The development and assessment of ATMPs could be made significantly more efficient and therefore more affordable by adopting a platform approach rather than the current ‘one product at a time’ approach. But what exactly is a platform, and how do you define it in such a way that the desired simplification is safe and legally acceptable and does not exclude developers? A conversation with Sean Russell, who holds various positions in the worlds of consultancy and regulatory science.

‘What we mean exactly by a platform is the million-dollar question. All stakeholders are working towards a definition that will make therapy development more efficient and sustainable,’ says Russell. He is uniquely qualified to view the importance of platforms from different perspectives. He is Head of Regulatory Affairs at Fondazione Telethon, a non-profit organisation that funds research into treatments for rare genetic disorders. He also sits on the board of several companies and organisations in the field of regulatory science and consultancy. Earlier this week, he gave a lecture on platform technology during the CBG Science Day. 

More efficient than traditional development
‘In traditional drug development, you start with one target for one product, which is then used to treat one or a small number of indications. This also applies to most ATMPs. In vivo gene therapy targets a single gene; CAR-T cells target a single antigen that may occur in two or three different types of cancer. When we think of platforms, we are talking about developing different products using the same technology. This increases efficiency, making product development more attractive especially for rare diseases. You could foresee that a number of attributes in that product development process have now proven to contribute to product safety and quality, thus making it easier to obtain marketing authorisation if they can be reused.’

Russell emphasises that it is not yet easy to define such a platform properly. Which steps and procedures in the development belong to the platform and which do not? If there are ten analytical procedures and eight of them are always the same, can that be considered a platform that can be used for different products? What differences, what margins in measurement values are acceptable? We need to answer these questions if we really want to use the concept of ‘platform’ in therapy development. 

Reaching agreement
The various parties involved in therapy development and market authorisation see this development from different perspectives. Russell: ‘Therapy developers want as much efficiency and cross-utilisation as possible. Regulatory authorities must ensure that the safety, efficacy and quality of the product remain guaranteed. As developers, of course we want those guarantees too, but we also want to define platforms in such a way that efficiency and sustainability are given equal prominence. We want to ensure that the definition of a platform is not so conservative that it offers no advantages. In short, everyone has their own perspective and we are now seeking consensus.’

The US Food and Drug Administration (FDA) has stated that to be recognised as a platform, you must have one approved product that uses the technology. You could then say: I’ve already done this once, so why not do it again, but with a different transgene or a different product design? Here in Europe, we have started to think about it more fundamentally: if I have a series of conditions that all share similar clinical attributes, how can I use one technology to treat all of them? So we may use one vector design, but incorporate different transgenes each time. But what exactly is the platform: the vector design, all the procedures to demonstrate effectiveness, the entire product? We now need to reach agreement on this. 

Growing convergence
According to Russell, there is currently a favourable development underway in Europe, partly thanks to the new rules on clinical trials (Clinical Trial Regulation). He believes that there is a growing awareness worldwide that coordination on issues such as platforms is crucial to keeping ATMP development efficient and affordable. ‘Convergence on these issues is good for the industry, and overall from a regulatory perspective. However, it is very important that we keep pace with each other globally but equally don’t try to run before we can walk. Considering regulatory convergence where possible from the outset is critical when we think about defining new terms and approaches. We can already see that the FDA has moved in a certain direction in relation to defining platforms; the EU does not need to follow exactly and we will not agree on every parameter, but we need to find out where it is necessary to be on the same page.

Opportunities for treating rare diseases
A platform approach can offer opportunities for treating rare diseases where it is possible to use a technology (such as gene therapy) for different applications. Russell sees two possible significant opportunities for this, via academic groups and small companies or via CDMOs (contract development and manufacturing organisations): ‘Academic groups could work within a specific platform from the outset on developing therapies for a range of conditions. The ATMPs they develop could then be brought to market via start-ups. CDMOs could start with a process for the production of AAV vectors for gene therapy, for example, in which case you could assess part of such a platform in advance, thereby increasing its efficiency in development and marketing. The American definition of a platform, which is based on a product on the market, would largely exclude academic groups who are unlikely to reach commercialisation. That is why it is so important that we develop a European definition of platforms and aim towards global convergence on key aspects based on this as much as possible.

Focus on the bigger picture
Russell’s advice to Dutch developers and regulatory authorities is to be open to developments around platforms: ‘Be aware of the current frameworks and limitations, but also be open to the broader context and be forward looking. Try to understand how others define their parameters and attributes. We cannot work in isolation, because we need to ensure that our definitions are appropriate and that we arrive at widely supported solutions in order to ensure maximum benefit from such innovative regulatory paradigms.’