January 5, 2021

FDA Provides Guidance on the Regulation of Multiple Function Products with Some Functions that Fall Outside the Medical Device Umbrella

Author: Suzanne Broussard, PhD 

The increasing number and complexity of medical devices with several functions prompted FDA to provide medical device manufacturers with premarket and postmarket regulatory guidance. In a nutshell, FDA states that it shall not regulate non-device functions of a product with multiple functions – but can consider the impact of non-device functions on the device functions. The guidance identifies the principles and premarket review practices, postmarket requirements, and multiple examples of the application of the policy. 

The term “multiple function” device was first officially addressed by FDA in the 21st Century Cures Act Section 3060 that amended the Federal Food, Drug, and Cosmetic Act (FD&C Act). The guidance amended the definition of “device” removing certain software functions (medical and decision software support) and clarifies which software functions (analyze or interpret medical data) remain under FDA’s oversight.    

The Multiple Function Device Products: Policy and Considerations Guidance for Industry and Food and Drug Administration extends that policy to the assessment of all multiple function device products, whether those functions are hardware-based, software-based, or both.  

Guidance Scope 

The guidance document is intended to clarify FDA’s policy approach to all multiple function devices, considerations for the design and risks of multiple function device products, and impact assessment of non-device software functions or “other functions” on safety and effectiveness. Furthermore, the guidance provides recommendations on the premarket submission content FDA expects for a device function that is part of a multiple device product. Modifications and postmarket requirements are also addressed. 

The policy is risk based with a functionally focused approach to software that is platform independent. The regulation is narrowly tailored to the device’s risk based on the function with the ultimate intent to protect patient safety. 

In the guidance, FDA clearly delineates “other functions” and device function-under review.  

Definitions 

To begin, FDA defines function as a “distinct purpose of the product” and further clarifies that function could be the intended use or a subset of the intended use of the product. For example, a device with the intended use of storing, transferring, and analyzing data has three functions while a device with the intended use of analyzing data has only one.  

“Other function” is considered a function that: 

  • Does not meet the definition of device; 
  • Meets the definition of device, but is not subject to premarket review (e.g., 510(k)-exempt); or 
  • Meets the definition of device, but for which FDA has expressed its intent not to enforce compliance with applicable regulatory controls.  

Multiple function devices are comprised of functions that are subject to FDA’s regulatory oversight and “other functions” that are not.  

Device function-under review is defined as a function for which FDA is conducting premarket review. 

Policy: Premarket Review Considerations for Multiple Function Device Products 

The guidance clarifies that while “other functions” that are part of a multiple-function device are not the subject of FDA review, FDA may assess the impact of “other functions” when conducting the premarket review to determine the devices safety and effectiveness.  

Other Functions Should be Separated in Design and Implementation 

FDA considers the separation of functions of the device-under-review from “other functions” important for risk control. Ideally, the separation occurs early in the design with a higher degree of separation allowing for easier review of the independent safety and effectiveness of the devices function.  

Making architecture decisions early in the design cycle that facilitate risk control especially allow for the evaluation of optimal separation and support segregation of: 

  • Logic  
  • Architecture 
  • Code 
  • Data partitioning 

This separation is considered “especially important when considering cyber security risk and mitigations.” 

Risk Analysis Needs to Consider the Impact of Other Functions 

The guidance outlines the following as critical for manufacturers to consider regarding the impact of other functions. 

  • Role of the “other function” in the devices function-under-reviewperformance
  • Limitations of the device function-under-review when using the “other function:” 
  • Developing appropriate hardware and software resources specifications(s) for the product with multiple functions to ensure minimal impact of the “other function” on the performance of the device functions-under-review; 
  • How to ensure appropriate actions are taken by the end user when using the device function-under-review with the “other functions;” and 
  • Identification, evaluation, and mitigation of any additional risks, including cybersecurity risks, in the device-functions-under-review when used in combination with the “other function.” 

