Impurity Traceability & Control

The production of APIs often involves complex chemical and biological changes. As the production processes are based on chemical unit reactions and chemical unit operations, resulting in by-products, purification and refinement is necessary. Impurities such as API-related substances, residual organic solvents, and inorganic impurities, as well as their physical and chemical properties, the stability of APIs, and the possibility of contamination and cross-contamination are key considerations regarding the quality, safety and effectiveness of APIs.

Medicilon offers API related services including impurity identification and separation, as well as quality research and stability testing.

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(1) Preparation (or purchase) and standardization of impurities/standard samples
Preparation and standardization of API standard samplesPreparation and standardization of API and intermediate standard samplesImpurity standard samples (impurity preparation or purchase; structure identification and standardization if necessary, with impurity content of 10mg-500mg)Impurity research and impurity profiling
Medicilon employs multiple methods to determine metal impurities in API processes including inductively coupled plasma mass spectrometry (ICP-MS), inductively coupled plasma optical emission spectrometry (ICP-OES), and graphite furnace atomic absorption spectrometry (GFAAS).
(2) Quality research
Critical quality attributes (CQA)Physical and chemical properties (salt types, crystal forms, and particle sizes)Impurities (related substances, residual solvents, genotoxic impurities, elemental impurities, and chirality)Preparation of draft material quality standardsDevelopment of analytical methodsContent analysisMaterial inspections and releaseCentral control analysisValidation of analytical methods (HPLC, chiral HPLC, GC-HS)
(3) API stability tests
Influencing factors (1 month)Accelerated stability (6 months)Long-term stability (24 months)

FAQs

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

• Determination of synthesis route
• Optimization of process parameter, studies of salt structure and crystal structure process, preparation and calibration of reference product
• Confirmation of laboratory process
• Production of safety assessment batch
• Production of pilot scale up
• Production of clinical batch sample (GMP)
What are API Quality Study Processes in IND Phase?

1) Development of analytical method (starting materials, intermediates, API, Middle controlled Analysis, preliminary degradation tests)
2) Validation of analytical method (use pilot batch samples, if no pilot batch, use safety assessment batch)
3) Stability study (pilot batch or safety assessment batch + GMP batch)
• Influence factor study (in early stage, use Laboratory scale for pre-influencing factor test)
• 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
How to Control Impurities in Pharmaceutical? To What Extent are Impurities Controlled?

•Laboratory scale batch: purity 98.0%, with no significant impact on the limit of single impurity
• Safety assessment batch: purity 97.5%, the maximum single impurity control within 1.0%.
•Pilot batch: purity 99.0%, specific impurity control is less than the safety assessment batch, unknown single impurity 0.10%
•Clinical batch: purity 99.0%, specific impurity control is less than the safety assessment batch, unknown single impurity 0.10%

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