# Presentation: 270269

## How We Got Here: A Brief History of Vaccine Safety 

- Robert Ball, MD, MPH, ScM
- Chief, Vaccine Safety Branch
- Division of Epidemiology, OBE, CBER, FDA
- Vaccine Safety Evaluation: Post-marketing Surveillance Conference
- April 10, 2007

## “The Cow Pox-or-the Wonderful Effects of the New Inoculation”

**(From the publications of the Anti-Vaccine Society/J. Gilray, 1802)**

## Lessons from History	

- Vaccines have real risks that may include serious adverse effects
- Despite favorable benefit-to-risk ratio in favor of vaccination, public is concerned about adverse effects and coincidental adverse events

## Some Important Events in Vaccine Safety History	

- 1901 “Horse Named Jim” – beginning of regulation in US
- 1955 – “Cutter Incident” with incompletely inactivated polio vaccine

## Lessons from History	

- Pre-licensure safety testing, vaccine manufacturing process control, and clinical trials are critical foundations, but post-licensure monitoring is essential to ensure safety when vaccines are used in large numbers of people
- Government agencies, both regulatory and scientific, play important and beneficial roles in ensuring vaccine safety

## Some Important Events in Vaccine Safety History	

- 1976-77 - “Swine flu” vaccine and Guillain Barré Syndrome (GBS)
- 1980’s – Concern about DTP vaccine and encephalopathy leads to decline in vaccine coverage in some countries

## Lessons from History	

- 5.	Surveillance and observational studies after licensure are necessary to detect and evaluate vaccine safety concerns

## National Childhood Vaccine Injury Act of 1986

- Address vaccine liability concerns:
- limited to universally recommended childhood vaccines
- Mandated U.S. vaccine safety infrastructure
- National Vaccine Program Office (NVPO)
- National Vaccine Injury Compensation Program (NVICP): Vaccine Excise Tax + Vaccine Injury Table
- Vaccine Information Statements (VIS)
- Institute of Medicine (IOM) review committee
- Vaccine Adverse Event Reporting System (VAERS)

## Some Important Events in Vaccine Safety History Post-NCVIA

- 1990’s - Development of Vaccine Safety Data Link
- 1999 - Rotashield vaccine and intussusception
- 2000’s - Development of Clinical Immunization Safety Assessment Centers
- 2000’s – FDA/CMS collaboration to evaluate vaccine safety in Medicare beneficiaries

## Some Important Events in Vaccine Safety History Post-NCVIA

- 1998 – Concern about MMR and autism
- 1999 – Concern about thimerosal, neurodevelopmental conditions and autism
- 2005 – Concern about Menactra and GBS

## Child Develops Eczema Vaccinatum After Father Has Smallpox Vaccination

- Reuters Health Information 2007. © 2007 Reuters Ltd.
- By Maggie Fox
- WASHINGTON (Reuters) Mar 19 - The 2-year-old son of a soldier deployed to Iraq is in critical condition after developing a reaction to his father's smallpox vaccination, the U.S. Centers for Disease Control and Prevention said on Saturday.
- The child, being treated in a Chicago hospital, has eczema vaccinatum, the CDC said. It is the first such case since vaccination against smallpox resumed in 2002, said CDC pox virus expert Dr. Inger Damon.  The toddler's father is a soldier vaccinated while on deployment to Iraq. The father was unexpectedly furloughed and evidently his wife and son touched the vaccine site and became infected, the CDC said.  "They can get a particularly noxious and sometimes fatal rash," Dr. Damon said in a telephone interview. Because smallpox vaccine uses live vaccinia virus, it can sometimes cause severe and sometimes fatal side effects.
- "The child is a dependent of a U.S. Army Service member deploying to Iraq," the CDC said in a statement. "We don't know what the soldier's reaction was like at his vaccination but he is doing well now and hasn't described any illness that we are aware of," Dr. Damon said.The child has been treated with immune globulin, the antiviral drug cidofovir, and an experimental antiviral made by Siga Technologies called SIGA-246, Dr. Damon said.  "We are cautiously optimistic that the child is improving," Dr. Damon said.  Between 1959 and 1968, when smallpox vaccination was common, 12 cases of eczema vaccinatum were reported in the United States, with an 18% fatality rate.  The United States resumed vaccinating some people in 2002, including 40,000 civilian health workers and hundreds of thousands of military personnel. Many civilians resisted getting inoculated because of the vaccine's notorious side effects, but the CDC has reported only two very severe cases, both involving heart conditions that potentially could have been caused by the vaccine.  Dr. Damon said a stringent screening program had made vaccination safer than in years past. Anyone predisposed to side effects, such as people known to have eczema, are not supposed to get the vaccine.“So I think this is one of those unfortunate events where a family member who was at risk from vaccinia ends up coming in contact with a vaccinated individual," she said.

## Lessons from History	

- Need for robust continuously operating and technologically advanced safety monitoring systems including epidemiological, clinical and laboratory assessment of causality and etiology
- Public engagement and maintenance of confidence in validity and independence of vaccine safety system is needed to ensure vaccine coverage is optimal
- What’s old is new again!

## Lessons from History	

- Vaccines have real risks that may include serious adverse effects
- Despite favorable benefit-to-risk ratio in favor of vaccination, public is concerned about adverse effects and coincidental adverse events
- Pre-licensure safety testing, vaccine manufacturing process control, and clinical trials are critical foundations, but post-licensure monitoring is essential to ensure safety when vaccines are used in large numbers of people
- Government agencies, both regulatory and scientific, play important and beneficial roles in ensuring vaccine safety
- Surveillance and observational studies after licensure are necessary to detect and evaluate vaccine safety concerns
- Need for robust continuously operating and technologically advanced safety monitoring systems including epidemiological and clinical laboratory assessment of causality and etiology
- Public engagement and maintenance of confidence in validity and independence of vaccine safety system is needed to ensure vaccine coverage is optimal
- What’s old is new again!

## Lessons from History	

- Vaccines have real risks that may include serious adverse effects
- A strong post-marketing safety evaluation system is needed
- founded on pre-marketing safety evaluation and manufacturing process control
- rooted in surveillance and controlled epidemiological studies
- extended to include clinical and laboratory study of etiology, prevention, and management
- Despite favorable benefit-to-risk ratio of vaccination, public concern about vaccine safety is legitimate and is best dealt with through engagement to understand the public’s concerns and clear risk communication

## Conclusion	

- We must strive for continuous improvement of the vaccine safety system and the safety of vaccines
- If safety is seen as part of a quality improvement process – right system will emerge

## Acknowledgements	

- M. Miles Braun, MD, MPH
- Leslie Ball, MD