General Investigation of COMIRNATY Intramuscular Injection (Follow-up Study for Subjects [Healthcare Professionals] Who Are Vaccinated at an Early Post-Approval Stage)
Conditions: COVID-19
Sponsor: Pfizer

COMIRNATY Intramuscular Injection  
C4591006 NON-INTERVENTIONAL STUDY PROTOCOL 
Amended 5, 06 September 2022  
PFIZER CONFIDENTIAL  
 
 
Page 1 of 32 
(Appendix) 
General Investigation of COMIRNATY Intramuscular Injection 
(Follow-up study for Subjects [Healthcare Professionals] Who are Vaccinated at an Early 
postApproval Stage)  
Full Protocol 
Pfizer Japan Inc. 
This document contains confidential information belonging to Pfizer. Except as otherwise agreed to in 
writing, by accepting or reviewing this document, you agree to hold this information in confidence and not 
copy or disclose it to others (except where required by applicable law) or use it for unauthorized purposes. 
In the event of any actual or suspected breach of this obligation, Pfizer must be promptly notified.  

COMIRNATY Intramuscular Injection  
C4591006 NON-INTERVENTIONAL STUDY PROTOCOL  
Amended 5, 06 September 2022  
PFIZER CONFIDENTIAL  
 
 
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STUDY INFORMATION  
Title  
General Investigation of COMIRNATY Intramuscular  
Injection 
(Follow-up 
study 
for 
Subjects 
[Healthcare Professionals] Who are Vaccinated at 
an Early  postApproval Stage)  
Protocol ID  
C4591006  
Protocol version identifier  
Amended 5  
Date  
06 September 2022  
Active substance  
Tozinameran  
Medicinal product  
COMIRNATY Intramuscular Injection  
Research question and objectives  
The healthcare professionals who are vaccinated with 
this product early after the marketing approval of this 
product (participants in the Investigation of Health 
Status of Recipients Vaccinated First conducted by the 
Science Research Group of the Ministry of Health, 
Labour and Welfare) will be followed for 11 months 
from the day following 28 days after the final 
vaccination of the initial immunization with this 
product (end date of observation period in Investigation 
of Health Status of Recipients Vaccinated First) to 12 
months after the final vaccination of the initial 
immunization with this product, information on serious 
adverse events and COVID-19 observed during the 
follow-up period will be collected.  
If booster vaccination isn’t conducted, the long-term 
safety after the initial immunization of this product 
during the follow-up period will be assessed. 
If booster vaccination is conducted, the long-term 
safety after the initial immunization of this product up 
to the day before booster vaccination will be 
confirmed, and information on serious adverse events 
and COVID-19 will be continuously obtained after 
booster vaccination. 
Author  
PMS Affairs 
  
  
  
  
  
PPD

COMIRNATY Intramuscular Injection  
C4591006 NON-INTERVENTIONAL STUDY PROTOCOL  
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PFIZER CONFIDENTIAL  
 
 
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1. 
TABLE OF CONTENTS  
1. 
TABLE OF CONTENTS ........................................................................................................................3 
2. 
LIST OF ABBREVIATIONS .................................................................................................................6 
3. 
RESPONSIBLE PARTIES .....................................................................................................................7 
4. 
AMENDMENTS AND UPDATES ........................................................................................................8 
5. 
MILESTONES .....................................................................................................................................10 
6. 
RATIONALE AND BACKGROUND .................................................................................................10 
7. 
RESEARCH QUESTION AND OBJECTIVES ...................................................................................12 
7.1. 
Safety specifications .....................................................................................................................12 
8. 
RESEARCH METHODS .....................................................................................................................12 
8.1. 
Study design ..................................................................................................................................12 
8.2. 
Setting ...........................................................................................................................................12 
8.2.1. 
Registration criteria ...........................................................................................................12 
8.2.2. 
Exclusion criteria ..............................................................................................................13 
8.2.3. 
Study sites .........................................................................................................................13 
8.2.4. 
Planned study period .........................................................................................................13 
8.2.5. 
Study procedures ...............................................................................................................13 
8.2.6. 
Observation period ............................................................................................................13 
8.3. 
Variables .......................................................................................................................................14 
8.3.1. 
Characteristics of subjects.........................................................................................................15 
8.3.2. 
Pregnancy and lactation (women only) .....................................................................................16 
8.3.3. 
End-of-study/discontinuation record ........................................................................................16 
8.3.4. 
Information on inoculation of vaccines ....................................................................................16 
8.3.5. 
Information on COVID-19 pathogen (SARS-CoV-2 infection) test .........................................16 
8.3.6. 
Information on COVID-19 .......................................................................................................16 
8.3.7. 
Serious adverse events ..............................................................................................................17 

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8.3.7.1. 
Severity assessment ..........................................................................................................17 
8.3.7.2. 
Criteria for seriousness .....................................................................................................18 
8.4. 
Data sources ..................................................................................................................................18 
8.5. Study size ...........................................................................................................................................18 
8.5.1. Planned sample size ....................................................................................................................18 
8.5.2. Rationale for sample size ............................................................................................................18 
8.6. 
Data management .........................................................................................................................19 
8.6.1. 
Case report forms (CRFs)/Electronic data record .............................................................19 
8.6.2. 
Record retention ................................................................................................................19 
8.6.3. 
Data collection method .....................................................................................................19 
8.6.4. 
Subject registration (EDC) ................................................................................................20 
8.6.5. 
Points to consider for completion, revision, and submission of case report form (EDC) .20 
8.7. 
Data analysis .................................................................................................................................20 
8.7.1. 
Definition of analysis set ..................................................................................................20 
8.7.2. 
Safety analyses ..................................................................................................................20 
8.7.3. 
Analyses of information on COVID-19 ............................................................................20 
8.8. 
Quality control ..............................................................................................................................21 
8.9. 
Limitations of the research methods .............................................................................................21 
8.10. 
Other aspects .............................................................................................................................21 
9. 
PROTECTION OF HUMAN SUBJECTS ...........................................................................................21 
9.1. 
Information of subjects .................................................................................................................21 
9.2. 
Consent of subjects .......................................................................................................................22 
9.3. 
Subject withdrawal .......................................................................................................................22 
9.4. 
Institutional review board (IRB)/Independent ethics committee (IEC) ........................................23 
9.5. 
Ethical conduct of the study ..........................................................................................................23 
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS .............23 

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10.1. 
Record and report requirements ................................................................................................23 
10.2. 
Reporting period .......................................................................................................................24 
10.3. 
Evaluation of causal relationship ..............................................................................................24 
10.4. 
Safety event definition ..............................................................................................................25 
10.4.1. 
Adverse events ..................................................................................................................25 
10.4.2. 
Serious adverse events ......................................................................................................26 
10.4.3. 
Scenarios necessitating reporting to Pfizer Safety within 24 hours ..................................27 
10.5. 
Single Reference Safety Document ..........................................................................................30 
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS ............................30 
12. NAME, AND ADDRESS OF CONTRACTOR AS WELL AS SCOPE OF WORK  
CONTRACTED ...........................................................................................................................................31 
13. ADDITIONAL MEASURES THAT MAY BE TAKEN BASED ON THE STUDY RESULTS  
AND CRITERIA FOR DETERMINATION OF THE INITIATION ...........................................................31 
14. SCHEDULED TIMING OF MILESTONES AND THEIR RATIONALES FOR 
EVALUATION OF STUDY IMPLEMENTATION STATUS AND RESULTS AND REPORTING 
TO THE PMDA ............................................................................................................................................31 
15. OTHER ASPECTS ...............................................................................................................................31 
16. CONTACT INFORMATION ...............................................................................................................32 
16.1. 
Contact information for inquiries about the study ....................................................................32 
16.2. 
Contact information for inquiries about the EDC system .........................................................32 
17. REFERENCES .....................................................................................................................................32 
18. LIST OF TABLES ................................................................................................................................32 
19. LIST OF FIGURES ..............................................................................................................................32 
APPENDIX 1. LIST OF STAND ALONE DOCUMENTS .........................................................................32 
APPENDIX 2. ADDITIONAL INFORMATION .........................................................................................32 
 
