COVID-19 vaccine safety update

SPIKEVAX
Moderna Biotech Spain, S.L.

The safety of Spikevax is continuously monitored and safety updates are
regularly provided to the public. This document outlines the outcomes
from the assessment of emerging worldwide safety data carried out by
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) (see section
1). It also contains high-level information from the reporting of suspected
adverse reactions, which PRAC takes into account in its assessments (see
section 2).

This safety update follows the update of 6 October 2021.

Main outcomes from PRAC’s latest
safety assessment

There are no updates to the product
information. Further assessment of myocarditis and
pericarditis is ongoing. There is currently insufficient evidence of a
possible link between Spikevax and very rare cases of multisystem inflammatory syndrome (MIS).

The safety updates are published regularly at COVID-19 vaccines:
authorised. All published safety updates for Spikevax (previously known
as COVID-19 Vaccine Moderna) are available at Spikevax: safety updates.
Since its marketing authorisation in the European Union (EU) on 6 January
2021 until 29 October 2021, more than 61.6 million doses of Spikevax
have been administered in the EU/EEA1
.

1. Updates on safety assessments for
Spikevax

During its meeting held 27 to 30 September 2021, PRAC assessed new
safety data for Spikevax (see section 2 ‘How safety is monitored’).
Myocarditis and pericarditis
PRAC is assessing further data on the risk of myocarditis and pericarditis
following vaccination with Spikevax.
Myocarditis and pericarditis are inflammatory conditions of the heart.
Symptoms can vary but often include breathlessness, a forceful heartbeat
that may be irregular (palpitations), and chest pain.
PRAC had previously reviewed cases of myocarditis and pericarditis
spontaneously reported in the European Economic Area (EEA). The review
concluded in July 2021 with a recommendation to list both conditions as
side effects in the product information for Spikevax, together with a
warning to raise awareness among healthcare professionals and people
receiving this vaccine.

The committee has now asked the company that markets Spikevax to
perform an in-depth review of all published data on the association of
myocarditis and pericarditis with the vaccine, including clinical trial data,
data from the literature and other data available in the public domain.
EMA will continue to monitor the vaccine’s safety and effectiveness and
will communicate further when new information becomes available.

Multisystem inflammatory syndrome (MIS)
PRAC has concluded that there is currently insufficient evidence of a
possible link between Spikevax and very rare cases of multisystem
inflammatory syndrome (MIS).
MIS is a rare, serious inflammatory condition affecting many parts of the
body, and symptoms can include tiredness, persistent severe fever,
diarrhoea, vomiting, stomach pain, headache, chest pain and difficulty
breathing. MIS has previously been reported following COVID-19 disease.
The committee’s assessment is based on available spontaneously reported
adverse events and currently does not warrant an update of the product
information. Information to aid the diagnosis of MIS, such as laboratory
markers of inflammation, measures of disease activity, and the duration of
fever, and information excluding diagnosis of other infections was missing
in the majority of cases. A small number of cases did meet the diagnostic
criteria for MIS. However, these cases were missing information about
prior or current SARS-CoV-2 infection, which is important to assess
causality with the vaccine.

Capillary leak syndrome
PRAC has started a review of a safety signal to assess reports of capillary
leak syndrome in people who were vaccinated with Spikevax.
Six cases of this very rare disorder, characterised by leakage of fluid from
blood vessels causing tissue swelling and a fall in blood pressure, were
reported in the EudraVigilance database. At this stage, it is not yet clear
whether there is a causal association between vaccination and the reports
of capillary leak syndrome. These reports point to a safety signal –
information on new, or changes in, adverse events that may potentially be
associated with a medicine or vaccine and that warrant further
investigation. The review will also assess the risk in the population with a
medical history of the condition in question.
PRAC will evaluate all the available data to decide if a causal relationship
is considered likely or not. EMA will further communicate on the outcome
of PRAC’s review.

2. How safety is monitored

As for all COVID-19 vaccines, relevant new information emerging on
Spikevax is collected and promptly reviewed. This is in line with the
pharmacovigilance plan for COVID-19 vaccines of the EU regulatory
network (comprising the regulatory bodies of the EU Member States, EMA
and the European Commission).

Summary safety reports
The pharmacovigilance plan for COVID-19 vaccines includes Monthly
Summary Safety Reports (MSSRs) which are compiled by the marketing
authorisation holders to support timely and continuous benefit-risk
evaluations for COVID-19 vaccines used during the pandemic. MSSRs are
intended to be compiled for at least the first six months of marketing
(afterwards, pandemic summary safety reports may cover time periods
longer than a month). These reports complement the submission of
Periodic Safety Update Reports (PSURs).

