Explained: Why Covishield Has Been Excluded For EU Digital Green Pass

India's act of not consulting with the European Union when the latter conceived the Green Pass programme in January 2021 is to blame for Covishield not being on the list of vaccines approved for the EU's vaccine passport, according to Murali Neelakantan.

The Green Pass programme has been conceived by the EU wherein holders of the Digital Green Pass will be certified healthy and move freely in Schengen countries without COVID-19 screening and mandatory quarantines.

While Vaxzevria, the Oxford-AstraZeneca vaccine being sold in the EU, has been approved for vaccine passport, Covishield, which is the Oxford-AstraZeneca vaccine being manufactured in India by Serum Institute of India, has not been approved. The move has left thousands of Indians who were planning to travel to European countries for higher education and employment in a lurch.

However, neither the EU nor the European Medicines Agency is to be blamed for the scenario according to Neelakantan, Former Global General Counsel at Cipla and Glenmark.

"I do not have any sympathy for the Government. I have some sympathy on why we did not engage with the EU last year but in January, the EU announced that it was going to have a Green Pass programme, there was a widespread consultation on this. We had a chance to engage with them to understand how it will work. All the members of the EU had a discussion. Some outside the EU like Iceland, Liechtenstein, Switzerland also participated to understand how their citizens can move within the EU," Neelakantan told BOOM.

While Neelakantan believes that India could try negotiating with the EU and individual countries, Dr Shahid Jameel, Virologist and Director of the Trivedi School of Biosciences at the Ashoka University, holds the opinion that the available real-world data as well as the fact that the vaccines have been proven to stave of severe infection should be enough for the EU to come up with a solution even if temporary.

"Covishield has been given to about 280 plus million people in India. So that is a hell of a lot of data compared to what you do in a clinical trial. What you will not have is efficacy because that is done in a controlled trial," Dr Jameel told BOOM.

"But what you have is vaccine effectiveness which is real world data on vaccines. So, I think that data itself should stand," he added.

Edited excerpts follow

Vaxzevria is the made in Europe version of the vaccine and Covishield is the made in India version of the vaccine. Is there any difference?

Dr Shahid Jameel: For Covishield we do not know the efficacy because the bridging trials of Covishield have not really been published. I haven't seen any efficacy for Covishield. The only efficacy data I have seen has come for the AstraZeneca vaccine.

So according to Indian regulator, they were supposed to do a bridging trial, which I believe they have done but the results of that trial have not been published. What Covishield got in India was an emergency use approval based on the AstraZeneca vaccine results.

We use the term AstraZeneca and Covishield quite seamlessly? So, you are also painting out that therefore that is not the way to do it, right?

SJ: The EU passport is something that is very new. But the Indian regulators considered that data and gave the approval. So that is why in India, Covishield is still on emergency use approval. It doesn't have full approval in India yet. And Murali can maybe enlighten us better on that. That is a fact. But what we do have now from India, just like we have from the UK, is real world data for Covishield. And the real-world data looks as good as AstraZeneca looks in the UK. But strictly speaking, we do not have the efficacy.

By inference we know that the version that is available in India works as well as the version that is available internationally but there is no hard data to go with at this point. Murali, from a process point of view what happened here?

Murali Neelakantan: AstraZeneca when it applied for approval to the EMA, it listed the sites which were producing this vaccine. And those sites were in Switzerland, the UK, some sites in Europe, a site in China, South Korea, and the United States. So, at that time when it applied for approval, and produced the data to the EMA for the approval of the vaccine, there was no data from Serum Institute's facility that was submitted. Therefore, it was not listed as a site from which this vaccine can be produced and sold in the European Union. So that is the situation now.

That obviously opens another can of worms. First of all, who is the principal here, is it AstraZeneca or the Serum Institute? People are asking Serum Institute questions, and Serum Institute is a contract manufacturer for AstraZeneca, is that not, right?

MN: That is exactly right. And that is the reason why if Serum had no intention of selling these vaccines in the EU, it would not have any incentive to go and apply by itself for the approval of this drug in the EU. As far as I understand it, the license from AstraZeneca to the Serum Institute does not include Europe as a territory. So, Serum does not have a license from AstraZeneca to manufacture this vaccine to sell in the European Union. And therefore, may not have been considered as a necessity to even seek an authorisation. Why should it?

