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Ref. Ares(2021)496499 - 21/01/2021
 
  
 
 

Public Assessment Report  
Authorisation for Temporary Supply 
 
 

 
 
COVID-19 Vaccine AstraZeneca, solution for 
injection in multidose container 
COVID-19 Vaccine (ChAdOx1-S 
[recombinant]) 
 
 
 
 
 

Department of Health and Social Care (DHSC) 
AstraZeneca AB

COVID-19 Vaccine AstraZeneca, solution for injection in multidose 
 
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LAY SUMMARY 
 
 
COVID-19 Vaccine AstraZeneca, solution for injection in multidose container  
COVID-19 Vaccine (ChAdOx1-S [recombinant]) 
 
This is a summary of the Public Assessment Report (PAR) for COVID-19 Vaccine 
AstraZeneca, solution for injection in multidose container. It explains how this product was 
assessed and its authorisation recommended, as well as its conditions of use. It is not 
intended to provide practical advice on how to use this product. 
 
This product will be referred to as COVID-19 Vaccine AstraZeneca in this lay summary for 
ease of reading. 
 
For practical information about using COVID-19 Vaccine AstraZeneca, patients should read 
the Information for UK recipients on COVID-19 Vaccine AstraZeneca or contact their doctor 
or pharmacist. 
 
What is COVID-19 Vaccine AstraZeneca and what is it used for? 
COVID-19 Vaccine AstraZeneca is a vaccine indicated for active immunisation of individuals 
18 years of age and older for the prevention of coronavirus disease 2019 (COVID-19). 
How does COVID-19 Vaccine AstraZeneca work? 
COVID-19 Vaccine AstraZeneca stimulates the body’s natural defences (immune system) 
and causes the body to produce its own protection (antibodies) against the virus. None of the 
ingredients in this vaccine can cause COVID-19. 
 
How is COVID-19 Vaccine AstraZeneca used? 
The pharmaceutical form of this medicine is a solution for injection and the route of 
administration is intramuscular injection. COVID-19 Vaccine AstraZeneca will be given to 
you by an authorised practitioner as an intramuscular injection into the muscle at the top of 
the upper arm (deltoid muscle). 
 
You will receive 2 injections of COVID-19 Vaccine AstraZeneca, each of 0.5ml. You will be 
told when you need to return for your second injection of COVID-19 Vaccine AstraZeneca. 
The second injection can be given between 4 and 12 weeks after the first injection. 
 
For further information on how COVID-19 Vaccine AstraZeneca is used, refer to the 
Information for UK recipients on COVID-19 Vaccine AstraZeneca and Information for 
Healthcare Professionals on COVID-19 Vaccine AstraZeneca 
available on the Medicines and 
Healthcare products Regulatory Agency (MHRA) website. 
 
This vaccine can only be obtained with a prescription. 
 
If a person has any questions concerning the vaccine, they should ask the administering 
healthcare practitioner. 
 
What benefits of COVID-19 Vaccine AstraZeneca have been shown in studies? 
COVID-19 Vaccine AstraZeneca has been given to approximately 24,000 individuals aged 
18 years or older in four ongoing clinical trials in the UK, Brazil and South-Africa. Most 
 
Regulation 174 
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were equally allocated to COVID 19 Vaccine AstraZeneca or a control (another vaccine not 
targeting SARS-CoV-2 or a placebo). 
 
In a pre-specified preliminary analysis, those who received the vaccine had a reduction in the 
rate of COVID-19 illness compared to those who received the control (30 cases of COVID-
19 illness in the vaccinated group compared to 101 cases in the control group). These results 
were observed two weeks or more after the second dose in study participants with no 
evidence of prior SARS-CoV-2 infection. 
 
A similar benefit was observed in participants who had one or more other medical conditions 
that increase the risk of severe COVID-19 disease, such as obesity, cardiovascular disorder, 
respiratory disease or diabetes. 
 
What are the possible side effects of COVID-19 Vaccine AstraZeneca? 
The most common side effects with COVID-19 Vaccine AstraZeneca (which may affect 
more than 1 in 10 people) were tenderness, pain, warmth, redness, itching, swelling or 
bruising where the injection is given, generally feeling unwell, feeling tired (fatigue), chills 
or feeling feverish, headache, feeling sick (nausea), joint pain or muscle ache. In clinical 
studies, most side effects were mild to moderate in nature and resolved within a few days 
with some still present a week after vaccination 
 
For the full list of all side effects reported with this medicine, see Section 4 of the 
Information for UK recipients on COVID-19 Vaccine AstraZeneca or the Information for 
Healthcare Professionals on COVID-19 Vaccine AstraZeneca 
available on the MHRA 
website. 
 
Why was COVID-19 Vaccine AstraZeneca approved? 
It was concluded that COVID-19 Vaccine AstraZeneca has been shown to be effective in the 
prevention of COVID-19. Furthermore, the side effects observed with use of this product are 
considered to be similar to those seen for other vaccines. Therefore, the MHRA concluded 
that the benefits are greater than the risks and recommended that this medicine can be 
authorised for temporary supply during the COVID-19 pandemic. 
 
What measures are being taken to ensure the safe and effective use of 
COVID-19 Vaccine AstraZeneca? 
All new medicines approved require a Risk Management Plan (RMP) to ensure they are used 
as safely as possible. An RMP has been agreed for the use of COVID-19 Vaccine 
AstraZeneca in the UK.  Based on this plan, safety information has been included in 
the Information for UK Healthcare Professionals and the Information for UK recipients, 
including the appropriate precautions to be followed by healthcare professionals and patients.   
 
All side effects reported by patients/healthcare professionals are continuously monitored. 
Any new safety signals identified will be reviewed and, if necessary, appropriate regulatory 
action will be taken. The MHRA has also put in place an additional proactive safety 
monitoring plan for all COVID-19 vaccines to enable rapid analysis of safety information 
which is important during a pandemic.  
 
Other information about COVID-19 Vaccine AstraZeneca 
Authorisation for the temporary supply of COVID-19 Vaccine AstraZeneca was granted in 
the UK on 29 December 2020. 
 
 
Regulation 174 
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The full public assessment report for COVID-19 Vaccine AstraZeneca follows this summary.  
 
This summary was last updated 31 December 2020. 
 
 
Regulation 174 
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TABLE OF CONTENTS 
 

INTRODUCTION ......................................................................................................... 6 
II 
QUALITY ASPECTS ............................................................................................................. 9 
III  
NON-CLINICAL ASPECTS .............................................................................................. 15 
IV  
CLINICAL ASPECTS ......................................................................................................... 24 

USER CONSULTATION ................................................................................................... 56 
VI  
OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND     
RECOMMENDATION ....................................................................................................... 56 

TABLE OF CONTENT OF THE PAR UPDATE ....................................................................... 57 
  
 
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INTRODUCTION 
This report is based on the information provided by the company in a rolling data submission 
procedure and it covers the authorisation for temporary supply of COVID-19 Vaccine 
AstraZeneca. At the time of writing the company have provided sufficient information to 
make a decision on the vaccine but final reports for all studies have not yet been received: in 
addition, a reproductive toxicology study is ongoing. 
Quality aspects of the vaccine are reviewed on a batch-specific basis. 
 
In December 2019, a pneumonia outbreak of unknown cause occurred in Wuhan, China and 
in January 2020, a novel coronavirus was discovered as the underlying cause. Infections by 
the virus, named SARS-CoV-2, and the resulting disease, COVID-19, have spread globally. 
On 11 March 2020, the WHO declared the COVID-19 outbreak to be a pandemic.  
 
The number of COVID-19 cases in the UK now stands at more than 2 million and over 
70,000 deaths have been attributed to the disease. The elderly and those with pre-existing 
medical conditions are at particular risk of severe disease and death from COVID-19. A new 
variant of SARS-CoV-2 has recently been identified which has a higher transmission rate 
than the other variants in circulation. Currently there is no evidence that this variant causes 
more severe disease or higher mortality. Vaccination is the most effective medical 
intervention to decrease risk and reduce spread of the SARS-CoV-2 virus.  
 
The Department of Health and Social Care (DHSC) is leading the Government’s deployment 
of vaccinations against COVID-19. In order to save lives, and to reduce the number of people 
who need hospital treatment due to COVID-19, the DHSC have sought to deploy a safe and 
effective vaccine as soon as possible. In a letter dated 24 November 2020, the DHSC 
requested authorisation, on a temporary basis, of its proposed supply of a vaccine 
manufactured by AstraZeneca AB named “COVID-19 Vaccine AstraZeneca”, under 
Regulation 174 of the Human Medicines Regulations 2012, (“the Regulations”).  
Development of COVID-19 Vaccine AstraZeneca was initiated by the University of Oxford 
with subsequent transfer of development activities to AstraZeneca AB. In a subsequent letter 
dated 22 December 2020, and in light of knowledge of the new variant of SARS-CoV-2, the 
DHSC requested MHRA to consider the time interval between initial and booster doses of 
vaccine in which efficacy has been demonstrated, in order to provide operational flexibility 
and to enable a larger proportion of the population to receive a first dose in a shorter 
timeframe.  
 
Following an extensive review of the quality, safety and efficacy data, COVID-19 Vaccine 
AstraZeneca has been authorised for temporary supply in the UK for the following 
indication: active immunisation of individuals ≥18 years old for the prevention of 
coronavirus disease 2019 (COVID-19). COVID-19 Vaccine AstraZeneca is a solution for 
injection stored at 2 – 8°C intended for intramuscular administration (IM). A single 4 mL vial 
contains 8 doses (each 0.5 mL) and a single 5 mL vial contains 10 doses (each 0.5 mL).  
 
The SARS-CoV-2 virus uses proteins on its outer surface, called spike (S) proteins, to enter 
the cells of the body and cause disease. The active substance of COVID-19 Vaccine 
AstraZeneca is a monovalent vaccine composed of a single recombinant, replication-deficient 
chimpanzee adenovirus (ChAdOx1) vector that codes for the S glycoprotein of SARS-CoV-2 
(ChAdOx1-S [recombinant]). Following vaccine administration, this vector enters into the 
cells of the body and produces the S glycoprotein of SARS-CoV-2 which is then expressed 
on the surface of the cells. Expression of the spike protein induces neutralising antibodies and 
 
Regulation 174 
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T-cells to be raised against it. Should the body then become infected with SARS-CoV-2, the 
immune system will recognise the SARS-CoV-2 virus and attack it.  
 
The authorisation is for specific batches of the vaccine, after confirmation that detailed 
conditions are met. The Conditions for Authorisation for COVID-19 Vaccine AstraZeneca 
are published on the MHRA website. 
 
The MHRA has been assured that acceptable standards of Good Manufacturing Practice 
(GMP) are in place for this product at all sites responsible for the manufacture, analysis, 
assembly and batch release of this product.  
 
A Risk Management Plan (RMP) and a summary of the pharmacovigilance system have been 
provided with this application and are satisfactory. 
 
This batch, and any future batches, of COVID-19 Vaccine AstraZeneca are subject to 
Qualified Person (QP) certification and batch evaluation by an independent control 
laboratory before the vaccine is released into the UK.  
 
The COVID-19 Vaccine Benefit Risk Expert Working Group (Vaccine BR EWG) have met 
several times to review and discuss the quality, safety and efficacy aspects in relation to 
batches of COVID-19 Vaccine AstraZeneca.  
 
The Vaccine BR EWG gave advice to the Commission of Human Medicines (CHM) on 29 
September 2020, 14 October 2020, 10 November 2020, 7 December 2020, 10 December 
2020, 17 December 2020, 22 December 2020, 24 December 2020, 29 December 2020 and 31 
December 2020, regarding the requirements for authorisation for the temporary supply of 
COVID-19 Vaccine AstraZeneca. The requirements for quality, safety and efficacy were 
considered, taking into account the urgent public health need and risk to life, the pandemic 
situation and limited options for prevention and treatment of COVID-19. As well as data on 
quality, safety, efficacy and the timing of the second dose, specific conditions on the product 
were discussed to ensure adequate standards of quality and safety are met.  
 
The CHM concluded that the proposed supply of COVID-19 Vaccine AstraZeneca for active 
immunisation to prevent coronavirus disease 2019 (COVID-19), in individuals 18 years of 
age and older, is recommended to be suitable for approval under Regulation 174 provided the 
company meets the Conditions for Authorisation for COVID-19 Vaccine AstraZeneca set out 
by the MHRA.   
 
Authorisation for the temporary supply of COVID-19 Vaccine AstraZeneca was granted in 
the UK on 29 December 2020. This report covers data received and reviewed for this 
authorisation only. This authorisation is valid until expressly withdrawn by MHRA or upon 
issue of a marketing authorisation by MHRA. 
 
Whilst an acceptable level of information has been received to provide assurance that 
appropriate standards of quality, safety and efficacy have been met for authorisation of 
specific batches for temporary supply under Regulation 174 of the Regulations, it should be 
noted that COVID-19 Vaccine AstraZeneca remains under review as MHRA continues to 
receive data from the company as it becomes available. This will include, for example, final 
study reports for all studies, long-term follow-up efficacy and safety data. Further 
information that is received by the MHRA will be reviewed as part of the ongoing 
 
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assessment for this product and updates will be made to this PAR to reflect that in due 
course.  
 
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II 
QUALITY ASPECTS 
II.1 
Introduction  
This product is a colourless to slightly brown solution provided in a multidose vial of 2 
different sizes: 10-dose drug product presentation (5 mL of vaccine) in a 6 mL vial or 10R 
vial, and an 8-dose drug product presentation (4 mL of vaccine)  in a 5 mL vial. 
 
One dose (0.5 mL) contains COVID-19 Vaccine (ChAdOx1-S recombinant) 5 × 1010 viral 
particles (vp), where ChAdOx1-S means the recombinant, replication-deficient chimpanzee 
adenovirus vector encoding the SARS-CoV-2 Spike (S) glycoprotein. The adenovirus is a 
non-enveloped virus. 
 
The vaccine is produced in genetically modified human embryonic kidney (HEK) 293 cells. 
COVID-19 Vaccine AstraZeneca contains genetically modified organisms (GMOs). 
 
In addition to ChAdOx1-S (recombinant) this product also contains the excipients L-
histidine, L-histidine hydrochloride monohydrate, magnesium chloride hexahydrate, 
polysorbate 80, ethanol, sucrose, sodium chloride, disodium edetate dihydrate and water for 
injections. 
 
The finished product is packaged in multidose vials of either: 5 ml of solution in a 10-dose 
vial (clear type I glass) with a halobutyl rubber stopper and an aluminium overseal with a 
plastic flip-off cap (in packs of 10 vials); or 4 ml of solution in an 8-dose vial (clear type I 
glass) with a halobutyl rubber stopper and an aluminium overseal with a plastic flip-off cap.  
 
Satisfactory specifications and Certificates of Analysis have been provided for all packaging 
components. All primary packaging complies with European Pharmacopoeia requirements.   
 
II.2 

ACTIVE SUBSTANCE 
rINN:  not assigned 
The active substance is a clear to slightly opalescent solution. 
 
Structure 
The active substance, ChAdOx1-S (recombinant), is a recombinant, replication-deficient (E1 
and E3 deleted) chimpanzee adenovirus that encodes the SARS-CoV-2 spike protein with a 
tissue plasminogen activator (tPA) leader sequence. 
 
Adenoviruses are non-encapsulated, icosahedral particles (virions) between 80 and 100 nm in 
diameter, with prominent fibres protruding from the 12 vertices. The viral capsid is 
composed of three major proteins (fibre, hexon and penton) with four minor proteins (IIIa, 
VI, VIII and IX). The particles contain a single copy of the double-stranded DNA genome. 
The manufacturer has provided the DNA sequence of the 35,539 bp ChAdOx1-S 
(recombinant) genome. 
 
The expression cassette for the SARS-CoV-2 spike protein fused to the tPA leader uses a 
modified human cytomegalovirus (CMV) promoter and a bovine growth hormone 
polyadenylation sequence. 
 
The nucleotide sequence of the SARS-CoV-2 spike protein fused to the tPA leader encoded 
by ChAdOx1-S (recombinant) have been provided by the manufacturer.  
 
 
 
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General properties 
Adenoviruses such as ChAdOx1-S (recombinant) are non-encapsulated, icosahedral particles 
(virions) between 80 and 100 nm in diameter, with prominent fibres protruding from the 12 
vertices. The particles contain a single copy of the double-stranded DNA genome (contains a 
transgene to express the SARS-CoV02 virus spike [S] protein). 
 
Viral genome size 
The active substance, ChAdOx1-S (recombinant), has a genome size of 35,539 base pairs 
(bp).  
 
ChAdOx1-S (recombinant) is not the subject of a European Pharmacopoeia (Ph. Eur.) 
monograph. 
 
Manufacture of the drug substance 
The manufacturer has provided details of the responsibilities of each facility involved in 
manufacture and testing including responsibilities performed by contract laboratories. A 
description of the manufacturing process and controls has been provided for each 
manufacturing site, including material inputs, critical and non-critical process parameters, 
and process outputs. The upstream process consists of working host cell bank vial thaw, 
inoculum expansion, infection with working virus seed and further expansion in the 
production bioreactor to generate ChAdOx1-S (recombinant). The downstream process 
consists of lysis of the production bioreactor cell culture, nuclease digestion of the host cell 
DNA, clarification and further processing through a series of purification/concentration steps 
to remove process-related impurities and then formulation with excipients and aseptic 
filtration. 
 
The comparability between drug substance batches manufactured for the clinical program 
and drug substance batches representative of the commercial process has been evaluated.  
The data generated indicate consistency between the drug substance described for this 
application and that used in the clinical programme. 
 
GMP certificates or a QP declaration have been provided for all relevant manufacturing sites, 
testing sites and QP release site. There are no GMP concerns. 
 
Control of Materials 
Raw materials are purchased from quality-approved suppliers according to approved 
procedures and are either compendial grade (i.e. defined in a Pharmacopoeia) or purchased in 
accordance with the vendor’s and/or manufacturer’s written specifications. No materials of 
human origin were used in the manufacturing process for COVID-19 Vaccine AstraZeneca 
other than the host cells, which are derived from the HEK293 human embryonic kidney cell 
line. Materials of animal origin used in pre-GMP virus seed development, GMP cell banking, 
virus seed banking and the manufacturing process have been adequately described. 
Information, certificates of origin and TSE certificates of suitability have been provided. 
 
Satisfactory descriptions have been provided for all starting materials. Detailed descriptions 
are given for the development of the ChAdOx1 adenoviral vector, development of the 
recombinant spike protein gene, construction of the intermediate ChAdOx1 nCoV-19 BAC 
plasmid, and generation of the host cell line as well as the generation of the viral isolate and 
preparation of the research virus seed (RVS). 
 
