May 16, 2022 Post Marketing

Post-market Surveillance under MDR & USA

Post-market surveillance (PMS) was first discussed by defunct Global Harmonization Task Force (GHTF). They are the ones defined required tasks necessary for PMS plus shows how each task is involved in PMS be harmonized through regulatory environment. About PMS, Europe’s Medical Device Directive (MDD) did not have any specific control, yet Medical Device Regulation 2017/746 (MDR) stated PMS is

About all the activities taken care by manufacturer in association with economic operators to establish and maintain an organized procedure to proactively collect and review knowledge gained from medical devices they place & make available on market, or put into service for the purpose of any necessary corrective or preventive actions to apply immediately.

What MDR says about Post-market Surveillance?

PMS is a process of gaining experience from medical devices that were released in the market and proactively collecting, analyzing the device performance information. We never know when the risk may occur from the device, it can be during use, during transportation to other places, during cleaning or storing of the device. The main agenda behind PMS under MDR is to put in a continuous cycle of device improvement, and should say that it is in compliance with regulations. Therefore, companies must oblige to quality monitoring process, performance, safety of a device through out its lifecycle and implement corrective/preventive actions wherever/whenever necessary.

Few of the regulations and standards for PMS are MDR 2017/745, ISO/TR 20416:2020, ISO 13485:2016, ISO 14971:2019. In MDR 2017/745 – article 15,83,84,85,86, and annex 3 explains about a person responsible for regulatory requirements, post-market surveillance system for the manufacturer, post-market surveillance plan, post-market surveillance report, periodic safety update report and technical documentation for post-market surveillance system respectively.ISO/TR 20416:2020, ISO 13485:2016 & ISO 14971:2019 tells about the requirements for Post-market surveillance for manufacturers, Quality management systems — Requirements for regulatory purposes, Clause 8& Application of risk management to medical devices, clause 10.

PMS Purpose

The main purpose of a well organized PMS system is to identify risks on timely basis that are not identified during manufacturing process, and also it is an opportunity to improve the device’s performance. Furthermore, this PMS system is aimed to make sure about safety and intended use of the device, to meet regulatory compliance and to ensure lifecycle management. Along with the adverse effects, PMS also gains the information on the positive effects of the device. Other essential activities in PMS include off-label device use, problems associated with clinical trials. Let’s see here some of the inputs to PMS, and based on this inputs – what decisions and preventive actions to take for improvement. If any design and development changes are required by the patient or user through PMS that has to be implemented – for example: increase in the digital thermometer’s diameter belt for obese people.

PMS is to check about the risk management file – for example: if any complaint from user or competitor has been noticed; that should be analyzed and controlled by the manufacturer. Clinical and performance evaluation is a continuous process and if any new information regarding safety of the device is observed – related purpose should be analyzed, discussed in the upcoming clinical evaluation report to submit to the regulatory bodies. If any adverse events occur after the device is released in the market that has to report to the regulatory authorities, similarly advisory notices should be issued to distributors, users, and the general public through regulatory bodies. For some medical devices after releasing on the market – need some improvements based on the risks from survey and complaints or from user; that may lead to necessary changes in the quality system by initiating corrective and preventive actions. Despite of all the PMS processes and decisions, marketing strategies also need to be balanced for sales. Always the information gathered from PMS should be implemented in several elements of the quality system and if any major changes of risk and clinical evaluation shows greater impact on technical documentation of the device.

Who Shall Take the Responsibility of PMS?

As stated above regarding Article 15 – person responsible for regulatory requirements is the one responsible for PMS also.This person will be nominated by manufacturer itself based competences determined in article 15.Among ISO guidelines, ISO/TR 20416:2020, chapter 5.4 is about responsibilities and authorities explain that top most management of the company must form the PMS team and assign responsibilities. The team should co-ordinate with cross functional departments and process owners i.e., design and development department, risk management, quality assurance department, complaint handling department, etc. Each and every process owner is responsible for analyzing and data collection from their respective departments and number of people involved in PMS depends on the company size, complexity & risk of the medical device. The duty of a person responsible for regulatory compliance (PRRC) is to keep, maintain, and monitor the PMS up to date.

Procedure for Conducting PMS

In the ISO guidelines, a clear picture about how to conduct PMS for a medical device was given. Top management of the manufacturer must follow clause 8 of ISO 13485:2016, and clause 10 of ISO 14971:2019 for collecting, analyzing, and documentation of production, post production works. As per the article 83, manufacturer must prepare documentation with information of how PMS is going to be organized and the step by step procedure that will be followed to implement PMS system. Also to explain about what type of data from the user is necessary to follow, data collecting & analyzing methods from user, delivering conclusions from the data analysis, and which tells about how to implement concluded decisions in quality, technical documentations. Designated PRRC must co-ordinate and conduct review meetings with team to prepare PMS plan by taking results, inputs, outcomes of various PMS activities. PMS plan should discuss about how manufacturer anticipates the data to gather and evaluate about the significance. Also it must include PMS plan’s scope, what are the objectives proposed, duties and authorities, data collection & analysis, and review process of PMS plan. As a part of technical documentation, PMS plan must prepare ahead of launching a new medical device for the fist time in the market and continue to update at its life cycle.

