Whole Virion, Inactivated Corona Virus Vaccine

 
1.8 Information relating to Pharmacovigilance
1.8.1 Pharmacovigilance system
Pharmacovigilance system SOP is enclosed overleaf.

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
UNCONTROLLED COPY
 Whole Virion, Inactivated Corona Virus Vaccine

 
1.8.2 Risk-management System
Risk Management System enclosed overleaf.
 

 
 

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

RISK MANAGEMENT PLAN FOR

COVAXINTM (Whole-Virion Inactivated Corona Virus Vaccine) is a white translucent liquid free
from particulate matter containing 6 mcg of Whole-Virion, Inactivated Corona Virus Antigen
(strain NIV-2020-770).

Bharat Biotech International Ltd

Genome Valley, Shameerpet Mandal,
Hyderabad, Telangana

Confidentiality Statement:

This document represents proprietary information belonging to Bharat Biotech International Ltd.
Unauthorized reproduction of the whole or part of the document by any means is strictly
prohibited. Persons to whom the information is disclosed in confidence must be informed that
the information is confidential and must not be disclosed by them to a third party.
 Whole Virion, Inactivated Corona Virus Vaccine

RMP version to be assessed as part of this application

RMP Version number 1.0

Data lock point for this RMP 16-01-2021

Date of final sign off 20-01-2021

 Whole Virion, Inactivated Corona Virus Vaccine
Name of active pharmaceutical ingredient by
International Nonproprietary Name
Pharmaco-therapeutic group (ATC Code)
Name of registration certificate
holder/applicant
Medicinal product which risk management
plan refers
Trade name(s) of medicinal product(s)
COVAXINTM (Whole-Virion Inactivated Corona
Virus Vaccine) is a white translucent liquid free
from particulate matter containing 6 mcg of
Whole-Virion, Inactivated Corona Virus Antigen
(strain NIV-2020-770).
J07BX03
Bharat Biotech International Limited,
Genome Valley, Shameerpet
Hyderabad 500078, INDIA
COVAXINTM
COVAXINTM
 Whole Virion, Inactivated Corona Virus Vaccine

Product Overview

Trade name COVAXINTM

Active substance (s) Whole-Virion, Inactivated Corona Virus Antigen

(Strain: NIV-2020-770)

Anatomical Therapeutic Chemical (ATC) J07BX03

Classification

Name of the Marketing Authorization holder Bharat Biotech International Limited, Hyderabad,
India

Medicinal product(s) to which this RMP COVAXINTM

refers

Authorization procedure Not applicable

Invented name(s) in the European Economic Not applicable

Area (EEA)

Brief description of the product including:

Chemical class Active substance

COVAXINTM (Whole-Virion Inactivated Corona

Virus Vaccine) is a white translucent liquid free
from particulate matter containing 6 mcg of
Whole-Virion, Inactivated Corona Virus Antigen
(strain NIV-2020-770).

Summary of mode of action NA

 Whole Virion, Inactivated Corona Virus Vaccine

Important information about composition of
MP
(information about composition of the
medicinal shall be provided: active
pharmaceutical ingredient and its origin (e.g.
biological or other), relevant adjuvant or
residues for s)
For two doses (0.5 mL) Whole Virion,
Inactivated Corona Virus Vaccine is presented
as Single dose (0.5 mL) and multidose (5 mL
and 10 mL) in transparent vial (USP type I glass)
with a stopper (Bromobutyl rubber) and a flip-off
plastic cap with aluminium seal. Each vial of
single dose contains 0.5 mL, each vial of
multidose contains 10 doses (5 mL) and 20
doses (10 mL) respectively.

eCTD link to the proposed product

information, as appropriate Not applicable

Indication(s) for use; Approved (current) (if Whole Virion, Inactivated Corona Virus Vaccine
applicable); Proposed for approval (if indicated for active immunization against SAR
applicable) CoV-2 Virus infection for age ≥18years.

Posology and method of application:
Proposed for approval (if applicable)
Pharmaceutical form(s) and strengths
Whole Virion, Inactivated Corona Virus Vacci
should be administered as two doses on Day 0 a
Day 28.
Route of administration: intramuscular injection (IM
Current: Sterile solutions for Injection

Is/will the product be subject to additional Yes

monitoring ?

India, 2021
Country and date of first authorization worldwide

India, 2021
Country and date of first launch worldwide

India,2021
Country and date of first authorization of the medicinal product
 Whole Virion, Inactivated Corona Virus Vaccine

Risk Minimisation Plan (RMP)

Brief details of the safety concern which was identified from Phase-1/2 data:

Safety of the COVAXINTM vaccine was established in Phase 1 and Phase 2 studies.

