MDCG guidance tries to reduce burden of bringing orphan devices to EU market

Manufacturers developing orphan medical devices in the EU should be given extra leeway to bring their products to market, especially considering the higher evidence threshold set by the Medical Device Regulations (MDR), according to a new guidance from the Medical Device Coordination Group (MDCG). The group also emphasized that manufacturers may need to rely more on postmarket studies and non-clinical data to support such products.

On 25 July, MDCG published guidance for manufacturers and notified bodies detailing considerations for defining an orphan device and the potentially limited evidence needed to determine whether it has proven to be safe and effective.

“The level of clinical evidence that is required to place medical devices on the market has been increased by the MDR, including an increased need for pre-market clinical investigations for certain higher risk devices to verify their safety and clinical performance,” said MDCG. “These increased clinical evidence requirements present a challenge for devices specifically intended for use in rare diseases/conditions, or in specific indications for rare cohorts of patients with an otherwise non-rare disease/condition.”

“The increased, and at times unpredictable, financial costs associated with compliance with MDR requirements, including MDR certification, can make it prohibitive for manufacturers to place orphan devices on the EU market, as the low volumes of sales may not offset the financial costs,” the group added.

The guidance notes that some manufacturers may develop devices with both orphan and non-orphan indications, which may be challenging to prove safe and effective in a smaller population. In such situations, the MDCG emphasized that the guidance only applies to the orphan indication and can’t be used to leverage authorization for the more general indication.

The guidance states that applying MDR requirements to orphan devices should be balanced and proportionate so that they don’t unduly prevent such products from coming to market.

“There are circumstances where it is acceptable to place an orphan device on the market with limitations in pre-market clinical data,” said MDCG. “In such circumstances, it is important that there is an appropriate level of transparency for health care professionals, patients, and members of the public, so that they are aware of the orphan status of the device, any relevant limitations in clinical data, and any relevant conditions or provisions of certification that have been applied.”

To qualify as an orphan device, the manufacturer should provide evidence that the intended indication it treats is limited to conditions that afflict at most 12,000 people in the EU every year. The guidance also states that the manufacturer can justify their product as an orphan device if it afflicts a subpopulation where a disease affects at most 12,000 people annually, even if the broader disease indication affects more than 12,000 people annually.

“In cases where the device is intended to treat, diagnose, or prevent a rare disease as defined in the EU and affecting no more than 5 in 10,000 persons in the EU, and where the device is expected to be used in not more than 12,000 such individuals per year, this can be accepted as sufficient justification of the epidemiological part of the criteria,” the guidance added.

While trying to give manufacturers some leeway to get orphan devices to market, MDCG also emphasized that it’s up to the manufacturer to provide a description of their product, its intended purpose, and a scientific rationale for why their product should be considered an orphan device. They may describe a specific indication for use instead of or in addition to an intended use in their justification. Furthermore, their justification should include details on the current state of the art and alternative therapies available to the patient population the product is intended to diagnose or treat.

MDCG said that it may be challenging for manufacturers to generate sufficient clinical trial data in the premarket setting, considering the difficulty of enrolling enough subjects. With that in mind, orphan devices may be allowed on the market based on limited premarket data, but manufacturers must take appropriate measures such as agree to conduct post-market clinical follow-up (PMCF) studies.

“There must be sufficient clinical evidence to demonstrate an expected clinical benefit and that the device performs as intended with an acceptable level of safety,” said MDCG. “To address and resolve any limitations in pre-market clinical evidence as soon as possible, an adequate PMCF plan must be developed to ensure appropriate collection and generation of post-market clinical data.”

Non-clinical data may also play a key role in allowing orphan devices on the market, especially when it is difficult to generate clinical trial data said MDCG. The group added that all sources of non-clinical data should be considered when developing orphan devices.

“If the non-clinical data provide substantial high-quality evidence to support the safety and performance of the orphan device and its expected clinical benefit, this can reduce the burden of required pre-market clinical data and can help to justify CE marking with limitations in clinical data that can be met through PMCF activities,” the guidances added.

Besides providing recommendations on developing evidence to justify bringing an orphan device to market, the guidance also includes details on how manufacturers and notified bodies can get advice from European Medicines Agency (EMA) expert panels to help their product development.

MDCG guidance

MDCG guidance tries to reduce burden of bringing orphan devices to EU market

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