Main findings:

1. Institutions and Personnel. There lacked training for the personnel at some posts.

2. Premises and Facilities. The contamination and cross contamination cannot be effectively controlled.

3. Equipment. Some sensors failed to cover the actual use range; some instruments and equipment for testing were not regularly calibrated or insufficiently calibrated, and the records were incomplete; the equipment had no status identification and calibration identification.

4. Materials and Products. There lacked the source, validity period and other information on the label of the cryo in allocated supply, and the label was a card, which was easy to be lost and confused.

5. Verification and Qualification. In simulated filling test of culture media, sampling monitoring was conducted for both hands, forearms and chest of operators only after the production was over, and the sampling of clothes as well as the confirmation was not specified.

6. Documentation Management. The technological procedure and operating procedure was not specific in content, poor in operability and not standardized in the provisions..

7. Production Management. There lacked microbial control measures for the octylic acid sodium solution added before inactivation; The time to place the settlement plate under Level A laminar flow was not confirmed.

8. Quality Control and Quality Assurance

(1) Management of quality control laboratories: the machine account for the receiving and dispatching of tested products had incomplete content, and there was no receiving information of the test samples of intermediates and semi-finished products; the plate culture medium outsourced for environmental monitoring was not tested; negative control was not set for sterility test in accordance with the pharmacopoeia;

(2) Product stability study: Invalidity period was formulated for intermediate products, but there lacked the support of continuous stability investigation or validation data;

(3) Change control: Change control and management was not in place. Some changes were not or insufficiently assessed;

(4) Deviation handling: the enterprise failed to timely initiate the investigation for individual deviation; some deviation investigation and corrective and preventive measures were insufficient;

(5) Supplier management: The allocated suppliers of cryo was not included in the directory of qualified suppliers of the enterprise;

(6) Product quality review: Some information was not included in annual product quality review;

(7) Product delivery and recall: The enterprise failed to specify the shipment means for the sample in batch release;

(8) Computer System: there were incomplete documents for computer system, and there lacked comprehensive and effective control and assessment for internal computer system and relevant data. There was no auditing and tracking function for some instruments and equipment in QC laboratory; the system did not set access permission at different levels, and there was a risk of data and system modification; the safety and reliability of HPLC data transfer was not confirmed.

(VI) The manufacturers issued with Warning Letter in 2015

For the inspections on 32 manufacturers, a total of 2 critical deficiencies, 32 major deficiencies and 328 general deficiencies were identified.

　　Main findings were as follows:

1. Problems in data integrity

2. No records and investigations for the deviations

3. There were certain problems in sterility guarantee and relevant verification and qualification work was inadequate.

(VII) The Sterile Drug Manufacturers Passing Provincial Certification

In the inspections on 21 enterprises, a total of 15 major deficiencies and 209 general deficiencies were identified, but no critical deficiency was identified.

　　The main problems identified manifested as: there is insufficient risk assessment for sharing production line in the production of small volume injection; there was cleaning validation for single variety, but no cleaning risk assessment for all the varieties; some inspection records had incomplete content; the validation and audit of computer system has not yet been carried out; materials were improperly managed, and there were risks of confusion and error.

(VIII) Special inspections on high-risk varieties

In the inspections on 61 enterprises, a total of 3 critical deficiencies, 64 major deficiencies and 658 general deficiencies were identified.