In mid-December, as vaccine doses started debuting in some countries, India’s health secretary Rajesh Bhushan announced guidelines for Indian states to start beefing up their cold chain infrastructure to store vaccines supplies. Bhushan said the government would put to action electrical and non-electrical cold chain equipment – 29,000 cold chain points, 240 walk-in coolers, 70 walk-in freezers, 45,000 ice-lined refrigerators, 41,000 deep freezers and 300 solar refrigerators – once vaccines are rolled out.
“It is expected that the vaccine will be available in the coming few weeks and the vaccination process will kickstart in India as soon as it is approved by the regulatory agency,” India’s Health Minister Harsh Vardhan said on 10 December 2020 addressing a virtual inter-ministerial meeting on ‘Vaccination of South Asia against COVID-19’ organised by the World Bank.
Vardhan assured that there would be no compromise on the scientific and regulatory norms around the safety or efficacy of the vaccines being trialled in India.
India has witnessed a flurry of research on vaccine development and some candidates are awaiting a nod from the regulator for emergency use. Three COVID-19 vaccines developed by Bharat Biotech, Serum Institute of India and Pfizer are under active consideration of India’s drug regulator and an early license may be possible for all or any of them. Bhushan confirmed that eight vaccines were in different stages of development. “There are multiple vaccine candidates in different stages of development and some may get licensed in the next few weeks. These vaccines require 2-3 doses, 3 to 4 weeks apart,” Bhushan told mediapersons.
Adar Poonawalla, CEO of vaccine manufacturers Serum Institute of India recently tweeted that his company has applied for emergency use authorisation for “the first made-in-India vaccine”. Poonawalla said a good vaccine would be safe, offer long term protection, can be transported and stored at a manageable temperature, and affordable.
Randeep Guleria, Director of the All India Institute of Medical Sciences and a member of the national task force on COVID- 19, is hopeful that by January 2021 India will get an emergency use approval for a vaccine. “The large database that we have accrued over the trials reflects that the safety and efficacy of the vaccines have not been compromised,” he told Nature India . Around 7000-8000 volunteers are currently a part of the trials and this number is increasing. Guleria said no significant adverse effect has been noted in any of the trials. The central and state governments were working together for a smooth vaccine roll out in the country ensuring that cold chains are maintained, vaccinators trained and infrastructure available, he said.
Public health experts maintain that the massive vaccination drive in India will face significant challenges. While India has been at the forefront of child immunisation, adult immunisation at such a grand scale is an unexplored territory. “Even though India has the largest vaccination programme in the world, we have no adult immunisation platform,” says Gagandeep Kang, Professor in the Wellcome Trust Research Laboratory Division of Gastrointestinal Sciences at Christian Medical College, Vellore. “The government has invested in developing systems, but even with the best logistics, there are still operational failures that will tell us what needs to improve – and until we get going with rolling out vaccines, we will not know what the gaps are,” Kang says.
“A major challenge is going to be the right communication from the right people at the right time, so that the vaccination programme builds trust and performs at a high level,” she says.
Chandrakant Lahariya, an expert in public policy and health systems and author of ‘Till We Win: India’s fight against COVID -19 pandemic’ says roping in the private sector and establishing a harmonious public-private partnership will be a daunting task. The challenges can be tackled via public communication and building a mechanism to negate any adverse affect. “This would require participation of various stakeholders including the private sector, to ensure success,” Lahariya feels.
The real challenge, says Prashant Yadav, senior fellow at the Center for Global Development and Professor at INSEAD, will be to integrate the vast private sector health infrastructure to the COVID19 vaccine delivery system. “The private sector can provide the much needed capacity augmentation in the area of supply chain and vaccine administration,” says Yadav, whose work focuses on improving healthcare supply chains. The success of a vaccination program of this scale will also require immense collaboration between the central and state governments. “Supply chains where trust between different actors is in deficit cannot work well.”
