It is important to note that the US FDA is undergoing a major change that will affect the entire US regulatory process. Called “Case for Quality” or CFQ. To understand CFQ, it is best to first understand the current process.

The FDA “510K” refers to what is known as the predicate system, where to show what your device does, you compare it to a similar, or “predicate” device, and then develop an “intended use” case compared against the predicate device.  Specifically, the agency intends to “harmonize and modernize” its medical device Quality System Regulation (21 C.F.R. Part 820) with an international consensus standard for medical device manufacturing (ISO 13485). So, while ISO 13485 has been the important quality driver behind the scene, now the FDA is creating a new system that will align very closely with ISO 13485, ISO 60601-2, and ISO 62304.

ISO 60601 IEC Medical Electrical Standards. There is a specific standard for many types of medical devices and measurements relative to various specific aspects of physiological measurement, reporting, and alarms.

ISO 60601-2-1: General requirements for safety. This is the basic ISO 60601 requirement that calls out the minimum electrical isolation standards, which are BTW, 100 microamps. Any device connected to the mains electrical supply shall have no more than 100 microamperes of leakage current. This, for instance, prevents the patient from being electrocuted.
ISO 60601-2-2 Medical electrical equipment – Part 1-2: General requirements for basic safety and essential performance – Collateral Standard: Electromagnetic disturbances – Requirements and tests. This should be of interest to SIMULIA as they can simulate for these tests and save $ by not having to re-test
ISO 60601-2-3 Collateral Standard: Radiation protection in diagnostic X-ray equipment
ISO 60601-2:12 Particular Requirements for the safety of lung ventilators (link). For instance, back during the COVID-build-a-ventilator-from-an-Arduino rage, most people did not know that in order to FDA 510K clear a ventilator, you must also adhere to ISO 60601-2-12. Here is the complete list:

