So at what point did you recognise that you were going to need to get a fairly large pharmaceutical company on board too,
to get the scale up to the scale that it would need to be to provide enough doses to essentially the world?
Good question. I personally.
I think we were all figuring out how to do this and just how far the university was would be able to proceed itself.
And many people would have said that a university couldn't do a pivotal Phase three trial very rapidly and efficiently on its own.
And it proved that we could in the end and virtually everybody would have said it
wouldn't be possible to do large scale manufacturing for the university or a,
you know, a small single purpose spin out from the university, which was something that at least some of us considered.
It's not it's not just the manufacturing is it's it's you've got regulation to deal with.
You've got distribution. You've got it's more than just making it.
Yeah, absolutely. But the the a lot of functions in the global pharma industry are outsourced.
You know, there are there are consultancies, the regulatory affairs manufacturing is often outsourced to contract manufacturers.
And indeed, that's what has happened. Most of the manufacturing is not.
None of the manufacturing virtually has actually been done in AstraZeneca facilities.
And so one one possibility that some of us entertained, as I said, was the idea of a single post,
single purpose university spin out company, obviously, with very heavy government backing.
And I think for some of us who were, you know, interested in global health thought I'd had some attraction.
And also we there was the question of we were working, we had a memorandum of understanding or something,
you know, a preliminary agreement with the Serum Institute of India from March 2020.
And so I think there was a there was a question in my mind,
and I don't think I was the only one as to whether this could be done without a large, you know, Western pharmaceutical company.
Paul I think in retrospect, the answer is no, it couldn't have been done.
So I think the decision to partner was, was right on the, you know, the drive towards the.
Large part of that came from John Bell. And what the AEC as a partner brought in.
And that in the end really was the. Massive bandwidth needed to do the coordination of multiple regulatory submissions globally very,
very quickly, and also to coordinate the very large number of manufacturing sites.
I don't think anything other than a multinational Western pharma company could have
managed that and indeed I think it was quite challenging even for AstraZeneca.
You know, they're not the biggest of the multinational pharma companies and they have only one licensed vaccine product.
They did a great job. They continue to be through the steps of how how they got to that point.
Yeah. So March 2020, I don't think there really was a plan.
You know, we had Adrian had the Hill and set up this memorandum of understanding with the services of India.
But Top Brass University wasn't really yet engaged in thinking this was, you know, a real Goa that needed a partner rapidly.
April That changed. And clearly the decision had been taken by John Bell,
and it was working closely with the Vice Chancellor and, and Gavin Scruton and Oxford University Innovation.
And a decision had been taken that we did need a large pharma partner.
And it's in the public domain that I spoke initially with Merck.
And that came very close to an agreement.
I mean, one of the. The university had a major priority for the university, and the negotiations was.
Equitable access.
Very early on, a public pledge had been made that none of the universities innovations would be licensed exclusive, licensed exclusively.
And it wasn't possible for university to find a partner that was willing to accept a non-exclusive license for the vaccine.
And so if we were going to be locked into one partner,
it was clearly absolutely critical that they were going to do a good job in terms of rapid and efficient submission of,
you know, regulatory filings and and pulling the clinical data together to, you know,
actually get the vaccine licensed and alongside the manufacturer related data.
It was important that they share the university vision on pricing, and there was some discussion about exactly what that should be.
But the really low pricing was a was a very high priority.
And then there was a question about the degree of commitment and ambition to large volume manufacturing,
and in particular manufacturing with a view of supplying low and middle income countries LMI sees.
And. Mm hmm.
One of the stumbling blocks with with Merck, really,
was that they did not appear willing to commit to a manufacturing plan of the scale and ambition that we had in mind.
And they didn't know, from what I remember, appear enthusiastic about, you know, working with the Serum Institute of India, you know,
to whom we'd already begun transferring the know how on how to make the vaccine and who were the,
you know, the world's biggest vaccine manufacturer by volume. So.
A discussion then started with AstraZeneca and.
Again, the you know, it had to be global exclusive.
They would only entertain the idea of a global exclusive license.
One of the reasons being concern about is possible variability of quality of the
product if it was made in different places and not under a centralised control.
But I don't know. I think there was a genuine difference fortitude from A-Z as compared to me,
but I suspect there was also some increase in understanding on the university
side of what we what our priorities should be and what we needed to negotiate.
And by the time of discussions with AstraZeneca, what I was I was not in the room for the discussions,
but at least I was having discussions with John Bell and Gavin about, you know,
what, what might be important to negotiate for with respect to manufacturing and.
