Strategies Of Impurity Control In Active Pharmaceutical Ingredients For Generic Drugs

Quality control should be implemented from the source. Quality control of active pharmaceutical ingredients (API) is the key in the production of pharmaceuticals. Effective control of API quality not only reduces the safety problem, but also reduces the unnecessary spending on drug development and production. China is one of the largest API production bases in the world with products exported to the international market. Effectively quality control of API may impact to the health of all mankind as well as the winning of more international drug markets.The unknown impurities in API were which not listed in the"related substance"of drug standard. Chinese Pharmacopoeia states that the"related substance"is the impurity which occurred during the established manufacturing process in the normal production and storage. Changing the manufacturing process needs to consider amending the relevant specification. The above statement leads to 3 issues: 1. Even in the established API manufacturing process, the API manufacturer has the potential possibility to source different qualities of raw materials due to the unspecified starting point of API manufacturing process. The unstable quality of raw materials may lead new impurity into the final product. 2. More and more API manufacturers improve production process to reduce the cost and increase the efficiency with the technology progress. New process may cause new by-product, thus increase the possibility to generate new impurity. Even though the Pharmacopoeia claims that changing the manufacturing process needs to consider amending the relevant specification, the industries still need a practical and systemic way to discover and control the new impurity. 3. Generic API just needs to do the bioequivalent trial instead of the clinical trial, so the new impurity maybe very hard to be detected once it was delivered into the product. With the purpose of solving the above issues, this paper firstly introduced the importance of impurity control and the current situation of Chinese impurity control. Secondly, the differences of API impurity control between China and ICH countries were compared and their advantages and disadvantages were summarized. Thirdly, Paracetamol was used as a case study to represent China's disadvantage of impurity control according to Chinese impurity control method. Finally, 4 suggestions were given to the drug authority to improve the regulations and a management system for control impurity was introduced to API industry.