I. Overview of Inspections

　　In 2016, it was planned in the Announcement to conduct follow-up inspection on 215 enterprises, a total of 228 inspections. Among them, 58 inspections were conducted on the enterprises out of production or having no production for a long time, and other 170 inspections have all been conducted.

In addition, follow-up inspection was conducted on 21 sterile drug manufacturers passing provincial certification, and double random inspection was conducted on 13 enterprises. A total of 204 follow-up inspections were completed.

　　12 enterprises failed in follow-up inspection, accounting for 5.9%, and 58 enterprises were issued with Warning Letter, accounting for 28.9%.

Among 12 enterprises failing in the inspection, there were 5 enterprises unqualified in casual inspection in 2015, 4 enterprises subject to double random inspection, 2 manufacturers of citicoline sodium injection and 1 manufacturer of ossotide injection. (All issues found in inspection have been dealt in accordance with the law.)

(I) The situation of casual inspection of the varieties in quality report in 2015

10 enterprises accepted the follow-up inspection on such dosage forms and varieties as eye drops, bendazol tablets and APIs of sodium benzoate, of which 5 enterprises failed, accounting for 50%, and 4 enterprises were issued with Warning Letter.

(II) Double random inspection

In order to implement the requirements of innovating the supervision inwards and afterwards by the State Council, in accordance with the unified arrangement by CFDA, double random inspection system for pharmaceuticals was initially operated in December 2016, follow-up inspection was conducted on the 13 selected enterprises. The inspections distributed in 9 provinces and involved 3 chemicals, 2 APIs and 8 TCMs. 4 enterprises failed in the inspection, and the pass rate was only 69%. In addition, 3 enterprises were issued with Warning Letter.

(III) Vaccine manufacturers

38 vaccine manufacturers that have obtained GMP certificate were marketed in the follow-up inspection plan in 2016. Except for 1 enterprise having production license and GMP certificate revoked in 2014 and 1 enterprise failing to get GMP certification in 2015 due to the application for the change of production address, the follow-up inspection was conducted on other 36 vaccine manufacturers. All 36 enterprises passed the inspection, and 7 enterprises which found general risks and can be improved by rectification were issued with Warning Letter. According to experts assessment that one critical deficiency that was evaluated by inspectors on site should be decreased to major deficiency, being low risk. On the whole, the quality risks in vaccine production are controllable and the manufacturers have a standardized production and quality management.

(IV) Blood product manufacturers

26 blood product manufacturers were marketed in the follow-up inspection plan in 2016. Except for 1 enterprise in production suspension and rectification, the follow-up inspection was conducted on other 25 blood product manufacturers. All 25 enterprises passed the inspection, and 4 enterprises which found general risks and can be improved by rectification were issued with Warning Letter. On the whole, the quality risks in blood product production are controllable, the manufacturers have a standardized production and quality management, but the supervision shall be intensified for individual enterprises.

(V) The manufacturers issued with warning letter in 2015

Follow-up inspection has been conducted on 32 manufacturers issued with warning letter in 2015. The manufacturers were basically met the requirements, but 14 manufacturers were issued with warning letter again.

(VI) The situation of casual inspections on the sterile drug manufacturers passing provincial certification after the decentralization of certification

21 sterile drug manufacturers passing provincial certification received casual inspection. All of them passed the inspection and 6 enterprises were issued with Warning Letter. According to the inspection result, the Provincial Bureau can undertake the GMP certification inspection functions smoothly down.

(VII) Special inspection on high-risk varieties

This year, follow-up inspection was mainly conducted on the injection of three products including ossotide, fructose diphosphate and citicoline sodium. It was planned to conduct 114 special inspections on high-risk varieties. 47 enterprises were not inspected because of failing in GMP (2010 version) certification, out of production for a long time and transfer of approval number, and 67 inspections were actually conducted. In the inspections, 1 ossotide injection manufacturer and 2 citicoline sodium injection manufacturers failed, and 21 manufacturers were issued with Warning Letter.

　　II. Main findings

　　(I) Overall situation

A total of 2271 deficiencies were identified in 204 inspections, of which there were 22 critical deficiencies, 210 major deficiencies and 2039 general deficiencies. Compared with GMP certification and follow-up inspections in 2015, the number of critical deficiencies was increased.

Among the manufacturers of high-risk varieties subject to special inspection, out of production for a long time or failing in pharmaceutical GMP (2010 version) certification were prominent. The common problems identified in the inspections were as follows:

1. Individual enterprise had inconsistency between its production process and registered process.

2. The problems in data integrity and authenticity still existed, including falsification of production records, indiscriminate use of maps and arbitrary modification of data in inspection records and inconsistency in relevant content in production, equipment and material records.

3. The process validation was insufficient, and the enterprises failing to conduct process validation after changing production lot size had more problems.

4. The problems in the standardization of data management were prominent, mainly manifesting as failing to control the permission setting of the system, audit tracking function and the permission for the modification and deletion of documents and data, and having no reasonable control and explanation for deleting, selecting and using data.

5. There was certain gap between the implementation of the Appendix of Computer System and Appendix of Qualification and Validation and regulatory requirements, and many problems were identified.

6. There was a weak management of deviations and changes, mainly manifesting as failing to effectively identify and record the deviations that occurred, and lacking necessary assessment and validation for the changes.