And also the fact that commitments on volume of manufacturing at risk ahead of a clinical trial result were potentially,
you know, the most important thing in terms of active access rather than the price.
You know, the price doesn't matter if there isn't any vaccine to distribute.
And ah, I remember that.
You know, trying to make the case that actually the. You know, this vaccine's major contribution was probably going to be about speed.
You know, it may not turn out to be the very best vaccine in the long run.
It would be a bit surprising if it did.
You know, if everyone if the rest of the world kept on investing and researching and nobody came up with anything better.
But. It's we were in a position to be ready first or very close to first early on.
And so not commitment to manufacture very large volumes of the vaccine at financial risk ahead of clinical trial results was really important.
And so was the willingness to, you know, work with partners that.
They had the capability to do that and be out of business model,
which was about supplying Alamo CS and really not mean Serum Institute of India and also that I'd started work with
which she biologics and in China which had very large volume capability and more more contract manufacturing you know,
more capacity to bring volume of bioreactors on line.
But either we she or serum learn either Merck or AstraZeneca had in-house.
So willingness to partner was really important and things move very rapidly in the AstraZeneca negotiation.
It was, but I think badly more than a week between initial contact and the being, you know,
heads of terms which was essentially saying we are going to partner, but who's going to be?
And that was about April the 30th was had two terms, I think.
And then there was a two week formal negotiation period which went out the 15th of May.
But really it was practically a done deal by the time of the heads of terms and so so in in the week between preceding that,
things move very rapidly and we couldn't get a Z to commit firmly in the period that they would be willing to work with the Serum Institute of India,
which was fair because, you know, they had no experience of working with them.
They had no idea, you know, what their quality of operations manufacturing were, were like, whether they could do business with them.
But we did. The university did manage to get wording in the agreements about making very best efforts to supply analyses and to work with partners,
including the services of India, to do so.
But I think the deal we had with ICI had it in.
It sort of crystallised what by that point was it?
It was clear in our minds that that partnership was important.
That ended up represented on paper. It ended up clear to AstraZeneca the.
Those of us leading the program in the university that was very important to us and for us to be happy and willing to to,
you know, get you know, can I need you to.
Exactly, exactly. Exactly. Yeah.
And I think also, genuinely, AstraZeneca did the senior leadership in AstraZeneca genuinely did have a vision,
a positive, you know, remarkable willingness to share the vision of a vaccine for the world.
I think they genuinely did have time. And I I'm not sure that we saw a lot.
Ethos from from Cohanim. Anyone else?
So I think the spirit with which they approached it was very positive from the beginning.
And so we had this idea of terms in place of around about the 30th of April, and things then proceeded very rapidly.
I think really in in parallel with the negotiations to finalise the deal.
You know, we were already getting into fairly detailed technical discussions with the AC manufacturing team about what they would need to do.
And you were still working in parallel with Paul and Paul?
Yeah. And Oxford Medical and the other companies that you've been talking to that was just in relation to the clinical trial, was it?
No, no, no, no. So so what happened to Paul was the first proof of concept of manufacturing at a, you know, commercially viable scale.
Okay. 200 litres. And but that didn't actually get used.
That wasn't going to get used, right? No. But it was proving that the process could work.
Yeah. It was the process that was designed for large scale, you know, non clinical trial supply,
but just executed outside of a clean room, you know, in an experimental lab.
Yeah. And Cobra Biologics.
And Alex. And Alex. The Biomedical Biomedica with the promise of the UK government funding,
which was I don't know to what extent that was tied in because obviously we all were aware of what was going on in the negotiations with Merck and AC.
But the impression I had was certainly that the funding would have come anyway.
You know, the fact that actually the task force wanted us to get on with the manufacturing, whoever we were going to partner with.
So all of that worked as set up for commercial scale manufacturing to supply the UK.
And similarly the the technology transfer to Russia and China and Serum Institute of India for commercial scale manufacturing.
That was all happening in parallel with the negotiations and you know, well advanced before AstraZeneca joined us.
Something quite important.
Was that we had actually shipped the cells used to make the manufacture to the Serum Institute of India.
Surely before the agreement with AstraZeneca.
And that was because growing those cells and making a frozen bank of them with which future batches of vaccine could be made.
We expected that to be the the rate limiting thing, the slowest step in making the vaccine at large scale.
So you just needed to start regardless of who, you know, we may or may not end up partnered with, but we'd shipped them before we partnered with AEC.
So they already happened.
And we'd also shipped them for, you know, experimental process development work, some research grade virus, not clinical grade virus.
But is actually that the same thing really that it would be possible to make
clinical grade virus from the research grade virus if you knew what you were doing.
