When to Use Device Risk Management and/or Human Factors in Device Design

IEC 62366-1 outlines a process (9 stages) to follow to perform a Use Engineering / Human Factors analysis.  The specifics for the actual UE/HF tests (formative / verification or summative / validation) is found in other standards and guidances.  UE/HF is only needed where the user interface presents challenges of use[r] error and/or the device is specifically listed by the US FDA as needing such. 

In other cases it does not have to be used, e.g., where the use(r) interface (device shape, weight, color, knob usage, graphic output, alarm output, keyboard input, on-unit labeling, etc.), is intuitive, familiar, not prone to excessive use[r] error, et al.  

On the other hand, device Risk Analysis / Management per ISO 14971 (patient / user / environment  safety (and regulatory compliance), is always required, for both new product development as well as in significant changes - this will be more emphasized with the new device QMSR (new 21 CFR 820), but it is a current expectation of the FDA.

Both these tools, when used, are to be used to feed into any new designs or design changes, to use the design process to reduce use risk or use error or both. 

Possible UE/HF File Format (IEC 62366-1):  1) Intro, device description, approvals, discussion of device under evaluation, executive summary of findings, and similar background; 2) A section on each of the 9 stages in IEC 62366-1 (discuss specific tests used under Stage 5 -  5.7.1, 5.7.2 and 5.7.3 - of IEC 62366-1 in the UE/HF File); 3) Conclusions (mitigations...).

Possible Device Risk Management File (ISO 14971, or ICH Q9):  Intro, as above, assumptions, risk management team, preferably including a clinician familiar with the device's use; 2) Hazard Analysis; 3) Expand Hazards with a Fault Tree Analysis; 4) Expand Hazards with three FMEAs / FMECAs:  I) Design FME[C]A, II) Process FME[C]A, and III) Use  FME[C]; 5)Review/Report - Residual Risks, Benefit / Risk analysis / statement.   Use FTA and FME[C]As with the addition of a "Normal Usage Causing Problems" Matrix.  This format has been reviewed in detail by the FDA in 2003 and extensively used and subject to FDA and Notified Body inspections and remediation projects since then with no negative comments / findings / 483s. 

-- John E. Lincoln

 

One of the most important CGMP requirements for Vendors / Suppliers...

Change Control, documented, and reviewed agreed to prior to implementation by the customer(s).  This is a hard one to get vendor buy-in or enforce.  However, failure to do so will get the customer (contracting company)  into major trouble with the user / market and regulatory agencies.  Device changes have to be documented, validated, and compared to the last cleared 510(k) per two guidance documents (device itself, and device software / firmware) on  device changes and the 510(k) with analysis of the last change and the cumulative change since the last cleared 510(k) documented - usually done by the company, not the vendor.

-- jel@jelincoln.com 

 Q&A from a recent one of my VMP (Validation Master Plan[ing]) Webinars

Ques:  Using vendor developed/administered tests as part of a company's qualification for vendor-supplied production / test equipment.

Many times vendor templates are not meeting internal documentation requirements. For example all tests are not signed/checked individually; one signed at the end of page or document.

How to handle this when vendor documentation is not fulfilling internal requirements?

Ans:  As mentioned, you would have to "fill in the blanks" with supplemental verifications/testing, so the vendor's documentation and the additional verifications complete your company's SOP requirements for the validation.

 

Ques:  Risk based validation.

Is validation really risk based if it is based just on URS requirements. A Validation is checking just URS requirements and maybe some internal documents. Should there be a formal risk assessment on which validation is based?

 

Ans:  Risk, i.e., patient safety (ISO 14971, ICH Q9)-based Risk Management Reports/Files addressing the subject being validated, are used to direct the test cases focus, depth, size, sampling, design, et al - not just the URS.  The higher the risk based on the Risk Management File / ISO 14971:2019, the more detail, et al, included in the V&V Report's test cases as per an example test case in the webinar (the test case introduction / narrative ties that test case to specific references / line items on a Risk File document, e.g., FMECA) to define the patient risk associated with that test case.     

 

Ques:  Documentation practices.

Test should be signed individually and at right time (in real time).

In some cases multiple tests are on same page and only one signature at the end of the page. Is this really fulfilling the requirement of right time?

 

Ans:  It depends.  FDA's Guidance Document on Data Integrity on test data does not agree with different test's data being combined under one signature  (in my opinion).  However, if one signature is used  to certify the accuracy of the report, with supporting information and signatures for the individual reports readily available elsewhere, that may be allowable, depending...  And would have to be clearly stated how it can be viewed as allowable in an SOP which is then followed!

 

Ques:  Document templates. During the webinar  specific example test templates weren’t available. Are they now?

 

Ans:  No,  That would be a specific consulting project. Complete validation templates are very specialized / unique and I don't supply them in an "all-purpose" webinar.  I do develop them as part of a dedicated consulting project.  However, the basic /generic format / outline was provided a couple of times on the slides, as well as an example of an IQ check list, an OQ test case and a PQ multiple sample (n=10, n=30 ...) test case, which all also can vary.  A list of product tests / verifications was also included in the slides:

E.g., Basic Test Report Format:

• Control Number, Title
• Scope, Purpose
• Pre-Approval
• Test description, lay-out, drawings / pix...
• Pre-determined test acceptance criteria
• Test materials (P/N, Lot No., description, Qty...)
• Test equipment (asset no., S/N, Model, Description...)
• DQ, IQ, OQ, PQs -list or test cases
• Software 10 elements (see Blog, elsewhere) if applicable, Pt 11 (OQ), Cybersecurity (OQ, if applicable
• Results:  Filled-in test cases. data sheets
• Conclusions:  Compare test case results to pre-determined acceptance criteria
• Appendix:  Training Record copies, calibration ccs,  red-lined SOPs, etc.

