Production Process Optimization

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Service

• Medicilon’s API production process optimization services include:
  Establishment of API quality standardsEstablishment of central control standardOptimization and determination of important process parametersOptimization and determination of post-processing methodOptimization and determination of purification methodEvaluation and control of process risksProcess safety evaluationAutomatic reaction calorimeter RC1mx, differential scanning calorimeter (DSC) and accelerating rate calorimeter (ARC) to evaluate reaction calorimetry, secondary reactions of raw materials, intermediates, and products (thermal stability evaluation) Establishment of quality standards for raw materials, intermediates, and finished productsImpurity profile researchPreparation of CTD documents

FAQs

• To What Extent does Process Optimization Need to be Done?

  Meet the quality requirements of laboratory scale, safety, pilot, and clinical batches, with appropriate attention to yield and process fluency.

• Process Development Stage

  1. Literature research, patent evaluation report.

  (1) Find out as much relevant information that is already publicly available as possible.    
  (2) Design multiple possible synthesis routes.    
  (3) Evaluate whether there is intellectual property risk in the synthesis route.

  2. Selection of synthesis route and reaction design

  (1) Complete the design of each step and evaluate the profile, impurity spectrum, yield, and quality of each reaction step based on previously accumulated knowledge.
  (2) Complete the post-treatment design of each step, including quenching, purification, filtration, and drying.
  (3) RFT (Right First Time).

  3. Process optimization.

  (1) Comparation of before-and-after optimization and determination of "key process points."   
  (2) Draft preliminary quality standards for starting materials and intermediates.

  4. Impurity spectrum study.

  (1) A comprehensive study is not required.   
  (2) There should be an overview of the major impurities.

  5. Analysis of the reaction mechanism.

  (1) Analyze the reaction mechanism of each step and find the direction of controlling side reactions.
  (2) Choose the conditions that are favorable for the primary reaction.

• Process Research Methods

  • DOE and Parallel reaction 

  Optimization of reaction conditions: reagent equivalent, temperature, concentration, reaction time, etc. 

  It can significantly improve the efficiency of condition optimization and get the optimal condition quickly.

  • Destructive test (Stress test) 

  It is essential to do destructive tests for laboratory-scale batches, including the stability of starting materials, intermediates and products. 

  After the initial optimization of the process, it tests the applicable scope of the process.

  • The Spiking experiments 

  Verify process performance, such as whether the spec setting is reasonable and whether impurities can be removed.

Relevant laboratories

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