And so Serum Institute, you know, had possession of the materials that they needed to proceed.
Independent of AstraZeneca trying to claim, no, we didn't think they would.
Although it would be technically possible to make clinical grade virus from research grade virus,
we didn't think that that was something they were too likely to do.
And the material transfer agreement that we had with them didn't.
I think I think that made them from doing that. But.
There was. A certain amount of momentum and also sort of established facts on the ground and possession being nonsense.
The law type thing about the circumstances of India, you know, were going to be involved and we very strongly wanted them to be involved.
And so. Easy.
You know, I guess it became a priority for easy to negotiate the relationship with,
you know, high level between Pascal Soriot to the ICC and Adar Poonawalla.
The serum has changed the you know, it became important for them to negotiate a new arrangement in a way that I suspect it would not.
That would not have been a priority for any major Western pharma company, possibly including Asia,
if you know, the facts on the ground had not been established in quite that way.
So the way the deal was negotiated with was when I a the the amount of preparation we'd done with the Serum Institute and the university research.
His attitude towards the importance of working with Simmons to.
A letter, essentially Tracy partnering with Sarah and granting them a sublicense for so easily and sublicense to Sarah.
The rights to supply the vaccine across a large number of low and middle income countries India.
But. But also for coming.
So I think that that in the end, the fact that we ended up with Sarah on board proved to be hugely important.
They manufactured more than half of the global supply themselves.
You know, they manufactured more themselves than all these other manufacturing partners put together through 2021.
Most of most of what they made stayed in India, which was a, you know, problematic for supply to Africa.
But on the other hand, it was pretty much the only supply that India had.
So it was very important for India. So I think that the series of events that led to the partnership with Serum Institute,
trans universities partnership with Simmons transferring into an ABC University serum triangle was really hugely important.
So once the agreement was was was signed, was in existence, did you then begin to have direct contacts with Haiti?
Oh, yeah. So I mean, the the first there was one there was one call, which was the university research leaders.
So I think myself, Adrian and Sarah.
Don't think South Korean was on. I'm not sure about ties with Pascal Soriot.
Many Pangloss and their senior manufacturing people as well.
Senior clinical people. You know, so there was a there was a face to face.
You know, before anything was signed, before that terms, you know, by the 23rd of April.
And then after the two terms were signed, that became increasingly technical and detailed.
And we were.
We didn't actually transfer any physical cells or all the vaccine virus to Asia until after the law firm deal was signed, which was the 15th of May.
But we I think we had been talking with them a lot about what they would need to
do and how how the manufacturing process worked and what our vision was for.
You know, the five that we have set up, this pattern of franchising,
essentially the manufacturing to the different contract manufacturing sites and and partners.
And, you know, it was I think it was apparent to everyone that really that was why they would need to continue to do it,
because they didn't have the in-house capacity to do that.
So you'd actually saved them quite a bit of time by doing all that ahead of time.
Oh, those partnerships. Oh, and all. Yeah. Yeah.
I mean, I.
I. I mean, I don't think there would have been a way of getting that time back if we hadn't done it.
I don't really know whether a large pharma company would have.
I can't really see how a large pharma company could have signed on to the vision of.
Global scale, manufacturing and financial risk.
If there haven't been proof of concept that the vaccine could be made at commercial scale, which was what we'd provided Paul in March and April.
So we might have got a partner, but I think it would have been a partner with a view to, okay, we'll keep going.
Going on the clinical trials will develop a manufacturing process,
a normal commercial pace, you know, perhaps slightly accelerated because of the pandemic.
But I don't really we we were starting from the point it is possible to make this vaccine.
It is possible to transfer the manufacturing to lots of different places.
Let's transfer it to as many places as possible.
And I think that was very, very different from how well radio is, different from how any vaccine manufacturer had ever worked.
I think at that stage when we were still in phase one clinical trial in mid-May.
So, yes, I think we should say some time, but also I think the the model that we had developed,
the proof of concept we provided and the model we had developed.
And just the idea that, you know, we would try and commit to making billions of doses before there was a clinical trial results.
I think that probably contributed a bit more than just saving time.
I think it actually shaped Daisy's level of ambition.
So yeah, after the firm deal was signed on the 15th of my, you know, things became concrete, you know, we started shipping things to to the, you know,
everything they would need to actually do, um, both sort of manufacturing, you know,
continuing the manufacturing process development and optimisation in their labs and also actually.
Making more cells, making more virus with which to to seed manufacturing is at the contract manufacturing sites.
What's their scope for much improvement to that stage? Do you think you can make that the big leap with Kareena's work?
Yeah. So there were two significant things that were changed.