  • EC 60601-1-2 Medical electrical equipment – Part 1-2: General requirements for basic safety and essential performance – Collateral Standard: Electromagnetic disturbances – Requirements and tests
  • IEC 60601-1-3 Medical electrical equipment – Part 1-3: General requirements for basic safety and essential performance – Collateral Standard: Radiation protection in diagnostic X-ray equipment
  • IEC 60601-1-6 Medical electrical equipment – Part 1-6: General requirements for basic safety and essential performance – Collateral standard: Usability
  • IEC 60601-1-8 Medical electrical equipment – Part 1-8: General requirements for basic safety and essential performance – Collateral Standard: General requirements, tests and guidance for alarm systems in medical electrical equipment and medical electrical systems
  • IEC 60601-1-9 Medical electrical equipment – Part 1-9: General requirements for basic safety and essential performance – Collateral Standard: Requirements for environmentally conscious design
  • IEC 60601-1-10 Medical electrical equipment – Part 1-10: General requirements for basic safety and essential performance – Collateral Standard: Requirements for the development of physiologic closed-loop controllers
  • IEC 60601-1-11 Medical electrical equipment – Part 1-11: General requirements for basic safety and essential performance – Collateral Standard: Requirements for medical electrical equipment and medical electrical systems used in the home healthcare environment
  • IEC 60601-1-12 Medical electrical equipment – Part 1-12: General requirements for basic safety and essential performance – Collateral Standard: Requirements for medical electrical equipment and medical electrical systems intended for use in the emergency medical services environment
  • IEC 60601-2-1 Medical electrical equipment – Part 2-1: Particular requirements for the basic safety and essential performance of electron accelerators in the range 1 MeV to 50 MeV
  • IEC 60601-2-2 Medical electrical equipment – Part 2-2: Particular requirements for the basic safety and essential performance of high frequency surgical equipment and high frequency surgical accessories
  • IEC 60601-2-3 Medical electrical equipment – Part 2-3: Particular requirements for the basic safety and essential performance of short-wave therapy equipment
  • IEC 60601-2-4 Medical electrical equipment – Part 2-4: Particular requirements for the basic safety and essential performance of cardiac defibrillators
  • IEC 60601-2-5 Medical electrical equipment – Part 2-5: Particular requirements for the basic safety and essential performance of ultrasonic physiotherapy equipment
  • IEC 60601-2-6 Medical electrical equipment – Part 2-6: Particular requirements for the basic safety and essential performance of microwave therapy equipment
  • IEC 60601-2-8 Medical electrical equipment – Part 2-8: Particular requirements for basic safety and essential performance of therapeutic X-ray equipment operating in the range 10 kV to 1 MV
  • IEC 60601-2-10 Medical electrical equipment – Part 2-10: Particular requirements for the basic safety and essential performance of nerve and muscle stimulators
  • IEC 60601-2-11 Medical electrical equipment – Part 2-11: Particular requirements for the basic safety and essential performance of gamma beam therapy equipment
  • IEC 60601-2-12 Medical electrical equipment – Part 2-12: Particular requirements for the basic safety and essential performance of critical care ventilators
  • IEC 60601-2-13 Medical electrical equipment – Part 2-13: Particular requirements for basic safety and essential performance of anaesthetic systems
  • IEC 60601-2-16 Medical electrical equipment – Part 2-16: Particular requirements for basic safety and essential performance of haemodialysis, haemodiafiltration and haemofiltration equipment
  • IEC 60601-2-17 Medical electrical equipment – Part 2-17: Particular requirements for the basic safety and essential performance of automatically controlled brachytherapy afterloading equipment
  • IEC 60601-2-18 Medical electrical equipment – Part 2-18: Particular requirements for the basic safety and essential performance of endoscopic equipment
  • IEC 60601-2-19 Medical electrical equipment – Part 2-19: Particular requirements for the basic safety and essential performance of infant incubators
  • IEC 60601-2-20 Medical electrical equipment – Part 2-20: Particular requirements for the basic safety and essential performance of infant transport incubators
  • IEC 60601-2-21 Medical electrical equipment – Part 2-21: Particular requirements for the basic safety and essential performance of infant radiant warmers
  • IEC 60601-2-22 Medical electrical equipment – Part 2-22: Particular requirements for basic safety and essential performance of surgical, cosmetic, therapeutic and diagnostic laser equipment
  • IEC 60601-2-23 Medical electrical equipment – Part 2-23: Particular requirements for the basic safety and essential performance of transcutaneous partial pressure monitoring equipment
  • IEC 60601-2-24 Medical electrical equipment – Part 2-24: Particular requirements for the basic safety and essential performance of infusion pumps and controllers
  • IEC 60601-2-25 Medical electrical equipment – Part 2-25: Particular requirements for the basic safety and essential performance of electrocardiographs
  • IEC 60601-2-26 Medical electrical equipment – Part 2-26: Particular requirements for the basic safety and essential performance of electroencephalographs
  • IEC 60601-2-27 Medical electrical equipment – Part 2-27: Particular requirements for the basic safety and essential performance of electrocardiographic monitoring equipment
  • IEC 60601-2-28 Medical electrical equipment – Part 2-28: Particular requirements for the basic safety and essential performance of X-ray tube assemblies for medical diagnosis
  • IEC 60601-2-29 Medical electrical equipment – Part 2-29: Particular requirements for the basic safety and essential performance of radiotherapy simulators
  • IEC 60601-2-31 Medical electrical equipment – Part 2-31: Particular requirements for the basic safety and essential performance of external cardiac pacemakers with internal power source
  • IEC 60601-2-33 Medical electrical equipment – Part 2-33: Particular requirements for the basic safety and essential performance of magnetic resonance equipment for medical diagnosis
  • IEC 60601-2-34 Medical electrical equipment – Part 2-34: Particular requirements for the basic safety and essential performance of invasive blood pressure monitoring equipment
  • IEC 60601-2-36 Medical electrical equipment – Part 2-36: Particular requirements for the basic safety and essential performance of equipment for extracorporeally induced lithotripsy
  • IEC 60601-2-37 Medical electrical equipment – Part 2-37: Particular requirements for the basic safety and essential performance of ultrasonic medical diagnostic and monitoring equipment
  • IEC 60601-2-39 Medical electrical equipment – Part 2-39: Particular requirements for basic safety and essential performance of peritoneal dialysis equipment
  • IEC 60601-2-40 Medical electrical equipment – Part 2-40: Particular requirements for the basic safety and essential performance of electromyographs and evoked response equipment
  • IEC 60601-2-41 Medical electrical equipment – Part 2-41: Particular requirements for the basic safety and essential performance of surgical luminaires and luminaires for diagnosis
  • IEC 60601-2-43 Medical electrical equipment – Part 2-43: Particular requirements for the basic safety and essential performance of X-ray equipment for interventional procedures
  • IEC 60601-2-44 Medical electrical equipment – Part 2-44: Particular requirements for the basic safety and essential performance of X-ray equipment for computed tomography
  • IEC 60601-2-45 Medical electrical equipment – Part 2-45: Particular requirements for basic safety and essential performance of mammographic X-ray equipment and mammomagraphic stereotactic devices
  • IEC 60601-2-46 Medical electrical equipment – Part 2-46: Particular requirements for the basic safety and essential performance of operating tables
  • IEC 60601-2-47 Medical electrical equipment – Part 2-47: Particular requirements for the basic safety and essential performance of ambulatory electrocardiographic systems
  • IEC 60601-2-49 Medical electrical equipment – Part 2-49: Particular requirements for the basic safety and essential performance of multifunction patient monitoring equipment
  • IEC 60601-2-50 Medical electrical equipment – Part 2-50: Particular requirements for the basic safety and essential performance of infant phototherapy equipment
  • IEC 60601-2-52 Medical electrical equipment – Part 2-52: Particular requirements for the basic safety and essential performance of medical beds
  • IEC 60601-2-54 Medical electrical equipment – Part 2-54: Particular requirements for the basic safety and essential performance of X-ray equipment for radiography and radioscopy
  • IEC 60601-2-57 Medical electrical equipment – Part 2-57: Particular requirements for the basic safety and essential performance of non-laser light source equipment intended for therapeutic, diagnostic, monitoring and cosmetic/aesthetic use
  • IEC 60601-2-62 Medical electrical equipment – Part 2-62: Particular requirements for the basic safety and essential performance of high intensity therapeutic ultrasound (HITU) equipment
  • IEC 60601-2-63 Medical electrical equipment – Part 2-63: Particular requirements for the basic safety and essential performance of dental extra-oral X-ray equipment
  • IEC 60601-2-64 Medical electrical equipment – Part 2-64: Particular requirements for the basic safety and essential performance of light ion beam medical electrical equipment
  • IEC 60601-2-65 Medical electrical equipment – Part 2-65: Particular requirements for the basic safety and essential performance of dental intra-oral X-ray equipment
  • IEC 60601-2-66 Medical electrical equipment – Part 2-66: Particular requirements for the basic safety and essential performance of hearing instruments and hearing instrument systems
  • IEC 60601-2-68 Electrical medical equipment – Part 2-68: Particular requirements for the basic safety and essential performance of X-ray-based image-guided radiotherapy equipment for use with electron accelerators, light ion beam therapy equipment and radionuclide beam therapy equipment
  • IEC 60601-2-75 Medical electrical equipment – Part 2-75: Particular requirements for the basic safety and essential performance of photodynamic therapy and photodynamic diagnosis equipment
  • IEC 60601-2-76:2018 Medical electrical equipment – Part 2-76: Particular requirements for the basic safety and essential performance of low energy ionized gas haemostasis equipment
  • IEC 60601-2-83:2019 Medical electrical equipment – Part 2-83: Particular requirements for the basic safety and essential performance of home light therapy equipment
  • IEC 60601-2-84:2018 Medical electrical equipment – Part 2-84: Particular requirements for the basic safety and essential performance of emergency and transport ventilators