But the person who applies for these licenses is the person who owns the original patent. Am I right? Or can a Serum Institute, who is a manufacturer, also go and apply?

MN: If the manufacturer intends to market it, and sell it in the European Union then it would have applied for a license. In this case, since it never intended to, the license did not permit it to, it perhaps had no reason to go and apply for an authorisation in the European Union. So, AstraZeneca did not intend perhaps for Serum to manufacture a vaccine and be sold in the European Union. Therefore, again, AstraZeneca did not see any need to include the Serum manufacturing facility during the application for approval.

Is this what happens usually when any drug is also manufactured in India like we do have so many cases of drugs?

MN: There are two scenarios. The marketing authorisation could be held by one entity, it could be subcontracted for manufacture to India, but the authorisation is still held by, let us say, the European entity. That is one scenario.

The second scenario is the manufacturer intends to market this drug in the European Union, has rights to sell it in the EU, and therefore could also be the marketing authorisation owner, the MA holder, in this case. So, there are two scenarios possible.

Assuming that Serum Institute or AstraZeneca with Serum Institute go and apply to the EU saying that here is a drug that we may not sell in the EU, but we want approval so as to allow those vaccinated in India to travel to the EU. How long would that take in a normal situation?

MN: It depends on what data they have. So, if they have done a trial, they have batch records, the manufacturing records are there, the QA records are there, the testing process is there, protocol is there, that data is there.

Now do they have clinical data? Have they done enough clinical trials to say that this is the same or this is the same product? So, I do not know if they have enough data. And that process, there is no time limit for it. I suspect it could take a few months if they had applied for it and had all the data. But there is no way of saying, give it to me today and you can have it tomorrow. So, I do not know what data Serum has that is enough for a European dossier.

Dr Jameel, if you were to look back now at the last year and the way that data is being generated including on trials, what is your sense? Do you feel that we have sufficient data to understand how this vaccine is working or do you see gaps and if so, where do we fill them and how could we fill them?

SJ: Well, what we have is, Covishield has been given to about 280 plus million people in India. So that is a hell of a lot of data compared to what you do in a clinical trial. What you will not have is efficacy because that is done in a controlled trial.

But what you have is vaccine effectiveness which is real world data on vaccines. So, I think that data itself should stand but of course I am not aware of the legalities here. Just on the basis of that vaccine being given to 280 million people and showing reasonably good protection in the real world, it should qualify.

Going by what we have seen in the real world in the sheer number of people who have been given this jab, and the fact that it largely seems to be working, is that enough for countries to now say that ok, we have had some success with the vaccination programme. Not in proportion to the population but in proportion to the number of people who have been given this.

Now, the trouble here is that there are two kinds of data available at this point from India. But neither of them classifies vaccine data into Covishield or Covaxin. One is a study published by the Christian Medical College, Vellore which came out in the Mayo Clinic proceedings, which does not partition the data into Covishield or Covaxin.

They are simply saying that since 90% of the vaccine is Covishield and we did not have enough Covaxin recipients to really achieve statistical significance, therefore most of it is Covishield.

The other data which has just come out in the Indian Journal of Medical Research is the vaccination of the people in the Tamil Nadu Police Department. And there the end point is mortality. And that shows that people who have not taken the vaccine have a certain level of mortality, those who have taken one dose have significantly less, and those who have taken second is much much more less (sic).

So, the risk is one for those who have not taken the vaccine, the risk is.05 or twenty times less but that is measuring mortality. Again, this study does not say whether people got Covaxin or Covishield. So that is the real-world data available from India.

The real-world data available from Public Health England and from Imperial College and Warwick and several other places in the UK are all with AstraZeneca and not with Covishield. So that is the technicality, I guess.

Dr Jameel, if you were sitting outside India, in Europe, and looking at this picture that you have just painted of India, would you say that it would be safe to allow people to travel from India into Europe?