One of them. Related to the way in which the virus was grown in the cells.
This is a bit technical but basically hazy.
Were concerned about how much seed virus they would need to make.
As an input to the manufacturing.
And so they change the manufacturing process from one which used a single viral lifecycle and needed quite a lot of input seed virus,
which was on our original two one which used to viral lifecycle and used much less in, let's say, virus.
Personally, I'm not. I remain unsure whether that was.
I hope for all, whether it actually created problems downstream.
I think that make making enough seed virus would have been a real challenge.
But personally, I think it may have been possible.
But anyway, that that change was made and then and driven by as a the other was something that we had started working on in,
in April here ahead of the A-Z partnership which was.
Trying to simplify the purification process. So what would you do in that proof of concept?
Run it to hundred litres. Gallup poll was really just linearly scale scaled up.
It was a, you know, just a bigger copy of what we had done, a very small scale in the lab and some of the components, some of the filters.
Were bigger than they needed to be. I knew.
Oh. And bigger than would be practical to use, as you know, repeatedly a very large scale bigger.
You know, they were too big to allow it to scale another ten times from 200 litres to 2000 litres.
And so we you know, we were conscious of this, you know, the whole the Hollyoaks and Oxford,
Biomedica and Cobra and Paul and everyone was in agreement that this would be challenging with a
particular problem as well as the first tangential flow filtration or one step and to the purification.
And so we'd started it, you know, tiny scale, you know, ten tens of millilitres,
seeing whether we could eliminate that by basically skipping it and instead of doing that filtration stuff.
Moving straight on to the next step in the process.
And it wasn't very good bedtime football with a lot of good work, but at small scale it did seem to work and.
I think we've got lots a couple of litres Gayle working in my lap and everyone agreed that it had to be done.
That was the only real option for a 2000 metre scale.
So sort of that changed. And what came out of it, the vaccine that came out of it was the, you know, entirely acceptable purity and and quality.
Removing the stuff, the filtration stuff didn't didn't seem to be a problem.
It just made things simpler. So, yeah,
everyone was sort of moving us one towards thinking that thought a simplified purification process would want to be done for the commercial scale.
So those were the two technical changes that were made, the two lifecycle processes less see and a simplification of the purification process.
But the the backbone of the process remained the same, you know, same same cells,
same medium, same purification process with with the exception of the removal of hot last.
So didn't change all that much. And and really actually it was remarkable how.
You know how how effectively it did scale of you know, there weren't huge surprises or problems long along the way.
So did AstraZeneca actually stop making. Lots of doses while the clinical trial was still underway?
Or did it just set itself up so that it could?
The setting up is much more difficult than the the preparation is is the time consuming part, both in terms of developing the method.
In characterising the method in depth. You know, we, we, we gave them the method with the exception of the to life cycle growth of the virus.
But to use it commercially, you have to do a whole lot of experimental work, you know, in depth characterisation, you know, exactly.
You know, if I tweak this, what happens, you know, really in-depth understanding the, you know,
it was beyond what we could do ourselves and so needed that you need to prepare a huge amount of documentation.
You need to prepare plans for testing, and you need to procure all the equipment.
You need to procure all the materials. So they.
So for much of the period of, you know, sort of May through to about October, what they were doing was that preparation.
But just doing the preparation was very committing the whole bit.
Yeah. So the fact that they weren't actually churning out huge amounts of vaccine in that period doesn't reflect them not having been committed.
Um, the, um, and what was happening was that the, the manufacturing sites that we had gone a bit further along with the,
you know, were the, we had started before A-Z and you know, it had a head start on getting the equipment and, and so on.
They actually were making vaccine.
So Cobra biologics and stuff which they did a first run, a 200 litre scale using exactly the methods the poll had used.
So without without the tweaks that we introduced to allow it to get to 2000 leagues a scale.
And that batch was made in June, July.
So that was incredibly quick to have gone from, you know, our lab in February poll in March,
April to actual GMP production and to release the scale in June, July.
And you know, a lot of people's.
I think most people in the industry would have thought that that was unrealistically fast, but they did it a very good job and they used,
you know, in order to do that, we'd had to prepare a bunch of cells so it could burn a bank virus, seed oil, which was done in the Netherlands.
So there was a lot and all the documentation, materials, equipment, and so a lot came together in that first batch from COBRA.
We were very nervous. Everyone was very nervous about whether it would work or was it.
It was largely, largely a repeat of what had been done, a poll and how it worked.
But we'd made some tweaks, you know. To essentially try and, you know, some learning from what happened to Paul.
So it was the first time had been run in exactly that way and.
