II. Main findings

　　(I) Main problems identified in TCMs manufacturers

In 2016, a total of 66 person-times in 18 teams of inspectorates were sent for unannounced inspections on 20 TCMs manufacturers, of which there were 6 manufacturers involving letter reporting, there were 3 manufacturers of calculus bovis factitious, 7 manufacturers of the products containing bezoar, 3 enterprises identified to have problems in exploration study and inspection and 1 manufacturer of prepared slices of Chinese crude medicines.

In the unannounced inspection on 20 TCMs manufacturers, 12 manufacturers failed to meet pharmaceutical GMP requirements, of which three manufacturers were transferred to provincial administration for handling relevant problems, one manufacturer was issued with Warning Letter, one manufacturer had no relevant production and three manufacturers met the requirements.

1. Chinese patent medicine manufacturers

(1) The problem of unauthorized changes to the process was prominent.

In order to reduce the production cost of oral preparation of Chinese patent medicine, the phenomenon of unauthorized changes to the pretreatment and extraction process is still a prominent problem. The unannounced inspections conducted this year were due to the problems identified in exploratory inspection, such as the enterprise failed to extract some Chinese herbal medicine in the prescription that should be extracted in accordance with technological procedure, but conducted a direct feeding after smashing.

(2) The Chinese herbal medicine and prepared slices of Chinese crude medicines was in disordered management.

In order to cope with the supervisory inspection by the drug regulatory authorities at all levels, individual manufacturer of Chinese patent medicine falsified machine account of warehouse materials and stock in and stock out record. The relevant machine account and records of the materials for internal operation in such enterprises can correspond to each other, but failed to respond to the invoice or voucher for the purchase. Or, such enterprises took advantage of such policy that the Chinese herbal medicine can be purchased directly from farmers, reversely inferred the usage of Chinese herbal medicine from the production of Chinese patent medicine, and then fabricated the machine account of materials according to the demand.

(3) The purchased Chinese herbal medicine and prepared slices of Chinese crude medicines were not subject to strict full inspection and the data integrity was doubtable.

Traditional manufacturers of Chinese patent medicine have many varieties of products and involve may varieties of Chinese herbal medicine and prepared slices of Chinese crude medicines. Because the precision analysis instruments and QC personnel equipped were not adapted to the scale of production, it cannot be ensured that each batch of the purchased Chinese herbal medicine and prepared slices of Chinese crude medicines can be inspected, resulting in no full inspection for the Chinese herbal medicine and prepared slices of Chinese crude medicines of some batch, or using a graph for multi-purpose to deal with the inspection.

2. Calculus bovis factitius

Because calculus bovis factitious is marketed under the classification of “Medicinal Materials and Prepared Slices” in the Chinese pharmacopoeia, it belongs to raw materials for Chinese patent medicine, resulting in that relevant enterprises cannot organize the production in accordance with pharmaceutical GMP requirements. In particular, there were seriously insufficient requirements for the auditing and management of the suppliers of upstream industry chain of calculus bovis factitious, causing that hygienic conditions of processing site were bad, the raw materials could not be traced and the processing process was uncontrollable. Main fingings:

(1) The management of suppliers was weak.

(2) The authenticity of microbial limit test was doubtful.

(3) It failed to be included in quality assurance system.

3. Prepared slices of Chinese crude medicines

A variety of information showed that the dispensing for sales was very common for the prepared slices of Chinese crude medicines outsourced. The problems in content determination of purchased Chinese herbal medicines or process products were prominent, dyeing and weight increment problems occurred occasionally, and authenticity of batch production records was doubtful.

(1) Untruthful batch production records.

(2) Being suspected of dispensing and sale of outsourcing prepared slices.

(3) Authenticity problems in data integrity.

(II) Biochemical drugs

1. Inspection on " monosialotetrahexosylganglioside sodium”

In 2016, a total of 4 manufacturers of " monosialotetrahexosylganglioside sodium” were inspected, and it was found that there was certain risk in the management of the quality of raw materials and the pig brain suppliers.

(1) Supplier management shall be improved, for the management of suppliers by the enterprise cannot ensure effective traceability.

(2) There was insufficient management of electronic data of the monitoring of cold chain transport of pig brain.

2. Inspection on " hepatocyte growth-promoting factors for injection”

In 2016, a total of 4 manufacturers of " hepatocyte growth-promoting factors for injection” were inspected, of which 2 manufacturers had their Pharmaceutical GMP Certificate revoked while 2 manufacturers were issued with Warning Letter.

(1) Fabricate the record file.

(2) Problems in data integrity

(3) Inconsistency with registered production process

(4) Unable to effectively ensure the quality of the liver as raw material.

Part V Overseas Inspections for Imported Pharmaceuticals