 
 

COMIRNATY Intramuscular Injection  
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PFIZER CONFIDENTIAL  
 
 
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2. 
LIST OF ABBREVIATIONS  
Abbreviation
Definition  
ECMO  
Extracorporeal membrane oxygenation  
ICU  
Intensive care unit  
IEC  
Independent ethics committee  
IRB  
Institutional review board  
N/A  
Not applicable  
SAP  
Statistical analysis plan  
SRSD  
Single reference safety document  
VAED  
Vaccine-associated enhanced disease  
VAERD  
Vaccine-associated enhanced respiratory disease  
WHO  
World Healthcare Organization  
  
  
 

COMIRNATY Intramuscular Injection  
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3. 
RESPONSIBLE PARTIES  
The Japan Good Post-marketing Study Practice officer  
  

COMIRNATY Intramuscular Injection  
C4591006 NON-INTERVENTIONAL STUDY PROTOCOL  
Amended 5, 06 September 2022  
PFIZER CONFIDENTIAL  
 
 
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4. 
AMENDMENTS AND UPDATES  
Protocol 
version 
identifier 
Date  
Protocol section(s) 
changed  
Summary of 
amendment(s)  
Reason  
Amended 5
06 September 2022
10. MANAGEMENT 
AND REPORTING OF 
ADVERSE 
EVENTS/ADVERSE 
REACTIONS 
Description adjustments 
such as changes in 
Japanese translation 
Changes 
associated with 
the amendment 
of in-house 
form 
12. 
ORGANIZATIONAL 
SYSTEM FOR 
STUDY 
IMPLEMENTATION
Deletion of the section 
(The numbers of the 
subsequent sections were 
moved up.) 
Amendment 
associated with 
the notification 
“Planning and 
publication of 
Risk 
Management 
Plan” dated 18 
March 2022 
12. NAME, AND 
ADDRESS OF 
CONTRACTOR AS 
WELL AS SCOPE OF 
WORK  
CONTRACTED 
Pfizer R&D Japan: 
Change in the scope of 
work contracted 
Due to 
expansion of the 
scope of work 
contracted 
16. CONTACT 
INFORMATION 
16.1. Contact 
information for 
inquiries about the 
study 
Name: Change in the 
name of department 
Change 
associated with 
the change of 
in-house 
organization 
Amended 4
24 November 2021
STUDY 
 INFORMATION 
Research question 
 and objectives 
7. RESEARCH 
 QUESTION AND 
 OBJECTIVES 
With the approval of 
booster vaccination, a 
description was added 
that the long-term safety 
will be confirmed with 
the information up to the 
day before booster 
vaccination if booster 
vaccination is conducted.
Changes due to 
the approval of 
the booster 
vaccination 

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6. RATIONAL 
 AND  
BACKGROUND 
8.2.6. Observation 
 period 
8.3.3. End-of- 
study/ 
discontinuation 
record 
8.5.1 Planned 
 sample size 
8.6.3.2. Health 
 status record form 
The definition of the 
final vaccination with 
this product was clarified 
along with the approval 
of booster vaccination. 
Changes due to 
the approval of 
the booster 
vaccination 
8.3. Variables 
 
Table 1: “Other” was 
removed from the title 
“Information on 
inoculation of other 
vaccines”. 
To be consistent 
with other 
sections 
8.3. Variables 
20. LIST OF 
FIGURES 
(If booster vaccination 
isn’t conducted) was 
added to the title of 
Figure 1. 
Figure 2: Schedule (If 
booster vaccination is 
conducted) was added. 
Changes due to 
the approval of 
the booster 
vaccination 
8.3.4. Information on 
inoculation of 
vaccines 
“Other” was removed 
from the title 
“Information on 
inoculation of other 
vaccines”, “the 
information of the 
booster vaccination 
including this product 
will be collected” was 
added. 
To collect the 
information of 
the booster 
vaccination 
including this 
product 
Amended 3
14 October 2021 
8.2.1. Registration 
criteria 
Description of 
registration criteria was 
added. 
To give more 
detailed and 
appropriate 
explanation 
8.2.5.1. Study method
8.5.1. Planned sample 
size 
8.5.2. Rationale for 
sample size 
In accordance with 
description of 
registration criteria, text 
was added in related 
sections. 
To make target 
subjects clearer 

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Amended 2
27 May 2021 
7.1 Safety 
specifications  
Risk categories for 
safety specifications 
were added.  
Due to an 
omission of the 
description 
8.3. Variables  
8.3.1.  
Characteristics of 
subjects  
8.6.1. Case report 
forms  
(CRFs)/Electronic data 
record  
8.6.4. Subject 
registration  
(EDC)  
"Consent for 
participation in the 
study" is to be  
checked in the EDC for 
this study and the  
description was changed 
according to actual 
specifications.  
Due to change in 
the 
specifications 
for data linkage 
from the 
Investigation of 
Health Status of  
Recipients 
Vaccinated First
Amended 1 
26 February 2021
8.3. Variables  
 Remove the item 
of “History of 
other 
vaccinations” 
 Change from  
“Pregnancy” to 
“Suspected 
pregnancy/Lactation” 
To be consistent 
with the 
Investigation of 
Health Status of
Recipients 
Vaccinated First
Final 
13 February 2021
N/A  
N/A  
N/A  
  
5. 
MILESTONES  
Milestone  
Planned date  
Start of data collection  
March 2021  
End of data collection  
August 2022  
Interim report 1   
To be determined  
Final study report  
To be determined  
   
6. 
RATIONALE AND BACKGROUND  
In December 2019, pneumonia of unknown cause became epidemic in Wuhan China. In January 
2020, it was revealed that a novel coronavirus (2019-nCoV) was the cause. On 12 February 2020, 
the virus was officially named SARS-CoV-2 and the WHO officially named the disease caused by 

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SARS-CoV-2 as COVID-19. SARS-CoV-2 and the resultant COVID-19 have spread globally with 
a steadily increasing number of individuals infected.  
BioNTech has developed RNA vaccine candidates using a platform that enables rapid development 
of vaccines against emerging viral diseases, including SARS-CoV-2. RNA vaccines encoding viral 
antigens have a significant advantage compared to conventional vaccines because they express 
proteins that induce a protective immune response in the vaccinated body and can be developed 
and manufactured rapidly.  
COMIRNATY intramuscular injection (generic name: tozinameran) (hereinafter referred to as this 
product) is an RNA vaccine containing mRNA encoding the spike protein of SARS-CoV-2, and its 
marketing approval was obtained in February 2021 with the indication of prevention of infection 
with SARS-CoV-2.  
Since this product is a highly novel vaccine, it has been decided to conduct focused investigation 
during an early period after the start of vaccination for the novel corona virus in the subjects 
(healthcare professionals) vaccinated at an early timing after approval of this product (hereinafter 
referred to as Investigation of Health Status of Recipients Vaccinated First) as Science Research of 
the Ministry of Health, Labour and Welfare (designated research) for the purpose of large-scale and 
prompt collection and publication of safety information immediately after the start of vaccination 
with this product. 
  
