Outsourcing Pharma caught up with experts from the global CDMO, CordenPharma, to learn how they maintain their competitive edge.
Brittany Hayes, Global Platform Director for Highly Potent & Oncology, and Ilia Freifeld, Global Platform Director for Small Molecules at CordenPharma, shared their insights with Outsourcing Pharma at CPHI.
How would you describe the current global landscape of API and drug product development and manufacturing, including trends and recent developments?
Ilia Freifeld: As medicines become more efficient and the demand for high-quality products increases, there is a greater need for more high-efficiency drugs in lower quantities. In other words, the efficiency of drugs goes up, but the quantities recorded on the market decrease. At the same time, as the complexity of molecules and modalities increases, the regulatory requirements are also becoming more demanding.
One of the main challenges drug developers face is that molecules are getting less soluble, especially in water, and more sensitive to different environments. This means that the solubility and stability of molecules are decreasing, which we, as a CDMO, must address.
Brittany Hayes: For example, we have established the Drug Product Innovation Centre of Excellence for drug product manufacturing and development, in Plankstadt, Germany, where we work with solubility- and permeability-challenged molecules that need different technologies to support them in bypassing the digestive tract and reaching the target area in the body.
Now, not every technology will be suitable for each complex molecule. So we have taken a flexible “toolbox approach” with several different technologies available, including spray drying, hot melt extrusion, micronization, and nanomilling.
In terms of highly potent and non-potent solid dosage forms, CordenPharma has also invested in the Oral Solid Dose capabilities in Plankstadt. We’re adding co-precipitation and lipid-based systems that can address the permeability and other bioavailability challenges of our customers’ APIs, including the increasingly popular GLP-1 peptides.
As the need for highly potent APIs increases, what challenges do companies face in manufacturing them? How does CordenPharma address these challenges?
Brittany Hayes: There are many challenges around highly potent molecules because these molecules are toxic and/or cytotoxic. At CordenPharma, our main focus lies on their handling and containment during manufacturing to ensure the safety of our workers.
We have robust industrial hygiene protocols in place at the manufacturing sites that can handle highly potent molecules. The engineering controls in the manufacturing areas are highly efficient so personal protective equipment (PPE) is secondary. Technically, in some areas, a worker could enter a room without PPE and still be safe. Of course, everybody wears PPE for peace of mind and in case there is a failure.
How does CordenPharma approach current market trends to support customers with the most novel drug products?
Ilia Freifeld: We are continuously investing in modern technologies that address the market needs. Alongside the technologies for enhancing bioavailability (spray drying, hot melt extrusion, micronization, and nanomilling), we have also recently invested in continuous flow chemistry, chemical manufacturing, and supercritical fluid chromatography for the purification of lipids and peptides. We are working on steadily increasing our experience with these technologies and building a strong track record of using them.
While it is important to react to market needs – which we have done with our most recent investments – it is also important to be innovative and work ahead of the market needs, for instance, by following the most modern quality by design (QBD) paradigms and regulatory strategies.
CordenPharma can support its customers with several different platforms. How does the synergy between the platforms work to enhance API and drug product development?
Brittany Hayes: One of CordenPharma’s unique strengths is the fact that all of the different platforms synergistically integrate with each other and that sets us apart from other CDMOs. Many take a mono-technology approach to traditional drug product delivery, however, we feel that because each molecule is very different, maybe 95% of the time a technology won’t be successful, so we need to take a flexible, synergistic approach.
Take a lipid nanoparticle (LNP) drug product, for instance. We can handle all of the steps that go into that formulation across different technology platforms or collaborations that we have with partners. We offer integrated services, manufacture lipids, LNP starter kits for early phase development, and we have a partnership with Wacker Biotech where we can create mRNAs, and then we can also do the liquid or solid formulation of the LNPs themselves. This means we have an end-to-end integrated offering for mRNA-based or LNP-based drug products.
Similarly, we can do that with peptides. We have one of the largest peptide manufacturing capabilities on the planet. We can make peptides that go into injectable drugs or they become oral solid drugs.
With small molecules too, we are covering non-potent and highly potent small molecules and can develop injectable or oral solid dose formulations.
Ilia Freifeld: We also have several Centers of Excellence where we focus on finding the best drug product and drug substance combinations to develop drug substances that lead to smoother formulation development into drug products.
For this purpose, our experts from different disciplines collaborate – for example, chemists working on solid-state processes and pharmacists focusing on bioavailability enhancement – in a multidisciplinary approach that helps us achieve the highest output in integrated drug development and formulation activities.
What is CordenPharma focusing on for the future of API and drug product development and manufacturing?
Ilia Freifeld: Often, companies work with separate CDMOs for drug substance and drug product development, which can lead to a disconnect in information flow between these two
groups. At our centers, we eliminate this issue because both groups work closely together within the same organization. This ensures that there are minimal gaps in information transfer, providing a more seamless experience for the customer and more efficient development of the molecule.
So although our platforms are large and spread across different geographic locations, we are establishing regular communication between subject matter experts and scientists across our sites to ensure everyone stays on top of developments. Teamwork is key—it's our top priority, especially when it comes to innovation, where our global R&D organization is leading projects to stay ahead of the market and anticipate future trends.
One thing we're seeing in the market is the increasing complexity of drugs where we expect to see more complex modalities and evolving customer needs. While it's impossible to fully predict all future developments, we need to remain flexible. Flexibility in our mindset, operational setup, R&D resources, and capacities is essential to meet market demands, which can often be difficult to forecast.
Nobody predicted the pandemic four years ago, and if we had, we would have been better prepared. This experience highlights the importance of flexibility—being able to respond quickly to changes in the market. To address this, we focus on innovation, which opens the door to new technologies and processes that help us react to changes, or better yet, anticipate them and lead the market with forward-thinking solutions.
Additionally, we're aligning ourselves with modern manufacturing trends, particularly those related to reducing the CO2 footprint and implementing green chemistry and environmental practices. This is becoming a major focus in the industry, and its importance will only continue to grow in the future.
