allocated to study groups following the review of data
collected prior to the initiation of dosing and using a computer -assisted randomization
procedure based on bod y weights.
5.4.Housing and Environmental Conditions
Caging: Housed individually in suspended cages
Bedding: Enrich -n’Pure ®, The Andersons, Inc.
Temperature: 68F-79F
Humidity: 30%-70%
Lighting: Approximate 12 -hour light, 12 -hour dark cycle.
Water: Municipal drinking water, further purified by reverse osmosis, w as
provided ad libitum.
Diet: Certified Irradiated Rodent Diet 5002 (PMI Feeds Inc.) w as provided ad
libitum. Lot number(s) are included in the raw data.
There are no known contaminants in the food or water that interfered with the quality or
integrity of the data.
5.5.Experimental Groups
Group
NumberTest Article or Vehicle
Dose (µg RNA/Dose Day)Dose Volume
(µL/injection site)aAnimal Numbers
Males Fem ales
1 0b60 1-15 46-60
2 30c60 16-30 61-75
3 30d60 31-45 76-90
a. Each animal received a single intramuscular injection on each dose day.
b. Sterile saline .
c. BNT162b2 (V9) .
d. BNT162b3c .
Doses were administered by a single intramuscular injection (60 µL) on each dosing day
(Day s 1, 8, and 15) into the left hindlimb quadriceps muscle.
The first 10 animals/sex/group, b y ascending animal order, were designated for necrops y at
the end of the dosing phase. The remaining 5 animals were retained for the recovery phase. Report for Study 20GR142
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5.6.Observations and Measurements
5.6.1. Clinical Observations/Measurements
General (Cageside) Clinical
Observations: Days of Study Time Points
Prior to the Initiation of Dosing
(PID) Once daily
Nondosing Days (Dosing Phase) Twice daily, except on days when detailed
clinical observations were performed, then
only once daily
Dosing Days (Dosing Phase) Predose, except on days that predose
detailed clinical observations were
performed, 4 hours after the last animal
was dosed, and at the end of the w orkday .
On 06 Jul 2020 (Day 1), clinical signs
were not conducted at the end of the
workday for Animals 001 -090.
Recovery Phase Days Twice daily
Detailed Clinical
Observations:Detailed clinical observations were performed twice prior to the initiation of
dosing, twice weekly at approximately the same time body weights were
performed, and on the day(s) of necropsy.
Body Weight: All animals were w eighed twice prior to the initiation of dosing on PID Phase
Days 1 and 6, predose on Dosing Phase Days 1, 8, and 15; on Dosing Phase
Days 4 and 11 (nondosing) , and a fasted w eight wa s collected just prior to
scheduled necropsy . Body weights were collected on Recovery Phase Days 1,
4, 8, 11, 15, 18, and 21.
Food Consumption: Quantitative food consumption was recorded on Dosing Phase Days 4, 8, 11,
and 15 and on Recovery Phase Days 4, 8, 11, 15, 18, and 21 .
Ophthalmology: Ophthalmic examinations were performed once prior to the initiation of dosing
(follow ing randomization) on PID Phase Days 7/8 (males/females) and on
Dosing Phase Days 15/16 (males/females).
Recovery animals were not examined at the end of the recovery phase.
See the Ophthalmology Report in Appendix B for complete materials and
methods.
Injection Site Scoring
(Dermal Assessment):Injection sites were observed during the dosing phase once predose and
approximately 4 and 24 hours postdose on all animals. Animals with a score
of 2 or greater at 24 hours postdose had additional evaluations at 48 and 72
hours postdos e. Animals with a continued score of 2 or greater at 72 hours
postdose had additional evaluations at 120 and 144 hours postdose. After
dosing on Day 15, a 72 -hour postdose evaluation was conducted on recovery
animals only. Injection site score w as recorded according to a standardized
rating scale ( Draize, 1959 ).
On Dosing Phase Day 1 (06 Jul 2020), predose dermal assessments were
collected on all animals for right -side injection sites (noninjection site), and at
4 hours postdose, dermal assessments were collected on Animals 1 -7, 9
(Group 1, Males), and 46 -58 (Group 1, Females) for right -side injection sites
(noninjection site).
Body Tem perature: Body temperature w as collected on all animals once prior to the initiation of
dosing on PID Phase Day 6, predose on Dosing Phase Days 1, 8, and 15, and
at approximately 4 and 24 hours postdose from all animals. Report for Study 20GR142
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5.6.2. Clinical Laboratory Measurements
Schedule for Collection of Sam ples for Clinical Laboratory Measurements
Param eter Day of Study
Dosing Phase Recovery Phase
Day
4Day
17eDay
22
Hem atology Xa,cXcXc
Coagulation NA XcXc
Clinical Chemistry
(Core Chemistry)Xb,cXcXc
Clinical Chemistry
(Other Biomarkers –Acute
Phase Proteins)/SerumdXb,cXcXc
Urinalysis NA X X
NA = Not applicable; X = Scheduled collection.
a.First 7 animals/sex/group.
b. Last 8 animals/sex/group.
c. Blood samples were collected from animals in a fasted state, w ith the exception of same day redraws.
d. Assay performed using shared clinical chemistry sample.
e. Evalua ted on animals scheduled for necropsy.
See the Clinical Pathology Report in Appendix B for complete materials and methods.
5.6.3. Antibody (Serology) Response to Vaccine Components
Sample Collection and Storage Conditions
Groups: 1-3
Collection Intervals: PID Phase Day 8 and Dosing Phase Day 17a, and Recovery Phase Day 21a
Collection Time Points: PID Phase Day 8, Dosing Phase Day 17, and Recovery Phase Day 21 : Once
Animals/Time Point: All animals
Anticoagulant: No anticoagulant
Collection Volume per
Sample: PID Phase Day 8: Approximately 0.7 mL
Dosing Phase Day 17 and Recovery Phase Day 21: Approximately 1 mL
Sample Processing: Samples were processed and stored as appropriate w ithin 2 hours of
collection
Sample Storage Conditi ons: Approximately -60C or low er
PID = Prior to initiation of dosing.
a. Samples collected prior to necropsy.
All samples collected were sent in one shipment after completion of the last blood sample
collection.
Antibody Analysis
Analysis of Samples from Control Animals (Group 1): All samples were analyzed
Analysis of Samples from Animals Administered Test
Article:All samples were analyzed for a neutralizing
antibody response to the antigens in BNT162b2
(V9) and BNT162b3cReport for Study 20GR142
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Incurred Sampl e Reanalysis (ISR)/Project Numbers
Antibody (Serology) Sample Analysis was
conducted under the following Qualified
Method
ID:PFZ_20GR142 -WO4_MN SarsCov2_V2_20200924_GL
See the Serology Report in Appendix B for complete materials and methods.
5.7.Postmortem Observations
Animals (10/sex/group) were euthanized on Dosing Phase Day 17 (2 day s after the last dose).
Remaining animals were euthanized on Recovery Phase Day 22, the last day of the Recovery
Phase (surviving animals).
Necrops y, tissue colle ction, organ weights, macroscopic tissue evaluation, and microscopic
examination were performed.
Bone marrow smears were collected from all animals.
See the Anatomic Pathology Report in Appendix B for complete materials and methods.
5.8.Statistical Analysis
Statistical analy ses of body weight, bod y weight change, and food consumption data were
conducted in Pristima and anal yses of bod y temperature and injection site scores were
conducted b y DSRD Statistics using iStats v1.0 with the methods outlined below. A ll
analyses were performed separately for each sex.
Descriptive statistics were generated for each parameter and group at each scheduled
sampling time or each time interval. Statistical tests were conducted at the 5% and 1%
significance levels.
Analy sesof bod y weight and food consumption parameters were done on measurements
collected for each animal at the scheduled sampling times or time intervals. I n addition,
body weight change at selected intervals was analy zed. Anal ysis of body temperature was
based on the maximum body temperature after injection for each animal. Analy sis of
injection site score was based on the average irritation score after injection for each animal.
A nonparametric (rank -transform) one way anal ysis of variance (ANOVA) on all g roups was
conducted, with two -sided pairwise comparisons of Groups 2 and 3 to Group 1 using
Dunnett's test. Average ranks were assigned to ties.
For statistical anal ysis performed for contributing scientist activities/measurements, see the
corresponding r eport in Appendix B .Report for Study 20GR142
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5.9. Data Acquisition
The following primary computer applications were used for the collection of data.
Computer Application Data Collected/Usage
Pristima Preclinical Data Management Suite
(Version 7.4.3)In-life activities
DVMAX Research Version 3.1.2 Animal health records
Microsoft Excel Sample tracking and antibody immunoassay
result storage. Duplicate titration for each
sample, provided tw o neutralization titers (MNt)
for each sample.
Information was documented according to
VisMederi, Srl Standard Operating Procedures
(WI-MNSARS -CoV -2)arestored in an Excel
sheet (the basic format isprovided in dedicated
VisMederi, Srl procedure).
iStats Version 1.0 Statistical analysis
For data acquisition sy stems and version numbers of each of these s ystems used for
contributing scientist/principal investigator activities/measurements, see the corresponding
report in Appendix B .
5.10. Data Management and Archives
Data Location of Archive
Raw data, documentation, protocol and amendments,
final report, and any specimens generated at the Test
FacilityPfizer, Groton, CT
Raw data and documents electronically archived Pfizer OpenLab archive system or locked and
retained in the source computerize d system, as
defined as per SOP.
Materials are retained in accordance w ith the Enterprise Records Retention Schedule.
Raw data, w orking sheets and any template required by method procedure are archived as hard copies
(original documents) in fireproof archives up to 25 years. Electronic format outputs are regularly backed up
and archived in Microsoft cloud.
6.RESULTS
6.1.Clinical Observations/Measurements
6.1.1. Mortality
Individual animal mortality data are included in Appendix 1 .
There was no unscheduled euthanasia. All animals administered BNT162b2 (V9) or
BNT162b3c survived to scheduled necrops y at the end of the dosing or recovery phase of the
study .
6.1.2. Clinical Signs
An incidence summary of clinical signs is presented in Table 1. Individual animal clinical
signs are included in Appendix 2 .Report for Study 20GR142
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There were no test article -related clinical signs noted for animals administered BNT162b2
(V9) or BNT162b3c during the dosing or recovery phase.
6.1.3. Body Weight
Group mean bod y weight data are presented in Table 3 . Group mean bod y weight change
during interval data are presented in Table 4 . Individual animal body weight data are
included in Appendix 4 . Individual animal bod y weight change during interval data a re
included in Appendix 5 .
Dosing Phase
No test article -related mean body weight changes were noted for animals administered
BNT162b2 (V9) during the dosing phase.
Test article -related lower mean bod y weight (0.93x -0.94x control) was noted in males only
onDays 11 and 15 for BNT162b3c during the dosing phase.
Recovery Phase
Test article -related higher mean body weight (1.05- 1.06x control) was noted in males only on
Recovery Day s 11, 15, 18 and 21 for animals administered BNT162b2 (V9).
No test article re lated body weight changes were noted for animals administered BNT162b3c
during the recovery phase.
Other differences between test article and control group were not test article -related due to
the small magnitude of the change, inconsistent direction of t he difference, and/or
inconsistency of the response.
6.1.4. Food Consumption
Group mean food consumption data are presented in Table 5. Individual animal food
consumption data are included in Appendix 6 .
Dosing Phase
Test article -related lower mean food consump tion (0.83x -0.87x control) was noted on Day s
4 and 11 for animals administered BNT162b2 (V9) during the dosing phase.
Test article -related lower mean food consumption (0.76x -0.92x control) was noted on Day s
4 and 11 for animals administered BNT162b3c duri ng the dosing phase.
Recovery Phase
Test article -related higher mean food consumption (1.08x -1.35x control) was noted
throughout the recovery phase for male animals administered BNT162b2 (V9).
Test article -related higher mean food consumption (1.08x -1.30x control) was noted on
Recovery Phase Day s 4 and 11 for male animals administered BNT162b3c.Report for Study 20GR142
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Other differences between test article and control group were not test article -related due to
the small magnitude of the change, inconsistent direction of the diffe rence, and/or
inconsistency of the response.
6.1.5. Dermal Assessment
Group mean dermal assessment data are included in Table 12. Individual dermal assessment
data are included in Appendix 12 .
Dosing Phase
BNT162b2 (V9) -related injection site edema Grade 2 (s light, edges of area well defined b y
definite raising) or Grade 3 (moderate, raised approximately 1 mm) were noted in all animals
(except Animal 17) , and occurred following dosing on Day s 1, 8 and/or 15 (see Text
Table 1). The edema was generall y observed up to 72 hours postdose, and fully resolved
prior to dose administration on Day s 8 and 15. Ery thema was also observed at the injection
site in all animals (except Animals 16- 21 and 30), following each dose administrati on,
however, it was only a Grade 1 (very slight, barely perceptible) and full y resolved prior to the
next dose administration.
BNT162b3c -related injection site edema Grade 2 (s light, edges of area well defined b y
definite raising) or Grade 3 (moderate, ra ised approximately 1 mm) were noted in all
animals, and occurred following dosing on Day s 1, 8 and/or 15 (see Text Table 2 ). The
edema was generall y observed up to 72 hours postdose, and full y resolved prior to dose
administration on Day s 8 and 15. Ery thema was also observed at the injection site in all
animals (except Animal 39), following each dose administration, however, it was only a
Grade 1 (very slight, barely perceptible) and full y resolved prior to the next dose
administration.
Text Table 1. BNT162b2 (V9) Animals with Injection Site Edema Score 2
Animal Clinical Sign Total Number of Days ( Dosing Phase Study Day of
Occurrence)
16 M Edema, Grade 2 1 (D16: 24 HPD)
18 M Edema, Grade 2 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
19 M Edema, Grade 2 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
20 M Edema, Grade 2 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD; D17:
48 HPD)
21 M Edema, Grade 2 6 (D2: 24 HPD; D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16:
24 HPD; D17: 48 HPD)
22 M Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D11: 72 HPD; D16: 24 HPD; D17:
48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)
23 M Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D11: 72 HPD; D16: 24 HPD; D17:
48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)
24 M Edema, Grade 2 3 (D11: 72 HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)
25 M Edema, Grade 2 3 (D11: 72 HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)Report for Study 20GR142
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Text Table 1. BNT162b2 (V9) Animals with Injection Site Edema Score 2&RQW
G
Animal Clinical Sign Total Number of Days ( Dosing Phase Study Day of
Occurrence)
26 M Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D11: 72 HPD; D16: 24 HPD; D17:
48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)
27 M Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D9: 24 HPD; D10: 48 HPD; D11: 72
HPD)
Edema, Grade 3 2 (D16: 24 HPD; D17: 48 HPD )
28 M Edema, Grade 2 3 (D2: 24 HPD; D3: 48 HPD; D11: 72 HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
29 M Edema, Grade 2 1 (D11: 72 HPD)
Edema, Grade 3 2 (D 9: 24 HPD; D10: 48 HPD)
30 M Edema, Grade 2 5 (D9: 24 HPD; D10 : 48 HPD; D11: 72 HPD; D16: 24 HPD; D17:
48 HPD)
61 F Edema, Grade 2 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD; D17:
48 HPD)
62 F Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7: 144
HPD)
Edema, Grade 3 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD; D17:
48 HPD)
63 F Edema, Grade 2 8 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7: 144
HPD; D9: 24 HPD; D10: 48 HPD; D11: 72 HPD)
Edema, Grade 3 2 (D16: 24 HPD; D17: 48 HPD)
64 F Edema, Grade 2 9 (D2: 24 HPD ; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7: 144
HPD; D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D17: 48 HPD)
Edema, Grade 3 1 (D16: 24 HPD)
65 F Edema, Grade 2 2 (D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 3 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD)
66 F Edema, Grade 2 6 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7: 144
HPD; D11: 72 HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
67 F Edema, Grade 2 6 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120, D7: 144;
D17: 48 HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD)
68 F Edema, Grade 2 2 (D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 3 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD)
69 F Edema, Grade 2 8 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7 : 144
HPD; D9: 24 HPD; D10: 48 HPD; D17: 48 HPD)
Edema, Grade 3 1 (D16: 24 HPD)
70 F Edema, Grade 2 2 (D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 3 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD)
71 F Edema, Grade 3 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16 : 24 HPD; D17:
48 HPD)
72 F Edema, Grade 2 6 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7: 144
HPD; D11: 72 HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
73 F Edema, Grade 2 10 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6 : 120 HPD; D7:
144 HPD; D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24
HPD; D17: 48 HPD)
74 F Edema, Grade 2 7 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7: 144
HPD; D11: 72 HPD; D16: 24 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)Report for Study 20GR142
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Text Table 1. BNT162b2 (V9) Animals with Injection Site Edema Score 2&RQW
G
Animal Clinical Sign Total Number of Days ( Dosing Phase Study Day of
Occurrence)
75 F Edema, Grade 2 8 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD; D7: 144
HPD; D9: 24 HPD; D10: 48 HPD; D11: 72 HPD)
Edema, Grade 3 2 (D16: 24 HPD; D17: 48 HPD)
Note: Dosing Days = 1, 8, and 15 .
D = Dosing Phase Day; F = Female; HPD = Hours postdose M = Male.
Grade 0 = No edema; 1 = Very slight edema (barely perceptible); 2 = Slight edema (edges of area well
defined by definite raising ); 3= Moderate edema (raised approximately 1 millimeter); 4 = Severe edema
(raised more than 1 millimeter and extend s beyond the area of exposure).
Text Table 2. BNT162b3c Animals with Injection Site Edema Score 2
Animal Clinical Sign Total Number of Days ( Dosing Phase Study Day of Occurrence)
31 M Edema, Grade 2 4 (D2: 24 HPD; D3: 48 HPD ; D11: 72 HPD; D16: 24 HPD)
Edema, Grade 3 3 (D9: 24 HPD; D10: 48 HPD; D17: 48 HPD)
32 M Edema, Grade 2 2 (D9: 24 HPD; D10: 48 HPD)
33 M Edema, Grade 2 3 (D11: 72 HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD: D10: 48 HPD)
34 M Edema, Grade 2 6 (D2: 24 HPD; D3: 48 HPD; D9: 24 HPD; D11: 72 HPD;
D16: 24HPD; D17: 48 HPD)
Edema, Grade 3 1 (D10: 48 HPD)
35 M Edema, Grade 2 3 (D11: 72 HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)
36 M Edema, Grade 2 5 (D9 : 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
37 M Edema, Grade 2 7 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D11: 72HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)
38 M Edema, Grade 2 3 (D11; 72 HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10:48 HPD)
39 M Edema, Grade 2 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
40 M Edema, Grade 2 3 (D11: 72 HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D 9: 24 HPD; D10: 48 HPD)
41 M Edema, Grade 2 1 (D11: 72 HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
42 M Edema, Grade 2 3 (D11: 72 HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD; D10: 48 HPD)
43 M Edema, Grade 2 5 (D2: 24 HPD; D3 : 48 HPD; D4: 72 HPD; D6: 120 HPD;
D11:72 HPD)
Edema, Grade 3 4 (D 9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
44 M Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D11: 72HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D16 : 24 HPD; D17: 48 HPD)
45 M Edema, Grade 2 7 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D11: 72HPD; D16: 24 HPD; D17: 48 HPD)
Edema, Grade 3 2 (D9: 24 HPD: D10: 48 HPD)
76 F Edema, Grade 3 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
77 F Edema, Grade 2 1 (D13: 120 HPD) Report for Study 20GR142
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Text Table 2. BNT162b3c Animals with Injection Site Edema Score 2&RQW
G
Animal Clinical Sign Total Number of Days ( Dosing Phase Study Day of Occurrence)
Edema, Grade 3 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
78 F Edema, Grade 2 1 (D13: 120 HPD)
Edema, Grade 3 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
79 F Edema, Grade 2 7 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D7:144HPD; D11: 72 HPD; D17: 48 HPD)
Edema, Grade 3 3 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD;)
80 F Edema, Grade 2 6 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D7:144HPD; D11: 72 HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
81 F Edema, Grade 2 2 (D9: 24 HPD; D11: 72 HPD)
Edema, Grade 3 3 (D10: 48 HPD; D16: 24 HPD; D17: 48 HPD)
82 F Edema, Grade 2 2 (D11: 72 HPD; D17: 48 HPD)
Edema, Grade 3 3 (D9: 24 HPD; D10: 48 HPD; D16: 24 HPD)
83 F Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D7:144HPD;)
Edema, Grade 3 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
84 F Edema, Grade 2 9 (D2: 2 4 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D7:144HPD; D9: 24 HPD; D10: 48 HPD; D11: 72 HPD;
D17: 48HPD)
Edema, Grade 3 1 (D16: 24 HPD)
85 F Edema, Grade 2 6 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D7:144HPD; D16: 24 HPD)
Edema, Grade 3 4 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D17: 48 HPD)
86 F Edema, Grade 2 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
87 F Edema, Grade 2 5 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D7:144HPD;)
Edema, Grade 3 5 (D9 : 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
88 F Edema, Grade 2 6 (D2: 24 HPD; D3: 48 HPD; D4: 72 HPD; D6: 120 HPD;
D7:144HPD; D9: 24 HPD)
Edema, Grade 3 4 (D10: 48 HPD; D11: 72 HPD; D16: 24 HPD; D17: 48 HPD)
89 F Edema, Grade 2 5 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D16: 24 HPD;
D17: 48HPD)
90 F Edema, Grade 2 6 (D9: 24 HPD; D10: 48 HPD; D11: 72 HPD; D13: 120 HPD;
D16: 24HPD; D17: 48 HPD)
Note: Doing Days = 1, 8, and 15 .