Since the long-term safety information obtained by the time of marketing approval of this product 
is limited, "Drug Use Investigation of COMIRNATY Intramuscular Injection (follow-up 
investigation of subjects [healthcare professionals] vaccinated at an early timing after approval of 
this product)" will be conducted to collect and confirm the long-term safety information after 
vaccination of the initial immunization with this product, including the risks of enhancement of the 
disease and respiratory diseases. The subjects will be those participating in the Investigation of 
Health Status of Recipients Vaccinated First, and will be followed for 11 months from the day 
following 28 days after the final vaccination of the initial immunization with this product (end date 
of observation period in Investigation of Health Status of Recipients Vaccinated First) to 12 months 
after the final vaccination of the initial immunization with this product. Thus, information on 
serious adverse events and COVID-19 observed during the follow-up period will be collected.  
This Study shall be conducted in strict compliance with the "MHLW Ordinance on the Standard for  
PostMarketing Studies and Clinical Trials of Medical Products" (MHLW Ordinance No. 171, dated 
December 20, 2004), the "Enforcement of the MHLW Ordinance on the Standard for Post-
marketing Studies and Clinical Trials of Medical Products" (PFSB Notification No. 1220008, dated 
December 20, 2004), "MHLW Ordinance to Partially Amend the MHLW Ordinance on the 
Standard for Post-marketing Safety Control of Medical Products, Quasi-medical Products, 
Cosmetics, and Medical Devices and to Partially Amend the MHLW Ordinance on the Standard for 
Post-marketing Studies and Clinical Trials of Medical Products" (MHLW Ordinance No. 26, dated 
March 11, 2013), the "Enforcement of the MHLW Ordinance to Partially Amend the MHLW 
Ordinance on the Standard for Post-marketing Safety Control of Medical Products, Quasi-medical 
Products, Cosmetics, and Medical Devices, and to Partially Amend the MHLW Ordinance on the 
Standard for Post-marketing Studies and Clinical Trials of Medical Products" (PFSB Notification 
No. 0311-7, dated March 11, 2013)., "MHLW Ordinance to Partially Amend the MHLW Ordinance 
on the Standard for Post-marketing Studies and Clinical Trials of Medical Products" (MHLW 
Ordinance No. 116, dated October 26, 2017), and "Announcement of the MHLW Ordinance to 
Partially Amend the MHLW Ordinance on the Standard for Post-marketing Studies and Clinical 

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Trials of Medical Products (Regarding the MHLW Ordinance on the Standard for Post-Marketing 
Studies and Clinical Trials of Medical Products)" (PSEHB Notification No. 1026-1, dated October 
26, 2017).  
 
7. 
RESEARCH QUESTION AND OBJECTIVES  
In this investigation, the healthcare professionals who are vaccinated with this product early after 
the marketing approval of this product (participants in the Investigation of Health Status of 
Recipients Vaccinated First conducted by the Science Research Group of the Ministry of Health, 
Labour and Welfare) will be followed for 11 months from the day following 28 days after the final 
vaccination of the initial immunization with this product (end date of observation period in 
Investigation of Health Status of Recipients Vaccinated First) to 12 months after the final 
vaccination of the initial immunization with this product, information on serious adverse events 
and COVID19 observed during the follow-up period will be collected.  
If booster vaccination isn’t conducted, the long-term safety after the initial immunization of this 
product during the follow-up period will be assessed. 
If booster vaccination is conducted, the long-term safety after the initial immunization of this 
product up to the day before booster vaccination will be confirmed, and information on serious 
adverse events and COVID-19 will be continuously obtained after booster vaccination. 
7.1. 
Safety specifications  
[Important Potential Risks]  
• 
Vaccine-associated enhanced disease (VAED) and vaccine-associated enhanced respiratory 
disease (VAERD)  
[Important Missing Information]  
• 
Safety of administration to pregnant or lactating women  
8. 
RESEARCH METHODS  
8.1. 
Study design  
This is a multicenter cohort study, and the investigator will enter the information required in this 
study in the case report forms based on the information obtained through medical interview, etc. 
and records such as medical records. A health status record form will be distributed to the subjects 
participating in this study and they will be requested to record information on serious adverse events 
and COVID-19 that occurred during the observation period. The investigator will collect 
information on the details from the subjects and enter them in the case report forms (CRFs) with 
reference to the information recorded in the health status record forms by the subjects after the end 
of the observation period.  
All assessments described in this protocol are performed as part of normal clinical practice or 
standard practice guidelines for the subject population and healthcare provider specialty in the 
countries where this study (non-interventional study) is being conducted.  
8.2. 
Setting  
8.2.1. 
Registration criteria  
Subjects must meet all of the following inclusion criteria to be eligible for inclusion in the study:  

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 
Subjects who have participated in the Investigation of Health Status of Recipients Vaccinated 
First and have provided written consent to continue participation in this study*.  
 
*: Subjects who have discontinued the Investigation of Health Status of Recipients Vaccinated 
First are not included. However, subjects who have discontinued the Investigation of Health 
Status of Recipients Vaccinated First at the discretion of the investigator and have provided 
written consent to participate in this study may be registered in this study. 
8.2.2. 
Exclusion criteria  
There are no exclusion criteria for this study.  
8.2.3. 
Study sites  
This study will be conducted at up to 100 institutions that have participated in the Investigation of 
Health Status of Recipients Vaccinated First and cooperate with this study by participation.  
8.2.4. 
Planned study period  
The planned period covered by this study is as follows.  
 
Investigation period: From the day following the day of completion of the observation period 
for the first subject who has completed the observation period in the Investigation of Health 
Status of Recipients Vaccinated First to the end of the observation period for the last subject 
investigated in this study (scheduled from March 2021 to August 2022)  
8.2.5. 
Study procedures  
8.2.5.1. Study method  
This study will be conducted in all subjects who meet the registration criteria, have been vaccinated 
with this product and have consented to participate in this study during participation in the 
Investigation of Health Status of Recipients Vaccinated First at contract sites.  
8.2.6. 
Observation period  
The observation period will be 11 months from the day following 28 days after the final vaccination 
of the initial immunization with this product (end date of observation period in Investigation of 
Health Status of Recipients Vaccinated First).  
In this study, information will be collected using booklet type CRF. Information for the following 
periods will be entered in each booklet.  
• 
Booklet 01: From the day following 28 days after the final vaccination of the initial 
immunization with this product to 6 months (24 weeks) after the final vaccination of this 
product  
• 
Booklet 02: From the day following 6 months after the final vaccination of the initial 
immunization with this product to 12 months (52 weeks) after the final vaccination of this 
product  
However, in cases where treatment has been discontinued, observation is continued until 
discontinuation of treatment.  

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8.3. 
Variables  
This study will be conducted according to the following schedule.  
 
○: For patients consented to participate in this study, the data collected in the Investigation of Health Status of 
Recipients Vaccinated First will be replicated and stored in the database for this study.  
  