Case reports of suspected side effects
Collecting reports of medical events and problems that occur following the
use of a medicine, and therefore might be side effects, is one of the pillars
of the EU safety monitoring system. Healthcare professionals and
vaccinated individuals are encouraged to report to their national
competent authorities all suspected side effects individuals may have
experienced after receiving a vaccine even if it is unclear whether the
vaccine was the cause. For more information on how to report, including
the importance of detailing the vaccine product name and the batch, see
Reporting suspected side effects.
These spontaneous reports are collected in EudraVigilance, the EU
database used for monitoring and analysing suspected side effects.
Publicly available information can be accessed via EudraVigilance –
European database of suspected drug reaction reports in all EU/EEA
languages. Search for “COVID-19 MRNA VACCINE MODERNA (CX024414)” to see all suspected side effect cases reported for Spikevax.
As of 28 October 2021, a total of 94,636 cases of suspected side effects
with Spikevax were spontaneously reported to EudraVigilance from
EU/EEA countries; 549 of these reported a fatal outcome2,3
. By the same
date, more than 61.6 million doses of Spikevax had been given to people
in the EU/EEA4
.
These reports describe suspected side effects in individuals, i.e.
medical events observed following the use of a vaccine. The fact
that someone has had a medical issue or died after vaccination

does not necessarily mean that this was caused by the vaccine.
This may have been caused, for example, by health problems not
related to the vaccination.
The EU regulatory network continuously monitors EudraVigilance to detect
any new safety issues. EudraVigilance relies on individual healthcare
professionals and patients to report their own experience. The monitoring
detects unusual or unexpected patterns in the reports received for further
investigation and risk assessment. EMA’s detailed assessments take into
account all available data from all sources to draw a robust conclusion on
the safety of the vaccine. These data include clinical trial results, reports
of suspected side effects in EudraVigilance, epidemiological studies
monitoring the safety of the vaccine, toxicological investigations and any
other relevant information.

Planned and ongoing studies
The company that markets Spikevax will continue to provide results from
the main clinical trial, which is ongoing for up to two years. It will also
conduct additional studies to monitor the safety and effectiveness of the
vaccine as it is used in vaccination campaigns and other clinical practice.
For the list of planned and ongoing safety studies for Spikevax, see the
risk management plan.
A paediatric investigation plan (PIP) for Spikevax is in place. This
describes how the company collects data on the vaccine’s efficacy and
safety for its use in children.
In addition, EMA is coordinating observational studies in EU Member
States looking at real-world data from clinical practice to monitor the
safety and effectiveness of COVID-19 vaccines, including in pregnant
women.

3. Other information for Spikevax
Spikevax (previously known as COVID-19 Vaccine Moderna) is a vaccine
that was authorised in the EU on 6 January 2021 to prevent COVID-19
when infected with the coronavirus SARS-CoV-2. COVID-19 is a
potentially severe disease that may result in death. The initial marketing
authorisation was for use in people aged 18 years and older; on 23 July
2021, the marketing authorisation was extended to use in individuals aged
12 years and older.

Spikevax contains a molecule called mRNA, which the body uses to
temporarily produce the SARS-CoV-2 spike protein. The mRNA is broken
down shortly after vaccination. The spike protein does not cause COVID19.
Before Spikevax was granted an EU marketing authorisation, the efficacy
and safety of the vaccine were assessed through pre-clinical studies and large clinical trials. More than 14,000 participants had been given the
vaccine in clinical trials.
Like all medicines, this vaccine can cause side effects, although not
everybody will experience them. The most common side effects known for
Spikevax are usually mild or moderate and get better within a few days
after vaccination.More information on how Spikevax works and its use is available in allEU/EEA languages in the medicine overview. This includes information on use in pregnant and breastfeeding women and immunocompromisedindividuals. The full product information with the summary of product characteristics and the package leaflet is also available in all EU/EEA languages

1 The European Centre for Disease Prevention and Control (ECDC) collects these exposure data from EU Member States as well as from the additional countries of the European Economic Area (EEA) Norway, Iceland and Liechtenstein.

2 These figures have been calculated excluding cases reported from Northern Ireland (EU reporting requirements for suspected adverse reactions to EudraVigilance apply to Northern Ireland in accordance with the Protocol on Ireland/Northern Ireland).

3 Source: EudraVigilance. These figures cannot be extracted directly from the public database of suspected adverse reactions, which groups information per type of side effects. As more than one suspected side effect may have been included in a single case report, the total number of side effects will never match the number of individual cases.Similarly, this public database does not provide the total number of cases reported with a fatal outcome.

4 The European Centre for Disease Prevention and Control (ECDC) collects theseexposure data from EU Member States as well as from the additional countries of the European Economic Area (EEA) Norway, Iceland and Liechtenstein.

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Via https://www.ema.europa.eu/en/documents/covid-19-vaccine-safety-update/covid-19-vaccine-safety-update-spikevax-previously-covid-19-vaccine-moderna-11-november-2021_en.pdf