ISO 13485 – is a quality management system for medical devices that established several sections for quality management including:

DHF – Design History File: This cache of information relates to the design of the device. The point of the DHF file is to show that the end design is exactly what the requirements and engineering files called for.  Some have called this the “eDHF” (as should DS), to refer to an electronic DHF that can automatically receive and index DHF messages in an HTTP PUT format. The DHF file should have every piece of information related to the design of the device including:

Requirements – engineering specifications for software, hardware, human factors, ISO 60601-2, and ISO 62304
Simulations: all simulations should also be included in the DHF file, ie, SPICE, SIMULIA EMF, or thermal simulations
CAD – all 2D, 3D drawings
schematics: PCBs, wiring harnesses
PCB layouts
BOM
SySML files
Device architecture: most devices have multiple PCBs with individual parts and software revision numbers. These need to be clearly delineated on a high-level schematic or block diagram.
DMR – Device Manufacturing Record: The Device manufacturing record includes all of “how to” build the device. This can include snippet of information such as how to connect to the console port to upload firmware, or how to align a roller to a certain tolerance.

In the typical 510K submission as the CSL listing for their Logic 3.0 software shows below, they have identified a substantial equivalence which they list their substantially equivalent to Logic 2.0, its predecessor on page one. This is usually a different manufacturer/device. For instance, if I was to file a 510K on an ECG management system, I would want to use the GE MUSE system as a substantial equivalent, as it gives the FDA researchers an idea of what your product does.

and on page two they list the intended use. When filing 510K updates (as this is), the intended use should be the same if you want to update the 510K in a faster manner.

…and on page three they include a comparison chart between the last software version which is the predicate device.

In this CSL example, it shows that there was a previous submission for CSL’s Logic software and this should have been the first stop for anyone wanting to know how to submit a revision submission for the CSL WMS software. In fact, in order to submit, they will have to prove substantial equivalence as with the example above, and chart the differences (features).

Case For Quality (CFQ)