  
Figure 1.  
Schedule (If booster vaccination isn’t conducted) 
  
*1: 28 days after 1st vaccination if the subject is vaccinated only once  
*2: 6 months after 1st vaccination if the subject is vaccinated only once  
*3: 12 months after 1st vaccination if the subject is vaccinated only once  
 
Table 1.  
Variables  
 
*  : Identify subjects consented to participate in this study. 
Written consent to participate in this study
●*
〇
 
〇
 
〇
 
〇
 
〇
 
〇
 
〇
 
〇
 
●
 
●
Information on COVID-19 pathogen test
Information on COVID-19 
Serious adverse events 
End-of-study discontinuation record (reason)
Gender 
Date of birth
Allegy information
Current medications 
Pregnancy and lactation (woman only)
Information on inoculation of vaccines 
Variable 
CRF 
Booklet 01 
CRF 
Booklet 02 
Characteristics
of subjects 
Record of vaccination with this 
product
Clinical  history (concurent
illness/past history)
Suspected pregnancy/Lactation
) 
(women only
Subject ID

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Figure 2.  
Schedule (If booster vaccination is conducted) 
 
 
 
 
 
 
CRF 
Investigation of Health 
Status of Recipients 
Vaccinated First 
 
 
 
Entry in health status 
record form 
 
 
 
Collection/verification 
of health status record 
form  
 
 
*4 
  
*1: 28 days after 1st vaccination if the subject is vaccinated only once  
*2: 6 months after 1st vaccination if the subject is vaccinated only once  
*3: 12 months after 1st vaccination if the subject is vaccinated only once  
*4: Health status record may be collected as needed, the form for remaining period may be distributed again. 
 
8.3.1. 
Characteristics of subjects  
Enter the presence or absence of written consent for participation in this study.  
Identify subjects from whom written consent was obtained through entry, and the following data of 
relevant subjects collected in the Investigation of Health Status of Recipients Vaccinated First will 
be replicated and stored in the database for this study.  
Such information will be used as subject characteristics for this study.  
• 
Subject ID  
• 
Gender  
• 
Date of birth  
• 
Record of vaccination with this product (date of vaccination/name of vaccine/lot 
number/side of vaccination)  
• 
Clinical history (concurrent illness and past history)  
• 
Allergy information (information on presence/absence of allergy and allergen)  
• 
History of other vaccinations (within 1 month after the first or second vaccination with this 
product)  
• 
Suspected pregnancy/Lactation (women only)  
• 
Current medications (names of drugs concomitantly used at the time of 1st or 2nd 
vaccination)  
  
Booklet 01 
Booklet 02 
1st vaccination 2nd vaccination 28 days after 2nd 
vaccination*1 
12 months after 2nd 
vaccination (Week 52)*3 
3rd vaccination 
6 months after 2nd 
vaccination (Week 24)*２ 

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8.3.2. 
Pregnancy and lactation (women only)  
If the subject participating in this survey is female, the presence or absence of pregnancy and 
lactation during the observation period will be entered.  
8.3.3. 
End-of-study/discontinuation record  
The investigator shall enter the date when the information of subject is confirmed at the end of the 
observation period for each booklet, that is, at 6 months after the final vaccination of the initial 
immunization with this product (Booklet 01) and at 12 months after the final vaccination of the 
initial immunization with this product (Booklet 02) (or later), as the date of completion of 
observation for each booklet (date of final observation).  
For confirmation of information of subjects, inquiries by telephone etc. are acceptable.  
If information on the subject cannot be confirmed and the date of final confirmation of the 
information on the subject does not meet the observation period, the date on which information on 
the subject can be confirmed for the last time will be entered as the date of discontinuation of 
observation (date of final observation) and the reason for discontinuation will be entered.  
1. Date of the end of observation (discontinuation) (date of final observation)  
2. End of study or reason for discontinuation  
• End of study  
• Adverse events  
• Death  
• Lost to follow-up  
• Consent withdrawal  
• Other  
8.3.4. 
Information on inoculation of vaccines  
The investigator will confirm the presence or absence of vaccine including vaccination for the novel 
corona virus* inoculated during the observation period and enter the information. If a vaccine 
including vaccination for the novel corona virus is inoculated during the observation period, the 
type of vaccine and the date of vaccination will be entered. (*: Booster vaccination of this product 
is included.) 
8.3.5. 
Information on COVID-19 pathogen (SARS-CoV-2 infection) test  
The investigator will confirm the presence or absence of the test for COVID-19 pathogen (SARS-
CoV-2) received during the observation period and enter the information. If a pathogen test is 
performed, enter the date of test (date of specimen collection), type of test and test results in the 
CRF for each test.  
8.3.6. 
Information on COVID-19  
The investigator will confirm the presence or absence of the onset of COVID-19 during the 
observation period and enter the information.  

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• 
Presence or absence of occurrence of COVID-19  
If The occurrence of COVID-19 is "present," the following information will also be entered.  
• 
Date of diagnosis of COVID-19  
• 
Presence or absence of actions/procedures taken (hospitalisation, oxygen administration, ICU 
admission, use of mechanical ventilation, and use of ECMO)  
• 
Outcome (resolved/recovered, resolved with sequelae, death, not resolved, and unknown) and 
date of outcome  
The outcome should be followed up as much as possible after the end of the observation period.  
8.3.7. 
Serious adverse events  
The investigator will provide the health status record form to the subjects participating in the study, 
perform medical interview, etc. with reference to the information in the record form entered by the 
subjects to confirm the presence or absence and details of serious adverse events, and enter the 
following information in the CRF.  
Also, further investigation should be separately conducted, if deemed necessary by Sponsor for 
subjects who experienced a serious adverse reaction.  
• 
Presence/absence of adverse event  
• 
Name of adverse event  
• 
Severity  
• 
Date of occurrence  
• 
Presence or absence of treatment  
• 
Seriousness  
• 
Criteria for seriousness  
• 
Outcome (including the date of outcome)  
• 
Causal relationship to this drug  
8.3.7.1. Severity assessment  
The investigator will assess the maximum severity of serious adverse events reported during the 
observation period from onset to confirmation of outcome and classify them into one of the 
following categories. Severity is defined as follows.  

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Table 2.  Definition of Severity  
Severity  
Definition  
Mild  
Not interfering with usual activities of subjects  
Moderate  
Interfering with usual activities of subjects to some extent  
Severe  
Markedly interfering with usual activities of subjects  
Life-threatening  
Life-threatening, or necessitating urgent intervention  
8.3.7.2. Criteria for seriousness  
The investigator will select and enter the applicable criteria for serious adverse events reported 
during the observation period.  
• 
Results in death  
• 
Is life-threatening  
• 
Requires inpatient hospitalisation or prolongation of existing hospitalisation  
• 
Results in persistent or significant disability/incapacity  
• 
Is a congenital anomaly/birth defect.  
• 
Other medically important events  
8.4. 
Data sources   
In this study, the investigator will extract necessary information based on the full protocol from the 
information obtained by medical interview, etc. based on the health status record form filled in by 
the subject as needed, and the records including medical records.  
8.5. Study size  
8.5.1. Planned sample size  
All subjects who meet the registration criteria and have consented to participate in the 11-month 
follow-up investigation from 28 days after the final vaccination of the initial immunization with 
this product to 12 months after the final vaccination of the initial immunization with this product 
among those who participated in the Investigation of Health Status of Recipients Vaccinated First 
(up to 20,000 subjects).  
8.5.2. Rationale for sample size  
Follow-up investigation will be conducted in all of the subjects who meet the registration criteria 
and have given informed consent after participating in the Investigation of Health Status of 
Recipients Vaccinated First conducted in healthcare professionals who are the candidates for 
prioritized vaccination with this product, for whom early investigation results are expected to be 
obtained, and whose health condition can be easily monitored continuously.  