-- jel@jelincoln.com  

 

 The New US FDA Predetermined Change Control Plans (PCCPs)

The US FDA is proposing a new addition to 510(k)s and PMA submissions:  Predetermined Change Control Plans (PCCPs) for devices requiring premarket approval (PMA) or premarket notification (510(k)).  A PCCP is the documentation describing what modifications will be made to a device and how the modifications will be assessed.

A recently published draft guidance, “Predetermined Change Control Plans for Medical Devices”, Draft Guidance for Industry and FDA Staff, for comment only, issued on August 22, 2024, provides FDA’s current thinking on the information to include in a PCCP.  It is also soliciting comments from stakeholders as to the proposals it discusses.  This draft guidance recommends that a PCCP describe the planned device modifications, the associated methodology to develop, validate, and implement those modifications, and an assessment of their impact.

FDA reviews the PCCP as part of a marketing submission for a device to ensure the continued safety and effectiveness of the device, without necessitating additional marketing submissions for implementing each modification described in the PCCP.  By including a PCCP in a marketing submission for a device, manufacturers can prospectively specify and seek premarket clearance / approval for intended future modifications to a device without needing to submit additional marketing submissions or obtain further FDA authorization before implementing such modifications – provided the changes are consistent with the PCCP that has been submitted and FDA-reviewed / cleared / approved.

Obviously this is a provision where future changes / models / improvements are basically known at the time of the original 510(k) or PMA submission.  For changes made to address unforeseen issues at the time of initial submission, the two guidance documents of changes to devices needing a new submission would apply instead.  

-- jel@jelincoln.com

US FDA and Device AI/ML

The US FDA has announced steps toward a new regulatory framework to promote the

development of medical devices that use advanced artificial intelligence / machine

learning algorithms - AI algorithms that can learn from and act on data. They have

already authorized some devices having AI capabilities. Their AI Good Machine

Learning Practice lists 10 “guiding principles” for ML/AI¹ to apply FDA’s current

authorities in new ways to keep up with the rapid pace of innovation and still ensure

device safety and performance.

The Agency is looking beyond elemental “locked” algorithm AI devices – devices that

don’t continually adapt or learn - to “true” AI - machine learning algorithms that

continually evolve, often called “adaptive” or “continuously learning” algorithms, that

learn through real-world use. The FDA is exploring a framework to allow modifications

to algorithms to be made from real-world learning and adaptation, while still ensuring

safety and effectiveness of the software required for premarket review. They include the

algorithm’s performance, the added concerns for AI / ML software verification and

validation, the manufacturer’s plan for modifications, and the ability of the manufacturer

to manage and control risks of the modifications, including the software’s

"predetermined change control plan".

¹ https://www.fda.gov/medical-devices/software-medical-device-samd/good-machine-

learning-practice-medical-device-development-guiding-principles

-- jel@jelincoln.com 

 Major FDA Changes – The Final Rule on LDTs (Lab Developed Tests):  Many companies who sell home test kits for STDs, drug abuse tests and similar OTC, e.g., on Amazon, CVS, Walgreens, etc., have relied heavily on the FDA’s tacit neglect under FDA’s “selective enforcement” of LDTs and their definition and legal requirements.  This now has changed radically with the issuance of the FDA’s Final Rule in the Federal Register (US law) on LDTs, on July 5, 2023¹.

 In their Final Rule, the FDA has brought LDT’s back to their original intent, i.e., a limited category of tests, manufactured / assembled by CLIA (Clinical Laboratory Improvement Amendments of 1988) labs, for which no viable alternative in IVT’s / other medical devices exist and for which “targeted selective enforcement” would be employed. All other “LDT” devices will be treated by the FDA as medical devices / IVDs. There will be a 5-stage 4-year phase-out² to full compliance. The phase-out dates start with the publication date of May 6, 2024. This Final Rule will pose major problems for current suppliers of so-called LDTs to clinicians, Amazon, CVS, Walgrens, etc.

 All LTV’s are medical devices, and now will be regulated as such, per the Final Rule, including company (commercial manufacturer / lab) registration, device listings, premarket review (510(k), PMA, IDE, De Novo) where applicable (Class II and III), adherence to the CGMPs for devices (21 CFR 820 / ISO 13485), FDA inspections, US FDA MDR reporting  (Medical Device Reporting), Labeling requirements, et al.  

 ¹Final Rule, LDTs:  https://www.federalregister.gov/documents/2024/05/06/2024-08935/medical-devices-laboratory-developed-tests

 ²Phase-out Schedule:  https://www.fda.gov/medical-devices/laboratory-developed-tests-faqs/phaseout-policy-and-enforcement-discretion-policies-laboratory-developed-tests-faqs

-- jel@jelincoln.com

 APQP - Advanced Product Quality Planning

APQP had its start with the auto industry (1980s).  Some of its basic principles are taken from ISO 9001, QS 9000, and IATF 16949 (International Automotive Task Force).  Its goal is to provide a guide to assist sharing of development and other key data between suppliers and automotive companies to meet "customer" requirements and support continuous improvement .  Focus is on design, specification compliance, production processes, QC, process capability, product testing  and training.  Obviously compatible with ISO 13485 for the US and EU / Asia.  APQP tools include the 8Ds, SPC, FMEA, 6 Sigma, GR&R+, V&V, design reviews, and similar (see also the US FDA Production and Process Control for devices, pharma, combination devices).  

Some are promoting key elements of APAP for the medical device industry. As you can see by the above, the key elements are already in the US QSR and new QMSR, as well as Europe's MDR / ISO 13485 (and now with the US as well).

jel@jelincoln.com