PMS plan also must include if the Post-Market Clinical Follow-up (PMCF) is required, implement the plan and generate PMS reports based on the survey findings. PMS technical documentation must outline the measures for the risk/benefit assessment of the device and processes for follow up on complaints, information communicating to regulators & users, employing corrective action on devices, producing PMCF plan or writing a rational for why PMCF is not required.

PMS Reporting

Different submitting regions require different documents like, if to submit in USA, FDA look for Periodic Adverse Drug Experience Report (PADER/PAER) from manufacturer, similarly in EU, PMS report should be submitted to low risk class I devices and periodic safety update report (PSUR) for Class IIa, Class IIb, and Class III devices. As a part of technical documentation, these PSUR, PMSR should contain data analysis and a description of the corrective and preventative actions taken and updated by manufacturer regularly based on the relevant regulatory bodies’ timelines.

FDA 21 CFR part 822 in US summarizes key requirements for PMS of a medical device if the device fall under class II & III. The criteria of Class II & III devices are

1) Failure of the device would likely have a serious adverse health consequence

2) The device is intended to be implanted in human body for more than one year & a life-sustaining of life-supporting device used outside of a user facility.

PMS is response for the devices adverse event reports, safety and effectiveness of limited pre-market testing devices or to gather device’s real world clinical practice information. FDA used MedWatch for health care professionals and consumers to submit adverse event reports, MAUDE database for manufacturers, importers and device user facilities and voluntary reporters such as health care professionals, patients and consumers to submit medical device mandatory reports. Class I medical devices typically do not need PMS, as they are lower risk.

Annex III of the MDR 2017/745 details the EU requirements for PMS, unless US- EU mandated to have PMS for all class devices and expanded requirements that increase compliance efforts. In EU market PMCF is an added component in PMS activities and criteria for PMCF mandate is device’s risk and novelty. In Article 86, PSUR mandated special attention for conclusions of the benefit/risk determination. Time span for reviewing the PMS activities for class I devices are as and when needed based on new input, for class IIa & b devices are as needed at least biannually & annually respectively. For class IIa, IIb implantable, class III are at least annual PSUR updates are required. It also should be updated for class II & III devices with volume of device sales, estimated evaluation of size and other characteristic of population using it and device usage frequency. PMSR’s apply to class I medical devices under MDR and Class A, B devices under the new in-vitro diagnostic regulation (IVDR) mandate.

Typical inclusions of PMS report are regulatory history, device background, device description and indications for use, PMS plan purpose-objectives-hypothesis-design, patient population with inclusion & exclusion criteria, statistically justified sample size calculation. Also it should include primary and secondary endpoints, definitions, study success criteria, expected adverse events of complications list, and an agreement to collect unexpected adverse events. PMS report also must include with follow-up schedule, length, and assessment procedures description, data collection & analysis procedure, statistics, reporting schedules for interim and final reports, milestones/timeline analysis, and effective tools to trace and identify devices for which corrective actions may be needed. Furthermore, Annex III of the MDR 2017/745 describes some more points on PMS reporting is – threshold values for assessing risk-benefit and effective risk management, methods for managing events subject to the trend report, protocols for communicating effectively with the competent authorities, notified bodies, economic operators, and users, reference for procedures to fulfill the manufacturer’s obligations for PMS system, PMS plan, and PSUR.

How to Make a Strong PMS system?

For preparing a strong PMS system the device must compliant with regulatory guidelines when it is on the market. Defining the data for a medical device is the biggest task in building a strong PMS system and the monitored data should be in proportion to risk associated with device proposed use. A well defined PMS system helps to identify anissue in the design and production of a medical deviceas well as a guide to solve the issues in no time with low cost effect. In this system, economic operators will play a crucial role in collecting feedback as high as they can – which will help the manufacturer in delivering a safe, qualitative performance device to the end user and meet regulatory compliance.

Bottom Line

US or EU market standards are quickly harmonizing and showing more focus on PMS and risk management. Any manufacturer to sell their medical device in US & EU must act quickly to understand PMS requirements, to develop a plan and to build a strong compliant PMS system. Since PMS is a part of good business strategy, it alerts manufacturer to react quickly on potential flaws in the design or implementation of the device. This effective PMS system with continuous improvements and outcomes build up a trust to the end user and shows manufacturer’s commitment towards user safety.