The International Council for Harmonization of technical requirements for pharmaceutics for human use (ICH) defines an impurity as any component present in a drug whose chemical structure is not consistent with that of the drug. Impurities contained in drugs can reduce their efficacy, affect their stability, and some may even have toxic side effects on human health. Therefore, impurities have become one of the key concerns of domestic and foreign drug regulatory agencies.
One of the key requirements of generic drug consistency evaluation is to ensure that the impurity profile of the API is consistent with that of RLD as much as possible. Our company provides specific and sensitive analysis methods for impurities in RLD to help generic drug manufacturers clarify product development goals and improve the success rate of generic drugs passing consistency evaluation.
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The ICH guidelines classify impurities into organic impurities, inorganic impurities, and residual solvents.
Organic impurities whose chemical structure is similar to or related to an API are often called related substances. The analysis of the source and destination of organic impurities, as well as accurate and effective control, is one of the key items in chemical generics research.
Organic impurities mainly originate from the impurities contained in the starting raw material and itself, the synthetic intermediates and side reaction products brought into the production process, the degradation products of the finished product during the storage process, the impurities brought into the excipients or the impurities generated by the degradation of the excipients, and the impurities generated by the interaction between drugs and packaging materials.
For UV-absorbing substances, we can use LC / MS and HPLC / UPLC to analyze organic impurities in RLD.
For no UV absorbent substances, we can use RI, HPLC-CAD and IC-ED to analyze organic impurities in RLD.
Genotoxic impurities are substances that damage DNA directly or indirectly and produce mutagenic and carcinogenic effects, which include impurities produced during production or degradation products produced during storage.
Features of genotoxic impurities
- High requirements for specificity and lots of auxiliary materials
- The limit is very low, requiring high sensitivity and stability of the instrument
- The structure is so diverse that it is difficult to find a universal approach
- Some compounds are unstable and some are insoluble
For stable and non-volatile compounds in the solution/mobile phase, we can employ HPLC / UPLC / 2D-LC.
For volatile and stable compounds, we can employ GC.
For the analysis of unstable, chiral and other difficult to separate impurities, we can employ Supercritical Fluid Chromatography (SFC).
Inorganic impurities refer to impurities produced during the production or delivery of APIs and preparations, which are usually known. Sources may include reagents in the production process, such as catalysts, ligands, etc. Metals are introduced at other stages, such as reaction vessels, transfer pipes, filtration materials, etc.
Methods such as ICP-MS and the incandescent residue method are available for the analysis of inorganic impurities in RLD.
Residual solvent refers to the organic solvent used in the production process of APIs and preparations, which is difficult to completely remove. Residual solvents are often harmful to people or the environment, or cause degradation of APIs. GC is generally used to study residual solvents in RLD.
It is essential for generic drugs to conduct adequate impurity comparisons and research with RLD, and to combine them with the quality standards of RLD to ensure that impurities are controlled. Our company provides Comparative Analysis of Impurity Profile services for RLD and generic drugs.