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8.6. 
Data management  
8.6.1. 
Case report forms (CRFs)/Electronic data record  
As used in this full protocol, the term CRF should be understood to refer to an electronic data record, 
depending on the data collection method used in this study.  
A CRF is required and should be completed for each included subject. The completed original CRFs 
are the sole property of Pfizer and should not be made available in any form to third parties, except 
for authorized representatives of Pfizer or appropriate regulatory authorities, without written 
permission from Pfizer. The investigator shall ensure that the CRFs are securely stored at the study 
site in the encrypted electronic form and will be password protected or secured in a locked room to 
prevent access by unauthorized third parties.  
The investigator has ultimate responsibility for the collection and reporting of all clinical, safety, 
and laboratory data entered on the CRFs and any other data collection forms (source documents) 
and ensuring that they are accurate, authentic/original, attributable, complete, consistent, legible, 
timely (contemporaneous), enduring, and available when required. The CRFs must be signed by 
the investigator or by an authorized staff member to attest that the data contained on the CRFs are 
true.  Any corrections to entries made in the CRFs or source documents must be dated, initialed 
(or stamped "correction seal"), and explained (if necessary) and should not obscure the original 
entry. In most cases the source documents are the hospital or the physician's chart. In these cases, 
data collected on the CRFs must match those charts.  
 
In some cases, the CRF may also serve as the source document. In these cases, a document should 
be available at the investigator site and at Pfizer that clearly identifies those data that will be 
recorded on the CRF, and for which the CRF will stand as the source document.  
The ownership of the data replicated from the Investigation of Health Status of Recipients 
Vaccinated First and stored in the database for this study is specified in the contract with the 
Science Research Group of the Ministry of Health, Labour and Welfare.  
8.6.2. 
Record retention  
The records related to this study should be retained at the study site until the End of Study Letter 
by Pfizer is received or during the period defined by the study site, whichever is longer.   
8.6.3. 
Data collection method  
8.6.3.1. Case report form (EDC)  
The data for this study will be collected and confirmed by using the electronic system on the internet 
designed for collecting post-marketing survey data (Electronic Data Capture, EDC).  
8.6.3.2. Health status record form  
The investigator will distribute a health status record form to the subjects participating in this study, 
and request them to record the information on the occurrence of events and COVID-19 in order to 
obtain as accurate information as possible about severe symptoms, etc. accompanying 
hospitalisation in the subjects during the observation period.  
The investigator will collect the health status record form recorded by the subject during the 
observation period (6 months after the final vaccination of the initial immunization with this 
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(collection by mail is also acceptable), check the detailed contents at the time of medical interview 
if necessary with reference to the entered information, collect information on serious adverse events 
and COVID-19, and enter the information in the CRF. For confirmation of information of subjects, 
inquiries by telephone etc. are acceptable.  
8.6.4. 
Subject registration (EDC)  
The investigator will enter the presence or absence of written consent in the EDC if he/she has 
obtained written consent for participation in this study. Background data of consented subjects 
collected in the Investigation of Health Status of Recipients Vaccinated First will be replicated and 
stored in the database as that of registered subjects in this study, and therefore a registration form 
will not be prepared.  
8.6.5. 
Points to consider for completion, revision, and submission of case report form (EDC)  
8.6.5.1. Data entry  
The investigator will check the survey items and enter the data in the EDC based on the source 
documents such as medical records and the information in the health status record form entered by 
the subject.  
8.6.5.2. Data revision  
Upon receiving query from Sponsor on the contents of the CRF (follow-up survey), the investigator 
will again confirm the contents of medical records, and as required, correct relevant sections and 
save the data.  
8.6.5.3. Submission  
After data entry and revision are completed, CRFs should be signed electrically by the investigator 
following confirmation of entry and follow-up survey.  
8.7. 
Data analysis  
Detailed methodology for summary and statistical analyses of data collected in this study will be 
documented in a Statistical Analysis Plan (SAP), which will be dated, filed and maintained by the 
sponsor. The SAP may modify the plans outlined in the protocol, and any major modifications will 
be reflected in a protocol amendment.  
8.7.1. 
Definition of analysis set  
The safety analysis set will be the full analysis set as close as possible to all subjects who have 
given consent to participate in this study.  
8.7.2. 
Safety analyses  
Serious adverse events entered in the CRF submitted by the investigator for which the causal 
relationship with this product cannot be ruled out will be handled as serious adverse reactions, and 
the number and proportion of subjects with serious adverse reactions ([%]: number of patients with 
adverse reactions/number of subjects included in safety analysis) will be tabulated. Exploratory 
analyses will be performed as needed.  
8.7.3. 
Analyses of information on COVID-19  
By using the information on COVID-19 entered in the CRF submitted by the investigator, subjects 
who are considered to be in a severe condition will be identified and the number and proportion of 

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the subjects will be tabulated with reference to the severity classification in the "Guidance for 
Treatment of Novel Coronavirus Infection (COVID-19)." Exploratory analyses will be performed 
as needed.  
8.8. 
Quality control  
Prior to conducting the study, the site staff will explain to the investigator about the contents of the 
protocol, etc. and ask the investigator to create CRFs based on medical interview based on health 
status record forms and records such as medical records.  
8.9. 
Limitations of the research methods  
There may be potential limitations in this study:  
1. Since no control group is included in the study, there is a limitation in determining whether or 
not a risk of developing adverse events and adverse reactions increases with inoculation of this 
product.  
2. Due consideration may not be given to confounding factors due to insufficient background 
information collected.  
3. Since this study collects the information from medical interview based on health status record 
forms and records such as medical records, specified data may not be collected or may be 
missing.  
8.10. Other aspects  
Not applicable.  
9. 
PROTECTION OF HUMAN SUBJECTS  
9.1. 
Information of subjects  
All parties will comply with all applicable laws, including laws regarding the implementation of 
organizational and technical measures to ensure protection of personal data of subjects. Such 
measures will include omitting subject names or other directly identifiable data in any reports, 
publications, or other disclosures, except where required by applicable laws. The personal data will 
be stored at the study site in encrypted electronic and/or paper form and will be password protected 
or secured in a locked room to ensure that only authorized study staff have access. The study site 
will implement appropriate technical and organizational measures to ensure that the personal data 
can be recovered in the event of disaster. In the event of a potential personal data breach, the study 
site shall be responsible for determining whether a personal data breach has in fact occurred and, if 
so, providing breach notifications as required by law.  
To protect the rights and freedoms of natural persons with regard to the processing of personal data, 
when study data are compiled for transfer to Pfizer and other authorized parties, subject names will 
be removed and will be replaced by a single, specific, numerical code, based on a numbering system 
defined by Pfizer. All other identifiable data transferred to Pfizer or other authorized parties will be 
identified by this single, subject-specific code. The investigator site will maintain a confidential list 
of subjects who participated in the study, linking each subject's numerical code to his or her actual 
identity. In case of data transfer, Pfizer will maintain high standards of confidentiality and 
protection of subjects' personal data consistent with the clinical study agreement and applicable 
privacy laws.  

