On April 15, China National Medical Products Administration (NMPA) issued the Pharmacovigilance Inspection Guidelines with immediate effect. The Guidelines lists key points for national and provincial medical products administrations to carry out pharmacovigilance inspections.1
The key points include the inspections' items and methods, which are worth the attention of marketing authorization holders (MAHs) for fulfilling pharmacovigilance responsibilities.
1. What is Pharmacovigilance?
Pharmacovigilance refers to the monitoring, identifying, evaluating and control of adverse drug reactions (ADRs) and other negative reactions related to medication.2
In China, pharmacovigilance is also a legal obligation of drug MAHs and applicants since the GVP came into force in December 2021. An MAH can entrust pharmacovigilance activities to a third party but the MAH is still the main legal entity to bear the liability.
2. What Does the Pharmacovigilance Inspection Guidelines Apply to?
The Guidelines applies to inspections of pharmacovigilance activities conducted by the MAH itself or by an entrusted third party.
The Guidelines can also be a reference for inspections for pharmacovigilance activities of drug applicants who have been authorized to carry out clinical trials and are applying for marketing authorization.
3. What Kind of MAHs Will Receive Special Attention in Routine Inspections?
In routine inspections, inspectors will pay special attention to MAHs with any of the following characteristics:
The MAH owns numerous drug products with high sales.
The MAH has never received a pharmacovigilance inspection before.
The MAH has obtained drug marketing authorization in China for the first time.
The MAH is experiencing a merger or structural change, leading to a major change in the pharmacovigilance system or significant influence on the pharmacovigilance organization's structure.
The MAH has entrusted manufacturing activities to a third party.
The MAH has entrusted pharmacovigilance activities to a third party.
4. How and Where Will the Inspections Take Place?
Pharmacovigilance inspections take place in two forms:
Remote inspection via phone, video, etc.
Inspections sites are mainly where the MAHs carry out critical pharmacovigilance activities. When necessary, inspections will also cover sites where the entrusted pharmacovigilance activities are conducted.
5. Pharmacovigilance Inspection Items and Deficiency Levels
NMPA lists 100 pharmacovigilance inspection items in 28 categories. The deficiencies are classified into three levels:
12 items that could be evaluated as with severe deficiency;
40 items that could be evaluated as with major deficiency;
48 items that could be evaluated as with moderate deficiency.
An MAH's pharmacovigilance compliance will hinge upon the deficiency levels. An MAH will be evaluated as not complying with requirements if it meets any of the following conditions:
One or more items have severe deficiencies;
10 or more items have major deficiencies, and no items have severe deficiency;
0-9 items have moderate deficiencies and no items have severe deficiency. The number of total deficient items exceeds 25.
The following table lists the 28 categories of pharmacovigilance inspection items. Contact ChemLinked BaiPharm Portal via firstname.lastname@example.org if you need the specific items of pharmacovigilance inspections or guidance for accomplishing pharmacovigilance activities.
Category of Pharmacovigilance Inspection Items
1. Personnel and Resources
Drug Safety Committee: e.g. if the MAH has established such a committee; if the committee has clear and reasonable responsibilities.
Pharmacovigilance Department: e.g. if the MAH has launched such a special department.
Relevant Departments: if the MAH has assigned pharmacovigilance responsibilities to other departments (perhaps involving R&D, manufacturing, sales, marketing, quality assurance & control, etc.)
Responsible Person for Pharmacovigilance
Special Staff for Pharmacovigilance
Devices and Resources
2. Quality Management and Document & Record
Quality Management System
Internal Review of the Pharmacovigilance System
Management of Documents about Systems and Procedures
Pharmacovigilance Master Files
Records and Data Management
Entrusted Management: e.g. whether the MAH has evaluated the entrusted party's pharmacovigilance conditions and capabilities, whether the two parties have signed agreements in paper, etc.
Information Registration and Updates, e.g. if the MAH has registered the drug information and updated the drug label in the National ADR Monitoring System.
3. Monitoring and Report
Approaches to Collecting ADR Information
Handling of ADR Information
ADR Evaluation and Report
Enhancing Post-market Monitoring
4. Risk Identification and Evaluation
Monitoring of ADR Signals
Signal Analysis and Evaluation
Post-market Safety Research
Periodic Safety Update Report (PSUR)/Periodic Benefit-Risk Evaluation Report (PBRER)
5. Risk Control
Risk Control Measures
Investigation and Handling of Intensive Adverse Events (AE)