The Small-Molecule Problem Solver

Having worked with generic drugs since the 1990s, Paul Evans, Vice President and General Manager at Johnson Matthey, has seen the industry go through many changes. Today, small molecules are becoming more sophisticated, posing challenges to both innovators and generics manufacturers alike. Four years ago, Evans joined Johnson Matthey, tasked with the aim of creating additional value for the company by finding innovative ways to expand the generic API portfolio – and he believes that jumping in at the deep end and lending a hand in product development is key.

What are the main challenges with today’s small molecules?

Scientists now have a good understanding of how biological processes work, leading to more complex and efficacious medicines. Today’s small molecules are increasingly potent and targeted, and can involve challenging chemistries or handling procedures that companies may not want to – or may be unable to – do themselves, especially when it comes to moving from the small scale to the larger scale. Sophisticated molecules can also pose challenges to formulators, particularly as drug substance and drug product are traditionally viewed as quite separate areas – usually, the API is developed and then samples sent over to formulators to solve issues with bioequivalence and bioavailability in a trial and error approach. A far better method would be to collaborate at the intersection.

Generic manufacturers have to follow the trends that are happening in the originator space and be prepared to deal with complex molecules, since today’s originator molecules are future targets for the generics industry. The difference for the generics space is twofold: speed to market and navigating the intellectual property landscape. To achieve these targets, you have to bring your own development skills and technology to bear.

Why is differentiation in the marketplace so important for generics?

Generic molecules are by definition the same, but manufacturers can differentiate through manufacturing processes, intellectual property and creative business models. Good chemistry skillsets are important because you need the ability to dive into the physical properties of products, such as how they are formulated and how they perform in the body, and technical expertise to identify intellectual property opportunities. Of course, generics companies know that differentiation is important but in reality it’s difficult to achieve. It is also a difficult field to collaborate in because collaborations involve trust, which takes time to build – and time isn’t always available when you are rushing to get to market.

How is Johnson Matthey adapting to changing industry needs?

Johnson Matthey is over 200 years old, but to get to our next centenary it is important to adapt. We have been making APIs since the 1970s, but with small molecules and drug development becoming more challenging, we started to ask what more we could do for our customers. And the answer was collaboration. When you are in the API business, you accumulate a lot of technical capability and chemistry skills that can be applied to a wide portfolio of products. We came up with the idea of investing and developing generic products in collaboration with our customers, believing that the sharing of risks would be very valuable. Most generics companies seek a large portfolio of products but their R&D teams can only do so much. With our model, the two teams work together collaboratively to find the best overall solution for the API and drug product, which allows for a quality-by-design led approach to development. For example, using particle science and upfront characterization provides a better understanding of how an API is going to work in the formulation – and the drug substance can then be tailored to help the formulator reach their target faster, and with a more sophisticated design space. Collaboration can really help accelerate development times – a valuable edge given that speed to market is key with generics.

Collaboration is not just important with our customers, but with other companies who have technology that we don’t, and who can potentially make a difference. In June of this year, we announced our collaboration with Intrexon. Intrexon is an expert in the engineering and industrialization of biology and we will be working to use its technologies to help with the production of peptide-based APIs.

Any final tips for small molecule success?

The technical toolbox is incredibly important. It’s common to find experts in a specific technology, but the danger is that they will try to force fit that technology to solve all problems. In my view, it is far better to look at a range of solutions and to examine which ones provide the best outcomes. The synthetic pathway can greatly influence how you purify and isolate the product, so your chemistry approach influences your solid form and can impact yield, cycle time, and further processing requirements. Marry these technical capabilities with a collaborative approach and I feel you have a powerful combination.