 
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Details of the master host cell bank and working host cell bank have been provided as well as 
details of the master virus seeds (MVSs), working virus seeds (WVSs) and control cell 
cultures. Testing of the cell banks is in line with ICH Q5A (R1) and ICH Q5D. The cell 
banks were tested for identity, safety, and purity, and all test results met the acceptance 
criteria.  
 
Tests include sterility, mycoplasma, adventitious and endogenous viruses and cell line 
species identification. A test for replication competent adenovirus (RCA) is conducted on 
every AZD1222 MVS and on every drug substance at the bulk harvest step to confirm the 
absence of replication competent adenovirus. 
 
Controls of Critical Steps and Intermediates 
Synthesis of the active substance from the designated starting materials has been adequately 
described and appropriate in-process controls and intermediate specifications are applied. 
The microbial controls (in-process bioburden and endotoxin measurements) used to 
demonstrate microbial control of the manufacturing process for drug substance are described 
and found acceptable.   
 
Process validation 
Drug substance process validation studies are not yet complete, however, the general 
validation plans described appear acceptable. Full validation study results must be provided 
once available. 
 
Characterisation 
Appropriate proof-of-structure data have been supplied for the active substance.  
 
Impurities 
All potential known product-related impurities have been identified and characterised. The 
process-related impurities are divided into three categories: biologically-derived 
macromolecules, small molecules and synthetic macromolecules. These have been 
adequately evaluated and described.  
 
Control of drug substance 
An appropriate release specification is provided for the active substance. The manufacturer 
has provided adequate justification for these limits, based on efficacy and safety 
considerations, and/or well-established limits for other medicines (where this is appropriate). 
It is agreed that due to the relatively limited manufacturing experience to date the proposed 
specifications can be accepted at this time, by taking into account the efficacy and safety 
justifications. The specifications will be revisited and revised if appropriate after a suitable 
number of commercial batches have been prepared.   
 
Validation of analytical procedure 
Validation of the analytical methods used for the control of the drug substance are 
satisfactory for ensuring compliance with the relevant specifications.  
 
Batch analyses 
Batch release results for all batches used in the clinical trials, along with site of manufacture, 
have been provided and show that all batches conformed to the specifications in force at time 
of manufacture.  
 
 
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Batch release data for the commercially manufactured drug substance lots that have been 
provided to date are all within specification and no major trends are apparent between the 
different manufacturing facilities.  
 
All batch release results are provided and confirmed to be within specification before 
approval of each batch under Regulation 174. 
 
Justification of specification 
Acceptance criteria for stability and lot release testing are established within limits that 
ensure the safety and efficacy of the product and allow for reliable manufacturing and 
adequate shelf life needed for continued product supply. Some specifications are further 
justified based on manufacturing experience with other adenoviral products and/or 
compliance with regulations, guidance, and compendial monographs.  
 
Reference Standard 
The reference standard used for routine drug substance and drug product lot release and 
stability testing has been described. The reference standard is placed on stability. Preparation 
and qualification of the reference standard has been provided and is adequate.  
 
Container Closure System 
Suitable specifications have been provided for all packaging used. The two primary container 
closure systems for the drug substance have been described and are suitable for the intended 
use. Stability testing has shown the primary containers to be compatible with the drug 
substance. Long-term storage of the drug substance in the primary containers has been 
provided and is adequate.  
The primary packaging has been shown to comply with the quality standards of the Ph.Eur. 
 
Stability 
The stability data provided are sufficient to support the proposed shelf-life of 6 months for 
the drug substance. The company has committed to continue the stability studies.  
 
II.3 
DRUG PRODUCT 
COVID-19 Vaccine AstraZeneca is a sterile liquid dosage form intended as a multiple-dose 
vial for administration by intramuscular injection. The drug product is supplied in 
presentations containing either 8 doses or 10 doses per vial. COVID-19 Vaccine AstraZeneca 
is manufactured with clear and colourless vials, closed with elastomeric stoppers, and sealed 
with aluminium overseals. The drug product vials are packaged 10 vials in a carton. 
 
Pharmaceutical development
 
A satisfactory account of the pharmaceutical development has been provided. The sterile 
drug product dosage form was developed to ensure COVID-19 Vaccine AstraZeneca stability 
and to meet clinical dose level needs by intramuscular administration. The formulation 
composition was developed based on experience with adenoviruses. 
 
All excipients, including water for injection (WFI) comply with the specifications of the Ph. 
Eur. None of the excipients are of animal or human origin, nor are any novel. The excipients 
are well established for pharmaceutical products. 
  
This product consists of genetically modified organisms (GMO).  
 
 
 
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COVID-19 Vaccine AstraZeneca, solution for injection in multidose 
 
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Manufacture of the drug product 
A description of the manufacturing method has been provided. Drug product manufacturing 
consists of thawing, dilution, mixing sterile filtration, aseptic filling, visual inspection and 
labelling. The finished drug product is stored at 2-8°C. 
The development of the clinical manufacturing processes have been adequately described. 
Comparability studies demonstrate that drug product from each process is comparable and 
conform to pre-defined comparability criteria. 
 
A satisfactory batch formula has been provided for the manufacture of the product for 
presentations with 8 doses/vial, 5 mL vial size, 10 doses/vial, 6 mL vial size, and 10 
doses/vial, 10R vial size. 
 
An appropriate account of the manufacturing process has been provided for each drug 
product manufacturer. The manufacturing process has been adequately described and the 
manufacturing process controls in place are acceptable. 
 
Controls of critical steps and intermediates 
Adequate information on critical process parameters and in-process controls has been 
provided. Control of critical process steps for the manufacture of COVID-19 Vaccine 
AstraZeneca is described through critical process parameters, in-process controls, and in-
process hold time. 
 
Process validation 
Drug product process validation studies are not yet complete, however, the general validation 
plans described appear acceptable. Full validation study results must be provided once 
available. 
 
Control of excipients 
All excipients are of compendial grade and none of the excipients are of human or animal 
origin. As the drug product excipients are tested according to compendial methods, no 
validation of the analytical procedures is required to be submitted for review. 
 
Control of drug product 
The finished product specification is satisfactory. The manufacturer has provided adequate 
justification for these limits, based on efficacy and safety considerations, and/or well-
established limits for other medicines (where this is appropriate). It is agreed that due to the 
relatively limited manufacturing experience to date the proposed specifications can be 
accepted at this time by taking into account the efficacy/safety justifications. The 
specifications will be revisited and revised if appropriate after a suitable number of 
commercial batches have been prepared.   
 
Analytical procedures 
Validation of the analytical methods used for the control of the drug product are satisfactory 
for ensuring compliance with the relevant specifications.  
 
Batch analyses 
Batch release results for all batches used in the clinical trials, along with site of manufacture, 
have been provided and show that all batches conformed to the specifications in force at time 
of manufacture.  
 
 
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Batch release data for the commercially manufactured drug product lots that have been 
provided to date are all within specification.  
 
All batch release results are provided and confirmed to be within specification before 
approval of each batch under Regulation 174. 
 
Independent Batch testing  
Independent batch testing provides additional assurance of quality before a batch is made 
available to the market. Independent batch testing is a function that is undertaken by an 
Official Medicines Control Laboratory (OMCL) and, under Regulation 174A, the UK 
National Institute for Biological Standards and Control (NIBSC) is responsible for this 
function.  
 
Independent batch testing is product-specific: it requires specific materials and 
documentation from the manufacturer and comprises laboratory-based testing and review of 
the manufacturer’s test data. If all tests meet the product specifications a certificate of 
compliance is issued by the OMCL. NIBSC has developed the capability and capacity to 
undertake the independent batch tests for this product.  
 
Characterisation of impurities
 
There are no new process related drug product impurities in addition to those described for 
the drug substance. 
 
Justification of specifications 
Acceptance criteria for stability and lot release testing are established within limits that 
ensure the safety and efficacy of the product, ensure consistent manufacturing and allow an 
adequate shelf life for continued product supply. Some specifications are further justified 
based on manufacturing experience with other adenoviral products and/or compliance with 
regulations, guidance, and compendial monographs.  
 
Reference standards or materials 
The reference standard used for the drug substance and the drug product are the same. This is 
acceptable as both drug substance and drug product have the same composition.  
 
Container closure system 
The container closure system has been well described and complies with the relevant quality 
standards of the Ph.Eur. 
 
Stability 
Finished product stability studies include batches of the finished product stored in the 
packaging proposed for marketing. The manufacturer has provided all stability data available 
to date. Based on the results, a shelf-life of 6 months at 2°C to 8°C for the unopened 
multidose vials is recommended.  
 
The product should be stored in the original package in order to protect from light. During 
use, vials can be handled in room light conditions. It should not be frozen. 
 
Since the vaccine does not contain a preservative, once the stopper has first been punctured, 
the vial should be used within 6 hours. After the first dose is withdrawn, the vaccine should 
be stored between 2°C to 25°C and used as soon as practically possible. After 6 hours, any 
unused vaccine left in the vial should be discarded.  
 
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Suitable post approval stability commitments have been provided to continue stability testing 
on batches of COVID-19 Vaccine AstraZeneca. The manufacturer has committed to provide 
these data to the MHRA on an on-going basis as it becomes available. 
 
Handling and disposal 
Distribution during deployment should be controlled at 2-8°C throughout its shelf life of 
6 months. 
 
Further packing down (splitting of packs) of lots to aid deployment, can occur at 2-8°C 
within its shelf life. This can also be implemented at ‘room temperature’ (less than 25°C), if 
completed within 2 hours, immediately prior to final pre-use distribution (at 2-8°C). GMP 
controls are required to ensure there is no detrimental impact to quality, safety or efficacy of 
the lots by this processing. 
 
After first use, the vials should be marked with the date and time. 
 
Disposal should take account of the fact that COVID-19 Vaccine AstraZeneca contains a 
genetically modified organism (GMO). Any unused vaccine or waste material should be 
disposed of in accordance with local requirements. Spills should be disinfected with an 
appropriate antiviral disinfectant. 
 
II.4  

Regulation 174 
Authorisation for temporary supply of COVID-19 Vaccine AstraZeneca under this 
Regulation 174 has been given following review of batch specific data by MHRA.  
 
Independent batch release by the National Institute for Biological Standards and Control 
(NIBSC) is performed on all batches to be supplied to the UK. 
 
The quality data currently available for COVID-19 Vaccine AstraZeneca can be accepted as 
sufficient with specific conditions in place. There are no scientific objections arising from 
this review to the authorisation for temporary supply for this product under Regulation 174 of 
the Human Medicine Regulations. 
 
 
III  
NON-CLINICAL ASPECTS 
 
III.1  Introduction 
In vivo animal safety testing with the vaccine has been conducted and it was well tolerated 
with no adverse findings. At the time of writing, the only remaining data expected, that are in 
compliance with Good Laboratory Practice (GLP) are from a reproductive toxicity study in 
mice.  This will be reported in 2021. The primary pharmacology data reviewed do use 
COVID-19 Vaccine AstraZeneca. 
 
The following non-clinical information was reviewed for this application.  
 
Primary Pharmacology 
Graham, S. P. et al. Evaluation of the immunogenicity of prime-boost vaccination with the 
replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19. npj 
Vaccines. 
5, 69 (2020) 
Study INT-ChAdOx1 nCov19-POT-002 – To determine potency of the CBF manufacturing 
batch of COVID-19 Vaccine AstraZeneca in mice 
 
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Study 20-01125 - Assessment of efficacy of SARSCoV-2 vaccine candidates in the ferret 
model 
Study 6285 – Efficacy of ChAdOx1 nCoV-19 against coronavirus infection in ferrets 
van Doremalen, N. et al. ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in 
rhesus macaques. Nature. 586, 578-582 (2020) 
Study 6284 – Efficacy of ChAdOx1 nCoV-19 against coronavirus in rhesus macaques 
 
Safety Pharmacology 
Study 617078-1158zm – Safety pharmacology study to assess potential effects on vital 
systems (cardiovascular, respiratory) of AZD1222 in male mice given a single intramuscular 
dose of AZD1222 (GLP) 
 
Pharmacokinetics 
Study uno0009/MAB-001 – AdCh63ME-TRAP tissue distribution study by intra-dermal 
administration to mice (GLP) 
Study uno0014/RMBBioDIST-001- AdCh63 MSP-1 and MVA MSP-1 tissue distribution 
study by intra- muscular administration to mice (in-life phase conducted to GLP) 
Study 514559 (protocol, study ongoing) – AZD1222 (ChAdOx1-nCovd-19): A single dose 
intramuscular vaccine biodistribution study in the mouse (GLP) 
Study 0841mv38-001 (protocol, study ongoing) – ChAdOx-1 HBV and MVA-HBV 
biodistribution study in BALB/c mice with shedding assessment (GLP) 
 
Toxicology 
 
Study 513351 - AZD1222 (ChAdOx1-nCovd-19): A 6 week intermittent dosing 
intramuscular vaccine toxicity study in the mouse with a 4 week recovery (GLP) 
Study QS18dl – ChAdOx1 Chik Vaccine or ChAdOx1 MERS: toxicity study by 
intramuscular administration to mice (GLP) 
Study uno0013 - Mouse toxicity AdCh63 MSP-1 and MVA MSP-1 or a combination of 
AdCh63 ME-TRAP and MVA METRAP (GLP) 
Study XMM0003 - ChAdOx1 NP+M1 and MVA NP+M1: toxicity study by intramuscular 
administration to mice (GLP) 
Study 490838 - ChAdOx1-nCovd19: A preliminary intramuscular injection vaccine 
development and reproductive study in female CD-1 mice (GLP) 
Study 490843 (ongoing) - AZD1222 (ChAdOx1 -nCovd19): An intramuscular vaccine 
development and reproductive study in female CD-1 mice (GLP) 
 
Studies that were carried out in accordance with Good Laboratory Practice (GLP) are 
indicated above. There are no concerns in relation to GLP. In the study titles above COVID-
19 Vaccine AstraZeneca is sometimes referred to as AZD1222. 
 
III.2  Pharmacology 
Immunogenicity studies were conducted in animal models responsive to COVID-19 Vaccine 
AstraZeneca in order to evaluate the immunological properties of this COVID-19 vaccine 
candidate to support first in human (FIH) clinical trials. COVID-19 Vaccine AstraZeneca has 
been shown to be immunogenic in BALB/c, CD-1 mice, ferrets, non-human primate (NHP) 
and pig models.  
 
The studies summarised below included evaluation of humoral, cellular and functional 
immune responses. It is noted that the number of animals in groups was limited in some 
studies.  
 
 
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In the immunogenicity study, published by Graham et al, 2020, ‘prime-boost’ vaccinated 
inbred (BALB/c) and outbred (CD1) mice (9-10 weeks of age) were immunised by 
intramuscular (IM) injection of 108 infectious units (IU) of COVID-19 Vaccine AstraZeneca 
on 0 and 28 days post-vaccination, whereas, ‘prime-only’ mice received a single dose of the 
vaccine on day 28. Results showed a significant increase in antibody titre on prime-boosting 
in inbred mice when compared to primed-only mice but there was no boosting response seen 
in outbred mice. In both mouse strains the cellular response was primarily driven by CD8 +ve 
T cells. The absence of a booster response in outbred mice may have been due to the effect of 
a single dose being near to the maximal response. Mice showed Th1-like CD4+ and CD8+ve 
T cell responses. Both antibody- and T cell responses are thought likely to contribute to 
controlling infection. This study also investigated the immunogenicity of one or two doses of 
COVID-19 Vaccine AstraZeneca in pigs. Responses seen in pigs may be more representative 
of the likely human response. Pigs showed a booster response in serum antibody and showed 
Th1-like CD4+ and CD8+ve T-cell responses which are thought likely to contribute to 
controlling infection. In pigs, titres after a single dose of vaccine were similar to those in 
asymptomatic humans, whereas those after boosting were comparable to those in patients 
who recovered from COVID-19 disease. 
 
Study 20-01125 evaluated the immunogenicity and protective activity of COVID-19 Vaccine 
AstraZeneca on challenge with SARS CoV-2. Ferrets can be infected with SARS-CoV-2 
after its intranasal application, with virus shedding from the upper respiratory tract occurring 
for at least 9 days post exposure; however, they do not show signs of ill health. In this study 
no ferrets in either the vaccinated or control groups developed any signs of disease, 
indicating that the virus is not pathogenic in ferrets. Nevertheless, antiviral activity of the 
vaccine can be shown in this species. Data were presented on immunological analyses of 
ferret immune cell populations, cytokine profiles and proportions of IFN-γ producing cells 
following immunisation and subsequent challenge with SARS-CoV-2.  Ferrets given a single 
intramuscular injection of COVID-19 Vaccine AstraZeneca developed neutralising 
antibodies, boosted by challenge with SARS-CoV-2. Ferrets given COVID-19 Vaccine 
AstraZeneca showed a faster reduction to undetectable limits of SARS CoV-2 virus in nasal 
samples than did ferrets not given COVID-19 Vaccine AstraZeneca.  
 
Study 6285 assessed the immunogenicity of COVID-19 Vaccine AstraZeneca and its 
protective activity against SARS CoV-2 challenge in ferrets. A vector control group were 
given ChAdOx-1 GFP in which the gene insert for the viral spike protein was replaced by 
that for Green Fluorescent Protein (GFP) and a further group were assigned as unvaccinated 
controls. Twelve ferrets were vaccinated with COVID-19 Vaccine AstraZeneca, six with a 
prime only regime and six with a prime and boost doses, 28 days apart. Eight ferrets also 
received viral particles of ChAdOx1-GFP, four prime only and four prime boost. Six further 
ferrets were immunised with formalin-inactivated SARS CoV-2.  Ferrets were challenged 
with SARS-CoV-2 via the intranasal route at 4 weeks after their last dose of vaccine (2 weeks 
for those given formalin-inactivated SARS CoV-2).  The challenge was done on two separate 
days giving a cohort (a) that were all dosed on one day and cohort (b) that were all dosed on a 
different day. Overall, COVID-19 Vaccine AstraZeneca appeared to offer protection in this 
challenge model. Dosing was well tolerated and induced neutralising antibodies with booster 
dosing increasing neutralising antibody titres significantly although this enhancement did not 
appear to be sustained for much longer than a week. There was a good correlation between 
neutralising antibody titre with antibody binding to spike protein, suggesting that binding to 
spike protein is contributing to the neutralising activity of serum from vaccines. After viral 
challenge, vaccinated ferrets showed reduced challenge viral RNA in the upper respiratory 
tract and this was cleared earlier compared to controls. These results were mirrored by tissue 
 
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PCR results, which showed that in the upper respiratory tissues there was less detectable viral 
RNA in vaccinated ferrets. Lung histopathology in vaccinated ferrets appeared to be reduced, 
one-week post-challenge compared to controls but a deterioration was seen in vaccinated 
ferrets and the difference in lung histopathology between groups at two weeks post-challenge 
was negligible. The vaccine appeared to delay the appearance of lung pathology.  
 
