One-stop API Process R&D

Strengths and Features:

• The process department currently has a total area of about 6000 m2, including 2000 m² of R&D lab, 800 m² of non-GMP pilot scale up workshop, 1000 m² of GMP API workshop and 1000 m² of analysis and testing center, 800 m² of GMP compliant QC lab, and 200 m² of microbiology lab. A strong R&D team supports API process development services covering areas such as synthesis, analysis, microbiology, QA and QC. The team has rich experience in innovative drugs, consistency evaluation, successful R&D of improved new drugs, in China-US dual filing and in project management.
  From pre-clinical trial synthesis, process development to commercial production and the whole supply chain system of R&D, procurement and production, we provide innovative process development and large-scale production services for enterprises. With the establishment of GMP-compliant API workshops we can provide customized services for GMP production, helping more R&D-oriented companies to carry out practical technology transformation, shorten time-to-market and promote commercialization.
• One-stop Process R&D Service
  Medicilon's Process Department aims to meet customers' needs for a one-stop service for API development, and to utilize our extensive medicinal chemistry experience to efficiently drive our customers' drug development projects, to facilitate the development of new drug to enter earlier into the clinical phase, and to effectively help our customers to control the costs of development.
• From CRO to CDMO
  Medicilon Process Department can not only perform R&D, testing and stability studies of generic drugs for customers, but can also deliver R&D, production, testing and stability studies of innovative drugs in clinical phase I and phase II,developing from process R& to industrial commercial production and transforming from CRO to CDMO
• Equipment
  Our experimental equipment and the technologies we use are  advanced. Analytical instruments include UPLC, HPLC, GC, IC, LC-MS, GC-MS and other chromatographic analyzers, as well as laser particle size sizer (PSD), constant temperature and humidity test chamber, differential scanning calorimeter (DSC), thermogravimetric analyzer (TGA), X-ray powder diffraction (XRPD), nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FT-IR) UV spectrophotometer, cyclometer, muffle furnace, melting point meter, moisture meter (KF) conductivity meter, TOC and ICP-MS.
  Through continuous investment in laboratory instrumentation and the establishment of GMP workshops, we are committed to providing customers with high-quality products and services through productive, rapid, problem solving and active communication. We have expanded the scope of pharmacy services while enhancing the capability and level of pharmacy services to offer a full CDMO service.

Innovative Drug Process Research & Declaration

• We provide preclinical and clinical stage API process development, optimization, manufacturing and filing services. We have established a GMP-compliant API research platform and have successfully developed APIs for innovative drugs for several pharmaceutical companies in accordance with the latest regulations and guidelines. We also have developed GMP APIs for preclinical trials for innovative drug companies.
• Our services
  Customized starting materialsSynthesis process researchRoute design and determination | Process optimization | Impurity/specimen preparation (or purchase) and standardization | Laboratory process confirmation 1 batch | Pilot scale up production 2 batches (pilot batch (non-GMP)) | Safety assessment 1 batch (toxicology batch (non-GMP)) | GMP production 1 batch (cGMP batch production)Quality StudiesEstablishment of material quality standards | Development and optimization of analytical method | Material testing and release | Central control analysis | Validation of analytical methodStability StudiesInfluencing factors experiment (1 month) | Accelerated stability (6 months) | Long-term stability (tentative 24 months)Crystal Structure Screening & Process DevelopmentCrystal Structure Screening | Crystal Structure Process StudyFiling Services in Both China & U.S.Reports and information: Process Optimization Report | Pilot test production report | Method validation report | Stability report | CTD format reporting materials.

Process Route Screening

• Medicilon provides customized starting materials, design and confirmation of synthesis process routes. We conduct research on the product to be developed, review a large amount of data, analyze the synthesis route and the original source of synthesis, and analyze the synthesis equipment and synthesis cost to understand whether the synthesis route has intellectual property issues, whether the production cost is acceptable, whether it can meet the green chemistry, etc. We conduct route screening, process optimization, quality research, and process validation.
• Our services
  Route design & screeningSalt screening, crystal structure study and crystal process developmentSalt ScreeningCrystal structure screeningCrystal structure process studies (laboratory test processes, kilo-scale processes)Statistics and experimental design by using quality by design (QbD) and multivariate data analysis Quality studies of APIs and intermediatesDevelopment and validation of analytical methodTechnology transfer and process validation
  Medicilon helps customers to select an API process routewhich is stable, of high quality, reliable, low cost and suitable for large-scale production by evaluating the technical feasibility, equipment availability, availability of principles and reagents, number of reaction steps, patent protection and environmental impact.

Generic Drug Process Research & Declaration

• Provide generic API manufacturing process development, optimization, production and declaration (DMF) services
• Our services
  Design intellectual property and cost-competitive synthetic routesRoute screeningConfirmation of API crystal structureOptimization of processQuality studiesThree batches of laboratory test & pilot tests and at least three batches of cGMP process validationAPI stability testingDevelopment & validation of API analytical methodPreparation and writing of API declaration, Medicilon provides all API work and CTD format declaration information required for generic API declaration (DMF)Declaration services for both China and US
  Establish a database of key process parameters by continuously optimizing the process to obtain a mature and easy-to-industrial process route. According to the characteristics of the process route, to establish the complete impurity profile of starting materials, intermediates and APIs, so that the prepared APIs can meet the requirements of generic formulations and thus industrial production at a given scale can be achieved.

