On September 24, 2024, the China National Medical Products Administration (NMPA) issued the draft “Guidelines for Post-Marketing Safety Evaluation of Drugs” for public consultation. These guidelines aim to strengthen post-marketing safety measures in alignment with Good Pharmacovigilance Practice (GVP) and international standards, ensuring the well-being of patients. This article provides a detailed overview of the draft’s critical aspects and its implications for pharmaceutical companies operating in China.
Scope of Application:
The guideline applies to post-marketing safety evaluations conducted by marketing authorization holders (MAHs) to address identified safety issues, as mandated by relevant laws, regulations, or regulatory authorities. These evaluations, referred to as “causal evaluations,” aim to determine the causal relationship between the drug and safety concerns.
Signal evaluation and risk assessment activities performed under Good Pharmacovigilance Practice (GVP) may also reference this guideline for additional guidance. However, the scope does not extend to evaluations focused solely on product quality issues or periodic safety updates (e.g., PSURs).
Framework of Safety Evaluation:
The guideline outlines a structured approach:
1. Signals and Objectives:
Post-marketing safety evaluations are initiated to address safety issues identified through various sources, such as signal monitoring, regulatory inquiries, or external reports (e.g., media or consumer complaints). The key aspects include:
a) Sources of Safety Issues:
By channel:
- Detected through routine signal monitoring conducted by the Marketing Authorization Holder (MAH).
- Raised through inquiries or requests from regulatory authorities.
- Highlighted via media reports or consumer complaints.
By Region:
- Domestic safety issues
- International safety issues
b) Nature of Safety Issues and Objectives:
- Unexpected Adverse Events: The goal is to confirm the causal relationship between the drug and adverse events. If the risk is confirmed, further evaluations may address its characteristics, mechanisms, and influencing factors.
- Risk Factors: For known or confirmed risks, the evaluation focuses on factors that may increase the likelihood of the risk.
- Drug Use-Related Issues: The goal is to determine the extent and impact of usage problems on product safety.
- Other Safety Concerns: Evaluation objectives depend on the nature of the problem. For regulatory-required evaluations, goals should be fully communicated with the authorities.
2. Data Collection:
- Collect global and domestic evidence from safety databases like FAERS (FDA), EudraVigilance (EMA), and literature searches.
- Use broad retrieval strategies to ensure comprehensive case capture.
- The data should be as comprehensive as possible to support the evaluation, covering both domestic and international information.
- For safety issues exposed abroad, evaluations may rely on foreign evidence if domestic data is insufficient.
- Usage-related safety issues should prioritize domestic evidence.
Data Sources Include:
a) Pharmacovigilance Databases:
- Domestic and international pre- and post-marketing databases, e.g., FDA’s FAERS, EMA’s EudraVigilance, Uppsala Monitoring Centre’s Vigibase.
b) Scientific Literature:
- Case reports, observational studies, systematic reviews, and meta-analyses from reputable databases.
c) Research and Investigations:
- Studies previously conducted or participated in by the holder, including non-clinical and clinical trials, epidemiological studies, etc.
d) Expert Opinions:
- Internal or external experts, documented via meeting minutes or advisory forms.
e) Regulatory Websites:
- Safety updates, risk assessments, and regulatory guidance from domestic (e.g., NMPA) and international authorities (e.g., FDA, EMA).
3. Evaluation Considerations:
Analyze unexpected events, associated risk factors, and usage patterns for causality and impact.
a) Unexpected Adverse Events:
- Reports of adverse drug reactions.
- Epidemiological studies.
- Comparisons of disease background incidence with adverse event rates.
- Mechanistic analysis (pharmacological, pharmacokinetic, interactions, etc.).
b) Risk Factors:
- Factors increasing the likelihood of known risks, such as patient characteristics, underlying diseases, co-administered drugs, storage conditions, etc.
c) Drug Use Issues:
- Misuse, abuse, off-label use, medication errors, and irrational drug use.
d) Benefit Analysis:
- Conducted in cases of severe risks potentially impacting benefit-risk balance.
4. Report Compilation:
The report should present the analysis process and results, including:
- Reasons and objectives.
- Background information on the drug and its risks.
- Evidence analysis.
- Results and discussion.
- Conclusions and recommendations.
Writing Requirements:
- Clear structure, logical flow, concise language.
- Evidence selection and utilization should directly relate to safety concerns and evaluation objectives.
5. Quality Assurance:
Ensure evaluations are backed by experts with medical or pharmacological expertise, supported by robust data systems
- Establish and improve standards for safety evaluations.
- Provide sufficient resources, including domestic and international literature retrieval tools and funding for post-marketing studies.
- Ensure trained professionals with expertise in medicine, pharmacy, or epidemiology conduct evaluations.
- Pharmacovigilance leaders supervise the evaluation process, coordinating with authorities as needed.
- The Drug Safety Committee oversees resource allocation, reviews conclusions, and determines risk management measures.
Contact Us for Support
For expert assistance with post-marketing safety evaluations and ensuring compliance with NMPA regulations, reach out to Accestra—your trusted partner in navigating China’s complex pharmaceutical regulatory framework.
📧 Email: info@accestra.com
🌐 Website: www.ChinaPvHub.com
Source: https://www.cdr-adr.org.cn/tzgg_home/202409/t20240924_50855.html