The pursuit of "zero defects"

Time:2021-04-15

On July 6, 2018, Yangzijiang Pharmaceutical Group Beijing Haiyan Pharmaceutical Co., Ltd. Starfish QC team lives up to the public's expectations and won the first prize and the certificate of best publication in the 39th National Pharmaceutical Industry QC Team Achievements Publishing Exchange Meeting. The joy of every member of the group was palpable. A year ago, however, they were frowning over a statistic.


In the midsummer of 2017, the sound of cicadas outside the window disturbed people's mind. The process optimization of the S API, a key research and development project of Haiyan Pharmaceutical, entered the bottleneck period. The Institute of Materia Medica decisively established the "Starfish QC Group", hoping to break the bottleneck.


Through the in-depth analysis and repeated measurement of the status quo, the starfish QC team put forward the goal of "reducing the content of isomer A and isomer B in S API respectively to less than 0.10%". In order to achieve this goal, the group quickly held a brainstorming meeting to analyze the reasons for the formation of the isomer of S API. We gathered our wisdom and listed the factors that affect the content of isomer one by one.


After a large number of experiments, correlation Pearson analysis and ANOVA analysis were used to make a comprehensive analysis of the experimental data. After 3 months of unremitting efforts, 6 major factors affecting the content of isomers were finally screened out from 13 terminal factors. That is, "improper proportion of starting material, high pH of reaction liquid, long reaction time, improper proportion of recrystallization solvent, high crystallization temperature and short crystallization time".


After identifying the key factors, the starfish team took advantage of the victory to pursue the success. In order to complete the process optimization better and faster and achieve the established goals, Dr. Xiaobo Wang introduced the new experimental Design concept of "Box-Behnken-Design Response Surface Optimization Method". After repeated exploration, the team finally combined this method with the experiment of the project successfully, and obtained the experimental scheme of "ring closing process" and "refining process" respectively.


Immediately, the team members carried out the relevant experiments in full force, and the late-night observation data became commonplace. Finally, by summarizing and sorting out the experimental data, regression analysis was carried out, and quadratic polynomial regression equation was established. By referring to the contour map and three-dimensional effect surface map, the group selected the optimal process parameters of ring closing reaction and refining process. With anxiety and excitement, the team members verified the improved process parameters, and 6 batches of samples in A row all reached the target. The content of isomers A and B in S API was far below the limit requirement of 0.10%, which was A complete success.


Every member of the team helped the writer to cross-check the data, refine the sentences, revise the PPT again and again, rehearse it again and again, and try to make it perfect. Action comes from the heart, force comes from the will, although the process is full of hardships, but the pride of challenging success makes everyone feel that all the efforts are worthwhile.