December 7, 2020

Risk Benefit Analysis and Residual Risk are Key Components of ISO 14971:2019

Author: Nupur Srivastava, PhD 

The International Organization for Standardization (ISO) 14971:2019 places more emphasis on the risk to benefit ratio of medical devices, asking manufacturers to show that their device is not only safe but also provides a medical benefit. The reference to benefit is included throughout the standard, and the definition for “benefit” is included for the first time.  

ISO 14971:2019 Definition of Benefit: a positive impact or desirable outcome of the use of a medical device on the health of an individual, or a positive impact on patient management or public health. 

As outlined in the standard, risk has two key components:  

  • The probability of occurrence of harm; and 
  • The consequences of that harm, that is, how severe it might be. 

The newest ISO 14971:2019 standards emphasize that manufacturers need to demonstrate that the benefits outweigh the risks, as well as mitigating risks. Clause 7.4 of ISO 14971:2019 has even been retitled “Risk/Benefit Analysis” to align with regulatory changes.   

Examples “benefits” provided ISO 14971:2019: 

  • Positive impact on clinical outcome 
  • Patient’s quality of life 
  • Outcomes related to diagnosis 
  • Positive impact from diagnostic devices on clinical outcomes 
  • Positive impact on public health 

The guidance document ISO/TR 24971:2020 also provides clarification and examples of risk-benefit decisions. The TR 24971 provides three-page guidance on figuring out benefits and includes examples. The draft standard comprehends that manufacturers can change a product only if residual risks offset the benefits. 

Closeup of risk and benefit wooden blocks on seesaw against gray background

Risk-Benefit Analysis 

Industry expert and convener of ISO Technical Committee 210 and Joint Working Group 1 (TC210/JWG1), Jos Van Vroonhoven, and a member of ISO TC210/JWG1 and long-time industry expert, Don Powers, provided some insight on what this means for industry in an interview with Medtech Insight. The objective when developing the revision was to keep the reference standard document the same (as much as was possible) while aligning with global regulatory requirements and providing more clarification on how manufacturers can achieve regulatory compliance and provide benefit to patients. 

They stressed that manufacturers need to consider that this further guidance on risk-benefit analysis is designed to help in the estimation of anticipated benefits that is based on positive impact on clinical outcomes and related factors. Many factors can influence the risk-benefit balance, such as changes to medical practice, clinical data that confirms additional benefits to patients, change in the patient population that uses the device, and the introduction of other devices on the market.  

It is also recommended that manufacturers take a close look at Clause 10 of TR 24971:2020, which is full of helpful post-production information.  

Residual Risk 

In addition to defining benefits, ISO defined residual risk as the “risk remaining after risk control measures have been implemented.” 

ISO TR 24971:2020 provides further guidance on benefit-risk analysis, firstly by helping in estimation of anticipated benefits, based on positive impact on clinical outcomes and related factors, and then providing criteria for comparing benefit and risk to find if the overall residual risk is outweighed by the benefits. 

“In general, the benefit-risk analysis should not only include theoretical risks and benefits, but rather be supported by objective evidence. The benefit-risk evaluation can be done on individual residual risk or on the overall residual risk,” said Van Vroonhoven.  

In summarizing the benefit to risk analysis, Don Powers said companies should look at their overall residual risk, which they will always need to do in comparison to the benefits, regulatory requirements, and all applicable processes based on the guidelines of ISO 14971:2019 and TR 24971:2020.  

Regulatory authorities are now demanding that the balance for medical devices must favor the benefits and device manufacturers must conform to ISO 14971:2019 over the next few years if they have not done so already.  


Deadlines to Meet? 

Criterion Edge has a team of expert medical writers available to help your organization with Risk to Benefit Analysis in the Risk Management Reports and integration throughout the MDR and IVDR documents as you get ready to meet these new global regulatory challenges.  Please reach out to us for a free consult. 

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November 18, 2020

Medical Device Manufacturers Transitioning to ISO 14971:2019 Need to Perform a Gap Analysis and Create a Cross-Functional Risk Management Team

Author: Nupur Srivastava, PhD 

There has been a lot of discussion on the updated International Organization for Standardization (ISO) 14971:2019,  and experts agree that medical device manufacturers need to perform a gap analysis and create a cross-functional team to meet these risk management requirements.  

Risk management plays a critical role in getting medical devices into the market, and ISO 14971:2019 “was designed to better align with medical device regulations around the world.” The global regulatory landscape has been very dynamic around the areas of risk management, as well as safety and performance. 