To cut a long story short that that first batch from Cobra through three June and July,
we would run out of vaccine basically late June and July would run out of vaccine for clinical trials.
We'd used up all the vaccine had been made in clinical biomanufacturing facilities
and we'd used up all the vaccine from the box that came from from Italy,
from our funds. They'd all gone into giving people the first doses in a clinical trial.
We didn't have enough to boost people. And so that first bunch from from Cobra using what was a, you know,
a precursor to the commercial scale process that ended up being used to boost people in clinical trials.
So a lot of things are happening in parallel. And and the fact that the fact that we had run out of vaccine, you know,
originally the clinical trial was was designed, you know, the original plan was for it to be a single dose vaccine.
And a handful of people were given two doses and then immune responses after the second dose looked better.
But. We'd prioritise.
You know, we've given as many people as possible the first dose.
And you know, because we would be thinking, well, if there's a wave of infection in the summer,
then, you know, maybe we'll get a clinical trial result from that.
But we hadn't that we'd ended up with no vaccine to boost people in clinical trials.
And so the you know,
the plan had been a for we you know went well what we what we thought was going
to be the way of using two doses was to have a four week gap between them.
But by the time that batch from COBRA became available,
a lot of the people who'd had their first dose early on in the clinical trial should have been much more than four weeks.
Some of them had out it later. It was less then, you know, it was about four weeks.
And so what we ended up with was this very unusual variation in the in the dosing interval between the first and second doses in a clinical trial.
That was that was entirely because the original design had been to do a single dose trial.
And then one of the deaths of both the given two doses, the, you know, the vaccine wasn't available.
So getting that and getting that batch from from COBRA.
I'm unlocked, you know, essentially doing a two dose clinical trial, which meant getting ethics and other kinds of approval, presumably.
Oh, yeah. I mean, the trial had the chance to be amended in order to give everyone the second doses.
And the second shot is the the.
But no, it doesn't seem to be possible to turn it off.
I don't remember. I'm sorry. Yeah.
So the trial had the protocol not to be amended to give everyone a second dose.
We had to give the order by this point.
It was a they had to prepare the documentation about the manufacturing process that had been done at COBRA in order to supply that to the regulators,
in order to use that material in the trials. We it was very, very, very close.
We we didn't get as much from the first batch of Cobra as we'd hoped.
And it was, it was very, very close to being too diluted to use.
We, you know, it was. I mean, at one point it looked like we weren't going to be able to use us, which would have been an absolute disaster.
Um, I would have.
Yeah, I'd have felt pretty terrible, but, you know, it would have been really a failure of hope,
you know, that that was the most important job from what my team had been doing up to that point.
So that was pretty nerve wracking. And also that batch, I think Glenn ended up supplying the US phase three.
I think the US phase three trial was done entirely and material from that first batch from COBRA.
Yeah. So you, you, you were asking whether AC were just preparing to, to manufacture vaccine or whether they were actually doing it.
And I was saying so in short, the preparation was a major investment and a major commitment,
and that had to be started and took a certain amount of time before large scale manufacturing could happen.
But also, COBRA had starts manufacturing in 200 to scale ahead of everyone else.
Alex also and Serum also had done runs a large scale as well during summer 2020.
So that was the beginning of large scale manufacturing.
I can I think I think I don't know when serum did that first.
I can't remember when Serum did that first. Ultimately, they ended up operating at 4000 leaves a scale.
I can't remember when they did their first run in large scale.
You know, the final commercial scale, I don't think I don't think a GMP clinical grade on a thousand litre scale at Oxford,
Biomedica happened until about October. There's just a little this is just dotting and I'm crossing a T, but there's a step called fit and finish.
Is that something you were concerned with at all with other people? Yeah.
And we knew it was a concern because it just means putting the thing in a vial and labelling it.
Is that right? Yeah. Yeah. Which on the surface seems relatively simple,
but is clearly a heavily regulated process to make sure there's no contamination introduced at that stage,
to make sure it doesn't damage the vaccine during that process.
And there's quite a finite number of facilities and capacity for doing that and so on.
I remember back in March 2020 when I was on in these sort of initial discussions with Chuck from the World Bank saying,
you know, everyone's going to be wanting the fill and finish capacity.
And for that was one of the brilliant things of our service sheet of India was that they had the massive capacity and it
was on site and they were able to very efficiently move from manufacturing the bulk vaccine to putting it into vials.
And, you know, they make more doses of vaccine than anyone else in the world.
They had the biggest filling lines in the UK.
It was we had started working with a German company called IGT in March 2020 and they were going to be all fill finish partners.
