EU’s ‘Green Pass’ Plan Leaves Out Covishield, Serum Didn’t Apply for Approval

Covishield is derived from AstraZeneca’s shot, called Vaxzevria outside India. As such, virologist Shahid Jameel told The Wire Science, Vaxzevria and Covishield are qualitatively similar.

However, Serum Institute, Pune, which makes Covishield in India with a license from AstraZeneca, didn’t apply to have the vaccine approved by the European Medicines Agency (EMA).

The EMA confirmed to The Wire Science it has thus far not received an approval application for Covishield. An email to Serum Institute hadn’t elicited a response at the time of publication.

However, Serum Institute CEO Adar Poonawala had said in September last year that the company and the Government of India had “committed to reserve half the company’s stock … for India, and to supply half to low-income nations through GAVI, a funder of immunisations for low-income nations”. So Serum Institute didn’t have to apply for the EMA’s approval.

Covishield is an important part of the international COVAX alliance. Vaccines in this initiative need to have the WHO’s approval. On the other hand, the ‘Green Pass’ initiative is based on the EMA’s approval.

Covishield and Vaxzevria

The EMA regulates drugs and medical products in European nations. The nations’ ‘vaccine passport’ programme, formally called the ‘Green Pass’, has approved only four vaccines, according to Economic Times. They are Vaxzevria (Oxford-AstraZeneca), Comirnaty (Pfizer-BioNTech), Spikevax (Moderna) and Janssen-Johnson & Johnson.

Iceland had earlier reopened its borders to international travellers after vaccinating most of its tiny population of 3.6 lakh (2019), allowing anyone who had received a WHO-approved vaccine to enter the island country. Covishield has the WHO’s approval. However, the ‘Green Pass’ programme only accommodates EMA-approved vaccines.

Doses of the Oxford-AstraZeneca COVID-19 vaccine – Vaxzevria – are produced largely by three firms: Serum Institute of India, S.K. Biosciences in South Korea and AstraZeneca’s four manufacturing sites.

WHO has given an emergency nod to eight COVID-19 vaccines so far, including AstraZeneca’s Vaxzevria and the corresponding ‘versions’ of Serum Institute and S.K. Biosciences. India’s other major COVID-19 vaccine, Covaxin, has been approved neither by the WHO nor the EMA.

Jameel, who is director of the Trivedi School of Biosciences, Ashoka University, Haryana, told The Wire Science that Vaxzevria and Covishield are biologically equivalent despite being produced by different manufacturers. “They are just made at different locations using the same manufacturing and quality assurance and quality control protocols” he said.

In November 2020, Serum Institute had launched a clinical trial to test the safety of Covishield and compare its immunogenicity with AstraZeneca’s Vaxzevria, with 1,600 trial participants. The results from this trial are yet to be published. However, the data on immunogenicity, available with India’s Central Drug Standards Control Organisation, suggested that Vaxzevria and Covishield generate a comparable level of antibodies. (Note that the trial predates the rise of the delta variant in India.)

The study recruited around 1,600 participants. Its administrators assigned 1,200 to a group that they would follow up to assess the vaccine’s safety. The remaining 400 were assigned to a group to assess the vaccine’s immunogenicity. The latter were further divided – 300 received Covishield and 100 received Vaxzevria.

The antibody titre against the spike protein of the novel coronavirus was 9,988.1 among those who received Covishield and 6,738.5 among those who received Vaxzeria at 29 days after receiving the first dose, and up to 33,331.6 and 33,263.6 after 57 days. Note that this data is based only on a fourth of the trial’s participants. Serum Institute has not yet published the complete data after 57 days nor data pertaining to the safety cohort.

In a February 2021 assessment of Covishield, after Serum Institute filed an application for ’emergency use’ approval, experts of the WHO also noted that the various parameters of the immune response induced by the two vaccines – Covishield and Vaxzevria – were comparable. Interestingly, they admitted Serum Institute’s application after considering data from the Vaxzevria trial as well.

Receiving applications

Each major drug-regulating body, like the EMA or India’s Drug Controller General, receives applications from manufacturers for approval. Different manufacturers of the same vaccine need to submit separate applications. One reason for this is that the approval process involves an inspection of the manufacturing facilities.

For example, earlier last week, an investigation team from the WHO visited Ufa in southern Russia, where some of the manufacturing facilities of the country’s Sputnik V vaccine are located. The investigators reported issues at one plant that Russia had said had been resolved. Until all issues are resolved, the approval may not be granted.

Bharat Biotech, the maker of Covaxin, had run into similar trouble in Brazil, whose health authorities had flagged issues at manufacturing facilities in India. Though the issue was later resolved, the authorities hadn’t disallowed the company’s overall application itself.

Murali Neelakantan, principal lawyer at amicus and the former global general counsel at Cipla, said the EMA had approved each of AstraZeneca’s manufacturing sites that would make Vaxzevria.

“The AstraZeneca website lists sites in South Korea, China, Netherlands, the UK, Belgium and the US. Serum Institute should explain why it does not feature here,” he said. “Was it because SII didn’t have a license from AZ to sell in the EU? Was the issue of vaccine certificates not considered?”

Following the public backlash about Covishield’s exclusion from the ‘Green Pass’, Serum Institute CEO Adar Poonawalla tweeted on June 28: “I … hope to resolve this matter soon, both with regulators and at a diplomatic level with countries.”

I realise that a lot of Indians who have taken COVISHIELD are facing issues with travel to the E.U., I assure everyone, I have taken this up at the highest levels and hope to resolve this matter soon, both with regulators and at a diplomatic level with countries.

— Adar Poonawalla (@adarpoonawalla) June 28, 2021

Easing restrictions

The emergence of new variants of the virus that causes COVID-19 – but especially the WHO-recognised ‘variants of concern’, recently dubbed alpha, beta, gamma and delta – has significantly restricted international travel. While the rules for entry differ across countries, travellers’ vaccination status has a significant role to play in easing travel.

For example, there are two two different levels of restrictions for passengers travelling from India to France. All travellers are required to produce a negative RT-PCR report at the point of boarding and will be tested again once they reach France. Those who have been vaccinated will have to “pledge to self-isolate for seven days”. Those who have not been vaccinated will have to undergo “mandatory 10-day quarantine supervised by security forces”.

France only considers EMA-approved vaccines. And since none of the vaccines approved for use in India – Covaxin, Covishield and Sputnik V – have the EMA’s approval, even vaccinated Indians will be considered to be “unvaccinated”, according to the French government’s rules. The situation is the same in Germany.

In fact, with the ‘Green Pass’ programme, scheduled to launch from July 1, this will be the case in all European Union nations.

With inputs from Vasudevan Mukunth. This article was updated at 1:16 pm on June 28, 2021, to include details of Serum Institute’s bridging trial in India and Murali Neelakantan’s quotes.