Vaccine Safety Affirmed in Review of FDA Approvals

By Marilynn Larkin

July 29, 2020

NEW YORK (Reuters Health) - Vaccines are "remarkably" safe and the US Food and Drug Administration (FDA)'s approval and postmarketing system is "robust," a cohort study reveals.

Dr. Daniel Shepshelovich of Tel Aviv Sourasky Medical Center, Israel, told Reuters Health by email, "Vaccines are clearly safer as a group than drugs or medical devices, with significantly less post-marketing safety issues, most of which were not clinically important, and a more effective post-marketing surveillance program."

"We show that (over 20 years), the aggregation of hundreds of thousands of reports from the public and healthcare professionals to the FDA's Vaccine Adverse Event Reporting System, following hundreds of millions of administered vaccines, has not resulted in the identification of clinically important safety data," he said. "This supports the quality and thoroughness of the FDA's mechanism for the approval of new vaccines."

As reported in Annals of Internal Medicine, Dr. Shepshelovich and colleagues studied data on all 57 vaccines approved by the FDA from 1996 through 2015. The initial approval trials were similar in vaccines with and without post-marketing safety-related label modifications.

For 53 vaccines (93%), initial approval was supported by randomized controlled trials, with a median cohort size of 4,161 participants. Most vaccines were for seasonal influenza (37%), followed by combinations for diphtheria, tetanus, pertussis, polio, Hemophilus influenza type b, hepatitis B and hepatitis A (28%).

The most common source of safety data was postmarketing surveillance (48%).

Twenty-five vaccines had a total of 58 post-approval, safety-related label modifications (49 warnings and precautions, eight contraindications, and one safety-related withdrawal).

The most common safety issue triggering label modifications was expansion of population restrictions (36%) - e.g., to immunocompromised patients, pregnant women, those with pre-existing medical conditions. This was followed by allergies (22%), mostly to latex-containing packaging.

Dr. Shepshelovich noted that the COVID-19 pandemic "is a frightening reminder of life with contagious infectious diseases without an effective vaccine."

"While we cannot deduce from this study that the expected COVID-19 vaccine will be safe, as the development and approval process will likely be considerably more rapid than any previous vaccine, our study does show that the regulatory body responsible for vaccine approval is competent and well aware of the importance of approving safe vaccines, both for preventing direct harm and for preventing decline of trust in other vaccines," he said.

Further, he added, "the post-marketing vaccine safety surveillance is effective, so that any rare\unexpected side effect will be identified and addressed quickly."

Dr. Daniel Kuritzkes, Chief, Division of Infectious Diseases at Brigham and Women's Hospital in Boston commented in an email to Reuters Health, "The data reported in the article are a ringing endorsement of the care with which the FDA reviews new vaccine candidates and provides confirmation that the current approval process ensures that only vaccines with demonstrated safety and efficacy are allowed onto the market"

"Given the size of the phase 3 trials currently planned for testing candidate COVID-19 vaccines (20,000-30,000 participants), we can feel confident the same rigorous standards are being applied to evaluating the safety and efficacy of coronavirus vaccines," he said.

"A coronavirus vaccine will be successful in curtailing the COVID-19 pandemic only if a large majority of people in the US and around the world accept it as safe and effective," he noted. "For this reason, it is essential that the studies that are about to be launched proceed as planned and not be short-circuited in a rush to meet arbitrary deadlines."

"What is being expedited is the speed with which vaccine candidates are being moved from phase 1-2 trials into phase 3," he said, "and preparations to manufacture vaccines at scale prior to knowing if they are effective--a huge risk being shared by companies and governments."

"This accelerated progress of vaccine candidates is not the result of undue haste, but deliberate speed with enormous effort being brought to bear by the biotech and pharmaceutical industry, academic and government scientists, regulatory agencies such as the FDA and EMA, and the individuals who volunteer to participate in these trials," he concluded.

SOURCE: Annals of Internal Medicine, online July 27, 2020.