So, you know, that was it was part of the plan from actually from February.
I think when my very early discussions with John Humphrys of V-neck, we, we were trying to find places to do, fill and finish.
I'll admit I didn't see it as being I saw it as being a capacity challenge, but not a not a huge technical challenge.
So it was scientifically it wasn't really where my focus was on.
But we we the was work going on to make sure that the you know,
to make sure we could do it initially led by John Humphrys and then that was something that the to be
a vaccine manufacturing task force led by Ian McCubbin one of their work groups was was felt finish
so that we gratefully on the part off to them really in April and they secured for UK supply they
basically I think they read I think their reef first refitted and then bought out a filling line,
a company called Walk Hard in Wrexham.
How do you spell that? w0ckhardt Thank you.
So that's where some of the majority of the UK's supply of this vaccine was was filled and finished.
In the end was why Boris Johnson won for his photo opportunities and so on.
Yeah. So the next landmark is the landmark the for the outcome of the.
Phase three trial. The next thing that you were waiting for?
Oh, I think I think that I think that probably was the next the next landmark.
So I think by the time the that result came along, which was.
I think very early December on Pfizer Moderna's results had been mid-November and also a couple of weeks after.
By that time, large scale manufacturing was actually on way uneasy, you know, underway at Oxford, Biomedica and Halix for the for the UK and A-Z.
By that point a have this network of. A dozen or so manufacturing sites globally.
I'm not sure exactly how many of them were actually up and running and manufacturing at that point.
But in order to have vaccine released.
In, you know, around the time the turn of the year is actually is it's nearly 100 day process from
the first in the forms to make a batch of the vaccine which is thawing the cells.
You doesn't need to spend basically a month growing the cells to have enough cells.
It takes about a a week to from adding the seed virus to grow the vaccine virus and then to purify it.
That's only about a week. But then there's another.
It takes, you know, 30, 40 or 50 days from there to get the product into vials,
especially if that's happening at a different site from where the bulk vaccine is being made,
which was the case for most of the manufacturer with the exception of the same industry to India.
It takes about another 50 days to get it put into vials and then to get it tested.
You need all the test results before the vaccine can be released to be given to people.
And that includes testing that was done by the manufacturer,
also includes the testing was done by a national centralised laboratory in the in the it was called Aqaba OCA.
B.R., I can't remember exactly what that stands for, but the.
So there's this long process of testing even after the vaccine is in the vials.
So. The.
The first batches of vaccine that actually went into people had started being made quite a bit of time before, you know, physically being made.
And they got quite a bit of time before the clinical trial result came.
It was reasonably possible to predict when the clinical trial was going to report yes or no,
because the timing of reporting of the clinical trial was dependent upon how many cases of, of course, COVID came along.
And so you could forecast forward, but it was dependent upon what was happening with a wave of COVID.
Yes. You know, so for a long time,
there were very few cases in the clinical trial being more complicated because there were people vaccinated in Brazil and South Africa.
So it was it was a it was a function of how much COVID there was in Brazil and South Africa and the UK.
But for a long time with a lot of people vaccinated and not much happening.
And then suddenly there was a wave of infection in the in the autumn of 2020 and things happened very quickly.
So, you know, I didn't have sort of access to the trial database.
I didn't think it was a it was a very closely guarded secret.
How many cases there were. In fact, I'm not sure, even though I think it might have just been the trial statistician Narain who knew that it was.
Yeah, I think we. But by late November, early December, those of us who didn't have access to that data,
I think we were able to figure out that it must be pretty soon that there would be resolved.
And I think we yeah, if you take a step back,
I think we would most people would have expected from from October also most people would have expected a result before the end of the year.
So everything was being lined up to get the regulatory submissions done and so on for for that,
for it to be possible to release vaccine for around the end of the year.
You know, and it all did come together, you know, almost to the day, really.
The regulatory approval and the release of the first batch of vaccine has been fit for use in the week between Christmas and New Year.
And how did your responsibilities change after that?
And then eventually handed off the manufacturing to AC.
And yeah, the trial was over. So did you have a break?
So I had really largely handed off my responsibilities by the time the first part came from Cobra.
You know, I think it was the end of July or early August that we finally confirmed that I was going to be okay,
two years and my father died on the 23rd of August.
So, um. It was like stepping in.
I think I think I spent quite a bit of time in Scotland with my, with my mother around then.
And yeah, I had less or less responsibility for the manufacturer from from that point, but remained in very close contact with Daisy.
And the main, main thing are things I did on my on the manufacturing.
From there, I guess were like a bit of a nuisance of myself in terms of telling them to.
