Table 1.
The Vaccine Development Stages and the Process.
| Phase | Aim | Features |
|---|---|---|
| Exploratory | Develop a vaccine. | Research intensive phase. Identify synthetic or natural antigen. Develop a vaccine (natural or synthetic). Time: 25 years.b The success rate to proceed is 40%.g Causes of failure based on the nature of the pathogen. |
| Preclinical |
The vaccine is safe and immunogenic. Evaluate the starting dose for human studies. |
Subjects: Vaccine is studied in Cell culture & animals. Design: Toxicity and antibody response, challenge studies. Time: <1 year. The success to proceed is 33%.g Causes of a failure—vaccine toxic or ineffective immune response, underfunding. |
| Clinical Trial Authorization | Allow human experiments (Application for IND) | The basis for authorization-Manufacturing steps & analytical methods for vaccine & placebo production, Availability and stability of vaccine & placebo during clinical studies. Time: within 30 days. |
| Phase Ic | First-in-human testing. Vaccine safety and immune response. | Subjects: Healthy volunteers (20-100). Site: vicinity of the tertiary care for close observation. Design: Escalation study to avoid severe adverse effects (SAEs). Monitor: Health outcomes (clinical and laboratory) and antibody production Time: a few mon. Success rate to proceed 66%.g Caution: Follow strict go/no-go criteria based on safety and immunity data |
| Phase IIc,d,e |
Vaccine safety, immunity/partial efficacy. Dose–response, schedule, and method of delivery |
Subjects: Healthy volunteers (hundreds), may include a diverse set of humans. Site: Community-based (university, colleges, schools, etc). Study design: Studied against a placebo, adjuvant, or established vaccine. Dose: Test vaccine in different schedules and a diverse set of humans. Monitor: Health outcomes (clinical and laboratory) and antibody response Partial efficacy data can be procured under circumstances. Time: 2yr. Success rate to proceed 30%. g |
| Phase IIIc | Vaccine efficacy and safetya | Subjects: Target population (thousands). Site: Field conditions similar to future vaccine use. Design: Vaccine randomized vis-a-vis a placebo, adjuvant, or an established vaccine. Monitor: Vaccine efficacy and SAE. Time: Many years. Success rate to proceed 70%.g |
| Biologic License Application | Marketing of vaccinef | The basis for approval-The vaccine is safe and effective in humans (Efficacy >95%). Capacity to produce in bulk for market demand. Affordable cost to a susceptible population. |
| Phase IV | Postmarketing surveillance | Spontaneous reporting (Adverse Events Reporting System). Monitor: Data collected by the end-users. |
This figure includes vaccines that are abandoned during the development process.
Vaccine Efficacy (VE) = (Iu-Iv/Iu) ×100= (1-Iv/Iu) ×100= (1-RR) ×100%. (Iv = incidence in vaccine group, Iu = incidence in unvaccinated group, RR = relative risk).
Platform technology has shortened time for vaccine production from years to days.
Clinical trials are rate-limiting in vaccine marketing.
Human challenge studies can be done in phase IIa in certain diseases where the challenge is ethical.
Phase IIb studies can provide data on efficacy in regions with a high prevalence of the disease in the community.
The cost of developing a vaccine from research and discovery to product registration is around US$ 1 Billion.
The overall success rate for vaccine development is around 15%.