D = Dosing Phase Day; F = Female; HPD = Hours postdose ; M = Male.
Grade 0 = No edema; 1 = Very slight edema (barely perceptible); 2 = Slight edema (edges of area well
defined by definite raising ); 3= Moderate edema (raised approximately 1 millimeter); 4 = Severe edema
(raised more than 1 millimeter and ext ends beyond the area of exposure ).Report for Study 20GR142
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Recovery Phase
BNT162b2 (V9) -related injection site edema Grade 2 (slight, edges of area well defined b y
definite raising) or Grade 3 (moderate, raised approximately 1 mm) was noted in 2/5 males
and 5/5 females foll owing dosing on Day 15 (see Text Table 3). The edema was generall y
observed up to 72 hours postdose, and fully resolved. Ery thema was also observed at the
injection site in 2/5 females after the final dose administration, however, it was only Grade 1
(very slight, barel y perceptible) and fully resolved.
BNT162b3c -related injection site edema Grade 2 (slight, edges of area well defined b y
definite raising) or Grade 3 (moderate, raised approximately 1 mm) was noted in 4/5 males
and 5/5 females following do sing on Day 15 (see Text Table 4 ). The edema was generall y
observed up to 72 hours postdose, and fully resolved. Ery thema was also observed at the
injection site in 4/5 females after the final dose administration, however, it was only Grade 1
(very sligh t, barel y perceptible) and fully resolved.
Text Table 3. BNT162b2 (V9) Animals with Injection Site Edema Score 2
Animal Clinical Sign Total Number of Days ( Recovery Study Day of Occurrence)
26 M Edema, Grade 2 1 (RPD1; 72 HPD)
30 M Edema, Grade 2 1 (RPD1; 72 HPD)
71 F Edema, Grade 2 1 (RPD1; 72 HPD)
72 F Edema, Grade 3 1 (RPD1; 72 HPD)
73 F Edema, Grade 2 1 (RPD1; 72 HPD)
74 F Edema, Grade 2 1 (RPD1; 72 HPD)
75 F Edema, Grade 3 1 (RP D1; 72 HPD)
F = Female; HPD = Hours post dose ; M = Male; RPD = Recovery Phase Day
Grade 0 = No edema; 1 = Very slight edema (barely perceptible); 2 = Slight edema (edges of area well
defined by definite raising ); 3= Moderate edema (raised approximately 1 millimeter); 4 = Severe edema
(raised more than 1 millimeter and extends beyond the area of exposure).
Text Table 4. BNT162b3c Animals with Injection Site Edema Score 2
Animal Clinical Sign Total Number of Days ( Recovery Study Day of Occurrence)
41 M Edema, Grade 2 1 (RPD1: 72 HPD)
43 M Edema, Grade 2 1 (RPD1: 72 HPD)
44 M Edema, Grade 2 1 (RPD1: 72 HPD)
45 M Edema, Grade 2 1 (RPD1: 72 HPD)
86 F Edema, Grade 2 1 (RPD1: 72 HPD)
87 F Edema, Grade 3 1 (RPD1: 72 HPD)
88 F Edema, Grade 3 1 (RPD1: 72 HPD)
89 F Edema, Grade 3 1 (RPD1: 72 HPD)
90 F Edema, Grade 2 1 (RP D1: 72 HPD)
F = Female; HPD = Hours post dose ; M = Males; RPD = Recovery Phase Day.
Grade 0 = No edema; 1 = Very slight edema (barely perceptible); 2 = Slight edema (edges of area well
defined by definite raising ); 3= Moderate edema (raised approximately 1 millimeter); 4 = Severe edema
(raised more than 1 millimeter and extends beyond the area of exposure ).Report for Study 20GR142
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6.1.6. Body Temperature
Group mean bod y temperature data are included in Table 13. Individual body temperature
data are included in Appendix 13 .
Test article -related higher mean body temperature differences from control were noted on
Days 1 (+0.42°C- 0.54°C), 8 ( +0.66°C- 0.98°C), and 15 (+0.13°C-1.03°C) following dose
administration of BNT162b2 (V9).
Test article -related higher mean body temperature differences from control were noted on
Days 1 (+0.50°C- 0.71°C), 8 ( +0.92°C- 1.26°C) and 15 ( +0.33°C-1.09°C) following dose
administration of BNT162b3c.
Additional body temperature evaluations were not needed at 48 and 72 hours postdose as
individual animal body temperatures were ≤40C at 24 hours postdose.
6.1.7. Ophthalmology
The complete Ophthalmology Report is included in Appendix B and a summary of the results
is included below.
There were no test article -related ophthalmic findings noted at the conclusion of the dosing
phase. Recovery phase examinations were not performed due to no findings observed at the
conclusion of the dosing phase.
6.2.Clinical Laborat ory Measurements
The complete Clinical Pathology Report is included in Appendix B and a summary of the
results is included below .
Dosing Phase
Test article -related hematology and coagulation findings were similar in rats administered
either BNT162b2(V9) or BNT162b3c and included higher mean white blood cell (WBC)
counts and fibrinogen concentrations, lower (Day 4) and higher (Day 17) reticulocy te counts,
and lower red blood cell mass (red blood cell count, hemoglobin and hematocrit ) as
compared with contro ls.
Higher WBC primaril y involved higher neutrophils, monocytes and large unstained cells ,
but also eosinophils and basophils. They were present on Day s 4 and 17, with higher counts
on Day 17 than Day 4. On Day 17, there were also test article -related hi gher fibrinogen
concentrations in both sexes. Hy persegmented neutrophils were present on peripheral blood
smears of test article -dosed animals.
In addition, there were test article -related transiently lower reticulocy te counts on Day 4, and
higher reticulocy tes on Day 17 (females only ) with attendant expected changes in RBC
indices (higher mean cell hemoglobin concentration; males on Day 4; lower mean cell
hemoglobin [MCH] and higher red cell distribution width on Day 17; both sexes). These Report for Study 20GR142
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were associat ed with lower RBC mass on Days 4 and 17 (comparable on both day s or
slightly lower on Day 17).
Test article -related clinical chemistry findings were similar in rats administered either
BNT162b2(V9) or BNT162b3c and included higher mean alpha- 1 acid gl ycoprotein and
alpha -2-macroglobulin and lower AG ratios ( primarily due to lower albumin with slight
contribution from higher globulins ) on Day s 4 and 17 in both sexes.
Recovery Phase
All test article- related hematology and coagulation changes noted in the dosi ng phase were
fully reversed after a 3 -week recovery phase, with the exception of higher red cell
distribution width .
All test article- related clinical chemistry changes noted in the dosing phase were fully
reversed after a 3- week recovery phase , with the exception of higher globulins in males
administered BNT162b2(V9) and females administered BNT162b2(V9) and BNT162b3c and
lower AG ratio in females administered BNT162b2(V9).
There were no test article -related findings noted in urinaly sis parameters in the dosing or
recovery phase.
6.2.1. Bone Marrow Assessment
The complete Clinical Pathology Report is included in Appendix B and a summary of the
results is included below .
Bone marrow smears were prepared for all animals and were not examined .
6.3. Antibody (Serology) Analysis
The complete Serology Report is included in Appendix B and a summary of the results is
included below.
Administration of 3 once weekl y doses of BNT162b2 (V9) or BNT162b3c elicited
SARS -CoV -2 neutralizing antibod y responses in males and females a t the end of the dosing
(Day 17) and recovery phases (Day 21) of the study .SARS -CoV -2 neutralizing antibody
responses were not observed in animals prior to vaccine administration or in
saline -administered control animals.
6.4.Postmortem Observations
The complete Anatomic Pathology Report is included in Appendix B and a summary of the
results is included below .
Dosing Phase
Test article -related organ weight differences included higher absolute and relative (to body
and brain weight) spleen weights in males and females administered BNT162b2 (V9) or
BNT162b3c. Report for Study 20GR142
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Test article -related macroscopic findings included large draining l ymph nodes (abnormal
size, enlarged) and dark/pale and/or firm injection sites (abnormal color, dark/pale and /or
abnormal consistency , firm) in animals administered BNT162b2 (V9) or BNT162b3c, and
large spleen and inguinal ly mph nodes (abnormal size, enlarged) in animals administered
BNT162b3c.
Organs with test article -related microscopic findings included the injection site (mixed cell
inflammation and edema), draining and inguinal ly mph nodes (increased cellularity , plasma
cells and germinal centers), liver (hepatocellular vacuolation), spleen (increased cellularity ,
hematopoietic cells and germinal centers), and bone marrow (increased ce llularity ,
hematopoietic cells) in both males and females administered BNT162b2 (V9) or
BNT162b3c.
Recovery Phase
No test article -related organ weight changes were noted at the end of the recovery phase.
Test article -related macroscopic findings observed at the end of the recovery phase were
limited to large draining lymph nodes (abnormal size, enlarged) in 1 male administered
BNT162b2 (V9) and 1 female administered BNT162b3c and large inguinal ly mph nodes
(abnormal size, enlarged) in 1 female administered BNT162b3c, indicating a partial recovery
of these findings. Pale/dark and/or firm injection sites and enlarged spleen were not
observed at the end of recovery phase in BNT162b2 (V9) or BNT162b3c administ ered males
and females, indicating a complete recovery of these findings.
Test article -related microscopic findings noted at the end of the dosing phase including
edema at the injection site, hepatocellular vacuolation in the liver, and increased cellulari ty of
hematopoietic cells in the spleen and bone marrow were not observed at the end of recovery
phase in BNT162b2 (V9) or BNT162b3c administered males and females, indicating a
complete recovery of these findings. Inflammation at the injection site was c haracterized b y
mostly lymphocy tes and plasma cells with few neutrophils (indicating partial recovery ) and
no edema (full recovery ). However, increased cellularity of the germinal centers in the
spleen partiall y recovered, as the incidence and/or severit yof these findings were lower in
recovery phase animals as compared with dosing phase animals in both males and females
administered BNT162b2 (V9) or BNT162b3c. At the end of recovery phase , mature plasma
cells had replaced the plasmablasts identified in the inguinal and draining ly mph nodes in the
dosing phase animals. In recovery phase animals, infiltration of macrophages was observed
in the draining l ymph nodes (minimal to mild) in both sexes administered BNT162b2 (V9) or
BNT162b3c and in the inguinal l ymph nodes (minimal) in both sexes administered
BNT162b2 (V9). This finding was considered indicative of a reparative process
(consequence of phagocytosis), which can be seen following inflammatory reactions at the
injection sites.
7.INTEGRATED SUMMARY AND DISCUSSION OF RESULT S
Intramuscular administration of BNT162b2 (V9) and BNT162b3c at 30 µg RNA/dose day
once weekl y for a total of 3 doses to Wistar Han rats was tolerated during the dosing phase
without evidence of s ystemic toxicity , generated a SARS -CoV -2 neutralizing antibod y Report for Study 20GR142
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response, and produced nonadverse changes consistent with inflammatory and immune
responses to vaccine administration.
At the conclusion of the dosing phase, test article -related responses to both vaccines were
evident as transient edema (very slight to moderate) and ery thema (very slight) at the
injection site after each dose of BNT162b2 (V9) and BNT162b3c. Test article -related
erythema and edema fully resolved prior to subsequent dose administration on Day s 8 and 15
with findings genera lly resolved by 72 hours after the final dose administration (Recovery
Phase Day 1). Transiently higher body temperature differences compared with concurrent
controls were noted on Day s 1 (up to +0.71°C), 8 (up to +1.26°C) and 15 (up to +1.09°C)
post administration of BNT162b3c and on Days 1 (up to +0.54°C), 8 (up to +0.98°C), and
15(up to +1.03°C) after administration of BNT162b2 (V9). Additional body temperature
evaluations were not needed at 48 and 72 hours postdose as individual animal body
temperatures were ≤40°C at 24 hours postdose.
Changes secondary to inflammation included lower mean bod y weight (0.93x -0.94x control
on Day s 11 and 15) in male animals administered BNT162b3c and lower mean food
consumption (0.83x-0.87x control on Day s 4 and 11) for animals administered BNT162b2
(V9) and BNT162b3c (0.76x- 0.92x control on Days 4 and 11) during the dosing phase.
These changes fully resolved in the recovery phase as higher mean bod y weight (1.05- 1.06x
control) was noted in males only administered BNT162b2 (V9). Additionally , higher mean
food consumption (1.08x -1.35x control) was noted throughout the recovery phase for male
animals administered BNT162b2 (V9) and BNT162b3c (1.08x -1.30x control).
At the conclusion of the dosing phase, all clinical p athology findings (t ype and magnitude)
were generally similar between rats administered BNT162b2 (V9) or BNT162b3c, and
consistent with expected immune responses to vaccines or secondary to inflammation. The
main findings were present in both sexes on Day s 4 and/or 17 and included higher acute
phase proteins (alpha -1 acid gl ycoprotein; 7.0x -42x controls], alpha -2-macroglobulin
(3.3x -128x] and fibrinogen [2.4x -2.6x]) and white blood cell count (1.28x -2.95x; primarily
involving neutrophils, monocy tes and lar ge unstained cells , which ty pically represent large
mononuclear cells) and lower albumin:globulin (0.90x- 0.82x). Hypersegmented neutrophils
present on peripheral blood smears were considered to be secondary to the robust increases in
neutrophil counts and likely related to mobilization of bone marrow storage neutrophils and
prolonged neutrophil lifespan in circulation ( Ulich et al, 1988) . Collectively , these findings
were consistent with immune responses to vaccines. Microscopic correlates included
minimally increased cellularity of hematopoietic cells (primaril y myeloid) in the bone
marrow and the spleen, minimal to moderate mixed cell inflammation at the injection site
and increased cellularity in germinal centers of l ymphoid organs. In addition, there were
transiently lower reticulocy te counts on Day 4 (0.44x -0.27x), and higher reticulocytes on
Day 17 (1.20x -1.31x; females only ), with minor lower red cell mass on Day s 4 and 17 (HCT;
0.93x- 0.89x). L ower reticulocy tes were interpreted to be a transient effect of innate immune
responses ( Abreu et al, 2018 ; Brooks et al, 2017 ; Kim et al, 2014 ; Wrighting & Andrews,
2006 ).
All test article- related clinic al pathology parameter changes were full y reversed after a
3-week recovery phase , with the exception of higher red cell distribution width in males and Report for Study 20GR142
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females administered BNT162b2(V9) (1.13x and 1.21x, respectively ) and BNT162b3c
(1.12x and 1.23x, respec tively ), higher globulins in males administered BNT162b2(V9)
(1.08x) and females administered BNT162b2(V9) (1.06x) and BNT162b3c (1.07x) and lower
AG ratio in females administered BNT162b2(V9) (0.91x).
Test article -related microscopic pathology findings we re observed at the injection site and in
the ly mph nodes, spleen, bone marrow, and liver for both vaccine candidates. All
microscopic findings were nonadverse, as there was no evidence of s ystemic toxicity or
clinical signs of illness or lameness.
At the end of the dosing phase, test article -related mixed cell inflammation (mild to
moderate) and edema (mild to moderate) at the injection site were consistent with findings
typicall y associated with the IM administration of lipid nanoparticle (LNP)- encapsula ted
mRNA vaccines ( Hassett et al, 2019). These findings correlated with macroscopic
observations of abnormal color (dark/pale) and consistency (firm). At the end of the 3-week
recovery phase , full recovery occurred for macroscopic findings of pale/dark a nd firm
injection sites and the microscopic finding of edema, whereas partial recovery occurred for
inflammation at the injection sites.
At the end of the dosing phase, test article -related findings in the l ymph nodes (increased
cellularity of plasma cells [minimal to moderate] and germinal centers [minimal to mild]),
spleen (increased cellularity of hematopoietic cells [minimal] and germinal centers
[minimal]), and the bone marrow (minimal increased cellularit y of hematopoietic cells) were
secondary to imm une activation and/or inflammation at the injection site. The presence of
plasma cells (interpreted as plasmablasts) in the draining and inguinal l ymph nodes was
interpreted to reflect a robust immunological response to the vaccines. These observations
correlated with macroscopic observations of abnormal size (enlarged) in the ly mph nodes and
spleen and increased spleen weights. At the end of the 3- week recovery phase , full recovery
occurred for higher spleen weights, macroscopic find ing of enlarged spleen, and microscopic
findings of increased cellularity of hematopoietic cells in the spleen and bone marrow,
whereas partial recovery occurred for macroscopic findings of enlarged draining and inguinal
lymph nodes, microscopic findings o f increased cellularity of plasma cells and germinal
centers in the draining and inguinal l ymph nodes, and increased cellularity of the germinal
centers in the spleen.
At the end of the dosing phase, test article -related microscopic finding of minimal portal
hepatocy te vacuolation was not associated with hepatic tissue damage or liver enzy me
alterations. This change may be related to hepatic clearance of the pegy lated lipid in the
LNP ( Ivens et al, 2015 ). At the end of 3- week recovery phase , this finding was completel y
recovered.
Administration of 3 once weekl y doses of BNT162b2 (V9) or BNT162b3c elicited
SARS -CoV -2 neutralizing antibod y responses in both males and females at the end of the
dosing (Day 17) and recovery phases (Day 21) of the study . SARS -CoV- 2 neutralizing
antibody responses were not observed in animals prior to vaccine administration or in
saline -administered control animals.Report for Study 20GR142
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There were no other test article- related effects in the study .
