Regulatory Open Forum

 View Only
Expand all | Collapse all

Risk Management Severity Matrix - Feedback Requested

  • 1.  Risk Management Severity Matrix - Feedback Requested

    This message was posted by a user wishing to remain anonymous
    Posted 19-May-2020 17:15
    This message was posted by a user wishing to remain anonymous

    We are trying to move away from a one-size fits all risk severity/rating and description approach to allow for a better risk scoring outcome for manufacturing. Ultimately, we're trying to tie processing risks (i.e. production delays, reprocessing, scrap) to patient risks without trying to break down these risks into potential clinical harms since they may be unknown or difficult to determine.

    For example, a patient sample mix-up during processing could lead to a patient receiving a false positive, false negative, or physiologically impossible result depending on the symptoms they're exhibiting. Each of these hazards could present different clinical harms (i.e. unnecessary treatment, no treatment given, progression of disease). From a process analysis perspective, trying to identify these potential clinical outcomes does not provide much value since ultimately we know the risk is that the test result would be impacted, and our mitigation activities would be focused on controls to prevent mix-ups. Using our proposal, we would identify the hazard (incorrect sample processed) potentially leading to an incorrect test result being obtained, which would be our highest severity ranking since from a processing perspective since our concern wouldn't necessarily be whether or not the patient would not receive necessary treatment but rather they would receive an incorrect report.

    Ultimately we're trying to use that same methodology throughout our analysis of processes and identifying where failures can occur that would impact the test result, not necessarily trying to break down the possible outcomes of an incorrect test results since this is done in our Hazard Analysis and User/Design FMEA. Overall, this process is similar to our software risk management activities where they define software severities on its own scale (i.e. annoyance to user, no result generated) and do not identify clinical harms. That process allows them to conduct their risk analysis within the scope of their own work, but still be within the framework of our risk management process.

    As reference, here is a draft of what we're hoping to implement. As you'll note the process severities align clinical risks, so there shouldn't be an issue of low patient risks correlating to high manufacturing risks and vice versa.

    Really, we're just thinking it's a more appropriate scaling method for the end users and the activity being assessed. In addition, I would think an auditor would appreciate us making use of an approach that is more suited for the activity being assessed and which results in more meaningful and actionable risk outcomes.

    As always, I welcome comments from those interested in offering their perspetive. Regardles, wishing everyone healthy vibes!



  • 2.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 20-May-2020 09:32
    Greetings and thank you for posting this question.

    I think you are on the right track, but it is difficult to provide specific suggestions without first understanding the overall context of your operation. I would recommend reviewing ISO 14971 and examples provided in the Annexes, as well as the ISO/TR 24971. AAMI also has guidance documents you can review.

    You seem to be experiencing a common challenge in the industry. That is, how to link process failures to patient harms. It is not always, at least in most cases, a 1-to-1 relationship. So you are doing the right thing by not taking a one-size-fits-all approach to risk rating and acceptability decisions. It is not an easy exercise but it can be done in a systematic way so it can seamlessly integrate with your overall risk management process. 

    I have a lot of experience building highly efficient and effective risk management systems. Please reach out directly if you would like to discuss in more detail. 

    Best regards

    ------------------------------
    Naveen Agarwal
    Jacksonville FL
    United States
    ------------------------------



  • 3.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 20-May-2020 13:18

    An ultimate essence and distinction of ISO 14971 risk management compared to traditional FMEA is the extrapolation of reasonably foreseeable sequences of events and hazardous situations into reasonably foreseeable "harms" rather than just product-centric or process-centric failure modes and effects.

    ISO 14971 officially defines "harm" as damage or injury to the health of people [paraphrased].  In these terms then, I would suggest that descriptors like "unnecessary treatment", and "no treatment given" are hazardous situations rather than harms.  "Progression of disease" is a borderline descriptor containing attributes of a hazardous situation and a harm.  Consequently I typically encourage folks to try and press that descriptor further into a projected adverse health consequence(s) (if any).

    In the IVD industry, especially in the FDA jurisdiction, it is common and expected that the sequences of events (i.e., the device or manufacturing process failure modes and effects, i.e., FMEA) and consequent hazardous situations (i.e., false negatives, false positives, delayed results, and inconclusives) be extrapolated into reasonably foreseeable harms (i.e., damage to the health of people).

