In a press release of the German Hospital Association DKG from June 2022 the chairman reports about the dramatic situation of newborns with heart defects: the balloon catheters previously used for them have already disappeared from the market.[1] Manufacturers of those orphan devices most likely didn’t find a notified body or didn’t have the necessary resources to take the steps for transformation to the MDR.

The so called “orphan devices” or “Humanitarian Use Devices (HUD)” (FDA) are “medical devices intended for the in-vivo diagnosis, prevention or treatment of a very rare life-threatening or chronically debilitating condition”[2] or – as the FDA defines it – “that are intended to benefit patients in treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United State per year”[3].

Frederike from confinis had the chance to get an interview with Dr. Marc-Pierre Möll, Managing Director of BVMED and BVMED Academy, the German Medical Technology Association after they met at the Swiss MDR & IVDR Conference.

About the general situation: are there any numbers about for example how many companies stopped selling their orphan products in Europe?

Since there is no general data base there is also no list of Orphan Devices or manufacturers of them in the European Union. 

Most affected are the fields of paediatrics and oncology. But for the big picture there has also to be considered that a lot of devices in these areas are used off label. This could also be reduced with a proper definition and clear regulatory requirements. 

For the patients this could mean a treatment without the actual technical standards in the best case or no medical treatment in the worst case.

What are the biggest challenges for manufacturers of Orphan Devices?

The problem is acute right now because of the revision of the European medical device legislative from the directives to the MDR. All existing products need to undergo a new conformity assessment including a new certification in case of the need for including a Notified Body (class Is/m/r, IIa, IIb and III devices). 

The MDR sets higher requirements within the conformity assessment and especially to clinical data. Therefore, a lot of manufacturers decided to stop these products. 

Orphan Devices are not covered by the MDR. There is no pathway for those products. 

Medical devices used for the treatment of rare diseases or for a small patient population have different market dynamics than general medical devices, due to low sales and a reduced return on investment. 

This automatically leads to higher risks of being removed from product portfolios within the manufacturers when additional barriers arise, for example from increased regulatory requirements and costs or from longer approval times.


What are the possible solutions?

Possible solutions are for example certificates under conditions with a focus on post market data or through existing procedures like Art. 59. Derogations like these could be widened within the whole Union via an implementing act. 

Another option would be to amend the MDR and implement specific rules for orphan devices.

So either the manufacturers of orphan products wait for an implementing act, the amendment of the MDR or they take action now by applying Article 59:

  • A “technical file” needs to be prepared that is needed to demonstrate to a national competent authority that the device is compliant to Article 59.
  • The manufacturer must ensure that PMS data of other markets, or equivalent or similar devices exists,
  • The critical importance must be manifested and that there is no alternative.

As a manufacturer of orphan products, a way to survive the wait for changes would be to look at the US market where FDA has already a solid regulation of HUD devices. The manufacturer needs to follow the Human Device Exemption (HDE) Program.

A HDE application is submitted to FDA to obtain approval for an HUD. It is a 2-step process:

  1. The manufacturer needs to file a humanitarian use device designation request. This request is handled by FDA´s Office of Orphan Products Development (OOPD) within 45 days until its approval.
  2. Afterwards the manufacturer needs to submit an HDE application.

The HDE application has some similarities to the PMA application:

  • HDE amendments, supplements, and reports are generally subject to similar requirements as those for PMAs
  • A quality system (QS) according to 21 CFR part 820 must be in place (but there is as well the possibility to request an exemption, or a variance form any QS regulation requirements).

But there as well some differences:

  • HDE is exempt from the requirement of establishing a reasonable assurance of effectiveness
  • HDE applications are reviewed in 75 days (not 180 days)
  • Medical device reports shall also be submitted to the IRB of record
  • Use of HUDs in the clinical care of patients requires approval prior to use by either and IRB or an appropriate local committee
  • An HDE holder can only sell a certain number of devices per calendar year
  • A declaration is needed about no alternative treatments

So, there are efforts in Europe to keep the most vulnerable patient populations and those who suffer from rare diseases safe, but with all other issues existing around the MDR, it is unfortunately not sure when this will happen.

[1] Press release DKG 09. Juni 2022

[2] Dooms MM. Orphan devices: yesterday is history; tomorrow is mystery: towards a European orphan device directive? Orphanet J Rare Dis. 2016 Mar 3;11:22. doi: 10.1186/s13023-016-0393-3. PMID: 26939863; PMCID: PMC4778287.

[3] Guidance for Industry and Food and Drug Administration Staff Humanitarian Use Device Designations.