Drug Inspections of Manufacturers and Suppliers in China: Regulation Revised

On July 21, 2023, China National Medical Products Administration (NMPA) released the revised Administrative Measures for Drug Inspections (Trial) (hereafter referred to as the Inspection Measures) with immediate effect. The revisions mainly took place in “Chapter 3 Inspection Procedures” and “Chapter 9 Handling of Inspection Conclusion”.

The Inspection Measures, first issued in May 2021, has replaced two abolished regulations—Administrative Measures Good Supply Practices (GMP) Certification and Administrative Measures on Good Manufacturing Practices (GSP) Certification, as China has cancelled the GMP and GSP certifications since the revised Drug Administration Law took effect in 2019. 

The following passages outline China’s drug inspection requirements. The regulatory framework remains unchanged, but details have been maneuvered regarding inspection conclusions and deadlines for corrections by manufacturers and suppliers. The revised parts are marked blue in this article.

1. The Inspection Measures’ Application Scope

The Inspection Measures applies to drug regulators’ activities to inspect, investigate, collect evidence of, and deal with the manufacture, supply, and use of drugs with marketing authorization in China. 

For manufacturing sites outside China, drug regulators will conduct inspections according to the Administrative Provisions on Overseas Inspection of Drugs and Medical Devices.

2. Definition of Drug Inspection

Drug inspection refers to drug supervision & administration departments’ activities to inspect whether the companies, which engage in drug production, supply and use, abide by laws and regulations, carry out quality management practices, and meet relevant standards.

3. Companies/Organizations in the Inspection Scope

Drug marketing authorization holders (MAHs), manufacturers, wholesalers, retail headquarters, retailers, online transaction (e-commerce) platforms, institutions that use drugs are all in the scope of inspections.

4. Inspection Types

There are four types of drug inspections in China:

• Pre-approval inspection;

• Routine inspection;

• For-cause inspection;

• Other inspections.

4.1. Pre-approval Inspection

Pre-approval inspection focuses on confirming whether the applicants who manufacture or supply drugs are qualified to carry out these activities. It has two sub-types, one for manufacturers, the other for suppliers.

4.2 Routine Inspection

4.2.1. Routine inspection is conducted according to drug supervision and administration departments’ annual inspection plan.

4.2.2. Drug supervision and administration departments will manage the inspections according to different risk levels. The following are the key points that will be assessed to determine the risk level:

• Attributes and intrinsic risks of the drug product;

• Drug sampling test result of MAHs, manufacturers, suppliers and institutions using the drug product;

• Whether there is illegality in MAHs, manufacturers, suppliers and institutions using the drug product;

• Adverse drug reactions (ADRs), investigational research, complaints & reports, and other clues that indicate potential risks.

4.2.3. Routine inspection contents:

• Whether the inspected organization obeys drug administration laws and regulations;

• Whether the company implements relevant drug quality management practices and follows relevant standards;

• Authenticity and completeness of the materials and data of drug manufacture, supply and use;

• MAHs’ capability in quality management and risk prevention & control;

• Other contents considered necessary by drug supervision and administration departments.

4.2.4. Inspection Frequency

• No less than once every quarter for:

        - Companies producing anesthetics, class 1 psychotropic drugs, and precursor chemicals.

• No less than once half a year for:

        - Manufacturers of class 2 antipsychotic drugs;

        - National wholesalers of anesthetics and class 1 psychotropic drugs

        - Regional wholesalers of anesthetics and class 1 psychotropic drugs;

        - Wholesalers of active pharmaceutical ingredients (APIs) of precursor chemicals.

• No less than once a year for:

        - Manufacturers and suppliers of radioactive drugs and toxic drugs for medical use.

RELATED: China Reins in Supervision of Anesthetics and Psychotropic Drugs; Catalog of Anesthetics and Psychotropic Drugs

Notes: Companies may not be notified by inspectors in advance for routine inspection.

4.3 For-cause Inspection

For-cause inspection is a targeted investigation on specific potential or reported problems with drug MAHs, manufacturers, suppliers, and institutions that use drugs.

Companies in any of the following situations will be subject to for-cause inspections if regulators find the inspection necessary after risk assessment.

• Complains, reports, or any other clues indicate potential safety risks in the product;

• Safety risks are found in drug testing.

• ADR monitoring signals quality safety risks.

• The application dossier’s authenticity is suspected.

• The company is suspected to violate the quality management practices.

• The company has a severely terrible credit record.

• The company changes its registered management personnel frequently.

• Safety risks are identified in the process of authorizing biologics lot release.

• Risks are identified in the safety management of special drugs;

• Special drugs are suspected to enter an illegal area.

• Other situations that require for-cause inspections.

Notes: Companies won’t be informed by drug inspectors in advance.

4.4 Other Inspections

Other inspections refer to inspections other than the three types mentioned above.

5. Drug Inspection: Conclusion and Correction

5.1 Conclusion of Drug Inspection

On-site inspection conclusion, made by on-site inspectors, are divided into three categories:

1. Compliant;

2. Pending until correction;

3. Non-compliant. 

The following table specifies the standards for determining on-site inspection conclusions:

Based on the on-site inspection conclusion, the drug supervision & administration department that send out the inspectors will form a comprehensive evaluation conclusion, which is determined according to the following standards:

The inspector department will then send the "Comprehensive Evaluation Report on Drug Inspection" to drug supervision and administration departments. The report includes:

• MAH’s information: company name and address;

• Inspector department;

• Inspection scope;

• Source of the inspection task;

• Specific inspectors who carried out the task;

• Inspection time;

• Problems or deficiencies found in the inspection;

• Comprehensive evaluation conclusion, etc.

5.2 Correction after Drug Inspection

After the on-site inspection, the inspected company should correct the deficiencies and submit the correction report to the inspector department within 30 workdays.

If the 30 days is not enough for rectification, a 10-day grace period will be granted if the inspector institution finds it necessary.

If the company still fails to complete correction before the postponed deadline, it should formulate a feasible and practical correction plan and submit it to the inspector department. After rounding off the correction, the company should submit a supplemental correction report to the same department. 

The correction report should include at least the following contents:

• Description of the deficiency;

• Investigation and analysis of the deficiency;

• Risk assessment;

• Risk control plan;

• Review of the correction;

• Evaluation of the correction’s effectiveness.

6. Punishment for Illegalities, Deficiencies, and Uncooperative Actions

If inspectors find safety risks in drug quality, competent drug supervision & administration departments will evaluate the risks within 3 days. Based on the evaluation, the department will decide whether to take measures, such as suspending drug manufacture, sales, use, and import. The inspected organization will be ordered to review and analyze the risks comprehensively and make corresponding measures, including drug recall. 

If a drug company refuses or escapes inspection, or forge/destroy/hide relevant evidence, its products will be considered to have possible safety problems. These situations will be disposed according to the Article 99 of China’s Drug Administration Law.

Contact BaiPharm if you need to consult about drug inspections in China.

BaiPharm Resources:

• China to Initiate Pre-Approval Inspections Based on Risk Levels of Drug Registration Applications

• Key Points for China Pharmacovigilance Inspections