8.CONCLUSIONS
In conclusion, BNT162b2 (V9) and BNT162b 3c administered via intramuscular injection
once weekl y for a total of 3 doses to Wistar Han (Crl:WI [Han]) rats was tolerated without
evidence of s ystemic toxicity , generated a SARS -CoV -2 neutralizing antibody response, and
produced nonadverse changes cons istent with an immune or inflammatory response at the
conclusion of the dosing phase. At the end of the 3- week recovery phase, full or partial
recovery of all findings was observed . Other nonadverse findings included vacuolation in the
liver which may berelated to hepatic clearance of PEGy lated lipids and was noted at the
conclusion of the dosing phase and completely recovered. The findings in this study are
consistent with those ty pically associated with the intramuscular administration of L NP-
encapsul ated mRNA vaccines. Animals administered BNT162b2 (V9) or BNT162b3c
elicited SARS -CoV -2 neutralizing antibody responses at the end of the dosing and recovery
phases of the stud y.Report for Study 20GR142
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9.REFERENCES
Abreu R, Quinn F,GiriPK. Role of the hepcidin -ferroportin axi s in pathogen -mediated
intracellular iron sequestration in human phagocy tic cells. Blood Adv 2018;2 (10): 1089-100.
Brooks MB, Turk JR, Guerrero A, et al. Non- Lethal Endotoxin I njection: A Rat Model of
Hypercoagulability . PLoS One 2017;2(1),e0169976.
Draize JH. 1959 (2nd printing 1965). Appraisal of the Safet y of Chemicals in Foods, Drugs
and Cosmetics. Dermal Toxicity , pp. 46 -59. Published by : The Association of Food and Drug
Officials of the United States, Topeka, Kansas.
Hassett KJ, Benenato KE, Jacquin et E et al. Optimization of L ipid Nanoparticles for
Intramuscular Administration of mRNA Vaccines. Mol Ther Nucleic Acids 2019 ;15:1-11.
Ivens IA, Achanzar W, Baumann A, et al. PEGy lated biopharmaceuticals: current experience
and considerations for nonclinical development. Toxicol Pathol 2015 Oct;43(7):959 -83.
Kim A, Fung E, Parikh SG, et al. A mouse model of anemia of inflammation: complex
pathogenesis with partial dependence on hepcidin. Blood 2014; 123(8) 1129-136.
Ulich TR, del Castillo J, Souza L.Kinetics and mechanisms of recombinant human
granulocy te-colon y stimulating factor -induced neutrophilia. Am J Pathol 1988; 133(3):630-
38.
Wrighting DM and Andr ews NC. Interleukin -6 induces hepcidin expression through
STAT3. Blood 2006;108 (9):3204-09.Report for Study 20GR142
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Table 1
Clinical Signs - Daily Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Note: Animals were considered normal (data not displayed in table) unless indicated otherwise.
PID = Prior to Initiation of Dosing
- = Value not applicable.
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Table 1
Clinical Signs - Daily Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Males (PID)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
15 15 15
15 14 15Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
0 0 1 12 0 0 Tail Crooked
Note: a = Number of animals with Observation
b = Number of days Observation seen
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Table 1
Clinical Signs - Daily Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Males (Dosing)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
15 15 15
14 13 15Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
0 0 1 17 0 0 Tail Crooked
1 1 0 0 0 0 Thin Appearance
0 0 1 2 0 0 Hair Loss
Note: a = Number of animals with Observation
b = Number of days Observation seen
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Table 1
Clinical Signs - Daily Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Males (Recovery)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
5 5 5
5 4 5Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
0 0 1 22 0 0 Tail Crooked
Note: a = Number of animals with Observation
b = Number of days Observation seen
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Table 1
Clinical Signs - Daily Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Females (Dosing)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
15 15 15
15 14 14Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
0 0 0 0 1 1 Lesion
0 0 1 1 0 0 Hair Loss
Note: a = Number of animals with Observation
b = Number of days Observation seen
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Table 2
Ocular Exam Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Note: Animals were considered normal (data not displayed in table) unless indicated otherwise.
PID = Prior to Initiation of Dosing
- = Value not applicable.
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Table 2
Ocular Exam Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Males (PID)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
15 15 15
0 0 0Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
1 1 0 0 1 1 Keratic Precipitates
11 1 15 1 14 1 No Ocular Abnormality
1 1 0 0 0 0 Retina, Tortuous Vessels
1 1 0 0 0 0 Vitreous, Hemorrhage
1 1 0 0 0 0 Vitreous, Hyaloid Remnant
Note: a = Number of animals with Observation
b = Number of days Observation seen
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Table 2
Ocular Exam Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Males (Dosing)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
15 15 15
0 0 0Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
1 1 0 0 1 1 Keratic Precipitates
11 1 15 1 14 1 No Ocular Abnormality
1 1 0 0 0 0 Retina, Tortuous Vessels
1 1 0 0 0 0 Vitreous, Hemorrhage
1 1 0 0 0 0 Vitreous, Hyaloid Remnant
Note: a = Number of animals with Observation
b = Number of days Observation seen
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709480
Table 2
Ocular Exam Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Females (PID)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
15 15 15
0 0 0Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
15 1 15 1 15 2 No Ocular Abnormality
Note: a = Number of animals with Observation
b = Number of days Observation seen
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709481
Table 2
Ocular Exam Summary Report by Interval
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Females (Dosing)
Group Number:
Number of animals:
Number Examined:
Number Normal:1 2 3
15 15 15
15 15 15
0 0 0Dose: 30 µg/day
30 µg /day 0 µg/day
a b a b a b Observations
1 1 0 0 0 0 Keratic Precipitates
14 1 15 1 15 1 No Ocular Abnormality
Note: a = Number of animals with Observation
b = Number of days Observation seen
Pfizer CONFIDENTIALReport for Study 20GR142
Page 41PFIZER CONFIDENTIAL
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FDA-CBER-2021-5683-0709482
Table 3
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
N = Sample Size; SD = Standard Deviation; - = Value not applicable;
@ = Number examined reduced due to excluded data; e = Group mean excluded from statistics;
REF = Denotes group used as reference in the statistical tests;
* = Statistically significant pairwise comparison at 0.05 level;
† = Statistically significant pairwise comparison at 0.01 level;
‡ = Statistically significant trend at 0.05 level;
§ = Statistically significant trend at 0.01 level.
+ = Ascending trend sign;
- = Descending trend sign;
_______ ______
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709483
Table 3
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Group Number: REF 2 3
0 µg/day 30 µg/day 30 µg /day Dose:
SD Mean N SD Mean N SD Mean N
Day Phase
PID 15 187.71 8.56 188.41 7.75 15 188.03 6.62 1 15
15 225.28 9.66 226.59 8.47 15 225.85 8.67 6 15
Dosing 15 264.80 11.89 267.18 8.15 15 263.46 12.10 1 15
15 252.16 10.99 247.61 10.02 15 242.54 13.20 4 15
15 280.60 25.91 283.61 12.16 15 276.29 15.86 8 15
15 295.83 17.57 283.71 13.88 15 274.58 18.39 11 15 †
15 311.47 17.82 302.53 15.32 15 293.29 17.38 15 15 *
Recovery 5 307.70 21.74 308.50 12.01 5 295.92 9.49 1 5
5 316.08 25.11 320.72 13.14 5 306.16 9.09 4 5
5 326.54 29.34 332.88 15.20 5 320.72 10.07 8 5
5 330.74 30.51 346.54 14.64 5 327.60 8.95 11 5
5 333.60 32.63 354.64 18.28 5 334.80 12.51 15 5
5 341.42 35.91 359.48 16.87 5 344.14 12.32 18 5
5 347.88 39.32 369.60 21.74 5 354.24 11.39 21 5
Pfizer CONFIDENTIALReport for Study 20GR142
Page 43PFIZER CONFIDENTIAL
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FDA-CBER-2021-5683-0709484
Table 3
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Group Number: REF 2 3
0 µg/day 30 µg/day 30 µg /day Dose:
SD Mean N SD Mean N SD Mean N
Day Phase
PID 15 158.37 7.52 159.83 7.42 15 159.57 6.72 1 15
15 176.36 7.52 176.31 7.51 15 175.61 9.68 6 15
Dosing 15 194.79 8.63 191.53 8.38 15 192.68 9.71 1 15
15 183.19 8.90 177.31 6.25 15 176.93 7.46 4 15
15 206.53 11.91 202.51 7.98 15 198.91 12.14 8 15
15 210.23 12.88 203.88 8.25 15 202.83 11.29 11 15
15 214.29 11.95 214.02 11.69 15 213.93 14.12 15 15
Recovery 5 215.08 14.40 207.22 4.75 5 211.92 22.04 1 5
5 217.14 16.97 213.00 7.23 5 214.38 17.62 4 5
5 224.02 20.44 220.14 7.28 5 219.88 17.62 8 5
5 224.02 17.73 221.50 7.28 5 218.22 15.76 11 5
5 224.24 13.98 220.58 5.81 5 217.30 19.01 15 5
5 225.54 15.89 224.56 7.07 5 225.18 20.90 18 5
5 228.86 14.34 231.32 10.43 5 224.46 18.18 21 5
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709485
Table 4
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
N = Sample Size; SD = Standard Deviation; - = Value not applicable;
@= Number examined reduced due to excluded data; e= Group mean excluded from statistics;
REF = Denotes group used as reference in the statistical tests;
* = Statistically significant pairwise comparison at 0.05 level;
† = Statistically significant pairwise comparison at 0.01 level;
‡ = Statistically significant trend at 0.05 level;
§ = Statistically significant trend at 0.01 level;
+ = Ascending trend sign;
- = Descending trend sign;
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709486
Table 4
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Group Number:
REF 2 3
0 µg/day 30 µg/day 30 µg /day Dose:
SD Mean N Days Phase N N Mean Mean SD SD
PID 15 37.57 5.03 15 38.17 3.68 15 37.81 5.25 1-6
Dosing 15 -12.64 6.48 15 -19.57 4.15 15 -20.92 5.13 1-4 † †
15 28.44 20.74 15 36.01 5.43 15 33.75 6.25 4-8
15 15.23 13.92 15 0.10 4.24 15 -1.71 4.92 8-11 † †
15 15.64 6.06 15 18.82 3.78 15 18.71 3.81 11-15 *
15 46.67 11.76 15 35.35 9.13 15 29.83 7.68 1-15 † †
Recovery 5 8.38 6.59 5 12.22 3.59 5 10.24 1.50 1-4
5 10.46 5.99 5 12.16 3.36 5 14.56 2.43 4-8
5 4.20 2.25 5 13.66 5.19 5 6.88 2.09 8-11 †
5 2.86 5.01 5 8.10 4.39 5 7.20 4.36 11-15
5 7.82 4.23 5 4.84 2.74 5 9.34 1.78 15-18
5 6.46 3.71 5 10.12 5.61 5 10.10 4.17 18-21
5 40.18 23.53 5 61.10 11.09 5 58.32 2.92 1-21
Pfizer CONFIDENTIALReport for Study 20GR142
Page 46PFIZER CONFIDENTIAL
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FDA-CBER-2021-5683-0709487
Table 4
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Group Number:
REF 2 3
0 µg/day 30 µg/day 30 µg /day Dose:
SD Mean N Days Phase N N Mean Mean SD SD
PID 15 17.99 2.73 15 16.48 4.42 15 16.03 5.51 1-6
Dosing 15 -11.61 4.28 15 -14.21 4.68 15 -15.75 4.41 1-4
15 23.34 6.05 15 25.19 3.75 15 21.98 6.34 4-8
15 3.71 6.72 15 1.37 5.88 15 3.92 6.86 8-11
15 4.06 2.94 15 10.14 5.89 15 11.09 7.60 11-15 † †
15 19.50 10.28 15 22.49 7.98 15 21.25 9.62 1-15
Recovery 5 2.06 4.97 5 5.78 7.47 5 2.46 8.25 1-4
5 6.88 5.44 5 7.14 3.16 5 5.50 2.38 4-8
5 0.00 6.15 5 1.36 4.33 5 -1.66 4.65 8-11
5 0.22 5.29 5 -0.92 3.88 5 -0.92 7.60 11-15
5 1.30 3.45 5 3.98 3.54 5 7.88 2.12 15-18 †
5 3.32 6.18 5 6.76 7.21 5 -0.72 6.12 18-21
5 13.78 7.24 5 24.10 9.09 5 12.54 9.04 1-21
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709488
Table 5
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
N = Sample Size; SD = Standard Deviation; -= Value not applicable;
@= Number examined reduced due to excluded data; e= Group mean excluded from statistics;
REF = Denotes group used as reference in the statistical tree;
* = Statistically significant pairwise comparison at 0.05 level;
† = Statistically significant pairwise comparison at 0.01 level;
‡ = Statistically significant trend at 0.05 level;
§ = Statistically significant trend at 0.01 level;
+ = Ascending trend sign;
- = Descending trend sign;
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709489
Table 5
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
REF Group Number: 2 3
Phase Days
N Mean SD SD Mean N SD Mean NMale
0 µg/day 30 µg/day 30 µg /day Dose:
Dosing 15 50.88 4.05 15 42.59 4.28 15 38.69 5.13 1-4 † †
15 90.87 21.27 15 96.75 8.55 15 91.37 11.71 4-8
15 64.77 5.09 15 54.02 6.13 15 50.45 7.45 8-11 † †
15 89.35 5.58 15 92.22 8.57 15 88.80 8.32 11-15
15 295.87 26.49 15 285.59 25.00 15 269.31 27.34 1-15 *
Recovery 5 48.02 6.41 5 64.74 3.38 5 62.26 4.67 1-4 † †
5 82.12 11.18 5 92.92 7.90 5 86.64 6.45 4-8
5 58.12 6.67 5 68.00 5.18 5 62.70 4.15 8-11 *
5 76.42 9.49 5 84.72 7.87 5 79.20 6.20 11-15
5 59.70 8.18 5 64.46 3.81 5 62.60 5.08 15-18
5 59.28 9.02 5 66.44 4.09 5 62.14 7.53 18-21
5 383.66 49.21 5 441.28 29.93 5 415.54 31.74 1-21
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709490
Table 5
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
REF Group Number: 2 3
Phase Days
N Mean SD SD Mean N SD Mean NFemale
0 µg/day 30 µg/day 30 µg /day Dose:
Dosing 15 37.79 4.28 15 33.02 3.62 15 34.63 12.73 1-4 † †
15 74.46 8.29 15 70.83 4.58 15 71.73 6.76 4-8
15 48.27 6.64 15 41.85 2.97 15 40.42 6.17 8-11 † †
15 65.27 7.36 15 66.59 6.62 15 68.50 8.71 11-15
15 225.80 24.33 15 212.29 13.55 15 215.28 24.59 1-15
Recovery 5 47.60 5.58 5 49.72 4.93 5 49.02 5.33 1-4
5 63.32 7.66 5 66.68 2.93 5 66.88 9.55 4-8
5 46.32 4.38 5 46.70 3.76 5 42.72 6.58 8-11
5 59.08 7.68 5 60.98 4.18 5 57.88 11.68 11-15
5 42.44 5.72 5 43.64 5.88 5 44.76 7.31 15-18
5 45.00 4.09 5 46.80 4.13 5 44.76 6.43 18-21
5 303.76 32.65 5 314.52 18.16 5 306.02 44.46 1-21
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709491
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Parameter Description
RBC Red Blood Cells
HGB Hemoglobin
HCT Hematocrit
MCV Mean Cell Volume
MCH Mean Cell Hemoglobin
MCHC Mean Cell Hemoglobin Conc
RDW Red Cell Distribution Width
RETIC Reticulocyte, Absolute
PLT Platelets
MPV Mean Platelet Volume
WBC White Blood Cells
NEUT Neutrophil, Absolute
LYM Lymphocyte, Absolute
MONO Monocyte, Absolute
EO Eosinophil, Absolute
BASO Basophil, Absolute
LUC Large Unstained Cells, Absolute
PT_Rat Prothrombin Time, Rat
APTT Activated Partial Thromboplastin Time
FIB Fibrinogen
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709492
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Footnotes
Note: Sample size is displayed in ( ) before the mean value.
SD = Standard Deviation; - = Value not applicable;
Units are displayed in the ( ) under each parameter name;
HPD = Hours Post Dose; U = Unscheduled;
e = Group mean excluded from statistics;
REF = Denotes group used as reference in the statistical test;
* = Statistically significant pairwise comparison at 0.05 level;
† = Statistically significant pairwise comparison at 0.01 level;
‡ = Statistically significant trend at 0.05 level;
§ = Statistically significant trend at 0.01 level.
+ = Ascending trend sign;
- = Descending trend sign;
# = Individual parameter values reported as less than or greater than limit of quantitation are set equal to the limit to calculate the average.
