Medics at a vaccination centre in Patna. Photo: Moniza Hafizee
India’s vaccination COVID-19 formally began today, with Prime Minister Narendra Modi flagging off the behemoth effort via video at 11 am.
On January 3, the country’s drug regulator approved two COVID-19 vaccine candidates for distribution, named Covaxin and Covishield. In the first phase of the vaccination drive, the government plans to inoculate 3 crore frontline workers, by July 2021.
To this end, the government has purchased 5.5 million doses of Covaxin from its maker, Bharat Biotech, and 11 million doses of Covishield from the Serum Institute of India. The following Q&A breaks down what we do and don’t know about different aspects of the drive.
What did the regulator approve Covaxin and Covishield for?
Both Covaxin and Covishield are two-dose vaccines: one dose followed by a booster a stipulated amount of time later. And the inter-dose period for both vaccine candidates is 28 days.
How do the vaccine candidates work?
Covaxin contains an inactive whole virus – that is, an entire virus (as opposed to specific parts of it) whose ability to replicate has been destroyed in the lab is exposed to the body’s immune system.
In Covishield’s case, researchers from the University of Oxford took a respiratory virus known to affect chimpanzees, destroyed its ability to replicate and tweaked its genetic material to produce the spike protein of the novel coronavirus. This way, the respiratory virus becomes a tiny factory that, when injected into the body, produces the spike protein that then provokes the immune system.
At what temperatures do these candidates have to be stored?
Both vaccine candidates can be stored at 2-8º C.
How are they being distributed?
India’s COVID-19 vaccination drive is divided into multiple phases. In the first phase, frontline workers, including healthcare workers, and people at risk of death by COVID-19 – the elderly and those with comorbidities – will be inoculated, in that order.
Union health secretary Rajesh Bhushan has said that the government India will be using a network of 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 to store the vaccine candidates.
According to one estimate, a 225-litre medical refrigerator can store up to 60,000 vials – where each vial contains one dose of a vaccine candidate.
How can people avail the vaccine candidates?
For now, the vaccine candidates are available only to frontline and healthcare workers, especially those registered on the government’s Co-WIN platform. According to Bhushan: “There are five modules in Co-WIN app – administrator module, registration module, vaccination module, beneficiary acknowledgment module and report module.”
According to Dr Samiran Panda, a scientist at the Indian Council of Medical Research (ICMR), the state government has set up designated booths where eligible people can go to be inoculated.
Each such person will receive a message 24 hours in advance, inviting them to be inoculated. If they agree, they have to visit the booth, where they will be presented with factsheets for both vaccine candidates and be guided through the details of their inoculation.
Once they are ready, they will have to sign a consent form and proceed to inoculation.
What information will the factsheets contain?
Such factsheets typically contain information about the disease-causing virus (in this case SARS-CoV-2), the disease (COVID-19) and its common effects, the checks to which the vaccine candidate has already been subjected, what we still don’t know about the candidate, potential side effects, and the recipient’s rights and entitlements from the vaccine-maker (Serum Institute of India or Bharat Biotech) and the government.
Can the recipient choose which vaccine candidate to receive?
No, the recipient cannot choose between Covaxin and Covishield. The government has designated different vaccine candidates for different booths around every state. While the recipient can consent or not to being inoculated, the choice is beyond them.
Why is there no choice?
From the government’s point of view, the contention is that both vaccine candidates have been approved using a common regulatory framework, so giving recipients a choice at this phase may lead to supply issues that the government would rather not focus on now.
This said, the government has also stopped short of explaining “the criteria adopted to determine which vaccine goes where amid the constraint that the two-dose vaccines cannot be interchanged,” The Telegraph reported on January 15.
However, experts have contested this argument, saying Serum Institute seems capable of producing all the doses required for the government to complete the first vaccination phase without having to depend on Covaxin. So, they continue, the government could have allowed Bharat Biotech to complete phase 3 trials for Covaxin, in 12 weeks or so, and in the meantime distribute Covishield alone.
What if a recipient doesn’t wish to receive one of the vaccine candidates?
There have been scattered, but nonetheless significant, reports of vaccine hesitancy among healthcare workers.
Thus far, the government has been disinclined to offer options. Government officials have gone a step ahead, citing the pandemic’s unprecedented nature to push through the approval for Covaxin despite the fact that its phase 3 trials had barely begun at the time of approval.
In his previous comments to The Wire Science, Dr Samiran Panda had indicated that when the two vaccine candidates are later available to the general population, people will have the option to choose.
What happens after a recipient is inoculated?
Once a recipient has received a dose of a vaccine candidate, they will be monitored at the facility to make sure they don’t develop a severe allergic reaction (anaphylactic shock). After doctors at the facility have made sure, the recipient can leave.
N.K. Arora, head of the operations research group of the ICMR’s National COVID-19 Task Force, told The Hindu last week:
India has an existing vaccine safety surveillance mechanism called AEFI (Adverse Events Following Immunisation) surveillance. It comprises a national secretariat under the Universal Immunisation Programme (UIP), including doctors, data specialists and public health specialists. The vaccine safety surveillance network extends up to every district where a panel of doctors and health workers monitor events of concern after getting any vaccine, investigate and report to state and national level.
