Notice: Changes to Evidence Requirements for Class II and Class III Infusion Pumps

August 13, 2018

Our file Number: 18-109825-412

Scope

Delivery accuracy testing requirements for infusion pumps to support new and amended medical device licence applications.

Context

This Notice serves to formalize and communicate Health Canada's expectations regarding the scientific evidence required to demonstrate the delivery accuracy of infusion pumps through performance testing for new and amended licence applications. Post-market safety concerns have been raised about the delivery accuracy of these medical devices, which resulted in an under- or an over-infusion of therapeutic agents.

Effective immediately, new Class II and Class III medical device licence applications for infusion pumps will require infusion delivery accuracy performance testing data over the range of characteristics and environmental factors mentioned below unless otherwise justified. In addition, amendments to Class II and Class III medical device licence applications for infusion pumps and accessories will require infusion delivery accuracy performance testing data, as described below, if the change affects:

• the pumping mechanism
• any software component which could affect fluid delivery accuracy, and/or,
• a tubing set, where the change impacts the delivery accuracy range stated in the labelling of the pump

Manufacturers will need to include in their licence application the following performance testing data which clearly demonstrates that the infusion pump can reliably deliver therapeutic agents within the accuracy ranges specified in the product labelling. These performance tests should be done with the complete infusion pump system and required accessories, and within the context (i.e., conditions/factors and characteristics) of the intended use of the device and indicated infusion treatments. The tests should include a statistically justified sample size as defined by international standards or justified internal processes such that the accuracy performance is demonstrated, at adequate reliability and confidence levels, to be within the claimed accuracy range. Please note that a comparison to existing licensed devices alone will not be sufficient to support a new infusion pump's performance testing data; device-specific testing will be required.

Examples of characteristics and environmental factors that should be considered when determining infusion accuracy specifications include:

• infusion sets (length, diameter, number and type of flow restriction devices on the set, number and relative location of access points)
• cannulas and catheters (length and diameter)
• drug reservoir (size and position relative to pump)
• pump model/configurations (flow rate limits and volume limits)
• Time period over which the accuracy is specified
• ambient temperature
• fluid or drug temperature
• pressure (e.g., head-height, backpressure, atmospheric pressure)
• fluid or drug viscosity
• consideration to test clinically relevant worst-case scenario permutations or combinations of the above factors, based on reasonably foreseeable use, justified by the sponsor

This performance testing may go beyond the scope of testing required by the international standards for infusion pumps (IEC 60601-2-24 and ISO 28620). Testing that is limited to only these standards is no longer considered to be sufficient. These requirements will be imposed on all pump types (e.g., large volume peristaltic, elastomeric, syringe, etc.). Manufacturers of more specialized pumps (e.g., insulin pumps) may provide a rationale for a more limited battery of testing, providing the testing is adequately representative of foreseeable use conditions.

The results of the performance tests cited above, including the testing required by the international standards, the clinically relevant range of characteristics and environmental factors, and the clinically relevant worst-case scenario permutations or combinations of characteristics and environmental factors, need to be clearly and quantitatively outlined in the labelling of the device to ensure that healthcare facilities may make an informed decision regarding procurement of devices, and healthcare professionals may make informed decisions regarding the treatment of their patients. For greater clarity, Health Canada considers reliance on labelling warning statements as insufficient risk mitigation for these devices (for example, a statement which reads "environmental factors might affect infusion accuracy").

According to subsection 10(c) (iii) of the Medical Devices Regulations (MDR), manufacturers are required to take reasonable measures to identify the risks inherent in the device and if the risks cannot be eliminated, to reduce the risks to the extent possible and provide information relative to the risks that remain. Therefore, device labelling which inaccurately portrays infusion accuracy in real-world situations (such as, when infusing a drug), or which only provides performance data under nominal conditions, is a contravention of the MDR.

Failure to provide the required testing at the time of submission of a licence application may result in a request for Additional Information under subsection 35(1) of the MDR at any time during the review (i.e., during either the screening or review phase). Failure to provide evidence of adequate testing under a request for Additional Information may subsequently result in a Refusal to Issue a licence, under subsection 38(2) of the MDR.

While this Notice primarily targets new and amended licence applications submitted to the department, in the event that infusion accuracy concerns are brought to our attention about a licensed infusion pump, Health Canada reserves the right to request the above-noted evidence to support continued licensing of that licensed device via a request for Additional Information under section 39 of the MDR.

This Notice is one element of Health Canada's modular approach to guidance development for infusion pumps. It aligns with the recommendations made by the United States Food and Drug Administration (FDA) in their latest 2014 iteration of the Infusion Pumps Total Product Life Cycle, Guidance for Industry and FDA staff. As per the August 4th, 2016 Notice: Use of United States Food and Drug Administration (FDA) Guidance Materials to support Canadian Medical Device License Applications, Health Canada encourages the use of FDA guidelines to address premarket submission requirements for medical devices.

Please direct any questions or comments regarding the content of this Notice to the following:

• Medical Devices Bureau
  Therapeutic Products Directorate
  Health Products and Foods Branch
  Health Canada
• Email: mdb_enquiries@canada.ca
• Telephone: 613-957-7285

References

• Notice: Use of United States Food and Drug Administration (FDA) Guidance Materials to support Canadian Medical Devices Licence Applications. Document issued on: August 4, 2016
• Infusion Pumps Total Product Life Cycle, Guidance for Industry and FDA Staff. Document issued on: December 2, 2014.