A post-vaccination SARS-CoV-2 challenge in rhesus macaques was conducted to evaluate 
protection and the potential for vaccine-associated enhanced respiratory disease (ERD) (van 
Doremalen et al 2020). This study showed that COVID-19 Vaccine AstraZeneca reduced 
clinical disease score in monkeys and prevented damage to the lungs upon challenge to the 
upper and lower respiratory tract with SARS-CoV-2 virus; a prime-boost regimen induced 
humoral immune responses. COVID-19 Vaccine AstraZeneca reduced viral load in the lungs, 
reducing virus replication in the lower respiratory tract. Despite this, there was no reduction 
in viral shedding from the nose with either prime-only or prime-boost regimens. These data 
support an interpretation that COVID-19 Vaccine AstraZeneca may not prevent infection nor 
transmission of SARS-CoV-2, but it may reduce illness. The immune responses were not 
skewed towards a Th2-type and there was no suggestion of disease aggravation following 
COVID-19 Vaccine AstraZeneca.  
  
Study 6284 was done to test potential activity of COVID-19 Vaccine AstraZeneca to protect 
rhesus monkeys from a challenge with SARS-CoV-2 virus. In this study 3 male and 3 female 
monkeys were vaccinated once with COVID-19 Vaccine AstraZeneca and 3 male and 3 
female monkeys with phosphate buffered saline, by intramuscular injection. Monkeys were 
challenged with SARS-CoV-2 virus four weeks later and killed on days 7 or 13 or 14 after 
viral challenge. COVID-19 Vaccine AstraZeneca induced neutralising antibodies and had an 
effect to reduce the magnitude of weight loss or temperature increase caused by SARS CoV-
2 challenge. The vaccine appears to prime the immune system to release activated monocytes 
and T helper cells within the early days following SARS CoV-2 challenge and vaccinated 
monkeys appeared to have increased antigen-specific T cells following challenge. 
Vaccination offered some protection against disease as shown on a CT scan 5 days after 
challenge, this had abated by day 12. Lung lesion severity appeared to be reduced in most 
vaccinated monkeys at 1 or 2 weeks after the viral challenge and there was a reduction in 
viral RNA in the lung and bronchoalveolar lavage fluid in most vaccinated monkeys. There 
was, however, little evidence of reduction in viral RNA in the upper respiratory tract and at 
day 7 post-challenge, there appeared to be an increase in viral RNA in the large intestine of 
vaccinated monkeys. In summary, COVID-19 Vaccine AstraZeneca did offer a level of 
protection in this challenge experiment and did not appear to cause vaccine-enhanced 
disease. 
 
Study 617078 was a safety pharmacology study designed to assess the potential effects of 
COVID-19 Vaccine AstraZeneca on the vital systems (cardiovascular, respiratory) in male 
mice given a single intramuscular dose of COVID-19 Vaccine AstraZeneca. Administration 
of COVID-19 Vaccine AstraZeneca resulted in a statistically significant decrease in 
respiratory rate and increase in inspiration and expiration time throughout the whole 4-hour 
recording period. These statistically significant differences were considered to be a 
consequence of the variability in pre-dose data and that the profile of these respiratory 
parameters appeared similar across all recording days and therefore these respiratory changes 
were considered not to be associated with COVID-19 Vaccine AstraZeneca. Dosing with 
COVID-19 Vaccine AstraZeneca did not result in changes in any of the other parameters 
monitored in this study: there were no changes in arterial blood pressure, heart rate, body 
temperature or respiratory parameters.   
 
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In summary, neither ferrets nor monkeys developed clinically evident disease after SARS 
CoV-2 and this places limitations on the ability to show that vaccination reduced disease.  
However, small group sizes contribute to the difficulty.  
 
In the studies in ferrets and monkeys, evaluations were made of the safety profile of the 
vaccine. These evaluations confirmed changes at injection sites in the injected muscle and 
reactions consistent with a minor local inflammatory effect. These changes attributed to 
COVID-19 Vaccine AstraZeneca suggest that it is likely to be tolerable as an intramuscular 
injection and to have effects consistent with an immunogen.   
 
There was, however, a finding of hepatitis in ferrets. In the literature, vaccination against 
SARS (not SARS CoV-2 note) was reported to enhance hepatitis in ferrets (Weingartl H et al 
2004 J Virol 78(22) 12672-12676) but the vaccine used in that study was a modified vaccinia 
virus Ankara based vaccine, containing the gene for the SARS viral spike protein: neither of 
these characteristics offer insight as to whether COVID-19 Vaccine AstraZeneca might 
induce hepatitis. General toxicity studies are reported from mice as reviewed in this 
assessment report below. Further comment and a conclusion on potential liver toxicity is 
given there. 
 
There is a theoretical concern of vaccine-associated disease enhancement, where use of 
COVID-19 Vaccine AstraZeneca might put vaccinated individuals at risk of worse disease if 
they later encounter SARS CoV-2. The study in rhesus monkeys, however, did not identify 
evidence of concern of this effect following vaccination with COVID-19 Vaccine 
AstraZeneca.   
 
The safety pharmacology investigations did not identify a concern for use of COVID-19 
Vaccine AstraZeneca. Although there was an apparent effect of the vaccine, examination of 
the trace above shows that at baseline, the respiratory rate was already lower in those mice 
who later were dosed with COVID-19 Vaccine AstraZeneca: all the groups showed a 
reduction and that in those given COVID-19 Vaccine AstraZeneca seemed no greater than in 
the other groups.   
 
III.3  Pharmacokinetics 
The vaccine is intended to be given as an intramuscular injection. Two biodistribution studies 
were performed which suggest that, after injection, the virus does not replicate, or persist and 
it is not detectable except at the injection site.  
 
Absorption 
No absorption studies were performed with COVID-19 Vaccine AstraZeneca since the route 
of administration is intramuscular (IM). 
 
Distribution 
COVID-19 Vaccine AstraZeneca has been manufactured so that it is unable to replicate in 
cells. Therefore, after infecting a cell, there is expected to be no further spread of the virus.  
 
Study uno0009/MAB-001 was a biodistribution study performed in compliance with Good 
Laboratory Practice, in which mice were injected with AdCh63METRAP virus. The study 
was carried out to determine the distribution of infectious adenovirus particles in mouse 
organs one week after a single intradermal dose in the ear. Two mice were also analysed 
immediately after injection. The results suggest that the virus is lost from the injection site 
over time and a lack of replication in tested mouse tissues. AdCh63METRAP was only 
 
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detected at the injection site, and not in any other organs. These results are consistent with the 
injection of a non-replicating virus. However, of note when interpreting these data, the study 
report notes that immediately after injection, AdCh63METRAP will begin to enter cells and 
is no longer available to infect the HEK 293 cells used in the assay.   
 
Study uno0014/RMBBioDIST-001 evaluated tissue distribution following a single IM dose 
in mice each of different viruses, AdCh63 MSP-1 and MVA MSP-1.  Results for the virus 
MVA MSP-1, an attenuated pox virus, are not described here as they are not relevant for 
what is expected with COVID-19 Vaccine AstraZeneca. Results showed AdCh63-MSP1 was 
detected at the injection sites on the day of dosing but not at 24 hours or 7 days later. No 
AdCh63-MSP1 was detected in any internal organ. Comparing between these two studies 
into distribution, the report comments that the route of administration appears to affect the 
persistence of infectious virus at the injection site as by the intramuscular route, virus was 
only detectable at the injection site immediately after injection. These results are consistent 
with the injection of a replication deficient virus for AdCh63-MSP1. 
 
Study 0841mv38-001 was a biodistribution and shedding study using the ChAdOx1 vector 
with a hepatitis B virus (HBV) insert after IM injection on days 1 and 28 in mice. 
Distribution to some samples of all tissues was noted on day 2 and day 29. The highest levels 
(copies/mg sample) were noted at the site of administration (skeletal muscle), ranging from 3 
x 108 to 9.97 x 109 copies/mg sample. In the majority of samples of other tissues taken on day 
56, the levels were below the level of quantification, indicating elimination. Low levels were 
noted in 1 sample (of 6) for each of heart and liver, 1 of 3 for ovary and testes, and 3 of 6 
lymph node samples at this timepoint. This study does not contain assessment of CNS, 
relevant peripheral nerves or bone marrow and it does not include analysis at shorter time 
points compared to the already available studies and no description of the validation of 
method analysis. This platform study will be superseded by Study 514559, designed to 
explore the distribution of COVID-19 Vaccine AstraZeneca after a single intramuscular 
injection in male and female mice. A draft report is expected February 2021. 
 
Metabolism 
No metabolism studies were performed. 
 
Excretion 
No excretion studies were performed. 
 
In summary, COVID-19 Vaccine AstraZeneca is an unadjuvanted vaccine containing a 
replication-incompetent virus. As such, the virus should not spread at all far from the site of 
its administration and this profile was confirmed for the viruses tested where it was identified 
at the injection site and its draining lymph node. These results are considered suitable to 
stand in place of a dedicated study with COVID-19 Vaccine AstraZeneca as the same results 
would be expected. It is agreed that it is reasonable to omit an in vivo study in mice, as 
animal use for this purpose is not expected to provide any additional useful information on 
COVID-19 Vaccine AstraZeneca.  
 
The active principle is not the immunogen but is the induced immune response. The time 
course of immune response induced is of interest: this has been characterised to a sufficient 
extent in the pharmacodynamic studies described above.   
 
 
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Absorption, metabolism and excretion studies are not required for vaccines: this position is in 
line with relevant regulatory guidance (WHO guidelines on nonclinical evaluation of 
vaccines, 2005).   
 
The pharmacokinetic data presented are acceptable. 
 
III.4  Toxicology 
Single dose toxicity 
No single dose toxicity studies have been performed with COVID-19 Vaccine AstraZeneca. 
This is acceptable and in line with relevant guidelines (WHO 2005; WHO 2014). 
 
Repeat dose toxicity 
Study 513351 was a 6-week intermittent dosing intramuscular vaccine toxicity study in the 
mouse with a 4-week recovery. The objective of this study was to determine the potential 
toxicity of COVID-19 Vaccine AstraZeneca (total viral particle dose of 3.7x1010) when given 
by IM injection intermittently (on days 1, 22 and 43) to mice, with a 28 day recovery period 
to evaluate the potential reversibility of any findings. In addition, the immunogenicity was 
evaluated. Scheduled necropsies were conducted either at the end of the 6-week treatment 
period (day 45) or at the end of the 28 day recovery period. 
 
Administration of COVID-19 Vaccine AstraZeneca to CD-1 mice (total viral particle dose of 
3.7 x 1010) by intramuscular injection on 3 occasions (once every 3 weeks) over a 43 day 
period was well tolerated, with a transiently higher body temperature in males, decreases in 
monocytes in males and females (consistent with the expected pharmacology of COVID-19 
Vaccine AstraZeneca) and increase in globulin and decrease in albumin and albumin/globulin 
ratio, consistent with an acute phase response, observed. In all animals dosed with COVID-
19 Vaccine AstraZeneca, antibodies against the S-glycoprotein were raised and maintained 
throughout the dosing and recovery periods in all animals. In COVID-19 Vaccine 
AstraZeneca animals, higher spleen weights were observed but with no correlating 
macroscopic or microscopic changes. Non adverse, mixed and/or mononuclear cell 
inflammation was observed in the subcutaneous tissues and skeletal muscle of the 
administration sites and adjacent sciatic nerve of animals dosed with COVID-19 Vaccine 
AstraZeneca which were consistent with the anticipated findings after intra-muscular 
injection of an immunogenic vaccine. 
 
Study QS18dl was performed to investigate the potential toxicity of ChAdOx1 Chik or 
ChAdOx1 MERS in inbred (Balb/c) mice, aged 8 weeks old and weighing ~20g, when given 
as an IM injection on two occasions, 14 days apart. Following a 13 day observation period 
the mice were killed and subject to post mortem examinations. The doses of ChAdOx-1 Chik 
and of ChAdOx-1 MERS were each 1 x 1010 viral particles, in 25 or 35 μl per injection. Each 
mouse was injected twice on each dosing day, in the left and the right hindlimb. These 
vaccines were in development to prevent chikungunya (a viral infection spread by mosquito 
bites) and middle eastern respiratory syndrome (MERS, camel flu; a coronavirus that causes 
a respiratory illness) and can be considered to be similar to COVID-19 Vaccine AstraZeneca. 
Results showed that each of these vaccines were well tolerated and was not associated with 
any adverse effects. All the effects described are expected as responses to injection of a 
vaccine, reflecting immune stimulation and/or the response to introduction of the injecting 
needle into muscle tissue. The changes in the lumbar lymph node reflect that this is the 
lymph node local to the injection site in the hindlimb. The slight increases in glucose, 
potassium and phosphorus and decreases in triglycerides and liver weight may not be direct 
 
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effects of vaccination and there was a reduction in body weight gain, but the magnitude of 
these effects was small, and these changes were not considered adverse.  
 
Study un0013 evaluated the potential toxicity of AdCh63 MSP-1 and MVA MSP-1 or a 
combination of AdCh63 ME-TRAP and MVA ME-TRAP in inbred (Balb/c) mice when 
given as an IM injection on two occasions, 14 days apart, followed by a 13 day observation 
period, when mice were killed and subject to post mortem examinations. These vaccines 
were developed to prevent malaria. Results showed that there were no signs of toxicity in 
response to these vaccines: the changes noted are consistent with effects of an immune 
response to a vaccine, including a mild inflammatory reaction at intramuscular injection sites.   
 
Study xmm0003 was performed with vaccine containing the ChAdOx1 construct but with a 
gene insert other than from SARS-CoV-2. Ten male and 10 female BALB/c mice were given 
one IM injection with vaccine ChAdOx1 NP+M1 then 14 days later were given a booster 
dose with a different vaccine, MVA NP+M1. Control mice were given saline on days 1 and 
15. Mice were followed to day 13 after their second dose and then killed for post mortem 
analyses. The antigen in this vaccine was derived from influenza. The results demonstrated 
changes considered to be consistent with an immune response to vaccination, reflecting in the 
lymph nodes, likely, B cell proliferation, and of increased white blood cells with some local 
inflammation at the injection site.   
 
Genotoxicity 
No genotoxicity studies were performed. 
 
Carcinogenicity 
No carcinogenicity studies were performed. Carcinogenicity testing is generally not 
considered necessary to support the development and licensure of vaccine products for 
infectious diseases (WHO, 2005). 
 
Reproductive and developmental toxicity 
An evaluation of the impact of COVID-19 Vaccine AstraZeneca on embryo-fetal 
development was completed in a dose-range study (Study 490838). The main GLP embryo-
fetal development study, Study 490843, is ongoing with an audited draft report due at the end 
of January 2021. 
 
Prenatal and postnatal development  
In Study 490838, control (group 1) or COVID-19 Vaccine AstraZeneca (group 3) was 
administered via the IM route to groups of outbred (CD-1) female mice on day 1 (13 days 
prior to pairing for mating to a non-dosed male) and again on gestation day (GD) 6 at 2.59 x 
1010 per occasion (embryofetal development phase). In further mice, control (group 2) or 
COVID-19 Vaccine AstraZeneca (group 4) was administered via the IM route on GD 6 and 
GD 15 at 2.59 x 1010 per occasion (littering phase). Mice were killed either on day 17 (groups 
1 and 3) or followed to day 14 post birth (groups 2 and 4). The dose used was either 0 
(controls) or 2.59 x 1010 viral particles per dose, considered as a maximum feasible dose. For 
a 40g mouse, the dose represents an excess over humans of ~906.5 fold. A dose of 1.7x1010 
virus particles in mice has been previously shown to induce an appropriate immune response. 
Results showed that anti-S glycoprotein antibody responses were raised in dams following 
administration of COVID-19 Vaccine AstraZeneca and these were maintained through the 
gestational and lactation periods. Seropositivity of fetuses and pups was confirmed and was 
indicative of placental and lactational anti-S glycoprotein antibody transfer, respectively. 
There were no COVID-19 Vaccine AstraZeneca -related effects seen for dams in-life 
 
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including at the injection site, for female reproduction, fetal or pup survival and no abnormal 
gross pathology findings in pups or in dams in either phase. There were no COVID-19 
Vaccine AstraZeneca -related fetal visceral or skeletal findings. 
 
Prenatal and postnatal development, including maternal function 
See above.   
 
Studies in which the offspring (juvenile animals) are dosed and/or further evaluated  
See above: no studies have been done in which juvenile animals were dosed directly.   
 
Local tolerance 
No such studies have been done. This was evaluated in general toxicity studies which is 
preferred to the conduct of separate studies to evaluate local tolerance.    
 
Other toxicity studies 
No such studies have been done.   
 
Toxicity conclusions 
The vaccine is to be provided as two doses (each 0.5 mL) given intramuscularly. One dose 
(0.5 mL) contains COVID-19 Vaccine (ChAdOx1-S* recombinant) 5 x 1010 viral particles 
(vp). * Recombinant, replication-deficient chimpanzee adenovirus vector encoding the 
SARS-CoV-2 Spike (S) glycoprotein.   
 
Adenoviruses are double-stranded DNA viruses naturally present in the environment: some 
can cause mild illness. They have the capacity to infect mammalian cells independent of the 
cell cycle stage and so can infect post-mitotic cells and they can produce large amounts of 
progeny. However, removal of genes responsible for adenoviral replication eliminates this 
and the degree of pathogenicity should be reduced.   
 
Mice were used in all toxicity studies and were selected as they show a reliable immune 
response to ChAdOx-1 vaccines and this was confirmed for COVID-19 Vaccine 
AstraZeneca. The choice of mouse for safety studies is accepted. A single species is 
acceptable; both males and females were evaluated. 
 
The nature of toxicity was similar across these different studies: there were minor 
inflammatory reactions at the injection site and lymphoid organs showed an expected 
response to vaccination. Of note, the usual study design is to give one more dose to animals 
than is intended in humans. The general toxicity study with COVID-19 Vaccine AstraZeneca 
met this expectation. Given that the toxicity seen was minimal and the dose of vaccine used 
was in large excess of that to be used in humans, the general toxicity data presented suffice to 
support human use.  
 
