Impurity Elementanalysis Methods And Case Analysis Of Pharmaceutical Raw Material In The Drug Registration Regulations Of Europe And United States

The any other ingredients outside of drug chemical entities in the API can be called as impurities strictly.What's more,those not belong to the prescription drug ingredients composition in the drug product also can be defined as impurities.The existence of impurities not only affects the quality of the drugs,but also can reflect the storage problems in the process of manufacturing,such as the degradation impurities.The detection of impurities in API can ensure the safety,effectiveness,and as well as provides the reference for production,distribution and enterprise management.According to the chemical categories and characteristics of impurities in ICH,it can be classified into the following categories: organic matter,inorganic impurities and residual solvents.And inorganic impurities include: reagents,ligands and catalysts;heavy metals or other residual metals;inorganic salts;other materials(e.g.,filter aids,charcoal).In 2008,European Medicines Agency(EMA)published the relevant guideline?Guideline on the specification limits for residues of metal catalysts or metal reagents?.In the guideline,classification,concentration limits and specification are introduced.In December 2014,ICH published the newest guideline for element impurities?ICH Q3 D Guideline for elemental impurities ?,element impurities were reclassified in this guideline,the control elements were increased to 24 kinds,which contains the commonly metal catalysts,heavy metals and some highly toxic nonmetallic elements,such as arsenic,mercury,selenium,etc.So,we can know the monitoring is becoming stricter and the scope is wider.This paper sum up the related laws and regulations of elemental impurities,and compare the similarities and differences between national laws and regulations;And study on the modern analysis method of the detection element impurities and discuss the advantages and disadvantages of various methods.Through the literature review,laws and regulations,registered case analysis to explore the evaluation for international registration and control limits.And take the CEP apply as examples,analyze the frequently encountered problems in the registration and discuss how to reply the deficiency letter.At the same time,put forward some ideas and method to reduce the deficiency letter,which can accelerate the review and better serve the drug registration work for pharmaceutical enterprises.