The elaborated stages contained in its entire development cycle collectively represent one of the challenges or factors affecting the development of vaccines. In fact, more specific issues arise from each stage of vaccine development. To understand the complication better, it is important to note that the process combines scientific and economic considerations.
Processes: The General Stages of Vaccine Development
There are three general stages involved in the development of a vaccine. These are the pre-clinical phase, the clinical phase, and the post-licensure phase. Present in these three are the utmost objectives of ensuring safety, immunogenicity, and efficacy, as well as eventual effectiveness of the final product.
However, the National Center for Immunization and Respiratory Diseases of the U.S. Centers for Disease Control and Prevention breaks down these stages further in six specific stages. Take note of the following:
1. Exploratory Stage
A research-intensive phase that involves the identification of natural or synthetic antigens that have the potential to prevent or treat a disease. The research commences with the introduction of an idea or vaccine concept followed by sponsorships from governments, foundations, or corporations, and preliminary research by universities, research institutions, biotechnology, and pharmaceutical companies. A candidate vaccine emerges from this stage.
2. Pre-Clinical Stage
The introduced candidate vaccine will undergo the pre-clinical stage that involves using tissue-culture or cell-culture systems and animal testing in a laboratory setting. The purpose of this stage is to determine if the candidate vaccine will produce immunity. Note that most candidate vaccines do not move past this stage because they fail to demonstrate immunity, or there are indicators that they are harmful to test subjects.
3. Clinical Development
Following pre-clinical research is the clinical development stage centered on a series of clinical trials in humans. These trials commence from the submission of application from a regulatory body by the vaccine developer. Regulators must first approve this application before the developer can proceed with human testing. Nevertheless, depending on the jurisdiction, the clinical development stage consists of three to four phases of human testing.
4. Regulatory Review and Approval
The fourth stage of vaccine development has some overlaps with the clinical development phase. Remember that a manufacturer must secure a license first before they can commence clinical trials. Both the manufacturer and regulators work in close collaboration to continuously evaluate and audit trial results during the clinical development stage and even beyond phase III or clinical trials. The regulatory body grants the manufacturer a license to produce and market the vaccine upon satisfying all criteria pertaining to potency, safety, and purity.
Once approved, the developed vaccine enters mass production. Of course, regulators need to inspect each facility used for manufacturing the vaccine. It is worth mentioning that one of the challenges and cost-drivers of vaccine development come from the fact that reproducing an existing vaccine formulation from a new facility would require undergoing complete clinical testing and licensing processes. Product labeling and distribution models are also part of manufacturing considerations.
6. Quality Control
The licensed vaccine in the market still undergoes continued quality control. The same is true during the entire manufacturing stage. A particular manufacturer activates a dedicated team of post-marketing surveillance professionals to monitor for potency and safety. Because clinical trials involved relatively small numbers of people compared to the entire population, there is a need to continuously study the vaccine confirm or reject related issues, or refine the formulation.
Clinical Trials: Specific Phases of Clinical Development for Vaccines
In both biomedical and behavioral research, clinical trials are experimental or observational studies involving human participants designed to determine whether a medical strategy, novel treatment option, or new device is safe for human use or consumption, or to answer specific questions about known interventions that warrant further investigation and comparison.
The purpose of clinical trials in vaccine development revolves around the same need to determine the safety and effectiveness of a candidate vaccine. There is a general three-phase process involved in the clinical development of a vaccine. Take note of the following:
Phase I: The first phase is a small-scale trial involving a small sample of the population conducted to evaluate whether the vaccine is safe in humans, as well as to determine what immune response it produces. The number of participants is between 20 to 100 in general. More specific objectives of Phase I are to screen for safety, determine safe dosage range, and identify side effects.
Phase II: In the second phase, participants number to not less than 100. The purpose is to establish a proof of concept, as well as evaluate further safety and effectiveness of the vaccine in consideration of population characteristics such as age and sex. There are two sub-phases under Phase II. Phase IIA assesses further dosing requirements while Phase IIB investigates vaccine efficacy or, more specifically, how well the vaccine works at the prescribed doses.
Phase III: The third phase involves a larger trial consisting of hundreds to thousands of participants across identified geographic locale aimed at evaluating further safety and efficacy under natural disease conditions. The general purpose of this phase centers on the final confirmation of safety and efficacy. If the vaccine demonstrates a capability to retain safety and efficacy over a defined period, the manufacturer can proceed to apply a license to regulatory authorities for mass production, marketing, and human consumption.
Researchers and manufacturers also include a fourth phase in the clinical development of the vaccine. Phase IV or post-marketing surveillance transpires after the vaccine has been licensed and administered to the public or, more specifically, within the quality control stage of vaccine development. The purpose is to evaluate long-term safety and efficacy, identify rare adverse effects, address relevant issues, and determine potentials for refining the formulation.
FURTHER READINGS AND REFERENCES
- National Center for Immunization and Respiratory Disease. 2014. Vaccine Testing and Approval Process. Vaccines & Immunizations. National Center for Immunization and Respiratory Disease, Centers for Disease Control and Prevention. Available online
- Stern, P. L. 2020. Key Steps in Vaccine Development. Annals of Allergy, Asthma & Immunology. DOI: 1016/j.anai.2020.01.025