Policy Playbook: COVID-19 Vaccine Development

Authors: Gregory Jasani, MD (Resident Physician, University of Maryland) and Summer Chavez, DO, MPH, MPM (Attending Physician, The University of Texas Health Science Center at Houston) // Reviewed by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)

What is the issue?

To date, the coronavirus pandemic has claimed the lives of over 220,000 Americans and led to significant disruptions to everyday life for millions more.1  Mask mandates and various degrees of lockdowns have been adopted by elected officials at all levels to try and limit the spread of COVID-19.  Yet, as summer turns to fall, there are concerns that a second wave is coming as many states are seeing increases in their number of cases.2  Many, however, hope that developing a successful COVID-19 vaccine will stem the tide of cases and allow for a more complete reopening of businesses.  During the most recent Presidential debate, President Trump promised that a coronavirus vaccine was “weeks away” from approval.3

How does the vaccine approval process work?

The approval of vaccines in the United States is a highly regulated and lengthy process.4  It is overseen by the Food and Drug Administration’s (FDA) Center for Biologics Evaluation and Research (CBER).4  Once a vaccine has been developed by a pharmaceutical company, it will enter phased trials.5  A vaccine must pass three phases before it may seek final approval.5  During Phase I trials, small groups of people receive the vaccine and are monitored for a safety profile and side effects.5 Effectiveness and different doses are studied.5  Phase II expands the study to include individuals who have similar characteristics (such as age and underlying medical conditions) to the target audience of the vaccine.5 Additional information about short-term side effects is also obtained.5  In Phase III, the last stage before approval, the vaccine is given to an even larger group of participants, usually thousands.5  After a vaccine has passed Phase III, CBER will review the data from the phased trials and grant approval.5  Once this is done, pharmaceutical companies can begin distributing their vaccine.5

Throughout this process, the FDA will seek guidance from a group known as the Vaccines and Related Biological Products Advisory Committee (VRBPAC).10  VRBPAC is a group of outside experts who offer advice to the FDA regarding the development and implementation of vaccines.10  Often, the FDA will pose specific questions to this group and seek their guidance.10 It is important to note that this group acts in a purely advisory capacity–the FDA is not bound to follow their recommendations.11

However, there is an accelerated option for COVID-19 vaccines and that is an Emergency Use Authorization (EUA).12  An EUA can be given by the FDA during an emergency to allow unapproved medical products to be used or to allow approved medical products to be used in unapproved ways to when no alternative exists.12 The FDA has already stated that pharmaceutical companies can apply for EUAs for their vaccines.13  The FDA, in their guidance to the pharmaceutical industry, has stated that an EUA may be provided if “the vaccine’s benefits outweigh its risks based on data from at least one well-designed phase III clinical trial that demonstrates the vaccine’s safety and efficacy in a clear and compelling manner.”13   The FDA has made clear, however, that any COVID vaccine must meet a 50% efficacy standard, meaning that the data must show that a vaccine prevents the disease or decreases severity in at least 50% of people who are vaccinated.14

Once a vaccine has been approved by the FDA, the Centers for Disease Control (CDC) will seek recommendations from the Advisory Committee on Immunization Practices (ACIP), a federal advisory committee composed of medical and public health experts.15,16 The ACIP will make decisions regarding their recommendation of administering the vaccine and who should receive the vaccine, especially if the supply is limited.15,16 Once approved by the Director of the CDC, this then becomes official CDC policy.15,16

Even after a vaccine is being produced and administered to the general public, there will be on-going surveillance for adverse events.5 Any adverse event to a vaccine can be reported to the Vaccine Adverse Event Reporting System (VAERS) which is overseen by the Department of Health and Human Services.6  Many federal agencies are also establishing additional vaccine safety tracking capabilities for coronavirus vaccines.7  The CDC has established a tool called V-SAFE which will be a smartphone based, after vaccination health tracker for healthcare workers who receive the vaccine.8  Recipients will receive text messages and web surveys asking about symptoms and will also provide telephone follow up for anyone who reports an adverse event.8  The CDC has also established the National Healthcare Safety Network (NHSN), which allows acute and long term care facilities to report any adverse events to COVID vaccines that staff observe in patients.9 The Department of Defense, Department of Veteran’s Affairs, and even the Indian Health Service are all collaborating with VAERS to identify and track adverse reactions in the populations they serve.7

How close are we to vaccine approval?

The government established Operation Warp Speed (OWS) to accelerate the discovery, approval and production of an effective COVID vaccine. 17  OWS is a collaboration between several federal agencies (including the Departments of Health and Human Services, Agriculture, Energy, and Veterans Affairs) and the private sector.17  OWS has provided funds to many different pharmaceutical companies to support their vaccine development including Johnson and Johnson, Moderna, AstraZeneca, and Pfizer.18  Currently, OWS has selected multiple vaccine candidates for financial support, with the most prominent ones being Moderna’s mRNA-1273, University of Oxford and AstraZeneca’s AZD1222, and Pfizer and BioNTech’s BNT162.19

There have been setbacks: AstraZeneca had to suspend their trial shortly after it began due to safety concerns.20  They have recently been given approval by the FDA to resume their trial.20  Johnson and Johnson also recently resumed their trial after a pause due to safety concerns.21  Moderna and Pfizer, however, are still progressing with their Phase III trials.20  Eli Lilly recently ended their trial of the antibody drug bamlanivimab after federal researchers concluded it provided no additional benefit to hospitalized patients.22  There is a data safety and monitoring board, consisting of 10 to 15 anonymous experts, who are reviewing the data from all current vaccine trials to determine their safety.23 AstraZeneca, Pfizer, and Moderna, in an effort to promote transparency, have provided their study protocols to the public24,25,26  The head of OWS, Dr. Moncef Slaoui, believes that vaccines could reach all Americans by as early as June 2021.27

What can I do about it?

