The TLDR: The Indian government started the year with a series of big bang moves. Multiple cities held vaccine dry runs. Soon after, regulatory authorities approved two ‘Made in India’ vaccine candidates: Covishield, which is Serum Institute’s version of the Oxford vaccine; and the fully shuddh desi Covaxin developed by Bharat Biotech. The shockingly hasty Covaxin approval, however, has raised more worries than hopes. 

A flurry of big moves

Gearing up: Last week, the government conducted a series of practice runs—116 districts across 259 sites—to test the country’s vaccine-readiness. The Health Minister says the cold storage chain has been upgraded and ready to distribute the vaccines the moment they are rolled out.

The plan: In the first phase—between now and July—300 million Indians will get the vaccine. The target groups: 30 million healthcare and frontline workers and 270 million people who are either above the age of 50 or suffer from serious underlying conditions. The government will soon roll out the Co-WIN app and website. People who qualify will have to register their details, and wait for the call. More on that here. 

The approval process: The Central Drugs Standard Control Organisation (CDSCO) appointed a Subject Expert Committee (which is exactly what it sounds like). Vaccine manufacturers submitted their trial data to this committee, which then sent its recommendations to the Drugs Controller General of India: 

The Oxford approval: 

• On January 1, the panel approved Serum Institute of India’s version of the Oxford vaccine for “restricted emergency use.” 
• Developed by AstraZeneca in collaboration with Oxford University (our Oxford explainer is here), it’s manufactured by Pune-based Serum which sells to middle and lower income nations. 
• The company already has 50 million doses in stock, and most of these will be distributed in India. 

Key point to note: According to Serum, it has been banned from exporting the vaccine—and from selling it to individual consumers… for now. And it isn’t clear when the government will okay private sales of vaccines—be it Oxford or any other kind.

The Covaxin approval: This vaccine has been developed by Bharat Biotech in partnership with the government-run National Institute of Virology (our Covaxin explainer is here). Bharat Biotech says it can supply around 150 million doses a year at current capacity and scale it up to 500 million doses. On January 2, the panel greenlit Covaxin for, er, this: 

“Grant of permission for restricted use in emergency situation in public interest as an abundant precaution, in clinical trial mode, specially in the context of infection by mutant strains.”

Don’t know what that means? Well, neither do the experts, as one made plain on NDTV, calling the language “new, and not something that is based in the regulations.” Also this: a mass vaccination campaign cannot be conducted in “clinical trial mode”—which requires close supervision of participants. And it isn’t clear who will track its results:  

“Will the companies evaluate efficacy? Or will it be done by the health ministry or its agencies? There is no clarity on this. What protocols will be used to evaluate efficacy?”

What’s going on here?

An attempt to fast-forward the approval process—especially in the case of Covaxin. To explain that, let’s first lay out how vaccine trials work:

Stage 1: The vaccine is tested on animals to ensure it is safe, and triggers an immune response—i.e. triggers the production of antibodies and/or protective T cells.

Stage 2: The vaccine is tested on a small sample of human participants—again to check for safety and immune response. 

Stage 3: The vaccine is tested on large numbers of participants with double blind testing. This means half of them receive a placebo, while the other half receive the vaccine. But neither the participant nor the doctor knows who is getting what. This stage determines efficacy—i.e. how good is the vaccine in protecting the body against a Covid infection. 

A vaccine is typically approved only after Stage 3 data is submitted to regulatory authorities—and also published in peer-reviewed medical journals. 

Ok, got it! So what’s with Covaxin?

Bharat Biotech has only conducted Stage 1 and 2 trials and published that data. Here’s what its Stage 3 timeline looked like:

• November 9: Received permission to conduct Stage 3 trials with 25,800 volunteers.
• November 16: Began recruiting volunteers.
• December 22: Had only recruited 13,000 volunteers—seriously short of its target.
• January 2: Bharat Biotech says it has managed to get that number up to 23,000.

But here’s the problem with that timeline, as one healthcare expert explains: 

• Like other Covid vaccines, Covaxin is a two-jab regimen—with the second injection administered 28 days after the first. 
• If the first jab was given on November 16, then the second could have only been administered mid-December. 
• Now investigators start tracking data on the vaccine’s efficacy 42 days after the first injection—which is December 28.
• And yet, the vaccine was cleared for use on January 2. 

So what data did they use for approval? 

The government has not released any information on the data used to greenlight the vaccines—which is worrying. An unnamed source told The Print:

“The company has submitted immunogenicity data for 10,000 people after they have received the first dose of the vaccine and for 10,000 people after two doses. The SEC has reviewed the data and has taken a call to give conditional approval.”

Given the timelines above, the claim is astonishing and perhaps revealing. ‘Immunogenicity’ is a fancy word that measures a body’s immune response, typically a Stage 2 concern. It says absolutely nothing about the vaccine’s efficacy which is critical in Stage 3. 

Most likely answer: Covaxin was approved purely on the basis of its Stage 2 data—which involved only 755 volunteers. The Drug Controller General of India also only referenced “safety and robust immune response” of Stage 1 and 2 trials when justifying its decision.

Why did they do it? 

No one has officially come out to bat for Covaxin. But here are some of the rationales offered by (mostly unnamed) government experts:

• One: “The pandemic has given rise to extraordinary circumstances that require extraordinary responses.”
• Two: Stage 2 data shows that it “produces high levels of antibodies that promise an immune response of six to 12 months” and triggers T cells which offer long-term protection.
• Three: The scary new strain shows mutations in the spike protein of the virus (explained here)—which is targeted by most other vaccines. OTOH, Covaxin is made from the inactivated whole virus and will target different proteins—and may have a better chance against mutations.

However, the advocacy organisation, All India Drug Action Network (AIDAN) isn’t impressed by their logic:

"It is not clear if there is any scientific basis to claim that COVAXIN will be effective in the ‘context of infection by mutant strains’ when its efficacy has not been established and is currently unknown against any strain of the virus.”

And most leading experts—including the highly respected Dr Gagandeep Kang—strongly agree.

But the Oxford vaccine is fine, right?

Yes, in that AstraZeneca has conducted massive stage 3 trials in the UK and Brazil— and all that data (however messy) has been rigorously vetted by medical experts and UK regulators. But it is important to note a few distinctions:

• Serum’s Covishield is the equivalent of but not the same as the Oxford vaccine. 
• Serum is currently conducting a limited “bridging” Stage 2/3 trial with 1,600 participants in India. Bridging studies look at safety and immune response to prove that the version being contract manufactured is the same as the original. It does not measure efficacy. No one has seen any results from this trial.
• The approval is actually based on “the nod by the UK regulator and data from a phase 2 trial on 100 volunteers in India, antibody levels generated in the volunteers in response to the vaccine, and safety data from phase-1 studies.” 

But yes, all things considered, there is far less reason to worry about its approval.

The bottomline: We wonder how many netas will line up to get the Covaxin jab as opposed to the Oxford vaccine.

Reading list

• The Print has a good overview of Covaxin’s issues
• The Telegraph has more on the issues with Covaxin’s ‘clinical trial’ guideline.
• Deccan Herald explains how you can register to be vaccinated.
• Indian Express explains what to expect over the next 6-8 months.
• The Wire offers a well-reasoned critique of the rush to approve vaccines. 
• Dr Sumanth Raman in New Indian Express and Jacob John in The Hindu point out that India has never had a sound vaccine game plan.
• The Hindu has more on when you can expect to buy a vaccine of your choice.
• This isn’t the first time the government has tried to push through Covaxin without proper testing. Our explainer has details of the August 15 debacle.
• We also explained the Oxford vaccine’s efficacy data.