How about ambition in terms of how much that make? Although really the pattern of law had been set in 19 2020.
And we also started working on, you know, basically improving the manufacturing process so that it could make more.
And in your lab. In my life. Yeah. Yeah.
Um, and we do, you know, we were able to improve it very significantly, but unfortunately,
it's very, very hard to change the manufacturing process once it's got regulatory approval.
And I see and in the end, never, um, but they basically stuck to the original, the original process.
Um, I think if we'd had another, you know.
Six months or so before things had gone life.
We, you know, might have been able to make vaccine more than twice as efficiently.
But it did require it was significant changes to the to the process to do the.
But all the way along, you've had this tension between trying to do things well and trying to do things quickly.
It sounds to me, from what you've said so far, that your priority was always, did you do things well enough but do it quickly?
Yeah. I mean, I guess the. I guess.
Well well, as a I think it's important to stress that, you know, at no point did we compromise on the quality of the product, but we did, you know,
have to take decisions about whether to, you know,
it clearly would not have been the right thing to do to invest six months in fine tuning the process,
to get as much financing out of it as possible or or indeed to say, well,
we're not going to set up the process in the original way because we think this new way of doing it,
which in the end required, you know, some different equipment and so on, might prove to be better, but it might not.
You know, the decision just had to be taken to to to get on go ahead.
And, you know, we were. Reasonably clear from the mouth so that you know the yield of the original process.
That it could make a lot of vaccine.
And I you know, if you have a process which is commercially viable.
You know, in the sense that it is capable of making enough vaccine, that, you know, the vaccine doesn't cost £200 a dose or something,
then actually, even if it's not a perfect process, you know, even if you are arguably improving the yield of it doesn't matter that much.
You just book more manufacturing facilities and. But.
The counterargument to that, of course, is that in reality there is a finite number of individual facilities,
and there's also a finite supply of raw materials.
So for a period of time, the outpost was constrained by availability, you know, global supply of raw materials.
But yeah, there's no question that the decision had to be taken to proceed with, you know, a version of one process very, very, very rapidly.
I think just sort of thinking a little bit more widely about what was going on around that time in early 2021,
when large scale supply of vaccine started.
Those facilities that, you know, we'd started working with very early, especially Oxford Biomedica were able to.
Begin to produce the vaccine quite efficiently. Some of the facilities that AstraZeneca had set up subsequently were not quite on the same stage.
Everyone was still on a learning curve in terms of, you know, how do we make this run as smoothly as as possible.
And so the the rate of output.
Both in terms of the sort of total global input and output from each of the individual
facilities was not maximal at the beginning and also for the output from Oxford,
Biomedica and Horlicks and Cobra.
Was, you know, it had been sold to the UK government as part of the original £65 billion.
And the wasn't. So that just wasn't. And that was before there was any interaction with the.
So. In January and February 21.
There was there was global scarcity of vaccine and.
What vaccine was being made from that original network of Cobra and Horlicks and and also Biomedica.
The priority was to supply the UK and I think personally I think that was right,
it was the UK that had made the investment in making it possible and easy.
I don't I don't know what lawyers might have been able to achieve, but on a very simplistic level,
I don't think they could have sold the initial product to the EU even if they wanted to.
When the EU, you know, started trying to buy vaccine in late May or June, they were a month, a month or two late.
So ease the EU.
You know, really last night, because it was I haven't been the initial funder and there was a period of the
production ramping up of the sites that were meant to supply the and elsewhere.
And so there was this very, very difficult period of scarcity.
And, you know, really, I think ABC being made a scapegoat, which was, I think, quite something for everyone.
You know, it I think it was purely political, you know, mccrone needed or needed a scapegoat.
And they were at that point.
You know, fire fighter. But, uh, how you see change?
I had licensed products. Several companies that had contracts with the EU to supply were not supplying anything.
GSK and Gil Vodka and so on. They didn't get the political heat.
But AC and made a contract to supply large quantities with best efforts the EU had, I think.
Made a mess of its procurement by comparison to the UK and as he became a scapegoat and
the decision to make the interval 12 weeks rather than fall was not to do the scarcity.
It was that genuinely from data from the trial, showing that a longer tool gave you a better protection.
Both. But I think I mean, I, I wasn't involved, you know, that that decision would have been made by the, the JCPOA.
But I, I wholly supported a, you know, the,
the initial discussion around the data from the trial was suggesting that it might be that giving people a lower,
you know, the people the people who had a lower dose of vaccine first seem to have better protection.
And to be honest, really, from the really from the moment the result appeared,
I, I personally didn't believe that that was at all likely to be the case.
