Periodic Risk Evaluation Report in China

Periodic Risk Evaluation Report

(Chinese PSUR)

Background of Chinese Periodic risk Evaluation Report

NMPA issued guidance “Periodic risk evaluation report (PRER) of medical device” on 02,07,2020. It applies to class II and III of medical device. For class I medical device, only filing of PRER internally is essential.

PRER is also called Chinese periodicic safety updated reports (PSUR) because it is very similar to European PSUR required at MDR. In the fact it is a mixture of a part of European PUSR and risk analysis in term of vigilance (passive) and post market surveillance (active).

NMPA want to strength the control of safety of in China approved medical device and monitor its post market records in China and worldwide.

For required PRER in China it contains worldwide marketing history, vigilance summary, literature evaluation and risk analysis related to adverse effects, adverse events and recalls.

PRER for overseas products can be bilingual: English and Chinese and will be submitted electronically through Chinese agent annually.

Timeline of Periodic Risk Evaluation Report

PRER period starts from approval date on NMPA certificate and ends at the same day (ending date), throughout first 5 years annually. The deadline of submitting PRER is within 60 days of ending date of PRER.

How to submit PRERs depending on product classes and how to calculate first 5 years of PRER period, below we give a clear insight.

Frequency of PRER to NMPA

The manufacturers of class I medical device should

FILE PRER annually as record after initial registration (5 times) till next renewal

The manufacturers of class II and III medical device should

SUBMIT PRER annually after initial registration (5 times) till next renewal
FILE PRER as record since first renewal (once every 5 years)

Example of PRER period

PRER starts always from the fist approval date. Very important date to determine whether PRER applies to is 01, 01, 2019. The reason is that the PRER guidance is valid as of 01, 01, 2019.

Case 1: If first renewal occurs already before 01, 01, 2019, there is only need to FILE every 5 years one PRER as record, not to submit to NMPA.

Case 2: If the NMPA certificate is dated on e.g. 05, 06, 2018, you should submit:

PRER in 2019: from 05, 06, 2018 to 04, 06, 2019
PRER in 2020: from 05, 06, 2019 to 04, 06, 2020
PRER in 2021: from 05, 06, 2020 to 04, 06, 2021
PRER in 2022: from 05, 06, 2021 to 04, 06, 2022

Ending date of PRER: 05, 06

In the first 4 years the manufacturer has to submit PRER till 04, 09 (within 60 working days of ending date of PRER periodic)

At the 5th PRER it is a bit complicated. Man has to submit 60 working days earlier before expiration date. Normally the manufacturer renews the product to NMPA more than 6 months earlier till expiration date of NMPA certificate. In this case, the 5th PRER ends still 60 days before expiration date.

PRER in 2023: from 05, 06, 2022 to 04, 03, 2023 (=04, 06, 2023 – 60 days)
2024-2029: only FILE PRER as record etc.

Case 3: If the NMPA certificate is dated on e.g. 05, 06, 2019, you should submit:

PRER in 2020: from 05, 06, 2019 to 04, 06, 2020
PRER in 2021: from 05, 06, 2020 to 04, 06, 2021
PRER in 2022: from 05, 06, 2021 to 04, 06, 2022
PRER in 2023: from 05, 06, 2022 to 04, 06, 2023
PRER in 2024: from 05, 06, 2023 to 04, 03, 2024
2025-2030: only FILE PRER as record etc.

With the time scale at figure 1 you can match your product correspondingly.

Analysis of Periodic Risk Evaluation Chapter

Marketing history

It refers to registration information in which model and variants and in which other countries medical device is also approved.

Previous risk control measures

Here is control measures mainly of AE and recall asked.