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709493
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
RBC
(10^6/uL)Dosing 4 Mean
SD(7) 8.117
0.265(7) 7.774
0.292* (7) 7.596
0.273† --
17 Mean
SD(9) 7.584
0.512(10) 7.169
0.292(10) 7.113
0.326-
Recovery 22 Mean
SD(5) 7.950
0.480(5) 8.064
0.261(5) 7.886
0.427-
HGB
(g/dL)Dosing 4 Mean
SD(7) 15.01
0.57(7) 14.16
0.62* (7) 14.01
0.38† --
17 Mean
SD(9) 13.82
0.72(10) 12.53
0.63† (10) 12.81
0.49† -
Recovery 22 Mean
SD(5) 14.36
1.02(5) 14.38
0.41(5) 14.00
0.45-
HCT
(%)Dosing 4 Mean
SD(7) 48.04
1.33(7) 43.37
1.69† (7) 43.79
1.16† --
17 Mean
SD(9) 42.61
2.44(10) 38.40
1.64† (10) 39.29
1.49* -
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709494
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
HCT
(%)Recovery 22 Mean
SD(5) 42.78
3.12(5) 43.72
1.44(5) 42.98
2.00-
MCV
(fL)Dosing 4 Mean
SD(7) 59.19
1.21(7) 55.81
1.28† (7) 57.69
1.52--
17 Mean
SD(9) 56.24
1.37(10) 53.58
1.36† (9) 54.99
1.35-
Recovery 22 Mean
SD(4) 53.80
1.15(4) 54.00
1.03(4) 54.30
1.25-
MCH
(pg)Dosing 4 Mean
SD(7) 18.51
0.48(7) 18.20
0.49(7) 18.50
0.47--
17 Mean
SD(9) 18.27
0.42(10) 17.48
0.51† (10) 18.01
0.60-
Recovery 22 Mean
SD(5) 18.06
0.43(5) 17.84
0.64(5) 17.80
0.66-
MCHC
(g/dL)Dosing 4 Mean
SD(7) 31.24
0.57(7) 32.64
0.40† (7) 32.04
0.26† --
Pfizer CONFIDENTIALReport for Study 20GR142
Page 54PFIZER CONFIDENTIAL
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FDA-CBER-2021-5683-0709495
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
MCHC
(g/dL)Dosing 17 Mean
SD(9) 32.46
0.36(10) 32.65
0.53(10) 32.61
0.64-
Recovery 22 Mean
SD(5) 33.60
0.71(5) 32.90
0.74(5) 32.60
0.63* -
RDW
(%)Dosing 4 Mean
SD(7) 12.27
0.47(7) 12.83
0.70(7) 12.44
0.49--
17 Mean
SD(9) 11.63
0.39(10) 14.12
0.73† (9) 13.73
0.46† -
Recovery 22 Mean
SD(4) 11.93
0.42(4) 13.48
0.29† (4) 13.33
0.46* -
RETIC
(10^3/uL)Dosing 4 Mean
SD(7) 392.1
51.5(7) 107.4
46.9† (7) 104.6
27.3† --
17 Mean
SD(9) 178.8
24.1(10) 185.4
25.9(10) 194.0
12.4-
Recovery 22 Mean
SD(5) 180.8
28.9(5) 190.8
30.4(5) 186.6
25.4-
Pfizer CONFIDENTIALReport for Study 20GR142
Page 55PFIZER CONFIDENTIAL
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FDA-CBER-2021-5683-0709496
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
PLT
(10^3/uL)Dosing 4 Mean
SD(7) 1012.7
169.9(7) 1039.7
94.7(7) 945.1
132.1--
17 Mean
SD(9) 881.3
69.0(10) 801.3
119.9(10) 739.0
133.1* -
Recovery 22 Mean
SD(5) 847.8
40.0(5) 904.4
115.4(5) 837.6
115.3-
MPV
(fL)Dosing 4 Mean
SD(7) 8.87
0.35(7) 9.14
0.71(7) 9.70
0.37† --
17 Mean
SD(9) 9.12
0.36(10) 9.55
0.47(10) 9.93
0.51† -
Recovery 22 Mean
SD(5) 9.00
0.23(5) 8.84
0.24(5) 8.88
0.26-
WBC
(10e3/uL)Dosing 4 Mean
SD(7) 7.60
1.08(7) 10.70
3.01* (7) 9.70
1.64--
17 Mean
SD(9) 3.84
1.67(10) 8.83
3.62† (10) 8.60
1.15† -
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709497
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
WBC
(10e3/uL)Recovery 22 Mean
SD(5) 5.26
2.64(5) 5.98
1.16(5) 4.90
1.18-
NEUT
(10^3/uL)Dosing 4 Mean
SD(7) 1.083
0.420(7) 2.470
0.834† (7) 2.161
0.521* --
17 Mean
SD(9) 0.674
0.387(10) 4.449
1.890† (10) 4.351
0.696† -
Recovery 22 Mean
SD(5) 0.898
0.372(5) 1.070
0.215(5) 1.276
0.329-
LYM
(10^3/uL)Dosing 4 Mean
SD(7) 6.284
1.048(7) 7.727
2.157(7) 7.030
1.150--
17 Mean
SD(9) 3.009
1.282(10) 3.792
1.624(10) 3.547
0.574-
Recovery 22 Mean
SD(5) 4.158
2.205(5) 4.672
1.107(5) 3.408
0.839-
MONO
(10^3/uL)Dosing 4 Mean
SD(7) 0.109
0.021(7) 0.199
0.079* (7) 0.214
0.022† --
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709498
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
MONO
(10^3/uL)Dosing 17 Mean
SD(9) 0.071
0.042(10) 0.234
0.121† (10) 0.254
0.077† -
Recovery 22 Mean
SD(5) 0.074
0.031(5) 0.106
0.021(5) 0.104
0.021-
EO
(10^3/uL)Dosing 4 Mean
SD(7) 0.081
0.059(7) 0.086
0.054(7) 0.091
0.034--
17 Mean
SD(9) 0.056
0.024(10) 0.141
0.053† (10) 0.122
0.061† -
Recovery 22 Mean
SD(5) 0.068
0.042(5) 0.074
0.024(5) 0.074
0.038-
BASO
(10^3/uL)Dosing 4 Mean
SD(7) 0.016
0.005(7) 0.030
0.014* (7) 0.037
0.014† --
17 Mean
SD(9) 0.003
0.005(10) 0.017
0.013† (10) 0.019
0.007† -
Recovery 22 Mean
SD(5) 0.008
0.013(5) 0.008
0.004(5) 0.008
0.004-
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FDA-CBER-2021-5683-0709499
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
LUC
(10^3/uL)Dosing 4 Mean
SD(7) 0.046
0.011(7) 0.187
0.139† (7) 0.183
0.104† --
17 Mean
SD(9) 0.026
0.013(10) 0.209
0.145† (10) 0.323
0.118† -
Recovery 22 Mean
SD(5) 0.034
0.027(5) 0.048
0.011(5) 0.026
0.009-
PT_Rat
(sec)Dosing 17 Mean
SD(8) 14.64
0.76(9) 15.63
1.20* (10) 16.35
0.71† -
Recovery 22 Mean
SD(5) 15.34
1.30(5) 16.64
1.51(5) 18.68
1.78* -
APTT
(sec)Dosing 17 Mean
SD(8) 14.41
1.81(9) 16.50
2.65* (10) 16.78
1.78* -
Recovery 22 Mean
SD(5) 16.44
0.50(5) 17.76
0.79* (5) 18.12
0.67† -
FIB
(mg/dL)Dosing 17 Mean
SD(8) 253.1
14.3(9) 596.7
39.6† (10) 606.1
53.9† -
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709500
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
FIB
(mg/dL)Recovery 22 Mean
SD(5) 264.8
30.7(5) 266.6
21.9(5) 264.0
10.8-
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709501
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
RBC
(10^6/uL)Dosing 4 Mean
SD(7) 7.903
0.370(7) 7.381
0.190* (7) 7.470
0.206* --
17 Mean
SD(10) 7.423
0.183(9) 6.872
0.195† (7) 6.836
0.343† -
Recovery 22 Mean
SD(5) 7.262
0.267(5) 7.838
0.256† (5) 7.704
0.208* -
HGB
(g/dL)Dosing 4 Mean
SD(7) 14.53
0.59(7) 13.56
0.62* (7) 13.56
0.58* --
17 Mean
SD(10) 13.83
0.31(9) 12.38
0.34† (7) 12.24
0.68† -
Recovery 22 Mean
SD(5) 13.64
0.67(5) 13.92
0.37(5) 14.14
0.57-
HCT
(%)Dosing 4 Mean
SD(7) 44.91
1.91(7) 41.79
1.79* (7) 41.81
1.29* --
17 Mean
SD(10) 41.67
0.70(9) 38.09
0.98† (7) 37.21
1.75† -
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FDA-CBER-2021-5683-0709502
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
HCT
(%)Recovery 22 Mean
SD(5) 40.78
1.82(5) 42.46
0.93(5) 42.98
1.99-
MCV
(fL)Dosing 4 Mean
SD(7) 56.84
0.87(7) 56.59
1.75(7) 56.03
1.91--
17 Mean
SD(10) 56.16
1.19(9) 55.43
1.71(6) 54.40
1.97-
Recovery 22 Mean
SD(4) 55.80
2.62(5) 54.22
1.55(5) 55.78
2.21-
MCH
(pg)Dosing 4 Mean
SD(7) 18.37
0.22(7) 18.39
0.67(7) 18.16
0.75--
17 Mean
SD(10) 18.62
0.35(9) 17.99
0.49† (7) 17.89
0.60† -
Recovery 22 Mean
SD(5) 18.78
0.97(5) 17.76
0.38(5) 18.38
0.82-
MCHC
(g/dL)Dosing 4 Mean
SD(7) 32.34
0.30(7) 32.49
0.78(7) 32.41
0.63--
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FDA-CBER-2021-5683-0709503
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
MCHC
(g/dL)Dosing 17 Mean
SD(10) 33.18
0.32(9) 32.50
0.41† (7) 32.84
0.59-
Recovery 22 Mean
SD(5) 33.46
0.56(5) 32.78
0.33(5) 32.96
0.75-
RDW
(%)Dosing 4 Mean
SD(7) 11.11
0.29(7) 11.39
0.40(7) 11.97
0.68† --
17 Mean
SD(10) 11.33
0.43(9) 13.34
1.04† (6) 13.38
0.64† -
Recovery 22 Mean
SD(4) 10.80
0.33(5) 13.04
0.23† (5) 13.32
0.50† -
RETIC
(10^3/uL)Dosing 4 Mean
SD(7) 301.7
39.4(7) 129.7
35.7† (7) 133.6
39.1† --
17 Mean
SD(10) 168.9
34.7(9) 222.1
54.7* (7) 203.3
45.8-
Recovery 22 Mean
SD(5) 153.2
36.2(5) 155.0
16.0(5) 136.2
49.9-
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FDA-CBER-2021-5683-0709504
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
PLT
(10^3/uL)Dosing 4 Mean
SD(7) 927.1
116.6(7) 1003.9
70.9(7) 973.6
168.1--
17 Mean
SD(10) 906.9
124.5(9) 778.0
88.3* (7) 757.6
151.1-
Recovery 22 Mean
SD(5) 787.6
77.7(5) 838.2
88.0(5) 782.0
56.6-
MPV
(fL)Dosing 4 Mean
SD(7) 8.67
0.91(7) 8.91
0.25(7) 8.99
0.81--
17 Mean
SD(10) 9.50
0.49(9) 9.40
0.21(7) 9.73
0.72-
Recovery 22 Mean
SD(5) 9.20
0.42(5) 9.02
0.34(5) 9.18
0.33-
WBC
(10e3/uL)Dosing 4 Mean
SD(7) 6.01
2.38(7) 7.84
1.98(7) 8.57
0.92* --
17 Mean
SD(10) 2.16
0.45(9) 5.70
1.33† (7) 6.37
2.46† -
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FDA-CBER-2021-5683-0709505
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
WBC
(10e3/uL)Recovery 22 Mean
SD(5) 2.34
0.87(5) 2.62
0.69(5) 2.72
1.16-
NEUT
(10^3/uL)Dosing 4 Mean
SD(7) 0.920
1.220(7) 2.306
0.683(7) 2.879
0.478† --
17 Mean
SD(10) 0.409
0.198(9) 2.469
0.711† (7) 2.879
1.238† -
Recovery 22 Mean
SD(5) 0.252
0.051(5) 0.482
0.279* (5) 0.278
0.051-
LYM
(10^3/uL)Dosing 4 Mean
SD(7) 4.911
1.263(7) 5.136
1.368(7) 5.169
0.932--
17 Mean
SD(10) 1.651
0.289(9) 2.833
0.872† (7) 3.030
1.209† -
Recovery 22 Mean
SD(5) 2.016
0.899(5) 2.050
0.554(5) 2.316
1.068-
MONO
(10^3/uL)Dosing 4 Mean
SD(7) 0.093
0.092(7) 0.176
0.054(7) 0.234
0.062† --
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FDA-CBER-2021-5683-0709506
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
MONO
(10^3/uL)Dosing 17 Mean
SD(10) 0.056
0.025(9) 0.154
0.033† (7) 0.176
0.068† -
Recovery 22 Mean
SD(5) 0.028
0.013(5) 0.048
0.011(5) 0.060
0.025* -
EO
(10^3/uL)Dosing 4 Mean
SD(7) 0.057
0.011(7) 0.087
0.023* (7) 0.123
0.039† --
17 Mean
SD(10) 0.029
0.013(9) 0.092
0.043† (7) 0.097
0.042† -
Recovery 22 Mean
SD(5) 0.032
0.011(5) 0.028
0.011(5) 0.036
0.021-
BASO
(10^3/uL)Dosing 4 Mean
SD(7) 0.009
0.007(7) 0.017
0.010(7) 0.024
0.005† --
17 Mean
SD(10) 0.001
0.003(9) 0.008
0.004† (7) 0.010
0.006† -
Recovery 22 Mean
SD(5) 0.000
0.000(5) 0.000
0.000(5) 0.002
0.004-
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FDA-CBER-2021-5683-0709507
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
LUC
(10^3/uL)Dosing 4 Mean
SD(7) 0.030
0.028(7) 0.126
0.093† (7) 0.133
0.060† --
17 Mean
SD(10) 0.010
0.005(9) 0.132
0.101† (7) 0.190
0.096† -
Recovery 22 Mean
SD(5) 0.014
0.005(5) 0.012
0.008(5) 0.022
0.016-
PT_Rat
(sec)Dosing 17 Mean
SD(10) 14.12
0.84(9) 14.89
1.02(9) 15.38
0.93* -
Recovery 22 Mean
SD(5) 13.10
0.83(5) 13.66
0.83(5) 13.58
0.62-
APTT
(sec)Dosing 17 Mean
SD(10) 15.45
0.80(9) 15.56
1.39(9) 14.78
3.08-
Recovery 22 Mean
SD(5) 16.82
0.85(5) 17.26
0.90(5) 16.96
0.72-
FIB
(mg/dL)Dosing 17 Mean
SD(10) 217.2
25.0(9) 541.9
63.4† (9) 563.1
56.7† -
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FDA-CBER-2021-5683-0709508
Table 6
Hematology and Coagulation
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
FIB
(mg/dL)Recovery 22 Mean
SD(5) 186.4
17.2(5) 196.6
18.4(5) 185.0
16.6-
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FDA-CBER-2021-5683-0709509
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Parameter Description
ALT Alanine Aminotransferase
AST Aspartate Aminotransferase
ALP Alkaline Phosphatase
GGT Gamma Glutamyl Transferase
TBIL Bilirubin, Total
CHOL Cholesterol
TRIG Triglycerides
GLUC Glucose
TP Protein, Total
ALB Albumin
GLOB Globulin
AG Albumin/Globulin Ratio
BUN Blood Urea Nitrogen
CREA Creatinine
PHOS Phosphorus
CA Calcium
NA Sodium
K Potassium
CL Chloride
A2M Alpha-2-MacroglobulinParameter Description
A1AGP Alpha-1 Acid Glycoprotein
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709510
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Footnotes
Note: Sample size is displayed in ( ) before the mean value.
SD = Standard Deviation; - = Value not applicable;
Units are displayed in the ( ) under each parameter name;
HPD = Hours Post Dose; U = Unscheduled;
e = Group mean excluded from statistics;
REF = Denotes group used as reference in the statistical test;
* = Statistically significant pairwise comparison at 0.05 level;
† = Statistically significant pairwise comparison at 0.01 level;
‡ = Statistically significant trend at 0.05 level;
§ = Statistically significant trend at 0.01 level.
+ = Ascending trend sign;
- = Descending trend sign;
# = Individual parameter values reported as less than or greater than limit of quantitation are set equal to the limit to calculate the average.
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FDA-CBER-2021-5683-0709511
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
ALT
(U/L)Dosing 4 Mean
SD(8) 29.1
6.9(8) 33.3
6.5(8) 28.8
5.6---
17 Mean
SD(10) 18.1
2.4(10) 22.9
4.7* (10) 20.8
3.0-
Recovery 22 Mean
SD(5) 19.2
3.3(5) 17.6
2.5(5) 17.4
3.0-
AST
(U/L)Dosing 4 Mean
SD(8) 94.5
8.3(8) 103.1
14.7(8) 97.8
14.0---
17 Mean
SD(10) 71.7
5.3(10) 84.2
15.4* (10) 86.8
8.5† -
Recovery 22 Mean
SD(5) 91.8
10.3(5) 94.0
13.5(5) 97.0
4.6-
ALP
(U/L)Dosing 4 Mean
SD(8) 166.6
50.3(8) 195.4
28.2* (8) 188.3
29.0---
17 Mean
SD(10) 97.6
25.9(10) 103.4
18.9(10) 110.0
22.8-
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FDA-CBER-2021-5683-0709512
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
ALP
(U/L)Recovery 22 Mean
SD(5) 84.4
17.0(5) 79.6
9.3(5) 83.4
18.6-
GGT
(U/L)Dosing 4 Mean
SD(8) 3.0
0.0 #(8) 3.0
0.0 #(8) 3.0
0.0 #---
17 Mean
SD(10) 3.0
0.0 #(10) 3.0
0.0 #(10) 3.0
0.0 #-
Recovery 22 Mean
SD(5) 3.0
0.0 #(5) 3.0
0.0 #(5) 3.0
0.0 #-
TBIL
(mg/dL)Dosing 4 Mean
SD(8) 0.10
0.00 #(8) 0.10
0.00 #(8) 0.10
0.00 #---
17 Mean
SD(10) 0.10
0.00 #(10) 0.10
0.00 #(10) 0.10
0.00 #-
Recovery 22 Mean
SD(5) 0.10
0.00 #(5) 0.10
0.00 #(5) 0.10
0.00 #-
CHOL
(mg/dL)Dosing 4 Mean