Tips on Putting Risk Management into Quality Systems During the Transition to ISO 14971:2019 

Two experts shared insights during an interview with Medtech Insight. Jos Van Vroonhoven, convener of ISO Technical Committee 210, Joint Working Group 1 (TC210/JWG1) and a senior manager for standardization for device giant Philips Healthcare, and Don Powers, a member of ISO TC210/JWG1 and long-time industry expert, said that the third edition of ISO 14971 provides more precise guidance and greater detail in the application of risk management concepts.  

These experts provided specific tips on how to transition ISO 14971:2019 into your device’s quality systems.  

Since ISO 14971:2019 instructs manufacturers how to best put together risk management programs, this is a good time to review risk management procedures and perform Gap Assessments. 

  • Develop a Gap Assessment Team 
    • Led by quality assurance or a designated risk manager 
    • Consisting of members with expertise in:
      • Clinical knowledge of the device 
      • Regulatory knowledge, global if needed 
      • Manufacturing of the device 
      • Design and development 
      • Marketing 
      • Reliability engineer and service organization, if available 
  • Divide the Gap Assessment Team and Conquer Each Area 
    • Compare required ISO 14971:2019 to current company processes 
    • Determine how this will impact each department 
  • Document Risk Management to Evaluate Residual Risk 
    • The panelist placed particular emphasis on residual risk, or the risk that remains after risk control measures have been implemented, which is new in ISO 14971:2019. Evaluating and Setting criteria for risk management can be found in Clause 4.4e Risk Management. 

How Do You Know If You are On the Right Track? 

Create another team to evaluate residual risks. This group needs to form a cross-functional team of experts with application and clinical knowledge that can provide good judgment for the residual risk of the medical device.  

The example provided explored the residual risk of x-ray equipment. In this case, the residual risk team might be comprised of individuals with expertise in the following areas. 

  • Radiation  
  • Technical director 
  • Chief medical officer  
  • Clinical scientist that understands how the equipment is used in hospitals. 

The standards outlined in ISO 14971:2019, like benefit-risk analysis, are now in demand by global regulators.  

Global Regulations 

The ISO 14971 standards were updated in 2019 in the United States and the European Union to conform to the higher expectation of identifying and mitigating risks associated with a medical device throughout its lifecycle.  

In the US, FDA requires device manufacturers to align with ISO 14971:2019 by the end of the transition period December 25, 2022, after which time FDA will no longer accept the previous ISO 14971:2007 version.  

In Europe, ISO 14971:2019 (EN version) aligns with the Medical Device Regulations (MDR) and In Vitro Diagnostic Regulation (IVDR) safety and performance requirements. Although it is not yet harmonized with these standards, ISO 14971:2019 is expected to become a Harmonized standard, which will make it state-of-the-art. The date of application for MDR (26 May 2021) and IVDR (26 May 2022) is quickly approaching.   

Globally, ISO 14971:2019 is considered the international standard for risk management and is referenced, if not endorsed, by all other major markets that require the application of risk management including, Australia TGA, Brazil, Health Canada, and Japan MHLW.  

Therefore, device manufacturers must begin to transition into compliance with the revised version of ISO 14971:2019 to align with global regulations. 

History of ISO 14971

The first edition of ISO 14971 was released in 2000 to assist manufacturers, regulatory bodies, and healthcare providers in managing the medical devices’ potential risks. This picture depicts the evolution of ISO 14971 from 2000 to 2019.  

Progression of ISO 14971  

As global regulations for medical devices are becoming more stringent, clear documentation of the process and presentation of the data are essential components of getting medical devices to market. Criterion Edge has a team of expert medical writers that can help your organization get the required documents completed in a timely manner.   
Please reach out to us for a free consult. 

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September 28, 2020

Notified Bodies Received New Guidance from MDCG on the Use of MDSAP Audit Reports for MDR and IVDR

Author: Dr. Suzanne Broussard

Medical device manufacturers received clarification on how the European Commission’s Medical Device Coordination Group (MDCG) will allow Notified Bodies (NBs) to use Medical Device Single Audit Program (MDSAP) audit reports. The punch line of the MDCG 20-14 guidance document published in August 2020 is that NBs can possibly “take into account the scope and outputs of manufacturers’ recent MDSAP audit reports as an input for developing surveillance audit programs.”    