There was no indication of liver toxicity in mice and at necropsy livers appeared normal. It is 
possible that mice recovered from liver changes before the assessments of liver function and 
post mortem evaluations were made but this seems unlikely. Based on the biodistribution 
data presented, COVID-19 Vaccine AstraZeneca is not expected to reach the liver. Although 
identified in ferrets this was not seen in monkeys: overall, the vaccine seems to pose no 
special risk of liver toxicity.    
 
 
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The study reports did not indicate any changes of relevance to the brain and peripheral 
nervous system and there are no statements to the effect of any adverse or unusual behaviour 
in vaccinated mice.  
 
Concerning the potential for induction of antibody-dependent disease enhancement, whereby 
use of the vaccine might put vaccinees at risk of worse disease, this risk is not well 
characterised. It is not clear at present even if this can be assessed appropriately in studies in 
animals. The general toxicity studies do not give any insights on this as the study designs do 
not include exposure to virus. 
 
The mouse may not be the best choice of species for the evaluation of potential reproductive 
toxicity as the exposure to the organs of the fetus during their development to antibody 
induced by the vaccine probably did not occur.  Nevertheless, international guidelines 
indicate that mice are an acceptable species for testing potential reproductive toxicity and no 
indication of harm was identified. Further information from the company will be supplied.   
 
Considering potential use in women who are breastfeeding, the preliminary study does not 
give sufficient evidence of lack of risk and therefore a final recommendation on use in 
pregnant or lactating women cannot be made at this time. The ongoing GLP-compliant study 
should provide more information once it is completed. The information provided to 
healthcare professionals states that COVID-19 Vaccine AstraZeneca should only be 
considered in pregnancy when the potential benefits outweigh any potential risks for the 
mother and fetus.   
 
The conclusion of this assessment is that COVID-19 Vaccine AstraZeneca could be 
supported for use in humans to prevent COVID-19. Further information is awaited to define 
the recommendation on use in women who are or may be pregnant or who are breastfeeding.   
 
III.5  Ecotoxicity/Environmental Risk Assessment 
It is agreed that, in accordance with CHMP guidance EMEA/CHMP/SWP/4447100 entitled, 
"Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use" 
published 01 June 2006, due to their nature, vaccines are unlikely to result in a significant 
risk to the environment. Therefore, an environmental risk assessment is not provided in this 
application. This is acceptable.  This vaccine contains a genetically modified organism 
(GMO).  However, consequences of release and persistence of the GMO in the environment 
are regarded as negligible.  
 
III.6  Discussion on the non-clinical aspects 
The non-clinical data currently available for COVID-19 Vaccine AstraZeneca can be 
accepted as sufficient with specific mitigations in place. There are no scientific objections 
arising from this review to the authorisation for temporary supply for this product under 
Regulation 174. 
 
 
IV  
CLINICAL ASPECTS 
IV.1   Introduction 
The immunogenicity, efficacy and safety data supporting this authorisation for temporary 
supply have been generated by four studies, presented below. COVID-19 Vaccine 
AstraZeneca is referred to as AZD1222 in this clinical review. 
 
 
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Table 1: Overview of AZD1222 studies 
 
COV001 
COV002 
COV003 
COV005 
Abbreviated Title 
A phase I/II study to 
A phase 2/3 study to 
A Randomized, Controlled, 
An adaptive phase I/II 
determine efficacy, 
determine efficacy, 
Phase III Study to 
randomized placebo-
safety and 
safety and 
Determine Safety, Efficacy, 
controlled trial to 
immunogenicity in 
immunogenicity; safety 
and Immunogenicity 
determine safety, 
healthy adult volunteers   and immune-genicity 
immunogenicity and 
sub-studies: 
efficacy in subjects 
• healthy children aged 5 
without HIV; and safety 
to 12 years, inclusive 
and immunogenicity in 
• HIV+ adults aged 18 -
subjects with HIV.  
55 years 
Region  
United Kingdom  
United Kingdom  
Brazil  
South Africa  
Control 
MenACWY (D1&2) 
MenACWY (D1&2) 
D1 MenACWY 
D1&2:Placebo: Normal 
D2 Placebo (0.9% saline 
saline (0.9% NaCl) 
solution) 
Age (years) 
18-55 
≥ 18 
≥ 18 
≥ 18-65 
Paracetamol use  
Prophylactic for a 
Prophylactic for a portion 
Prophylactic for all  
As clinically needed  
portion of participants  
of participants  
Primary endpoint 
Virologically-
Virologically-confirmed 
Virologically-confirmed 
PCT+ COVID-19 cases > 
confirmed (PCR+) 
(PCR+) symptomatic 
(PCR+) symptomatic cases 
14 days after booster dose 
symptomatic cases of 
cases of COVID-19 
of COVID-19 
in participants COVID-19 
COVID-19 
naïve at the time of 
randomization and who 
received 2 doses of test 
product 
No subjects 
 
 
 
 
Planned/completed 
1122/1077 
12390 
10300 
2070 
In the safety set 
1067 
10663 
10002 
2013 
 
All studies have completed enrolment of their respective efficacy cohorts and are in the 
follow-up phase, with the exception of the paediatric group in COV002. 
 
All studies were originally planned to investigate a single dose regimen but were amended in 
July 2020 to investigate a two-dose regimen in view of early immunogenicity results. The 
booster was planned to be given at the earliest possible time (in principle, 28 days after the 
prime dose), but due to logistical constraints, this interval was very variable. 
 
All studies were conducted in line with current Good Clinical Practice (GCP).  
 
IV. 2  Pharmacokinetics 
 
No pharmacokinetic data have been submitted for this application and none were required.  
 
IV.3  Clinical immunogenicity 
 
Bioanalytical assays 
The qualification or validation reports for each bioanalytical assay have been provided. These 
include the neutralising assays (pseudoneutralisation and live neutralisation), binding anti-
spike and anti-RBD antibody assays, ELISpot assay, and intracellular cytokine staining 
assay. Overall, the methods were considered acceptable and fit for purpose. 
 
Study COV001 
Initial data described hereafter were published in Lancet 2020; 396: 467–78 (Folegatti PM et 
al); Nat Med. 2020 (Ewer K et al). Overall, 88 healthy adults aged 18–55 years were 
randomly assigned to receive ChAdOx1 nCoV-19 (AZD1222) at a dose of 5 × 10¹⁰ viral 
particles or MenACWY as a single intramuscular injection. Blood samples were drawn at 
days 3, 7, 14, 28, and 56 after vaccination. Ten participants assigned to a non-randomised 
group received a two-dose regimen, with the booster vaccine administered 28 days after the 
 
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first dose. 
 
A single dose elicited both humoral and cellular responses against SARS-CoV-2, with a 
booster immunisation augmenting neutralising antibody titres. After the booster dose, the 
levels of binding and neutralising antibodies were comparable to those of a panel of 
convalescent serum samples. 
 
Anti-spike IgG responses at the peak of the response after vaccination (day 28) showed a 
polarized IgG1 response, consistent with naturally acquired antibodies against SARS-CoV-2, 
as well as an IgG3 response in most vaccinees. A mixed IgG1 and IgG3 response, with low 
levels of IgG2 and little detectable IgG4 is consistent with induction of Th1-type human IgG 
subclasses (IgG1 and IgG3). 
 
Flow cytometry with intracellular cytokine staining (ICS) of peripheral blood mononuclear 
cells (PBMCs) stimulated with peptides spanning the S1 and S2 subunits of SARS-CoV-2 
spike protein demonstrated antigen-specific cytokine secretion from CD4+, and to a slightly 
lesser extent CD8+, peaking 14 days after the vaccine dose. CD4+ responses were heavily 
biased toward secretion of Th1 cytokines (IFN-γ and IL-2) rather than Th2 (IL-5 and IL-13). 
 
Based on this finding, it was decided to further investigate a prime-boost regimen of two 
doses of 5 × 10¹⁰ viral particles (20 subjects) or one dose of 5 × 10¹⁰ viral particles followed 
by one half dose (2.5 × 10¹⁰ viral particles) administered 8 weeks apart. These data were 
published in Nat Med 2020 (Barrett et al). 
 
They confirmed that a second vaccine dose enhances both the titre and the functionality of 
the antibody response measured 28 days after the booster dose. Fc-mediated anti-spike 
antibody effector functions, which may have a role in the protection against COVID-19, were 
in the same range or higher than those measured in sera from convalescent patients. A 
booster dose of vaccine induced stronger antibody responses than a dose-sparing half dose 
boost, although the magnitude of T cell responses did not increase with either boost dose.  
 
Study COV002 – Phase II part 
These data were published in Lancet 2020 Nov 18:S0140-6736(20)32466-1 (Ramasamy MN 
et al). The study aimed at evaluating the impact of age on antibody and T cell responses to 
the vaccine. Three different age groups of subjects, 18-55, 56-69, and ≥ 70 years, 
respectively, received two doses of vaccine, 4-6 weeks apart. After a change in manufacturer, 
it was found that the first dose received by these subjects contained about half the intended 
number of viral particles; for the second dose, it was decided to administer the same lower 
dose and to recruit three other similar age groups that would receive two doses of the 
intended amount (5 × 10¹⁰) of viral particles. 
 
The median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar 
across the three age cohorts, and likewise, the neutralising antibody titres. The antibody 
response was generally comparable after the first dose and at its peak, 14 days after the 
booster dose, but tended to be slightly lower with the lower dose regimen compared to the 
standard dose regimen at day 56. T-cell responses peaked at day 14 after a single standard 
dose and did not increase significantly after the boost vaccination, with no trend according to 
dose or age.  
 
In this study, the antibody response to the viral vector was also investigated. Anti-ChAdOx1 
neutralising titres increased in all groups to similar levels but were not increased further after 
 
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a boost dose of vaccine at day 28. A weak negative correlation was found between anti-
ChAdOx1 levels before the booster dose and the anti-spike IgG response to the booster dose. 
 
Pooled analysis (COV001, -002, -003, -005) 
The immune response to vaccination was assessed 28 days after the first and second doses in 
a subset of the trial subjects. Subgroup analyses were conducted by baseline serostatus 
(positive/negative), by age (18-64/ ≥ 65 years), by country (UK/Brazil/South Africa), and 
comorbidity (yes/no). A proportion of vaccines received a lower priming dose and the 
standard booster dose (LDSD) while the majority received two standard doses (SDSD). The 
results were presented overall (SDSD + LDSD) and in the two subsets (LDSD and SDSD). 
 
The rate of seroconversion (≥4-fold increase from baseline) by S-binding antibodies was 
≥ 98% at 28 days after the first dose and > 99% at 28 days after the second dose for 
seronegative participants at baseline. The rate of seroconversion with a live neutralisation 
assay was high (> 80%) at 28 days after the first dose and > 99% at 28 days after the second 
dose for seronegative participants. 
 
For seronegative participants at baseline, an increase in S-binding antibodies was observed at 
28 days after the first dose with a notable further increase at 28 days following the second 
dose. Of note, baseline seropositive participants also had increased S-binding responses after 
the first dose, but in contrast to the baseline seronegative group, antibody levels were not 
further increased by the second dose, which is consistent with an ‘immune plateau’ noted 
with other vaccines. 
 
Geometric mean titres (GMT) for S-binding antibodies in the SDSD subgroup were 
numerically higher after the first dose compared with the GMT for the LDSD subgroup. 
Following the second dose, GMT further increased for both regimens, with an apparent 
higher GMT for the LDSD regimen. Similar results were observed for the other antibody 
assays. 
 
Table 2: SARS-CoV-2 S-binding antibody levels by serostatus at baseline 
 
 
 
SDSD + LDSD 
SDSD 
LDSD 
Subgroup 
Timepoint  Statistic 
AZD1222 
Control 
AZD1222 
AZD1222 
SEROSTATUS   

1655 
1197 
1356 
299 
Seronegative 
Post Dose 1  n / Nsub 
885 / 1617 
704 / 1166 
817 / 1320 
68 / 297 
 
 
GMT 
8156.07 
56.85 
8386.46 
5836.18 
 
 
(95% CI) 
(7563.3, 8795.3) 
(51.6, 62.6) 
(7758.6, 9065.1) 
(4340.4, 7847.4) 
 
Post Dose 2  n / Nsub 
886 / 1617 
705 / 1166 
819 / 1320 
67 / 297 
 
 
GMT 
30206.20 
62.70 
29034.74 
48986.76 
 
 
(95% CI) 
(28271.0, 32273.9) 
(56.3, 69.8) 
(27118.2, 31086.7) 
(38483.3, 62357.0) 
Seropositive 
Post Dose 1  n / Nsub 
29 / 38 
28 / 31 
28 / 36 
1 / 2 
 
 
GMT 
178522.42 
7303.99 
175120.84 
305936.00 
 
 
(95% CI) 
(123872.3, 257283.1)  (3307.9, 16127.4)  (120096.9, 255354.8) 
(NE, NE) 
 
Post Dose 2  n / Nsub 
29 / 38 
25 / 31 
28 / 36 
1 / 2 
 
 
GMT 
114488.67 
8296.39 
112978.13 
166062.00 
 
 
(95% CI) 
(74664.2, 175554.8)  (4233.6, 16258.1)  (72553.8, 175925.4) 
(NE, NE) 
 
In the SDSD group, after starting from similar immune responses to the first dose there is a 
clear trend that longer dose intervals are associated with higher responses induced by the 
 
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second dose. The same pattern is reflected in the nAb responses. When comparing SDSD and 
LDSD groups with the same dose interval, the immune response after the second dose is 
similar. Given that the median dose interval in the LDSD group was 12 weeks compared with 
5 weeks in the SDSD group in Brazil and 10 weeks in the SDSD group in the UK, these data 
suggest that the higher levels of immunogenicity engendered in the LDSD group are 
influenced more by interval than by dose level. 
 
Table 3: SARS-CoV-2 S-binding antibody levels by dose level and interval (seronegative at 
baseline) 
SDSD 
LDSD 
AZD1222 
AZD1222 
< 6 wks 
6-8 wks 
9-11 wks 
≥ 12 wks 
< 6 wks 
6-8 
9-11 wks 
≥ 12 wks 
wks 
Visit 
Window 

Statistic 
N=677 
N=239 
N=169 
N=235 
N=3 

N=126 
N=168 
Baseline 

481 
137 
110 
154 

NA 
30 
35 
GMT 
60.51 
58.02 
48.79 
52.98 
50.92 
NA 
64.09 
52.42 
95% CI 
(54.1, 
(46.3, 
(39.6, 
(44.4, 
(3.9, 
NA 
(40.4, 
(37.7, 
for GMT 
67.7) 
72.6) 
60.1) 
63.2) 
669.2) 
101.6) 
72.9) 
Min, 
16.5, 
16.5, 
16.5, 
16.5, 
16.5, 
NA 
16.5, 
16.5, 
Max 
71694.0 
7228.0 
4497.0 
827.0 
127.0 
565.0 
304.0 
Day 28 

479 
99 
87 
152 

NA 
30 
35 
post the 
GMT 
8734.08 
7295.54 
7492.98 
8618.17 
7496.44 
NA 
4803.21 
6750.27 
first dose 
95% CI 
(7883.1, 
(5857.4, 
(5885.1, 
(7195.4, 
(1461.4, 
NA 
(3255.7, 
(4184.6, 
for GMT 
9676.9) 
9086.7) 
9540.2) 
10322.3) 
38454.7) 
7086.4) 
10889.0) 
Min, 
16.5, 
426.0, 
46.0, 
93.0, 
3922.0, 
NA 
268.0, 
51.0, 
Max 
126108.0 
84533.0 
82133.0 
263135.0 
14622.0 
35010.0 
85889.0 
Day 28 

443 
116 
106 
154 

NA 
29 
35 
post the 
GMT 
22222.73 
24363.10 
34754.10 
63181.59 
22121.36 
NA 
36928.89 
66274.91 
second 
dose 
95% CI 
(20360.5, 
(20088.5, 
(30287.2, 
(55180.1, 
(8547.7, 
NA 
(24509.6, 
(49546.6, 
for GMT 
24255.3) 
29547.3) 
39879.8) 
72343.4) 
57250.2) 
55641.2) 
88651.1) 
Min, 
101.0, 
40.0, 
3590.0, 
4612.0, 
14411.0, 
NA 
3713.0, 
6456.0, 
Max 
178580.0 
276501.0 
579194.0 
767654.0 
30100.0 
559449.0 
481664.0 
 
High seroconversion rates by S-binding antibodies were observed in older adults (≥65 years) 
after the first SD (97.8% [N=136, 95% CI: 93.7; 99.5]) and the second SD (100.0% [N=111, 
95% CI: 96.7; NE]). The GMT for S-binding antibodies were lower in adults ≥ 65 years of 
age than in younger adults after both the first dose and second dose. Similarly, nAb 
(pseudoneutralisation) GMTs were lower in the older adults. These data differ from those of 
Phase II in that the sample size is larger and draws from a broader population that includes 
older adults with comorbidities. Furthermore, the majority of participants ≥ 65 years old had 
a dose interval of <6 weeks, which may have contributed to the lower titres observed after the 
second dose. 
 
 
 
 
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Table 4: SARS-CoV-2 nAbs Levels (by Pseudoneutralisation Assay) by Age (seronegative 
at baseline) 
 
 
 
LDSD + SDSD 
SDSD 
LDSD 
Subgroup 
Timepoint 
Statistic 
AZD1222 
Control 
AZD1222 
AZD1222 
Age 18-64 
Post Dose 1 
n / Nsub 
645 / 1373 
522 / 994 
500 / 1104 
145 / 269 
 
 
GMT 
58.124 
20.374 
59.026 
55.120 
 
 
(95% CI) 
(52.69, 64.12) 
(19.99, 20.76) 
(52.87, 65.90) 
(44.35, 68.51) 
 
Post Dose 2 
n / Nsub 
651 / 1373 
501 / 994 
497 / 1104 
154 / 269 
 
 
GMT 
181.790 
21.487 
173.708 
210.528 
 
 
(95% CI) 
(166.36, 198.66)  (20.67, 22.33)  (156.52, 192.78)  (178.31, 248.57) 
Age ≥65 
Post Dose 1 
n / Nsub 
75 / 244 
77 / 172 
75 / 216 

 
 
GMT 
37.103 
21.105 
37.103 

 
 
(95% CI) 
(29.26, 47.05) 
(18.96, 23.49) 
(29.26, 47.05) 

 
Post Dose 2 
n / Nsub 
52 / 244 
54 / 172 
52 / 216 

 
 
GMT 
109.212 
21.066 
109.212 

 
 
(95% CI) 
(77.58, 153.73) 
(18.98, 23.38) 
(77.58, 153.73) 

 
 
IV.4  Clinical efficacy 
 
A pooled efficacy analysis, justified by the similar design of the four COV studies, has been 
conducted to support the use of AZD1222 to immunise adult subjects against COVID-19. 
 
