The need to ensure patient safety and drug efficacy in pharmaceuticals is only increasing. With the sudden disruption caused by the COVID-19 pandemic, the Chemistry and Manufacturing Controls (CMC) process has been thrown into the spotlight as critical to drug manufacturing and to pharma regulation in general. But this same pandemic has also altered what many thought to be the future of the industry, and where CMC will go from here is an increasingly uncertain question. Proventa spoke to Jean-Pierre Metabanzoulou, Senior Director, MBA, PhD, CMC & RA at Acasti Pharma, to hear more about his work in CMC and how the field will progress over the next five years. 

Proventa: Tell us about your role within CMC, and which parts of the area you enjoy most?

Jean-Pierre Metabanzoulou: I am actually currently Senior Director of CMC at Acasti. Day to day, I lead a cross-functional internal team of 10 people and external CDMO/CRO resources to ensure anything to do with process development and analysis runs smoothly, and as we’re using QbD, that we have a robust development program. I also ensure we have a strict set of specifications for our processes and that other critical quality attributes are set and in line with what the process can deliver. 

I also deal with the troubleshooting of any program issues, and ensure we have a risk-based system in place to investigate problems thoroughly and ensure they cannot happen again. This is what we call the CAPA system – corrective action, preventative action.

A lot of the enjoyment I find in my role stems from introducing new concepts and innovation. I’m keen on looking at new technologies and new ways of doing things – for example when I joined the team, they were performing continuous manufacturing, but they were missing continuous quality control. I looked at the process and decided that there was an opportunity to include this element. At the time we didn’t have the right internal resources, so we worked with academia to gain access to these. Continuous quality control is not yet implemented because we’re not at the commercial manufacturing stage yet, but we have the elements to include the quality control continuous monitoring. Once the batch is manufactured at the end, the quality testing will be completed at the same time. This is how I envision CMC.

Proventa: Which technologies would you want to implement into CMC, or adopt more to progress the sector?

JPM: What I’m seeing more of, and what the CMC professional must do, is reduce the siloing that occurs in the pharma industry. We have medicinal chemistry experts who design the molecule, and then the development side who take over when the lead is optimised. The drug can then be developed and moved along the clinical pipeline. 

But what we should be doing, as soon as some candidate leads have been identified, is to ensure those currently involved at later stages are brought in earlier, so they can have more input on the molecule’s design. This is vital because in development these people will be familiar with some attributes that medicinal chemistry experts perhaps are not, and so by involving them issues that might come up later can be prevented. So we definitely need to break down these silos!

Right now there’s a lot of innovation and new technology on the discovery side of things, and how professionals there are developing and designing new molecules and validating targets is changing. So this makes it even more important to work as a team. For global companies this can be difficult, but it’s much more achievable for biotechs and smaller companies. So greater collaboration is something the industry desperately needs. 

On the technology side, we’ve talked about it a lot but it’s worth repeating: AI. There’s a lot of data gathered in pharmaceuticals and CMC, but this data is scattered across different systems which don’t interact with one another. There’s an opportunity here, and I’m seeing more and more tools which can be applied to this – but none that are commercial and off the shelf at present that can facilitate the data acquisition and exchanging from early development up to commercialisation. This is vital if we want to understand our processes, improve them, and use the data to feedback into our systems. This will not only improve quality but also reduce costs. 

Proventa: How do you see CMC changing over the next five years?

JPM: The industry is definitely moving towards improving drug quality and greater standardisation. This concept has been around for quite a while, with Process Analytical Technologies (PAT) gaining fame in the early 2000s after it was introduced by the FDA and other regulatory bodies and pharma companies were encouraged to adopt them. PAT standards were introduced to combat batches being recalled and bad product quality within the industry. As a side effect of PAT, the costs also decreased as fewer batches were lost.

We are seeing more and more online testing, meaning you implement some probes on your process that monitor the quality of your product. As soon as you see that there’s a risk, you can make sure you immediately put in measures so the process will be back in control. So this is what we’re looking at also.

In terms of technology, one tech that’s changing things is NIR – Near Infrared Tech. That’s very interesting – it’s very sensitive to the environment. That means we won’t have the same response when you’re testing for a material, as it’s like a fingerprint. Different molecules have different fingerprints. It’s a very interesting technology in the small molecule arena. 

I definitely see silos being reduced over the next five years. Other than that, COVID-19 has of course changed how the industry is collaborating. We see more and more people working as a team, and reaching out to other organisations more than we used to. 

I can see these cross-functional teams continuing post-pandemic. These are very important, and we need the different perspectives of people in separate departments, sciences etcetera. Our work needs experts from early development, pharmacology, CMC, manufacturing, quality control and assurance, all working together to develop processes. We need those different perspectives. By bringing these together, we’ll see improved final results – but this isn’t easy to do! I think it will take time for this to become a norm in the industry. But the more we do it, the easier it will be to break those silos. 

Joshua Neil, Editor
Proventa International