CMC Solution Services

CMC Solution Services


We provide “CMC solution service” (Sample synthesis, Analytical test, Development of synthetic procedure, Development of analytical procedure, and CMC developmental support) as One-Stop Service at all Research and Developmental stages.

Development of Synthetic Procedure

We support the process development from sample synthesis to synthetic procedure studies, scale-up studies.

We meet the various customer's needs by offering the service of “API process development and Quality design” based on our experiences and know-how accumulated in contract manufacturing for API or intermediates so far. Experts of the process development provide CMC solution services seamlessly and speedily from synthetic procedure studies including synthetic route scouting to API manufacturing.

  • Synthesis of API/intermediate samples for various tests
  • Synthetic route scouting based on reaction safety, production cost, etc. (SELECT criteria)
  • Extraction of issues that may occur in actual manufacturing and confirmation of tolerances. (PAR study)
  • Synthesis and identification for impurities, metabolites, decomposition product, standard reference material, etc.
  • Investigate the causes of problems identified in actual manufacturing and propose improvements.
Case examples
  • Synthetic route scouting for API and intermediates (Major pharmaceutical company)
  • The drastic improvement of API manufacturing process (Major pharmaceutical company, Bio-venture)
Case examples
Case A;Synthetic route scouting for APIs/intermediates (for a major pharmaceutical manufacturer)
Items Original Route Improved Route
Steps 6 Steps 4 Steps
Overall Yield 70% 70%
  • Many chemical transformations, concerns about analogous materials control
  • Long process and complicated operation such as solvent replacement
  • Extremely long equipment occupancy period
  • Setting the appropriate intermediate isolation point
  • Robust and simple setting of operating conditions
  • Cut equipment occupancy time in half
Case B;Drastic improvement of API production method (for bio-venture)
Items Original Method Improved Method
Clinical Stage Phase 1 Phase 2
Steps 8 Steps 8 Steps
Challenge Early development level manufacturing methods
  • column purification
  • Unsatisfactory impurity control (ICH-Q3A)
  • Unsatisfactory control of elemental impurities(ICH Q3D)
  • Complicated to operate throughout the process
  • Starting material in the application for approval is not defined
Manufacturing methods for commercial production
  • All processes are column free
  • Establishment of an impurity management strategy (ICH-Q3A)
  • Establishment of elemental impurity management strategy (ICH-Q3D)
  • Robust and simple setting of operating conditions
  • Proposed starting materials for approval applications

Development of Analytical Procedure

We support swiftly the development of analytical method from setting at early development stage to robust setting in the late development at commercial production stage.

Experts of CMC development meet the various supports of customer’s quality issues at every stage of drug development. We can develop analytical methods that can evaluate the quality of drug substance. Thanks to our internal close relationship, collaboration and communication among R&D and manufacturing members we can surely grasp impurity management strategies of drug substance and intermediate. Furthermore, we can conduct various analytical tests based on both quality standards of GMP and regulations for quality.

  • Analytical method scouting
  • Development of test methods (including validation of analytical methods) and setting of standards for physical and chemical tests, microbiological tests, evaluation of physical properties, related substances, etc. according to the development stage.
  • Development of high-sensitivity analytical method (including validation of analytical methods)
  • Development of elemental impurities analytical method using ICP-MS (including validation of analytical methods)
Case examples
  • Proposal of quality control strategy for APIs according to development stage (for major pharmaceutical manufacturer)
  • Analytical method development and method validation for investigational new drugs, intermediates, starting materials and in-process control test (for major pharmaceutical manufacturers & drug discovery bio-ventures)
  • Setting of specifications and test methods for APIs according to the development stage (for a drug discovery bio-venture)
  • Data acquisition for pharmaceutical manufacturing and marketing approval application (for a major pharmaceutical manufacturer)
  • Preparation of IND application materials and investigational new drug summaries (for a drug discovery biotech company)
  • Support for responding to inquiries from regulatory authorities (for a major pharmaceutical manufacturer)

CMC Developmental Supports

Our service covers the CMC development from early development stage to new drug application.

Experts of CMC development meet the various customer's needs from early development stage to new drug application. We provide long-term process management strategy (various regulation correspondence, construction of the supply chain, new drug application, commercial manufacturing) through the whole drug life cycle as "One-Stop" service by fully utilizing our production facilities.

  • Propose CMC development strategies according to the drug development stage
  • Obtaining data for application using PAT (Process Analytical Technology) tools
  • Conduct risk assessment (FMEA) for QbD application, and obtain Design Space using DoE and provide the results.
  • Preparation and documentation for IND, NDA and Drug Master File, official inquiry correspondence
  • CMC developmental supports by outsourcing (e.g. polymorph screening, in silico screening (ICH M7), synthesis of radio-labeled compounds, MSDS authoring service, CMC consulting, intellectual property investigations, etc.), and project management
  • Management of raw material pharmaceutical suppliers compatible with PIC/S GMP and construction of the supply chain
Case examples
  • Process parameter studies for application using the PAT equipment (Major pharmaceutical company)
Case examples
Case C;Support for supplying APIs for formulation studies using PAT tools (for a major pharmaceutical company)Process parameter studies for application using the PAT equipment (Major pharmaceutical company)

Repeated Ostwald ripening and crystallization trends

Repeated Ostwald ripening and crystallization trends

Repetition of Ostwald ripening and transition of crystal appearance

Ripening n=0

Ripening n=1

Ripening n=2

Ripening n=3

Ripening n=4

Ripening n=5

Ripening n=10

Repeated Ostwald ripening promotes crystal growth to the desired grain size.

Case D;Support for acquisition of laboratory data for approval application (for a major pharmaceutical company)

Image of obtaining lab data for approval application (CPP identification and PAR/design space construction)

Process Operation Process Parameters Significance
Reaction Reagent [eq.] Critical
Solvent [vol/wt] Not critical
Temperature [°C] Critical
Pressure [MPa] Not critical
Agitation [rpm] Not critical
Work up Extraction solvent [vol/wt] Not critical
End point of Concentration [vol/wt] Critical
Temperature [°C] Not critical
And more...
Small scale, small case, anyone please inquire.
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