Phase 1 clinical trial was conducted in India in 375 adult healthy volunteers. The most common
local adverse event reported was Injection site Pain. The most common systemic adverse
events reported were headache, followed by fatigue, fever, body ache, abdominal pain, nausea,
and vomiting. The other less common adverse events were dizziness/giddiness, tremor,
sweating, cold, cough, and injection site swelling. No vaccine related serious adverse events
(SAE) were reported.

A Phase 2 clinical trial was conducted in India in 380 adolescents and adult healthy volunteers.
Similar adverse events were reported in the phase 2 clinical trial. No serious adverse events
(SAE) were reported.

A Phase 3 efficacy study is on-going. About 25800 participants (12900: vaccine & 12,900
placebo) have been administered with 1st dose of vaccination with BBV152B (COVAXINTM) and
approximately 10,000 participants have been received the 2nd dose of vaccine/placebo. No
vaccine related adverse events were observed.

The benefit/risk assessment is considered to remain favourable (and unchanged). The following
routine pharmacovigilance activities and the risk minimization activities are carried out to
mitigate the safety concerns.

Clinical Trial Mode activities:

Recently CovaxinTM has been approved in India for restricted use under clinical trial mode.
Vaccine recipients are followed to identify and/or characterize the risks associated with
vaccination. These include the identification of new safety concerns and further characterization
of known safety concerns including elucidation of risk factors. SmPC is attached as Annexure-1.

Risk minimization activities:

The risk in individuals receiving vaccine can be managed by the prescribing information or
package insert and factsheet. The vaccine recipients are provided with factsheets to know the
details about CovaxinTM. The prescribing information on the Package Insert is provided with
vaccine vials. The vaccine recipients are followed for any risk associated with the vaccination.
 Whole Virion, Inactivated Corona Virus Vaccine

The risk management team will re-evaluate based on the signals detected from the ongoing
clinical trials and pharmacovigilance activities for restricted use approval under clinical trial
mode.

The prescribing information or package insert that is provided with the vaccine contains the
following details for the proper use of the vaccine such as name and description of the medicinal
product, qualitative and quantitative composition, pharmaceutical form, therapeutic indications,
posology and method of administration, dosage & schedule, contraindications, special warning/
precautions, interaction with other medicinal products/ other forms of interaction, use during
pregnancy and lactation, effect on ability to drive and use machines, list of common and
uncommon adverse events, immune response, overdose, pharmacodynamic properties, list of
excipients, incompatibilities, the shelf life of the product, special precautions for storage and
presentation of the vaccine in the various vial.
ANNEXURE -I
 Whole Virion, Inactivated Corona Virus Vaccine

 
1.3 Product Information:
1.3.1 Summary of product characteristics, Labelling, Package leaflet
Summary of Product Characteristics:
1. Name of the Medicinal Product
COVAXINTM (Whole Virion Inactivated Corona Virus Vaccine)

2. Qualitative and Quantitative Composition

Each Single human dose (0.5 mL) contains
Active Ingredient
Whole Virion Inactivated Corona Virus Antigen
6µg
(Strain NIV-2020-770)
Inactive ingredients
Aluminium hydroxide gel equivalent to Al+3 250 µg
TLR 7/8 Agonist 15 µg
2-phenoxyethanol 2.5mg
Phosphate buffered saline q.s. to 0.5mL

3. Pharmaceutical Form
Sterile liquid for Injection

4. Clinical Particulars
It is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-
2 virus, in individuals 18 years of age and older. The use of this vaccine should be in
accordance with official recommendations. This vaccine is permitted for restricted
use in Emergency situation in Clinical Trial mode, under the provisions of New Drugs
and Clinical Trials Rules, 2019, under Drugs & Cosmetics Act 1940.
4.1 Therapeutic indication
Whole Virion, Inactivated Corona Virus Vaccine is indicated for active immunization
against SARS-CoV-2 Virus infection for age ≥18years.
4.2 Posology and method of administration.
Whole Virion, Inactivated Corona Virus Vaccine should be administered as two
doses on Day 0 and Day 28.
Route of administration: intramuscular injection (IM).

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
4.3 Contraindications
 Hypersensitivity to any constituents of the vaccine.
 Pregnant and lactating mothers.
 During fever or severe infection.
 Individuals below 18 years.
4.4 Special warnings and precautions for use
 Do not administer intravenously, intradermally, or subcutaneously.
 Like all other vaccines, supervision and appropriate medical treatment should
always be available to treat any anaphylactic reactions following immunization.
 The vaccinee should remain under medical supervision for at least 30 minutes
after vaccination.
Before use, Whole Virion, Inactivated Corona Virus Vaccine should be shaken well
to obtain a uniform, whitish translucent suspension. Vial should be visually checked
for the presence of any particulate matter or other coloration, if any, prior to its
administration. If in doubt, do not use the contents of the vial.
Whole Virion, Inactivated Corona Virus Vaccine should not be mixed with other
vaccines.
4.5 Interaction with other medicinal products.
Chloroquine and Corticosteroids as they may impair the antibody response.
4.6 Pregnancy and Lactation
Safety and effectiveness have not been established in pregnant women and in nursing
mothers.
4.7 Effects on ability to drive and use machines
No studies on the effect of Whole Virion, Inactivated Corona Virus Vaccine on the
ability to drive and use machines have been performed.
4.8 Undesirable effects
Clinical Trial Experience
Safety of the Whole Virion, Inactivated Corona Virus Vaccine was established Phase
1 and Phase 2 studies and study is ongoing.
Phase 1 clinical trial was conducted in India in 375 adult healthy volunteers, which
is still ongoing. The most common local adverse event reported was Injection site
Pain. The most common systemic adverse events reported were headache, followed