The COVID-19 vaccine delivery system could also be an opportunity to reform the supply chain for routine vaccines by adopting a direct delivery model and avoiding multiple layers between the central government and the clinics.
The delivery strategy will have to be supplemented by a robust communication plan to take care of safety concerns. “An effective communication strategy and a robust awareness generation programme are needed,” says Lalit Kant, an independent public health consultant. Kant who is the former Head of the Division of Epidemiology and Communicable Diseases of the Indian Council of Medical Research (ICMR) acknowledges that no vaccine is one hundred percent safe. “We have to look at the adverse reactions. A single manufacturer will not be able to provide all the vaccines that India needs and different states may need different vaccines,” Kant says.
Virologist Shahid Jameel, director of Trivedi School of Biosciences at Ashoka University in Sonepat, sees two major challenges in india's vaccine roll out. “The first challenge would be the capacity to deliver injectable vaccines. At the present capacity of 18 million doses annually, the delivery of 500 million doses to the 250 million priority list would be a serious challenge.”
Secondly, with the fast tracking of COVID-19 vaccines, there is an apprehension that safety could be compromised, Jameel says. “This fear should be dispelled via proper communication and transparency. There should be a proper public discussion of the vaccine rollout plan before we have approvals and licensing in India.”
Transportation of the vaccines across the length and breadth of the country could also be hamstrung with hurdles. The vaccines require an excellent cold chain management. Moderna’s vaccine needs minus 20 degrees celsius, and Pfizer/BioNTech’s vaccine requires minus 70 degrees celsius temperatures.
India’s present cold chain system has 85,634 equipment in about 28,947 cold chain points. Besides temperature, these equipment require mapping of air replenishment, humidity and external pathogen loads. Vaccines that require a temperature below -70 °C can be handled by deploying dry-ice in insulated carrier boxes. The monitoring tools should include temperature data-loggers, temperature sensitive labels (thermo-chromic inks) and location tracking; besides batch-wise details.
Pawanexh Kohli, former CEO of National Centre for Cold-chain Development (NCCD), stresses the need for strategy in managing the supply chain. “The reach can be widened by special vaccine trains and mobile refrigerated trucks.” The vaccines, Kohli says, should be used and replenished periodically. “We will need small vaccine holding fridges or a series of passive cooled holding boxes.”
Vaccines that need freezing will not work in India, according to Satyajit Rath, a former scientist at the National Institute of Immunology, New Delhi. Adenoviral vaccines like those of Oxford-AstraZeneca or Gamaleya, and protein vaccines like the Novavax one, which need only refrigeration, would be most suitable, he says. Besides, building a robust cold chain system, collection and disposal of medical waste like the used vials, syringes also need specific attention. Kohli suggests that instead of hospitals, vaccine centers should be created in convention halls, hotels, movie halls and schools that are currently vacant.
Trial designs, priority groups
Almost all COVID-19 vaccine trials are using approximately the same broad trial design. Rath, who is also a visiting professor at the Indian Institute of Science Education and Research (IISER), Pune, says one limitation is that they are all designed to look for protection against symptomatic COVID-19, and not specifically for protection against either severe COVID-19 illness, or against all the SARS-CoV-2 infection (including the asymptomatic).
“We know that these emergency-licensed vaccines do work but we don't know just how well they work, and how long to expect them to work,” says Rath.
The government will vaccinate priority groups in the first two phases – frontline workers and healthcare professionals in the first phase and emergency workers in the second. From the third phase onwards, people with co-morbidity will be given vaccines through registration on a monitoring app called CO-WIN created by the government for monitoring the process. The app will allow citizens to self-register for vaccination, monitor status and get a QR code-based electronic vaccination certificate.
“Given the limited number of doses available, identification of priority groups, and provision of vaccines to these groups will require a vibrant plan,” says bioethicist Anant Bhan. A strong pharmacovigilance system will also be needed to identify any safety concerns post-immunisation, Bhan says.