High-pressure Hydrogenation Reaction
Anhydrous anaerobic reaction
Chiral compound synthesis technology
Cyanide reaction; (Qualified to use 30% sodium cyanide (NaCN) aqueous solution, annual usage> 1000 tons)
Methylation reaction; (Formaldehyde participates in the reaction and dimethyl sulfate participates in the reaction)
Friedel Crafts (Annual usage of aluminum trichloride> 200 tons)
Oxidation reaction; (H2O2, KMnO4……)
Polymerization; (VA044……)
Ultra low temperature reaction; (-78 oC, 1000-2000L, SS+GL；-30oC, 500-1000L, GL)
High temperature reaction; (>200 oC, 500-1000L)
High vacuum distillation system (vacuum degree up to< 20 pa)
High efficiency film evaporation system (solvent can be removed quickly)
Rapid and accurate measurement of reaction heat, exothermic rate, heat accumulation, reaction outgassing rate, total outgassing, etc. in the reaction process
Measure the initial decomposition temperature, decomposition heat, temperature and pressure changes during sample decomposition. Evaluate the thermal stability of the sample
Assess the hazard level of the process
Based on the reaction scale and equipment parameters, evaluate the feeding rate of process amplification, etc
According to the detailed analysis on process validation in ICH-Q7, in the product production process, it is proved that theproduction used for products meets theGMP requirements through systematic and documented evidence of process validation. And the process is stable and reliable,
Process validation process
Process validation documents: process report, method validation report, batch production record master, process validation scheme
Process validation batch generally includes 1 to 2 pre validation batches and 3 process validation batches
Accelerated and long-term stability tests can be conducted according to customer requirements
Define and confirm key quality influencing factors of the process
Study the fate of actual impurities (greater than 0.10%) and potential impurities in the registered starting materials and separated intermediates
Collect information on registered starting materials and separated intermediates from different batch sources
Redeveloping or adjusting the analytical methods of registered starting materials and separation intermediates to ensure that the actual impurities, potential impurities and impurities generated in the subsequent reaction can be well separated
Carry out corresponding addition experiments on actual isomers, potential isomers, analogues and other by-products in the synthesis process of registered starting materials
Collect the experimental data of the study on the fate of impurities in the registered starting materials and separated intermediates, and compare them with the CQA of API to establish the control strategy for the registered starting materials and separated intermediates
Write quality standard report (record the process research and analysis research data of registered starting materials and intermediates in detail)
Route design and development
Evaluate whether the existing route and related steps meet the requirements of amplification, cost, safety and quality control
A doctor chemist with rich experience can suggest new synthetic routes and carry out laboratory exploration of new routes
Route exploration usually takes 2~3 steps/person week. The process chemist has the authority to operate LC-MS, GC-MS and other equipment, so as to quickly open up the route for subsequent process development
Quickly get through and optimize key steps through parallel reaction equipment
Apply new technology to make unacceptable steps acceptable
Rapid handling and production capacity of hazardous chemicals help route development and promote drug R&D progress
Process development and optimization
Fit for purpose process development and control strategy formulation
Completely carry out new drug IND research and support the application work
API process development and synthesis, supporting GLP TOX research and clinical research
Final process development for commercial production and supply
Process optimization to obtain robust process, reduce cost and improve output
High throughput screening and optimization of high cost catalysts
Salt type screening, crystal type screening, and then salt type crystal type characterization, selection and process development
API recrystallization process development and crystallization process optimization
Heterogeneous mass spectrometry analysis, impurity identification, synthesis and index setting
Application of online monitoring technology to guide process development, such as online infrared, online liquid phase, FBRM, etc
Apply QbD principles to guide process development, such as using DoE tools to conduct design space research
Capable of handling highly active compounds (OEL< 0.1 ug/m3)
Process safety test and evaluation (RC1, DSC, TGA, ARC, TSU)
Chemical engineering simulation capability supports process development (such as filtration rate simulation, oxygen content control assessment) and equipment risk assessment of project transfer (such as selection of kettle and paddle type, simulation and application of distillation parameters and azeotropic efficiency)