  • Review all available safety data about the vaccines.
  • Stay informed about the progress of the various vaccines through the approval process.
  • Receive a vaccine yourself once it has been approved.
  • Encourage your patients to do so as well.
  • Continue to emphasize social distancing, frequent hand washing and mask wearing.

Helpful Resources:

References/Further Reading:

  1. Coronavirus Resource Center. Johns Hopkins University & Medicine. https://coronavirus.jhu.edu/. Accessed October 21, 2020
  2. New cases hit three month high as COVID-19 hospitalizations soar. https://www.cnn.com/2020/10/23/health/us-coronavirus-friday/index.html. Accessed October 23, 2020
  3. Covid-19 vaccine ready & coming within weeks: Trump at final Presidential debate with Biden. Times of India. https://timesofindia.indiatimes.com/world/us/us-presidential-elections/covid-19-vaccine-ready-coming-within-weeks-trump-at-final-presidential-debate-with-biden/articleshow/78820410.cms. Accessed October 23, 2020.
  4. Center for Biologics Evaluation and Research (CBER).  https://www.fda.gov/about-fda/fda-organization/center-biologics-evaluation-and-research-cber. Accessed October 20, 2020
  5. Vaccine Testing and Approval Process. Centers for Disease Control. https://www.cdc.gov/vaccines/basics/test-approve.html. Accessed October 20, 2020
  6. VAERS.  Department of Health and Human Services. https://vaers.hhs.gov/. Accessed October 26, 2020
  7. Ensuring the Safety of COVID-19 Vaccines in the United States. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety.html. Accessed October 30, 2020
  8. Enhanced safety monitoring for COVID-19 vaccines in early stage vaccination. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2020-09/COVID-03-Shimabukuro.pdf. Accessed October 30, 2020
  9. National Healthcare Safety Network. https://www.cdc.gov/nhsn/index.html. Accessed October 30, 2020
  10. Vaccines and Related Biological Products Advisory Committee. U.S. Food and Drug Administration. https://www.fda.gov/advisory-committees/blood-vaccines-and-other-biologics/vaccines-and-related-biological-products-advisory-committee. Accessed October 26, 2020
  11. Why this week’s meeting of an FDA advisory panel on Covid-19 vaccines matters. STAT News. https://www.statnews.com/2020/10/20/dry-technical-but-important-why-an-fda-advisory-panels-meeting-on-covid-19-vaccines-matters/. Accessed October 26, 2020
  12. Emergency Use Authorization.  U.S. Food and Drug Administration. https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization#covid19euas. Accessed October 26, 2020
  13. Emergency Use Authorization for Vaccines to Prevent COVID-19. U.S. Food and Drug Administration. https://www.fda.gov/media/142749/download. Accessed October 26, 2020
  14. Coronavirus (COVID-19) Update: FDA Takes Action to Help Facilitate Timely Development of Safe, Effective COVID-19 Vaccines. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-action-help-facilitate-timely-development-safe-effective-covid. Accessed October 28, 2020
  15. Advisory Committee on Immunization Practices. https://www.cdc.gov/vaccines/acip/index.html. Accessed October 28, 2020
  16. Advisory Committee on Immunization Practices: General Committee-Related Information. https://www.cdc.gov/vaccines/acip/committee/index.html. Accessed October 28, 2020
  17. US Department of Defense. Coronavirus: Operation Warp Speed. https://www.defense.gov/Explore/Spotlight/Coronavirus/Operation-Warp-Speed/. Accessed October 28, 2020.
  18. Fact Sheet: Explaining Operation Warp Speed. Department of Health and Human Services. https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html. Accessed October 26, 2020
  19. COVID-19 vaccine tracker. Regulatory Affairs Professional Society. https://www.raps.org/news-and-articles/news-articles/2020/3/covid-19-vaccine-tracker. Accessed October 20, 2020
  20. FDA authorises restart of COVID-19 AZD1222 Vacinne US Phase III Trial. https://www.astrazeneca.com/media-centre/press-releases/2020/fda-authorises-restart-of-the-covid-19-azd1222-vaccine-us-phase-iii-trial.html. Accessed October 28, 2020
  21. Two Companies Restart Virus Trials in US After Safety Pauses. New York Times. https://www.nytimes.com/2020/10/23/health/covid-vaccine-astrazeneca-johnson-and-johnson.html. Accessed October 28, 2020
  22. Eli Lilly Ends Antibody Trial In Hospitalized COVID-19 Patients, Other Trials Go On. NPR. https://www.npr.org/sections/coronavirus-live-updates/2020/10/26/928072014/eli-lilly-ends-coronavirus-antibody-treatment-trial-other-studies-go-on. Accessed October 30, 2020
  23. Secret Safety Panels Will Pick the COVID Vaccine Winners. Kaiser Health News. https://khn.org/news/these-secret-safety-panels-will-pick-the-covid-vaccine-winners/. Accessed October 28, 2020
  24. ModernaTX Inc. Clinical Study Protocol. https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf. Accessed October 28, 2020
  25. Clinical Study Protocol. https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf. Accessed October 28, 2020.
  26. Clinical Study Protocol. https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-09/C4591001_Clinical_Protocol.pdf. Accessed October 28, 2020
  27. Trump’s Operation Warp Speed advisor says all Americans could be immunized with COVID vaccine by June. ABC News. https://abcnews.go.com/Health/trumps-vaccine-adviser-americans-immunized-covid-19-june/story?id=73713347. Accessed October 23, 2020

 

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