(II) The enterprises unqualified in casual inspections in 2015

A total of 11 critical deficiencies, 27 major deficiencies and 84 general deficiencies were identified in the inspections on 11 enterprises.

　　Main findings were as follows:

1. Production process was inconsistent with registered process

2. Problems in data integrity

3. Problems in process validation

(III) Double random inspection

A total of 5 critical deficiencies, 24 major deficiencies and 123 general deficiencies were identified.

　　Main findings were as follows:

1. Record falsification

2. Potential hazards in product quality and safety

3. Problems in data integrity

4. Problems in process validation

5. Non-standardized material management with the risks in pollution, confusion and error.

6. Incomplete cleaning, which cannot effectively prevent contamination and cross-contamination.

(IV) Vaccine manufacturers

38 major deficiencies and 383 general deficiencies were identified.

　　Main findings:

1. Equipment. There was a too long stagnant water section between the stainless steel pipe valve through which water for injection preparation system enters into injection water storage tank and water generator; Individual device had rust.

2. Materials and Products. The quantity of the destructed items was not recorded in the destruction records of the non-conforming finished products; the enterprise failed to establish the background information of whole-genome sequence of main bacterial and viral seeds for production.

3. Documentation Management. Individual document was not specifically specified and was poor in its operability. The content specified in the document was inconsistent with the actual situation; individual record had incomplete content; the batch production records were unreasonably designed and were not timely filled in actual operation.

4. Quality Control and Quality Assurance

(1) Quality management of laboratories: the enterprise failed to request necessary test data and maps from the institutions conducting entrusted test; some material was subject to infrared test after sample mixing.

(2) the Deviation handling: The training and implementation of the documents related to deviation handling was not conducted; the enterprise failed to timely initiate the investigation for individual deviation; the reason analysis and corrective and preventive measures for a few deviations were not in place, and there was in adequate assessment on the potential impact of the deviations on the quality of products.

(3) Change control: The enterprise failed to handle the changes in accordance with change process and submit supplementary application for registration. There was no or inadequate assessment on some changes;

(4) Supplier management: There was incomplete auditing content for the suppliers of some materials, and the enterprise failed to determine the auditing content for suppliers based on the impact of the material on product quality.

(5) Product quality review: The enterprise failed to conduct annual quality review by varieties.

5. Computer System. The enterprise has developed document system for computer system management, but did not conduct classification management in accordance with the system, and did not take effective measures to reduce risks for the situation that existing conditions failed to comply with the document; there was no permission setting for the login screen of HPLC testing equipment in quality verification laboratory, and no measures to prevent the login by the unauthorized person.

(V) Blood product manufacturers

In the inspections on 25 enterprises, 13 major deficiencies and 241 general deficiencies were identified, and no critical deficiency was identified.

　　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.