Key Strategies for Successfully Passing NMPA Inspections for Medical Device Manufacturers | Part 2. China NMPA inspection process

In our previous blog post, we delved into the intricate landscape of regulatory inspections that foreign manufacturers may encounter when seeking to market or to maintain the registration status of their medica devices in China. We highlighted the importance of complying with the requirements set forth by the China National Medical Products Administration (NMPA) and discussed the various types of inspections that NMPA may conduct. 

These encompass pre-licensing inspections to assess a manufacturer's readiness to obtain regulatory approval, routine inspections to monitor compliance with existing regulations, for-cause inspections triggered by specific events or concerns, and post-market surveillance inspections to ensure ongoing product safety and quality. Understanding   the nature and scope of these inspections is crucial for foreign manufacturers seeking to enter the Chinese market and maintain regulatory compliance.

In this series we intend to explain the China NMPA inspection process and steps that inspected site needs to take to better prepare for the inspection.
The requirements for the inspection process were announced by NMPA on December 26, 2018 in the Announcement No. 101 on Issuing the Administrative Measures for Overseas Inspections of Drugs and Medical Device to ensure the quality and safety of drugs and medical devices developed or manufactured abroad. This marks the initial implementation of comprehensive operational protocols to provide NMPA with uniform guidance for conducting inspections abroad. The Chinese government has taken a firm stride towards establishing efficient post-market oversight and management. 

The overseas inspection concerns the foreign medical device legal manufacturer and legal manufacturer but also the extended partners such as R&D sites and contract manufacturers. Moreover, inspections may be expanded to include the production sites, suppliers, or other contractual parties providing raw materials, auxiliary materials, and packaging materials if deemed necessary.

The NMPA uses a combination of risk assessment and random selection to determine its annual inspection targets, taking into account certain risk factors, such as: 

• potential risks identified during the review and approval process, 
• risks in the quality management system detected during inspections or batch release, 
• potential safety risks associated with adverse reactions and events, 
• violations of laws or regulations reported through complaints, 
• adverse records of the marketing authorization holder, 
• major issues in a contract manufacturer quality management system discovered during on-site inspections by foreign regulators,
• cases where re-inspection is required after corrective actions.

The NMPA inspection process can be broken down into 3 main phases: pre-inspection, on-site inspection and post-inspection. The NMPA, the Inspection Center CFDI (Center for Food and Drugs Inspection of NMPA) and the companies being inspected have distinct responsibilities in the overseas inspection process. 
The following are the essential measures undertaken in each stage by the involved parties.

Pre-inspection Phase:

1. NMPA: Determines the annual inspection tasks and other inspections according to the law.
2. Inspection Center:
   
   • Send an “Overseas Inspection Notice” (Annex 1 of the Announcement No. 101).
   • Send “Pre-Notice of Overseas Inspection” (Annex 5 of the Announcement No. 101) at least 10 working days in advance. The notification will include the date, time, and scope of the inspection.
   • Create the inspection plan and formulate the inspection team. In principle, inspection teams shall be composed of three or more inspectors.
   
   
3. Inspected site (MAH, manufacturer, R&D center): 

• Submit the following documentation to the Inspection Center:
  “Power of Attorney” (Annex 2 of the Announcement No. 101) within 20 days from receiving the “Overseas Inspection Notice”.
  “Basic Information Form of the Product” (Annex 3 of Announcement No. 101) to be inspected within 20 days from receiving the “Overseas Inspection Notice”. 
  “Site Master File” (Annex 4 of Announcement No. 101) within 40 days from receiving the “Overseas Inspection Notice”.
• Appoint China Agent (in case of initial registration) to perform the relevant responsibilities and obligations for imported medical devices as stipulated by laws and regulations and cooperate with NMPA.   

On-site Inspection Phase:

1. NMPA: Inspection Center informs NMPA immediately in case of any serious quality risks or illegal activities are found during the inspection. 
2. Inspection Center (inspection team):
   
   • Opening Meeting: The inspectors will hold an opening meeting with the manufacturer to discuss the scope of the inspection and answer any initial questions.
   • Document Review: The inspectors will review all relevant documents to ensure compliance with Chinese regulations.
   • Facility Inspection: The inspectors will conduct a physical inspection of the manufacturing facility to assess compliance with regulations, including equipment and infrastructure, cleanliness, and personnel hygiene.
   • Sampling: The inspectors may take samples of the product being manufactured for testing and analysis.
   • Closing Meeting: The inspectors will hold a closing meeting with the manufacturer to discuss any findings and next steps.
   • Formulate the Inspection Report and provide to the Inspection Center of the NMPA with 10 days.
   
   
3. Inspected site (MAH, manufacturer, R&D center): 
   
   • Fully cooperate with the on-site inspectors.
   • Allowed to explain and discuss any disputes during the closing meeting. 

Post-Inspection Phase:

1. Inspection Center: 
   
   • Send “Notice of Overseas Inspection Results” (Annex 6 of Announcement No. 101) to the MAH within 20 days.
   • Send the final Comprehensive Evaluation Results to MAH and the NMPA. In case of rectification measures review, the Comprehensive Evaluation Results shall be prepared within 20 working days after receiving the rectification report from MAH. 
   
   
2. Inspected site (MAH, manufacturer, R&D center):
   
   • In case of objections to the inspection results, MAH may submit a written statement or explanation to the verification center within 10 working days after the "Notice of Overseas Inspection Results" is delivered to the MAH. 
   • The rectification measures shall be conducted within 50 working days and submitted to the Inspection Center (if any).

Follow-Up Inspection: If the plan is not satisfactory, the NMPA may conduct a follow-up inspection or take other appropriate actions.

There are 3 possible outcomes for comprehensive evaluations, depending on the context and criteria being evaluated:
Acceptable: when no defect was found through on-site inspection;
Acceptable after rectification: the company effectively rectified major defects found during the inspection and organized production according to laws, regulations, and technical specifications.
The evaluation results indicate that the object being evaluated does not fully meet the criteria and standards, but it can be improved through some corrective actions. After the necessary changes are made, the object is expected to meet the acceptable level.

Fail:

• The issue of authenticity or inconsistency with registered items and insufficient or unattainable rectification measures or failure to conform to laws, regulations and technical specifications may cause major defects.
• Company is deemed deferring, hindering, restricting or refusing inspection if they fail to provide documents on time, postpone inspection twice, restrict inspection team from certain areas, or otherwise not cooperate with the inspection.

Becoming curious about what the NMPA inspection process entails?
Read our blog series - 7 parts:

Part 1. China NMPA inspection types
Part 2. China NMPA inspection process
Part 3. Preparation for China NMPA inspection
Part 4. Verification of the QMS for Medical Device Registration
Part 5. Verification of the QMS for Medical Device Production
Part 6. Verification of the QMS for Medical Device Distribution
Part 7. China NMPA Inspection Results and Common Findings