Methods 
 
Study participants 
Healthy adults, with no history of laboratory confirmed COVID-19 were enrolled in the 
studies. The main other exclusion criteria were subjects with immunodeficiencies or on 
chronic immunosuppressant therapy; subjects with history of angioedema or anaphylaxis; 
subjects with severe and/or uncontrolled cardiovascular disease, respiratory disease, 
gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological 
illness (mild/moderate well controlled comorbidities are allowed); pregnancy, lactation or 
intention to become pregnant during the study (continuous effective contraception was 
required during the course of the study). Seasonal influenza and pneumococcal vaccinations 
were allowed with an interval of least 7 days before/after the study vaccine in some studies 
(otherwise 30 days). 
 
Statistical analysis 
The primary endpoint was the incidence of SARS-CoV-2 virologically-confirmed COVID-19 
occurring ≥ 15 days after the second vaccine dose. COVID-19 cases were PCR-confirmed 
with at least one of the following symptoms: objective fever (defined as ≥ 37.8 °C), cough, 
shortness of breath, anosmia, or ageusia, and confirmed by an adjudication committee. 
 
The statistical analysis of vaccine efficacy (VE) used a Poisson regression model with robust 
variance to estimate the relative risk (RR) of the incidence of cases in the AZD1222 and 
control groups. The model contained the terms of study code, treatment group, and age group 
at randomisation (18-55 years, 56-69 years, and ≥ 70 years). The logarithm of the period at 
 
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risk for primary endpoint was used as an offset variable in the model to adjust for participants 
having different follow-up times during which the events occur. 
 
VE, which is the incidence of infection in the vaccine group relative to the incidence of 
infection in the control group expressed as a percentage, was calculated as VE = 1- relative 
risk. The VE, and its corresponding 2-sided (1-α) % confidence interval (CI), was estimated 
from the model. 
 
One interim analysis and a primary analysis were planned. For an individual study to be 
included in the pooled analysis of efficacy, a minimum of 5 primary endpoint defined cases 
had to be accrued. The analyses were to be triggered based on counts of COVID-19 cases 
that occurred ≥ 15 days after the second dose in participants who were randomised between 
SDSD and control. The interim analysis was triggered when at least 53 COVID-19 cases 
fulfilling the criteria above had occurred. The primary analysis would have been triggered 
when 105 COVID-19 cases had occurred. While the analyses were triggered by the number 
of cases in participants who received SDSD, cases in participants who received LDSD were 
also to be included for the analysis of the primary endpoint. This was estimated to provide an 
additional 10 and 20 cases at the interim and primary analysis respectively. A gamma alpha-
spending function was used to control the overall Type 1 error at 5%. 
 
The combined analysis was to be considered positive if the alpha adjusted confidence interval 
at either analysis had a lower bound > 20%. With assumptions of a true VE of 60% a total of 
125 cases provides 96% power to achieve the pre-specified success criterion. Under the same 
assumption this number of events gives 83% power to achieve a confidence interval lower 
bound > 30%. 
 
The main secondary endpoints included severe COVID-19, defined as ≥ grade 6 in the WHO 
clinical progression scale, hospitalisation, and asymptomatic SARS-CoV-2 infection, defined 
as PCR-confirmed SARS-CoV-2 infection and no symptom record. 
 
The primary analysis was based on the SDSD + LDSD Seronegative for Efficacy Analysis 
Set, i.e., randomised participants who had received LDSD or SDSD, were seronegative at 
baseline, and had follow up data ≥ 15 days after the second dose. 
 
Results 
An interim analysis was conducted with a data cut-off date of 04 November 2020. Studies 
COV001 and COV005 were excluded as they had fewer than 5 cases eligible for the primary 
endpoint: 1 case and 2 cases, respectively. All 3 of the cases were in the control group. 
 
Due to the rapid accumulation of cases prior to database cut-off, 98 cases from participants 
randomised between SDSD and control were included in the interim analysis. The alpha level 
for the interim analysis calculated from the gamma (-2.5) alpha-spending function was 4.16% 
based the actual number of SDSD cases at the interim, meaning inferences on the primary 
endpoint were made using 95.84% confidence intervals. Whilst alpha was determined based 
on the 98 cases from participants who received SDSD, the primary analysis was prespecified 
to include participants who received either LDSD or SDSD (131 cases). 
 
Study population 
The efficacy population included a total of 11,636 individuals, 5807 in the test group and 
5829 in the control group. 
 
 
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The disposition of the participants for the efficacy analysis is summarised below. 
 
 
 
The dosing schedule and baseline characteristics of the primary analysis set are summarised 
hereafter. 
 
Table 5: Dosing intervals (SDSD + LDSD Seronegative for Efficacy Analysis Set) 
AZD1222 
Control 
Parameter 
(N = 5807) 
(N = 5829) 
 
Dose schedule n(%) 
< 6 weeks 
1702 (29.3) 
1698 (29.1) 
  
6-8 weeks 
568 (9.8) 
527 (9.0) 
  
9-11 weeks 
1444 (24.9) 
1488 (25.5) 
  
12+ weeks 
2093 (36.0) 
2116 (36.3) 
 
Table 6: Demographics (SDSD + LDSD Seronegative for Efficacy Analysis Set) 
 
 
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Table 7: Baseline characteristics (SDSD + LDSD Seronegative for Efficacy Analysis Set) 
 
 
The age in the primary analysis population ranged from 18 to 88 years, with a median of 40 
years; 88% of the population were adults between 18 and 55 years of age, 8% between 55 
and 69 years, and 4% ≥ 70 years. The population included a majority of female subjects 
(61%) and a vast majority of White subjects (83%) with 4% of Asian and 4% of Black 
people. The proportion of subjects with comorbidities was substantial (36%): obesity (20%); 
cardiovascular disease (11%), mainly hypertension (5%); respiratory disease (12%), mainly 
asthma (8%); and diabetes (2%). 
 
Primary efficacy endpoint 
Out of the 131 COVID-19 cases, 30 were reported in the vaccine group and 101 in the 
placebo group. The point estimate for VE was 70.4% with a 95.84% confidence interval 
ranging from 54.8 to 80.6%. The pre-specified criterion for study success was met; the lower 
bound of the 95.84% confidence interval was above 20%. The point estimate was above 50% 
and the confidence interval lower bound above 30%, so efficacy was also shown in line with 
 
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the target profile outlined by WHO for COVID-19 vaccines. 
 
Table 8: Vaccine efficacy for incidence of first SARS-CoV-2 virologically-confirmed 
COVID-19 occurring ≥ 15 days post second vaccine dose in participants seronegative at 
baseline 
 
Participants with events 
 
 
AZD1222 
Control 
VE  
95.84% CI  
 

n (%) 

n (%) 
(%) 
(%) 
Primary endpoint 
5807 
30 (0.52) 
5829 
101 (1.73) 
70.42 
(54.84, 80.63) 
 
Efficacy was also shown if only the subgroup of participants randomised between SDSD and 
control were considered (VE=62.10%, 95.84% CI [39.96, 76.08]). In the subgroup 
randomised between LDSD and control, VE was 90.05%, 95.84% CI (65.84, 97.10). 
 
The results were consistent in the subgroup of participants with a comorbidity at baseline, 
where a comorbidity is defined as BMI ≥ 30 kg/m2, cardiovascular disorder, respiratory 
disease or diabetes (VE=73.4%, 95% CI [48.5, 86.3]), and in the UK alone (VE=73.5%, 95% 
CI [55.5, 84.2]). 
 
There is limited information available on efficacy in participants aged 65 or over, although 
there is nothing to suggest lack of protection. In this subpopulation, there were only two 
COVID-19 cases in the primary analysis. When considering all cases from dose 1, there were 
2 cases on AZD1222 compared to 8 on control (VE=76%), although this result was 
associated with a wide confidence interval. 
 
Only one COVID-19 case (in the control group) was reported in participants seropositive at 
baseline. 
 
Severe cases and hospitalisations 
There was only 1 severe COVID-19 case in the primary efficacy analysis (from 15 days after 
dose 2) in the control group. Even considering all cases from dose 1 there were only 2 severe 
cases, both in the control group. 
 
There were 5 hospitalisations in the primary efficacy analysis, all on control. Considering all 
cases from dose 1, there were 2 hospitalisations in the AZD1222 group and 16 in the control 
group providing some evidence of an effect of the vaccine on COVID-19-related 
hospitalisations with a CI lower bound above 30% (VE=87.59%; 95% CI 46.03, 97.15). Both 
hospitalisations in the AZD1222 group were before 22 days after dose 1, as were 7 of the 16 
in the control group. The two cases of hospitalisation in the AZD1222 group occurred on 
days 1 and 10 post vaccination. 
 
Asymptomatic cases 
Participants in the COV002 study had weekly self-swabs using the central NHS Pillar 2 
testing mechanism. Analyses including asymptomatic cases demonstrated that the overall 
incidence of infections was decreased, not just the incidence of symptomatic COVID-19, 
thereby suggesting an effect on transmission as well. 
 
 
 
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Table 9: Vaccine efficacy for incidence of first SARS-CoV-2 symptomatic or symptomatic 
infection occurring ≥ 15 Days post second vaccine dose in participants seronegative at 
baseline 
 
Participants with events 
 
 
AZD1222 (N=3744) 
Control (N=3804) 
VE  
95.84% CI  
 
n (%) 
n (%) 
(%) 
(%) 
Symptomatic 
18 (0.48) 
68 (1.79) 
73.52 
(55.50, 84.24) 
Asymptomatic 
29 (0.77) 
40 (1.05) 
 
 
Total 
47 (1.26) 
108 (2.84) 
56.46 
(38.74, 69.05) 
 
Onset of protection 
The early onset of protection is illustrated in the figure below, which displays cumulative 
incidence for the first COVID-19 occurrence after Dose 1 among all vaccinated participants. 
Disease incidence is similar in the vaccine and placebo arms until approximately 21 days 
after Dose 1, at which point the curves diverge, with cases accumulating at a faster rate in the 
control group compared to the AZD1222 group. 
 
Figure 1: Cumulative incidence plot for time to first SARS-CoV-2 virologically-confirmed 
COVID-19 occurring post first vaccine dose 
 
 
Protection after the first vaccine dose 
Exploratory analyses were conducted to investigate whether protective immunity was 
induced by the first dose and what the duration of protection was. The follow-up time began 
at 22 days after the first dose and was censored at the time of the second dose. Results 
indicated that the first dose provided protective immunity at least until 12 weeks.  
 
 
 
 
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Table 10: Vaccine efficacy for incidence of first SARS-CoV-2 virologically-confirmed 
COVID-19 occurring post first dose + 22 Days and before second dose of vaccine 
 
Participants with events 
 
 
AZD1222 
Control 
VE  
95% CI  
 

n (%) 

n (%) 
(%) 
 
Cases to Week 12 
7998 
12 (0.15) 
7982 
44 (0.55) 
73.00 
(48.79, 85.76) 
 
Effect of dose interval on VE ≥ 15 days after dose 2 
The dataset in which efficacy of a two-dose regimen had been demonstrated contained data 
over a wide range of dose intervals (4 to 26 weeks): 29.3% were < 6 weeks, 34.7% were 6-
11 weeks, and 36.0% were ≥ 12 weeks. 
 
Subgroup analyses were conducted of vaccine efficacy by dosing interval. In line with 
immunogenicity data where increases in the binding and neutralising antibody responses 
were observed with increased dosing interval, efficacy was demonstrated with more certainty 
for dose intervals from 8-12 weeks. For the subgroup with dosing interval 8-11 weeks, VE 
was 72.85%, 95% CI (43.45, 86.97), for the subgroup with dosing interval > 11 weeks, it was 
81.90%, 95% CI (59.93, 91.90). Exploratory subgroup analyses showed vaccine efficacy 
around 80% for longer dosing intervals, but data were limited and estimates were associated 
with wide confidence intervals.  
 
Efficacy of using an initial half dose  
A proportion of participants received a half dose of vaccine for their first administration. 
Participants were not randomised between receiving a half dose (LD) or the standard dose 
(SD) for the first dose, and because of other confounding factors, it is not possible to 
confidently compare results from the two different dosing regimens. Such factors include 
differences in the dosing interval (generally longer for LD), population studied (younger 
population for LD), country (UK only for LD) and stage of pandemic (participants receiving 
LD were initially dosed at a time when the incidence of cases in the UK was low). There is 
not persuasive evidence of a real difference in VE between SD and LD, and the apparent 
difference is considered more likely to be the result of confounding factors, especially the 
dosing interval. Conclusions on vaccine efficacy were primarily based on the pre-planned 
primary analysis including both SD and LD participants, and not on subgroups. 
 
 
IV.5  Clinical safety 
 
Safety population and exposure 
 
The any dose safety analysis set comprises 23,745 subjects, pooled from the 4 multicentre 
trials, that received at least one dose of study intervention up to the data cut-off 04 November 
2020. Of these, 12021 received at least one dose of AZD1222; 8266 received 2 doses of 
which 6568 were SDSD. Approximately one third of subjects each had a dose schedule in the 
range of < 6 weeks, 6 to 11 weeks, or ≥ 12 weeks.  
 
 
 
 
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Table 11: Study drug exposure (any dose safety analysis set) 
 
Parameter 
AZD1222 
Control 
(N = 12021) 
(N = 11724) 
Dose levela n (%) 
LDSD 
1516 (12.6) 
1472 (12.6) 
 
LDLD 
127 (1.1) 
69 (0.6) 
SDSD 
6568 (54.6) 
6472 (55.2) 
SDLD 
55 (0.5) 
36 (0.3) 
LD 
305 (2.5) 
281 (2.4) 
SD 
3450 (28.7) 
3394 (28.9) 
Total 
12021 
11724 
Number of doses 

3755 (31.2) 
3675 (31.3) 
 n (%) 

8266 (68.8) 
8049 (68.7) 
Total 
12021 
11724 
Dose schedule n (%) 
< 6 weeks 
3412 (41.3) 
3234 (40.2) 
6-8 weeks 
680 (8.2) 
604 (7.5) 
9-11 weeks 
1558 (18.8) 
1550 (19.3) 
12+ weeks 
2616 (31.6) 
2661 (33.1) 
Total 
8266 
8049 
SD = Standard dose; LD = Low dose 
a Dose level of control group is decided by the dose level of the corresponding vaccine group 
Total row includes the number of participants with non-missing data for the corresponding characteristic and was used as the 
denominator for calculating percentages for all categories 
 
The median duration of follow-up in the AZD1222 group was 105 days post-dose 1, and 62 
days post-dose 2.  
 
The baseline demographics and characteristics of the safety population are presented below 
in Table 12. Overall these were balanced between the 2 study groups. 
 
Table 12: Baseline demographics and characteristic (any dose safety analysis set) 
Characteristic 
Statistics 
AZD1222 
Control 
Total 
(N = 12021) 
(N = 11724) 
(N = 23745) 
Age group at 
18 to 64 years 
10852 (90.3) 
10783 (92.0) 
21635 (91.1) 
screening, n (%) 
≥ 65 years 
1169 (9.7) 
940 (8.0) 
2109 (8.9) 
 
 
 
 
18 to 55 years 
9802 (81.5) 
9788 (83.5) 
19590 (82.5) 
56 to 69 years 
1398 (11.6) 
1296 (11.1) 
2694 (11.3) 
≥ 70 years 
821 (6.8) 
639 (5.5) 
1460 (6.1) 
Sex, n (%) 
Female 
6711 (55.8) 
6550 (55.9) 
13261 (55.8) 
Male 
5310 (44.2) 
5171 (44.1) 
10481 (44.1) 
Transgender 

1 (<0.1) 
1 (<0.1) 
Missing 

2 (<0.1) 
2 (<0.1) 
Racea, n (%) 
White 
9081 (75.5) 
8887 (75.8) 
17968 (75.7) 
Asian 
425 (3.5) 
371 (3.2) 
796 (3.4) 
Black 
1211 (10.1) 
1210 (10.3) 
2421 (10.2) 
Other 
798 (6.6) 
752 (6.4) 
1550 (6.5) 
Mixed 
489 (4.1) 
483 (4.1) 
972 (4.1) 
Unknown 
16 (0.1) 
17 (0.1) 
33 (0.1) 
Missing 
1 (<0.1) 
4 (<0.1) 
5 (<0.1) 
BMI category n 
<30 kg/m2 
9305 (77.4) 
8998 (76.7) 
18303 (77.1) 
(%) 
≥30 kg/m2 
2308 (19.2) 
2318 (19.8) 
4626 (19.5) 
Missing 
408 (3.4) 
408 (3.5) 
816 (3.4) 
 
Regulation 174 
36 
 
 
 

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Serostatus at Day 0 
Negative 
11445 (95.2) 
11139 (95.0) 
22584 (95.1) 
n (%) 
Positive 
345 (2.9) 
373 (3.2) 
718 (3.0) 
Missing 
231 (1.9) 
212 (1.8) 
443 (1.9) 
Cardiovascular 
Yes 
1540 (12.8) 
1435 (12.2) 
2975 (12.5) 
disorder n (%) 
No 
10477 (87.2) 
10287 (87.7) 
20764 (87.4) 
Missing 
4 (<0.1) 
2 (<0.1) 
6 (<0.1) 
Respiratory disease 
Yes 
1253 (10.4) 
1229 (10.5) 
2482 (10.5) 
n (%) 
No  
10764 (89.5) 
10493 (89.5) 
21257 (89.5) 
Missing 
4 (<0.1) 
2 (<0.1) 
6 (<0.1) 
Diabetes n (%) 
Yes 
39 (2.8) 
290 (2.5) 
629 (2.6) 
No 
11142 (92.7) 
10898 (93.0) 
22040 (92.8) 
Not collectedb 
534 (4.4) 
533 (4.5) 
1067 (4.5) 
Missing 
6 (<0.1) 
3 (<0.1) 
9 (<0.1) 
Comorbidity at 
Yes 
4293 (35.7) 
4217 (36.0) 
8510 (35.8) 
baselinec n (%) 
No 
6977 (58.0) 
6764 (57.7) 
13741 (57.9) 
Missing 
751 (6.2) 
743 (6.3) 
1494 (6.3) 
Current smoker n 
Yes 
991 (8.2) 
1034 (8.8) 
2025 (8.5) 
(%) 
No 
11026 (91.7) 
10682 (91.1) 
21708 (91.4) 
Missing 
4 (<0.1) 
8 (0.1) 
12 (0.1) 
aEach race category counts participants who selected that category. Arab is counted under white 
b COV001 does not collect this information; participants are counted in category ‘Not collected’ 
cCormorbidy at baseline = Yes if any comorbidity at baseline (BMI ≥30 kg/m2, cardiovascular disorder, respiratory disease 
or diabetes) is yes. 
 
