2019.11.29日14:30，阮海宁在巡查菌种室二楼仪器室时，发现

At 12:25 on November 24, 2019, analyst Xu Min checked the H0-QS-30061 "Micafungin Sodium Intermediate Quality Standards" version 00 and found "6.7 Micafungin crude and nanofiltration concentrate detection The description of the correction factor for impurities in Method B is "F is the correction factor: the diacyl impurity is 3.4, and the remaining impurities are 3.1". The remaining impurities include impurity 8 (side chain acid) and other unknown impurities. The samples of crude micafungin and nanofiltration concentrate are tested with side chain acid as the standard. According to the provisions of H0-SOP-72031 "Analysis Method Verification Management Procedure" for the calculation of the correction factor, the correction of impurity 8 (side chain acid) The factor should be 1.0. <br><br>The root cause of this deviation is due to the risk of the description of the impurity correction factor in the 01 edition of H3-QS-20214 "Micafungin Sodium Intermediate Quality Standard". During the revision of the 02 edition, the analysts mistaken the remaining impurities for other Single impurity, did not notice that the remaining impurities include the known side chain acid (impurity 8) and other single impurities, which led to the revision of the intermediate quality standard. In subsequent versions (03, 04, 05, 06, H0-QS) -30061/00 version) During the revision process, the analysts focused on the revision content. The other unrevised parts of the file were not carefully reviewed, so the failure to notice here is due to personnel reasons. <br><br>1. This deviation involves 18 batches of crude micafungin sodium and nanofiltration concentrate detected between 2015.12.18 and 2019.11.23. The results of the 18 batches of crude micafungin sodium and the impurities 8 (side chain acid) of the nanofiltration concentrate are calculated according to the correction factor of 3.1, and the test results meet the requirements. The calculation is performed according to the correct correction factor. The test results are more than the original test data On the small side, there is no impact on the product quality itself. Subsequent revisions to H3-QS-20214 "Micafungin Sodium Intermediate Quality Standards" version 02 after the implementation of the historical batch of test results and output reports, the original test results are invalid. 2. Plan to revise H0-QS-30061 "Micafungin Sodium Intermediate Quality Standards", and revise the "correction factor: diacyl impurity 3.4 in the" 6.7 Method B ", the remaining impurities 3.1" to "correct Factor: The diacyl impurity is 3.4, the side chain acid is 1.0, and the other single impurities are 3.1 ", ensuring no impact on subsequent production and testing.<br><br>1. Revise the test results of 18 batches of crude micafungin sodium and nanofiltration concentration tested from December 18, 2015 to November 23, 2019, and issue a test report. <br>2. Revise H0-QS-30061 "Micafungin Sodium Intermediate Quality Standards" and modify the "correction factor: diacyl impurity 3.4 in the" 6.7 Method B ", and the remaining impurities 3.1" to "correction factor : The diacyl impurity is 3.4, the side chain acid is 1.0, and the other single impurities are 3.1 ", and relevant personnel are trained. <br>3. Retrain the relevant personnel in H0-SOP-01010 "Quality Standards Formulation and Management Procedures", emphasizing that intermediate quality standards should be established on the basis of experimental data.

