The Comprehensive Affairs Department of NMPA Solicits Public Comments on “Inspection Procedures of Drug Product MAHs (Draft for Comments)”

1. Purpose

This procedure is formulated to implement the Drug Administration Law of the People's Republic of China and the Vaccine Administration Law of the People's Republic of China, fully implement the responsibility of drug marketing authorization holders (hereinafter referred to as holders) for the safety, effectiveness and quality controllability of drugs throughout the entire process of drug development, production, operation and use, and further standardize the inspection work of holders.

2. Basis

Drug Administration Law of the People's Republic of China, Vaccine Administration Law of the People's Republic of China, Drug Registration Management Measures, Drug Production Supervision and Management Measures, Drug Operation Supervision and Management Measures, Drug Production Quality Management Standards, Drug Operation Quality Management Standards, Drug Adverse Reaction Reporting and Monitoring Management Measures, Drug Non-clinical Research Quality Management Standards, etc.

3. Scope

This procedure applies to the inspection of the non-clinical research, clinical trials, production, operation, post-marketing research, adverse reaction monitoring and reporting and handling of drugs by domestic holders and domestic corporate legal persons designated by foreign holders to perform their obligations as drug marketing authorization holders.

4. Inspection Forms

Holder inspections include on-site inspections and written inspections. On-site inspections refer to inspections in which the drug regulatory department dispatches an inspection team to conduct on-site inspections of the holder's research, production, and business-related activities; written inspections refer to inspections in which the drug regulatory department requires the holder to submit inspection materials and conducts verification of the submitted materials.

Written inspections are applicable to inspection tasks with low quality and safety risks, such as routine inspections of holders who entrust other enterprises or units to carry out production and business-related activities. If no safety hazards are found in the written inspection, the inspection is terminated; if further on-site verification is deemed necessary, an on-site inspection should be initiated. The drug regulatory departments of each province, autonomous region, and municipality directly under the central government determine the specific form of the inspection based on the risk situation of the product and the holder.

5. Basic Inspection Procedures

(I) On-site Inspection

1. Inspection Plan and Program

Before inspecting the holder, the drug regulatory department or inspection agency shall formulate an inspection plan and an inspection program, clarifying the purpose, basis, scope, time, inspection team, inspection points, and report writing requirements. The inspection team shall conduct on-site inspections according to the inspection plan. Based on the on-site inspection situation and the principle of risk, the inspection content may be appropriately adjusted. If necessary, the inspection shall be implemented after the approval of the inspection dispatching unit.

2. Composition of the inspection team

The inspection team is usually composed of two or more inspectors, and a team leader is designated to be responsible for the on-site inspection. The inspectors shall be familiar with the relevant pharmaceutical laws and regulations and have professional knowledge of pharmaceuticals. The team leader shall have more than three years of experience in pharmaceutical supervision or management.

3. On-site inspection procedures

(1) Inspection notification

The drug supervision and administration department or inspection agency may notify the holder of the inspection matters and related requirements in advance according to the inspection plan, but the holder shall not be notified in advance for inspections with cause.

(2) First meeting

After the inspection team arrives at the inspection site, it shall hold the first meeting. The first meeting shall be chaired by the team leader, and the inspection team shall present the inspection certification documents. The main management personnel of the holder shall attend the meeting and introduce the basic situation of the holder, the establishment and operation of the quality management system, entrusted production and operation, drug quality, post-marketing research, pharmacovigilance and liability compensation capabilities, etc. In principle, no first meeting is held for unannounced inspections (for-cause inspections).

(3) On-site inspections

On-site inspections should be conducted on the basis of science, fairness and impartiality, and should be conducted around the key points of the inspection through on-site observation, interviews, questioning, document review, etc. The contents of the on-site inspection should be recorded in a timely manner. According to the actual situation, the inspection team may collect evidence on-site by means of collection, copying, recording, photography, videography, sampling, and inspection.

According to the actual inspection situation, if necessary, an extended inspection may be conducted on the entrusted enterprise and the associated review enterprise. If the entrusted enterprise is not located within the jurisdiction of the province, autonomous region or municipality directly under the Central Government, the two local drug regulatory authorities may negotiate to conduct a joint inspection if necessary. If an overseas manufacturer is involved, the relevant provisions on overseas drug inspections shall apply.

(4) Final meeting

At the end of the on-site inspection, a final meeting shall be held. The final meeting shall be chaired by the head of the inspection team and attended by the main management personnel of the holder. The inspection team shall report the basic situation of the inspection, the problems and defects found, the subsequent rectification requirements, and the measures that the drug regulatory authorities may take. If the inspected unit has any objection, it can make a statement and defense on the spot. The inspection team shall record it truthfully and conduct necessary verification of the disputed issues or defects.

4. Inspection report

Before the completion of the on-site inspection, the leader of the inspection team shall organize internal discussions, evaluate the inspection situation, and organize the writing of the inspection report. The inspection report shall describe the matters required to be inspected in the inspection plan, and shall include but not be limited to the scope, time, composition of the inspection team, basic inspection situation, problems found, and inspection conclusions or opinions.

5. Rectification

The holder shall rectify the problems and defects found in the inspection in accordance with the regulations, and submit a formal rectification report to the inspection dispatching agency within the prescribed time limit.

6. Inspection results and handling

The drug supervision and administration department or inspection agency shall review the holder's rectification report based on the on-site inspection situation, issue an audit opinion, and draw an audit conclusion. If necessary, an on-site inspection may be initiated for its rectification situation. If the inspection finds that the drug has quality problems or other safety hazards, appropriate measures should be taken immediately during or after the inspection to control the risks first.

If the rectification report is not submitted on time or safety hazards may still exist after rectification, the drug supervision and administration department shall, based on the inspection results, take risk control measures such as warnings, interviews, rectification within a time limit, and suspension of production, sales, and use, and shall promptly announce the inspection and handling results. If necessary, it may inform the drug supervision and administration department of the entrusted production enterprise's location of the relevant information.

Specific news link: The General Department of the National Medical Products Administration publicly solicits opinions on the "Drug Marketing Authorization Holder Inspection Work Procedure (Draft for Comments)"