    I would agree that from a process analysis perspective (e.g., from a process FMEA perspective, i.e., from the perspective of deriving process-centric sequences of events that could lead to hazardous situations), identifying clinical harms at that step of the analysis doesn't yet provide direct value.  ISO 14971 and ISO/TR/DTIR 24971 recognize this by reminding us that FMEA is just one part of the multifaceted risk analysis process.  Specifically, I'm suggesting that ISO 14971 for practical intents and purposes calls for traditional FMEA to be embedded within ISO 14971's steps for identifying sequences of events and hazardous situations.  Only once we extrapolate these into reasonably foreseeable harms can we say we've met the intent of ISO 14971.

    Remember also that ISO 14971 prescribes for risk to be estimated via the combination of probability of harm and severity of harm (i.e., of damage/injury to the health of people), not solely on probability/severity of product/process failure modes (though the probability of a failure mode is certainly a variable to be factored when estimating probability of harm).  Consequently, our ISO 14971 risk analysis severity ranking categories need to be articulated in terms of harm, not in terms of failure modes.  For example, the minor severity level might be characterized as minor discomfort not requiring clinical intervention; a moderate severity level might be characterized as non-serious injury or injury requiring clinical intervention to prevent serious injury; and a catastrophic severity level would be death.  Though this may seem to infringe on the goal of avoiding a one-size-fits-all approach, it really doesn't; don't forget that we are to pair the severity ranking paradigm with organically-estimated reasonably foreseeable harms (e.g., skin rash, headache, dizziness, heart attack, death, etc.) when calculating the risk.  It is via the organic derivation of reasonably foreseeable harms for the particular subject device that ISO 14971 alleviates and overcomes perceived concerns related to the generic nature of the severity ranking categories.

    For IVDs in particular, ISO/TR/DTIR 24971 states that this requires sufficient specificity to assign appropriate severity.  It guides us to answer the question "What harms might occur from a misdiagnosis or inappropriate therapy?".  Examples of "harms" given by ISO 14971 include things like heart fibrillation, infarct, brain damage, organ damage, decreased consciousness, death, infection, progression of disease, etc.  Such granularity needs to be preserved a) to prove that we've actually organically thought about the actual risks associated with the IVD instead of slighting it; b) so that the Quality/Regulatory Team can more effectively manage the product's market feedback; and c) objectively rather than subjectively meet the intent of ISO 14971.

    I find it refreshing to know that this stuff isn't just a bunch of theoretical gibberish.  For example, I worked on two IVD FDA premarket submissions in the last couple years where in one of those cases, the Sponsor properly articulated harms by naming specific disease / injury conditions that were germane for their product and its intended use.  In the other case, the Sponsor instead attempted a more generalized approach where specific clinical harms were not clearly articulated. That case resulted in a submission hold. Here is a redacted excerpt of the objections FDA lodged in that case, which shows the importance of being very specific regarding the harms:

    "…Under your Risk Management Plan document you identify the criteria used to evaluate risk severity. After review of these criteria, it is apparent that your risk severity criteria were not constructed in consideration of the possible severity of harm to the patient. For example, you list for a severity of critical as 'loss of function – no results' and severity of catastrophic as 'False Positive – Unnecessary observation'. These criteria for severity do not specifically address the severity of harm to the patient and are incongruent with the intended use of the [redacted] test…You should revise your Risk Management Plan by constructing risk evaluation criteria for severity which might more appropriately be applied when assessing risk of harm to a patient. When constructing the risk evaluation criteria for severity of harm, you should consider as an example of high severity the possible harm to a patient, i.e. [redacted…and tested as false negative]…Please provide for our review, your revised Risk Management Plan which incorporates severity criteria pertinent for assessing risk of harm to the patient…"

    Remember that because of precedents like this, as well as the fundamental standardization of these principles in ISO 14971, it is expected to be commonplace that firms will articulate the reasonably foreseeable injuries/damage to the health of people that could come from false, delayed, or inconclusive diagnostic test results (or, for non-IVD devices, other various hazardous situations). I can name multiple IVD companies who are in alignment with these precedents and I've been the primary architect and author of the remediation that was needed to resolve FDA objections for firms who weren't.

    Note also that these principles are generally uniform regardless of device technology (i.e., IVD or non-IVD), so they are applicable to any medical device company who is genuine about performing useful, organic risk analysis that will help maintain public health as well as the Sponsor's long term profits in the medical device marketplace.

    Hope this helps.



    ------------------------------
    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    ComplianceAcuity, Inc.
    Golden, CO
    United States
    www.complianceacuity.com
    Note that I'm now far older and even uglier than in the photo above. Brace yourselves for my updated photo coming soon.
    © Copyright 2020 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 4.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 21-May-2020 09:26

    Could you provide some context?

