Australia-Specific Annex for BNT162b2 [mRNA]

Version 0.2 Australia

RISK MANAGEMENT PLAN – AUSTRALIA-SPECIFIC ANNEX

Active ingredient(s) (INN): Not yet assigned.

COVID-19 mRNA Vaccine is single-
stranded, 5’-capped messenger RNA
(mRNA) produced using a cell-free in
vitro transcription from the corresponding
DNA templates, encoding the viral spike
(S) protein of SARS-CoV-2.
Product name: Comirnaty (proposed)

Pharmaco-therapeutic group (ATC Code): J07BX03

Sponsor: Pfizer Australia Pty Ltd

Regional Annex version number: 0.2

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Regional Annex version date: 17 January 2021

Referenced EU RMP: Version 1.0 dated 21 December 2020

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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................3
APPENDICES ...........................................................................................................................4
LIST OF ABBREVIATIONS....................................................................................................5
1. INTRODUCTION .................................................................................................................6
1.1. History of RMPs Submitted in Australia ..................................................................7
2. SAFETY SPECIFICATION..................................................................................................8
2.1. Epidemiology of the Indication(s) and Target Population(s)....................................8
2.2. Summary of the Safety Concerns..............................................................................8
2.2.1. Australia Specific Safety Concerns ..............................................................8
2.2.2. Proposed Changes to the Australia-specific Safety Concerns ......................8
3. PHARMACOVIGILANCE PLAN........................................................................................8
3.1. Routine Pharmacovigilance Activities in Australia ..................................................8
3.2. Additional Pharmacovigilance Activities................................................................10
3.2.1. Australia-Specific Additional Pharmacovigilance Activities.....................10
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4. CLINICAL STUDY PLAN FOR PROVISIONAL REGISTRATION ..............................10

5. RISK MINIMISATION PLAN ...........................................................................................10
5.1. Routine Risk Minimisation Activities in Australia .................................................10
5.2. Additional Risk Minimisation Activities ................................................................11
5.3. How Additional Risk Minimisation Activities will be Evaluated in Australia.......12
6. SUMMARY OF THE RMP IN AUSTRALIA....................................................................13

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LIST OF TABLES
Table 1. Sections of the EU RMP.............................................................................6
Table 2. History of RMPs Submitted in Australia....................................................7
Table 3. Summary of Safety Concerns in the EU RMP ...........................................8
Table 4. Routine Risk Minimisation Activities ......................................................11
Table 5. Summary of the RMP in Australia ...........................................................13
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APPENDICES
APPENDIX 1 FOLLOW-UP FORMS TO BE IMPLEMENTED IN AUSTRALIA
.........................................................................................................................NO DATA
APPENDIX 2 STUDY PROTOCOLS FOR PLANNED PHARMACOVIGILANCE
STUDIES IN AUSTRALIA .............................................................................NO DATA
APPENDIX 3 ADDITIONAL RISK MINIMISATION MATERIALS IN
AUSTRALIA....................................................................................................NO DATA
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LIST OF ABBREVIATIONS
AE adverse event
AESI adverse event of special interest
ASA Australian specific annex
CMI consumer medicine information (Australia)
COPD chronic obstructive pulmonary disease
COVID-19 coronavirus disease 2019
CSR clinical study report
DCA data capture aid
DNA deoxyribonucleic acid
eCTD electronic common technical document
EU European union
HLT high-level term
mRNA messenger ribonucleic acid
PhV pharmacovigilance
PI product information (Australia)
PSUR periodic safety update report
RMP risk management plan
SARS-CoV-2 severe acute respiratory syndrome coronavirus 2
SOC system organ class
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TGA therapeutic goods administration

VAED vaccine-associated enhanced disease
VAERD vaccine-associated enhanced respiratory disease

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1. INTRODUCTION
This Australia-Specific Annex (ASA) relates to the approved EU Risk Management Plan
(RMP) version 1.0 for COVID-19 mRNA vaccine dated 21 December 2020, with a data lock
point of 17 December 2020.

Australian context is provided in this Addendum for the RMP sections identified in Table 1.