There were more females (56%) than males. Twenty-four percent of subjects were from 
ethnic minority backgrounds. The majority of subjects in the safety population were in the 
younger age group 18-55 years (83%). Of the 1169 (9%) subjects in the AZD1222 group that 
were ≥65 years of age, 668 received 2 doses, of which 586 were SDSD. Overall three percent 
of subjects were seropositive at baseline, the percentage was highest in South Africa (14.8%) 
and much lower in Brazil (2.3%) and the UK (1.6%). Just over one third of subjects had at 
least one comorbidity at baseline. The most common comorbidities were obesity, 
hypertension and asthma.  
 
Local and systemic reactogenicity 
 
Solicited adverse events (AEs) were collected via a diary card for 7 days following each 
vaccination in a subset of 6,137 subjects, mainly from the UK and South Africa. Of these, 
5145 were in the Dose 1 SD subset (Table 13). There were some differences in how 
reactogenicity data was collected in the South African trial, in particular, solicited AEs were 
collected until Day 6 instead of day 7, there was no grade 4 severity option and fewer AE 
terms were solicited. 
 
Table 13: Reactogenicity population by subgroup (Dose 1 SD reactogenicity subset) 
Subpopulation 
Number of Participants evaluated for solicited AEs 
AZD1222 (N=2648) 
Control (N=2497) 
Country 
UK 
1636 
1497 
Brazil 
100 
99 
South Africa 
912 
901 
Comorbidity 
Yes 
822 
775 
 
Regulation 174 
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No 
1393 
1308 
Serostatus at baseline 
Positive 
160 
179 
Negative 
2387 
2224 
Age 
18-64 years 
2245 
2172 
≥ 65 years 
403 
325 
 
In the AZD1222 Dose 1 SD group, 2580 subjects were evaluated for solicited AEs after 
vaccination 1 and 1662 subjects after vaccination 2, of which 400 and 266 respectively were 
≥65 years of age. A slightly higher percentage of subjects were seropositive at baseline 
compared with the overall safety population, which likely reflects the higher number of 
subjects that were seropositive at baseline in South Africa. 
 
An overall summary of solicited AEs in the dose 1 SD safety analysis set is provided in table 
14 below. 
 
Table 14: Overall summary of solicited AEs (Dose 1 SD safety analysis set) 
Days 0 to 7 After Any 
Days 0 to 7 After First 
Days 0 to 7 After 
Dose 
Dose 
Second Dose 
Participants* 
AZD1222 
Control 
AZD1222 
Control 
AZD1222 
Control 
(N=10069)  (N=9902)  (N=10069)  (N=9902)  (N=10069)  (N=9902) 
Evaluated for solicited AEs, n 
2648 
2497 
2580 
2425 
1662 
1526 
Any solicited AE, n (%) 
2277 
1791 
2161 
1637 
1026 
722 
(86.0) 
(71.7) 
(83.8) 
(67.5) 
(61.7) 
(47.3) 
Any solicited local AE, n (%) 
1979 
1258 
1839 
1117 
778 
456 
(74.7) 
(50.4) 
(71.3) 
(46.1) 
(46.8) 
(29.9) 
Any ≥ Grade 3 severity solicited 
 252 (9.5) 
 138 (5.5) 
 210 (8.1) 
 112 (4.6) 
70 (4.2) 
38 (2.5) 
local AE, n (%) 
Any solicited systemic AE, n 
1932 
1488 
1817 
1320 
741 
545 
(%) 
(73.0) 
(59.6) 
(70.4) 
(54.4) 
(44.6) 
(35.7) 
Any ≥ Grade 3 severity solicited 
 221 (8.3) 
 63 (2.5) 
192 (7.4) 
41 (1.7) 
37 (2.2) 
27 (1.8) 
systemic AE, n (%) 
*Participants with multiple events in the same category are counted once in that category. Participants with 
events in more than 1 category are counted once in each of those categories. Denominators used in the 
percentage calculations are the number of participants “Evaluated for solicited AEs”. 
Solicited AEs were assessed daily after vaccination from Day 0 to Day 6 for COV0005 and to Day 7 for rest of 
studies via e-diary or diary card. 
No grade 4 severity option for events collected in COV005. Pain and warmth, malaise, nausea and vomiting 
were not assessed for COV005. Induration, feverishness and chills did not include COV005 since no severity 
grading collected. For redness, swelling and fever severity grading was derived based on reported value. 
Bruising only collected for COV005. 
 
Overall, 86% of subjects in the AZD1222 group (Days 0-7 after any vaccination) experienced 
at least one solicited AE compared to 72% in the control group. The majority of solicited 
AEs were mild or moderate. Ten percent of subjects in the AZD1222 group experienced at 
least one grade ≥3 local solicited AE and 8% at least one grade ≥3 systemic solicited event 
compared with 6% and 3% in the control group, respectively. Solicited AEs were milder and 
reported less frequently after the second dose compared with the first. 
 
 
 
Regulation 174 
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Table 15: Summary of Local Solicited Adverse Events (Dose 1 SD safety analysis set) – 
Days 0-7 after any vaccination 
Local solicited Adverse Events/  
AZD1222 
Control 
  Severity 
(N = 10069) 
(N = 9902) 
  
Participants with any local solicited AE 
1979 (74.7) 
1258 (50.4) 
  1: Mild 
1382 (52.2) 
967 (38.7) 
  2: Moderate 
345 (13.0) 
153 (6.1) 
  3: Severe 
252 (9.5) 
138 (5.5) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2497 
  
Pain 
941 (54.2) 
586 (36.7) 
  1: Mild 
776 (44.7) 
522 (32.7) 
  2: Moderate 
156 (9.0) 
61 (3.8) 
  3: Severe 
9 (0.5) 
3 (0.2) 
  4: ER or hospitalization 
0 (0.0)  
0 (0.0)  
  Total participants evaluated 
1736 
1596 
 
 
 
Tenderness 
1688 (63.7) 
987 (39.5) 
  1: Mild 
1398 (52.8) 
902 (36.1) 
  2: Moderate 
258 (9.7) 
78 (3.1) 
  3: Severe 
32 (1.2) 
7 (0.3) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2497 
 
 
 
Redness 
368 (14.0) 
218 (8.8) 
  1: 2.5-5 cm 
176 (6.7) 
123 (5.0) 
  2: 5.1-10 cm 
67 (2.6) 
36 (1.5) 
  3: >10 cm 
125 (4.8) 
59 (2.4) 
  4: Necrosis or ED 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2626 
2480 
 
 
 
Warmth 
308 (17.7) 
232 (14.5) 
  1: Mild 
301 (17.3) 
223 (14.0) 
  2: Moderate 
7 (0.4) 
9 (0.6) 
  3: Severe 
0 (0.0) 
0 (0.0) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
1736 
1596 
 
 
 
Itch 
335 (12.7) 
187 (7.5) 
  1: Mild 
272 (10.3) 
156 (6.2) 
  2: Moderate 
53 (2.0) 
26 (1.0) 
  3: Severe 
10 (0.4) 
5 (0.2) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2497 
 
Swelling 
262 (10.0) 
145 (5.8) 
  1: 2.5-5 cm and no IwA 
96 (3.7) 
52 (2.1) 
  2: 5.1-10 cm or IwA 
28 (1.1) 
26 (1.0) 
  3: >10 cm or PDA 
138 (5.3) 
67 (2.7) 
  4: Necrosis 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2626 
2481 
 
 
 
Regulation 174 
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Local solicited Adverse Events/  
AZD1222 
Control 
  Severity 
(N = 10069) 
(N = 9902) 
Induration 
164 (9.4) 
136 (8.5) 
1: 2.5-5 cm and no IwA 
66 (3.8) 
52 (3.3) 
2: 5.1-10 cm or IwA 
27 (1.6) 
27 (1.7) 
3: >10 cm or PDA 
71 (4.1) 
57 (3.6) 
4: Necrosis 
0 (0.0) 
0 (0.0) 
Total participants evaluated 
1736 
1596 
 
Bruising 
158 (17.3) 
60 (6.7) 
  1: <10 mm 
123 (13.5) 
48 (5.3) 
  2: 10-25 mm 
28 (3.1) 
8 (0.9) 
  3: >25 mm 
7 (0.8) 
4 (0.4) 
  Total participants evaluated 
912 
901 
Abbreviations: AE = Adverse Event, ED = Exfoliative dermatitis; ER=Emergency department; IwA = Interfere with activity; PDA = 
Prevent daily activity. 
Total participants evaluated was used as denominator in the percentage calculations. 
If a participant reported more than one occurrence of the same event, the event of greatest intensity was included in the analysis. 
Solicited AEs were assessed daily after vaccination from Day 0 to Day 6 for COV005 and to Day 7 for rest of studies via e-diary or diary 
card. 
No grade 4 severity option for events collected in COV005. Pain and warmth were not assessed for COV005. Induration did not include 
COV005 as grading scale was not compatible. 
For redness and swelling, severity grading was derived based on reported value. Bruising only collected for COV005. 
 
The most frequently reported local solicited AEs in the AZD1222 Dose 1 SD group after any 
vaccination were tenderness (64%) and pain (54%). The most comment events of Grade ≥3 
were swelling (5%) and redness (5%). No grade 4 AEs were reported. 
 
Table 16: Summary of Systemic Solicited Adverse Events (Dose 1 SD safety analysis set) – 
Days 0-7 after any vaccination 
Systemic Solicited Adverse Events/  
AZD1222 
Control 
  Severity 
(N = 10069) 
(N = 9902) 
 
Participants with any systemic solicited AE 
1932 (73.0) 
1488 (59.6) 
  1: Mild 
973 (36.7) 
1022 (40.9) 
  2: Moderate 
738 (27.9) 
403 (16.1) 
  3: Severe 
220 (8.3) 
63 (2.5) 
  4: ER or hospitalization 
1 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2497 
 
Fever 
208 (7.9) 
31 (1.2) 
  1: 38.0 - 38.4°C 
122 (4.6) 
18 (0.7) 
  2: 38.5 - 38.9°C 
67 (2.5) 
6 (0.2) 
  3: 39.0 - 40°C 
18 (0.7) 
7 (0.3) 
  4: >40°C 
1 (0.0) 
0 (0.0) 
  Total participants evaluated 
2644 
2493 
 
Feverishness 
583 (33.6) 
171 (10.7) 
1: Mild 
270 (15.6) 
153 (9.6) 
2: Moderate 
252 (14.5) 
16 (1.0) 
3: Severe 
61 (3.5) 
2 (0.1) 
4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
Total participants evaluated 
1736 
1596 
 
 
 
Regulation 174 
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 Systemic Solicited Adverse Events/  
AZD1222 
Control 
  Severity 
(N = 10069) 
(N = 9902) 
 
Chills 
554 (31.9) 
132 (8.3) 
  1: Mild 
278 (16.0) 
115 (7.2) 
  2: Moderate 
216 (12.4) 
17 (1.1) 
  3: Severe 
60 (3.5) 
0 (0.0) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
1736 
1596 
 
 
 
Joint pain 
698 (26.4) 
310 (12.4) 
  1: Mild 
492 (18.6) 
250 (10.0) 
  2: Moderate 
176 (6.6) 
48 (1.9) 
  3: Severe 
30 (1.1) 
12 (0.5) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2496 
 
 
Muscle pain 
1164 (44.0) 
540 (21.6) 
  1: Mild 
797 (30.1) 
452 (18.1) 
  2: Moderate 
317 (12.0) 
79 (3.2) 
  3: Severe 
50 (1.9) 
9 (0.4) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2496 
 
Fatigue 
1407 (53.1) 
955 (38.2) 
  1: Mild 
856 (32.3) 
704 (28.2) 
  2: Moderate 
466 (17.6) 
224 (9.0) 
  3: Severe 
85 (3.2) 
27 (1.1) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2497 
  
Headache 
1394 (52.6) 
975 (39.0) 
  1: Mild 
901 (34.0) 
743 (29.8) 
  2: Moderate 
422 (15.9) 
209 (8.4) 
  3: Severe 
71 (2.7) 
23 (0.9) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
2648 
2497 
  
Malaise 
768 (44.2) 
323 (20.2) 
  1: Mild 
417 (24.0) 
252 (15.8) 
  2: Moderate 
285 (16.4) 
64 (4.0) 
  3: Severe 
66 (3.8) 
7 (0.4) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
1736 
1596 
  
Nausea 
380 (21.9) 
209 (13.1) 
  1: Mild 
291 (16.8) 
173 (10.8) 
  2: Moderate 
74 (4.3) 
34 (2.1) 
  3: Severe 
15 (0.9) 
2 (0.1) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
1736 
1596 
 
 
 
Regulation 174 
41 
 
 
 

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Systemic Solicited Adverse Events/  
AZD1222 
Control 
  Severity 
(N = 10069) 
(N = 9902) 
 
Vomiting 
29 (1.7) 
14 (0.9) 
  1: Mild 
14 (0.8) 
8 (0.5) 
  2: Moderate 
9 (0.5) 
4 (0.3) 
  3: Severe 
6 (0.3) 
2 (0.1) 
  4: ER or hospitalization 
0 (0.0) 
0 (0.0) 
  Total participants evaluated 
1736 
1596 
Abbreviations: AE = Adverse Event, ER=Emergency department. 
Total participants evaluated was used as denominator in the percentage calculations. 
If a participant reports more than one occurrence of the same event, then the event of greatest intensity is included in the analysis. 
Solicited AEs were assessed daily after vaccination from Day 0 to Day 6 for COV005 and to Day 7 for rest of studies via e-diary or diary 
card. 
No grade 4 severity option for events collected in COV005. Malaise, Nausea and Vomiting were not assessed for COV005. Feverish and 
Chills did not include COV005 since no severity grading collected. 
For Fever, severity grading was derived based on reported value. 
 
The most frequently reported systemic solicited AEs in the AZD1222 Dose 1 SD group after 
any vaccination were fatigue (53%) and headache (53%). The most comment events of Grade 
≥3 were malaise (4%) and chills (4%). One grade 4 event of fever >40° was reported after 
vaccination 1.  
 
All of the local and systemic solicited events were reported more commonly in the AZD1222 
Dose 1 SD group compared with the control, including in the UK where active control was 
used for both doses, and are considered ADRs for AZD1222. This is reflected in the 
Information for Healthcare Professionals and the Information for UK recipients. 
 
The incidence of subjects with at least one local or systemic solicited event after any 
vaccination was highest on day 1 following vaccination, decreasing to 4% and 13 %, 
respectively, by day 7. The most common systemic solicited AEs at day 7 were fatigue, 
headache and malaise. Only 0.7% and 0.2% of subjects had a local or systemic solicited AE 
grade ≥3 at day 7 respectively. 
 
Data on solicited AEs by dosing interval were provided. However, this is difficult to 
interpret. Whilst post dose 2 the incidence of solicited AEs appeared lower in subjects with a 
dosing window <6 weeks, this pattern was also seen post dose 1 and may reflect potential 
differences in the population. No increase in the incidence of local or systemic solicited AEs 
≥ grade 3 was observed after vaccination 2 between subjects that had a dosing interval less or 
more than 6 weeks. 
 
The number of subjects in the reactogenicity subset that were seropositive at baseline is small 
limiting any firm conclusions that can be drawn. Except for a higher rate of subjects with any 
≥ grade 3 local solicited AE (15% vs 9%), the incidence of solicited AEs in the dose 1 SD 
AZD1222 group was similar in the seropositive and seronegative subjects. No seropositive 
subjects reported a grade 4 solicited AE, one grade 4 solicited AE (fever) was reported in the 
seronegative group.  
 
With regards to age, the number of subjects evaluated for solicited AEs in the ≥65 years 
group are relatively small. Whilst a similar percentage of subjects in the 18-64 years and ≥65 
years reported at least one solicited AE, fewer subjects in the ≥65 years reported a local or 
systemic solicited AE, or any ≥ grade 3 solicited AE. 
 
Currently there are insufficient data to support a recommendation for use of prophylactic 
paracetamol. However, information is included in the Information for Healthcare 
Professionals and the Information for UK recipients regarding symptomatic use of 
 
Regulation 174 
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paracetamol-containing products. 
 
Adverse events 
 
Unsolicited AEs were collected through 28 days post each dose. The overall incidence after 
any vaccination with any dose was higher in the AZD1222 group (38%) compared to the 
control (28%). However, the overall incidence of unsolicited AEs reported >7 days after any 
dose was similar between the 2 groups. Most of the unsolicited AEs were mild to moderate in 
severity. The incidence of unsolicited AEs with severity ≥ Grade 3 reported within 28 days 
after any dose was low (< 2%) and similar between the 2 groups. 
 
The most frequently reported AEs, occurring in ≥2% of the AZD1222 group, were consistent 
with AEs commonly observed following vaccination. These predominantly occurred ≤ 7 days 
of any dose. There were no AEs with an incidence ≥ 2% reported > 7 days of any dose. 
 
Adverse event data were evaluated at the preferred term level, and with reference to AE 
listings which included information on onset, duration, severity, seriousness and relatedness. 
AEs by System Organ Class (SOC) are summarised below: 
 
Table 17: Unsolicited Adverse Events by System Organ Class (Any dose for safety analysis 
set) 
 
Number (%) of Participantsa 
System Organ Class 
AZD1222 
Control  
(N= 12021) 
(N = 11724) 
Participants with any unsolicited AE 
4539 (37.8) 
3266 (27.9) 
System Organ Class uncoded 
85 (0.7) 
78 (0.7) 
Infections and infestations 
348 (2.9) 
364 (3.1) 
Neoplasms benign, malignant and unspecified (incl 
5 (<0.1) 
11 (<0.1) 
cysts and polyps) 
Blood and lymphatic system disorders 
40 (0.3) 
46 (0.4) 
Immune system disorders 
14 (0.1) 
16 (0.1) 
Metabolism and nutrition disorders 
41 (0.3) 
34 (0.3) 
Psychiatric disorders 
66 (0.5) 
45 (0.4) 
Nervous system disorders 
1408 (11.7) 
918 (7.8) 
Eye disorders 
68 (0.6) 
49 (0.4) 
Ear and labyrinth disorders 
42 (0.3) 
42 (0.4) 
Cardiac disorders 
30 (0.2) 
21 (0.2) 
Vascular disorders 
61 (0.5) 
59 (0.5) 
Respiratory, thoracic and mediastinal disorders 
401 (3.3) 
422 (3.6) 
Gastrointestinal disorders 
577 (4.8) 
414 (3.5) 
Hepatobiliary disorders 
1 (<0.1) 
3 (<0.1) 
Skin and subcutaneous tissue disorders 
180 (1.5) 
140 (1.2) 
Musculoskeletal and connective tissue disorders 
1261 (10.5) 
627 (5.3) 
Renal and urinary disorders 
26 (0.2) 
25 (0.2) 
Pregnancy, puerperium and perinatal conditions 
1 (<0.1) 

Reproductive system and breast disorders 
44 (0.4) 
35 (0.3) 
Congenital, familial and genetic disorders 
1 (<0.1) 
1 (<0.1) 
General disorders and administration site conditions 
3049 (25.4) 
1759 (15.0) 
Investigations 
205 (1.7) 
115 (1.0) 
Injury, poisoning and procedural complications 
87 (0.7) 
90 (0.8) 
 
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Social circumstances 
2 (<0.1) 
1 (<0.1) 
a Number (%) of participants with AEs, sorted on international order for system organ class. Participants with multiple 
events in the same preferred term are counted only once in each of those preferred term. Participants with events in more 
than 1 preferred term are counted once in each of those preferred term. Unsolicited AEs summarized from the start of each 
dose until Day 28. Unevaluable event is an event with pending query at the time of the interim analysis database lock. 
 