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9.2. 
Consent of subjects  
The informed consent documents must be in compliance with local regulatory requirements and 
legal requirements, including applicable privacy laws.  
The informed consent documents used during the informed consent process must be reviewed and 
approved by Pfizer, approved by the institutional review board (IRB)/independent ethics committee 
(IEC) before use, and available for inspection.  
The investigator must ensure that each subject, or his or her legally acceptable representative, or 
parent(s) or legal guardian if a minor, is fully informed about the nature and objectives of the 
study, the sharing of data relating to the study and possible risks associated with participation, 
including the risks associated with the processing of the subject's personal data. The investigator 
further must ensure that each subject, or his or her legally acceptable representative, or parent(s) or 
legal guardian if a minor, is fully informed about his or her right to access and correct his or her 
personal data and to withdraw consent for the processing of his or her personal data.  
Whenever consent is obtained from a subject's legally acceptable representative/parent(s) or legal 
guardian if a minor, the subject's assent (affirmative agreement) must subsequently be obtained 
when the subject has the capacity to provide assent, as determined by the IRB/IEC. If the 
investigator determines that a subject's decisional capacity is so limited that he or she cannot 
reasonably be consulted, then, as permitted by the IRB/IEC and consistent with local regulatory 
and legal requirements, the subject's assent may be waived with source documentation of the reason 
assent was not obtained. If the subject does not provide his or her own consent, the source 
documents must record why the subject did not provide consent (e.g., minor, decisionally impaired 
adult), how the investigator determined that the person signing the consent was the subject's legally 
acceptable representative, the consent signer's relationship to the subject (e.g., parent, spouse), and 
that the subject's assent was obtained or waived. If assent is obtained verbally, it must be 
documented in the source documents.  
If the study includes minor subjects who reach the age of majority during the study, as recognized 
under local law, they must re-consent as adults to remain in the study. If the enrollment of 
emancipated minors is permitted by the study age criteria, the IRB/IEC, and local law, they must 
provide documentation of legal status to give consent without the permission of a parent or legal 
guardian.  
The investigator, or a person designated by the investigator, will obtain written informed consent 
from each subject or the subject's legally acceptable representative, parent(s), or legal guardian if a 
minor, before any study‑specific activity is performed. The investigator will retain the original of 
each subject's signed consent document.  
9.3. 
Subject withdrawal  
Subjects may withdraw from the study at any time at their own request, or they may be withdrawn 
at any time at the discretion of the investigator or sponsor for safety, behavioral, or administrative 
reasons.  In any circumstance, every effort should be made to document subject outcome, if 
applicable. The investigator would inquire about the reason for withdrawal and follow-up with the 
subject regarding any unresolved adverse events.  

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If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be collected. 
The sponsor may retain and continue to use any data collected before such withdrawal of consent.  
9.4. 
Institutional review board (IRB)/Independent ethics committee (IEC)  
The informed consent documents used during the informed consent process must be reviewed and 
approved by Pfizer, approved by the institutional review board (IRB)/independent ethics committee 
(IEC) before use.  
9.5. 
Ethical conduct of the study  
This study will be conducted in compliance with the "MHLW Ordinance on the Standard for 
PostMarketing Studies and Clinical Trials of Medical Products" (MHLW Ordinance No. 171, dated 
December 20, 2004). Also, the study will be conducted in accordance with legal and regulatory 
requirements, as well as with scientific purpose, value and rigor.  
10. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS  
10.1. Record and report requirements  
The following table summarizes the requirements for recording safety events on CRFs and for 
reporting safety events to Pfizer Safety on a Non-Interventional Study Adverse Event Report Form 
(NIS AE Report Form). These requirements are described for three types of events: (1) serious 
adverse events, (2) nonserious adverse events (if applicable), and (3) drug exposure-related 
scenarios including exposure during pregnancy, exposure during breast feeding, medication error, 
drug overdose, drug misuse, extravasation, lack of efficacy, and occupational exposure. These 
events are defined in the section of “Safety event definition.”  
Safety event  
Record in CRF.  
Report to Pfizer Safety within  
24 hours of awareness of the 
event using the NIS AE 
Report Form.  
Serious adverse events  
All  
All  
Non-serious adverse events  
None  
None  
Scenarios related to exposure to this 
product including exposure during 
pregnancy, exposure during breast 
feeding, medication error, drug 
overdose, drug misuse, 
extravasation, lack of efficacy, 
occupational exposure  
None  
All (with or without adverse 
events)  
Note: All adverse events related 
to drug administration   
will be reported with exposure 
scenarios.  
For each adverse event, the investigator must obtain information adequate for confirming the 
outcome, and determining whether the event meets the criteria for a serious adverse event (see the 
section of "Serious adverse events" below).  

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The safety events for which reporting to the Safety division is required in the above table must be 
reported to Pfizer within 24 hours of the investigator's knowledge of the event, regardless of 
whether the event is determined by the investigator to be related to this product. In particular, 
if the serious adverse event is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available information. This timeframe also applies to 
additional new (follow-up) information on previously forwarded safety event reports. In the rare 
event that the investigator does not become aware of the occurrence of a safety event immediately, 
the investigator is to report the event within 24 hours after learning of it and record the time of 
his/her first awareness of the event.  
For those safety events that are considered serious or that are specified in the far right column of 
the table above as requiring reporting to Pfizer within 24 hours of awareness, the investigator must 
conduct the follow-up investigation, and must provide any additional information to Pfizer in 
accordance with the 24hour timeframe. In addition, an investigator may be requested by Pfizer to 
obtain specific additional information in an expedited fashion. This information needs to be more 
detailed than that recorded on the CRF. In general, this information should include sufficient detail 
to allow for a complete medical assessment of the event and independent determination of causality. 
Information regarding this event, such as concomitant medications and illnesses, must also be 
provided. In the event of a subject's death, a summary of available autopsy findings must be 
submitted as soon as possible to Pfizer or its designated representative.  
10.2. Reporting period  
The reporting period for safety events (see the table above) in each subject to Safety division begins 
on the day of commencement of this study and ends at the completion of the observation period. If 
a safety event of the type described in the table above has occurred during the reporting period, the 
investigator will submit a report to Pfizer Safety (or its designated representative). If a subject is 
vaccinated with this product on the last day of the observation period, the reporting period should 
be extended by 28 calendar days after the end of the observation period. In most cases, the date of 
informed consent is the same as the date of enrollment. In some circumstances, there may be a 
difference between the date of informed consent and the date of enrollment. The reporting period 
will end on the day the decision is made not to include the subject if a subject has given consent 
but is not enrolled in the study (e.g., the subject has changed his/her intention to participate in the 
study).  
If the investigator becomes aware of the occurrence of a serious adverse event at any time after 
completion of the study and the serious adverse event is determined to be related to this product, 
the serious adverse event will also be reported to Pfizer Safety.  
10.3. Evaluation of causal relationship  
The investigator will be asked to evaluate and record the causal relationship. In addition, the 
investigator should obtain sufficient information to assess the causal relationship of each adverse 
event. For adverse events related to this product, follow-up investigation by the investigator is 
required until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, 
and Pfizer concurs with that assessment.  
The evaluation of the causal relationship by the investigator will be determined by whether there 
exists a reasonable possibility that the drug has caused or contributed to the adverse event. If the 
investigator’s final judgement regarding the causal relationship is "unknown," and it cannot be 

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decided whether this product has caused the event, the safety event must be reported within 24 
hours.  
If the investigator cannot identify the cause of the event, but judges that this product has not caused 
the event, it should be clearly stated in the CRF and the NIS AE Report Form.  
10.4. Safety event definition  
10.4.1. Adverse events  
An adverse event is any untoward medical occurrence in a subject. The event does not necessarily 
have a causal relationship with inoculation or use of the product. Examples of adverse events 
include, but are not limited to:  
• 
Abnormal test findings (see below for circumstances in which an abnormal test finding 
constitutes an adverse event)  
• 
Clinically significant symptoms and signs  
• 
Changes in physical examination findings  
• 
Hypersensitivity  
• 
Progression/worsening of underlying disease  
• 
Lack of efficacy   
• 
Drug abuse  
• 
Drug dependence  
In addition, they may include signs and symptoms resulting from:  
• 
Drug overdose  
• 
Drug withdrawal  
• 
Drug misuse   
• 
Off label use   
• 
Drug interaction  
• 
Extravasation  
• 
Exposure during pregnancy  
• 
Exposure during breast feeding  
• 
Medication error  

