We have real hands-on experience not only developing but also filing small molecule processes with regulatory agencies across the globe. We have developed processes that include a vast array of unit operations (reactions, extractions, solvent exchanges, distillation, adsorptions, crystallizations, and milling/micronization). To design and develop your process, we rely on the extensive experience of our team and the use of enabling technologies.

Unit Operations

We have the expertise and capabilities to develop any unit operation used for in a synthetic route. Some examples of what we have done include:

Reactions. We have experience with a variety of reactions, including condensation reactions, C-C cross-coupling reactions, hydrogenations, catalysis, protection and deprotection, to name a few. Moreover, we have experience with different operation modes, including batch, semibatch, and continuous reactions.

Liquid-liquid Extractions. We have extensive experience in efficiently developing and optimizing this type of extractions – commonly used to purify active pharmaceutical ingredients and intermediates - by leveraging our deep expertise determining liquid-liquid equilibrium (LLE) and our experience in developing targeted experiments.

Solvent exchange and distillations. As with liquid-liquid extractions, our deep expertise in understanding vapor-liquid equilibrium (VLE) and years of experience in the lab allow us to quickly design robust solvent exchange and distillation operations, whether it is to enable the transition to a new processing step that requires a different solvent, or a different concentration using the same solvent.

Adsorption. We have significant experience in developing impurity scavenging processes. Our expertise in mass transfer and thermodynamics makes our development process highly effective and efficient.

Crystallization. We design portable crystallizations and isolations. We have the tools and the knowledge to undertake complex crystallization development, particularly those processes where many drug substance critical quality attributes need to be met (form, purity profile, particle size). While quality is paramount, we keep in mind our client’s business goals (yield, cycle time, process greenness) and make relevant recommendations to ensure process robustness and scalability. We specialize in developing open/close loop crystallization policies that can be scaled up confidently. Based on our vast experience developing crystallizations, we avoid overengineering operations that do not translate well at large scale due to additional complexity or lack of access to specific technology at manufacturing facilities and contract manufacturing organizations. From simple kinetics of growth and nucleation, to multidimensional population balances, our team develop robust crystallization processes for free forms, salts, and cocrystals.

Milling. Our team has pioneered several new methodologies to design and scale up wet milling and dry milling operations. We characterize the main phenomena that affect particle size or form, including particle breakage and form transformation rate and build scale independent milling curves that can be translated between equipment and minimize the number of experiments.

Filtration and drying. We characterize filtration to understand scalability. We develop drying operations that ensure solvent removal but also more complex desolvation/dehydration/humidity-controlled processes to achieve the desired crystalline form at the drying end point.

Co-processing. We have experience developing co-processing steps for starting materials, intermediates, and drug substances, using a diverse set of techniques such as coprecipitation and incipient wetness impregnation.

Enabling Capabilities

Our expertise also encompasses all the key enabling capabilities for process development:

PAT. In addition to traditional off-line samples, we use the right technology to monitor your process. We define and implement sampling schemes and monitoring techniques that best suit your processes.

Modeling, simulation and data science/AI. Modeling and data science are one of our biggest strengths. We are “practical” modelers and data scientists that understand the need for developing scalable process based on detailed understanding of the underlying physicochemical phenomena of the process. Models are an integral part of our development approach, they are used to guide experimentation, design optimal target conditions, and explore operating regions. Our modeling and data science capabilities are extensively “agency tested”. We have experience filing low, medium, and high impact models.

Flow chemistry. Our extensive experience designing, modeling and scaling up continuous processes includes all types of reactors (e.g. CSTRs, MSMPRs, tubular reactors, and packed beds), and enabling operations (e.g. mixing, settling, and fluidization). We also have experience developing and filing residence time distribution (RTD) models to support lot genealogy and material diversion decisions. Our capabilities allow us to develop any continuous operation, based on the process needs, and the manufacturing constraints you may have your facilities and/or contract manufacturing organizations.