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
by fatigue, fever, body ache, abdominal pain, nausea, and vomiting. The other less
common adverse events were dizziness/giddiness, tremor, sweating, cold, cough, and
injection site swelling. No vaccine related serious adverse events (SAE) were
reported.
A Phase 2 clinical trial was conducted in India in 380 adolescents and adult healthy
volunteers, which is still ongoing. Similar adverse events were reported in the phase
2 clinical trial. No vaccine related serious adverse events (SAE) were reported.
A Phase 3 efficacy study is on-going in 25,800 participants and administered with 1st
dose of vaccination with Whole Virion, Inactivated Corona Virus Vaccine, no
vaccine related adverse events were observed.
4.9 Immune Response
COVID-19 disease is caused due to SARS-CoV-2 virus infection.
In Phase 1 clinical trial a total of 375 healthy participants were enrolled across the
three groups and received three vaccine formulations, BBV152A (3µg with Algel-
IMDG (Aluminium hydroxide gel- Imidazo quinolin gallamide (IMDG); a TLR 7/8
agonist), BBV152B (6µg with Algel-IMDG), and BBV152C (6µg with Algel). None
of the participants had detectable neutralizing antibodies at baseline analyzed by
MNT50. The proportion of participants seroconverted post 2 weeks after 2nd dose
was 87.9%, 91.9%, and 82.8% in the BBV152A, B, and C groups, respectively.
In Phase 2 clinical trial a total of 380 healthy participants were enrolled among two
groups and received two vaccine formulations, BBV152 A and BBV152B. None of
the participants had detectable neutralizing antibodies at baseline analyzed by
MNT50. The proportion seroconverted participants of Group 1 and Group 2, post 4
weeks of 2nd dose was 88.0% and 96.6% respectively.
4.10 Overdose
No case of overdose has been reported.

5. Pharmacological Properties
5.1 Pharmacodynamic properties
COVID-19 disease is caused due to SARS-CoV-2 virus infection. Whole Virion,
Inactivated Corona Virus Vaccine, has been studied in Phase 1 and 2 clinical studies
for safety and immunogenicity and found to be safe and immunogenic. Whole Virion,
Inactivated Corona Virus Vaccine has been shown to prevent COVID-19 following
Common Technical Document of COVAXIN™-Module-1 (Administrative information)
CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
2 doses given 4 weeks apart. The duration of protection against COVID-19 is
currently unknown.
5.2 Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not required for vaccines.
5.3 Preclinical safety data
All the formulations were tested for immunogenicity in mice, rats, and rabbits. Mice,
rats, and rabbits were vaccinated on days 0, 7, and 14 (n+1 doses). Further these
formulations are tested for immunogenicity, safety, and protective efficacy in Syrian
Hamster challenge model and Non-Human Primates (Rhesus macaque) challenge model.
The Hamsters were vaccinated on Days 0, 14, and 35 (n+1 doses), the live SARS-CoV-
2 virus was challenged through intranasal route on Day 50. Likewise, the Rhesus
macaques were vaccinated on Days 0 and 14, and live SARS-CoV-2 virus was challenged
through intranasal and intratracheal routes on Day 28. All the formulations were found
to be safe, immunogenic, and provided effective protection to both upper and lower
respiratory tract.

6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
 Aluminium hydroxide gel equivalent to Al+3
 TLR 7/8 Agonist
 2-phenoxyethanol
 Phosphate buffered saline
Note: TLR 7/8 agonist is an Imidazo quinolin gallamide (IMDG)
6.2 Incompatibilities
The product should not be mixed with any other medicinal products or active immunizing
agents.
6.3 Shelf life
The expiry date of Whole Virion, Inactivated Corona Virus Vaccine is indicated on the
label and carton of the product. Do not use the product after the expiration date shown
on the label and carton of the product.
6.4 Special precautions for storage
Store at +2° to +8 °C, do not freeze. Discard if frozen.
Shake well before use. Keep out of reach of children. Protect from light.
Common Technical Document of COVAXIN™-Module-1 (Administrative information)
CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
6.5 Nature and contents of container
Whole Virion, Inactivated Corona Virus Vaccine is presented as Single dose (0.5 mL)
and multidose (5 mL and 10 mL) in transparent vial (USP type I glass) with a stopper
(Bromobutyl rubber) and a flip-off plastic cap with aluminium seal. Each vial of single
dose contains 0.5 mL, each vial of multidose contains 10 doses (5 mL) and 20 doses (10
mL) respectively.
6.6 Handling of multi-dose vials
Opened vials should be used as soon as possible and within 6 hrs when kept between 2 -
8 ºC.
6.7 Disposal
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7. The Vaccine Vial Monitor (Optional)

