The State Drug Administration of China (SDA, formerly (before name change in 2018), CFDA) has issued the 2017 Drug Inspection Report recently (June 8) which summarizes, conducts statistics of, and analyzes the work of CFDA’s pre-approval inspection, pharmaceutical GMP follow-up inspection, unannounced inspection for pharmaceuticals, overseas inspections for imported pharmaceuticals, GSP unannounced inspection, GMP observation inspection by foreign organizations, etc. in 2017, and contains many highlights. Let’s check them.

Highlight I: Increased inspection density, surging number of pharmaceutical GMP follow-up inspections

Table 1 shows the completion situation of the pharmaceutical inspection tasks by CFDA in 2017 and 2016. Compared to 2016, the total number of inspections in 2017 increased greatly, wherein, the item mainly increased was pharmaceutical GMP follow-up inspection, with the increase of over 200 inspections, followed by overseas inspections for imported pharmaceuticals, with the increase of over 7 times.

Table 1 List of Pharmaceutical Inspection Tasks Completed in 2017 and 2016

Highlight II: Inspections of biological drugs and chemical drugs accounting for the majority of the pre-approval inspections

CFDA conducted pre-approval inspections mainly according to the Provisions for Drug Registration, Requirements for On-site Verification for Drug Registration, and Announcement on Matters Related to the Consistency Evaluation of the Quality and Efficacy of Generic Drugs, etc.

Fig. 2 Diagram of Dosage Form Distribution in Pre-approval Inspections in 2017

As shown in Fig. 2, biological products, chemical preparations and APIs were the main dosage forms inspected in pre-approval inspections in 2017. The increase of the inspection frequency on those types of drugs made sense as the development of biopharmaceuticals and chemical targeted drugs, etc. has been accelerated in China in recent years. The problems mainly detected in CFDA’s inspections were: (I) Insufficient implementation of pharmaceutical GMP in pilot scale experiment or technology transfer process; (II) Insufficient investigation of deviation and out-of-specification results; (III) Process validation being not scientific or sufficient.

Highlight III: Pharmaceutical GMP follow-up inspections mainly targeting high risk enterprises

As shown in Fig. 3 Distribution of Enterprises that Did Not Meet the GMP Requirements of Follow-up Inspections, CFDA’s GMP follow-up inspections in 2017 mainly targeted high risk enterprises, which followed the principle of "risk-based and variety-focused" of pharmaceutical GMP follow-up inspections.

Fig. 3 Distribution of Enterprises that Did Not Meet the GMP Requirements of Follow-up Inspections in 2017

There was nothing strange that there were many defects inspected as such follow-up inspections mainly targeted high risk enterprises. The inspections on 428 drug manufacturers in 2017 identified a total of 4,339 defects, including 3,512 defects involving the general rule of GMP for pharmaceuticals, 224 defects involving the computer system annex, 200 defects involving the annex for sterile drugs, and 116 defects involving the TCM decoction pieces.

Fig. 4 Distribution of Defect Items in GMP Follow-up Inspections

As shown in Fig. 4, the defects found in the Quality Control and Quality Assurance section ranked first among defects found in the inspections on various manufacturers, with a total of 1,205 defects, accounting for 28% of the total, followed by document management, accounting for 16% of the total, and then by equipment defects, accounting for 10%.

Highlight IV: Unannounced inspections focusing on TCM manufacturers, with prominent problems

The 2017 unannounced inspections focused more on the inspections on TCM manufacturers. 38 enterprises involved TCM preparations, TCM decoction pieces and TCM extracts among the 57 enterprises that received unannounced inspections (Fig. 5).

Fig. 5 Distribution of Serious Problems in Drug Unannounced Inspections

There were many prominent problems found in the unannounced inspections: 1. Some Chinese patent medicine manufacturers failed to conform to the prescription standards for the feeding; violated the legal preparation methods and changed the process without authorization; fabricated relevant record documents to cope with supervision and inspection. 2. TCM decoction piece manufacturers directly packaged and sold purchased decoction pieces; failed to follow the standards for the full inspection of purchased or sold traditional Chinese medicinal materials and TCM decoction pieces; problems were found with the production filing of TCM extracts. 3. Chemical drug production violated the registered and approved process; the original data of inspection could not be traced, and the data integrity was seriously compromised; unqualified raw materials were used for the drug production; 4. Biological product manufacturers had untruthful process control data or product result data; their actual production process and the product registration process were inconsistent; they used raw materials, intermediates and semi-finished products that did not meet quality standards for feeding, etc.

Highlight V: Increased frequency of overseas inspections for imported pharmaceuticals, showing the improvement of the law enforcement capacity of the drug regulator of China

From the perspective of comparison of CFDA’s overseas inspections for imported pharmaceuticals each year, the frequency was largely increased in 2017 (Fig. 6). The increased overseas inspections for imported pharmaceuticals showed the improvement of the law enforcement capacity of the drug regulator of China and enabled the effective control over the safety and effectiveness of imported pharmaceuticals.

Fig. 6 Overseas Inspection Tasks from 2011 to 2017

It is reported that the overseas inspections mainly took place in European and American regions, and the number of inspections on countries like India has also increased in recent years. Besides the common problems like those of Chinese pharmaceutical enterprises found in the inspections, there was also the situation that the overseas enterprises did not perform standards of Chinese Pharmacopoeia during the production.

Summary:

Drug inspection is an important means to ensure pharmaceutical product safety and reliability and prevent counterfeit or substandard pharmaceutical products. Problems in the pharmaceutical production and circulation can be found through inspections, which can then be improved in a targeted manner. And banning and shutting down pharmaceutical enterprises or corresponding pharmaceutical production lines that seriously violate corresponding pharmaceutical production and circulation regulations and laws can maximize the safety of the Chinese consumers. It’s hoped that the pharmaceutical enterprises could learn lessons from problems pointed out in 2017 Drug Inspection Report to create a safer and more worry-free environment for the drug market of China.

References:

1. http://cnda.cfda.gov.cn/WS04/CL2050/228316.html?from=singlemessage
2. http://samr.cfda.gov.cn/WS01/CL0844/173310.html