On November 24, 2019, at 12:25, analyst Xu Min looked at H0-QS-30061 "Mikafin Net Sodium Intermediate Quality Standard" 00 edition, found that "6.7 mkafen net coarse The correction factor described in the method B of the pin and nanofiltration concentrate B is described as "F is the correction factor: diyl-based impurity is 3.4 and the remaining impurity is 3.1", and the remaining impurities include impurities 8 (side chain acid) and other unknown impurities. Mikafen net crude and nanofiltration concentrate sample detection are based on side chain acid as the standard, according to H0-SOP-72031 "analytical method verification management procedure" on the correction factor calculation provisions, impurity 8 (side chain acid) correction factor should be 1.0. <br><br>The root cause of this deviation is the risk of the description of impurity correction factor in H3-QS-20214 Mikafen Net Sodium Intermediate Quality Standard 01, and during the revision of version 02, the analyst mistook the remaining impurities for other individual impurities, noting that the remaining impurities included known side chain acids (impurities 8) and other individual impurities, resulting in intermediates Quality standards revision errors, in the subsequent version (03, 04, 05, 06, H0-QS-30061/00) revision process, analysts focused on the revision, for the other unrevised parts of the file did not carefully review, so did not notice the error here, is a person's cause. <br><br>1. This deviation relates to 18 batches of micarfin net sodium crude and nanofiltration concentrate detected between 2015.12.18 and 2019.11.23. The results of 18 batches of Micarfin net sodium crude and nanofiltration concentrate impurities 8 (side chain acid) were calculated according to the correction factor of 3.1, and the test results met the requirements, according to the correct correction factor, the test results were smaller than the original detection data, and there was no effect on the product quality itself. Subsequent revision and output of the test results of the historical batch detected after the implementation of the H3-QS-20214 Mikafin Net Sodium Intermediate Quality Standard seine quality standard spree was revised and the report was output. 2. It is planned to revise the H0-QS-30061 Mikafen Net Sodium Intermediate Quality Standard, and to "correct factor: diylbase impurity is 3.4, the remaining impurity is 3.1" revised to "correction factor: diyl base impurity is 3.4, side chain acid is 1.0, and other individual individual impurities are 3.1" to ensure no effect on subsequent production and detection. <br><br>1. Modify the test results of 18 batches of micarfin net sodium crude and nanofiltration concentrate detected during the period from 2015.12.18 to 2019.11.23, and issue a test report.<br>2. To H0-QS-30061 "Mikafin net sodium intermediate quality standards" to be revised, "6.7 method B" in the "correction factor: diylbase impurities 3.4, the remaining impurities 3.1" modified to "correction factor: diyl base impurities 3.4, side chain acid 1.0, other individual impurities 3.1" and training relevant personnel.<br>3. Re-training the relevant personnel in H0-SOP-01010 Quality Standards Development and Management Procedures, emphasizing that intermediate quality standards should be established on the basis of experimental data.

At 12:25 on November 24, 2019, when Xu Min, an analyst, checked h0-qs-30061 quality standard for intermediate of micafun sodium, he found that the description of the correction factor of impurity in "6.7 micafun crude and nanofiltration concentrate detection method B" was "F is the correction factor: diacylimpurity is 3.4, the rest impurity is 3.1", the rest impurity includes impurity 8 (side chain acid) and other unknown impurities Quality. Both crude micafungin and nanofiltration concentrate samples are tested with side chain acid as the standard. According to h0-sop-72031 management procedure for validation of analytical methods, the correction factor of impurity 8 (side chain acid) should be 1.0.<br>The root cause of this deviation is that there is a risk in the description of impurity correction factors in h3-qs-20214 quality standard for micafen sodium intermediates (version 01). In the revision process of version 02, analysts mistook the remaining impurities for other single impurities, and did not notice that the remaining impurities include known side chain acid (impurity 8) and other single impurities, which led to the revision error of the quality standard for intermediates. Later, the In the revision process of the continued Version (version 03, 04, 05, 06 and h0-qs-30061 / 00), the analyst focused on the revision content, and did not carefully check other parts of the document that were not revised, so they did not notice the errors, which was the personnel reason.<br>1. This deviation involves 18 batches of crude micafen sodium and nanofiltration concentrate tested during December 18, 2015 to November 23, 2019. The results of impurity 8 (side chain acid) in 18 batches of crude micafen sodium and nanofiltration concentrate were calculated according to the correction factor of 3.1, and the test results were in line with the requirements, calculated according to the correct correction factor, the test results were smaller than the original test data, and there was no impact on the product quality itself. Subsequently, the test results of the historical batches tested after the implementation of h3-qs-20214 quality standard for micafen sodium intermediates (version 02) were revised and the report was output, and the original test results were invalid and retained. 2. It is planned to revise h0-qs-30061 quality standard for micafen sodium intermediates, and revise "correction factor: diacylimpurity is 3.4, other impurities are 3.1" in "6.7 method B" to "correction factor: diacylimpurity is 3.4, side chain acid is 1.0, other single impurity is 3.1", so as to ensure no impact on subsequent production and detection.<br>1. Modify the test results of 18 batches of crude micafen sodium and nanofiltration concentration tested during December 18, 2015 to November 23, 2019, and issue the test report.<br>2. Revise h0-qs-30061 "quality standard for micafen sodium intermediates", change "correction factor: diacylimpurity: 3.4, other impurities: 3.1" in "6.7 method B" to "correction factor: diacylimpurity: 3.4, side chain acid: 1.0, other single impurity: 3.1", and train relevant personnel.<br>3. Retraining the relevant personnel in h0-sop-01010 quality standard formulation and management procedure, emphasizing that the intermediate quality standard should be established on the basis of experimental data.<br>