What is your work stream trying to achieve?
Whenever we look at the quality of a drug product coming off the line there are two elements we examine. The control of critical material attributes and the control of critical process parameters. The combination of these two will deliver a product of the required quality. But you can’t work on them independently; you have to have an element of both so the workstream is looking at how we can take into account variable material attributes and variable process parameters to create an enlarged design space so that we can make robust products more repeatably and for a wider range of products.
So in simple terms your two questions are one does it work as a medicine and two does it hold together as a product physically?
It’s about ‘does it work?’ and ‘can you make it simply?’ and ‘can you make it flexibly?’. So, a drug product could be a blockbuster drug where you need to make many many tonnes, or it could be a very niche medicine for a relatively limited number of patients. The technology platforms that we choose to manufacture a drug substance or a drug product have to be flexible and agile enough to address the clinical and commercial supply chains at the volume and throughput for the products that are required.
Is it fair to say what we have seen in the past has been mass production for everything, irrespective of the size of the population of patients?
I think historically we have had blockbuster drugs so that approach has been thought the most cost effective way of producing a viable product for the market. But what we can refer to as personalised medicine, where you are targeting therapy at a very specific patient population, now seems to be the way forward and that is where the high value for the patient is to be found.
I think the industry generally is moving from a few products of absolutely huge volume to many products and smaller volumes, and manufacturing processes have to be able to accommodate both. And we have to be able to reduce the time it takes to develop those products as well. Generally keeping the process as simple as possible means that you have a quicker way forward in terms of development and getting a product to the market.
What are the implications of the work that you are doing?
There is a shift in the industry generally from large batch manufacturing to continuous manufacturing. Continuous manufacture offers you scalability. In a continuous manufacturing process, you either make a small amount because you run the process for short time or you make a large amount because you run the process for a longer time. The actual technology platform is doing the same thing so you develop it once for a small volume, but it’s applicable along the whole life-cycle of the product.
To do that are you in some cases having to turn chemistry on its head?
For App B it’s not so much chemistry. We are interested in physical properties of materials. We are not synthesising materials. So, it’s not turning the chemistry on its head but it is thinking, for example, how you define a batch in a different way.
Because you are operating continuously, you have the opportunity to monitor what you are making. So instead of making a big batch of material and testing it at the end when it might or might not be suitable – it may pass or fail a specification – once you are manufacturing in a continuous fashion if you can monitor the product as it is being made. You get an instantaneous readout of whether you’ve got an optimised, stable, robust product.
The mindset is one of ‘make, test, release’: you make, test instantaneously, then you can release from a GMP [Good Manufacturing Practice as set down by regulators] perspective the product to the patient. So, our interest is not about a change in chemistry, it is a change in how you view the process and having the tools that you need to monitor it while you are making it, rather than relying on make it and test it afterwards.
Is this potentially game changing?
Definitely. If we look at other industries we are probably a bit behind the curve and are playing catch up in the Pharma industry. Other industries use continuous manufacturing, such as food and automotive. All sorts of industries use continuous manufacturing and utilise the same principles as we are trying to do now in the Pharma industry.
I guess that one of the things that makes it more difficult for us is the fact that we are a highly regulated industry so any proposed paradigms shift in technology that we suggest has to be acceptable to the regulators, to ensure we are delivering the safeguards, in terms of the safety and the quality of the medicine that reaches the patient. That is not a blocker, but it means that we have to have a continuing discussion with the regulators about each of the technology platforms we are thinking of embarking upon.