FDA Vaccine Approval - Procedure

Introduction

No regulations for vaccine approval existed until the 19th century, and several vaccines for humans were developed, including the smallpox vaccine, plague vaccine, cholera vaccine, and typhoid vaccine. The origin of FDA (food and drug administration) started with the passage of the 1906 pure food and drugs act. This law was the final achievement after 100 bills over a quarter-century.

What Is a Vaccine?

It is a biological preparation that helps the body fight against a particular infection. The vaccine induces antibody production against a pathogen and provides active acquired immunity against diseases or disorders. Vaccines consist of a preparation that closely resembles the disease-causing microorganism and is given before one comes in contact with the pathogen. Most vaccines are given as injections, although a few are given orally.

What Is FDA?

The United States FDA (food and drug administration) is a federal government agency of the health and human services department. It is separated into divisions for protecting public health through controlling and supervising most of the organization's obligations involving drugs, blood transfusion, animal food, vaccines, dietary supplements, blood products, electromagnetic radiation devices, and biopharmaceuticals.

How Does FDA Approve a Vaccine?

All drugs, vaccines, and other medical treatments in the United States undergo a specific process to ensure safety and efficacy before releasing them to the public. For centuries, FDA-approved and authorized vaccines have prevented several severe diseases like influenza, measles, smallpox, etc. The FDA supervises the process from the beginning to the end and even after approval. The review process is a step-by-step procedure that includes:

• Exploratory Phase: This is the first stage of the process and includes research and discovery of the vaccine. The scientists develop a rationale for the vaccine based on how the pathogen causes the disease. This stage often lasts for two to four years.

• Preclinical Phase: This is when laboratory and animal testing is done. Before the vaccine can be used on humans, it is tested on animals to obtain information about how it works and to check its safety and efficacy before using it on humans. The animal subjects may include monkeys and mice. This phase often lasts one to two years; some vaccines may not go beyond this stage.

• After each step, the vaccine enters the next phase only if it is reviewed and approved by the FDA.

IND Application: After the preclinical phase, the sponsor submits an IND (investigational new drug) application to the United States FDA. The sponsor, the one who funds the whole clinical research, describes the manufacturing and testing process, provides a summary of the lab reports, and describes the purpose of the study. The IRB (institutional review board) approves the clinical protocol, and the FDA has 30 days to approve the IND application.

• Phase I Clinical Trial: Once the IND application is approved, the vaccine goes to phase I of clinical trials. Phase I is the first stage of testing in humans. The phase involves a small group of healthy candidates, around 20 to 100 subjects. The subjects involved are only adults, even if the vaccine is being developed for children.

Phase I trial is open-labeled (the researchers and the subjects know whether a vaccine or placebo is used) because this phase aims to determine the vaccine's safety, pharmacokinetics, and pharmacodynamics in the human body. In addition, the phase I trial helps determine the maximum tolerated dose by escalating the treatment. This phase lasts for six to 12 months.

• Phase II Clinical Trial: This phase is also called the therapeutic exploratory phase and is the first phase of a clinical trial on patients. The phase involves a larger group of 200 - 300 subjects. The phase II clinical trial helps monitor side effects and confirm the vaccine's effectiveness.

• Phase III Clinical Trial: This phase is called a therapeutic confirmatory phase. It is a large-scale trial involving thousands of subjects. The trials are randomized and double-blinded. The phase III trial monitors the overall therapeutic effect and the dosing schedule.

BLA Approval: After a successful phase III trial completion, a BLA (biologics license application) is submitted to the FDA. The FDA will examine the trial reports, inspect the factory where the vaccines are manufactured, and approve the labeling of the vaccine.

• Phase IV Trial: This phase is the post-marketing surveillance of the vaccine. The manufacturers can conduct trials on the vaccine and determine its safety and efficacy after it is released to the public. The FDA continues to monitor the adverse effects among people receiving the vaccine. The FDA maintains a VAERS (vaccine adverse event reporting system) to allow patients and healthcare providers to report any adverse health events that may have occurred due to the vaccine. The VAERS is monitored by the CDC (centers for disease control and prevention). In case of any serious adverse effects, the FDA can pause the administration of the vaccine to do more research and ensure that the risks do not outweigh the vaccine's benefits.

The FDA also sets manufacturing guidelines for the vaccine developers and requires that they test the vaccine in batches. This is to ensure that the quality and effectiveness of the vaccine remain reliable and consistent.

What Does Full FDA Approval of a Vaccine Mean?

Full FDA approval happens when there is enough evidence and data that the vaccines are safe and effective for most people who received them. Then the FDA reviews and approves the whole manufacturing process and facilities. So a fully FDA-approved vaccine indicates that the vaccine is safe and effective in most people and has more benefits than risks.

Examples of a few vaccines licensed by the FDA include:

• BCG vaccine.

• Influenza vaccine.

• Human papillomavirus bivalent vaccine.

• Hepatitis A vaccine.

• Hepatitis B vaccine.

• Measles, mumps, and rubella virus vaccine.

• Japanese encephalitis virus vaccine.

• Plague vaccine.

• Smallpox vaccine.

• Rabies vaccine.

• Tetanus toxoid.

• Yellow fever vaccine.

Conclusion

The FDA monitors each vaccine development step to ensure human subjects' safety and efficacy. The vaccines are monitored even more thoroughly than other medications because the number of human subjects in the vaccine trial is often more than that of other drugs. In addition, the FDA and the CDC ensure the post-marketing surveillance of vaccines to avoid serious adverse effects.