Important elements revolve around maintaining quality, performance and safety throughout the product lifecycle.
As the new In Vitro Diagnostic Regulation (IVDR) replaces the current In Vitro Diagnostic Directive (IVDD) in 2022, there are many significant changes that IVD manufacturers must consider from a risk management perspective, as well as those pertaining to Post-Market Surveillance (PMS) to meet compliance.
To begin, it is important to understand how PMS is defined under the IVDR:
“‘all activities carried out by manufacturers in cooperation with other economic operators to institute and keep up to date a systematic procedure to proactively collect and review experience gained from devices they place on the market, make available on the market or put into service for the purpose of identifying any need to immediately apply any necessary corrective or preventive actions.” Annex 2 (63)
The IVDR Preamble (75) gives direction that manufactures are to play an active role during the post-market phase of the product lifecycle. PMS programs should actively and systematically gather information from a device in a way which allows for regular updates to technical documentation and competent authorities’ communication in the areas of vigilance and market surveillance.
Due to these requirements, it is imperative that surveillance programs be implemented with a formal Post-Market Surveillance Plan (PMSP). The data gathered through PMS activities, such as Corrective Actions and Preventative Actions (CAPA), should be used to update technical documentation—for example, updates to risk management assessments, risk reports, performance evaluations—showing consistent, regular updates to PMS.
Previously, NAMSA’s blog series discussed the QMS application under the IVDR. As a reminder, Article 10(8i) states that a PMS system must be created and implemented and Article 10(9) states that this system must be kept up-to-date in accordance with Article 78.
I. Article 78: The Guide for Post-Market System of the Manufacturer
Post-Market Surveillance of products is not a new concept within the IVD regulatory framework. For example, ISO13485:2016 mentions PMS activities in Section 8.2.1 regarding feedback processes which should include provision to gather data from production, as well as post-production activities and 8.5.1 improvement actions from QMS sections including PMS.
Additionally, the current IVDD states the importance of the usage of a PMS system in Annex III (5) ad reviewing experience gained in the post-production phase. This includes the requirement of implementing appropriate and necessary CAPA activities and communication with competent authorities regarding:
- “Any malfunction, failure or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labelling or the instructions for use which, directly or indirectly, might lead to, or might have led to, the death of a patient or user or other persons or to a serious deterioration in his or their state of health;
- “Any technical or medical reason connected with the characteristics or the performance of a device for the reasons referred to in subparagraph (i) leading to systematic recall of devices of the same type by the manufacturer.”
The IVDR expands PMS activity requirements, even for those manufacturers who are ISO13485:2016 compliant, as the standard is not explicit enough to meet requirements of Article 78.
Article 78 states that manufacturers should have for each device, a well-structured PMS system that is appropriate for the risk class and device type (see previous NAMSA blog on IVDR technical documentation and risk). Furthermore, the PMS must be planned, documented, implemented, maintained, updated and integrated into the manufacturer’s QMS explained in article 10(8) and within the following blog post.
Quality, performance and safety of a device are the focus of a well-structured PMS system, and should actively and systematically gather, record and analyze relevant data throughout a device’s lifetime. This allows manufacturers to derive, conclude, implement and monitor CAPA actions and processes for all IVD devices.
II. What Type of Data Comprises PMS Data?
To be compliant, and as discussed earlier, all IVD manufacturers must have a PMS system under IVDR, and that data be utilized in particular as outlined in Article 79 (3):
- Updates to the benefit-risk determination and to improve risk management (Annex I Chapter 1);
- Update the design and manufacturing information, the instructions for use and the labelling;
- Update the performance evaluation;
- Update the summary of safety and performance referred to in Article 29;
- Identification of preventive, corrective or field safety corrective action;
- Identification of ways to improve the device by improving the usability, performance and safety of the device;
- When relevant, to contribute to the post-market surveillance of other devices; and
- To detect and report trends in accordance with Article 83.
With all the above, the IVDR states that a device’s technical documentation must be updated accordingly. To summarize, IVDR mandates that PMS must be comprised of the following elements:
- Post-market review of the device.
- Traceability/Documentation on device’s performance, quality and safety.
This expanded requirement for IVD manufacturers will evolve the pathways of change for devices previously observed in the marketplace. The integration of a PMS is demonstrated further in Article 79, which illustrates that a PMS system should be based on the PMSP.
III. The PMS Plan: The Road Map to your PMS System
A PMS plan is the blueprint for how a manufacturer should implement and carry out their PMS activities. Plans can stand alone or, for example, if you have a family of products that are similar, a standardised plan may be appropriate. The incorporation of the plan into the QMS as either a procedure or a template to be completed as part of a device’s technical file, may also be used.
