mRNA vaccines for COVID-19, such as the one developed by Moderna, requires ultralow temperature (-70-80 degree C) during storage. India never had this kind of storage requirement and building the infrastructure for ultracold storage requires considerable resources, as it needs not just the freezers, but also uninterrupted power supply, says Dr. Gagandeep Kang. The government may need to decide whether vaccines that require this form of storage should be used only in cities where such facilities can be built. It may make sense to even think about bringing people to the vaccine, instead of taking the vaccine to people in some settings.
The government recently said it will procure the vaccine and distribute it under a special COVID-19 immunisation programme to certain priority groups free-of-charge. The priority groups named are not exhaustive and there are challenges in distributing many COVID-19 vaccines that are in advanced stages of human trial. Professor of microbiology at CMC Vellore, Dr. Gagandeep Kang explains in an email the challenges that lie ahead.
Government has prioritised certain groups to receive the vaccine first. Which vulnerable groups do you think should receive the vaccine on priority?
Frontline healthcare workers at every level should receive vaccines when available. Offering the vaccines first to those who are most exposed to the virus owing to their professional responsibilities embodies the principle of reciprocity. Healthcare workers are not just nurses and doctors, they are ASHAs, village health nurses, technicians who collect and test samples, ward boys and drivers who transport patients, security staff in hospitals and so many more. Beyond that we have other frontline workers, sanitation and transport workers, police, etc, who should also be offered a vaccine.
Beyond the frontline workers we have a range of risk groups, starting with the elderly. The definition of elderly varies with country, with some setting the age for immunisation at 65 years, others at 60 years and India discussing an even lower age of 50 or 55 years above which people be classified as elderly for the purpose of vaccination. After the elderly we have those with co-morbidities.
All of those sounds like a simple rank-ordering, but it is not, hard choices may need to be made. For example, when there is insufficient supply to offer vaccines to all who would otherwise qualify, which group will be prioritised? Sometimes the choices will be dictated by the characteristics of the initial vaccines that become available. For example, early vaccines may not work well in older adults, and work very well in younger individuals. Should we then not vaccinate the elderly? Is there a bar below which vaccines should not be used in a particular group? As soon as we move beyond the big picture characterisation of initial priority groups, there are more questions for discussion than clear answers.
The Oxford vaccine that will be manufactured by Serum Institute requires about -20 degree C. Will distribution of a vaccine requiring this temperature even to rural areas be a challenge in India? Why does the vaccine that uses adenovirus vector require such low temperature?
Long term storage of oral polio vaccine is at -20 degree C, so there is -20 degree C capacity within the routine immunisation system. However, when the oral rotavirus vaccine was made by Bharat Biotech originally to fit into the available oral polio vaccine space as fewer campaigns were conducted, the national immunisation program asked the company to make a 2-8 degree C formulation instead; even if space exists, a vaccine that can be at a higher temperature is better for the programme.
My understanding was that the Oxford vaccine or Covishield was intended for 2-8 degree C storage, while the Gamaleya vaccine [Sputnik V vaccine] had a -18 degree C long term storage similar to oral polio vaccine.
The reason for low temperature storage is because the vaccines are stable for longer periods at lower temperature. Increasing thermostability of a vaccine so that it is stable at higher temperatures requires re-formulation of the vaccine so that the vaccine is appropriately composed to protect the virus or antigen from breaking down and being made ineffective.
Most of the COVID-19 vaccines in Phase-3 trials require ultralow temperature. How challenging will vaccine distribution be, particularly in rural areas? Does India have the infrastructure and experience to distribute ultralow temperature vaccines? How expensive will vaccine distribution be?
Many, not all, vaccines that are today’s front-runners in development have very challenging cold chain requirements. The RNA vaccines in particular need ultra-cold storage, -70 or -80 degrees Celsius. This kind of storage was used for the Ebola vaccines and was difficult to establish in West Africa, but was managed on the scale needed for Ebola — which is in the hundred thousand doses range. When we need tens and hundreds of millions of doses, I do not know how feasible that will be in the U.S. or UK, let alone in India. Although there are efforts to see if these storage conditions can be brought to what exists by modifying the vaccines and increasing their stability, it is unlikely that this will be done in the first-generation vaccines.
In India we have never had this kind of storage requirement and building the infrastructure for ultracold storage requires considerable resources, because you need not just the freezers, but also uninterrupted power supply. I think we may need to decide whether vaccines that require this form of storage should be used only in cities where such facilities can be built. It may make sense to even think about bringing people to the vaccine, instead of taking the vaccine to people in some settings. Not just the financial resources for the vaccines, the storage, transport and delivery are important, the logistics and temperature monitoring will be critical if we decide to use these vaccines.
I have no exact figure for how much this might cost, but this is a situation where doing a cost-utility analysis would be very valuable to see whether we might be better off waiting for vaccines with less demanding requirements — trading early vaccination for a few for slightly later vaccines for many more because of the costs involved.
Since almost all vaccines in advanced clinical trials require two doses, how challenging will it be to twice vaccinate a given population through injection a few weeks apart during the pandemic, particularly in rural areas?
Vaccinating twice one month apart is something we know and have done for polio programmes for well over a decade. Although oral vaccines are much easier to deliver than injectable vaccines, the logistics of storage, transport and delivery are similar. For injectable vaccines where two doses need to be given three or four weeks apart, we will need to learn from our experience with polio and measles-rubella campaigns. Our immunisation programme has core strengths in delivering vaccines to children with increasing coverage, and we will need to see how these can be expanded to deliver vaccines to age groups that are not children. We will have to think about workplace immunisation, since many priority groups will be identified based on their professions.
I find the challenge of identifying those with co-morbidities the most difficult one. At least for age group-based identification, it is possible to say everyone over the age of XX years should come to this facility on these dates to get their vaccines. But after that, for the next risk group, what do we do? Say everyone with hypertension, diabetes etc come to a facility? How will we then verify medical information? How will we deal with fraud?
There are going to be challenges in urban and in rural areas, and I hope that with the approach to micro-planning that the government is taking of identifying first healthcare workers and then people at the health-subcentre, primary health centre and district level, this will be a pattern we can repeat as vaccines become available for each new priority group. But there are still concerns about migrants, people with identification etc, that we will need think about strategies for.
Should vaccines be made available for free for all so as to quickly reach herd immunity and stop the pandemic? Or can a portion of the vaccines be sold even as they are available for free for people?
I think vaccines should be free if national public health policy is to use vaccines to prevent disease and transmission. Initially, I assume vaccines should be prioritised for groups as identified by the government, which might mean that all vaccines are only available in the public sector, at least when supplies are limited.
However, there have been discussions in the media about the government allowing companies to purchase vaccines to maintain business continuity. If that is the case, the percentage of doses that will be diverted, at what time and what cost should be available for the sake of transparency. And if that happens, it may be argued that such diversion should not be restricted to companies alone, which are a small percentage of employers in the country, but also for other groups that might be willing to pay for vaccines in order to maintain their functions — for example, what if temples want to vaccinate their priests and other staff, is that less important than companies? Of course, any vaccines being diverted at a time when supply is limited deprives priority groups, so perhaps another way to think about this, is that certain types of vaccines that are unsuitable for public programmes in India because of expense or cold chain requirements, might be opened up for purchase by companies, organisations and individuals as a premium product.
All this is ethically contentious, and needs discussion. There are no easy decisions or choices.
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