What defines a Class III medical device?
Class III is a diverse risk classification including a broad array of devices that are crucial to sustaining life or preventing disease. Categories of Class III device include:
- Implantable devices
- Invasive devices interacting with the central nervous or circulatory system
- Closed-loop systems
- Some active devices
- High-risk medical device software
- Combination products
- Special materials
Class III devices perform a vital function but have a higher corresponding risk profile due to the nature of their interaction with the human body and / or criticality of purpose. MDR Annex VIII sets out classification Rules that determine risk class of all devices, based on a combination of factors including invasiveness, duration of exposure, structures interacted with, and presence of complicating factors.
Implantable devices offer an intervention directly at the site of pathology; however, because they are implanted, device malfunction could be catastrophic and may require a surgical procedure in response. Rules 6 – 8 clarify that while not all invasive devices are Class III, long-term surgically invasive devices or those intended for implantation will be Class III via Rule 8, unless intended for use in the teeth or comprising ancillary components such as screws, wedges, or plates. Invasive devices interacting with the central nervous or circulatory system will be Class III regardless of duration of action.
A closed-loop system is a type of medical device that uses an algorithm or other means to measure its outputs and adjust inputs to the system to move subsequent outputs closer to a target value. In other words, closed loop devices constantly adjust their own activity in response to measurements, ‘intelligently’ making changes to achieve a certain outcome. Examples include artificial pancreas devices or insulin delivery systems, which neatly demonstrate the measure-adjust-deliver principle operating within. Rule 22 classifies all such devices as Class III, alongside automated electronic defibrillators, which operate through an analogous principle.
Active devices generally fall into a lower risk classification via Rules 9, 10 and 11 (with software being classed as a form of active device). As an exception to the norm, Rule 9 classifies devices that are intended for controlling, monitoring or directly influencing the performance of active implantable devices as Class III.
Rule 11 classifies medical device software as Class III if it is making decisions that could lead to death or an irreversible deterioration of a person’s state of health; software may otherwise fall into any other risk classification (with the exception of Class Is and Ir). Mantra Systems offers a dedicated software-as-a-medical-device (SaMD) consulting service to address the specific needs of software devices, including those falling into Class III.
Combination products include drug-device combination products such as gentamicin-eluting bone cement or drug-eluting vascular stents. Combination products must meet the definition of ‘medical device’ in MDR Article 2 – ie, their primary intended purpose must not be through pharmacological action. A medicinal product combined with the device then delivers an ancillary action complementing the action of the device component. Drug-device combination products require especially careful handling during regulatory submissions, as the interface with the definition of ‘medicinal product’ in Article 1 of Directive 2001/83/EC can lead to classification difficulties in some cases. The presence of a medicinal product also imposes additional obligations during the submission, as described below.
Are there any unique aspects of a Class III regulatory submission?
Primarily, Class III submissions have the same core components as submissions for the other risk classes, albeit with a significantly heightened level of scrutiny during Notified Body review. The exception to this is the requirement to complete a Summary of Safety and Clinical Performance (SSCP), which is required for all Class III and implantable devices under MDR.
An SSCP is a summary of pertinent clinical data intended to enable open access to evidence relating to safety and performance of a device. A ‘healthcare professional’ SSCP section will be required for all Class III and implantable devices. In addition, devices intended for use by laypersons or that are normally accompanied by an implant card will also need an SSCP section intended to be read by laypersons. In this case, the layperson section will also need to be evaluated for readability, to demonstrate that the choice of language is suitable for those without a formal medical education.
Depending on the nature of the device, some Class III submissions might also require one or more of the following additional components:
MDR Article 18 mandates production of an Implant Card for all implantable devices. This forms part of the ‘information supplied with the device’ and, as a minimum, must include the device name, serial number, lot number, UDI, device model, and the name, address and website of the manufacturer. However, the requirement for an Implant Card does not extend to sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors.
A Medicinal Dossier will need to be produced for drug-device combination products incorporating a medicinal substance with an ancillary action. This document is intended to present evidence relating to the safety, quality, and usefulness of the medicinal product, and will be reviewed by a Competent Authority or the EMA during consideration of the submission. It is, then, a pivotal document that requires specific focus and attention.
What level of evidence is required for a Class III submission?
According to MDR Article 61(4), the general position is that clinical investigations must be performed in relation to all Class III medical devices. In practical terms, there is little deviation from this stance and manufacturers with concerns over the availability of clinical evidence for their device are advised to book a free consultation early to ensure an optimal clinical strategy is in place.
MDR Article 61(4) does offer some exceptions to this requirement that may apply in some cases. According to this provision, clinical investigations may not be required for Class III devices that are:
- A modification of a device already legally marketed by the same manufacturer
- The device in question is shown to be equivalent to this predicate device
- The prior device has been subjected to a clinical evaluation, and that evaluation showed the device to meet the relevant GSPRs according to available evidence.
MDR Article 61(6) offers further exemptions in relation to legacy devices legally marketed and approved under Directives 90/385/EEC (active implantable devices) or Directive 93/42/EEC (Medical Device Directive (MDD)). For these devices, a clinical investigation is not required where the clinical evaluation:
- is based on sufficient clinical data, and
- is in compliance with any product-specific Common Specification (CS), where such a CS exists.
In other words, the manufacturer of a legacy device accompanied by sufficient evidence does not normally need to conduct a fresh clinical investigation for a submission under MDR.
Two further exceptions to the requirement to conduct a clinical investigation are:
- Sutures, staples, dental fillings, dental braces, tooth crowns, screws, wedges, plates, wires, pins, clips or connectors with sufficient clinical data and, where relevant, that comply with a product-specific CS
- Submissions including a compliant claim of equivalence to a device marketed by another manufacturer; however, in practical terms this is extremely unlikely to succeed. For an equivalence claim to succeed, the Regulation requires the existence of a contract offering full, unobstructed access to the equivalent device’s technical files. Naturally, where the candidate equivalent device is produced by a competitor, such a contract is highly unlikely to be secured.