    In one place you refer to manufacturing. From which I inferred the company is a test kit manufacturer.

    In another place you talk about handling samples and reporting test results. From this I inferred the company is a clinical lab.

    I suppose a company could be both if it were a lab manufacturing its own laboratory developed tests.

    In both the manufacturing and the clinical lab cases there is a process described in a process map and supplemented by an PFMECA. I think the question is how to connect failures in the PFMECA to patient or user harm. I also infer that you manage patient or user harm by implementing ISO 14971:2019.



    ------------------------------
    Dan O'Leary CQA, CQE
    Swanzey NH
    United States
    ------------------------------



  • 5.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 21-May-2020 11:35

    A fervent trend in the IVD space is clinical laboratories who've decided to transition their LDT to regulated medical device status.  An example I've recently worked with in the FDA PMA arena is Companion Diagnostics.  As clinical labs make the quantum leap from LDT to regulated medical device, I've observed that a key challenge for such firms is the reinterpretation and recategorization of traditional LDT operations with respect to medical device design control and manufacturing regulations.  The original post here shows elements of that very struggle. So I would say that, for folks with experience in this space, it seems readily apparent that this is the context (i.e., LDT to medical device transition) from which the post originated.

    Further to my prior post, a couple other points for consideration/reiteration:

    • Process FMEA / FMECA is linked to ISO 14971 medical device risk management in the form of the sequences of events called for by ISO 14971.  Traditional / pure process FMEA draws conclusions about the impact on the process, from the perspective of the process (which is what is meant in my prior narrative about FMEA being "process-centric"). But as has been discussed previously in this forum and by FDA and ISO, FMEA is not risk management.  Instead, FMEA is just an aspect of the risk analysis process that helps to discover the sequences of events that can lead to hazardous situations and harms.

     

    • When making the leap from LDT to regulated medical device, especially in the case of an automated (software-driven) LDT where large numbers of samples are simultaneously handled and processed, it can be tempting to believe that such sample-handling dynamics and workflow somehow alleviate the firm from identifying reasonably foreseeable sequences of events, hazardous situations, and harms that could come about in association with the test. I would strongly caution firms against avoiding all together the breaking down of process risks (discovered during pFMEA) into potential clinical harms (derived in order to complete ISO 14971 medical device risk analysis and management).  It is certainly okay to do so when strict/pure pFMEA is the interim goal and is followed up by correlating those pFMEA results to the sequence of events / hazardous situation step of ISO 14971 risk analysis.  But overall, make no mistake: The FDA and other public health agencies will demand that the firm's manufacturing hazards be extrapolated into clinical risks one way or another.  Whether that is done via a dedicated pure pFMEA that is secondarily mapped into a separate clinical risk analysis, or whether the pFMEA and clinical risk analysis are combined into a single master matrix, such considerations are only clerical in nature.  The problems arise when firms end their medical device risk analysis and management with the product or process-centric FMEA results, or when they end their efforts with the ultimate harm conclusion "false positive", "false negative' etc., when in fact those aren't harms; they are hazardous situations.  The aforesaid FDA PMA hold objection demonstrates this principle in action.

     

    • Though an LDT-turned-medical device may ultimately result in an incorrect diagnostic report being issued to a clinician and/or patient rather than directly affecting the patient, the firm is still obligated to project what would be the reasonably foreseeable clinical harms that could come about due to the false, delayed, or inconclusive report results.  This is driven by the principle mentioned in the ISO 14971 / ISO TR 24971 excerpts in my prior post.  This requirement is not only a given based on ISO 14971 principles, but it is also readily apparent in the risk / safety narratives of the other LDT-turned-device players in the arena who already have FDA-approved assays.


    ------------------------------
    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    ComplianceAcuity, Inc.
    Golden, CO
    United States
    www.complianceacuity.com
    Note that I'm now far older and even uglier than in the photo above. Brace yourselves for my updated photo coming soon.
    © Copyright 2020 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 6.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 21-May-2020 11:41

    You have received some good advice form Kevin and I wish to take this discussion in a slightly different direction, supporting some of what he said.  First of all, I would like to support him on the IVD advice.  It is unfortunate that ISO screwed up the release of ISO TR 24971 and moved it to 2020, instead of being released in parallel with the  release of ISO 14971:2019, as the technical committee intended.  ISO TR 24971:202X is loaded with 100 pages of good information on the implementation of ISO 14971:2019.