Uh, and I knew that those people who'd had a lower dose, they were the people who'd been given the first dose first.
And so they'd had a longer wait before the, the batch from Cobra that was used to these people came along.
And I knew that those people were likely to hold a longer interval I thought.
And it's immunologically it's entirely, you know, it's known that a longer interval gives you a better response.
It made, it made much more sense that a longer interval should give better protection than that.
A small first dose should give better protection.
So. I think it did make sense to to to spread the interval and also the early data supported the fact that a single dose was protective.
You know, it did give a significant degree of protection over, um, over the, you know, 12 week period.
So, and there was scarcity. So it all made perfect sense.
If the data had been the other way that a shorter interval was better, then it would have been a much more difficult decision.
So I mean, one of the fallout, if you like, of of the the vaccine program was that it was obviously extremely high profile.
Was that something that that you encountered directly when you called upon to give interviews?
Yeah, I I've given some interviews.
The I mean I've clearly not had the media profile of Articulate or Sara Gilbert or Tice or counsel Adrian.
But I've done I've done some I like some some of the media work I've done has been actually around the intranasal vaccination trial,
which I led later in 2021.
Oh, sorry. We should talk about that before we start. Uh huh.
Um. Yeah, I've talked to some media.
Um. Well, let's pick up on the intranasal drugs that had it.
How did that come about? That there might be an alternative way of delivering the vaccine?
So I think about January 21,
I read a paper that Haslam and colleagues that published a preprint of showing that getting the vaccine intranasally was effective in animals.
Exactly the same vaccine. Exactly. Exactly the same vaccine formulation.
Exactly the same way. And it looked as though giving it intranasal might actually be more more effective in.
Reducing shedding of the virus from the nose than giving it intramuscularly.
And by that point, it was becoming apparent that, you know,
preventing mild infection and transmission of the virus with intramuscular vaccine is actually quite difficult.
And it was quite a good fit with AstraZeneca because their only previous vaccine product was called FluMist, which is an intranasal flu vaccine.
And also there was, you know, debates starting about, well, you know, these vaccines do have some.
Side effects in the sense of making people feel that flu in the day after they've had it.
Covid's very mild in children. You know, all these intramuscular vaccines going to be the right thing to get into children.
So we thought an intranasal vaccine might be one might have fewer of those.
So, you know,
mild but noticeable reactions compared to injected vaccines and might also be more attractive and acceptable for for some people as a sort of option.
So there are a whole variety of reasons that it made sense to try and.
The the difficulties they have it.
The original idea we had was to move very rapidly from a small trial to a large trial and
actually go for an efficacy result in the same way as we'd done for the intramuscular vaccine.
That didn't work out for all for for a series of reasons.
You know, the hope had been that, you know, if we could get the early safety data and move forward,
then it seemed quite likely there was going to be a large wave of infection in summer 21.
As you know, the lockdown eased and indeed the walls.
But it took us a few weeks longer to get the trial started than we'd hoped.
Ironically, because we couldn't actually get supply of all the vaccine that exist,
you know, the commercial vaccine was actually in the sort of government supply chain,
and getting it outside to do a clinical trial was actually quite hard, even with AstraZeneca, and AstraZeneca couldn't do it.
There were a bunch of regulatory and sort of contractual hoops to jump through and it was quite
as it was sort of mundane things that we needed to change the labels on the vials and so on.
It was quite difficult getting a supply of vaccine for a trial. We didn't have a university owned supply just sitting in the freezer at that point.
So it took us a few weeks to get started. We gave it to the first volunteer on the 1st of April and then very, you know,
within the week after that with the first reports of blood clots related to intramuscular administration.
So everything went on hold for a number of weeks while we figured out whether it might affect getting intranasal given the vaccine intranasal,
we didn't think it would. But just, you know, when you've got very little clinical data on something, we have to be very cautious.
So it took us a few weeks to be able to start restart vaccination.
By that point it was mid-May and then by that point,
the rollout of intramuscular vaccination was going so rapidly that actually very rapidly we ran out of people who had
not had a vaccine before in the UK and then we had to amend the trial to we we gave some people who had had vaccines,
intramuscular vaccines before we gave them nasal spray vaccines as a booster to see if I could be a factor in a small number of people.
But yeah, for all those reasons, it's it wasn't really until September or October that we'd, you know, got data on an appreciable number of people.
And by that point, the ship itself with respect, a very rapid progression.
Um, we haven't. We haven't published today yet, but the immune responses we've seen have actually been a bit disappointing.
So yeah, I think it was an important thing to have explored.
But it is not in the end in something that's going to be taken forward.