SD(8) 63.0
9.3(8) 52.5
7.2(8) 51.8
15.3---
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FDA-CBER-2021-5683-0709513
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
CHOL
(mg/dL)Dosing 17 Mean
SD(10) 51.7
6.7(10) 40.2
6.1† (10) 37.2
8.6† -
Recovery 22 Mean
SD(5) 52.8
7.2(5) 61.0
5.7* (5) 56.2
4.4-
TRIG
(mg/dL)Dosing 4 Mean
SD(8) 62.0
25.8(8) 42.8
10.2(8) 51.9
19.6---
17 Mean
SD(10) 58.8
16.6(10) 33.6
7.2† (10) 35.9
10.3† -
Recovery 22 Mean
SD(5) 49.0
18.4(5) 50.8
15.1(5) 45.6
16.0-
GLUC
(mg/dL)Dosing 4 Mean
SD(8) 111.3
14.2(8) 98.1
12.6(8) 100.0
16.7---
17 Mean
SD(10) 131.7
17.0(10) 117.4
17.0(10) 122.6
23.9-
Recovery 22 Mean
SD(5) 137.0
30.1(5) 121.4
23.7(5) 119.8
16.1-
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FDA-CBER-2021-5683-0709514
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
TP
(g/dL)Dosing 4 Mean
SD(8) 6.10
0.21(8) 5.90
0.22(8) 5.85
0.22---
17 Mean
SD(10) 5.39
0.30(10) 5.51
0.36(10) 5.41
0.34-
Recovery 22 Mean
SD(5) 5.82
0.16(5) 6.08
0.11* (5) 5.90
0.14-
ALB
(g/dL)Dosing 4 Mean
SD(8) 3.98
0.14(8) 3.71
0.15† (8) 3.68
0.14† ---
17 Mean
SD(10) 3.50
0.19(10) 3.43
0.21(10) 3.38
0.22-
Recovery 22 Mean
SD(5) 3.72
0.11(5) 3.82
0.08(5) 3.72
0.13-
GLOB
(g/dL)Dosing 4 Mean
SD(8) 2.13
0.09(8) 2.19
0.10(8) 2.18
0.10---
17 Mean
SD(10) 1.89
0.12(10) 2.08
0.18* (10) 2.03
0.13-
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FDA-CBER-2021-5683-0709515
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
GLOB
(g/dL)Recovery 22 Mean
SD(5) 2.10
0.07(5) 2.26
0.05† (5) 2.18
0.04-
AG
(None)Dosing 4 Mean
SD(8) 1.88
0.07(8) 1.70
0.08† (8) 1.69
0.06† ---
17 Mean
SD(10) 1.85
0.05(10) 1.65
0.08† (10) 1.65
0.05† -
Recovery 22 Mean
SD(5) 1.76
0.05(5) 1.72
0.04(5) 1.70
0.07-
BUN
(mg/dL)Dosing 4 Mean
SD(8) 23.8
5.0(8) 26.0
4.0(8) 23.8
2.7---
17 Mean
SD(10) 18.8
3.9(10) 18.6
3.2(10) 19.9
2.8-
Recovery 22 Mean
SD(5) 17.0
1.7(5) 17.2
1.3(5) 16.4
3.8-
CREA
(mg/dL)Dosing 4 Mean
SD(8) 0.31
0.04(8) 0.29
0.04(8) 0.26
0.05* ---
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709516
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
CREA
(mg/dL)Dosing 17 Mean
SD(10) 0.25
0.05(10) 0.25
0.07(10) 0.27
0.05-
Recovery 22 Mean
SD(5) 0.28
0.04(5) 0.28
0.04(5) 0.28
0.04-
PHOS
(mg/dL)Dosing 4 Mean
SD(8) 7.34
0.56(8) 7.41
0.45(8) 7.58
0.38---
17 Mean
SD(10) 8.72
0.75(10) 8.11
0.58(10) 8.01
0.92-
Recovery 22 Mean
SD(5) 6.56
1.15(5) 6.86
0.46(5) 6.82
0.72-
CA
(mg/dL)Dosing 4 Mean
SD(8) 9.76
0.25(8) 9.65
0.28(8) 9.75
0.32---
17 Mean
SD(10) 9.86
0.34(10) 9.82
0.35(10) 9.59
0.30-
Recovery 22 Mean
SD(5) 9.44
0.11(5) 9.44
0.29(5) 9.48
0.27-
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FDA-CBER-2021-5683-0709517
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
NA
(mmol/L)Dosing 4 Mean
SD(8) 144.4
1.6(8) 144.1
1.4(8) 143.8
1.2---
17 Mean
SD(10) 144.0
1.2(10) 142.3
1.9(10) 142.7
1.9-
Recovery 22 Mean
SD(5) 142.4
0.5(5) 142.6
0.9(5) 143.4
0.9-
K
(mmol/L)Dosing 4 Mean
SD(8) 4.45
0.31(8) 4.55
0.18(8) 4.66
0.29---
17 Mean
SD(10) 4.30
0.16(10) 4.36
0.31(10) 4.32
0.19-
Recovery 22 Mean
SD(5) 4.12
0.28(5) 4.26
0.26(5) 4.20
0.20-
CL
(mmol/L)Dosing 4 Mean
SD(8) 102.4
2.8(8) 102.0
0.9(8) 101.3
1.3---
17 Mean
SD(10) 104.8
0.9(10) 103.4
1.8(10) 104.2
1.3-
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709518
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
CL
(mmol/L)Recovery 22 Mean
SD(5) 105.6
1.5(5) 106.0
1.0(5) 106.4
1.1-
A2M
(ug/mL)Dosing 4 Mean
SD(8) 113.4
228.9(8) 2318.1
922.4† (8) 3911.6
2866.1† ---
17 Mean
SD(10) 14.0
3.3(10) 990.6
730.0† (10) 1794.2
1234.1† -
Recovery 22 Mean
SD(5) 8.0
1.9(5) 19.4
14.3* (5) 16.2
2.3† -
A1AGP
(ug/mL)Dosing 4 Mean
SD(8) 174.358
312.769(8) 1642.265
312.914† (8) 2351.791
1053.465† ---
17 Mean
SD(10) 47.672
12.664(10) 1835.986
372.467† (10) 2021.083
673.967† -
Recovery 22 Mean
SD(5) 54.910
20.556(5) 75.740
26.083(5) 62.562
16.549-
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FDA-CBER-2021-5683-0709519
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
ALT
(U/L)Dosing 4 Mean
SD(8) 20.9
4.3(8) 24.9
4.3(8) 23.1
5.2---
17 Mean
SD(9) 11.3
1.3(9) 13.9
2.1† (8) 16.5
3.3† -
Recovery 22 Mean
SD(5) 11.8
2.2(5) 14.8
2.2(5) 13.6
1.8-
AST
(U/L)Dosing 4 Mean
SD(8) 81.8
11.5(8) 96.1
14.6(8) 91.3
10.4---
17 Mean
SD(9) 69.9
18.3(9) 81.7
15.9(8) 80.3
18.0-
Recovery 22 Mean
SD(5) 65.4
8.2(5) 73.6
10.2(5) 67.2
4.4-
ALP
(U/L)Dosing 4 Mean
SD(8) 92.9
21.7(8) 137.9
21.4† (8) 143.4
31.1† ---
17 Mean
SD(9) 50.9
10.3(9) 78.1
17.7† (8) 97.4
18.8† -
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FDA-CBER-2021-5683-0709520
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
ALP
(U/L)Recovery 22 Mean
SD(5) 34.0
6.2(5) 37.0
6.4(5) 29.0
7.6-
GGT
(U/L)Dosing 4 Mean
SD(8) 3.0
0.0 #(8) 3.0
0.0 #(8) 3.0
0.0 #---
17 Mean
SD(9) 3.0
0.0 #(9) 3.0
0.0 #(8) 3.0
0.0 #-
Recovery 22 Mean
SD(5) 3.0
0.0 #(5) 3.0
0.0 #(5) 3.0
0.0 #-
TBIL
(mg/dL)Dosing 4 Mean
SD(8) 0.10
0.00 #(8) 0.10
0.00 #(8) 0.10
0.00 #---
17 Mean
SD(9) 0.10
0.00 #(9) 0.10
0.00 #(8) 0.10
0.00 #-
Recovery 22 Mean
SD(5) 0.10
0.00 #(5) 0.10
0.00 #(5) 0.10
0.00 #-
CHOL
(mg/dL)Dosing 4 Mean
SD(8) 45.6
13.4(8) 47.3
12.3(8) 56.6
12.4---
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709521
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
CHOL
(mg/dL)Dosing 17 Mean
SD(9) 33.4
11.5(9) 33.7
6.3(8) 31.9
4.2-
Recovery 22 Mean
SD(5) 43.0
13.0(5) 54.2
18.9(5) 41.2
8.6-
TRIG
(mg/dL)Dosing 4 Mean
SD(8) 36.8
13.0(8) 29.4
6.8(8) 34.5
7.8---
17 Mean
SD(9) 27.8
8.4(9) 25.1
5.1(8) 26.5
5.1-
Recovery 22 Mean
SD(5) 30.8
8.7(5) 31.8
3.7(5) 37.2
7.9-
GLUC
(mg/dL)Dosing 4 Mean
SD(8) 102.5
8.4(8) 89.1
8.2† (8) 87.1
5.9† ---
17 Mean
SD(9) 111.4
16.4(9) 99.7
7.7(8) 99.5
8.8-
Recovery 22 Mean
SD(5) 119.4
14.3(5) 107.6
10.7(5) 118.0
22.2-
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709522
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
TP
(g/dL)Dosing 4 Mean
SD(8) 6.26
0.35(8) 5.65
0.17† (8) 5.94
0.23---
17 Mean
SD(9) 5.44
0.32(9) 4.98
0.21† (8) 4.96
0.29† -
Recovery 22 Mean
SD(5) 6.52
0.37(5) 6.54
0.21(5) 6.74
0.30-
ALB
(g/dL)Dosing 4 Mean
SD(8) 4.16
0.23(8) 3.56
0.09† (8) 3.73
0.14† ---
17 Mean
SD(9) 3.60
0.19(9) 3.07
0.11† (8) 3.09
0.14† -
Recovery 22 Mean
SD(5) 4.26
0.32(5) 4.14
0.11(5) 4.32
0.19-
GLOB
(g/dL)Dosing 4 Mean
SD(8) 2.10
0.14(8) 2.09
0.08(8) 2.21
0.10---
17 Mean
SD(9) 1.84
0.15(9) 1.91
0.12(8) 1.88
0.18-
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FDA-CBER-2021-5683-0709523
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
GLOB
(g/dL)Recovery 22 Mean
SD(5) 2.26
0.11(5) 2.40
0.10(5) 2.42
0.13-
AG
(None)Dosing 4 Mean
SD(8) 1.98
0.07(8) 1.71
0.04† (8) 1.69
0.04† ---
17 Mean
SD(9) 1.96
0.12(9) 1.61
0.06† (8) 1.66
0.12† -
Recovery 22 Mean
SD(5) 1.90
0.16(5) 1.72
0.04* (5) 1.80
0.07-
BUN
(mg/dL)Dosing 4 Mean
SD(8) 16.8
1.9(8) 18.8
4.2(8) 18.3
2.5---
17 Mean
SD(9) 17.0
3.0(9) 18.9
3.3(8) 20.0
1.3-
Recovery 22 Mean
SD(5) 16.6
3.0(5) 18.4
2.7(5) 18.2
1.8-
CREA
(mg/dL)Dosing 4 Mean
SD(8) 0.31
0.04(8) 0.23
0.05† (8) 0.25
0.05* ---
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709524
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
CREA
(mg/dL)Dosing 17 Mean
SD(9) 0.27
0.07(9) 0.22
0.04(8) 0.21
0.04-
Recovery 22 Mean
SD(5) 0.36
0.05(5) 0.30
0.00(5) 0.32
0.04-
PHOS
(mg/dL)Dosing 4 Mean
SD(8) 6.61
0.56(8) 6.81
0.57(8) 6.91
0.57---
17 Mean
SD(9) 7.37
0.95(9) 7.38
0.55(8) 7.73
1.03-
Recovery 22 Mean
SD(5) 6.48
0.78(5) 6.30
0.88(5) 6.76
0.94-
CA
(mg/dL)Dosing 4 Mean
SD(8) 9.70
0.26(8) 9.59
0.18(8) 9.81
0.29---
17 Mean
SD(9) 9.52
0.14(9) 9.53
0.27(8) 9.65
0.27-
Recovery 22 Mean
SD(5) 9.76
0.30(5) 9.80
0.12(5) 9.82
0.31-
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FDA-CBER-2021-5683-0709525
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
NA
(mmol/L)Dosing 4 Mean
SD(8) 143.8
0.9(8) 143.1
1.0(8) 143.8
1.4---
17 Mean
SD(9) 143.6
1.1(9) 143.0
1.3(8) 143.1
0.8-
Recovery 22 Mean
SD(5) 142.2
1.9(5) 143.2
0.8(5) 142.8
1.3-
K
(mmol/L)Dosing 4 Mean
SD(8) 3.85
0.14(8) 4.33
0.37† (8) 4.39
0.36† ---
17 Mean
SD(9) 4.46
0.28(9) 4.53
0.18(8) 4.75
0.24-
Recovery 22 Mean
SD(5) 3.84
0.32(5) 4.00
0.16(5) 4.00
0.22-
CL
(mmol/L)Dosing 4 Mean
SD(8) 104.1
1.4(8) 104.5
1.8(8) 105.1
2.0---
17 Mean
SD(9) 108.0
1.0(9) 107.7
1.8(8) 108.1
1.2-
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709526
Table 7
Clinical Chemistry
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase
DayGroup Number: REF 2 3
HPD 0 µg/day 30 µg /day 30 µg/day Dose :
CL
(mmol/L)Recovery 22 Mean
SD(5) 106.8
2.3(5) 106.0
1.2(5) 106.8
0.8-
A2M
(ug/mL)Dosing 4 Mean
SD(8) 212.1
241.1(8) 703.8
396.4† (8) 887.1
352.9† ---
17 Mean
SD(10) 33.1
49.7(9) 521.0
260.6† (8) 592.0
243.7† -
Recovery 22 Mean
SD(5) 17.2
8.5(5) 16.2
5.7(5) 16.0
4.3-
A1AGP
(ug/mL)Dosing 4 Mean
SD(8) 239.774
176.264(8) 1906.314
376.234† (8) 1677.103
269.796† ---
17 Mean
SD(10) 95.959
82.718(9) 1491.849
326.518† (8) 1651.071
404.600† -
Recovery 22 Mean
SD(5) 62.788
18.725(5) 47.912
12.620(5) 57.588
19.626-
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709527
Table 8
Urinalysis
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Parameter Description
pH pH
SG Specific Gravity
VOLUME Total Volume
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709528
Table 8
Urinalysis
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Footnotes
Note: Sample size is displayed in ( ) before the mean value.
SD = Standard Deviation; - = Value not applicable;
Units are displayed in the ( ) under each parameter name;
HPD = Hours Post Dose; U = Unscheduled;
e = Group mean excluded from statistics;
REF = Denotes group used as reference in the statistical test;
* = Statistically significant pairwise comparison at 0.05 level;
† = Statistically significant pairwise comparison at 0.01 level;
‡ = Statistically significant trend at 0.05 level;
§ = Statistically significant trend at 0.01 level.
+ = Ascending trend sign;
- = Descending trend sign;
# = Individual parameter values reported as less than or greater than limit of quantitation are set equal to the limit to calculate the average.
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709529
Table 8
Urinalysis
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Male
Phase DayGroup Number:
REF 2 3
Dose : 0 µg/day 30 µg/day 30 µg /day
pH
(None)Dosing 17 Mean
SD(10) 7.10
0.39(10) 6.75
0.35(10) 6.60
0.32†
Recovery 22 Mean
SD(5) 7.30
0.45(5) 7.20
0.27(5) 7.00
0.35
SG
(None)Dosing 17 Mean
SD(10) 1.0322
0.0205(10) 1.0260
0.0227(10) 1.0282
0.0183
Recovery 22 Mean
SD(5) 1.0556
0.0038(5) 1.0340
0.0146* (5) 1.0440
0.0234
VOLUME
(mL)Dosing 17 Mean
SD(10) 14.90
15.54(10) 17.80
16.95(10) 11.60
6.88
Recovery 22 Mean
SD(5) 3.70
0.97(5) 8.20
5.50(5) 8.00
10.68
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709530
Table 8
Urinalysis
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A
3-WEEK RECOVERY
Female
Phase DayGroup Number:
REF 2 3
Dose : 0 µg/day 30 µg/day 30 µg /day
pH
(None)Dosing 17 Mean
SD(10) 6.75
0.26(10) 6.20
0.26† (10) 6.20
0.35†
Recovery 22 Mean
SD(5) 7.00
0.61(5) 6.60
0.65(5) 6.50
0.35
SG
(None)Dosing 17 Mean
SD(10) 1.0243
0.0128(10) 1.0288
0.0164(10) 1.0250
0.0140
Recovery 22 Mean
SD(5) 1.0240
0.0174(5) 1.0364
0.0177(5) 1.0276
0.0198
VOLUME
(mL)Dosing 17 Mean
SD(10) 9.90
7.03(10) 9.60
9.05(10) 9.40
6.98
Recovery 22 Mean
SD(5) 11.00
7.38(5) 6.00
5.09(5) 9.00
7.52
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709531
Table 9
Organ Weights (g) and Ratios
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
ABS = Absolute Value; OW = Organ Weight; BWT = Body Weight; BRN = Brain Weight; OW:BW = (g/g)*100; OW:BRN = g/g.
- = Value not applicable; N = Sample Size; Ratio = Group Mean / Reference Group Mean; R REF = Denotes group used as reference in the ratiocalculations; SD = Standard Deviation;REF = Denotes group used as reference in the statistical test;e = Group mean excluded from statistics;@ = Number examined reduced due to excluded data;* = Statistically significant pairwise comparision at 0.05 level;† = Statistically significant pairwise comparision at 0.01 level;
‡ = Statistically significant trend at 0.05 level;§ = Statistically significant trend at 0.01 level;+ = Ascending trend sign;- = Descending trend sign;
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709532
FDA-CBER-2021-5683-0709533
FDA-CBER-2021-5683-0709534
FDA-CBER-2021-5683-0709535
FDA-CBER-2021-5683-0709536
FDA-CBER-2021-5683-0709537
FDA-CBER-2021-5683-0709538
Table 10
Summary Report of Macroscopic Observations
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Note: Animals that were examined and found to be normal are not included in this report and the number of animals examined
reflects the total number of animals examined grossly;
- = Value not applicable.