These measures come from worldwide registered AE and recalls. Besides it, NMPA requires whether

Withdraw of product certificate (should be a kind of marketing record above)
Manufacturing process changes
IFU are revised
Notifiable change happens
Clinical re-evaluation due to safety concerns

Summarised if the items above did take place, NMPA should have concerns about the safety of approved products in China. So think about being conservative by reporting. Otherwise you have to provide "countryspecific reasons" why these were not reported or integrated in change registration to NMPA. For manufacturing process changes and revised Chinese IFU you have to make an official application at NMPA in China.

Vigilance (adverse event and recall = FSCA)

Chinese PSUR requires report of individual and group adverse events and recalls worldwide. Actually in many countries the adverse events affecting group is regarding to severity of incidents regarded automatically to high risk event to register to authority.

Risk analysis

Here is focus on cause and control measure of risk derived from registered AE and recall.

The risk analysis in Chinese PSUR sounds for some manufacturers not immediately understandable. Actually periodic risk analysis at risk assessment of incident represents an output of post market activities of approved medical device. Adverse events, recalls or observed incidents of similar product at authority’s vigilance site have to be in risk analysis and adverse effects of medical device in literature should be evaluated. Subsequently, control measurement of these risks should be also analysed.

Template of Periodic Risk Evaluation Report

1. Basic info

PSUR
Info of legal manufacturer
Product name, variant and model
Product composition
Intended use
Certification number

2. Worldwide marketing history

Country
Product name, model and variant
Status of registration (Valid, obsolete)
Initial approved date
Desolate date if applicable

3. Previous risk control measures

Yes or no answers in relate to terms below, evidence record if applicable

Withdraw of approved product
Recall
Significant change of manufacturing process
Revision of IFU
Design change
Clinical re-evaluation

4. Worldwide adverse event and recall reporting (individual and group)

AE reporting number
Product name, model and variant
Venue of AE
Time of AE
Description of AE
Control Measures of AE

5. Risk analysis

Summary of safety hazards should be evaluated. If some incidents happen, the cause to this AE (performance or clinical features, design requirement, manufacturing process, storage and transport condition, operating environment) has to be analysed. The control measures are also a part of risk analysis to conclude that these hazards have no safety concerns left.

6. Conclusion

The current PRER compared to last periodic of PRER should be analysed. The acceptance of difference should be evaluated.

Comparison to Periodic safety update report PSUR at MDR (Article 86)

Items	Periodic risk evaluation report in China	Periodic safety update report in Europe
Product class	I, II, III	IIa, IIb and III
Frequency of report	Annually after initial product approval (5 years)	Class IIa: every 2 years; Class IIb and III: every year
Report to	NMPA in electronic format	Part of technical documentation. Class IIa, IIb and III: Report to Notified body, on demand to authority competency Class III: additionally at EUDAMED technical documentation.
Key contents at report	Worldwide marketing history, worldwide incident reporting and literature evaluation of vigilance, risk analysis (trend analysis, adverse event, recall, adverse effect, CAPA)	Worldwide marketing history, incident reporting, trend analysis, customer complaints, monitoring of similar products, literature evaluation, CAPA, PMCF, risk analysis and benefit to risk analysis in term of incident

Some thoughts about Periodic Risk Evaluation Report

NMPA has elite tempo to strength registration complexity of medical device since 2014. NMPA is aware that at submission dossier there is no post market information. After issuing guidance of adverse event and recall in 2019, Periodic risk evaluation report is born in 2020.

Actually European PSUR of medical device copies from PSUR of drugs focusing adverse effects. It is kind of mishmash of PMS required for medical device, one of the upregulation at MDR in Europa. China follows PSUR quickly adding requirements of risk analysis with new name Periodic risk evaluation report.

As shown in template there is too wide extent at risk analysis which related to registered adverse events, recall and co. We highly recommend you not seriously to report sensitive CAPAs, revision of IFU outside China, design change etc. Otherwise it raises concerns by NMPA that medical device has safety problem worldwide. Instead, provide complete worldwide marketing history, adverse events, recalls and its cause and control measurement in term of risk analysis.

Unfortunately NMPA is drafting already new guidance regarding post market surveillance, and PMCF follows:)