Table 1. Sections of the EU RMP

Part Module/Annex AUSTRALIA
Context Included

Part I See EU RMP

Product Overview
Part II SI Yes – See Section 2.1
Safety Specification Epidemiology of the Indications(s) and Target
Population(s)
SII See EU RMP
Non-Clinical Part of the Safety Specification
SIII See EU RMP
Clinical Trial Exposure
SIV See EU RMP
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Populations Not Studied in Clinical Trials

SV See EU RMP
Post-Authorisation Experience
SVI See EU RMP
Additional EU Requirements for the Safety Specification
SVII See EU RMP
Identified and Potential Risks
SVIII Yes – See Section 2.2
Summary of the Safety Concerns
Part III Yes – See Section 3
Pharmacovigilance
Plan (Including Post-
Authorisation Safety
Studies)
Part IV See EU RMP
Plan for Post-
Authorisation
Efficacy Studies
Part V Yes – See Section 5
Risk Minimisation
Measures (Including
Evaluation of the
Effectiveness of Risk
Minimisation
Activities)
Part VI See EU RMP
Summary of the RMP

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Table 1. Sections of the EU RMP

Part Module/Annex AUSTRALIA
Context Included

Part VII Annex 2 See EU RMP

Annexes to the Risk Tabulated Summary of Planned, On-going, and
Management Plan Completed Pharmacovigilance Study Programme
Annex 3 See EU RMP
Protocols for Proposed, On-going, and Completed Studies
in the Pharmacovigilance Plan
Annex 4 See EU RMP
Specific Adverse Drug Reaction Follow-Up Forms
Annex 5 See EU RMP
Protocols for Proposed and On-going Studies in RMP Part
IV
Annex 6 See EU RMP
Details of Proposed Additional Risk Minimisation
Activities

Annex 7 See EU RMP

Other Supporting Data
Annex 8 See EU RMP
Summary of Changes to the Risk Management Plan over
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Time

1.1. History of RMPs Submitted in Australia

COVID-19 mRNA vaccine will be included in the Black Triangle Scheme and the relevant
text is included on the proposed Product Information (PI) and Consumer Medicine
Information (CMI).

The history of EU RMPs submitted in Australia is provided in Table 2. This ASA is the first
version for COVID-19 mRNA vaccine to be submitted in Australia.

Table 2. History of RMPs Submitted in Australia

EU RMP ASA Date Application or Major changes to the
version version Submitted Update ASA/EU RMP from previous
version
EU RMP v 0.1 N/A 10 December PM-2020-05461-1-2 N/A
2020 Proposed EU RMP
EU RMP v 1.0 ASA v 0.1 11 January PM-2020-05461-1-2 Initial version of the ASA
2021 EU RMP updated as per Annex 8.
Summary of Changes to the Risk
Management Plan over Time

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2. SAFETY SPECIFICATION
2.1. Epidemiology of the Indication(s) and Target Population(s)
There are no significant differences between epidemiological information presented in the
EU RMP Module SI Epidemiology of the Indication(s) and Target Population (s) compared
to those applicable to the Australian population. Please refer to the EU RMP Part II- Module
SI.

2.2. Summary of the Safety Concerns

The safety concerns proposed in the COVID-19 mRNA vaccine EU RMP (version 1.0, dated
21 December 2020) are presented in Table 3.

Table 3. Summary of Safety Concerns in the EU RMP

Important Identified Risks Anaphylaxis
Important Potential Risks Vaccine-associated enhanced disease (VAED) including Vaccine-
associated enhanced respiratory disease (VAERD)
Missing Information Use in pregnancy and while breast feeding
Use in immunocompromised patients
Use in frail patients with co-morbidities (e.g. chronic obstructive
pulmonary disease (COPD), diabetes, chronic neurological
disease, cardiovascular disorders)
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Use in patients with autoimmune or inflammatory disorders

Interaction with other vaccines
Long term safety data

There are no safety concerns for Australia that are additional to those proposed in the EU
RMP.

2.2.1. Australia Specific Safety Concerns

Not applicable.

2.2.2. Proposed Changes to the Australia-specific Safety Concerns

Not applicable.

3. PHARMACOVIGILANCE PLAN
3.1. Routine Pharmacovigilance Activities in Australia
All routine pharmacovigilance (PhV) activities in the EU RMP will be implemented in
Australia. Refer to Part III, Section III.1 Routine Pharmacovigilance Activities of the EU
RMP.

