“Innovation for us means solving our clients’ challenges in smarter ways”, interview with our expert Charles Guérin, Ph.D

Read the full interview below :

What are the critical success factors in chemical development for Small Molecules drug substances today? 

“The key factors are speed, scalability, and reliability. We must deliver processes that are scientifically sound, cost-efficient, and safe, while always anticipating the needs of our production plants and the customer” 

“There is a rapidly evolving landscape in chemical development which is shaped by technological innovation and regulatory complexity. Indeed, the increasing complexity of molecular structures demands smarter synthetic strategies and specialized containment, especially for potent compounds. This complexity also impacts scalability and safety, requiring process design mindset from the start. Advanced process development technologies like flow chemistry, continuous manufacturing, and the use of HTE platform are transforming how chemists approach synthesis. These innovations improve efficiency, reproducibility, and sustainability, which are now essential rather than optional. “

“Importantly, regulatory expectations must be considered early. Scalable processes should be designed with GMP compliance in mind, including impurity control, reproducibility, and traceability.” 

 How do you ensure smooth transfer from lab to industrial scale ?

“We design with scale in mind from the beginning. By testing realistic conditions, anticipating variability, and applying rigorous risk assessments through Quality by Design, we make sure what works in the lab works just as reliably in production for our clients.” 

“From a process chemist’s perspective, it involves a combination of technical knowledge with robust methodologies, critical thinking, strategic planning, and cross-functional collaboration. The goal is to maintain product quality, safety, and efficiency while scaling up.” 

“It starts with developing a robust and scalable synthetic route during early development. This means choosing reactions and conditions that are not only efficient in the lab but also feasible and safe at larger volumes. Reactions should be reproducible, tolerant to slight variations, and avoid as much as possible hazardous intermediates or extreme conditions. “

Obviously, thorough process understanding is essential. This includes identifying critical process parameters (CPPs) and critical quality attributes (CQAs), and using tools like Design of Experiments (DoE) to map out the design space. This helps anticipate how changes in scale, equipment, or environmental conditions might affect the outcome. 

Material compatibility and equipment selection are also key. Mixing, heat transfer, and mass transfer behave differently at scale, so these considerations need to be addressed at early development stage. 

Safety assessments must be scaled accordingly. Reaction calorimetry, thermal stability studies, and hazard evaluations help ensure that exothermic reactions or gas evolution won’t pose risks during scale-up. 

Documentation and knowledge transfer are crucial. Clear, detailed process descriptions, risk assessments, and control strategies must be communicated to manufacturing teams. Collaboration with chemical engineers, analytical scientists, and quality assurance ensures alignment across disciplines. 

Can you share with us a particularly complex project and how did you overcome the challenges? 

“We developed an eight-step API synthesis that included a demanding metal-catalyzed reaction. By combining laboratory research with process engineering at plant scale, we managed to cut the catalyst load by a factor of five. It was a significant technical achievement and a real team success.” 

In another example, we replaced a linear 9-step synthesis into a more convergent route synthesis to reduce the number of steps and also to limit the handling of potent intermediates. 

 How do you integrate innovation into process development? 

“Innovation for us means solving our clients’ challenges in smarter ways – whether it’s through digital modeling, advanced analytical tools, or new process concepts. The goal is always to reduce risk, accelerate timelines to Drug Master File, and deliver a robust process.” 

We have adopted a suite of advanced technologies into process development which will enhance efficiency, scalability, and quality, with an impact on sustainability. 

Flow chemistry, often used in continuous setups, is a transformative innovation. It enables safer handling of hazardous reactions and improves reaction efficiency. Continuous manufacturing approach can replace traditional batch processes with streamlined, steady-state operations that improve product consistency, reduce costs, and allow for real-time quality control.  

Advanced Process Analytical Technology (PAT) supports real-time monitoring and control of critical parameters. Techniques like spectroscopy and chromatography are integrated into production lines to ensure product quality throughout the process, not just at the end.  

Digital and simulation tools are increasingly used to model process behavior under various conditions. These methods allow chemists to test different scenarios, optimize parameters, and anticipate scale-up challenges without risking actual production.  

Finally, green chemistry principles are being embedded into process development. This includes selecting environmentally friendly solvents, minimizing waste, and designing energy-efficient reactions. These practices not only meet regulatory and sustainability goals but also improve overall process robustness. 

Adapting processes to meet needs of biotech vs. big pharma 

“For biotech clients, agility and speed are crucial, while large pharma values robustness and supply reliability. We tailor our approach—flexible and fast for small players, but scalable and compliant for the larger programs.” 

To adapt chemical process development approach, you need to understand clients’ needs in terms of strategic priorities, operational models, and risk tolerance. 

Biotech companies often operate with leaner teams, tighter budgets, and aggressive timelines. Their focus is typically on speed to proof-of-concept or clinical milestones. For process chemists, this means prioritizing rapid route scouting, flexible and modular process design, and early-phase scalability. Processes must be robust enough to support clinical supply but adaptable for future optimization. Biotech firms also tend to outsource more, so clear documentation and tech transfer readiness are critical. 

In contrast, big pharma emphasizes long-term robustness, global scalability, and regulatory compliance from the outset. Their processes must be optimized not just for clinical trials but for commercial manufacturing across multiple sites. This requires deeper investment in process development and lifecycle management.  

Overall, the role of CDMOs has evolved. Companies are seeking partners with deep specialization in handling complex molecules and navigating regulatory landscapes. This shift reflects the need for agility and expertise in a competitive market. 

What is your background? 

“I hold a PhD in Organic Chemistry (2016) – University of Lyon. 
I started my career as R&D Project Manager for 4 years. Responsible of process development of several CDMO APIs, from early to late phase and DMF registration. Several projects transferred to Limay and Porcheville’s pilot as well as industrialization to production sites. Experienced in Quality by Design, designing Control Strategy. 
Since 2021, I am Head of Innovative Process Development team, managing the team of 10-15 chemists (up to 6 PhD Scientists, lab Engineers and Technicians), responsible for chemical and process development of APIs in the Seqens’Lab. Our work covers Preclinical to Late-stage project for both CDMO and Generics activities, including regulatory strategies in partnership with analytical development.  “