How far do you think the big companies are from bringing in continuous manufacturing for important front line medicines?
We are doing it now. In GSK’s manufacturing facility in Singapore we have an existing API (active pharmaceutical ingredient) that is currently manufactured by batch and we also now have a continuous processing facility working in parallel.
So it’s not yet replacing the batch manufacturing?
Not as yet but that’s not to say that it wouldn’t do at a later date but with the time it takes to get the necessary regulatory approval from every country to change the way we manufacture, then it’s not necessarily going to be easy or fast to switch all production across for everyone all at the same time for this particular product.
In general we select the optimum manufacturing technology for each product; this may be continuous, batch or a combination of the two. I don’t expect that continuous manufacture will replace all batch manufacture in the near future, but certainly is being used on increasingly more products in our development portfolio where it adds value, and I expect this trend to continue over the coming years.
So what are you seeking to do in App F?
App F is about using transaminases in flow. We are looking at two key technologies for GSK – and the broader pharmaceutical industry – that use biotransformations to catalyse reactions. This approach gives a more environmentally friendly, metal free way of catalysing chemistry. It also allows us to do chemistry that is more selective that we can’t do using traditional chemical catalysis. Then we also have the flow part, which is allowing us to do things more efficiently than we can do in a batch processing way and to do processing which is simply not possible in a batch process.
So this particular class of enzymes the transaminases are a very useful class of enzymes that allow us to take readily available ketones and convert them to more useful chiral amines. One of the complications is that you often see things like product inhibition or you need to drive the equilibrium of a reaction towards a product by removing something. That’s what we’re looking at in App F: can we use continuous processing to overcome some of these issues that we see with transaminases so we can have a technology that allows us to use transaminase in the manufacture of more products, and can we get this important class of enzymes into manufacturing across a broader suite of products.
How much of a game changer is this if you can get it right?
It’s huge. You could potentially cut out steps from the synthesis altogether so that you could give yourself a much shorter synthesis to API by, for example, eliminating some of the transformations. And, importantly, it can avoid the use of rare and potentially expensive transition metals as well, replacing them with something that you can easily and sustainably produce through fermentation processes.
The beauty of the bio catalytic enzymes is that you can evolve them very quickly and easily now, following advances in recent years, to be very selective for the molecule transformation you are looking at. At one time you might have got very low yield or a very high load of enzyme and it could have been a very long task to get that into something you could use on a manufacturing scale but with the recent advances in high throughput it means that you can very rapidly take something that doesn’t work very well and mutate the enzyme into an enzyme specific to the reaction you want to do.
So it can have huge benefits and again, within GSK, we have examples of existing products where we have had a chemical process and we have now developed an enzymatic process that offers huge cost savings in terms of sustainability and removing organic solvents.
What’s the buzz for you from all this. Do you feel that you are at the leading edge of this?
Yes definitely. Doing continuous processing and bio-catalysis is something that a lot of pharmaceutical companies have been involved with quite a number of years. It feels now as if it is a reality: we are seeing products being made with these technologies we have a whole raft of things coming through in the development portfolio that use this technology, so we were at the stage now where if we want to use, say, continuous processing then the benefits of this approach are accepted by the manufacturers.
So there is no debate now on whether we should do this by batch or flow, if flow shows benefit we will go for that. So the key thing from me is that it’s no longer something interesting that we talk about, it is something that is being used, that is being delivered.