Routine pharmacovigilance activities beyond adverse reaction reporting and signal detection
are planned to be implemented in Australia.

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Data Capture Aids have been created for this vaccine. They are intended to facilitate the
capture of clinical details about:

 the nature and severity of COVID-19 illness in individuals who have received the
COVID-19 mRNA vaccine and is anticipated to provide insight into potential cases of
vaccine lack of effect or VAED. The DCA is provided in Annex 4 of the EU RMP;

 potential anaphylactic reactions in individuals who have received the COVID-19 mRNA
vaccine. This DCA was internally approved on 22 December 2020.

Routine signal detection activities for the COVID-19 mRNA vaccine will include routine and
specific review of AEs consistent with the Adverse Events of Special Interest (AESI) list
provided in the EU RMP PART II.SVII.1.1 Risks not considered important for inclusion in
the list of safety concerns in the RMP.

Concise, critical analyses of adverse events (AEs) for COVID-19 mRNA vaccine will be
conducted and provided in the Periodic Safety Update Report (PSUR) in accordance with the
TGA requirements.

In addition to routine 6-monthly PSUR production, monthly summary safety reports will be
compiled to support timely and continuous benefit risk evaluations. Topics covered by
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monthly summary safety reports will include:

 Interval and cumulative number of reports, stratified by report type (medically

confirmed/not) and by seriousness (including fatal separately);
 Interval and cumulative number of reports (serious and non-serious), overall and by
age groups and in special populations (e.g. pregnant women);
 Interval and cumulative number of reports per HLT and SOC;
 Number of reports in Australia and Global;
 Exposure data, stratified by country, age groups, race and ethnicity;
 Changes to reference safety information in the interval;
 Summary of the designated medical events;
 Ongoing and closed signals in the interval;
 Reports on number and relevant cases, including time-to-onset and Observed/Expected
analyses for the following:
a. List of AESI
b. RMP safety concerns
 Fatal reports – numbers and relevant cases, including observed/expected analyses;
 Number and relevant cases:
a. Vaccination failure/lack of efficacy (including confirmed and suspected cases);
b. Vaccination errors;
c. Potential interaction with other vaccines/concomitant treatments
 Summary of any outcomes of routine pharmacovigilance activities (as presented in the
EU RMP Part III and applied in the Australian context) that have a potential impact on
the benefit/risk balance and or of the vaccine should be included for the purpose of
rapid signal detection and communication activities.
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 Risk/benefit considerations.

Monthly reports and PSURs will include results of the observed versus expected analysis for
AESI as appropriate, including cases of Bell’s palsy and will present the results and details of
the statistical approach.

3.2. Additional Pharmacovigilance Activities

All the additional pharmacovigilance activities for COVID-19 mRNA vaccine included in
the EU RMP are considered to apply to Australia.

3.2.1. Australia-Specific Additional Pharmacovigilance Activities

Not applicable.

4. CLINICAL STUDY PLAN FOR PROVISIONAL REGISTRATION

As agreed with the TGA at the pre-submission meeting held 18 September 2020 to discuss
the proposed application to register COVID-19 mRNA vaccine, data are being provided on a
rolling basis as it becomes available.

The pivotal trial Study C4591001 is an ongoing Phase 1/2/3, placebo-controlled, randomised,
observer-blind, dose-finding study to evaluate the safety, tolerability, immunogenicity, and
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efficacy of SARS-CoV-2 RNA vaccine candidates against COVID-19 in healthy individuals.

The primary efficacy analysis was efficacy against COVID-19 at least 14 days after the last
dose of vaccine in participants without evidence of prior SARS-CoV-2 infection at baseline.

The Phase 2/3 part of Study C4591001 commenced on 27 July 2020 and had met its primary
end points as at 14 November 2020. An interim clinical study report (CSR) comprising final
analysis for efficacy and safety data 1 month after Dose 2 for 37,586 participants with a
median of at least 2 months of follow-up, and available safety data for all 43,252 participants
was submitted 10 December 2020.

The final C4591001 CSR with supplemental follow-up is expected to be available for
submission by the end of 2023.

The study protocol for Study C4591001 is provided in Module 5.3.5.1 of the eCTD dossier.