SJ: I would because in the real world that vaccine is protecting. I would. But then if you were to say, would you allow on the basis of this data for Covishield to be sold in the EU, then that is a whole different ball game.

In the case of vaccines, but definitely things have been sped up. In the real world, given that this is how the vaccine is rolling out given the fact that some things have to come back to some degree of normalcy, could regulatory organisations move faster for granting approvals or for giving a certain pass when it comes for a specific approval in the case of the EMA?

MN: I do not think that it is likely that the EMA will now look at this data. I think there are two other likely scenarios. One is the EU, rather than the EMA, which deals with the free movement of people, will advise member countries that in addition to the four vaccines that are approved by the EMA, all vaccines approved by the WHO will be treated as if they are approved by the EMA not for the purposes of authorising it for sale but the for the purposes of travel.

So, this is not an EMA approval of the vaccine. This is just the EU saying that those who have been vaccinated with the vaccines approved by the WHO will be treated on par with those who have been vaccinated by the vaccines approved by the EMA.

So, they are two separate issues. And I think this is a more likely pathway than the EMA approving the vaccines approved by the WHO. I think that is one scenario that is possible.

The other scenario could be, and do not forget it is not just India, we are talking about Covishield in about 90 other countries under the COVAX programme. We have also shipped it to Australia, the UK and Canada. So, it is not just an Indian problem. We have people potentially from all over the world affected by this restriction on travel.

I think the second scenario could be that each of the member countries decides for itself that it will treat certain vaccines approved by the WHO on par with the vaccines approved by the EMA for the purposes of this travel.

I think the second is more likely because countries like Hungary have had Sputnik V and Sinopharm, neither of which is approved by the EMA. So, if they want their own citizens to be able to travel within the EU they will have to agree with the EU that Sinopharm's vaccine and Sputnik V are to be treated on par. So, it is in the interest of Hungary to them lobby to the rest of Europe to find this as the way forward.

Are you seeing anything discriminatory in this so far? In that, it is being manufactured in India, we maybe do not have so much oversight on those facilities and therefore we are not sure. That seems to be the suspicion in some cases.

MN: Not at all. As I said nobody is picking on India. The Indian facility was not ever considered, no data was considered, no application was made. You cannot say that somebody has been excluded, if you have not even knocked on the door yet.

So, this is not an issue of racism, there is a rule book. You should have applied for approval or authorisation in this case and you did not. So, how can a EMA authority grant you an approval when you have not even applied for it, you have not presented a dossier.

And the reason that it was not applied is that no one thought of it?

MN: I am sympathetic to the fact that nobody thought of it last year. I am less sympathetic of the fact that nobody thought of it in January. When the Green Pass programme was conceived in January, it was open for consultation. We should have engaged with the EU knowing that a lot of Indian citizens will want to travel to the EU. We should have worked with the other countries which are going to receive Covishield to present a United Front to the EU and say 'you are going to have a Green Pass system; how can we participate in it?'

Countries outside the EU have done it. Iceland, Liechtenstein, Switzerland have done it and Norway is doing it. So, there are countries outside of the EU which have understood that their citizens need to be travelling to the EU and have engaged with the EU. They have built an IT system, integrated it and tested it with the EU so that you can now have the process working on the first of July.

So, I do not have any sympathy for the Government. I have some sympathy on why we did not engage with the EU last year but in January the EU announced that it was going to have a Green Pass programme, there was a widespread consultation on this. We had a chance to engage with them to understand how it will work. All the members of the EU had a discussion. Some outside the EU like Iceland, Liechtenstein, Switzerland also participated to understand how is it that their citizens can move within the EU.

And so, at that time the Indian Government with the other nations of the world who will be vaccinated with Covishield — the US, Australia and the UK could all have had this discussion with the EU saying, 'this is an issue that is not only for the EU; it affects a significant part of the world. A 100 countries around the world. So how can we work with you at an early stage, so that when the Green Pass system comes into effect on the first of July, we are already in it?'

And these discussions are led by whom in a country?

MN: The European Commission starts off on this and each of the countries is discussing this because the systems are not set up by the EU. The certificate itself is issued by the National Authorities. So, they all have to build systems to work together with the EU.