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709539
FDA-CBER-2021-5683-0709540
FDA-CBER-2021-5683-0709541
Table 11
Summary Report of Microscopic Observations
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
NOS= Not otherwise specified; - = Value not applicable.Footnotes
Pfizer CONFIDENTIALReport for Study 20GR142
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FDA-CBER-2021-5683-0709542
FDA-CBER-2021-5683-0709543
FDA-CBER-2021-5683-0709544
FDA-CBER-2021-5683-0709545
FDA-CBER-2021-5683-0709546
FDA-CBER-2021-5683-0709547
FDA-CBER-2021-5683-0709548
FDA-CBER-2021-5683-0709549
FDA-CBER-2021-5683-0709550
FDA-CBER-2021-5683-0709551
FDA-CBER-2021-5683-0709552
FDA-CBER-2021-5683-0709553
FDA-CBER-2021-5683-0709554
FDA-CBER-2021-5683-0709555
FDA-CBER-2021-5683-0709556
FDA-CBER-2021-5683-0709557
FDA-CBER-2021-5683-0709558
FDA-CBER-2021-5683-0709559
FDA-CBER-2021-5683-0709560
FDA-CBER-2021-5683-0709561
FDA-CBER-2021-5683-0709562
FDA-CBER-2021-5683-0709563
FDA-CBER-2021-5683-0709564
* Statistically significant at 0.05 level ** Statistically significant at 0.01 levelREF: Denotes group used as reference in the statistical tests.Injection Site Score
20GR142: 17-DAY INTRAMUSCULAR TOXICITY STUDY OF BNT162B2 (V9) AND
BNT162B3C IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Parameter Phase Group N MeanStandard
Deviation
Edema - Left Recovery 2: BNT162b2 (V9) 4 1.08 0.17
3: BNT162b3c 5 0.80 0.18
Erythema - Left Recovery 2: BNT162b2 (V9) 4 0.00 0.00
3: BNT162b3c 5 0.00 0.00Report for Study 20GR142
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FDA-CBER-2021-5683-0709565
* Statistically significant at 0.05 level ** Statistically significant at 0.01 levelREF: Denotes group used as reference in the statistical tests.Injection Site Score
20GR142: 17-DAY INTRAMUSCULAR TOXICITY STUDY OF BNT162B2 (V9) AND
BNT162B3C IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Parameter Phase Group N MeanStandard
Deviation
Edema - Left Recovery 2: BNT162b2 (V9) 5 1.07 0.15
3: BNT162b3c 5 1.13 0.18
Erythema - Left Recovery 2: BNT162b2 (V9) 5 0.13 0.18
3: BNT162b3c 5 0.33 0.24Report for Study 20GR142
Page 125PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
FDA-CBER-2021-5683-0709566
* Statistically significant at 0.05 level ** Statistically significant at 0.01 levelREF: Denotes group used as reference in the statistical tests.Body Temperature (Deg C)
20GR142: 17-DAY INTRAMUSCULAR TOXICITY STUDY OF BNT162B2 (V9) AND
BNT162B3C IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Phase Day Group N MeanStandard
DeviationPairwise
p-value
Dosing 1 1: Saline 15 38.31 0.35 REF
2: BNT162b2 (V9) 15 38.85 0.36 0.001 **
3: BNT162b3c 15 39.02 0.40 0.001 **
Dosing 8 1: Saline 15 37.07 0.37 REF
2: BNT162b2 (V9) 15 38.05 0.62 0.001 **
3: BNT162b3c 15 38.33 0.43 0.001 **
Dosing 15 1: Saline 15 37.34 0.35 REF
2: BNT162b2 (V9) 15 38.37 0.42 0.001 **
3: BNT162b3c 15 38.43 0.36 0.001 **Report for Study 20GR142
Page 126PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
FDA-CBER-2021-5683-0709567
* Statistically significant at 0.05 level ** Statistically significant at 0.01 levelREF: Denotes group used as reference in the statistical tests.Body Temperature (Deg C)
20GR142: 17-DAY INTRAMUSCULAR TOXICITY STUDY OF BNT162B2 (V9) AND
BNT162B3C IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Phase Day Group N MeanStandard
DeviationPairwise
p-value
Dosing 1 1: Saline 15 38.08 0.44 REF
2: BNT162b2 (V9) 15 38.50 0.53 0.044 *
3: BNT162b3c 15 38.58 0.36 0.009 **
Dosing 8 1: Saline 15 37.81 0.38 REF
2: BNT162b2 (V9) 15 38.47 0.44 0.001 **
3: BNT162b3c 15 38.73 0.40 0.001 **
Dosing 15 1: Saline 15 38.02 0.74 REF
2: BNT162b2 (V9) 15 38.15 0.54 0.963
3: BNT162b3c 15 38.35 0.31 0.174Report for Study 20GR142
Page 127PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
FDA-CBER-2021-5683-0709568
Dead Animal Status Report Page 1 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
1677 22 Jul 2020 08:53:06 AM 22 Jul 2020 08:53:07 AM Y 17 Dosing 1 M 001
Death Status: Terminal Euthanasia Death Type: Scheduled
1787 22 Jul 2020 08:50:04 AM 22 Jul 2020 08:50:05 AM Y 17 Dosing 1 M 002
Death Status: Terminal Euthanasia Death Type: Scheduled
727 22 Jul 2020 08:57:39 AM 22 Jul 2020 08:57:40 AM Y 17 Dosing 1 M 003
Death Status: Terminal Euthanasia Death Type: Scheduled
598 22 Jul 2020 09:02:59 AM 22 Jul 2020 09:02:59 AM Y 17 Dosing 1 M 004
Death Status: Terminal Euthanasia Death Type: Scheduled
727 22 Jul 2020 09:37:05 AM 22 Jul 2020 09:37:06 AM Y 17 Dosing 1 M 005
Death Status: Terminal Euthanasia Death Type: Scheduled
1687 22 Jul 2020 09:46:22 AM 22 Jul 2020 09:46:22 AM Y 17 Dosing 1 M 006
Death Status: Terminal Euthanasia Death Type: Scheduled
807 22 Jul 2020 09:58:31 AM 22 Jul 2020 09:58:32 AM Y 17 Dosing 1 M 007
Death Status: Terminal Euthanasia Death Type: Scheduled
727 22 Jul 2020 10:17:27 AM 22 Jul 2020 10:17:28 AM Y 17 Dosing 1 M 008
Death Status: Terminal Euthanasia Death Type: Scheduled
808 22 Jul 2020 10:30:03 AM 22 Jul 2020 10:30:04 AM Y 17 Dosing 1 M 009
Death Status: Terminal Euthanasia Death Type: Scheduled
1777 22 Jul 2020 10:41:36 AM 22 Jul 2020 10:41:36 AM Y 17 Dosing 1 M 010
Death Status: Terminal Euthanasia Death Type: Scheduled
1057 13 Aug 2020 07:32:04 AM 13 Aug 2020 07:32:05 AM Y 22 Recovery 1 M 011
Death Status: Recovery Euthanasia 1 Death Type: ScheduledReport for Study 20GR142
Page 128PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709569
Dead Animal Status Report Page 2 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
232 13 Aug 2020 08:15:17 AM 13 Aug 2020 08:15:18 AM Y 22 Recovery 1 M 012
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1307 13 Aug 2020 08:29:36 AM 13 Aug 2020 08:29:37 AM Y 22 Recovery 1 M 013
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1777 13 Aug 2020 09:02:02 AM 13 Aug 2020 09:02:03 AM Y 22 Recovery 1 M 014
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
232 13 Aug 2020 09:23:27 AM 13 Aug 2020 09:23:28 AM Y 22 Recovery 1 M 015
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1057 22 Jul 2020 08:42:46 AM 22 Jul 2020 08:42:47 AM Y 17 Dosing 2 M 016
Death Status: Terminal Euthanasia Death Type: Scheduled
1777 22 Jul 2020 08:48:01 AM 22 Jul 2020 08:48:01 AM Y 17 Dosing 2 M 017
Death Status: Terminal Euthanasia Death Type: Scheduled
1307 22 Jul 2020 09:01:59 AM 22 Jul 2020 09:01:59 AM Y 17 Dosing 2 M 018
Death Status: Terminal Euthanasia Death Type: Scheduled
807 22 Jul 2020 09:08:39 AM 22 Jul 2020 09:08:39 AM Y 17 Dosing 2 M 019
Death Status: Terminal Euthanasia Death Type: Scheduled
1677 22 Jul 2020 09:41:57 AM 22 Jul 2020 09:41:57 AM Y 17 Dosing 2 M 020
Death Status: Terminal Euthanasia Death Type: Scheduled
1308 22 Jul 2020 09:53:57 AM 22 Jul 2020 09:53:58 AM Y 17 Dosing 2 M 021
Death Status: Terminal Euthanasia Death Type: Scheduled
598 22 Jul 2020 09:59:56 AM 22 Jul 2020 09:59:56 AM Y 17 Dosing 2 M 022
Death Status: Terminal Euthanasia Death Type: Scheduled
Report for Study 20GR142
Page 129PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709570
Dead Animal Status Report Page 3 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
1787 22 Jul 2020 10:29:38 AM 22 Jul 2020 10:29:38 AM Y 17 Dosing 2 M 023
Death Status: Terminal Euthanasia Death Type: Scheduled
1307 22 Jul 2020 10:38:09 AM 22 Jul 2020 10:38:10 AM Y 17 Dosing 2 M 024
Death Status: Terminal Euthanasia Death Type: Scheduled
807 22 Jul 2020 10:44:39 AM 22 Jul 2020 10:44:40 AM Y 17 Dosing 2 M 025
Death Status: Terminal Euthanasia Death Type: Scheduled
1777 13 Aug 2020 07:36:45 AM 13 Aug 2020 07:36:46 AM Y 22 Recovery 2 M 026
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
598 13 Aug 2020 08:25:28 AM 13 Aug 2020 08:25:29 AM Y 22 Recovery 2 M 027
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
807 13 Aug 2020 08:44:11 AM 13 Aug 2020 08:44:12 AM Y 22 Recovery 2 M 028
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1057 13 Aug 2020 09:12:59 AM 13 Aug 2020 09:13:00 AM Y 22 Recovery 2 M 029
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
598 13 Aug 2020 09:25:22 AM 13 Aug 2020 09:25:24 AM Y 22 Recovery 2 M 030
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1308 22 Jul 2020 08:47:19 AM 22 Jul 2020 08:47:19 AM Y 17 Dosing 3 M 031
Death Status: Terminal Euthanasia Death Type: Scheduled
1687 22 Jul 2020 08:55:08 AM 22 Jul 2020 08:55:08 AM Y 17 Dosing 3 M 032
Death Status: Terminal Euthanasia Death Type: Scheduled
808 22 Jul 2020 09:03:00 AM 22 Jul 2020 09:03:01 AM Y 17 Dosing 3 M 033
Death Status: Terminal Euthanasia Death Type: ScheduledReport for Study 20GR142
Page 130PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709571
Dead Animal Status Report Page 4 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
1057 22 Jul 2020 09:25:56 AM 22 Jul 2020 09:25:56 AM Y 17 Dosing 3 M 034
Death Status: Terminal Euthanasia Death Type: Scheduled
808 22 Jul 2020 09:45:48 AM 22 Jul 2020 09:45:49 AM Y 17 Dosing 3 M 035
Death Status: Terminal Euthanasia Death Type: Scheduled
1307 22 Jul 2020 09:56:54 AM 22 Jul 2020 09:56:55 AM Y 17 Dosing 3 M 036
Death Status: Terminal Euthanasia Death Type: Scheduled
1057 22 Jul 2020 10:14:20 AM 22 Jul 2020 10:14:21 AM Y 17 Dosing 3 M 037
Death Status: Terminal Euthanasia Death Type: Scheduled
1677 22 Jul 2020 10:27:35 AM 22 Jul 2020 10:27:36 AM Y 17 Dosing 3 M 038
Death Status: Terminal Euthanasia Death Type: Scheduled
1687 22 Jul 2020 10:38:42 AM 22 Jul 2020 10:38:43 AM Y 17 Dosing 3 M 039
Death Status: Terminal Euthanasia Death Type: Scheduled
598 22 Jul 2020 10:52:34 AM 22 Jul 2020 10:52:35 AM Y 17 Dosing 3 M 040
Death Status: Terminal Euthanasia Death Type: Scheduled
808 13 Aug 2020 08:12:59 AM 13 Aug 2020 08:13:00 AM Y 22 Recovery 3 M 041
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1057 13 Aug 2020 08:26:36 AM 13 Aug 2020 08:26:36 AM Y 22 Recovery 3 M 042
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
808 13 Aug 2020 08:59:12 AM 13 Aug 2020 08:59:13 AM Y 22 Recovery 3 M 043
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1307 13 Aug 2020 09:10:48 AM 13 Aug 2020 09:10:49 AM Y 22 Recovery 3 M 044
Death Status: Recovery Euthanasia 1 Death Type: ScheduledReport for Study 20GR142
Page 131PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709572
Dead Animal Status Report Page 5 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
807 13 Aug 2020 09:30:28 AM 13 Aug 2020 09:30:29 AM Y 22 Recovery 3 M 045
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
727 22 Jul 2020 10:55:54 AM 22 Jul 2020 10:55:55 AM Y 17 Dosing 1 F 046
Death Status: Terminal Euthanasia Death Type: Scheduled
808 22 Jul 2020 11:13:53 AM 22 Jul 2020 11:13:53 AM Y 17 Dosing 1 F 047
Death Status: Terminal Euthanasia Death Type: Scheduled
1307 22 Jul 2020 11:32:53 AM 22 Jul 2020 11:32:54 AM Y 17 Dosing 1 F 048
Death Status: Terminal Euthanasia Death Type: Scheduled
1777 22 Jul 2020 11:53:48 AM 22 Jul 2020 11:53:48 AM Y 17 Dosing 1 F 049
Death Status: Terminal Euthanasia Death Type: Scheduled
1307 22 Jul 2020 12:09:56 PM 22 Jul 2020 12:09:57 PM Y 17 Dosing 1 F 050
Death Status: Terminal Euthanasia Death Type: Scheduled
807 22 Jul 2020 12:17:24 PM 22 Jul 2020 12:17:24 PM Y 17 Dosing 1 F 051
Death Status: Terminal Euthanasia Death Type: Scheduled
1677 22 Jul 2020 12:29:39 PM 22 Jul 2020 12:29:39 PM Y 17 Dosing 1 F 052
Death Status: Terminal Euthanasia Death Type: Scheduled
1057 22 Jul 2020 12:41:24 PM 22 Jul 2020 12:41:24 PM Y 17 Dosing 1 F 053
Death Status: Terminal Euthanasia Death Type: Scheduled
1308 22 Jul 2020 01:06:59 PM 22 Jul 2020 01:06:59 PM Y 17 Dosing 1 F 054
Death Status: Terminal Euthanasia Death Type: Scheduled
1677 22 Jul 2020 01:13:05 PM 22 Jul 2020 01:13:06 PM Y 17 Dosing 1 F 055
Death Status: Terminal Euthanasia Death Type: ScheduledReport for Study 20GR142
Page 132PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709573
Dead Animal Status Report Page 6 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
808 13 Aug 2020 09:40:42 AM 13 Aug 2020 09:40:43 AM Y 22 Recovery 1 F 056
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1777 13 Aug 2020 10:06:54 AM 13 Aug 2020 10:06:55 AM Y 22 Recovery 1 F 057
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
808 13 Aug 2020 10:24:39 AM 13 Aug 2020 10:24:40 AM Y 22 Recovery 1 F 058
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1307 13 Aug 2020 10:37:40 AM 13 Aug 2020 10:37:41 AM Y 22 Recovery 1 F 059
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
598 13 Aug 2020 11:11:42 AM 13 Aug 2020 11:11:43 AM Y 22 Recovery 1 F 060
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1057 22 Jul 2020 10:59:29 AM 22 Jul 2020 10:59:30 AM Y 17 Dosing 2 F 061
Death Status: Terminal Euthanasia Death Type: Scheduled
1687 22 Jul 2020 11:28:12 AM 22 Jul 2020 11:28:13 AM Y 17 Dosing 2 F 062
Death Status: Terminal Euthanasia Death Type: Scheduled
807 22 Jul 2020 11:34:48 AM 22 Jul 2020 11:34:48 AM Y 17 Dosing 2 F 063
Death Status: Terminal Euthanasia Death Type: Scheduled
808 22 Jul 2020 12:02:00 PM 22 Jul 2020 12:02:01 PM Y 17 Dosing 2 F 064
Death Status: Terminal Euthanasia Death Type: Scheduled
1308 22 Jul 2020 12:10:34 PM 22 Jul 2020 12:10:35 PM Y 17 Dosing 2 F 065
Death Status: Terminal Euthanasia Death Type: Scheduled
598 22 Jul 2020 12:26:23 PM 22 Jul 2020 12:26:24 PM Y 17 Dosing 2 F 066
Death Status: Terminal Euthanasia Death Type: ScheduledReport for Study 20GR142
Page 133PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709574
Dead Animal Status Report Page 7 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
808 22 Jul 2020 12:39:45 PM 22 Jul 2020 12:39:46 PM Y 17 Dosing 2 F 067
Death Status: Terminal Euthanasia Death Type: Scheduled
1307 22 Jul 2020 12:48:19 PM 22 Jul 2020 12:48:20 PM Y 17 Dosing 2 F 068
Death Status: Terminal Euthanasia Death Type: Scheduled
1687 22 Jul 2020 01:10:04 PM 22 Jul 2020 01:10:05 PM Y 17 Dosing 2 F 069
Death Status: Terminal Euthanasia Death Type: Scheduled
598 22 Jul 2020 01:20:52 PM 22 Jul 2020 01:20:53 PM Y 17 Dosing 2 F 070
Death Status: Terminal Euthanasia Death Type: Scheduled
1307 13 Aug 2020 09:45:17 AM 13 Aug 2020 09:45:18 AM Y 22 Recovery 2 F 071
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
807 13 Aug 2020 10:10:49 AM 13 Aug 2020 10:10:51 AM Y 22 Recovery 2 F 072
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
232 13 Aug 2020 10:31:30 AM 13 Aug 2020 10:31:32 AM Y 22 Recovery 2 F 073
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
807 13 Aug 2020 10:57:42 AM 13 Aug 2020 10:57:44 AM Y 22 Recovery 2 F 074
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1057 13 Aug 2020 11:14:34 AM 13 Aug 2020 11:14:35 AM Y 22 Recovery 2 F 075
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1308 22 Jul 2020 11:01:58 AM 22 Jul 2020 11:01:59 AM Y 17 Dosing 3 F 076
Death Status: Terminal Euthanasia Death Type: Scheduled
727 22 Jul 2020 11:34:04 AM 22 Jul 2020 11:34:04 AM Y 17 Dosing 3 F 077
Death Status: Terminal Euthanasia Death Type: ScheduledReport for Study 20GR142
Page 134PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709575
Dead Animal Status Report Page 8 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
1057 22 Jul 2020 11:39:37 AM 22 Jul 2020 11:39:38 AM Y 17 Dosing 3 F 078
Death Status: Terminal Euthanasia Death Type: Scheduled
727 22 Jul 2020 12:04:24 PM 22 Jul 2020 12:04:26 PM Y 17 Dosing 3 F 079
Death Status: Terminal Euthanasia Death Type: Scheduled
1787 22 Jul 2020 12:15:12 PM 22 Jul 2020 12:15:13 PM Y 17 Dosing 3 F 080
Death Status: Terminal Euthanasia Death Type: Scheduled
1687 22 Jul 2020 12:23:21 PM 22 Jul 2020 12:23:22 PM Y 17 Dosing 3 F 081
Death Status: Terminal Euthanasia Death Type: Scheduled
727 22 Jul 2020 12:40:34 PM 22 Jul 2020 12:40:35 PM Y 17 Dosing 3 F 082
Death Status: Terminal Euthanasia Death Type: Scheduled
807 22 Jul 2020 01:00:12 PM 22 Jul 2020 01:00:12 PM Y 17 Dosing 3 F 083
Death Status: Terminal Euthanasia Death Type: Scheduled
1777 22 Jul 2020 01:15:45 PM 22 Jul 2020 01:15:45 PM Y 17 Dosing 3 F 084
Death Status: Terminal Euthanasia Death Type: Scheduled
727 22 Jul 2020 01:18:09 PM 22 Jul 2020 01:18:10 PM Y 17 Dosing 3 F 085
Death Status: Terminal Euthanasia Death Type: Scheduled
1057 13 Aug 2020 09:54:23 AM 13 Aug 2020 09:54:24 AM Y 22 Recovery 3 F 086
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
598 13 Aug 2020 10:20:29 AM 13 Aug 2020 10:20:29 AM Y 22 Recovery 3 F 087
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1057 13 Aug 2020 10:34:13 AM 13 Aug 2020 10:34:14 AM Y 22 Recovery 3 F 088
Death Status: Recovery Euthanasia 1 Death Type: ScheduledReport for Study 20GR142
Page 135PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709576
Dead Animal Status Report Page 9 of 10
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
Approx GroupDay of
Phase Phase NameDate/Time
of DeathDate/Time
EnteredUser
# SexAnimal
#
1777 13 Aug 2020 11:07:56 AM 13 Aug 2020 11:07:57 AM Y 22 Recovery 3 F 089
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
808 13 Aug 2020 11:19:57 AM 13 Aug 2020 11:19:58 AM Y 22 Recovery 3 F 090
Death Status: Recovery Euthanasia 1 Death Type: Scheduled
1077 01 Jul 2020 01:57:34 PM 01 Jul 2020 01:57:15 PM Y 8 PID - F P-054#
Death Status: Found Dead Death Type: Unscheduled Death
Comment: Died after blood collection
# = PretestReport for Study 20GR142
Page 136PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
(b) (6)
FDA-CBER-2021-5683-0709577
Page 10 of 10 Dead Animal Status Report Audit Trail
Printed: 19 Aug 2020 05:38:05 PM
Pristima® Version 7.4.3 Build 25 Pfizer
Study: 20GR142
StudyTitle: 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Test Article: BNT162b2(V9), BNT162b3c
Rat/Wistar Han Repeat Dose Toxicity/Toxicity with Recovery
No Audit TrailReport for Study 20GR142
Page 137PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
FDA-CBER-2021-5683-0709578
Appendix 2
Clinical Signs - Daily
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Note: Animals were considered normal (data not displayed in table) unless indicated otherwise.
Note: Each interval will be concatenated with the phase name abbreviation.
- Value not applicable
Day(s) Observed - PID = Prior to Initiation of Dosing, D = Dosing, R = Recovery
Pfizer CONFIDENTIALReport for Study 20GR142
Page 138PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
FDA-CBER-2021-5683-0709579
Appendix 2
Clinical Signs - Daily
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
012 Thin Appearance 1 D8 1 0 µg/day
024 Hair Loss 2 Abdomen, Thinning D8, 15 2 30 µg/day
029 Tail Crooked PID1-12, D1-17,
R1-2251
Pfizer CONFIDENTIALReport for Study 20GR142
Page 139PFIZER CONFIDENTIAL
090177e195d470f8\Approved\Approved On: 17-Dec-2020 21:42 (GMT)
FDA-CBER-2021-5683-0709580
Appendix 2
Clinical Signs - Daily
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
067 Hair Loss 2 Forelimb, Bilateral, Thinning D15 1 30 µg/day
083 Lesion 3 Lumbar, Dorsal D1 1 30 µg /day
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Appendix 3
Ocular Exam
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Note: Animals were considered normal (data not displayed in table) unless indicated otherwise.
Note: Each interval will be concatenated with the phase name abbreviation.
