Scientist and experts globally are raising several doubts about the Russian vaccine for COVID-19, Dr Syed Khalid Ali, Director Clinical R&D at MSD Wellcome Trust Hilleman Laboratories Pvt. Ltd elucidates to Prathiba Raju that vaccine developed with compressed timelines will be a campaign vaccine, which will require further studies even after its licensure of the vaccine in order to be available for wider use.
How much time does it take it to develop a vaccine? Why each stage of the clinical trial is crucial and why should we adhere to the same? What are the potential shortcuts?
Vaccine development is a long and arduous process. The amount of time needed to develop a vaccine varies and depends on multiple factors. Usually, a new vaccine may take 10 years or more from discovery to delivery.
Vaccines are given to healthy individuals and most of the vaccine recipients are children, hence the safety standards for vaccines are very high. Each stage of a clinical trial is designed to thoroughly evaluate the safety and efficacy of a vaccine, at the same time ensure safety of individuals participating in the clinical trials.
Simply put, there are no unnecessary steps in vaccine research & development process, hence no shortcuts. But in extraordinary situations, certain measures can be taken parallelly to save time. A detailed risk benefit analysis is recommended before any such decision is made.
Another area where vaccine development can be significantly expedited is the regulatory and ethical approvals of clinical studies. In normal circumstances approvals from regulatory bodies does take time but in the given situations, authorities can be requested to review the application on priority basis, which can save significant amount of time and help in fast tracking the process of developing an impactful vaccine solution in time
ICMR has informed that the fast-tracking is done as per globally accepted norms. Can you brief us about those norms? Is it possible to develop a safe vaccine within those norms?
Currently, there are 165 candidates which have all reached at least the pre-clinical trial phase. At least 23 of them are in the human trial phase. The scientific community, world over, is working together with regulatory authorities on the fast-tracked norms. That definitely doesn’t mean that science and ethics behind developing vaccines can be compromised.
While different academic institutions may adopt different ways of fast tracking the research, one of ways known to fast track vaccine development is to carry out activities in parallel. For instance, before a vaccine is tested in humans, preclinical toxicology studies in animal models is required. Studies to demonstrate immunogenicity and efficacy of vaccine animal models are also done prior to clinical studies. In the fast-track mode, preclinical toxicology studies, as well studies to demonstrate efficacy in animals can be done in parallel with a Phase I clinical study which usually involves a small number of healthy adult participants.
Another approach is grant of licensure for emergency use of vaccines in high-risk population, based on limited clinical data (immunogenicity in a few hundred participants, as opposed to efficacy which requires 1000s of participants). Vaccine manufacturers continue larger clinical studies even after initial (emergency) licensure and generate the required data to demonstrate safety and efficacy of a vaccine before full licensure.
The fast-tracking of vaccine development needs to be evaluated vis a vis the expected outcome from availability of a vaccine. These risks are transient as evaluation of a vaccine continues even after licensure, and in due time the safety profile of a vaccine is established. So, it is definitely possible to eventually develop a safe vaccine even after initial fast tracking to meet an emergency situation.
Vaccine development takes about 10 to 15 years. What are the risks involved in compressing the traditional timeline? Can you provide your thoughts both on the aspect of technological innovation and the monetary risk?
It is true that the traditional vaccine research and development process is a time-consuming process and requires at least 8-10 years. However, these are unprecedented times that require unprecedented efforts in a direction that will safeguard the world from the Covid crisis.
Data available for a vaccine developed in a fast track mode to control an ongoing pandemic will be limited. But the experience and knowledge of having dealt with similar epidemics (like SARS and MERS) in the past along with advanced technologies like Artificial Intelligence (AI) that are being deployed to study the genome of the virus can be leveraged to develop a safe and efficacious vaccine. Certain data on duration of protection and persistence of immune response, or impact of co-administration of this vaccine with other vaccines, may not be available. This data can be generated after licensure while the vaccine is being used, to support wider and more efficient use.
Primarily, a vaccine developed with compressed timelines will be a campaign vaccine which will require further studies even after licensure of the vaccine in order to be available for wider use.
For any drug approval, there’s always a balance between benefit and risk, if at all the vaccine is developed in a short span of time should it be used to people who are exceptionally at risk, based on expected benefit, or should they wait for proven benefit?
Vaccines are generally very safe, with a very minimal risk of minor adverse events. But there are other aspects like the health economics and competing priorities, which makes it important to do a benefit-risk analysis before any vaccine is introduced.
While vaccines should be made available to all who need it, in emergency situations those at the front line or those most at risk (high-risk groups or vulnerable populations), should be prioritized over others. Emergency can be shortage of supply of a perfectly well evaluated vaccine, or vaccine development in a short span of time to control an evolving pandemic. In the later scenario, prioritization of high-risk individuals, further improves the risk benefit ratio.