II. Main findings

　　In the pre-approval inspections in 2016, such problems in data integrity as untraceable data and untruthful application dossier were still prominent while insufficient process validation and instable production process and inconsistency between production process or parameters with approved ones were also identified, which were specifically as follows: (All issues found in inspection have been dealt in accordance with the law.)

(I) Problems in data integrity

1. Testing data were untraceable. A few enterprises failed to retain samples as required and conduct stability investigation. No retained preproduction samples and retained samples for stability test of the inspected varieties were found in pre-approval inspection, and enterprises also failed to provide both the requisition and destruction records of corresponding retained samples and the samples for stability test and use records of the equipment for stability test.

2. Batch production records were untruthful and incomplete and inconsistent with application dossier.

(II) The process validation was insufficient and production process was instable

The process validation for the variety was insufficient. During the dynamic production of the enterprises, some procedure had serious deviation or batch product yield had a greater deviation from the validated batch.

(III) The production process or key process parameters and inner packaging materials were inconsistent with the approved ones and no study and assessment was conducted

1. The production process was inconsistent with that approved / under application.

2. Key process parameters were inconsistent with the production process approved / under application.

3. The manufacturer of inner packing materials was inconsistent with that under registration application, and the enterprise did not conduct comparison study.

(IV) Necessary deviation investigation was not conducted

There was significant abnormality in dynamic production, but the investigation was insufficient and the primary cause was not identified. The results of the process validation of three batches and dynamic production batch of the chemical APIs under application by an enterprise showed that there was significant difference in the rate of finished products among four batches, but the enterprise did not analyze and identify the reasons.

Part II Pharmaceutical GMP Certification Inspection

　　I. Overview of Inspections

　　Based on the spirit in the Announcement of China Food and Drug Administration on Relevant Issues of Halting the Production by the Enterprises Failing to Pass the Pharmaceutical GMP (revised in 2010) Certification and Decentralizing the Certification of Sterile Pharmaceuticals (2015 No.285), China Food and Drug Administration no longer accepted the application for pharmaceutical GMP certification as of January 1st, 2016. For the certification applications that have been accepted, on-site inspection as well as review and certificate-issuing continued to be completed.

In view of above situation, the inspections on 16 pharmaceutical manufacturers have been arranged, 16 copies of on-site inspection reports have been received and 14 copies have been reviewed throughout the year of 2016. Among them, 12 pharmaceutical manufacturers passed pharmaceutical GMP certification inspection, 2 pharmaceutical manufacturers failed to pass pharmaceutical GMP certification inspection and 5 pharmaceutical manufacturers were issued with Warning Letter; and another two pharmaceutical manufacturers have not yet received approval document for registration so the GMP certification process is suspended.

The dosage forms under application for certification included large volume injection of three enterprises, small volume injection of three enterprises, c of three enterprises, powder injection of one enterprise, radiopharmaceutical of one enterprise, vaccine of two enterprises and other biologics of three enterprises.

　　II. Main findings

　　A total of 220 deficiencies were identified, including 23 major deficiencies and 197 general deficiencies. There were 41 deficiencies in Quality Control and Quality Assurance, 32 deficiencies in Documentation Management, 24 deficiencies in Institutions and Personnel, 23 deficiencies in Equipment and 21 deficiencies in Verification and Qualification. The distribution was basically consistent with that in 2015.

The two manufacturers of in vitro diagnostic reagents receiving certification inspection all failed this year. The main problems were as follows:

(I) Quality Management System. Quality management system could not be effective operated and failed to meet the production and quality requirements of the products; The personnel mobility was frequent, there lacked professionals and the training was not conducted, which could not meet the quality management requirements in routine production; The operability of the documents were poor and data were incompletely recorded; relevant changes were not subject to change control in accordance with change procedure.

(II) Verification and Qualification. The enterprises failed to conduct process validation for all the products under application for GMP certification, and the cleaning validation for public equipment and facilities was not in place; part of validation records was incomplete; and some re-validation work was not conducted as required.

Part III Pharmaceutical GMP Follow-up Inspection