Arora later added:
Right now, we are anticipating — theoretically — events of concern that might possibly happen after immunisation drive. The AEFI members will be trained to look for any adverse events before we start the immunisation process. Adverse event surveillance is being established to actively seek these events across designated health facilities across the country. Additionally, there are around 300 medical colleges and tertiary care hospitals across the country that have adverse drug reaction monitoring centres which also report adverse events after vaccines along with drugs.
What is “clinical trial mode”?
The drug regulator approved Covaxin for “restricted emergency use” in “clinical trial mode”. According to Dr Samiran Panda, this means whoever receives doses of Covaxin will be treated as a participant in a single-arm clinical trial.
That is, once doctors have administered the vaccine candidate, they will monitor the recipient as if the latter was a participant in a clinical trial: with regular follow-up calls as well as entitling them to free care and financial compensation in case they develop a severe adverse event directly related to vaccination.
Economic Times reported that in case recipients wish to report any adverse reactions, they may call the following 247 toll-free number: +91-1800-1200124.
Former Union health secretary J.V.R. Prasar Rao did tell The Quint: “Everyone who is getting the vaccine will be in the government records. But for those who get Covaxin, if they are observed under clinical trial mode, they will have to be closely monitored for adverse events.”
According to Dr Panda, “clinical trial mode” differs in three key ways from a regular phase 3 clinical trial:
- The results won’t be published in a peer-reviewed journal
- The trial won’t have a placebo arm – i.e. a group of participants who receive a placebo
- “Clinical trial mode” is as such not codified in any law or regulation
Can recipients mix and match their doses?
No. If a recipient’s first dose is Covaxin, the second dose also has to be Covaxin, and that too after the stipulated inter-dose period (28 days); so also for Covishield.
This condition is a result of how the two vaccine candidates have been trialled: with two doses, with both doses of the same composition. Getting one dose of Covaxin then switching to Covishield would be akin to violating the warranty conditions.
What happens if a recipient misses the deadline to receive the second dose?
The most advisable thing to do would be to consult your doctor, and proceed with their guidance.
What happens if a recipient develops a severe adverse event (SAE) following inoculation?
Dr Samiran Panda has said that the procedure to investigate an SAE in “clinical trial mode” will be the same as that used for regular clinical trials.
An adverse effect is qualified as ‘severe’ if one of the following occurs (quoted verbatim from Shreya Dasgupta’s report for The Wire Science):
… a patient or participant dies during a trial; the participant gets hospitalised whereas the study did not involve any hospital stay to begin with; the participant’s hospital stay gets prolonged (if the study was being conducted on in-patients); the participant suffers from a chronic or life-threatening disability; or a participant gives birth to a child with congenital defects.
There is a predetermined process to evaluate SAEs.
First, the trial’s principal investigator has to report the SAE to the sponsor (Bharat Biotech or Serum Institute), the drug regulator, and the ethics committee of the institute where the recipient in question was inoculated.
Second, the principal investigator uses the patient’s medical history, test reports and doctors’ opinions to assess whether the SAE could have been caused by the vaccine candidate.
Third, the principal investigator sends their assessment to the drug regulator – i.e. the Drug Controller General of India (DCGI), Dr V.G. Somani – and the chairperson of the ethics committee and the senior-most person at the institution where the trial is being conducted. This has to happen within 14 days of the SAE.
Fourth, the ethics committee will deliberate on the reports and notes to arrive at the final verdict. As Shreya Dasgupta reported, “If there’s any doubt about whether the trial could have caused the illness or death, and if a link can’t be ruled out, some ethics committees tend to give the affected participant the benefit of the doubt, several experts told The Wire Science.”
If committee members determine that the SAE was caused by the vaccine candidate, it will inform the trial sponsor, the DCGI and the principal investigator. The committee will also determine the financial compensation that the patient is owed, based on a formula specified in the New Drugs and Clinical Trials Rules 2019.
In parallel, the sponsor may also constitute a data and safety monitoring board (DSMB), which must be independent of the sponsor as well as other bodies. The DSMB acts as an advisor to the sponsor: its members regularly review the trial even if there are no SAEs, weigh in on SAE-related decisions and even recommend that the sponsor halt the trial if there are significant breaches of protocols or if an SAE warrants it.
Will all frontline workers be inoculated by July?
No. There are exceptions. For example, according to Economic Times, Covishield is disallowed for people with compromised immune systems, with blood disorders, who are pregnant or are lactating, and/or have previously experienced a severe allergic reaction to some or all of Covishield’s ingredients (as specified in the factsheet).
For the people in this excepted group, only a vaccine candidate that has also been tested for their respective conditions can be used to inoculate them.
Do recipients have to pay to be inoculated?
No. The government is offered the vaccine candidates for free in the first phase of the national vaccination drive.
Prime Minister Narendra Modi has said the cost of purchasing the doses from Serum Institute and Bharat Biotech will be covered by money from the PM CARES fund.