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• 
Occupational exposure  
Abnormal test findings  
The criteria for determining whether an abnormal test finding should be reported as an adverse 
event are as follows:  
• 
The test result is accompanied by associated symptoms.  
• 
Additional diagnostic testing or medical/surgical intervention is required.  
• 
The test result leads to a change in administration of this product, discontinuation of the study, 
or addition of concomitant drug treatment or other therapy.  
• 
The investigator or Pfizer regards the test result as an adverse event.  
A case in which none of the above situations is present but simply an abnormal value continues 
will not be regarded as an adverse event. Any abnormal test result that is determined to be due to a 
laboratory error does not require reporting as an adverse event.  
10.4.2. Serious adverse events  
A serious adverse event is any untoward medical occurrence in a subject who has received a 
medicinal or nutritional product (including pediatric formulas) at any dose that:  
• 
Results in death.  
• 
Is life-threatening.  
• 
Requires inpatient hospitalisation or prolongation of existing hospitalisation (see below for 
circumstances in which an abnormal test finding does not constitute an adverse event).  
• 
Results in persistent or significant disability/incapacity (substantial disruption of the ability to 
conduct normal life functions).  
• 
Is a congenital anomaly/birth defect.  
Medical and scientific judgment should be exercised in deciding whether an event is an important 
medical event. Significant medical events may not be immediately life-threatening or result in death 
or hospitalisation. However, if it is determined that the event may jeopardize the subject or may 
require intervention to prevent one of the other outcomes listed in the definition above, the event 
should be reported as serious.  
Examples of such events are intensive care in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalisation, or development 
of drug dependence or drug abuse.  
In addition, any suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
nonpathogenic, is considered serious. The onset of the event may be suspected from clinical signs 
or laboratory findings suggestive of infection in a subject exposed to a Pfizer product. The term 
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unexpected and will be handled as serious expedited cases by Safety division. Such cases should 
also be considered for reporting as product defects, if appropriate.  
Hospitalisation  
Hospitalisation is defined as any initial admission (even less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation of existing hospitalisation. Hospitalisation also 
includes transfer within the hospital to another department or an acute/intensive care unit (eg, from 
the psychiatric floor to the medical floor, from the medical floor to the coronary care unit, from the 
neurological floor to the tuberculosis unit, etc.). A visit to the emergency room is not necessarily 
regarded as hospitalisation; however, the event leading to the emergency room visit should be 
assessed for medical significance.  
Hospitalisation without a medical adverse event is not in itself an adverse event and are not 
reportable. For example, hospitalisation without any of the following medical adverse events need 
not be reported.  
• 
Hospitalisation for social reasons (e.g., no place of accommodation for subjects)  
• 
Administrative hospitalisation (eg, for yearly physical examination)  
• 
Optional hospitalisation not associated with a precipitating clinical illness (eg, for elective 
cosmetic surgery)  
• 
Hospitalisation for observation without a medical adverse event  
• 
Hospitalisation for treatment of a preexisting condition not associated with the occurrence of a 
new adverse event or with worsening of the preexisting condition (eg, for precise examination 
of abnormal laboratory test values observed before the start of the treatment)  
10.4.3. Scenarios necessitating reporting to Pfizer Safety within 24 hours  
Scenarios related to exposure during pregnancy, exposure during breast feeding, medication error, 
drug overdose, drug misuse, extravasation, lack of efficacy, and occupational exposure are 
described below.  
Exposure during pregnancy  
Exposure during pregnancy (EDP) occurs when:  
1. A female becomes, or is found to be, pregnant either while receiving or being exposed to (e.g., 
environmental) this product. A female becomes, or is found to be, pregnant after discontinuing 
or having been directly exposed to this product (maternal exposure).  
An example of environmental exposure would be a case involving direct contact with a Pfizer 
product in a pregnant woman (e.g., a nurse reports that she is pregnant and has been exposed to 
chemotherapeutic products).  
2. A male has been exposed, either due to treatment or environmental exposure, to a Pfizer 
product prior to or around the time of conception. A male has been exposed during pregnancy 
of his partner (paternal exposure).  

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For exposure during pregnancy in studies of pregnant women, data on the exposure to this product 
during pregnancy are not reportable unless associated with serious or non-serious adverse events. 
As a general rule, prospective and retrospective reports of exposure during pregnancy from any 
source are reportable irrespective of the presence of an associated adverse event and the procedures 
for reporting serious adverse events should be followed, with the exception of those studies 
conducted in pregnant women (as described in above), for which data on the exposure are not 
reportable unless associated with serious or non-serious adverse events.  
If a subject or a subject's partner becomes or is found to be pregnant during the period of treatment 
with this product, this information must be submitted to Pfizer, irrespective of whether an adverse 
event has occurred, using the NIS AE Report Form and the EDP Supplemental Form.  
In addition, information regarding environmental exposure to this product in pregnant women (e.g., 
a subject report that she is pregnant and has been exposed to a cytotoxic product by inhalation or 
spillage) must be submitted using the NIS AE Report Form and the EDP Supplemental Form. This 
must be done irrespective of whether an adverse event has occurred.  
The information submitted should include the anticipated date of delivery (see below for 
information on termination of pregnancy).  
Follow-up investigation should be conducted to obtain general information on the pregnancy. In 
addition, follow-up investigation of EDP outcome information is required for all EDP reports with 
an unknown pregnancy outcome. The pregnancy will be followed until completion or until 
pregnancy termination (eg, abortion induced) and the outcome should be reported to Pfizer. This 
information should be submitted as the follow-up investigation of the initial EDP report. In the case 
of a live birth, the absence of external malformations should be evaluated at birth. In the event of a 
termination, the reason(s) for termination should be specified and, if clinically possible, the 
structural integrity of the terminated fetus should be assessed by gross visual inspection (unless 
pre-procedure test findings are conclusive for a congenital anomaly and the findings are reported).  
If the outcome of the pregnancy meets the criteria for a serious adverse event (ie, ectopic pregnancy, 
abortion spontaneous, foetal death in utero, death neonatal, or congenital anomaly [in a live born, 
a terminated fetus, an foetal death in utero, or a death neonatal]), the procedures for reporting 
serious adverse events should be followed.  
Additional information on pregnancy outcomes that are reported as serious adverse events is as 
follows:  
• 
Abortion spontaneous includes abortion and abortion missed.  
• 
Death neonatal that occur within 1 month of birth should be reported as serious adverse events, 
without regard to causality. In addition, infant deaths after 1 month should be reported as 
serious adverse events when the investigator assesses the infant death as related or possibly 
related to exposure to the investigational product.  
Additional information on exposure during pregnancy may be requested. Further follow-up of birth 
outcomes will be handled on a case-by-case basis (eg, follow-up on premature baby to identify 
developmental delays).  