- Value not applicable
Day(s) Observed - PID = Prior to Initiation of Dosing, D = Dosing, R = Recovery
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Appendix 3
Ocular Exam
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
001 No Ocular Abnormality 1 Bilateral PID7, D15 2 0 µg/day
002 No Ocular Abnormality Bilateral PID7, D15 2
003 No Ocular Abnormality Bilateral PID7, D15 2
004 No Ocular Abnormality Bilateral PID7, D15 2
005 No Ocular Abnormality Bilateral PID7, D15 2
006 No Ocular Abnormality Bilateral PID7, D15 2
007 No Ocular Abnormality Bilateral PID7, D15 2
008 Vitreous, Hemorrhage Mild, Left, Temporal, Ventral PID7, D15 2
009 No Ocular Abnormality Bilateral PID7, D15 2
010 Retina, Tortuous Vessels Minimal, Left, Generalized,
MultifocalPID7, D15 2
011 Vitreous, Hyaloid
RemnantMinimal, Right, Central, Central PID7, D15 2
012 No Ocular Abnormality Bilateral PID7, D15 2
013 No Ocular Abnormality Bilateral PID7, D15 2
014 Keratic Precipitates Mild, Left, Equatorial PID7, D15 2
015 No Ocular Abnormality Bilateral PID7, D15 2
016 No Ocular Abnormality 2 Bilateral PID7, D15 2 30 µg/day
017 No Ocular Abnormality Bilateral PID7, D15 2
018 No Ocular Abnormality Bilateral PID7, D15 2
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Appendix 3
Ocular Exam
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
019 No Ocular Abnormality 2 Bilateral PID7, D15 2 30 µg/day
020 No Ocular Abnormality Bilateral PID7, D15 2
021 No Ocular Abnormality Bilateral PID7, D15 2
022 No Ocular Abnormality Bilateral PID7, D15 2
023 No Ocular Abnormality Bilateral PID7, D15 2
024 No Ocular Abnormality Bilateral PID7, D15 2
025 No Ocular Abnormality Bilateral PID7, D15 2
026 No Ocular Abnormality Bilateral PID7, D15 2
027 No Ocular Abnormality Bilateral PID7, D15 2
028 No Ocular Abnormality Bilateral PID7, D15 2
029 No Ocular Abnormality Bilateral PID7, D15 2
030 No Ocular Abnormality Bilateral PID7, D15 2
031 No Ocular Abnormality 3 Bilateral PID7, D15 2 30 µg /day
032 No Ocular Abnormality Bilateral PID7, D15 2
033 No Ocular Abnormality Bilateral PID7, D15 2
034 No Ocular Abnormality Bilateral PID7, D15 2
035 No Ocular Abnormality Bilateral PID7, D15 2
036 No Ocular Abnormality Bilateral PID7, D15 2
037 No Ocular Abnormality Bilateral PID7, D15 2
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Appendix 3
Ocular Exam
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
038 No Ocular Abnormality 3 Bilateral PID7, D15 2 30 µg /day
039 No Ocular Abnormality Bilateral PID7, D15 2
040 No Ocular Abnormality Bilateral PID7, D15 2
041 Keratic Precipitates Mild, Right, Equatorial PID7, D15 2
042 No Ocular Abnormality Bilateral PID7, D15 2
043 No Ocular Abnormality Bilateral PID7, D15 2
044 No Ocular Abnormality Bilateral PID7, D15 2
045 No Ocular Abnormality Bilateral PID7, D15 2
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Appendix 3
Ocular Exam
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
046 No Ocular Abnormality 1 Bilateral PID8, D16 2 0 µg/day
047 No Ocular Abnormality Bilateral PID8, D16 2
048 No Ocular Abnormality Bilateral PID8, D16 2
049 Keratic Precipitates Mild, Left, Equatorial D16 1
No Ocular Abnormality Bilateral PID8 1
050 No Ocular Abnormality Bilateral PID8, D16 2
051 No Ocular Abnormality Bilateral PID8, D16 2
052 No Ocular Abnormality Bilateral PID8, D16 2
053 No Ocular Abnormality Bilateral PID8, D16 2
054 No Ocular Abnormality Bilateral PID8, D16 2
055 No Ocular Abnormality Bilateral PID8, D16 2
056 No Ocular Abnormality Bilateral PID8, D16 2
057 No Ocular Abnormality Bilateral PID8, D16 2
058 No Ocular Abnormality Bilateral PID8, D16 2
059 No Ocular Abnormality Bilateral PID8, D16 2
060 No Ocular Abnormality Bilateral PID8, D16 2
061 No Ocular Abnormality 2 Bilateral PID8, D16 2 30 µg/day
062 No Ocular Abnormality Bilateral PID8, D16 2
063 No Ocular Abnormality Bilateral PID8, D16 2
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Appendix 3
Ocular Exam
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
064 No Ocular Abnormality 2 Bilateral PID8, D16 2 30 µg/day
065 No Ocular Abnormality Bilateral PID8, D16 2
066 No Ocular Abnormality Bilateral PID8, D16 2
067 No Ocular Abnormality Bilateral PID8, D16 2
068 No Ocular Abnormality Bilateral PID8, D16 2
069 No Ocular Abnormality Bilateral PID8, D16 2
070 No Ocular Abnormality Bilateral PID8, D16 2
071 No Ocular Abnormality Bilateral PID8, D16 2
072 No Ocular Abnormality Bilateral PID8, D16 2
073 No Ocular Abnormality Bilateral PID8, D16 2
074 No Ocular Abnormality Bilateral PID8, D16 2
075 No Ocular Abnormality Bilateral PID8, D16 2
076 No Ocular Abnormality 3 Bilateral PID8, D16 2 30 µg /day
077 No Ocular Abnormality Bilateral PID8, D16 2
078 No Ocular Abnormality Bilateral PID8, D16 2
079 No Ocular Abnormality Bilateral PID8, D16 2
080 No Ocular Abnormality Bilateral PID8, D16 2
081 No Ocular Abnormality Bilateral PID8, D16 2
082 No Ocular Abnormality Bilateral PID8, D16 2
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Appendix 3
Ocular Exam
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Dose Observations Day(s) Observed Modifier Total Days
SeenAnimal
NumberGroup
Number
083 No Ocular Abnormality 3 Bilateral PID8, D16 2 30 µg /day
084 No Ocular Abnormality Bilateral PID8, D16 2
085 No Ocular Abnormality Bilateral PID8, D16 2
086 No Ocular Abnormality Bilateral PID8, D16 2
087 No Ocular Abnormality Bilateral PID8, D16 2
088 No Ocular Abnormality Bilateral PID9, D16 2
089 No Ocular Abnormality Bilateral PID8, D16 2
090 No Ocular Abnormality Bilateral PID8, D16 2
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Grp Num = Group Number; Animal Num= Animal Number; - = Value not applicable; NW = Not Weighed; e = Excluded.
PID = Prior to the Initiation of Dosing.
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Animal
NumGrp
Num Phase
Day:Dose PID Dosing Recovery
1 6 1 4 8 11 15 1
1 0 µg/day 001 178.3 217.8 252.9 239.1 270.5 284.3 290.1 -
002 198.5 242.8 283.8 271.6 307.6 321.9 339.6 -
003 180.0 226.4 270.2 259.1 291.0 306.8 318.6 -
004 183.2 217.4 265.1 258.3 303.8 312.2 333.9 -
005 185.6 223.1 263.8 254.0 286.4 301.4 315.8 -
006 179.9 221.6 266.5 256.3 293.7 305.5 321.7 -
007 195.6 232.1 270.8 259.9 295.6 310.2 321.8 -
008 201.9 233.3 271.0 257.5 289.2 298.7 311.9 -
009 178.5 210.0 248.2 240.6 267.4 276.0 293.1 -
010 185.8 225.4 262.5 248.3 281.7 292.1 309.1 -
011 195.6 227.8 264.1 257.1 291.2 296.8 310.2 313.8
012 200.1 239.3 280.0 245.9 200.9 264.6 296.6 307.4
013 183.6 213.9 243.1 233.1 262.7 268.5 283.4 287.6
014 178.6 214.6 251.1 237.2 268.9 281.5 290.2 288.9
015 190.5 233.7 278.9 264.4 298.4 317.0 336.1 340.8
2 30 µg/day 016 199.1 231.5 262.6 237.4 274.1 270.5 289.2 -
017 182.0 218.3 266.9 249.5 291.2 292.1 307.0 -
018 186.8 227.1 267.1 253.9 283.3 283.7 298.2 -
019 193.4 233.0 269.3 258.6 287.4 292.6 309.8 -
020 178.1 216.7 253.1 230.2 265.7 261.6 276.3 -
021 185.4 228.6 269.4 248.9 279.2 276.5 296.0 -
022 193.3 235.0 265.8 243.9 276.6 276.2 298.3 -
023 184.6 222.6 259.9 241.4 273.0 281.2 296.1 -
024 175.1 213.4 257.4 234.4 267.7 261.0 275.4 -
025 200.1 239.9 284.6 268.0 311.6 307.9 325.5 -
026 192.2 231.0 274.9 249.7 293.8 298.6 317.7 310.9
027 186.8 222.2 265.8 243.4 286.4 284.0 306.3 306.0
028 194.4 224.6 262.6 244.2 276.7 275.1 299.5 290.0
029 195.7 239.4 280.0 259.6 295.1 297.4 320.4 312.8
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Animal
NumGrp
Num Phase
Day:Dose PID Dosing Recovery
1 6 1 4 8 11 15 1
2 30 µg/day 030 179.2 215.5 268.3 251.0 292.4 297.3 322.3 322.8
3 30 µg /day 031 191.0 216.0 244.2 224.5 250.4 250.3 268.7 -
032 178.1 210.7 254.6 234.7 264.1 258.3 274.4 -
033 194.1 236.2 291.6 269.8 310.8 315.8 330.5 -
034 187.5 222.4 259.6 233.8 267.7 264.5 280.4 -
035 188.1 227.2 256.5 227.2 259.4 245.6 267.8 -
036 195.0 239.8 274.1 254.1 288.9 287.8 308.0 -
037 192.8 235.5 275.8 249.6 293.7 290.9 313.1 -
038 187.6 223.9 256.2 236.1 267.4 268.3 285.9 -
039 187.9 224.4 264.2 239.6 281.4 274.0 292.6 -
040 177.5 216.5 255.9 240.4 271.1 268.0 293.1 -
041 197.7 231.3 270.2 262.3 290.2 290.9 303.5 300.9
042 187.4 228.6 259.5 243.0 269.5 273.4 290.9 289.7
043 195.2 232.1 273.3 252.9 280.3 285.3 306.7 302.6
044 183.6 229.0 266.9 243.7 287.0 285.6 299.3 304.1
045 177.0 214.1 249.3 226.4 262.5 260.0 284.4 282.3
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Animal
NumGrp
Num Phase
Day:Dose Recovery
4 8 11 15 18 21
1 0 µg/day 001 - - - - - -
002 - - - - - -
003 - - - - - -
004 - - - - - -
005 - - - - - -
006 - - - - - -
007 - - - - - -
008 - - - - - -
009 - - - - - -
010 - - - - - -
011 320.0 328.2 331.7 328.6 333.4 341.3
012 326.5 346.5 349.9 359.0 373.6 381.6
013 291.7 297.5 303.2 308.8 314.5 317.1
014 291.5 297.3 298.6 297.3 302.0 304.7
015 350.7 363.2 370.3 374.3 383.6 394.7
2 30 µg/day 016 - - - - - -
017 - - - - - -
018 - - - - - -
019 - - - - - -
020 - - - - - -
021 - - - - - -
022 - - - - - -
023 - - - - - -
024 - - - - - -
025 - - - - - -
026 326.6 336.1 345.8 354.4 362.2 369.9
027 312.9 327.4 335.6 344.3 347.4 359.0
028 303.3 310.9 331.8 335.2 341.1 344.1
029 323.2 337.7 350.5 355.5 361.9 371.9
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Animal
NumGrp
Num Phase
Day:Dose Recovery
4 8 11 15 18 21
2 30 µg/day 030 337.6 352.3 369.0 383.8 384.8 403.1
3 30 µg /day 031 - - - - - -
032 - - - - - -
033 - - - - - -
034 - - - - - -
035 - - - - - -
036 - - - - - -
037 - - - - - -
038 - - - - - -
039 - - - - - -
040 - - - - - -
041 312.3 327.1 331.7 340.8 351.0 357.8
042 299.5 311.4 320.1 328.4 336.8 344.2
043 313.6 331.7 336.5 344.4 355.5 362.5
044 311.9 324.6 333.6 344.6 351.3 366.3
045 293.5 308.8 316.1 315.8 326.1 340.4
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Animal
NumGrp
Num Phase
Day:Dose PID Dosing Recovery
1 6 1 4 8 11 15 1
1 0 µg/day 046 151.3 169.9 188.5 177.4 192.7 202.2 206.7 -
047 164.8 183.0 195.7 194.1 227.9 235.3 233.7 -
048 156.5 170.4 185.8 172.6 195.1 187.6 190.0 -
049 155.4 173.4 192.9 179.6 204.3 201.8 208.1 -
050 149.6 174.8 185.3 182.4 218.0 227.9 227.0 -
051 167.5 185.7 201.8 191.8 214.4 206.7 209.3 -
052 158.8 176.0 206.3 190.6 213.7 213.3 220.6 -
053 157.6 177.5 199.6 187.7 207.1 212.2 215.4 -
054 166.0 186.8 203.7 193.6 211.0 225.7 230.7 -
055 155.8 174.8 191.2 178.0 203.0 206.4 211.2 -
056 166.8 181.7 203.6 188.4 211.9 210.5 219.0 224.3
057 149.4 164.5 184.1 168.4 187.6 197.3 199.7 199.4
058 151.7 169.0 187.0 172.2 186.8 197.4 204.0 204.8
059 151.3 168.4 186.9 176.3 205.7 208.1 215.4 212.2
060 173.1 189.5 209.5 194.7 218.7 221.1 223.6 234.7
2 30 µg/day 061 163.9 180.5 202.1 181.3 209.9 210.3 229.7 -
062 157.5 172.7 183.1 174.6 203.0 205.8 208.9 -
063 160.0 171.0 186.2 178.0 197.2 195.8 201.9 -
064 162.7 184.5 198.0 187.2 215.7 208.9 216.1 -
065 157.2 182.6 188.7 173.3 199.0 207.9 219.0 -
066 171.4 186.7 203.9 187.0 215.0 215.8 219.6 -
067 156.8 168.5 192.0 182.3 207.4 208.7 217.5 -
068 152.0 169.9 187.6 169.0 190.5 187.7 196.9 -
069 163.9 181.5 197.2 177.4 200.3 213.1 232.7 -
070 174.1 188.9 202.5 185.8 206.0 211.6 227.2 -
071 167.1 175.4 180.3 171.3 195.0 202.6 212.3 205.5
072 153.5 174.3 196.8 177.1 207.9 198.7 213.4 206.6
073 146.6 163.7 176.7 168.0 190.9 195.5 198.3 203.7
074 154.4 168.3 186.3 173.0 195.0 192.4 196.3 204.8
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Animal
NumGrp
Num Phase
Day:Dose PID Dosing Recovery
1 6 1 4 8 11 15 1
2 30 µg/day 075 156.4 176.2 191.5 174.4 204.8 203.4 220.5 215.5
3 30 µg /day 076 169.2 176.6 204.0 186.9 204.0 209.1 215.5 -
077 155.0 167.5 181.6 171.1 184.4 194.2 213.2 -
078 158.2 182.3 207.2 181.9 217.2 208.4 231.7 -
079 159.0 175.8 194.7 175.2 191.4 206.9 227.1 -
080 159.3 181.9 195.2 184.6 216.0 220.7 223.6 -
081 158.6 168.4 192.4 178.0 194.7 201.5 208.6 -
082 148.7 162.1 187.5 177.1 196.6 192.1 204.4 -
083 154.1 166.2 187.3 175.1 197.5 204.6 207.0 -
084 165.1 188.8 200.6 184.3 213.6 210.8 217.8 -
085 159.2 174.0 189.3 168.8 187.3 193.9 199.1 -
086 154.4 173.5 180.3 166.1 183.6 192.9 207.6 213.3
087 162.2 180.8 198.4 182.2 204.0 215.8 241.3 242.5
088 150.5 159.0 172.9 161.5 180.3 176.1 182.5 180.6
089 170.6 185.8 204.4 184.1 211.3 209.9 218.4 208.1
090 169.5 191.4 194.4 177.1 201.8 205.6 211.1 215.1
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Animal
NumGrp
Num Phase
Day:Dose Recovery
4 8 11 15 18 21
1 0 µg/day 046 - - - - - -
047 - - - - - -
048 - - - - - -
049 - - - - - -
050 - - - - - -
051 - - - - - -
052 - - - - - -
053 - - - - - -
054 - - - - - -
055 - - - - - -
056 234.4 243.0 241.5 238.7 238.8 246.9
057 198.4 207.9 212.2 211.5 210.8 218.3
058 207.6 210.0 204.5 213.9 211.2 219.1
059 209.4 209.7 218.0 217.0 221.5 218.0
060 235.9 249.5 243.9 240.1 245.4 242.0
2 30 µg/day 061 - - - - - -
062 - - - - - -
063 - - - - - -
064 - - - - - -
065 - - - - - -
066 - - - - - -
067 - - - - - -
068 - - - - - -
069 - - - - - -
070 - - - - - -
071 212.7 221.2 226.2 218.8 225.0 235.6
072 217.4 227.3 224.6 225.6 224.6 242.1
073 200.9 207.9 210.8 213.6 215.3 215.5
074 219.4 221.2 217.4 217.4 222.8 226.7
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Appendix 4
Body Weight (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Animal
NumGrp
Num Phase
Day:Dose Recovery
4 8 11 15 18 21
2 30 µg/day 075 214.6 223.1 228.5 227.5 235.1 236.7
3 30 µg /day 076 - - - - - -
077 - - - - - -
078 - - - - - -
079 - - - - - -
080 - - - - - -
081 - - - - - -
082 - - - - - -
083 - - - - - -
084 - - - - - -
085 - - - - - -
086 207.2 209.8 215.1 221.0 228.4 220.1
087 235.5 239.1 233.2 241.0 252.5 246.1
088 188.7 194.7 192.5 188.4 194.3 197.3
089 217.4 225.8 226.0 222.2 229.6 234.3
090 223.1 230.0 224.3 213.9 221.1 224.5
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Grp Num = Group Number; Animal Num = Animal Number; - = Value not applicable; NW = Not Weighed; e = Excluded.
