RECAP with the RBDCOV Community Advisory Panel | Vaccines 101: How do they make it into the European market? (part 2)

PART 2

(LINK TO PART 1)

ReCAP is a series of interviews with the members of the RBDCOV Community Advisory Panel that will explore the world of community engagement in EU projects and the importance of including people living with immunocompromising conditions in clinical trials.

Let’s dive into the second part of the interview with Brian West and Christopher Mann! In the last blog article, Brian and Christopher talked about the vaccine regulations for the European market, highlighting the four major steps in the process: identifying the virus pathogen, manufacturing the vaccine, testing the safety of the vaccine in non-clinical trials (animal studies), and finally, clinical trials in humans to test dosage and efficacy. Christopher emphasised the expedited nature of COVID-19 vaccine approval, addressing misconceptions about inadequate testing and addressed the advantages and challenges of developing HIPRA vaccine’s role as a booster dose. Brian stressed the importance of early community involvement in drug and vaccine development, referring to EATG’s experience and the community’s role within the RBDCOV project. The conversation also addressed the evolving role of Health Technology Assessment agencies during the pandemic and the potential impact of cost considerations in the future, especially with the prospect of routine COVID boosters. Read on for part two, which takes a closer look into the regulatory aspects and HTA considerations of approved vaccines.

Brian West

I would like to ask you a question, Christopher: Once a vaccine is on the market, what mechanisms are in place in Europe to monitor its safety and effectiveness? And how does the regulatory framework ensure this ongoing surveillance?

Christopher Mann

Yes, so it is very normal to need to modify the conditions of the marketing authorisation once any kind of medicinal product is approved. For example, adding manufacturers or incorporating new safety data or addressing new populations. In the EMA or in the European Union, there is a procedure called variation. There are many different types of variations, but essentially, it involves submitting a proposal for changes to the regulatory authorities. These changes are then evaluated, and the summary of product characteristics and the prospectus are updated to reflect these modifications. Depending on the nature of the change, varying amounts of data may be required.

For instance, comparability of different products at the manufacturing level or providing clinical data. An important aspect for the HIPRA vaccine will be the addition of paediatric indications or licensing requirements. As the paediatric data from the trials become available, there will be updates to the label specifying which dose can be used in the paediatric population, for example.

Brian West

That is an interesting answer, and it just brings something to mind here. Once this vaccine is on the market, people evaluate the data and the safety, among other things. But what is in place to evaluate the benefits of vaccine A versus B or B versus C? Are there any systems in place to determine which vaccine is more effective?

Christopher Mann

There is not anything purely systematic or from the regulatory point of view to determine which vaccine is better. In fact, that would be quite challenging for a regulator to prescribe. I suppose that is the job of the medical practitioner in most cases. However, what could potentially happen is systematic safety data collection. For example, the vaccine monitoring platform in the EU collects vaccine safety data from large numbers of people in a real-world situation. There, you may be able to detect certain safety signals that might influence which vaccine would be used in a specific population. But a direct comparison between two vaccines would primarily be the responsibility of the different manufacturers and maybe at their own risk. Because, obviously, if you conducted a comparative study with the expectation of showing superiority and it did not turn out that way, it might be detrimental. Whether or not the companies would sponsor or conduct such studies remains unclear at this stage unless they were pursuing purely commercial interests.

There is also systematic analysis done by the scientific community and published, such as Cochrane reviews and meta-analyses, where multiple studies from various manufacturers are compared in a relatively neutral way to identify differences in efficacy and safety profiles. But again, the overall recommendation of which vaccine to use in a particular population or which is preferred may come down to what is available on a cost level, or it may also be based on the medical practitioner’s preference for that population if multiple vaccine options are available.

Brian West

As a follow-up to that, on some of the community group discussion lists, there is a lot of discussion about the mix-and-match approach for vaccination, essentially have on type of primary vaccine, and another type as a booster dose. There have been discussions about whether you could run a trial on that. I would be interested to know how possible you think it would be to run a trial on that. How do you mix and match? And secondly, presumably, what we are looking for is a more, if you like, sustained virological response, am I right?

Christopher Mann

Yes, exactly. So, the mix-and-match question is very interesting because there have already been quite a few studies exploring that concept to some extent. In fact, HIPRA has also employed a mix-and-match approach for boosting after a primary dose mRNA vaccine. Scientifically, this approach makes total sense and can be highly recommended for various reasons. In our company, we have worked on HIV vaccines that have used a mix-and-match approach. The reason behind this strategy is that each vaccine may stimulate a slightly different immune profile. By combining different vaccines, you are potentially stimulating various parts of the immune system or targeting different antigens, resulting in a broader and more comprehensive immune response. This, in principle, prepares the individual better for responding to the pathogen. There are already several studies and papers supporting the notion that a mix-and-match approach is a good strategy. However, it may not always be explicitly presented in the prospectus or guidelines, dictating which vaccines practitioners should use in a specific order. It may not be so systematic, but the data would be there to show that if you use an mRNA vaccine, such as Pfizer and Moderna, and a recombinant protein vaccine such as BIMERVAX, for example, it would be safe and still effective. Therefore, it is a good approach to consider.

Christopher Mann

Now Brian, I would like to come back to you and ask you a bit more about the future and the availability of the HIPRA vaccine on the market. For example, could you tell us if there are any regulatory or HTA challenges to being on the market and can you see any important future changes to market access? 

Brian West

Thanks for asking me this question. For me, one of the issues is that because it is not currently going through the conventional mechanisms of an HTA, it is all about being alert to what is happening in individual countries. We do not necessarily have uniform approaches throughout the whole of the United Kingdom; there are different strategies in England, Scotland, and Northern Ireland. The Joint Committee on Vaccination and Immunization (JCVI) is making decisions very quickly based upon new formulations of vaccines coming through. What that means is we need to be informed and up-to-date on the state of play in each individual country. That includes Spain, France, and Germany and so on. Are all the vaccines available? By this, I mean a choice of vaccines because not everyone can take an mRNA vaccine. Also, with the HIPRA vaccine, specifically designed for boosters, it is important that we gather information ourselves on the state of play in each individual country.

Christopher Mann

Thanks for that. I would like now to ask you about the representation of people living with HIV in the clinical development of the different vaccines. What is the status of this group of population in the HIPRA vaccine development as well at this stage?

Brian West

I do know that people living with HIV were allowed into the RBDCOV trials and we were obviously very pleased with that. We would not have come on board the RBDCOV project if that had not happened. But for a bit of history here, some of the original COVID vaccine trials, for instance, in Italy, they were just not allowing people living with HIV into some of the early trials. And that was a huge problem for us. Firstly, because exclusion from clinical trials for what we would consider to be no good reason is unacceptable. Secondly, it was obvious that we were going to be among the first groups of people to be offered a vaccine. So, you want that safety data as soon as possible. I think in the early days, with the first vaccines that were coming through, there was a tendency to play safe and exclude people living with HIV. To the best of my knowledge, that has not happened in any of the updated versions. Although it must be said that with companies like Pfizer and Moderna most of these trials are going on in the USA. In this case, we are reliant upon asking our American colleagues if there are issues going on there at all. But certainly, with HIPRA, there was not an issue, and I am very glad to hear that.

Christopher Mann

Yes, that is very good news indeed. Thank you very much for your time and your insights Brian. This discussion has indeed been really interesting.

Brian West

Likewise, Christopher. I am glad we could exchange views on this topic.

Disclaimer: This activity was developed under the RBDCOV Project, which has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101046118.