The IVDR pays particular interest to information regarding incidents (serious and non-serious), undesirable effects, field safety notices, information from trend reporting, literature database searches, feedback from multiple areas (complaints from users, distributors and importers) and public information from similar devices.
Annex III 1(b) provides manufacturers a list of minimum required categories to be included in a PMS plan:
- Indicators and threshold values for continuous reassessment of the benefit-risk analysis and risk management (Section 3 of Annex )I;
- Methods and tools to investigate complaints and analyze market-related experience collected in the field;
- Methods and protocols to manage the events subject to the trend report as provided for in Article 83, including the methods and protocols to be used to establish any statistically significant increase in the frequency or severity of incidents as well as the observation period;
- Methods and protocols to communicate effectively with competent authorities, notified bodies, economic operators and users; —
- PMS procedures to fulfil the manufacturers obligations laid down in Articles 78, 79 and 81; — systematic procedures to identify and initiate appropriate measures including corrective actions; —
- Trace and identify devices for which corrective actions might be necessary; and — a PMPF plan as referred to in Part B of Annex XIII, or a justification as to why a PMPF is not applicable.
The effectiveness of the processes regarding the above are taken into account during the technical assessment (Annex IX) as part of the technical documentation specified in Annex II, and the outputs of a PMS plan differ dependent on risk class.
- Classes A and B should prepare a PMS report (Article 80) summarizing findings, data and other attributes generated from the plan.
- Classes C and D must generate a Periodic Safety Update Report (PSUR) per Article 81.
- This report is similar to the PMSR outputs in Article 79, but also has set additional requirements such as findings from the Post-Market Performance Follow-Up (PMCF) and sales information of the device.
- The PSUR is to be created at least annually, whereas the PMSR can be created every five (5) years.
IV. Post-Market Performance Follow-Up Plan: Link Between the PMS System and Performance Evaluation
The PMPF is a proactive collection and evaluation of the performance and relevant data from the use of a device as described in Annex XIII (part B).
- PMPF is addressed in the PMSP and outputs are documented in a PMPF evaluation report (PMPFR).
- PMS processes should then inform the Performance Evaluation Report (PER) that is part of the technical documentation.
- PMPF plans ensure safety compliance, performance, identifying unknown/new risks or limits to performance, continued acceptability of the clinical risk and benefit-risk ratio as well as systematic misuse.
Please note: If the PMPF is not deemed appropriate for a specific device, then a justification shall be provided and documented in PER.
In conclusion, PMS system requirements introduced by the IVDR links to other mandatory elements of this regulatory change, and provides the ability for changes to the technical documentation through collected data. It is also connected to varied levels of QMS processes such as:
- Risk Management
- Scientific Validity
- Clinical Performance
- Analytical Performance (Performance Evaluation),
- Design and Development,
- Corrective and Preventive Actions (CAPA)
- Safety Monitoring
A PMS system is an integral part of any IVDR-compliant QMS and is key in establishing a robust systems and long-term success.
How Can NAMSA Help?
NAMSA is the industry leader in driving successful regulatory outcomes through effective interactions with the EU Commission and Notified Bodies. Our internal teams of medical device development and IVD experts communicate with EU entities nearly every day and are the most experienced in industry at accelerating regulatory submissions and approvals for IVD manufacturers.
Additionally, NAMSA provides support to market authorization holders, including implementation of IVDR requirements, IVDR conformity strategies and compilation of appropriate Technical Documentation for submission to Notified Bodies. NAMSA’s team of medical writers and regulatory specialists can provide full support to assist with all vital IVDR activities and processes.
Learn more about NAMSA’s IVDR resources here.
Warren Jameson is a Sr. Regulatory Consultant-IVD at NAMSA. His past experience includes Quality Manager ensuring compliance with relevant legislation (qualified ISO9001:2015 auditor and Data protection Officer (GDPR), managing quality documentation, risk assessments, risk management and audits. Further, Warren is expert at reviewing technical files and guiding IVD sponsors on the pathway to IVDR compliance. Warren has over 5 years’ experience in R&D, including development of clinical quality controls for IVD machinery. His work covered regulatory documentation such as design initiation, design scope, design history, verification and validation of the project and transfer of product. Warren has a PhD in Chronic Lymphocytic Leukemia (Hematology/Oncology) and a Bachelor of Science with Diploma in Industrial Studies (DIS) in Molecular Biology, both received from the University of Ulster.