    Now, let me take this the  new direction.  From your discussion, it appears as though your are attempting to use FMEA as your risk analysis, it is not.  FMEA is a reliability tool which can be used to identify failure modes of particular "components" of a subsystem, system, or a process.  Those failure modes then lead to effects of the failure.  If the effect is safety-related, then it becomes an input to risk analysis, the hazard (ISO 14971:2019 3.4-potential source of harm).  In Annex C of ISO 14971:2019 you will find an extensive discussion of the relationship of hazard, hazardous situation and risk.  The safety-related Effect output of FMEA is the input to the Hazard block in Figure C.1 in Annex C.  This is where risk analysis (and ISO 14971:2019 5 Risk Analysis) starts, and not in FMEA.  Note the standard uses the term "risk analysis" and not "hazard analysis".  In ISO 14971(all editions) we are not analyzing the hazard, we are analyzing the risk.  Therefore the use of the term hazard analysis is not correct.

    The use of Severity in FMEA relates to the impact on the design or the process and not the impact on the patient.  That impact analysis takes place much later, after commencing the risk analysis as shown in the afore mentioned diagram C.1.  Additionally, the probability of failure rating in FMEA is not the probability of harm rating in ISO 14971:2019, which occurs in analysis of the hazardous situation, again shown in Figure C.1. 

    I find that thee is the misconception of FMEA as risk analysis that leads to confusion such as yours.  FMEA is NOT risk analysis in ISO 14971:2019, but described in the website of  IEC the FMEA process described in the IEC 60812:2018 standard may be used as "a systematic method for identifying modes of failure together with their effects on the item or process, both locally and globally. It may also include identifying the causes of failure modes."  

    From your description of the Severity rating system you are trying to establish, you are mixing severity of the process or product failure with the severity of harm described in ISO 14971:2019.  They are not the same.  Perhaps after a review of the Annex C in the standard and also the extensive discussion of the topic in Clause 5-5.5 in ISO DTR 24971:2020 you will have a better understanding of the process.  I also highly recommend as Kevin that you review Annex H in ISO DTR 24971:2020 on IVDs.  

    The ISO TC 210 JWG1 that spent over three years updating the standard and the accompanying technical report responded to comments from the industry and regulators to meet the needs of industry in updating the standard to meet new regulations (MDR, IVDR, and FDA postmarket guidances.  There are over 51 new pages of informative annexes to provide assistance to users of the standard in implementing risk management.  The standard was immediately on release recognized by FDA and CEN published a version for the EU awaiting the Harmonization process implementation for the MDR / IVDR.  This will be updated with appropriate "Z Annexes" after Harmonization is 
    available>  Please note that EN ISO 14971:2012 is NOT harmonized to the MDR and IVDR.  Also many Notified Bodies, including BSI have recognized EN ISO 14971:2019 as the "state of the art" risk management standard and responded to CEN's withdrawal of the 2012 version.  Currently it is up to the Notified Body to determine how to act since the EC has not responded with a Harmonization process and a Standardization Request.

    I hope this diatribe helps you to move forward with your process improvements.



    ------------------------------
    Edwin Bills MEd, CQA, RAC, BSc, CQE, ASQ
    Principal Consultant
    Overland Park KS
    United States
    elb@edwinbillsconsultant.com
    ------------------------------



  • 7.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 21-May-2020 12:59
    It is important to remember that ISO 14971:2019 / EN ISO 14971:2019 and the pending ISO TIR 24971 (hopefully 2020) as well as their predecessors (ISO 14971:2007 / EN ISO 14971:2012 and ISO/TR 24971:2013) all make it abundantly clear that FMEA is a key (and in my experience, the most widely-used) risk analysis technique.  Refer to ISO 14971:2019 / EN ISO 14971:2019 clause 5.1 Note 2 and ISO DTIR 24971:2020 clause 5.1 and Annex B (corresponding to their predecessors ISO 14971 2007 / EN ISO 14971:2012 clause 4.1 and Annex G) all literally reminding us that FMEA is a risk analysis technique.

    Of course, to build upon Edwin's comments, practitioners surely need to be sensitive to distinguish pure product/component-based failure mode assessment  vs. extrapolating those for further risk assessment.  But ISO 14971 medical device risk management demands that practitioners adapt and correlate the general paradigms of pure traditional FMEA to align with and plug into the ISO 14971 process.