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In the case of paternal exposure, subjects will be provided with a document on "Disclosure of 
Information on Pregnant Partners," which is to be given to their partners. It must be documented 
that this document to be given to his partner has been provided to the subject.  
Exposure during breast feeding  
Scenarios involving exposure during breastfeeding must be reported, irrespective of the presence 
of an associated adverse event. A report of exposure during breast feeding will not be prepared 
when a Pfizer product specifically approved for use in breastfeeding women (eg, vitamins) is 
administered in accordance with authorized use. However, if an infant experience an adverse event 
associated with the use of these agents, the adverse event should be reported along with the 
exposure during breastfeeding.  
Medication error  
A medication error is any event which may cause or lead to inappropriate use of a medicinal product 
under the control of the healthcare professional, subject, or consumer, and which is preventable. 
Such events may be related to the medical practice, product, procedure, or system, including 
prescription, delivery of prescribing information, product labeling, packaging and name, 
compounding, dispensing, distribution, administration, education, monitoring, and use.  
Examples of medication errors include:  
• 
Medication errors prevented in advance, irrespective of whether or not having direct effects on 
recipients (e.g., inadvertent/incorrect administration by a healthcare professional or 
recipient/consumer using the product incorrectly at an administration method or dose level not 
indicated on the product label or prescription).  
• 
Confusion of names (e.g., trade name)  
The investigator must submit the following medication errors irrespective of the presence or 
absence of associated adverse events/serious adverse events:  
• 
Medication errors involving subject exposure to the product, whether or not the medication 
error is accompanied by an adverse event  
• 
Medication errors that do not involve a subject directly (e.g., possible medication errors or near 
misses, including potential ones or those prevented in advance). If the medication error does 
not involve subject exposure to the product, a medication error report will be created based on 
the following minimum criteria:  
• 
Identifiable reporter  
• 
Suspected product  
• 
Medication error events  
Drug overdose, drug misuse, and extravasation  

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The investigator must report drug overdose, misuse, and extravasation associated with the use of a 
Pfizer product to Pfizer, irrespective of the presence or absence of adverse events/serious adverse 
events.  
Lack of efficacy  
The investigator must report lack of efficacy of Pfizer products to Pfizer, irrespective of the 
presence or absence of adverse events/serious adverse events, and the indication of the Pfizer 
product.  
Occupational exposure  
The investigator must report occupational exposure to Pfizer products to Pfizer, irrespective of the 
presence or absence of adverse events/serious adverse events.  
10.5. Single Reference Safety Document  
In this study, the package insert of this product in Japan will serve as the Single Reference Safety   
Document. This document will be used by Pfizer Safety to assess any safety events reported to 
Pfizer Safety by the investigator during the course of this study.  
Single reference safety document should be used by the investigator for prescribing purposes and 
guidance.  
11. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS  
Information collected in this study will be used for reporting purposes to Ministry of Health, Labour 
and Welfare (MHLW), Pharmaceuticals and Medical Devices Agency (PMDA), Pfizer Inc. which 
is the corporate parent of the sponsor of this study, and the group companies, or regulatory agency 
in other countries. Also, it will be used for submitting application of re-examination (including 
Japan Periodic Safety Update Report), re-evaluation, preparation of material for proper use 
information of this drug, publications and activities for information provision. In addition, Pfizer 
may disclose the study results to provide information for proper use, as needed, on 
www.clinicaltrials.gov (ClinicalTrials.gov), publish as presentations at academic conferences or, as 
manuscripts, etc.   
Data obtained from the subjects registered in this Study will be reported to the MHLW pursuant to 
the Pharmaceutical and Medical Device Act. In this case, the data may be publicly posted in 
MHLW's "Pharmaceutical and Medical Device Safety Information" and "Pharmaceuticals and 
Medical Devices Information Website (http://www.info.pmda.go.jp)" as a listing of subjects, which 
will include the names of drugs, adverse reactions, gender, age (increment of 10 years), and other 
relevant information. Furthermore, data collected may also be disclosed if the MHLW is required 
to disclose such information in accordance with the "Act on Access to Information Held by 
Administrative Organs" (Law No. 42 dated May 14, 1999); provided that in no event will the names 
of physicians, medical institutions, and other personal information be subject to such disclosure, 
nor will it be posted or disclosed.   
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable 
Competent Authority in any area of the world, or if the investigator is aware of any new information 
which might influence the evaluation of the benefits and risks of a Pfizer product, Pfizer should be 
informed immediately.   

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In addition, the investigator will inform Pfizer immediately of any urgent safety measures taken by 
the investigator to protect the subjects against any immediate hazard, and of any serious breaches 
of this NI study protocol that the investigator becomes aware of.  
12. NAME, AND ADDRESS OF CONTRACTOR AS WELL AS SCOPE OF WORK  
CONTRACTED  
• 
Company name: Pfizer R&D Japan  
Address: Shinjuku Bunka Quint Bldg., 3-22-7, Yoyogi, Shibuya-ku, Tokyo  
Scope of work of contracted: Works related to planning of study, drafting of plan, 
implementation of study and monitoring, etc.  
• 
Company name: CMIC Co., Ltd.  
Address: Hamamatsucho Building, 1-1-1 Shibaura, Minato-ku, Tokyo  
Scope of work contracted: Establishment, operation and maintenance of the EDC system, etc.  
• 
Company name: EPS Corporation  
Address: 2-23 Shimomiyabicho, Shinjuku-ku, Tokyo  
Scope of work contracted: Monitoring operations, data management, statistical analysis etc.  
13. ADDITIONAL MEASURES THAT MAY BE TAKEN BASED ON THE STUDY 
RESULTS  AND CRITERIA FOR DETERMINATION OF THE INITIATION  
Review the risk management plan including the following contents at the scheduled timing of 
milestones.  
1. Review the necessity for changing the contents of risk minimization activities for the current 
safety specifications.  
2. Review the necessity for changing the contents of this study plan including the presence or 
absence of new safety specifications (continuation of the study, implementation of additional 
study, etc.).  
3. Review the necessity for formulating risk minimization measures for new safety specifications.  
14. SCHEDULED TIMING OF MILESTONES AND THEIR RATIONALES FOR 
EVALUATION OF STUDY IMPLEMENTATION STATUS AND RESULTS AND 
REPORTING TO THE PMDA  
Safety review and reporting at the time of preparing the Periodic Safety Update Reports and 
completion of the study.  
15. OTHER ASPECTS  
1. Revision of full protocol  
Based on the new knowledge to be obtained according to the progress of this study, the need for 
amendment of the full protocol will be examined and the full protocol will be amended if necessary. 
Also, the need for amendment of the full protocol will be examined and the full protocol will be 
amended when the partial change in the dosage and administration or indication is approved during 
the reexamination period (except when the reexamination period is newly designated), etc.  

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2. Actions to be taken for any problem or issue  
Revision of the package insert and conduct of a new Post-marketing surveillance or new Post-
marketing Clinical Trial should be considered for the following cases: any serious and unknown 
adverse reaction is suggested; a significant increase in the frequency of adverse reactions; any 
effectiveness or safety concern compared to pre-approval; rare adverse reaction is suggested.   
16. CONTACT INFORMATION  
16.1. Contact information for inquiries about the study  
Name  
PMS Affairs, Pfizer R&D Japan  
Address  
Shinjuku Bunka Quint Building, 3-22-7, Yoyogi, Shibuya-ku, Tokyo 151-8589  
FAX  
03-5309-9186  
E-mail address  
BNT_COM_EX_DRPMS@pfizer.com  
16.2. Contact information for inquiries about the EDC system  
Name  
CMIC HealthCare Institute Co., Ltd.  
For other information on contact information (telephone number/e-mail address/reception time, 
etc.), refer to the materials provided separately.  
17. REFERENCES  
1.  
Guidance for Treatment of Novel Coronavirus Infection (COVID-19)  
18. LIST OF TABLES  
• 
Page 14. Table 1.    Variables  
• 
Page 18. Table 2.    Definition of Severity  
19. LIST OF FIGURES  
• 
Page 14. Figure 1.   Schedule (If booster vaccination isn’t conducted) 
• 
Page 15. Figure 2.   Schedule (If booster vaccination is conducted) 
APPENDIX 1. LIST OF STAND ALONE DOCUMENTS  
Not applicable.  
APPENDIX 2. ADDITIONAL INFORMATION  
1. 
Drug Use Investigation case report form  
2. 
Health status record form