Q&A Session with our founders, Steve Winter and Victor Diaz

Over the past three years, we’ve had the privilege of collaborating with many of you, and we've compiled some of the most frequent questions that we have received from you, our clients, to provide deeper insights into our operations. Our founders are here to address your queries. This session aims to give you a clearer understanding of our capabilities and how we can support your projects effectively. Let’s dive into the answers to your burning questions!

Q: What specialist instrumentation do you use?

A: We offer a comprehensive range of solid-state characterization techniques; our labs are fully equipped for solid state work, including high resolution X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), optical microscopy, planetary milling for effective grinding, reflectance (turbidity) probes, multireactors and jacketed vessels, etc. We also have a few other pieces of equipment available in any chemistry lab, like balances, rotatory evaporators, vacuum ovens, etc, and can facilitate other specialist techniques through our collaborators dynamic vapor sorption (DVS), single crystal X-ray diffraction (SCXRD), scanning electron microscopy (SEM), Raman spectroscopy, particle size distribution (PSD), KF, IC, elemental analysis, BET, MED, and solid-state nuclear magnetic resonance (SSNMR). Basically, we will endeavor to provide access to every technology required to ensure the work is done effectively and efficiently.

Q: How do you handle solid form screening?

A: Our solid form screening process involves a systematic approach using various solvents and crystallization methods to identify different solid forms. We typically favor a medium throughput approach instead of a high throughput one. We believe there is more value investing time and effort to design a proper research space and generating sufficient material in each experiment to confirm or deny hits, rather than performing thousands of experiments that can often lead to false positive or negatives, and for which we do not generate enough material for subsequent testing. In the case of salts or cocrystals, we also ensure that the counterions or coformers selected are pharmaceutically acceptable ones and appropriate for the intended use for which the API has been designed. Recently, we have started to use a CSP-based cocrystal prediction method to rank 15-20 pharmaceutically acceptable coformers by the energy of the cocrystallization reaction with the API to guide experimental screening.

Q: Can you assist with the selection of the best solid form for development?

A: Absolutely! We provide expert guidance on selecting the optimal solid form based on its physicochemical properties, stability, manufacturability, and bioavailability. Our goal is to ensure the chosen form supports the API's development and commercialization.

Q: How do you optimize crystallization processes?

A: We optimize crystallization processes through a combination of experimental design, process analytical technology (PAT), and theoretical modeling. Our starting point is always a good understanding of the solubility of the desired solid form in different solvent systems, to which we then apply certain models that allow us to predict the behavior of the API and to determine the metastable zone width in specific solvent systems. This approach helps us control crystallinity, optimize yield and purity, and, often, modulate crystal size, shape and habit, ensuring a robust and scalable process.

Q: Can you scale up crystallization processes from lab to pilot scale?

A: We have extensive experience in scaling up crystallization processes from lab to pilot and commercial scales. We offer stage-appropriate development, understanding that some adjustments may be required as the synthesis develops and the impurity profile changes, or when the kinetics vary upon scaling up the process. Our approach helps us understand the thermodynamics of the system and which parameters affect the kinetics of the process, so we can anticipate potential issues. In our labs, we scale up to typically 2 L processes, but our team works closely with clients to ensure seamless technology transfer and process validation, even placing a scientist at the client’s plant to oversee the process transfer.

Q: What preclinical formulation development services do you provide for small molecule APIs?

A: We start by understanding the physical properties that can affect the performance of the drug substance, with that in mind, and with the refined developability classification system (rDCS) as our framework (for oral drugs, of course), we can anticipate the challenges in terms of solubility and permeability, and we can subsequently plan the development of preclinical formulations that will improve the performance of the drug substance, especially when an increase in solubility is required (let’s not forget that solubility and permeability are compensatory when defining the maximum adsorbable dose). Subsequently, we can offer excipient compatibility studies, excipient screening and preclinical formulation development, followed by performance and stability testing. We can also prepare relatively small amounts of drug product for in-vivo testing if required.

Q: How do you ensure the quality and compliance of your preclinical studies?

A: We are not currently GMP or GLP accredited, although having worked in GMP environments before, we are very familiar with their stringent regulatory guidelines and standards, and have built them in in our culture and in our own quality management system (ISO 9001 accredited) ensuring rigorous documentation, data integrity, and alignment with all relevant regulations.

Q: What sets your company apart from other service providers in the industry?

A: Our team is highly experienced, really, both in solid state research and as CRO service provider. Unlike other larger CROs, our only focus is the provision of solid state, crystallization and preclinical development services, we are not a supporting function, and every improvement that we can implement directly benefits our clients. Being an independent unit, we embrace a great deal of flexibility and have total freedom to work with our clients on solutions that otherwise would not form part of our portfolio, or going into industries which you couldn’t approach in a GMP accredited lab. And finally, we have purposely kept our overheads very low, allowing us to offer competitive prices and really good value for money for our clients. Our motto is ‘Delivering exceptional services that lower costs, increase success rates, and reduce the time to market for clients and patients’. We offer truly tailored solutions, rapid turnaround times, and a collaborative partnership to support our clients’ success.

Q: Can you provide case studies or examples of successful projects you've completed?

A: We maintain strict confidentiality for all our clients. However, at a very high level, we can share examples of actions that led to successful projects. For instance, I can think of an occasion in which a change in the seeding temperature of just 3°C led to control of a process that had been hit and miss until then. An understanding of the solubility curves and metastable zone width helped us reach that conclusion. There are many other instances in which we achieved significant success for other projects, but we can discuss those at a later time.

Thank you for joining our Q&A session. We hope the answers provide valuable insights into our services. Your questions are instrumental in driving our commitment to excellence and innovation. If you have any further queries or need more specific information, please don’t hesitate to contact us. Together, we can continue achieving outstanding results. Stay tuned for more updates and thank you for being a part of our journey!