MDCG stresses that the Medical Device Regulations (MDR) and In Vitro Device Regulations (IVDR) remain applicable in their entirety. Surveillance audits are mandated by law, as is their frequency, and the EU auditor’s competencies. Therefore, the “use of MDSAP audit reports is possible only where MDSAP audits covers similar of equivalent MDR/IVDR requirements.”  

Canada mandates the use of MDSAP audits, and 4 other countries allow their use.

MDSAP offers a harmonized auditing program to medical device manufacturers in Australia, Brazil, Canada, Japan, and US. See our previous posts for more information on MDSAP, what it is, what to expect, and tips to ace the MDSAP audit.

Are You a Global Medical Device Manufacturer That Is Tired Of Multiple Regulatory Audits? Consider Transitioning To The MDSAP Single Audit

What To Expect During An MDSAP Audit

9 Tips To Ace The MDSAP The First Time

The MDCG 20-14 guidance now allows NBs in the European Union to take into account the manufacturers’ recent MDSAP audit reports’ scope and outputs as input for developing the surveillance audit program that defines more precisely the manner of the surveillance audit. Several examples are provided in which conformity of a positive quality management system through MDSAP might lead to a reduction of aspects already covered by MDSAP audit reports.  

Non-exhaustive list of examples (in alphabetical order): 

  • Clinical evaluation/performance evaluation process (including post-market clinical/performance follow-up), 
  • EU authorized representative contractual provisions, 
  • EU UDI assignment with the quality management system, 
  • Manufacturer financial coverage in respect of potential liability, 
  • Person responsible for regulatory compliance qualification and role,  
  • Records control, 
  • System for risk management, 
  • Vigilance and post market surveillance activities, including the associated corrective actions and preventative actions. 

The focused surveillance may allow NBs to specify MDR/IVDR requirements either not covered or only partially covered by the MDSAP audit report. Comparablyany non-conformities identified in a recent MDSAP audit report will likely trigger NB attention to those aspects in the MDR/IVDR surveillance audits. 

The MDCG 20-14 guidance clearly states that the NBs are fully responsible for their decisions as to the use and to what extent they use the MDSAP audit reports. Note that MDSAP audit reports can only be presented to the NB for consideration during a regular surveillance audit. Manufacturers cannot use MDSAP for the MDR/IVDR initial quality management audits or unannounced audits.   

The MDCG 20-14 also includes 2 Annexes.  

Part I – Explanation of relevant information in MDSAP audit reports 

Part II – Examples on how to correlations between MDR requirements to sections of MDSAP audit reports may be established.  

The MDSAP was developed by the International Medical Device Regulators Forum (IMDRF) to provide improved medical device safety and oversight using a global approach to auditing and monitoring, and now the MDCG 20-14 guidance document provides NBs and medical device manufacturers with guidelines as to how MDSAP fits into the medical device regulations MDR and IVDR that will be in full application in the near future.  


If your organization needs guidance, or just some extra support, on preparing technical documents for MDR, IVDR or, an MDSAP audit, Criterion Edge has experienced medical writers in a wide variety of documents including medical affairs, clinical sciences, technical, safety, and regulatory.  

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September 16, 2020

[FREE WEBINAR] A Practical Guide: Conducting Systematic Literature Reviews in Support of IVDR Readiness

Get a copy of the slides from this webinar or click to watch the recording.

With the implementation of IVDR requirements, IVD manufacturers have been challenged to align their internal processes and systems to comply with these rigorous regulations. Companies realize the need to review published literature for device-specific clinical data to establish the state of the art (scientific validity) and clinical performance of their products, however many manufacturers may not be familiar with or have the capability to perform rigorous, IVDR-compliant systematic literature reviews (SLR), screening, selection and data extraction.

In this practical presentation, Criterion Edge breaks down the steps of the SLR process and takes a wholistic approach to conducting an IVDR-compliant SLR. Using case studies, the presentation illustrates the effective use of SLR-derived data to develop the Scientific Validity Report (SVR) and the Clinical Performance Report (CPR).

Key Takeaways:
• Review the essential steps for conducting a robust, methodologically-sound systematic literature review

• Using a typical case study scenario, learn how to effectively search, identify, screen, review and extract critical published clinical data on your subject IVD device to support the development of the Scientific Validity and Clinical Performance Reports.

Who should watch this webinar?
Those Regulatory, Quality and Clinical leaders and regulatory writers who are tasked with the development, writing, review or approval of Performance Evaluation Reports for EU IVDR submission, or anyone interested in learning more about IVDR requirements for PERs.