The imbalance in the SOC of Nervous system disorders was mainly driven by ‘headache’ 
events, reported by 9.3% subjects after AZD1222 vs 6.1% after control. There were also 
imbalances in events of ‘lethargy’ (0.4% vs 0.2%) and ‘somnolence’ (0.3% vs 0.2%) which 
are captured by the adverse drug reaction (ADR) ‘fatigue’ (see ‘General disorders and 
administration site conditions 
below).  A slight imbalance was seen in events of ‘dizziness’ 
(0.6% vs 0.5%) and it is noted that this is a known ADR for the control MenACWY vaccines. 
‘Headache’ and ‘dizziness’ are included as ADRs in the Information for Healthcare 
Professionals and the Information for UK recipients 
 
In addition, a detailed review of neurological AEs was undertaken which identified the 
following neurological cases of interest: 
 
•  A new diagnosis of multiple sclerosis in the AZD1222 group. Symptom onset was 
10 days after first AZD1222 dose. MRI of the brain and spinal cord demonstrated 
multiple lesions. All but one of these lesions were not gadolinium-enhancing 
suggesting that most lesions pre-dated the AZD1222 dose. 
 
•  A likely case of ‘short segment inflammatory myelitis’ in the AZD1222 group, 
although the diagnosis is not certain. Symptom onset was 14 days after second 
AZD1222 dose. 
 
Based on the available data, the presence or the absence of a causative association 
between the AZD1222 vaccine and these two cases cannot be concluded with 
certainty. 
 
•  A case of ‘transverse myelitis’ in the control group.  Symptom onset was 54 days 
after first control dose. 
 
•  Six cases of facial paralysis, three in each study group. The three cases in the 
AZD1222 group were all one-sided ‘facial nerve palsies’, two of which had features 
suggesting they were not related to AZD1222 vaccination (one case is considered 
related to chronic suppurative otitis media / mastoiditis, the other occurred 80 days 
after vaccination).  
 
•  Two cases of trigeminal neuralgia (both in the control group). 
 
These cases and other potential neurological events are covered by the list of adverse events 
of special interest (AESIs) previously defined by the MHRA for inclusion as part of the RMP 
for any potential COVID-19 vaccine and will be subject to routine and additional 
pharmacovigilance measures. In addition, ‘Neuroinflammatory disorders’ is included in the 
RMP as an ‘Important potential risk’. Section 4.8 of the HCP information reflects that “Very 
rare events of neuroinflammatory disorders have been reported following vaccination with 
COVID-19 Vaccine AstraZeneca. A causal relationship has not been established.’ 
 
The imbalance in the SOC of Gastrointestinal disorders was mainly driven by events of 
‘diarrhoea’ (1.3% vs 1.0%), ‘nausea’ (1.9% vs 1.2%) and ‘vomiting’ (0.7% vs 0.4%). In 
 
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addition, an imbalance in events of abdominal pain (0.4% vs 0.3%) and upper abdominal 
pain (0.2% vs 0.1%) was seen, particularly ≤7 days post any vaccination. Given the other 
ADRs in the gastrointestinal SOC, a relationship with AZD1222 is considered plausible. 
‘Diarrhoea’, ‘nausea’, ‘vomiting’ and ‘abdominal pain’ are considered ADRs and are 
included in the Information for Healthcare Professionals and the Information for UK 
recipients. 
 
The imbalance in the SOC of Musculoskeletal and connective tissue disorders was mainly 
driven by events of ‘arthralgia’ (1.4% vs 0.8%) and myalgia (7.6% vs 3.1%). These are 
considered ADRs and are included in the Information for Healthcare Professionals and the 
Information for UK recipients 
 
The imbalance in the SOC of General disorders and administration site conditions was 
mainly driven by events of asthenia (2.2% vs 1.1%), chills (3.4% vs 0.9%), fatigue (4.8% vs 
2.8%), malaise (2.3% vs 1.3%), pyrexia (7.5% vs 1.9%) and vaccination site pain (10.4% vs 
6.5%). With the exception of ‘asthenia’, based on the local and systemic reactogenicity data 
these are all considered ADRs and are included in the Information for Healthcare 
Professionals and the Information for UK recipients. In view of the similarity of the terms 
‘asthenia’ and ‘fatigue’, and given that ‘fatigue’ is included as an ADR with a frequency 
designation of ‘very common’, it is acceptable that ’asthenia’ is not included as an ADR. In 
addition, an imbalance in cases of ‘influenza-like illness’ (1.0% vs 0.6%) was noted and this 
has also been included as an ADR. 
 
The small imbalance in the SOC of Investigations was mainly driven by events of ‘body 
temperature increased’ (0.7% vs 0.1%) which is captured by the listed ADR ‘pyrexia’ 
(frequency ‘very common’). 
 
Within the SOC Skin and subcutaneous tissue disorders, 0.4% of subjects in the AZD1222 
group reported the event ‘hyperhidrosis’ compared with 0.2% in the control group. The 
majority of cases occurred ≤ 7 days post any dosing. The event ‘pruritus’ was reported by 
0.2% of cases in both treatment groups. The majority of cases, particularly in the AZD1222 
group, occurred ≤ 7 days post any dosing. Pruritus is a listed event for one of the 2 control 
MenACWY vaccines used. The event ‘rash’ was reported by 0.2% of cases in both treatment 
groups. Rash is a listed event for both of the control MenACWY vaccines used. 
‘Hyperhidrosis’, ‘pruritus’ and ‘rash’ have been included as ADRs in the Information for 
Healthcare Professionals and the Information for UK recipients 
 
Within the SOC Blood and lymphatic system disorders, 0.3% of subjects in both treatment 
groups reported the event ‘lymphadenopathy’. Lymphadenopathy is known to be associated 
with vaccines and is related to the immune response. Lymphadenopathy is a listed event for 
one of the 2 control MenACWY vaccines used. Lymphadenopathy has been included as an 
ADR in the Information for Healthcare Professionals and the Information for UK recipients. 
 
Within the SOC Metabolism and nutrition disorders the event ‘decreased appetite’ was 
reported by 0.2% subjects in the AZD1222 group and 0.1% in the control group. The 
majority of these events occurred ≤ 7 days post any dosing. Decreased appetite is a listed 
event for at least one of the 2 control MenACWY vaccines used. Decreased appetite has been 
included as an ADR in the Information for Healthcare Professionals and the Information for 
UK recipients. 
No serious cases of drug hypersensitivity have been reported with AZD1222 up to the data 
cut-off. One case of anaphylaxis was reported, this occurred 63 days after vaccination and 
 
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was considered related to antibiotics. In addition, one event of angioedema was reported 8 
days after vaccination and occurred after crab ingestion. One grade 1 AE of drug 
hypersensitivity was reported 11 days post vaccination. On the same day the subject reported 
a number of local grade 1 reactions and all AEs had a duration of 10 days. A MedDRA SMQ 
search of ‘narrow hypersensitivity’ revealed no imbalance in the percentage of subjects with 
at least one hypersensitivity AE. This remained the case if events including the listed ADR 
‘rash’ were excluded. Hypersensitivity is not considered an ADR at present; however, reports 
of hypersensitivity will be kept under review. 
 
A single case of erythema multiforme was reported 4 days post dose 2 in the AZD1222 
group. This was grade 2 in severity, considered unlikely related to study medication by the 
investigator and was ongoing. However, in view of the proximity to dose 2, erythema 
multiforme will also be kept under review. 
 
Subgroup data for unsolicited adverse events were provided by country, age, serostatus and 
comorbidity. In both the AZD1222 and control groups, the incidence of unsolicited AEs was 
higher in Brazil than in the UK or South Africa. This may in part reflect the fact that only 2% 
of the subjects in Brazil had solicited events collected, therefore more subjects may have 
reported typical reactogenicity AEs as unsolicited events. There is no indication of a worse 
safety profile in subjects aged ≥ 65 years, subjects who were seropositive at baseline or in 
subjects with at least one comorbidity. 
 
Serious adverse events 
 
Two deaths were reported in subjects that received AZD1222; one subject died 64 days after 
vaccination from Pneumocystis jirovecii pneumonia, they also had an AE of HIV test 
positive, and one subject died 86 days after their second dose of vaccine from metastatic 
ovarian cancer. Four deaths occurred in the control group (COVID-19 pneumonia, 
craniocerebral injury, injury, and homicide). None of the deaths were considered vaccine-
related by the investigator.  
 
Fewer than 1% of subjects reported a serious adverse event (SAE) and the reporting rate was 
balanced between the two study groups (0.7% AZD1222, 0.8% control). There were no clear 
imbalances by SOC. The most frequently reported SAEs by SOC were ‘Infections and 
Infestations’ (0.1% vs 0.2%) and ‘Injury, poisoning and procedural complications’ (<0.1% vs 
0.1%). 
 
Only 5 SAEs were considered related by the investigator, of which 3 were in the AZD1222 
group (pyrexia, C-reactive protein increased and transverse myelitis) and 2 were in the 
control group (autoimmune haemolytic anaemia, and myelitis). After the data cut-off, 
causality for the SAE of CRP increased was updated by the investigator to not treatment 
related. The case of pyrexia (40.5°) occurred 2 days after dose 1 of AZD1222. It was 
associated with increased sweating, shortness of breath, weakness, and loss of sense of smell 
and taste. The event was treated with paracetamol and resolved the same day. The case of 
transverse myelitis in the AZD1222 group and of myelitis in the control group are discussed 
in the ‘Adverse events’ section above. Overall within the SOC Nervous system disorders’
there were 7 SAEs in the AZD1222 group and 4 in the control group. 
 
There were no clinically meaningful imbalances in SAE incidence for any subgroup (country, 
age, serostatus or comorbidity).  
 
 
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Adverse events of special interest 
 
AESI were based on the Brighton Collaborative case definitions (SPEAC 2020), clinical 
experience and scientific interest. AESI were grouped under neurological, vascular, 
haematological and immunological (including anaphylaxis and vaccine associated enhanced 
disease). The incidence of AESI was low and balanced between the two treatment groups.  
 
Table 18: AESI by special interest category (any dose safety analysis set) 
Special Interest Category 
Number (%) of participantsa 
AZD1222 
Control  
(N = 12021) 
(N = 11724) 
Participants with any AESI 
95 (0.8) 
126 (1.1) 
Anaphylaxis 
1 (<0.1) 

Generalized convulsion 
1 (<0.1) 
1 (<0.1) 
Neurologic events-other 
64 (0.5) 
79 (0.7) 
Potential immune mediated conditions – 
1 (<0.1) 
3 (<0.1) 
Gastrointestinal disorders 
Potential immune mediated conditions – 
1 (<0.1) 
1 (<0.1) 
Musculoskeletal disorders 
Potential immune mediated conditions - 
5 (<0.1) 
4 (<0.1) 
Neuroinflammatory 
Potential immune mediated conditions –  
3 (<0.1) 
4 (<0.1) 
Skin disorders 
Potential immune mediated conditions – 

1 (<0.1) 
Vasculitides  
Potential immune mediated conditions –  
3 (<0.1) 
3 (<0.1) 
Other 
Thrombotic, thromboembolic, and 
4 (<0.1) 
8 (<0.1) 
neurovascular events 
VAERD 
12 (0.1) 
23 (0.2) 
aNumber (%) of participants with AEs, sorted in alphabetical order for special interest category. Participants with multiple 
events in the same preferred term are counted only once in each of those PTs. Participants with events in more than 1 PT are 
counted once in each of those PTs. 
 
The non-serious event of anaphylaxis is discussed in the ‘Adverse events’ section above. 
 
Vaccine associated enhanced disease (VAED), including vaccine associated enhanced 
respiratory disease (VAERD) is a theoretical risk, which is relevant to all COVID-19 
vaccines. Currently, there are only 2 cases of severe COVID-19 that have been reported in 
the any dose efficacy set, both in the control group, limiting any conclusions that can be 
drawn. However, the type of immune response triggered by the vaccine (Th1 skewed) and the 
number of COVID-19 hospitalisations in the any dose efficacy set (2 vs 16) provides 
reassurance. It is recognised that VAERD may not become apparent until efficacy of the 
vaccine starts to wane. This is an important potential risk in the RMP and will be monitored 
via routine and additional pharmacovigilance activities.  
 
There were no clinically meaningful imbalances in AESI incidence for any subgroup 
(country, age, serostatus or comorbidity).  
 
 
 
 
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Laboratory findings 
 
Laboratory testing was only conducted in a subgroup of subjects up to 28 days after each 
dose. The incidence of decreases in white blood cells, neutrophils, and platelets was slightly 
higher in the AZD1222 group compared with control. However, there were very few 
unsolicited haematology or biochemistry adverse events reported and these were balanced 
between the 2 study groups. 
 
Safety in special populations 
 
Pregnancy and breastfeeding 
Women who were pregnant or breastfeeding were excluded from the clinical trials. 
Pregnancy was reported for 21 subjects; 12 in the AZD1222 group and 9 in the control group. 
Of these pregnancies, 5 ended in spontaneous abortion – 2 in the AZD1222 group and 3 in 
the control group. Due to the limited duration of follow-up, the outcome of the remaining 
pregnancies is awaited. The results of preliminary studies in animals do not indicate direct or 
indirect harmful effects with respect to pregnancy, embryofetal development, parturition or 
post-natal development; definitive animal studies have not been completed yet. The full 
relevance of animal studies to human risk with vaccines for COVID-19 remains to be 
established. Therefore, administration of COVID-19 Vaccine AstraZeneca in pregnancy 
should only be considered when the potential benefits outweigh any potential risks for the 
mother and fetus. It is unknown whether AZD1222 is excreted in breast milk 
 
Information for Healthcare Professionals and the Information for UK recipients reflect these 
recommendations. Use in pregnancy and lactation is included in the RMP as missing 
information.  
 
Paediatric population 
In-line with the proposed indication, no data have been provided in subjects less than 18 
years of age. 
 
Immunosuppression 
No data are currently available in immunocompromised subjects or in subjects taking 
immunosuppressants. Safety data is awaited in a subgroup of HIV positive subjects that were 
included in studies COV002 and COV005. This will be followed up in the RMP.   
 
Safety related to interactions 
 
No data are available on use with concomitant vaccines, including influenza vaccines. 
 
Receipt of any vaccine, other than the study intervention within 30 days before and after each 
study vaccination, was an exclusion criterion in the clinical trials. In studies COV001 and 
COV002 there was an exception for licensed seasonal influenza and pneumococcal 
vaccinations. These were permitted at least 7 days before or after their study vaccine. 
 
Discontinuations due to adverse events 
 
No data were collected on adverse events leading to treatment or study withdrawal. However, 
the number of subjects who declined to receive a second dose of vaccine or withdrew early 
was balanced between the AZD1222 and control groups. 
 
 
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IV.6  Risk Management Plan (RMP) 
Every new medicine that is authorised has a Risk Management Plan (RMP) in place to ensure 
the medicine is used as safely as possible. An RMP details important risks for the medicine 
and how more information can be obtained about these. This includes important identified 
risks which have been demonstrated to be associated with the medicine and require additional 
measures as part of the authorisation to minimise any potential risk to users. Important 
potential risks are those where there is a potential association with the product but the 
association has not been confirmed and further information needs to be collected to establish 
whether this risk exists. Missing information topics are typically those which have not been 
fully evaluated in the clinical trials, are relevant to the use of the product and require further 
information to be gathered. 
 
The following section describes the RMP that has been agreed for the safe use of COVID-19 
Vaccine AstraZeneca. 
 
In addition to routine pharmacovigilance and risk minimisation measures, the MHRA has 
requested that all COVID-19 vaccines carry out further ad hoc pharmacovigilance activities 
specific to the pandemic situation. This includes more frequent safety signal detection 
activities with additional epidemiological analysis of potential safety signals and targeted 
safety events, frequent pharmacovigilance meetings with the MHRA, monthly 
pharmacovigilance safety update reports and batch specific surveillance. 
 
The important identified risks, important potentials risks and missing information for the 
COVID-19 vaccine AstraZeneca are as follows: 
 
Important Identified risk  None 
Important potential risk  Neuroinflammatory disorders 
Vaccine-associated enhanced disease (VAED) 
Missing information 
Use of COVID-19 Vaccine AstraZeneca in pregnant and breastfeeding 
women 
Use of COVID-19 Vaccine AstraZeneca in subjects with severe 
immunodeficiency  
Use of COVID-19 Vaccine AstraZeneca in subjects with severe and/ or 
uncontrolled underlying disease 
Use of COVID-19 Vaccine AstraZeneca with other vaccines 
Long-term Effectiveness 
 
There are no important identified risks for COVID-19 Vaccine AstraZeneca.  
 
Neuroinflammatory disorders has been included as an important potential risk. Very rare 
events of neuroinflammatory disorders were reported in clinical trials following vaccination 
with COVID-19 Vaccine AstraZeneca. A causal relationship has not been established. The 
pharmacovigilance plan will further investigate whether there is a link between the vaccine 
and neuroinflammatory disorders.  
 
Vaccine associated enhanced disease (VAED) has been included as a potential risk. This is a 
theoretical risk which is relevant to all COVID-19 vaccines based on VAED having been 
seen in animal models for vaccines developed for SARS-CoV-1 (a similar but not identical 
virus to SARS-CoV-2, the virus responsible for COVID-19). VAED has also been seen in 
association with use of another respiratory virus vaccine, the Respiratory syncytial virus 
(RSV) vaccine. There is currently no evidence from non-clinical or clinical data of an 
 
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association of VAED with COVID-19 Vaccine AstraZeneca; this potential risk will be 
further investigated as part of the pharmacovigilance plan for this vaccine. 
 