Presentation available with or without vaccine vial monitor
Vaccine Vial Monitors (VVM7) dot is on the seal of Vaccine vials supplied through
Bharat Biotech. VVM7 are supplied by TEMPTIME Corporation, USA. This is a time-
temperature sensitive dot that provides an indication of the cumulative heat to which the
vial has been exposed. It warns the end user when exposure to heat is likely to have
degraded the vaccine beyond an acceptable level.

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
The interpretation of the VVM7 is simple: Focus on the central square; its colour will
change progressively. As long as the colour of this square is lighter than the colour of
the ring, the vaccine can be used. As soon as the colour of the central square is the same
colour as the ring or of a darker colour than the ring, the vial should be discarded.
 
8. MARKETING AUTHORISATION NUMBER(S)
MF/BIO/21/000002, dated 3rd Jan, 2021

9. MARKETING AUTHORISATION HOLDER

Bharat Biotech International Ltd. 

Sy. No. 230, 231 and 235, Genome Valley, Turkapally, Shamirpet Mandal, Medchal-
Malkajgiri District - 500 078, Telangana State, India. 
E‐mail: feedback@bharatbiotech.com; Website: www.bharatbiotech.com 
 
For complaints and suggestions about the product, and any adverse event, please email
to feedback@bharatbiotech.com or call on Toll-free number: 1800 102 2245.

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
Labelling: Labelling contain following information
1) INN Name of the Product: Whole Virion, Inactivated Corona Virus Vaccine
2) Brand Name of the product: COVAXINTM
3) Composition:
Active Ingredient
Whole Virion Inactivated Corona Virus Antigen
6µg
(Strain NIV-2020-770)
Inactive ingredients
Aluminium hydroxide gel equivalent to Al+3 250 µg
TLR 7/8 Agonist 15 µg
2-phenoxyethanol 2.5mg
Phosphate buffered saline q.s. to 0.5mL

4) Storage Condition: Store at 2-8ºC

5) Dose of vial: 0.5 mL Single dose Vial, 2.5 mL Multi dose vial, 5.0 mL Multi dose vial
6) Route of Administration: Intramuscular
7) Manufacturing License No: 03/HD/AP/98/V/R
8) Address: Bharat Biotech International Limited Genome Valley, Shamirpet Mandal,
Medchal-Malkjajgiri District-500 078, Telangana, India
9) Batch Coding: Batch coding contains 1) Batch No. 2)Manufacturing Date 3) Expiry Date

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
Package insert:
Package insert contains below information.
1) Name and description of Medicinal Product
2) Qualitative and Quantitative Composition
3) Pharmaceutical form
4) Clinical particulars
4.1 Therapeutic indications
4.2 Posology and Method of administration
4.3 Contra Indications
4.4 Special Warnings and Precautions for use
4.5 Interaction with other medicinal products
4.6 Pregnancy and Lactation
4.7 Effects on ability to drive and Use Machines
4.8 Undesirable effects
4.9 Immune response
4.10 overdose
5) Pharmacological Properties
5.1 Pharmacodynamic properties
5.2 Pharmacokinetic properties
5.3 Preclinical safety data
6) Pharmaceutical Particulars
6.1 List of Excipients
6.2 Incompatibilities
6.3 Shelf life
6.4 Special precautions for Storage
7) Presentation
8) Vaccine vial Monitor (optional)

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
1.3.2 Mock ups (Artworks)
Mock ups (Art works) of 0.5 mL (single dose), 5.0 mL (10 doses) and 10 mL (20
doses) packs are enclosed overleaf.
Mock ups for 2.5 mL (5 doses) shall be provided later.

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
1.3.3 Specimens
Original package sample will be provided based upon request

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
1.3.4 Consultation with Target Patient Groups
Not Applicable

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
1.3.5 Product Information already approved in the Member State
Not Applicable

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission 
 
 Whole Virion, Inactivated Corona Virus Vaccine

 
1.3.6 Braille
Not Applicable
 

Common Technical Document of COVAXIN™-Module-1 (Administrative information)

CONFIDENTIAL: Not to be reproduced fully/partially without permission