When separation cannot be achieved, the interconnectedness and interdependencies of the devices function and “other function” needs to be included in the hazard analysis. Furthermore, an appropriate control must be created.  

Assessing the Impact of “Other Functions” on the Device Function-Under-Review 

FDA is clear on how it intends to assess the impact of “other functions” and provides a flow chart to guide manufacturers through the assessment.  

Manufacturers need to conduct a risk assessment to determine if the “other functions” impact the safety and effectiveness of the device under review. The other functions could act to have a positive effect or an adverse effect.  

A two-step process summarizes the premarket assessment.  

First, is there an impact on the Safety and Effectiveness of the device function-under review as a result of the “other function?” If yes, could this be a negative impact, meaning an increased risk or an adverse effect on performance of the device function under review?  

Positive impact assessments must include the beneficial impact of “other functions” on the device-under-review when the device is operating as intended. In addition, the manufacturer must confirm that the “other functions” do not impart an adverse impact if the device-under-review fails to operate as intended. 

Negative impact assessments must identify the potential for an increased risk and/or adverse effect on performance “due to the combination of the other function with the device-under-review. 

“Other functions” that impact the device under review must be evaluated and included in the hazard analysis.  

Manufacturers need only added other functions to the submission if the positive effects are represented on the device label – a labeled positive impact – or if it may negatively impact the device that is under review.  

Examples of Multiple Function Devices  

The FDA provides 7 examples of multiple function device products in Appendix 1. The examples provide a description of the product, product functions (see list below), description of the impact of the “other function” on the device function-under-review and an explanation of the impact assessment.  

Below is a list of the hypothetical example device products. See the guidance for details on impact assessment.  

  • Skin cancer detection software application 
    • Device function under review: 
      • Software app that detects skin cancer 
    • “Other function:” 
      • Smart phone computing platform 
      • Camera on the computing platform 
  • Hand-held coagulation device 
    • Device function under review: 
      • Hand help coagulation instrument 
      • Coagulation (prothrombin time) test 
    • “Other function:” 
      • Docking station 
      • Interface to transmit the data to the HIS 
  • Traumatic brain injury determination 
    • Device function under review: 
      • Collection and recording of EEG signals 
      • Analyzing EEG signals and diagnosing TBI 
      • Presentation of results 
    • “Other function:” 
      • General use computing platform 
      • Electronic administration of questionnaire 
  • Pain treatment app 
    • Device function under review: 
      • Electronic Nerve Stimulation as a treatment for pain 
      • App used to control the level of stimulation 
    • “Other function:” 
      • Mobil platform Bluetooth transceiver and connectivity 
  • Transmission of vital sign measures to an Electronic Health Record (HER) 
    • Device function under review: 
      • Vital signs acquisition 
    • “Other function:” 
      • Transmission software for sending data to the HER system 
      • Wi-Fi card  
  • Energy-delivering device with optional app (MDDS) 
    • Device function under review: 
      • Energy-delivering aesthetic device 
    • “Other function:” 
      • Mobil app that integrates with device and transfers treatment parameter data (e.g., number of treatments, treatment parameters) to a cloud-based storage – no real-time transmission is allowed 
      • Smart phone computing platform 
  • Pulsed ultrasound and biopsy needle guide kit 
    • Device function under review: 
      • General purpose diagnostic ultrasound system 
      • Biopsy needle tracking functionality 
    • “Other function:” 
      • 510(k)-exempt needle guide kit 

Postmarket Guidance 

The guidance applies to post-market regulations and implicitly states that device functions must comply with design control requirements and expectations surrounding adverse event reporting.  

FDA reinforced its position that it does not intend to “enforce general control requirements for device functions for which FDA has expressed its intention to not enforce applicable regulatory controls at this time.” 

Multiple function device products that have undergone modifications of the “other function” must be assessed to determine if the change has the potential to significantly impact the safety or effectiveness of the device function that was the subject of FDA review.  