Use in pregnant and breastfeeding women is included as missing information because this 
group was excluded from the clinical trials and further data need to be collected on the safety 
and efficacy of this use. 
 
Use of COVID-19 Vaccine AstraZeneca in subjects with severe immunodeficiency is 
included as missing information as this group was excluded from the clinical trials and 
further data need to be collected on the safety and efficacy of this use. 
 
Use of COVID-19 Vaccine AstraZeneca in subjects with severe and/ or uncontrolled 
underlying disease is included as missing information as this group was excluded from the 
clinical trials and further data need to be collected on the safety and efficacy of this use. 
 
Use of COVID-19 Vaccine AstraZeneca with other vaccines when co-administered with 
other vaccines (either interchangeably with alternative licensed COVID-19 vaccines, or 
concurrently with seasonal illness vaccines) has not been evaluated. Further data need to be 
collected on the safety and efficacy of this use. 
 
Vaccine efficacy for COVID-19 Vaccine AstraZeneca has been clearly demonstrated in 
clinical trials. Vaccine effectiveness relates to how well a vaccine works in the “real world” 
setting outside of clinical trials and being used in a wider variety of people. Therefore, long-
term real-world data on vaccine effectiveness need to be collected and this has been included 
as a missing information topic. 
 
The following studies have been proposed to gather more information on these topics: 
 
Study 
Summary of activity objectives 
Safety concerns addressed 
Status 
• D8111R00003  
Primary Objectives: 
•  Immune-mediated 
Planned 
• D8111R00004 
•  To assess the safety and tolerability of at least  neurological conditions  
• DSRU study (study 
1 dose of the AZD1222 in adults ≥ 18 years of 
•  Vaccine-associated 
code to be confirmed)  age for a predefined period (eg, 3 months) after 
enhanced disease 
 
vaccination with first dose of AZD1222. 
•  Use of AZD1222 in 
Enhanced active 
 
pregnant and breastfeeding 
surveillance A Phase 
Secondary Objectives: 
women 
IV Enhanced Active 
•  To assess the longer-term safety and 
•  Use of AZD1222 in 
Surveillance Study of 
tolerability of at least 1 IM dose of AZD1222 in 
subjects with severe 
People Vaccinated 
adults ≥ 18 years of age for 12 months after 
immunodeficiency 
with AZD1222 
vaccination with first dose of AZD1222 
• Use of AZD1222 in 
 
 
subjects with severe and/or 
 
Secondary Objectives (pregnancy sub-study):  
uncontrolled underlying 
•  To estimate the frequency of selected adverse 
disease 
pregnancy outcomes in women receiving the 
• Use of AZD1222 with 
AZD1222 vaccine during pregnancy or up to a 
other vaccines 
predefined period (eg, 60 days) before estimated 
date of conception 
•  To estimate the frequency of selected adverse 
fetal/neonatal outcomes at birth and up to 6 
months of life in infants from pregnancies in 
which the mothers received the AZD1222 
vaccine during pregnancy or up to a predefined 
period (eg, 60 days) before estimated date of 
conception. 
AZD1222 Pregnancy 
Primary Objectives: 
•  Use of AZD1222 in 
Planned 
Registry 
•  To estimate the frequency of selected adverse 
pregnant and breastfeeding 
 
Regulation 174 
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COVID-19 Vaccine AstraZeneca, solution for injection in multidose 
 
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pregnancy outcomes (ie, spontaneous abortions, 
women 
Pregnancy Registry 
stillbirths, and preterm births) in women 
of Women Exposed 
receiving at least 1 dose of the AZD1222 
to AZD1222 
vaccine during pregnancy or up to a predefined 
Immediately Before 
period (eg, 60 days) before estimated date of 
or During Pregnancy  
conception 
 
•  To estimate the frequency of selected adverse 
 
fetal/neonatal outcomes (ie, major congenital 
malformations and small for gestational age) at 
birth and up to at least the 6 months of life (to 
account for diagnosis of major congenital 
malformations that might be delayed) in infants 
from pregnancies in which the mothers received 
the AZD1222 vaccine during pregnancy or up to 
a predefined period (eg, 60 days) before 
estimated date of conception. 
Post-marketing safety 
Primary Objectives: 
•  Immune-mediated 
Planned 
study  
•  To estimate the incidence of safety concerns 
neurological conditions  
 
and AESIs in recipients and non-recipients of 
•  Vaccine-associated 
A post-
AZD1222, among all populations targeted for 
enhanced disease 
authorisation/post-
vaccination and in the specific populations 
•  Use of AZD1222 in 
marketing 
considered as missing information 
pregnant and breastfeeding 
observational study 
•  To estimate the relative risk (comparing 
women 
using existing 
exposed and unexposed person time) of safety 
•  Use of AZD1222 in 
secondary health data 
concerns including AESIs among all 
subjects with severe 
sources to evaluate 
populations targeted for vaccination and in the 
immunodeficiency 
the association 
specific populations considered as missing 
•  Use of AZD1222 in 
between exposure to 
information 
subjects with severe and/or 
AZD1222 and safety 
•  To characterise the use of AZD1222 among 
uncontrolled underlying 
concerns. 
all populations targeted for vaccination and in 
disease 
the specific populations considered as missing 
•  Use of AZD1222 with 
information 
other vaccines 
• D8111R00005 
Primary Objective: 
Vaccine effectiveness 
Planned 
 
• To estimate brand specific vaccine 
Post-marketing 
effectiveness against laboratory-confirmed 
effectiveness study 
SARS-CoV-2 in hospitalized patients, overall 
 
and by age group (< 18, 18-64 and ≥ 65 years 
Post-authorisation/ 
old), after adjusting for potential confounders. 
Post-marketing 
retrospective cohort 
study to evaluate the 
effectiveness of the 
AZD1222 vaccine to 
prevent serious 
COVID-19 infection 
in conditions of usual 
care through public-
private partnership 
with COVIDRIVE 
utilizing primary data 
collected 
prospectively through 
the COVIDRIVE 
platform 
 
The company is also planning an additional study to look at safety of COVID-19 Vaccine 
AstraZeneca in patients taking immunosuppressant medicines and with primary 
immunodeficiency.  
 
The following ongoing pivotal clinical studies will also provide further safety data:  
 
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Study name and description 
Summary of objectives 
Status 
Study COV001 
Primary Objectives: 
A Phase I/II Study to Determine 
•  To assess efficacy of AZD1222 against COVID-19 
Efficacy, Safety, and 
•  To assess the safety of AZD1222 
Immunogenicity of the Candidate 
Coronavirus Disease (COVID-19) 
Key secondary Objectives: 
Vaccine ChAdOx1 nCoV-19 in UK 
•  To assess the reactogenicity profile of AZD1222  
Healthy Adult Volunteers 
To assess cellular and humoral immunogenicity of AZD1222. 
 
•  Status: Ongoing 
Study COV002 
Primary Objectives: 
A Phase II/III Study to Determine the 
•  To assess efficacy and safety of AZD1222 against COVID-19 
Efficacy, Safety, and 
in adults aged 18 years and older in the UK 
Immunogenicity of the Candidate 
Coronavirus Disease (COVID-19) 
Secondary Objectives: 
Vaccine ChAdOx1 nCoV-19 
•  To assess the reactogenicity profile of AZD1222 
 
•  To assess efficacy of AZD1222 against severe and non-severe 
•  Status: Ongoing 
COVID-19 
•  To assess humoral immunogenicity of AZD1222 
•  To assess cellular immunity of AZD1222 in older adults 
•  To assess the safety and immunogenicity of a booster dose of 
AZD1222 in older adults aged 56 years or older (two-dose 
schedule).  
Study COV003 
Primary Objective: 
A Randomised, Controlled, Phase III 
•  To evaluate the efficacy of AZD1222 vaccine against 
Study to Determine the Safety, 
COVID-19 disease confirmed with PCR 
Efficacy, and Immunogenicity of the 
Non-Replicating ChAdOx1 nCoV-19 
Secondary Objectives: 
Vaccine 
•  To evaluate the safety, tolerability and reactogenicity profile 
 
of AZD1222 
•  Status: Ongoing 
•  To evaluate the efficacy of AZD1222 against severe and non-
severe COVID-19 disease 
•  To evaluate the humoral immunogenicity of AZD1222 
•  To assess the cellular immunogenicity of AZD1222. 
Study COV005 
Primary Objective: 
An Adaptive Phase I/II Randomised 
•  To assess the safety of AZD1222 in healthy HIV-uninfected 
Placebo-controlled Trial to 
adults 
Determine Safety, Immunogenicity 

and Efficacy of Non-Replicating 
  To assess efficacy of AZD1222 against COVID-19  
ChAdOx1 SARS-CoV-2 Vaccine in 
•  To assess the safety of the candidate vaccine AZD1222 in 
South African Adults Living Without 
adults living with HIV 
HIV; and Safety and Immunogenicity 
in Adults Living with HIV 
•  To evaluate the immunogenicity of AZD1222 after first and 
second doses of vaccine in adults living with HIV 
 
•  Status: Ongoing 
Secondary Objectives: 
To assess the immunogenicity of AZD1222 in healthy HIV-
uninfected adults. 
 
 
 
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IV.7  Discussion on the clinical aspects 
 
Clinical immunogenicity 
Although there are no defined immune correlates of protection against COVID-19, it is 
generally accepted that high-titre neutralising antibodies with a robust cytotoxic CD8+ T cell 
response and Th1-biased CD4+ effector response will be optimal for protective immunity 
after SARS-CoV-2 exposure. 
 
AZD1222 elicits the rapid development of binding and neutralising antibodies after a priming 
dose, which are further increased with a booster dose to levels comparable to those measured 
in serum samples from convalescent patients. 
 
The importance of the dosing interval is emphasised in the Phase III results. These seem to 
suggest that higher levels of antibodies are generated after a lower prime dose compared to 
the standard dose; however, this finding is confounded by the observation that the dose 
interval for the majority of participants in the standard dose group was shorter (< 6 weeks) 
than in the lower dose group (≥ 12 weeks). Antibody levels tend to increase as the interval 
between the prime and booster doses increases, so that, when considering antibody levels 
between lower and standard dose at the same intervals, there is no difference between the 
lower and standard dose. 
 
There is a general concern about immunosenescence, and therefore, immunogenicity data in 
the older subgroups are critical. High seroconversion rates but lower GMTs were observed in 
the elderly (≥ 65 years) compared to younger adults, although the differences in the dosing 
interval may have partly confounded the results after the booster dose. Furthermore, the level 
of T cell responses was comparable in the elderly and younger age groups. 
 
T cell responses are rapidly induced after the first dose of vaccine and are well maintained up 
to 28 days following the booster dose. The responses are heavily biased toward secretion of 
Th1 cytokines (IFN-γ, IL-2 and/or TNFα) while no response is found for cells secreting Th2 
cytokines (IL-4, IL5, IL-13). IgG serotypes, predominantly IgG1 and IgG3, are also 
consistent with a Th1-polarised response, which is the profile targeted for COVID-19 vaccine 
in order to avoid potential disease enhancement. 
 
Finally, although AZD1222 elicits the development of neutralising antibodies against the 
viral vector, they do not seem to interfere significantly with the magnitude of the anti-spike 
response. 
 
Clinical efficacy 
Based on the description of the study population presented with the interim analysis, the 
study results are considered to support vaccine efficacy in a population at risk of severe 
COVID-19 based on comorbidities. There is some uncertainty about the effects of the 
vaccine in subjects over 65 years of age as this population is currently not well represented. 
As good efficacy has been demonstrated in subjects with comorbidities and immunogenicity 
results in the elderly population are broadly comparable to those of younger adults, there is 
currently no indication of a significant loss of efficacy in this population. 
 
Overall, the current data show a high level of short-term efficacy. The median duration of 
follow-up after the second vaccine dose is slightly longer than 2 months, which is considered 
the shortest follow-up period required to achieve some confidence that any protection is 
likely to be more than very short-lived. 
 
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However, the data do not address the following aspects. 
 
•  Data are currently limited for dose intervals < 2 months. However, more data on 4 to 6 
week-intervals will be submitted with further analyses of the ongoing trials. Therefore, a 
pragmatic approach allowing for some degree of flexibility in dosing intervals is currently 
considered appropriate within the context. 
 
•  Data on severe disease are insufficient to draw any definite conclusion although no case 
has been reported in the AZD1222 group and the vaccine efficacy has been shown on 
hospitalisations occurring after the first dose. 
 
•  Although data in individuals above 65 year of age are currently limited, more information 
is expected in the near future, with the submission of further analyses of the ongoing 
trials.  
 
•  Regarding COVID-19 cases, no viral genomic sequencing data of the isolated strains and 
no immunogenicity data in these vaccine failures are currently available. This will be 
addressed at a broader level by the COVID-19 Genomics UK (COG-UK) Consortium and 
in the immunogenicity follow-up. 
 
•  There are no data in pregnant women and immunosuppressed patients as these subjects 
are excluded from the trial. These aspects are addressed in the Risk Management Plan. 
 
•  Data on vaccine protection after 2 doses are currently lacking beyond 2-3 months and this 
will be addressed with longer follow-up in the ongoing clinical trials and effectiveness 
studies in accordance with the Risk Management Plan. 
 
•  There are currently no data in adolescents (12 to 17 years old). Enrolment in a safety and 
immunogenicity sub-study is due to start and these data will be submitted when available. 
 
Clinical Safety 
As of the 04 November 2020 data cut-off, safety data were available for 23,745 subjects. Of 
these subjects, 12021 subjects received at least one dose of AZD1222 of which 8266 received 
2 doses of AZD1222. The median duration of follow-up post dose 2 was 62 days in the 
AZD1222 and control groups, which is acceptable in the context of this Regulation 174 
procedure.  
 
The safety profile is characterised by local and systemic reactogenicity, which is likely to 
affect most recipients to a mild or moderate degree for a few days after vaccination. By day 7 
the incidence of subjects with at least one local or systemic reaction was 4% and 13%, 
respectively. No major safety concerns are raised. Based on the solicited local and systemic 
reactogenicity data, and the adverse event data, the following adverse drug reactions have 
been included in the Information for Healthcare Professionals and the Information for UK 
recipients:  
 
•  Very common (≥ 10%): headache, nausea, myalgia, arthralgia, Injection site 
tenderness, injection site pain, injection site warmth, injection site erythema, injection 
site pruritus, injection site swelling, injection site bruising (including injection site 
haematoma – uncommon), fatigue, malaise, pyrexia (including feverishness – very 
common, and fever ≥ 38° - common), chills 
 
 
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•  Common (≥ 1% to < 10%): vomiting, injection site induration, influenza-like illness 
 
•  Uncommon (≥ 0.1% to < 1%): lymphadenopathy, decreased appetite, dizziness, 
abdominal pain, hyperhidrosis, pruritus, rash 
 
A very small number of neuroinflammatory events have been reported following vaccination 
with AZD1222 but a causal relationship with AZD1222 has not been established. 
‘Neuroinflammatory conditions’ is included in the RMP as an important potential risk and 
will be closely monitored by routine and additional pharmacovigilance activities. 
 
Analyses of safety data by age, comorbidity (yes/no), baseline SARS-CoV-2 status and 
country have been provided. These analyses do not raise any specific concerns. 
 
In the AZD1222 group, only 18% of subjects were >55 years of age and about 10% were 
≥ 65 years of age. Whilst data are therefore limited in older subjects, particularly those ≥ 65 
years, it is of reassurance that the frequency and severity of solicited adverse events was 
lower in subjects ≥ 65 years, and the incidence of serious adverse events and adverse events 
of special interest was similar between subjects less than and ≥ 65 years. In addition, no 
clinically relevant difference was seen in the larger population of subjects that had at least 
one comorbidity. Therefore, it is considered that the available evidence supports a broad 
indication. 
 
Whilst the number of subjects with severe COVID-19 is too low to assess the potential for 
vaccine-associated enhanced disease, the type of immune response triggered by the vaccine 
(Th1 skewed) and a review of the number of COVID-19 hospitalisations in the 2 treatment 
groups provides reassurance (2 vs 16) regarding this theoretical risk. As VAED may not 
become apparent until efficacy of the vaccine starts to wane this is included as an important 
potential risk in the RMP with both routine and additional pharmacovigilance activities 
planned. 
 
There are no data in pregnant or breastfeeding women or immunosuppressed subjects. These 
populations are identified as missing information in the RMP with both routine and 
additional pharmacovigilance activities planned. 
 
The safety population, exposure and length of follow-up are acceptable for authorisation for 
temporary supply under Regulation 174. Safety data corresponding to longer follow-up will 
be submitted as laid out in the RMP. 
 
Conclusion on the clinical aspects 
The short-term data for COVID-19 Vaccine AstraZeneca are supportive of a favourable 
benefit/risk. From a clinical perspective, based on the reviewed information, there is no 
objection to the temporary supply of COVID-19 Vaccine AstraZeneca under a Regulation 
174. 
 
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USER CONSULTATION 
Evaluation of the patient information for readability via a user consultation study is currently 
deferred in the context of emergency supply under a Regulation 174.  
 
VI  
OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND 
RECOMMENDATION 
The quality of the product is acceptable in the context of batch specific release under 
Regulation 174. The non-clinical and clinical data submitted have shown the positive 
benefit/risk of this product for active immunisation to prevent COVID-19 caused by SARS-
CoV-2 virus, in individuals 18 years of age and older. 
 
The use of COVID-19 Vaccine AstraZeneca should be in accordance with official guidance. 
 
The Information for Healthcare Professionals on COVID-19 Vaccine AstraZeneca and the 
Information for UK recipients on COVID-19 Vaccine AstraZeneca are satisfactory.  
 
The Information for Healthcare Professionals on COVID-19 Vaccine AstraZeneca and the 
Information for UK recipients on COVID-19 Vaccine AstraZeneca for this product are 
available on the MHRA website. 
 
 
 
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 TABLE OF CONTENT OF THE PAR UPDATE 
Steps taken after the initial procedure with an influence on the Public Assessment Report 
(non-safety variations of clinical significance). 
 
Please note that only non-safety variations of clinical significance are recorded below and in 
the annexes to this PAR. The assessment of safety variations where significant changes are 
made are recorded on the MHRA website 
 
Application 
Scope 
Product 
Date of grant 
Outcome 
Assessment 
type 
information 
report 
affected 
attached 
Y/N  

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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