5. RISK MINIMISATION PLAN

5.1. Routine Risk Minimisation Activities in Australia
The planned routine risk minimisation activities for COVID-19 mRNA vaccine applicable to
Australia are consistent with those detailed in Part V, Section V.1 Routine Risk Minimisation
Measures of the EU RMP.

The routine risk minimisation activities planned in Australia are described in Table 4.

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Table 4. Routine Risk Minimisation Activities

Safety Concern Routine Risk Minimisation Activities Differences Between EU RMP
and Australia Activities with
Justification
Important Identified Risks
Anaphylaxis Local Product Information: None
Section 4.4 Special warnings and
precautions for use
Section 4.8 Adverse effects (undesirable
effects)
Important Potential Risk
Vaccine-associated enhanced None None
disease (VAED) including
Vaccine-associated enhanced
respiratory disease (VAERD)
Missing Information
Use in Pregnancy and while Local Product Information: None
breast feeding Section 4.6 Fertility, pregnancy and
lactation
Use in immunocompromised Local Product Information: None
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patients Section 4.4 Special warnings and

precautions for use
Section 5.1 Pharmacodynamic properties
Use in frail patients with co- Local Product Information: None
morbidities (e.g. chronic Section 5.1 Pharmacodynamic properties
obstructive pulmonary disease
(COPD), diabetes, chronic
neurological disease,
cardiovascular disorders)
Use in patients with None None
autoimmune or inflammatory
disorders
Interaction with other vaccines Local Product Information: None
Section 4.5 Interactions with other
medicines and other forms of
interactions
Long term safety data None None

5.2. Additional Risk Minimisation Activities

There are no additional risk minimisation activities referenced in Part V, Section V.2
Additional Risk Minimisation Measures of the EU RMP. No risk minimisation activities
additional to the routine risk minimisation activities described in Table 4 are currently
planned to be undertaken in Australia.

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5.3. How Additional Risk Minimisation Activities will be Evaluated in Australia

Not applicable. There are no additional risk minimisation activities being undertaken in
Australia.
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6. SUMMARY OF THE RMP IN AUSTRALIA

Table 5. Summary of the RMP in Australia

Safety concern Routine Additional pharmacovigilance Routine risk minimisation Additional risk
pharmacovigilance activities activities minimisation
activities activities
Important identified Anaphylaxis Data Capture Aid Studies: Local Product Information: None
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risks  C4591001 Section 4.4 Special warnings and

 C4591010 precautions for use
 C4591011 Section 4.8 Adverse effects
 C4591012 (undesirable effects)
 ACCESS/VAC4EU
Important potential Vaccine-associated Data Capture Aid Studies: None None
risks enhanced disease (VAED)  C4591001
including Vaccine-  C4591011
associated enhanced  C4591012
respiratory disease  ACCESS/VAC4EU
(VAERD)
Missing information Use in Pregnancy and while None Studies: Local Product Information: None
breast feeding  C4591010 Section 4.6 Fertility, pregnancy
 C4591011 and lactation
 C4591015
 ACCESS/VAC4EU
Use in immunocompromised None Studies: Local Product Information: None
patients  BNT162-01 Cohort 13 Section 4.4 Special warnings and
 C4591018 precautions for use
 C4591011 Section 5.1 Pharmacodynamic
 C4591012 properties
 ACCESS/VAC4EU
Use in frail patients with co- None Studies: Local Product Information: None
morbidities (e.g. chronic  C4591001 Section 5.1 Pharmacodynamic
obstructive pulmonary  C4591011 properties
disease (COPD), diabetes,  C4591012
chronic neurological  ACCESS/VAC4EU
disease, cardiovascular  Safety and immunogenicity
disorders) in high risk adults

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Table 5. Summary of the RMP in Australia

Safety concern Routine Additional pharmacovigilance Routine risk minimisation Additional risk
pharmacovigilance activities activities minimisation
activities activities
Missing information Use in patients with None Studies: None None
autoimmune or  C4591011
inflammatory disorders  C4591012
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 C4591018
 ACCESS/VAC4EU
Interaction with other None Study: Local Product Information: None
vaccines Co-administration study with Section 4.5 Interactions with other
seasonal influenza vaccine medicines and other forms of
interactions
Long term safety data None Studies: None None
 C4591001
 C4591010
 C4591011
 C4591012
 ACCESS/VAC4EU

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