Sign up for future webinars here.


If you enjoyed this webinar and would like a free consultation, please contact us here.

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September 7, 2020

The Medical Device Regulation (MDR) and In Vitro Device Regulation (IVDR) Mandate that Device Manufacturers Have a Person Responsible for Regulatory Compliance (PRRC): Guidelines and Support

Author: Suzanne Broussard

The newly created Person Responsible for Regulatory Compliance (PRRC) position is a unique regulatory requirement that applies only to the European Union, and is a key area of responsibility for a person or persons under the Medical Device Regulation (MDR) and In Vitro Device Regulation (IVDR).  

The motivation for creating the PRRC positions is so that there is a qualified regulatory expert directly responsible for the manufacturing and the market surveillance and reporting systems to ensure the company is meeting the European Union requirements.  

The Regulations have a clear desire to add an additional level of scrutiny to the supervision and control of the manufacturing of medical devices, as well as relevant post-market surveillance and vigilance activities. Thus, the PRRC role is purposefully a unique position from the European Union Authorized Representative.  

The requirements, qualifications, and responsibilities of the PRRC is outline in Article 15 of both Regulation (EU) 2017/745 MDR and Regulation (EU) 2017/746 (IVDR). 

Article 15 of both MDR and IVDR state: 

“Manufacturers shall have available within their organisation at least one person responsible for regulatory compliance who possesses the requisite expertise in the field of in vitro diagnostic medical devices.” 

Manufacturers will be looking closely at how to fill these positions. Parent companies with more than one legal manufacturer under the organization needs to ensure that each legal manufacturer has its own PRRC. Micro or small business enterprises have the option to contract a PRRC (EU definition of micro and small businesses can be found in Regulation 2003/361/1C). 

Responsibilities 

The PRRC has at least 5 responsibilities clearly outline in Article 15. 

  1. Checking the conformity of medical devices in accordance with the quality management system (QMS) before the medical device is released; 
  1. Drawing up the technical documentation and keeping it up to date;  
  1. Making sure the post-market surveillance obligations are in compliance with EU regulations Article 10(9);  
  1. Fulfilling the reporting obligations referred to in reporting of serious incidents and field safety corrective actions (Article 82) and implementing acts (Article 86) 
  1. Ensuring the statement that investigational devices (Section 4.1 of Annex XIV) meet the GSPRs is signed. 

Guidance Document 

The Medical Device Coordination Group (MDCG) released a guidance document on 20 June 2020 addressing some of the questions about the person responsible.  

Medical Devices: Guidance document  

MDCG 2019-7 Guidance on Article 15 of the Medical Device Regulation (MDR) and in vitro Diagnostic Device Regulation (IVDR) regarding a “person responsible for regulatory compliance” (PRRC) 

The guidance clarifies the training and/or professional experience necessary to hold the position of PRRC. The qualifications for this role can be met with either education (certification/diploma) or experience. The PRRC does not have to perform all these duties themselves but is responsible for their completion.  

TEAM-PRRC 

To support those with the role of PRRC, a new not-for-profit European associating has been launched – TEAM-PRRC. The association represents it members at the highest level – the European Commission and Medical Device Coordination group (MDCG). TEAM-PRRC plans to provide the framework and rigorous analysis required to gain insight and influence the guidance that is being developed for the PRRC role. TEAM-PRRC aims to: 

  • Bring together all people with PRRC functions; 
  • Exchange experience on issues faced by PRRC in their daily activities; propose and exchange solutions. 
  • Establish, maintain, and develop a high level of professionalism of PRRC. 
  • Exchange information with health authorities in charge of national, European, and international regulation; promote understanding of PRRCs’ responsibilities to other stakeholders. 
  • Act as a moderator and support PRRCs in conflicts or disputes encountered during their day-to-day activities. 
  • Aim for enhancement of Public Health. 
  • Pursue for mutual assistance between TEAM-PRRC members. 

The newly created role of PRRC will bring many challenges for manufacturers and regulatory specialist, and there is a lot at stake for those considering taking this role. The regulations mandate penalties that are decided on the level of the member states for noncompliance and individuals taking this role need to be aware of the potential consequences.  

Criterion Edge is dedicated to providing support for medical device and pharmaceutical manufacturers, and we do this in part by keeping device manufacturers up to date on current events. For more information on the new MDR guidance documentsextension, and grace period, see our previous posts. 


Either way, Criterion Edge is prepared to provide expert medical writers to facilitate a timely submission.  

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