How COVID vaccines get regulated

There was cause for celebration as a covid vaccine became a regulator-approved reality in the UK and the UK has become the focus of world media attention as the first western nation to formally approve a coronavirus vaccine for public use. Nevertheless, some are questioning why Britain’s been able to move so fast. According to the UK Education Secretary Gavin Williamson, speaking to LBC, it’s because we live in GREAT Britain. But, if that’s true, what are we actually better at? Well, in reality, the buck stops with a body called the MHRA, the Medicines and Healthcare Products Regulatory Agency. And it’s down to them that we’ve been able to approve Pfizer’s new coronavirus vaccine in record time. And to explain what’s involved, what gaps still remain in our knowledge, and what’s happening with the other major vaccine contender, AstraZeneca, Chris Smith spoke with Gino Martini, from the Royal Pharmaceutical Society…

Gino - Any new medicine has to be reviewed and obviously tested. The MHRA, their job is to inspect and review the data that's been generated. So all pharmaceutical companies have to do a period of testing. What we call clinical trials testing, what we call phase one, phase two, phase three, where effectively the medicine, in this case, the vaccine is tested in human volunteers and subjects which are representative of the population of people you're going to be giving the vaccine to. So you create these clinical trials, the data's collated, and then the whole data are then put together in a dossier. And that's then reviewed by the MHRA. In this case, what's happened is that the MHRA have been working in real time with the manufacturers and reviewing the data in real time. So that's why we've been able to get an accelerated review.

Chris - Is it as simple as that? Because what some people, I think quite legitimately, are pointing out is that normally it takes 10 years to make a drug or a vaccine and get that to market, which means by the time it gets there, you've got 10 years - in some cases - of follow-up from the first time a person was exposed to that drug to the time at which you begin to market it. Here, we've got 10 months. So we don't have that long-term insight.

Gino - True. But what's happening here is that the MHRA will be actively reviewing people who have been vaccinated. So there's already a system, it's called surveillance. And so there'll be monitoring people being vaccinated just in case there are any adverse events out there. The point we need to understand is the MHRA is a very, very good regulatory agency. We've got great expertise in looking at biological drugs, such as vaccines and understanding what data is needed to ensure quality, safety, and of course, efficacy.

Chris - Interestingly though, the MHRA have approved this agent for UK use, but the EMA, the European counterpart for the MHRA, have not approved this more broadly across the rest of the EU. And other countries in the EU and haven't done what the UK has done. So why have we got that difference? And if it's good enough for us, why is it not good enough for the rest of Europe?

Gino - But these things do happen. I mean, differences do occur in interpretation, with data, particularly when you have dossiers such as this. But again, I think what I alluded to before is the MHRA have what we call a lead rapporteur. So that's a lead coordinator when they were part of the EMA for all the new drug applications. Like I said, 60% of new medicines, I think in the last 10 years or so, the MHRA were coordinating that. They've got a great experience in this kind of area and a great network of key opinion leaders and experts who can give counsel on this data. So, you know, I'm fairly confident that if the MHRA are happy with the safety and efficacy and quality, then I'll take the vaccine.

Chris - There are some gaps in our understanding and in the data we've had generated so far though, aren't there? For instance, no one under 18 has had the agent tried on them. So they won't be being vaccinated. Pregnant women currently they're regarded as a risk group, but they've not been included intentionally in the trials. They've been actually excluded from the trials. So how are we going to deal with the fact that there are these individuals or groups in the population that haven't been actively explored?

Gino - As time evolves, they will obviously investigate those subjects. There'll be evolving the plan with the MHRA and finding what's the best way to include those people.

Chris - Now what happened with AstraZeneca and where are they now in this whole situation? Because they described the fact that there appeared to have been this mix-up with dosing as serendipitous, because actually it revealed that if you give a lower dose and then a higher dose, you might get a stronger response, 90% protection compared with say 60% with two higher dose hits. We're still trying to get to the bottom of that. Where does that leave them though? Does this mean the regulator may say, "well, I'm really sorry. The trial didn't go according to plan, it's back to square one. You've got to start again." What do you think is going to happen with them?

Gino - A difficult question to answer. I think there will be dialogue between AstraZeneca and the MHRA and they will be looking at the data in its entirety and where the gaps are. And again, I think based on that experience, this is the MHRA, they'll make a judgment call, obviously working with AstraZeneca. So at the moment, it's hard for me to answer that question because that dialogue, those conversations are obviously happening. But ultimately the MHRA will have to make sure that safety, quality, efficacy has been maintained.

Chris - Once the vaccine goes into society and people start to receive it, what mechanism or instruments are in place to follow up to make sure a) it's working and b) that the people that have had it and are getting it, they stay well, there are no long-term side effects, etc. How do we monitor the situation going forward?

Gino - Typically when something hits the market anyway, it's called phase four, and that's a period of what we call surveillance. Any adverse events are monitored by healthcare professionals. And there will be launched what we call a yellow card system where the system flags if there's been an issue. But my understanding is that the MHRA have launched an active recall system, will ask vaccinated individuals to monitor what happens. So there's going to be two mechanisms to keep a watching brief on those people who have been vaccinated.