FDA issues draft guidance on assessing physiologic closed-loop control devices

The US Food and Drug Administration’s (FDA) Center for Devices and Radiological Health (CDRH) in late December issued a draft guidance on developing medical devices with physiologic closed-loop control (PCLC) technology to ensure their safe and effective use. Submissions should carefully weigh patient and device-related risks as well as use-related hazards.
 
These devices consist of a sensor that measures a physiologic variable from the patient, a controller/control algorithm, and an actuator that delivers, or removes, energy or an article such as a drug to the patient.
 
FDA says these devices, which provide automated therapy delivery to patients for fluid resuscitation, ventilation, and anesthesia, are “emerging applications for the critical and emergency care environments.” Some examples of PCLC devices include hemodynamic stability controllers and mechanical ventilation and oxygenation controllers.
 
Yet “introducing automation and reducing clinician involvement can incur new types of hazards which may render the medical device unsafe if not properly designed or evaluated,” according to FDA’s announcement of the draft guidance.
 
The guidance addresses design and risk management considerations for these devices, and covers patient-related hazards, device-related hazards, system safety features, the user interface, non-clinical testing considerations, human factors testing and labeling.
 
“Design inputs for a device with PCLC technology should consider the risks associated with the complete device and not only the PCLC functions,” according to the draft guidance. “The design of a PCLC device should support safe use in the patient population, clinical environment, and clinical workflow in which the device will be used.”
 
FDA recommends that manufacturers consult the International Electrotechnical Commission’s (IEC) standard 60601-1-10 on medical electrical equipment when designing these devices. The standard, General requirements for basic safety and essential performance – Collateral Standard: Requirements for the development of physiologic closed-loop controllers, should be used in conjunction with general standards risk management in medical devices..     
 
To ensure that the device performs safely in patients, manufacturers should identity the intended patient population and their diseases, health status and potential comorbidities; any contraindications for using the PCLC technology; the clinical environment where the device will be used; and the current standard of care. Manufacturers should also know how the PCLC device will differ from the current standard of care, and take into consideration how changes in the patient’s response could perturb the PCLC device’s operation.
 
To mitigate any device-related hazards, FDA says risk management plans should consider how uncertainties in design and proposed workflow could affect the operation of a PCLC device. The draft guidance provides examples of some uncertainties to consider, such as is the effect of either transient or persistent artifact in the feedback variable, or  whether delay times within the system and individual components can result in unsafe operating conditions.
 
Further, if a PCLC device uses a component that is a legally marketed device, such as a 510(k) cleared blood pressure monitor that serves as a physiologic-measuring sensor in the PCLC device, manufacturers should evaluate recall and medical device reporting (MDR) data.
 
To guard against hazards associated with the device’s use, manufacturers should “consider the possibility that users can experience reduced interactions with the patient and device compared to current standard of care. As a result of reduced interaction, the user could not have a complete understanding of the patient or device status (reduced cognitive awareness) jeopardizing their ability to provide appropriate interventional responses.”
 
Other considerations in designing PCLC devices include the potential for users to place unwarranted trust and reliance on the readouts, leading to a host of hazards including complacency and skill degradation, FDA cautioned. Keeping in mind who the anticipated users are and how they will interact with the proposed device, step by step, should be part of the recommended use-related risk analysis.
 
The draft guidance provides a basic block diagram showing how a PCLC device completes the closed loop from controller to actuator, on to the patient, back to the sensor, and finally to the comparator. Points of disturbance and variables are demonstrated along the closed loop path.
 
A section on control algorithms addresses a variety of scenarios, including more complex situations where “one control algorithm may not be sufficient to function as intended in the use scenario", giving examples of how these algorithms might function in automatic oxygen delivery and closed-loop anesthesia use cases.
 
Considerations for sensors to be incorporated into PCLC devices include sensor performance and linearity; response latency and its implications; performance change over a measurement range or because of environmental factors or signal artifact; and others.
 
Similar considerations for the other components of  PCLC device system are provided in the draft guidance, which addresses actuator performance and general system safety features that should be built into closed-loop systems. Aspects of the user interface are also addressed.
 
The section on verification and validation lays out considerations unique to closed-loop systems, while testing recommendations include the full span from pre-clinical to animal to human testing. The possibility exists for computational and mathematical modeling to inform PCLC design and evaluation, and the draft guidance also provides considerations on model-based evaluation.
 
Human factors testing, training, and labeling for PCLC systems is also covered in the draft guidance, with an emphasis on minimizing the potential for automation bias and the user having a solid understanding of the nature of a PCLC device, and its limitations.
 
Regarding training, FDA notes that “experiencing automation failures during practice sessions can help reduce automation-related use errors by encouraging critical thinking when using automated systems.”
 
The guidance covers premarket notification submissions, de novo requests, premarket approval applications (PMAs), and humanitarian device exemptions (HDEs); it incorporates feedback from a October 2015 public workshop on PCLC devices. The workshop’s goal was to promote discussion on design and evaluation considerations of PCLC devices used in critical care environments.
 
The guidance was issued on 23 December. The deadline for commenting is 22 February 2022.
 
FDA draft guidance