Optimization of API Production Process

• Medicilon Process Department applies the concept of QbD to the R&D of API process, devotes itself to creating a suitable process route tailored for customers, and optimizes the API production process to improve product quality and process efficiency.
• Our services
  Establishment of API quality standardsEstablishment of intermediate control standardsOptimization and determination of process parametersOptimization and determination of post-treatment methodsOptimization and determination of purification methodsProcess risk assessment and control (assessment of the risk level of the process)Safety evaluation of the processEstablishment of quality standards for raw materials, intermediates and final productsImpurity spectrometry studiesCTD documentation writing

Solids Screening Platform of Process Department

• The solids screening platform of Medicilon‘s process department strictly follows the registration regulations and regulatory requirements of the NMPA in China and the FDA in the U.S. to study and control the solid forms of drug molecules in APIs and formulations, and is able to develop the most effective screening strategies based on the characteristics of the substances, including but not limited to crystallization methods, selection of solvent, selection of the suitable salt-forming acid and base.
• Our services
  Discovery
  Various salt forms/crystal structure/co-crystal of APIs
  Evaluation  
  The drug-forming properties of different crystal structure of APIs
  Development
  API crystallization production process to obtain target crystal structure, morphology and particle size
• Salt Screening
  Goal
  Improve the drug propertiesDiscover the most suitable salt form for developmentEnsure the protection of the effective patentCircumventing the prior technology patents
  Technology package
  Characterization of free state propertiesSolubility in different solventsSelection of the suitable salt-forming acid and baseMultiple salt formation techniquesCharacterization of physicochemical propertiesStudies of solid state and solution stabilitySalt form selection and recommendationPatent deliverables
• Salt Screening Process

  

• Co-crystal Screening
  Goal
  Improve the defects of the free stateDiscover the most suitable cocrystal for developmentEnsure the protection of the effective patentCircumventing the prior technology patents
• Polymorph Screening
  Goal
  Discover the most suitable crystal structure for developmentEnsure the protection of the effective patentCircumventing the prior technology patents
  Technology package
  Analysis of existing technologyTechnologies of multiple crystallizationCharacterization of physicochemical propertiesStudies of solid state and solution stabilityAnalysis of the relative stability of polymorphCrystal structure selection and recommendationPatent deliverables
• Polymorph Screening Process

  

• Qualitative, quantitative and limit analysis method development and validation
  Analysis of raw material crystallinity or impurity crystal structureQualitative and quantitative analysis of raw material crystal structure in formulationsDevelopment & validation of particle size distribution analysis method

  

  X-Ray Powder Diffraction (XRPD)

Biotechnology Platform

• Medicilon's process department has established a biotechnology platform with corresponding chemical technology platform, testing platform and GMP production platform. The biotechnology platform focuses on the combination of chemical synthesis and bioenzyme-catalyzed synthesis, on the research, development and application of bioenzymes, on the R&D and production of pharmaceutical intermediates and APIs in using green biotechnology, and on providing high-end CRO and CDMO services and testing and quality research services for pharmaceutical companies.
  Biological enzyme catalysis is characterized by high efficiency, specificity, versatility and variability, and mildness of reaction conditions. At present, the biotechnology platform has established dozens of large bioenzyme libraries, such as ketone reductases (KRED), esterase, imine reductase (IRED), nitroreductase (NTR), cyclooxygenase (COX), amidase, etc. In addition, we will also carry out research in the direction of immobilized enzymes and coenzymes.
• Our services
  Study of enzyme-catalyzed conversion processDevelopment and validation of analytical methodsResearch, development and application of bioenzymes

  

FAQs

• Why is sample purity required for screening API crystal structures?

  Impurities can affect the dynamic stability of APIs in solution and suspension by affecting nucleation and growth rates. Therefore, the screening for polymorphs using earlier batches of APIs, which may still contain many impurities, could yield different results compared to screening with later, purer batches. In unfortunate cases, significant forms may not be identified during the initial screening. Therefore, it is recommended to repeat the polymorph screening several times for a batch of APIs that reflect the impurity characteristics of the final product manufactured under GMP procedures before market release.

• What are the Steps of API Process R&D in the IND Stage?

  • Determination of synthesis route

  • Optimization of process parameter, studies of salt structure and crystal structure process, preparation and calibration of the reference product

  • Confirmation of laboratory process

  • Production of safety assessment batch

  • Production of pilot scale up

  • Production of clinical batch sample (GMP)

  • Preparation and writing of declaration documents in CTD format

• What are API Quality Study Processes in the IND Phase?

  1) Development of analytical method (starting materials, intermediates, API, Middle controlled Analysis, preliminary degradation tests)

  2) Validation of analytical method (using pilot batch samples, if no pilot batch, use safety assessment batch)

  3) Stability study (using pilot batch or safety assessment batch + GMP batch)
   • Study of influencing factors (early stage testing using laboratory scale)
   • Accelerated stability study (6 months)
   • Long-term stability study (24 months or extended to 36 months)

  4) Preparation and writing of declaration documents in CTD format

• Characteristics of an Excellent API Synthesis Process

  • Feasibility

    Whether the adopted process route can produce the target compound

    Whether the reaction conditions can meet the requirements of the industrial process route for raw materials, equipment, and reaction conditions in the commercial production

    Resolution of waste management issues

  • Controllability

    Good reproducibility

    Consistency in product quality between batches, meeting expected quality standards

  • Rationality

    Raw materials: readily available

    Selection of solvents and reagents: Preferably low toxicity, in accordance with ICH guidelines

    EHS: Environmental protection and labor protection comply with laws and regulations

    Cost: Competitive

    

Relevant laboratories

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