COVID-19 Vaccine Safety Technical (VaST) 

Work Group 

Assessment of 3rd dose safety data

H. Keipp Talbot, MD MPH (VaST Chair)

Robert H. Hopkins, Jr., MD (NVAC Chair)

Advisory Committee on Immunization Practices

September 22, 2021
COVID-19 Vaccine Safety Technical (VaST) Work Group

Objectives

 Review, evaluate, and interpret post-authorization/approval 

COVID-19 vaccine safety data

 Serve as the central hub for technical subject matter expertise 

from federal agencies conducting post-authorization/approval 

safety monitoring

 Advise on analyses, interpretation, and data presentation

 Provide updates to the ACIP COVID-19 Vaccines Work Group and 

the ACIP on COVID-19 vaccine safety

2
VaST Activities

Dec 12 

Pfizer

(16+)

Feb 28 

Janssen 

(18+)

Apr 14 

CVST 

following 

Janssen

Dec 19 

Moderna 

(18+)

Apr 23 

TTS updates; 

Janssen 

resumed

Dec 21, 2020 – present

35 independent meetings to review vaccine safety data

8 joint meetings with COVID-19 Vaccines Work Group focused on safety

May 12 

Pfizer

(12-15)

Jan 27

Anaphylaxis 

following 

mRNA 

vaccination

Mar 1

Anaphylaxis 

updates;

Pregnancy 

vaccine 

safety data

May 12

TTS 

updates

Jun 23

Myocarditis 

updates

May 17 & 24

Myocarditis

ACIP 

votes

VaST 

assessments 

at ACIP 

meetings or 

website

CVST, cerebral venous sinus thrombosis; TTS, thrombosis with thrombocytopenia syndrome; GBS, Guillain-Barré syndrome 

July 22

GBS 

following 

Janssen

Aug 13

Additional 

mRNA 

vaccine 

doses 

3

Aug 30

Pfizer BLA 

(16+)

Aug 30

Safety 

overview

Sept 23

3rd dose

Sept 22

Pfizer 

3rd dose
VaST continues to review data on myocarditis, GBS, 

anaphylaxis, and TTS following COVID-19 vaccination

from passive and active surveillance systems

 U.S. safety monitoring systems including VAERS, VSD, CMS, 

VA, IHS, DoD

 Israel, Canada, Global Advisory Committee on Vaccine Safety

 Special evaluations underway, such as follow-up studies of 

myocarditis cases in VAERS, VSD, and DoD

VSD, Vaccine Safety Datalink; CMS, Centers for Medicare & Medicaid Services; VA, Veterans Affairs; 

IHS, Indian Health Service; DoD, Department of Defense 4
Safety data regarding 3rd dose COVID-19 vaccination 

reviewed by VaST 

 Israel – data from spontaneous reporting system*

 United States – data from v-safe 

*Also presented at VRBPAC meeting, September 17, 2021 5
Safety data regarding 3rd dose Pfizer-BioNTech 

COVID-19 vaccination, Israel

 3rd doses were phased in, first for persons ≥60 years; since the end of August 

everyone ≥12 years has been eligible for 3rd dose

 ~2.8 M 3rd doses administered to persons ≥12 years (through September 13)

– Most to persons ≥60 years 

 Rates of reported systemic, local, neurologic, allergic, and other reactions 

were substantially lower after dose 3 than after dose 1 or 2

– Suspected under-reporting 

 1328 non serious and 19 serious adverse events (SAE)

– All hospitalized patients and deaths investigated by a work group

– Among serious cases, 7 possibly associated with vaccination

https://www.fda.gov/media/152205/download 6
https://www.fda.gov/media/152205/download 7
8

Data from Israeli Ministry of Health 

https://www.fda.gov/media/152205/download
Safety data after 3rd dose COVID-19 vaccination, v-safe

 As of September 11, 3rd doses were recorded by 24,165 participants

 While 3rd doses are currently only recommended for persons with 

immunocompromising conditions in the United States, there are no data 

in v-safe to indicate underlying conditions 

 Compared with dose 2

– Larger proportion of participants report local reactions following 

mRNA vaccination dose 3 

– Smaller proportion of participants report systemic reactions following 

mRNA vaccination dose 3 

9
VaST assessment of 3rd dose Pfizer-BioNTech COVID-19 

vaccination safety data

 Safety data from Israel

– Assessment limited by likely underreporting of local, systemic, and SAEs. 

– The few SAEs potentially associated with vaccination need further follow-up. 

– VaST noted single case of myocarditis reported in male aged 30-34 years.

 Safety data from v-safe

– Systemic reactions following dose 3 slightly less than following dose 2.

– Assessment limited by lack of data on underlying conditions or whether 

recipients are individuals with immunocompromise. 

– v-safe data significance unclear given that local and systemic reactogenicity 

does not predict more severe adverse events. 

10
Safety monitoring and VaST next steps

 VaST will continue to:

– Review safety regarding 3rd doses as data become available

– Collaborate with global vaccine safety colleagues on key issues that 

impact benefit-risk balance

– Provide updates to the ACIP COVID-19 Vaccines Work Group and 

the ACIP at future meetings

11
VaST Members

VaST Members

Keipp Talbot (ACIP)

Robert Hopkins (NVAC)

Matt Daley

Grace Lee

Veronica McNally

Kathy Edwards

Lisa Jackson

Jennifer Nelson

Laura Riley

Robert Schechter

Patricia Whitley-Williams

CDC Co-Leads

Lauri Markowitz

Melinda Wharton

Ex Officio and Liaison Representatives 

Tatiana Beresnev (NIH)

Karen Farizo; Hui Lee Wong (FDA)

Judith Steinberg (OIDP)

Jeffrey Kelman (CMS)

Matthew Clark (IHS)

Mary Rubin (HRSA)

Fran Cunningham (VA)

Limone Collins (DoD)

Administrative Support

Jared Woo

12 12
https://www.fda.gov/media/152205/download 13
14

Safety monitoring

 mRNA COVID-19 vaccines 

– Anaphylaxis

– Myocarditis

 Janssen COVID-19 vaccine

– TTS

– GBS

 Pre-specified AESI

 Maternal immunization 

Incorporating safety data into decision-making

 Dynamic benefit-risk balance

 Risk mitigation strategies

– Support informed discussions about 

benefits and risks of available vaccines

– Clinical guidance to support early detection 

and appropriate management

 Guidance for use of post-approval safety 

data in GRADE

Monitoring and Responding to Safety Data

TTS, thrombosis with thrombocytopenia syndrome; GBS, Guillain-Barré syndrome; AESI, adverse events of special interest