Chemical Process Design, Development and Optimization
Syngene‘s chemical process design and development team comprise of 250+ scientists. The team has the skill sets and experience to meet a wide range of scientific requirements, including route scouting, chemical process optimization, chemical process familiarization, feasibility studies and scale up to support the development continuum. Working in state-of-the-art laboratories, equipped with high end Process Research & Development (PRD) tools such as QbD and PAT techniques, our scientists efficiently carry out studies for the different phases of product development. Contribution of our scientists is not only in the quick delivery of the project, but also advising our clients on synthetic methodology tools and development approach, based on scientific rationale. Our team follows phase appropriate – fit to purpose development approach.
- In depth route design and scouting exercise performed by a team of creative synthetic organic chemists with global experience.
- Thorough literature search using search tools such as SciFinder, Beilstein and online access to most of international journals in chemistry.
- Team is well versed with retrosynthetic approaches and possess broader experience in various fields of chemical process development.
- The combination of a large pool of discovery chemistry scientists and process development scientists makes a winning combination for the route design, development and optimization.
- Route selection is done by quickly down selecting a few promising routes for further laboratory experimentation.
- Proof of concept approach for further screening and the best route is developed into a large scale process.
- Development studies performed in a world class lab equipped with miniature reactors and relevant engineering tools.
- Engineering studies and analytical development as part of process development.
- Environmental factor (e-factor) and process mass intensity (PMI) built in the development approach.
- Translate chemical reactions into a safe, reliable, efficient and cost-effective manufacturing process for APIs, intermediates, regulatory starting materials and performance chemicals.
- To provide an economic, safer and more convergent way of the manufacturing process.
- Absorb chemical processes at any level of maturity to understand the critical process parameters and perform complete process optimization using classical or statistical tools such as Design of Experiments (DoE).
- Maximize potential economics of a chemical process by leveraging decision variables while staying within known constraints.
- Demonstration batches in the development/kilo lab to verify the preferred process conditions, once the preferred conditions are arrived.
Identification and Characterization of Impurities
- For understanding reaction pathway, impurity purge studies, fine tuning of process parameters and regulatory requirements.
- Identification of process impurities based on the knowledge of raw materials, synthesis method and storage stability.
- Postulating unknown impurities based on analytical techniques such as NMR and MS analysis.
- Impurities are isolated by purification techniques or synthesized via retrosynthetic analysis and characterized completely. Screened impurities include organic & inorganic molecules, metal and residual solvents.
- Extensive spiking studies in actual reactions to arrive at the tolerability of these impurities in the optimized process (fate of impurities and purging studies).
Syngene process engineers work closely with scientists from the beginning of the process development activity to identify the gaps and to bring in scalability aspects.
This unique approach has enabled our team to develop robust and scalable processes against challenging timelines.
This dedicated team of chemical engineers is specialized in unit operations.
A few examples of the various unit operations and studies are presented below:
- Software based DoE studies
- QbD and Process Control Justification (PCJ) studies
- Process intensification studies
- Kinetic studies and modelling
- Mass and energy balance studies
- Corrosion studies
- Filtration studies
- Drying studies
- Distillation studies: Regular and Packed columns
- Crystallization studies
- Scale-up/scale-down studies
- Batch to continuous (Flow chemistry)
- Development of flow process
- Particle engineering studies
DoE and QBD Studies
- This is one of our key differentiators in the development space and is recognized by our global customers. Syngene has developed the approach, methodology and tools, and evolved over the past several years of experience in this area.
- Syngene adopts a risk based systematic approach to design experiments for QBD.
- At Syngene, typically the experimentation is via Design of Experiments (DoE) approach, which provides substantial information on the process, and helps to optimize and develop a design space for the process.
- The developed design space is validated with experiments and considered for scale up.
- Our team has proven capabilities in Process Control justification studies (PCJ), Statistical process control (SPC), Regression analysis, Process Modelling to provide significant information on the processes. This understanding enables us to develop Robust, Quality focused, Reproducible, Economic and Safe Scalable Processes.
- Process safety is the core of Syngene‘s process development, wherein process safety considerations are brought in at the very first process discussion stage itself. This is well demonstrated by our impeccable safety record as well.
- Process safety is given its due importance at the stage of RFP evaluation and project execution. KRM consideration, reagent selection, route selection, experimental planning, batch size selection, equipment selection, manufacturing plans are evaluated thoroughly and systematically using our own approaches.
- The process safety team is equipped with the basic and advanced tools to evaluate the risk, both qualitatively and quantitatively.
- What-if, PHA, PHIRA, HAZOP, HAZAN, FMEA, LOPA, Process review and feasibility analysis etc. are used for qualitative analysis.
- Advanced tools such as DSC, RC1e, TGA, Chetah (Software based evaluation program), off-gassing studies for vent sizing, are used for quantitative analysis.
- Syngene also collaborates with external partners for performing studies such as MIE (Minimum Ignition energy), MIT (Minimum Ignition temperature), Percussion tests and dust explosivity tests.
- Our Unique approach of involving process safety team right from the beginning ensures a robust and safe process developed against challenging timelines.
Salt and Polymorph Screening
- At Syngene, the salt and polymorph screening studies are done by a cross functional team including experienced process chemists, solid state experts, process engineers, pre-formulation experts and formulators.
- A tiered approach for the salt and polymorph screening studies is followed at Syngene.
- Screening using neat and mixed solvents to identify the most stable thermodynamic polymorph.
- Salt screening Involves search for solid salts of ionisable drug products. Key factors considered during screening are pharmaceutically acceptable counter-ions, frequency of use in drug products, and manufacturability.
- The obtained information enables us to select the best physical properties of the drug substance to ensure efficacy and provide consistency during formulation and manufacture.