    Note also that hazard analysis is most definitely a critical aspect, indeed is generally the first step, of risk analysis.  For example, PHA is one of the risk analysis techniques prescribed by ISO 14971 / TR 24971.  In carrying out hazard analysis in preparation for the remainder of the risk analysis process, remember that the goal there is to first identify the basic generic categories of hazard types and permutations (e.g., biological hazard by way of bacteria, chemical hazard by way of contaminants or toxicants; mechanical hazard by way of pressure; energy hazard by way of electricity; process-based hazard by way of the manufacturing process as revealed via pFMEA, usability/human factors hazard by way of..., etc., etc.). See 14971:2019 Annex C, Table C.1 (previously ISO 14971 2007 / EN ISO 14971:2012 Annex E, Table E.1) for how ISO 14971 prescribes that we start with the applicable basic hazard categories and then apply techniques like FMEA to derive reasonably foreseeable sequences of events and hazardous situations relevant to the product.

    ------------------------------
    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    ComplianceAcuity, Inc.
    Golden, CO
    United States
    www.complianceacuity.com
    Note that I'm now far older and even uglier than in the photo above. Brace yourselves for my updated photo coming soon.
    © Copyright 2020 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 8.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 21-May-2020 16:54
    Thank you for this information, Edwin.  Is ISO DTR 24971:2020 available?  I went to the website and it says "in development" and that it will be released in June.  Is that correct?

    ------------------------------
    Katherine Rhodes
    Director of R&D
    Encinitas CA
    United States
    ------------------------------



  • 9.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 21-May-2020 18:53
    Though I am on the ISO 24971 development committee, I'm not allowed to share our pre-publication copies. But you can purchase a copy from AAMI here:
    https://my.aami.org/store/SearchResults.aspx?searchterm=management&searchoptions=ALL&Page=2
    or here:
    https://imis.aami.org/aami/ItemDetail?iProductCode=24971PREORDER&Category=GEN_ASP&WebsiteKey=fb98c6e5-92b6-4edf-960a-36b3cd610cab

    AAMI states that it will furnish a final copy without additional charge once published.

    ------------------------------
    Kevin Randall, ASQ CQA, RAC (Europe, U.S., Canada)
    Principal Consultant
    ComplianceAcuity, Inc.
    Golden, CO
    United States
    www.complianceacuity.com
    Note that I'm now far older and even uglier than in the photo above. Brace yourselves for my updated photo coming soon.
    © Copyright 2020 by ComplianceAcuity, Inc. All rights reserved.
    ------------------------------



  • 10.  RE: Risk Management Severity Matrix - Feedback Requested

    Posted 21-May-2020 22:29
    The final will be released after a successful vote on EN ISO DTR 24971:2020 is received.  It is anticipated to be complete in June, if all goes well.  From all the problems we have witnessed getting this published, I am reluctant to guarantee anything anymore.

    The document you are looking for is ISO DTIR 24971:2020 PREORDER. 

    https://my.aami.org/store/detail.aspx?id=24971PREORDER

    RODUCT DETAILS

    AAMI/ISO DTIR24971:2020 Preorder

    Medical devices-Guidance on the application of ISO 14971

    PLEASE NOTE: This document, known as a Draft Technical Information Report (DTIR), is not considered a final TIR and there may be slight editorial changes to the final publication. By ordering this draft, you'll be among the first to receive the final TIR, which is expected to be published in early 2020. When the final version is published, AAMI will send a link to download it to those who have purchased ANSI/AAMI/ISO DTIR24971.

    SUMMARY: This Technical Report will provide guidance that addresses specific areas that experience has shown are problematic for those implementing a risk management system. This guidance would not require any change to existing implementations of ISO 14971. The proposed document would not be a general guidance on implementation of risk management. Such documents already exist from various sources. Rather the document envisioned would focus on expectations in certain critical areas such as guidance on formulation of a risk management policy; the role of product and process standards in the risk management process; guidance on how the feedback loop can work; guidance on the differentiation of information for safety as a risk control measure and disclosure of residual risk; and an expansion of the discussion of overall residual risk.

    A preview of this document is available here.

    PDFs are available for download up to 60 days after purchase.
    Product Code:
    24971PREORDER
    Date:
    January 10, 2020
    Media:
    PDF
    Pages:
    100
    Available for Immediate Download
    AAMI Member:
    $74.00
    List Price:
    $131.00
    Your Price:
    $131.00


    ------------------------------
    Edwin Bills MEd, CQA, RAC, BSc, CQE, ASQ
    Principal Consultant
    Overland Park KS
    United States
    elb@edwinbillsconsultant.com
    ------------------------------