This guidance document was written to clarify current regulations as well as to promote innovation and patient engagement with digital health products.  

To catch up on FDA’s newest premarket guidance documents see our previous post on Nuances of Using the Safety and Performance Pathway for Submitting a 510(k) for Certain Device Types and FDA Experts Provide Tips to Eliminate eCopy Holds for Premarket Submission Applications: FDA Touts eSTAR Development. 


Document Experts 

The generation of technical documents that are required for medical device premarket approval requires time and expertise. Consider increases in your company’s efficiencies by working with a team of medical writers that are document experts. At Criterion Edge, we take pride in teaming up with industry experts to provide high quality support. Please reach out to us for a free consult. 

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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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November 12, 2020

[FREE WEBINAR] Hidden Traps That Derail PER Preparedness: Lessons Learned from the MDR-Compliant CER Writing Experience

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With the implementation of IVDR requirements, IVD manufacturers have been challenged to align their internal processes and systems to comply with these rigorous regulations. In this practical presentation, Criterion Edge uncovers what we have learned from our experience in writing MDR-compliant CERs, and how urgently applicable some of these key learnings are in preparing a robust Performance Evaluation Report (PER). 

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. 

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November 9, 2020

FDA’s Updated Electronic Medical Device Reporting (eMDR) System Aims to Harmonize Adverse Event Reporting

Author: Suzanne Broussard, PhD 

Two doctors discussing about medical report in clinic

FDA’s recently finalized modifications to the electronic Medical Device Reporting (eMDR) system include the addition of new fields to harmonize with terminologies set by the International Medical Device Regulators Forum (IMDRF). These changes are designed to “improve transparency and analysis of the MDR data contained in the public Manufacturer and User Facility Device Experience (MAUDE) database” and are part of the FDA’s push for regulatory harmonization. 

Device manufacturers now have until February 28, 2021 to use IMDRF codes instead of the retired Patient Problem Codes and Device Component Codes. The original production deployment date of September 7, 2020 was extended to give manufacturers a little more time to adapt to the changes.  

Here is a summary of the updates to the eMDR system

  • Includes new elements for Summary Report and NOE (Number of Events) based on FDA Form 3500A so that submitters will not need to report this information in B5 (Event Narrative) with precise text formatting  
  • Addition of adverse event codes to harmonize with IMDRF Annex E, F, G Codes  
  • FDA Adverse Event codes update that affect the Device Problem Codes and Manufacturer Evaluation Code 
  • New options in the patient gender field 
  • New elements or changes to Exemption Number reporting, indications to submission environments, and B5 and H1 (now mandatory) to reject options not reported properly 
  • Enable a reporter to identify whether the report relates to a combination product 
  • Combination product fields added to allow submitters to include information of up to 20 drugs within a device-led combination product adverse event report 

The current eMDR reflect FDA’s updates to Form 3500A, which is used by medical device manufacturers, importers, distributors, and user facilities to report diverse events and other system enhancements. 

FDA further aligned this reporting system by adding two fields from FDA Form 3500A to the public MAUDE database to provide additional information on related devices and the nature of adverse events. 
  • Patient problem codes 
  • Marketing submission number (for submissions such as 510(k) and PMA) 

To help manufacturers with a smooth transition to the newest eMDR format, the Center for Devices and Radiological health (CDRH) has created a downloadable file package to assist in implementing software for generating the HL-7ICSR XML for eDMR submissions. And updates on new and retired codes MDR Adverse Codes are easy to find. 

The updated eMDR is one of many changes being implemented by FDA. Indeed, 2020 has been an active year for FDA as they work to harmonize across systems.  

Here is a short list of posts with additional information on specific programs recently updated by FDA

It takes a team of experts to implement all the regulatory documentations required to get and keep your medical device in compliance, especially ever changing and demanding US and European regulatory requirements.  


If your organization needs support establishing or updating technical documents for medical devices, Criterion Edge has a team of document experts ready to partner with you. 
Please reach out to us for a free consult. 

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