Stages in Vaccine Development

The COVID-19 pandemic has created a dire need for a vaccine that can effectively immunize populations and stop the spread of the disease. Consequently, many pharma companies around the world are participating in the race to develop a vaccine. Governments are also supporting these activities with public funding and by expediting the regulatory process for vaccine approval. Vaccine development is a very complicated and expensive process that usually takes more than ten years to final approval. However, in this time of crisis, efforts and regulatory hurdles have been streamlined to shorten the process to 12-18 months.

In general, the vaccine development process can be categorized into three stages: exploratory research, testing, and manufacturing. The exploratory research stage starts with target discovery and antigen identification. The goal of this stage is to find a safe way to introduce our immune system to the virus, giving our body the raw materials it needs to create antibodies that combat the infection. There are several ways to safely trigger the immune response. Traditionally, attenuated vaccine relies on weakened viral strains that must be cultivated in non-human tissue over long periods of time. On the other hand, an inactivated vaccine uses heat, acid, or radiation to weaken the pathogen, thus cutting cultivation time. Similarly, a protein subunit vaccine only utilizes a harmless fragment of viral proteins or antigen, which takes less time to grow instead of the whole viral strain.

The newest generation of vaccine platform is the DNA and RNA-based vaccine. This type of vaccine directly gives a genetic “instruction” to our cells so that we can produce the correct antibody to fight the virus. DNA and RNA-based platforms can be built quickly because they do not require cultivation or fermentation, and genetic technologies have advanced tremendously in terms of speed. Using this new method, a vaccine candidate for the SARS-CoV-2 virus became ready for testing in just 42 days compared to months and years for conventional vaccines. This result was achieved thanks to the collaboration of many labs that worked simultaneously on different models in order to speed up the process. There are many analytical techniques in play to discover a vaccine candidate. Nucleic acid purification and extraction, Polymerase Chain Reaction (PCR), Next-Generation Sequencing (NGS), multiplex ELISA, transfection, and mass spectrometry are used for target identification, vaccine design/synthesis, and candidate analysis and optimization.  After a vaccine candidate is produced, a pre-clinical step, which involves animal testing, is then conducted. In vivo animal imaging can be applied in this step to study the effects of the vaccine on an organismal level.

After the vaccine candidate completes the pre-clinical step, it is now ready for the testing stage, which mainly includes three phases of clinical trials. The first phase focuses on making sure that the vaccine is safe and effective. A small group of participants (between 20-100) is tested with the vaccine, and the intensity of the triggered immune response for each participant is monitored. Phase II trials focus on determining the most effective dosage and delivery across a wider population (several hundreds of participants). In phase III, the safety, rare side effects, and adverse reactions of the vaccine are monitored across hundreds to thousands of participants, representing the vaccine’s primary intended population. This testing stage takes more time than the other two, and it is difficult to speed up clinical testing due to the high numbers of variables and risks involved in the process to ensure long-term safety. In extreme conditions such as the pandemic, researchers run multiple trials within one phase at the same time to shorten the testing time. Occasionally, labs can also expedite this process by leveraging previously approved treatments that have similar pathogens. However, the approval of the vaccine in this stage is mainly hindered by strict safety criteria regulated by the relevant government agencies. In order to produce reliable testing results, scientists utilize technologies such as bioreactors, chromatography, NGS, and PCR to extract the targeted substance from a biological sample and analyze the effect of the vaccine.

Once a vaccine has passed phase III of the clinical trials, it will then be subjected to regulatory review and approval. A national regulatory authority, such as the US FDA, will review the result and ratify that the vaccine is safe for manufacturing. However, a phase IV trial is usually underway even after the vaccine is licensed for commercial used. The goal of phase IV is for drug companies to monitor the vaccine for safety, efficacy, and other potential uses, as the vaccine is administered to the general population. In terms of manufacturing, FDA will also inspect the manufacturing facility to ensure product quality and safety. In order for these facilities to efficiently start production as soon as the vaccine is approved, manufacturing plans must be designed in parallel to research and testing stages. Therefore, continuous collaboration between research and manufacturing/production is required to adopt sudden changes in vaccine design. Multiple instruments are used in this stage to certify vaccine quality and safety. Various sample preparation techniques, along with liquid chromatography and mass spectrometry instruments, are utilized for QC applications in the vaccine manufacturing process.

Each of the stages of vaccine development is essential, and so are the analytical techniques that support them. Technology advances such as NGS, reverse genetics, and various automation technologies for analytical instruments will surely help in cutting vaccine development time, especially during this pandemic. The collaboration between different research labs and also with manufacturing facilities is a critical component in this vaccine race, which emphasizes the role of informatics and integrated software for analytical testing. The market for these technologies is experiencing a tremendous boost during this pandemic, as a surge of need for COVID-19 related technologies has offset the otherwise shrinking demand due to reduced lab operations. At SDi, we are continuously analyzing this complex dynamic of the analytical instrumentation market, most recently in our updated 2020 SDi Global Assessment Report (published in June) and in our forthcoming quarterly datastream product due this month.