Medical Devices: Substantial Equivalence vs. Demonstration of Equivalence

The following is the first in the series of blogs related to the recent updates to EU MDR

Recent updates to the European Union Medical Device Regulations (MDR) brings about a very important topic for the medical device industry – how to adequately demonstrate equivalence between the device under evaluation and a similar, currently marketed device.

When a medical device Premarket Notification (510k) is filed with the U.S Food and Drug Administration (FDA), the goal is for the agency to determine that the device under evaluation is substantially equivalent to a legally marketed (predicate) device. This substantial equivalence finding conveys that the new device is at least as safe and effective as the predicate device. The new device is then cleared to be legally marketed and is bound to the same classification and regulatory requirements as the predicate device. The message to the public is that the FDA does not have any concerns related to the new device’s safety or effectiveness.

Recently, the CE Marking process for medical devices has incorporated a similar but more strict approach to demonstrating equivalence between medical devices. As you may know, the regulatory submission for a medical device to achieve the CE Mark is a compilation of technical documentation focused on the device under evaluation and does not incorporate a mandatory comparison to any current CE Marked device. It is evaluated as a stand-alone submission. However, a demonstration of equivalence to a medical device with a current CE Mark may be used (optionally) to satisfy one aspect of the regulatory submission – the clinical data requirement. The Revision 4 update to MEDDEV 2.7/1 includes very specific and more strict requirements for a demonstration of equivalence, as compared to the requirements by FDA to support a finding of substantial equivalence.

The below tables summarize the differences in the way the FDA and the European Commission evaluate the clinical, technical and biological characteristics when comparing the device under evaluation and the proposed equivalent device.

For many companies, it is a challenge just to find adequate regulatory resources to compile this exhaustive list of medical device characteristics for both the device under evaluation and the proposed equivalent device. An adequate demonstration of medical device equivalency that meets the requirements of the regulations and passes review by your notified body or the FDA will require a substantial investment of both time and specialized expertise.

Celegence can provide you with subject matter experts, including both regulatory professionals and medical doctors, with relevant device expertise to complete this work for you or to supplement your internal team as needed.

 

Medical Device Equivalence Comparisons – Criteria

Clinical CharacteristicsTechnical CharacteristicsBiological Characteristics
U.S. FDA
510k Application
Substantial Equivalence
  • Multiple equivalent devices may be used to come to a cumulative conclusion
  • Same intended use
  • Risk-based comparison of indications for use – disease or condition 1
  • Risk-based comparison of indications for use – patient population or anatomical site1
  • Differences in technological characteristics are acceptable
  • Differences in technological characteristics must not raise
    different questions of safety and effectiveness that pose a
    significant safety or effectiveness concern for the device under evaluation
  • Differences in material or substances are acceptable
  • Differences in contact of human tissues or body fluids are acceptable
  • Similar biocompatibility performance testing is required
  • Differences in materials or substances and contact profile are evaluated by the affect it may have on
    known 2 safety or effectiveness aspects
European Union
CE Mark Technical File
Demonstration of Equivalence
  • Multiple equivalent devices may be used to come to a cumulative conclusion
  • Only a single device may be used to demonstrate equivalence
  • Same intended purpose
  • Same clinical condition
  • Same body site
  • Similar patient population
  • Performances not significantly different
  • Similar design
  • Same conditions for use
  • Similar specifications and properties
  • Similar deployment methods
  • Similar principles of operation
  • Similar critical performance requirements
  • Same materials or substances
  • Same contact of human tissues or body fluids

 

Medical Device Equivalence Comparisons – Content

Device Under Evaluation and Proposed Equivalent Device
Clinical ContentTechnical ContentBiological Content
U.S. FDA
510k Application
Substantial Equivalence
  • Regulatory classification
  • Indications for use
  • Environment of use
  • Patient population
  • Comparative drawings or pictures at a system level
  • Principles of operation
  • Description of technology used, design, features
  • Identification of significant design specifications, presented in comparative tabulations
  • Performance specifications, presented comparatively
  • Compliance with standards
  • Compatibility with other devices
  • If available, Instructions for Use or Manuals
  • Descriptive information alone may be sufficient
  • Materials information for patient contacting
  • Materials information for potentially patient contacting materials
  • Biocompatibility assessment and profile
  • Biocompatibility testing result and compliance to standards
European Union
CE Mark Technical File
Demonstration of Equivalence
  • Clinical condition including severity and stage of disease, medical indication, intended purpose
  • Anatomical body site
  • User population – age, gender, anatomy, physiology
  • Clinical performances – expected clinical effect, intended purpose, duration of use
  • Clinical literature and concise summaries of literature including methods, results, and conclusions
  • Evaluation of the methodological quality and scientific validity of clinical literature
  • Current knowledge/ the state of the art
  • Type of device-body interaction
  • Description of relevant clinical, biological and technical characteristics that affect clinical properties of the device
  • Any differences in intended purpose – indications, contraindications, precautions, target patient groups, target users, mode of application, duration of use/ number of re-applications
  • Whether the comparison carried out covers all products/ models/ sizes/ settings/accessories and the entire intended purpose of the device under evaluation, or only certain aspects
  • Conclusions on device equivalency including conformity to each of the relevant essential requirements
  • Explanations of differences in devices
  • If equivalence is concluded, confirmation that the differences are not expected to affect the clinical performance and clinical safety of the device under evaluation; description of any limitations and gaps
  • Identification of differences and evaluation of expected influence on clinical performance and clinical safety, and reasons for assumptions made
  • The relevance of each dataset from an equivalent device
  • The level of access to technical and clinical data from the proposed equivalent device
  • Manufacturer
  • Name, models, sizes, settings, components
  • Relationship to the device under evaluation
  • Regulatory status
  • Justification and validity of parameters and models for non-clinical determination of characteristics
  • Specifications and properties (type and intensity of energy, tensile strength, viscosity, surface characteristics, wavelength, surface texture, porosity, particle size, nanotechnology, specific mass, atomic inclusions, etc.)
  • Deployment methods
  • Principles of operation and the means by which the device achieves the therapeutic result
  • Critical performance requirements
  • Conditions of use
  • Field safety corrective actions
  • Product labels and Instructions for Use
  • Comparative drawings or pictures at a system level and for components / elements with body contact
  • Identification of pre-clinical studies
  • Original full text versions of pre-market study reports assessing parameters of interest, including summaries, methods, results, and conclusions
  • Evaluation of the methodological quality of the study and the scientific validity of the information
  • If measurements are possible, supporting non-clinical information and testing of clinically relevant specifications and properties measured both devices, presented comparatively
  • All information listed above must also be provided for software and accessories
  • Materials and substances with body contact, and their role and nature, and their risk analysis information
  • Type of body contact
  • Biological safety testing information (e.g. ISO 10993)
  • Manufacturing information for special treatments
  • Sourcing and manufacturing procedures
  • Analytical methods chosen for material characterization Histopathological studies on host response in vivo in the intended application and duration of contact
  • For animal tests, species identification and justification for the choice of the test and its predictive value
  • Abrasion, if relevant, and host response to particles
  • A justification explaining the situation should be provided for any difference in biological characteristics
  • 1 The comparison is risk-based and there is flexibility in a finding of “similarity”. When changes between the indications for use raise a new safety or effectiveness issue or have the potential to significantly increase a safety or effectiveness concern, equivalence is not supported.
  • 2 The flexibility in differences of materials or biological contact profile is dependent on FDA’s conclusions on what constitutes a significant difference to safety or effectiveness, based off industry meta-data (all relevant pre-market and post-market data).
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