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase
Days:Dose PID Dosing Recovery
1-6 1-4 4-8 8-11 11-15 1-15 1-4 4-8
1 0 µg/day 001 39.5 -13.8 31.4 13.8 5.8 37.2 - -
002 44.3 -12.2 36.0 14.3 17.7 55.8 - -
003 46.4 -11.1 31.9 15.8 11.8 48.4 - -
004 34.2 -6.8 45.5 8.4 21.7 68.8 - -
005 37.5 -9.8 32.4 15.0 14.4 52.0 - -
006 41.7 -10.2 37.4 11.8 16.2 55.2 - -
007 36.5 -10.9 35.7 14.6 11.6 51.0 - -
008 31.4 -13.5 31.7 9.5 13.2 40.9 - -
009 31.5 -7.6 26.8 8.6 17.1 44.9 - -
010 39.6 -14.2 33.4 10.4 17.0 46.6 - -
011 32.2 -7.0 34.1 5.6 13.4 46.1 6.2 8.2
012 39.2 -34.1 -45.0 63.7 32.0 16.6 19.1 20.0
013 30.3 -10.0 29.6 5.8 14.9 40.3 4.1 5.8
014 36.0 -13.9 31.7 12.6 8.7 39.1 2.6 5.8
015 43.2 -14.5 34.0 18.6 19.1 57.2 9.9 12.5
2 30 µg/day 016 32.4 -25.2 36.7 -3.6 18.7 26.6 - -
017 36.3 -17.4 41.7 0.9 14.9 40.1 - -
018 40.3 -13.2 29.4 0.4 14.5 31.1 - -
019 39.6 -10.7 28.8 5.2 17.2 40.5 - -
020 38.6 -22.9 35.5 -4.1 14.7 23.2 - -
021 43.2 -20.5 30.3 -2.7 19.5 26.6 - -
022 41.7 -21.9 32.7 -0.4 22.1 32.5 - -
023 38.0 -18.5 31.6 8.2 14.9 36.2 - -
024 38.3 -23.0 33.3 -6.7 14.4 18.0 - -
025 39.8 -16.6 43.6 -3.7 17.6 40.9 - -
026 38.8 -25.2 44.1 4.8 19.1 42.8 15.7 9.5
027 35.4 -22.4 43.0 -2.4 22.3 40.5 6.9 14.5
028 30.2 -18.4 32.5 -1.6 24.4 36.9 13.3 7.6
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase
Days:Dose PID Dosing Recovery
1-6 1-4 4-8 8-11 11-15 1-15 1-4 4-8
2 30 µg/day 029 43.7 -20.4 35.5 2.3 23.0 40.4 10.4 14.5
030 36.3 -17.3 41.4 4.9 25.0 54.0 14.8 14.7
3 30 µg /day 031 25.0 -19.7 25.9 -0.1 18.4 24.5 - -
032 32.6 -19.9 29.4 -5.8 16.1 19.8 - -
033 42.1 -21.8 41.0 5.0 14.7 38.9 - -
034 34.9 -25.8 33.9 -3.2 15.9 20.8 - -
035 39.1 -29.3 32.2 -13.8 22.2 11.3 - -
036 44.8 -20.0 34.8 -1.1 20.2 33.9 - -
037 42.7 -26.2 44.1 -2.8 22.2 37.3 - -
038 36.3 -20.1 31.3 0.9 17.6 29.7 - -
039 36.5 -24.6 41.8 -7.4 18.6 28.4 - -
040 39.0 -15.5 30.7 -3.1 25.1 37.2 - -
041 33.6 -7.9 27.9 0.7 12.6 33.3 11.4 14.8
042 41.2 -16.5 26.5 3.9 17.5 31.4 9.8 11.9
043 36.9 -20.4 27.4 5.0 21.4 33.4 11.0 18.1
044 45.4 -23.2 43.3 -1.4 13.7 32.4 7.8 12.7
045 37.1 -22.9 36.1 -2.5 24.4 35.1 11.2 15.3
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase
Days:Dose Recovery
8-11 11-15 15-18 18-21 1-21
1 0 µg/day 001 - - - - -
002 - - - - -
003 - - - - -
004 - - - - -
005 - - - - -
006 - - - - -
007 - - - - -
008 - - - - -
009 - - - - -
010 - - - - -
011 3.5 -3.1 4.8 7.9 27.5
012 3.4 9.1 14.6 8.0 74.2
013 5.7 5.6 5.7 2.6 29.5
014 1.3 -1.3 4.7 2.7 15.8
015 7.1 4.0 9.3 11.1 53.9
2 30 µg/day 016 - - - - -
017 - - - - -
018 - - - - -
019 - - - - -
020 - - - - -
021 - - - - -
022 - - - - -
023 - - - - -
024 - - - - -
025 - - - - -
026 9.7 8.6 7.8 7.7 59.0
027 8.2 8.7 3.1 11.6 53.0
028 20.9 3.4 5.9 3.0 54.1
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase
Days:Dose Recovery
8-11 11-15 15-18 18-21 1-21
2 30 µg/day 029 12.8 5.0 6.4 10.0 59.1
030 16.7 14.8 1.0 18.3 80.3
3 30 µg /day 031 - - - - -
032 - - - - -
033 - - - - -
034 - - - - -
035 - - - - -
036 - - - - -
037 - - - - -
038 - - - - -
039 - - - - -
040 - - - - -
041 4.6 9.1 10.2 6.8 56.9
042 8.7 8.3 8.4 7.4 54.5
043 4.8 7.9 11.1 7.0 59.9
044 9.0 11.0 6.7 15.0 62.2
045 7.3 -0.3 10.3 14.3 58.1
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase
Days:Dose PID Dosing Recovery
1-6 1-4 4-8 8-11 11-15 1-15 1-4 4-8
1 0 µg/day 046 18.6 -11.1 15.3 9.5 4.5 18.2 - -
047 18.2 -1.6 33.8 7.4 -1.6 38.0 - -
048 13.9 -13.2 22.5 -7.5 2.4 4.2 - -
049 18.0 -13.3 24.7 -2.5 6.3 15.2 - -
050 25.2 -2.9 35.6 9.9 -0.9 41.7 - -
051 18.2 -10.0 22.6 -7.7 2.6 7.5 - -
052 17.2 -15.7 23.1 -0.4 7.3 14.3 - -
053 19.9 -11.9 19.4 5.1 3.2 15.8 - -
054 20.8 -10.1 17.4 14.7 5.0 27.0 - -
055 19.0 -13.2 25.0 3.4 4.8 20.0 - -
056 14.9 -15.2 23.5 -1.4 8.5 15.4 10.1 8.6
057 15.1 -15.7 19.2 9.7 2.4 15.6 -1.0 9.5
058 17.3 -14.8 14.6 10.6 6.6 17.0 2.8 2.4
059 17.1 -10.6 29.4 2.4 7.3 28.5 -2.8 0.3
060 16.4 -14.8 24.0 2.4 2.5 14.1 1.2 13.6
2 30 µg/day 061 16.6 -20.8 28.6 0.4 19.4 27.6 - -
062 15.2 -8.5 28.4 2.8 3.1 25.8 - -
063 11.0 -8.2 19.2 -1.4 6.1 15.7 - -
064 21.8 -10.8 28.5 -6.8 7.2 18.1 - -
065 25.4 -15.4 25.7 8.9 11.1 30.3 - -
066 15.3 -16.9 28.0 0.8 3.8 15.7 - -
067 11.7 -9.7 25.1 1.3 8.8 25.5 - -
068 17.9 -18.6 21.5 -2.8 9.2 9.3 - -
069 17.6 -19.8 22.9 12.8 19.6 35.5 - -
070 14.8 -16.7 20.2 5.6 15.6 24.7 - -
071 8.3 -9.0 23.7 7.6 9.7 32.0 7.2 8.5
072 20.8 -19.7 30.8 -9.2 14.7 16.6 10.8 9.9
073 17.1 -8.7 22.9 4.6 2.8 21.6 -2.8 7.0
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase
Days:Dose PID Dosing Recovery
1-6 1-4 4-8 8-11 11-15 1-15 1-4 4-8
2 30 µg/day 074 13.9 -13.3 22.0 -2.6 3.9 10.0 14.6 1.8
075 19.8 -17.1 30.4 -1.4 17.1 29.0 -0.9 8.5
3 30 µg /day 076 7.4 -17.1 17.1 5.1 6.4 11.5 - -
077 12.5 -10.5 13.3 9.8 19.0 31.6 - -
078 24.1 -25.3 35.3 -8.8 23.3 24.5 - -
079 16.8 -19.5 16.2 15.5 20.2 32.4 - -
080 22.6 -10.6 31.4 4.7 2.9 28.4 - -
081 9.8 -14.4 16.7 6.8 7.1 16.2 - -
082 13.4 -10.4 19.5 -4.5 12.3 16.9 - -
083 12.1 -12.2 22.4 7.1 2.4 19.7 - -
084 23.7 -16.3 29.3 -2.8 7.0 17.2 - -
085 14.8 -20.5 18.5 6.6 5.2 9.8 - -
086 19.1 -14.2 17.5 9.3 14.7 27.3 -6.1 2.6
087 18.6 -16.2 21.8 11.8 25.5 42.9 -7.0 3.6
088 8.5 -11.4 18.8 -4.2 6.4 9.6 8.1 6.0
089 15.2 -20.3 27.2 -1.4 8.5 14.0 9.3 8.4
090 21.9 -17.3 24.7 3.8 5.5 16.7 8.0 6.9
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase
Days:Dose Recovery
8-11 11-15 15-18 18-21 1-21
1 0 µg/day 046 - - - - -
047 - - - - -
048 - - - - -
049 - - - - -
050 - - - - -
051 - - - - -
052 - - - - -
053 - - - - -
054 - - - - -
055 - - - - -
056 -1.5 -2.8 0.1 8.1 22.6
057 4.3 -0.7 -0.7 7.5 18.9
058 -5.5 9.4 -2.7 7.9 14.3
059 8.3 -1.0 4.5 -3.5 5.8
060 -5.6 -3.8 5.3 -3.4 7.3
2 30 µg/day 061 - - - - -
062 - - - - -
063 - - - - -
064 - - - - -
065 - - - - -
066 - - - - -
067 - - - - -
068 - - - - -
069 - - - - -
070 - - - - -
071 5.0 -7.4 6.2 10.6 30.1
072 -2.7 1.0 -1.0 17.5 35.5
073 2.9 2.8 1.7 0.2 11.8
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Appendix 5
Body Weight Change During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase
Days:Dose Recovery
8-11 11-15 15-18 18-21 1-21
2 30 µg/day 074 -3.8 0.0 5.4 3.9 21.9
075 5.4 -1.0 7.6 1.6 21.2
3 30 µg /day 076 - - - - -
077 - - - - -
078 - - - - -
079 - - - - -
080 - - - - -
081 - - - - -
082 - - - - -
083 - - - - -
084 - - - - -
085 - - - - -
086 5.3 5.9 7.4 -8.3 6.8
087 -5.9 7.8 11.5 -6.4 3.6
088 -2.2 -4.1 5.9 3.0 16.7
089 0.2 -3.8 7.4 4.7 26.2
090 -5.7 -10.4 7.2 3.4 9.4
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Footnotes
Num = Number; - = Value not applicable; NW = Not Weighed; e = Excluded; SP = Spilled.
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase:
Days:Dose Dosing Recovery
1-4
4-8 8-11 11-15 1-15 1-4 4-8 8-11
1 0 µg/day 001 53.4 92.3 66.2 87.0 298.9 - - -
002 53.5 100.9 66.5 92.1 313.0 - - -
003 53.6 92.7 70.2 85.0 301.5 - - -
004 51.8 106.3 66.5 96.8 321.4 - - -
005 50.4 95.2 67.9 87.4 300.9 - - -
006 54.3 100.3 62.6 95.1 312.3 - - -
007 54.4 106.8 70.4 92.3 323.9 - - -
008 45.3 89.9 64.8 84.1 284.1 - - -
009 50.5 86.2 58.9 87.2 282.8 - - -
010 46.8 88.5 67.6 87.4 290.3 - - -
011 51.5 97.4 59.9 85.1 293.9 48.2 74.0 55.8
012 39.7 18.5 58.5 101.2 217.9 56.2 97.1 63.2
013 51.9 85.1 53.2 81.5 271.7 39.6 72.9 52.6
014 53.3 95.8 69.8 84.2 303.1 44.4 75.5 52.0
015 52.8 107.1 68.5 93.9 322.3 51.7 91.1 67.0
2 30 µg/day 016 35.5 85.3 47.2 81.5 249.5 - - -
017 43.1 95.9 53.2 97.7 289.9 - - -
018 46.1 101.9 57.4 88.9 294.3 - - -
019 45.0 92.8 49.2 86.1 273.1 - - -
020 40.7 91.7 47.0 84.9 264.3 - - -
021 34.4 89.8 46.4 91.1 261.7 - - -
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase:
Days:Dose Dosing Recovery
1-4
4-8 8-11 11-15 1-15 1-4 4-8 8-11
2 30 µg/day 022 41.2 90.7 49.3 84.6 265.8 - - -
023 42.2 89.0 54.1 84.2 269.5 - - -
024 38.6 90.5 51.2 86.2 266.5 - - -
025 51.1 114.3 61.9 104.3 331.6 - - -
026 43.6 101.5 65.9 101.9 312.9 63.9 94.9 65.3
027 46.4 101.0 57.0 90.9 295.3 62.8 89.6 63.3
028 41.9 90.8 50.7 92.3 275.7 61.3 84.0 66.5
029 45.7 107.5 57.2 97.8 308.2 65.6 90.9 68.2
030 43.4 108.6 62.6 110.9 325.5 70.1 105.2 76.7
3 30 µg /day 031 33.4 75.7 45.2 74.5 228.8 - - -
032 40.9 85.0 41.1 86.8 253.8 - - -
033 36.3 116.5 63.6 100.2 316.6 - - -
034 36.3 84.9 47.1 80.6 248.9 - - -
035 33.4 80.0 35.7 80.5 229.6 - - -
036 42.4 87.4 55.1 89.2 274.1 - - -
037 39.4 105.8 56.7 103.3 305.2 - - -
038 39.2 79.7 52.5 82.9 254.3 - - -
039 33.8 97.4 49.6 87.1 267.9 - - -
040 38.6 95.1 44.6 101.0 279.3 - - -
041 53.9 105.4 61.5 93.1 313.9 70.0 94.5 67.3
042 34.0 91.5 46.9 82.2 254.6 59.8 79.8 56.9
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase:
Days:Dose Dosing Recovery
1-4
4-8 8-11 11-15 1-15 1-4 4-8 8-11
3 30 µg /day 043 39.6 78.2 50.6 86.5 254.9 58.4 83.2 61.6
044 38.7 98.2 55.6 94.1 286.6 63.2 92.5 61.6
045 40.4 89.8 50.9 90.0 271.1 59.9 83.2 66.1
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase:
Days:Dose Recovery
11-15
15-18 18-21 1-21
1 0 µg/day 001 - - - -
002 - - - -
003 - - - -
004 - - - -
005 - - - -
006 - - - -
007 - - - -
008 - - - -
009 - - - -
010 - - - -
011 69.1 53.3 50.5 350.9
012 87.6 68.2 66.9 439.2
013 68.6 54.3 51.6 339.6
014 70.9 53.6 56.9 353.3
015 85.9 69.1 70.5 435.3
2 30 µg/day 016 - - - -
017 - - - -
018 - - - -
019 - - - -
020 - - - -
021 - - - -
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase:
Days:Dose Recovery
11-15
15-18 18-21 1-21
2 30 µg/day 022 - - - -
023 - - - -
024 - - - -
025 - - - -
026 87.1 68.5 67.9 447.6
027 82.1 64.7 64.1 426.6
028 75.1 59.3 63.9 410.1
029 82.8 62.2 63.3 433.0
030 96.5 67.6 73.0 489.1
3 30 µg /day 031 - - - -
032 - - - -
033 - - - -
034 - - - -
035 - - - -
036 - - - -
037 - - - -
038 - - - -
039 - - - -
040 - - - -
041 85.4 70.3 70.0 457.5
042 71.6 58.4 53.6 380.1
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Male
Grp
Num Animal
NumPhase:
Days:Dose Recovery
11-15
15-18 18-21 1-21
3 30 µg /day 043 76.1 58.4 56.5 394.2
044 85.8 65.0 69.8 437.9
045 77.1 60.9 60.8 408.0
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase:
Days:Dose Dosing Recovery
1-4
4-8 8-11 11-15 1-15 1-4 4-8 8-11
1 0 µg/day 046 32.9 61.5 47.7 54.5 196.6 - - -
047 41.0 87.3 61.3 77.0 266.6 - - -
048 35.6 72.7 44.7 64.2 217.2 - - -
049 36.3 72.0 43.4 63.5 215.2 - - -
050 42.8 83.1 59.2 69.6 254.7 - - -
051 37.5 67.9 42.3 67.2 214.9 - - -
052 43.8 79.3 46.3 64.0 233.4 - - -
053 39.1 74.0 47.1 61.9 222.1 - - -
054 41.8 84.0 58.1 77.5 261.4 - - -
055 35.1 68.4 46.2 59.1 208.8 - - -
056 35.8 75.7 47.3 72.5 231.3 54.1 70.3 51.0
057 28.2 64.0 39.5 55.0 186.7 43.2 62.4 45.0
058 34.8 63.2 42.7 56.1 196.8 42.4 55.2 40.0
059 40.2 81.0 44.7 65.8 231.7 45.2 56.7 45.7
060 42.0 82.8 53.6 71.2 249.6 53.1 72.0 49.9
2 30 µg/day 061 30.3 74.3 44.2 80.6 229.4 - - -
062 34.0 65.9 40.3 61.5 201.7 - - -
063 36.7 70.6 38.7 66.5 212.5 - - -
064 36.6 77.5 46.5 71.6 232.2 - - -
065 23.9 72.6 42.7 66.2 205.4 - - -
066 29.5 71.5 41.1 56.8 198.9 - - -
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase:
Days:Dose Dosing Recovery
1-4
4-8 8-11 11-15 1-15 1-4 4-8 8-11
2 30 µg/day 067 37.3 78.2 45.8 68.4 229.7 - - -
068 30.0 59.8 37.7 56.7 184.2 - - -
069 34.0 71.0 44.2 72.5 221.7 - - -
070 32.9 70.8 41.7 71.7 217.1 - - -
071 37.4 72.6 40.4 66.9 217.3 55.6 67.9 51.2
072 34.0 71.0 38.4 66.1 209.5 47.7 68.7 47.1
073 32.9 72.4 39.6 63.5 208.4 44.2 63.3 44.1
074 31.4 67.3 40.0 58.1 196.8 54.2 63.8 41.9
075 34.4 66.9 46.5 71.7 219.5 46.9 69.7 49.2
3 30 µg /day 076 38.5 76.7 50.1 70.3 235.6 - - -
077 34.2 71.1 40.5 77.0 222.8 - - -
078 25.5 74.6 36.2 72.1 208.4 - - -
079 30.1 67.5 43.8 76.3 217.7 - - -
080 37.3 82.4 55.1 74.3 249.1 - - -
081 31.8 64.5 34.7 65.3 196.3 - - -
082 31.7 66.9 37.4 62.8 198.8 - - -
083 33.3 71.5 45.0 66.8 216.6 - - -
084 78.1 75.9 39.0 62.1 255.1 - - -
085 29.8 66.7 39.3 66.7 202.5 - - -
086 27.3 64.9 36.4 62.6 191.2 47.8 60.3 42.8
087 38.6 85.4 43.6 90.6 258.2 57.6 82.6 53.6
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase:
Days:Dose Dosing Recovery
1-4
4-8 8-11 11-15 1-15 1-4 4-8 8-11
3 30 µg /day 088 26.7 65.5 31.8 54.8 178.8 45.4 62.4 38.3
089 28.5 64.7 37.4 60.1 190.7 44.1 59.9 42.1
090 28.1 77.6 36.0 65.7 207.4 50.2 69.2 36.8
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase:
Days:Dose Recovery
11-15
15-18 18-21 1-21
1 0 µg/day 046 - - - -
047 - - - -
048 - - - -
049 - - - -
050 - - - -
051 - - - -
052 - - - -
053 - - - -
054 - - - -
055 - - - -
056 67.1 47.3 50.0 339.8
057 56.2 39.3 46.0 292.1
058 52.0 38.9 45.2 273.7
059 52.6 36.9 38.6 275.7
060 67.5 49.8 45.2 337.5
2 30 µg/day 061 - - - -
062 - - - -
063 - - - -
064 - - - -
065 - - - -
066 - - - -
Pfizer CONFIDENTIALReport for Study 20GR142
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Appendix 6
Food Consumption - Empty Feeder During Interval (g)
20GR142 : 17-DAY INTRAMUSCULAR TOXICITY STUDY IN WISTAR HAN RATS WITH A 3-WEEK RECOVERY
Female
Grp
Num Animal
NumPhase:
Days:Dose Recovery
11-15
15-18 18-21 1-21
2 30 µg/day 067 - - - -
068 - - - -
069 - - - -
070 - - - -
071 58.4 46.1 48.6 327.8
072 63.9 36.2 48.1 311.7
073 55.4 40.2 41.1 288.3
074 61.4 44.0 44.4 309.7
075 65.8 51.7 51.8 335.1
3 30 µg /day 076 - - - -
077 - - - -
078 - - - -
079 - - - -
080 - - - -
081 - - - -
082 - - - -
083 - - - -
084 - - - -
085 - - - -
086 60.1 44.2 41.1 296.3
087 77.3 57.0 55.9 384.0
Pfizer CONFIDENTIALReport
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