Lately I have thought a lot about future-proofing of the new EU regulation proposals for medical devices and IVDs, specifically with respect to the development of 3D printing of individualized (custom) medical devices – which is well on its way with more and more companies joining the fray. With companies like Siemens and GE investing big in manufacturing processes for complex parts in e.g. aircraft engines, it’s just a matter of time before Moore’s law seriously takes off in 3D printing.
Think devices like prosthetic limbs, custom exoskeletons, but also a wide variety of implants, like a an electronic glove for the heart that functions as pacemaker. Is the proposed medical devices regulation sufficiently equipped to regulate custom devices that are manufactured by 3D printing across the full risk profile spectrum?
My conclusion is: not even close, which is why we need to rethink the regime for custom made devices now that the regulations are still in the process of adoption. Here are some thoughts of mine in that respect.
Proposed low regulatory burden will not work
The big added value of 3D printed medical devices is the unlimited potential for customization of the devices, so they can be produced precisely to fit the individual patient’s needs and measurements. Custom made medical devices however currently enjoy a very light touch of regulation under the current MDD, and are proposed to continue to do so under the new regulation. The Explanatory Memorandum to the MDR states that
“Manufacturers of medical devices for an individual patient, so called ‘custom-made devices’, must ensure that their devices are safe and perform as intended, but their regulatory burden remains low.”
That kind of approach is of course perfectly OK for low risk medical devices traditionally produced by custom medical device manufacturers like orthopedic shoes, but is a lot less appropriate for high risk stuff like 3D printed orthopedic implants.
Annex I Essential Requirements and prescribers
Custom-made devices will still need to meet all Annex I requirements under the new MDR like they must under the MDD, but the only safeguards are the manufacturer’s diligence, the prescription that defines the custom made device and the ex-post controls exercised by competent authorities. This will not change under the new rules as they are currently proposed. Is that sufficient control? I am not so sure, even after the implementation of the Joint Immediate Action Plan and a possible action plan version 2.0 that I have heard rumors about.
What will change is the group of people allowed to prescribe a custom-made device. If the Parliament has its way, this will be extended to all “professional users” that are “appropriately qualified” (consisting of “a doctor of medicine, a dental practitioner or any other professional user”), which potentially is a frightfully big group of people with potentially very different levels of professional qualification and expertise. It’s also not clear what the member states are still allowed to do here since the proposal is a regulation, intended to give the member states only the freedom of implementation defined in the statute. This means that member states will each take their own view of what an appropriately qualified professional user is and this will likely become another situation of straight up CE (Confusion Everywhere). I think this really needs a more coherent approach.
Industrial manufacturing process / customization vs custom-made
We already know from existing guidance that custom-made devices cannot be mass-produced. This is clarified in the new regulation proposal as follows in one of the Parliament amendments to the MDR to article 2(3) MDR, which contains the definition of custom-made device:
“However, mass-produced devices which need to be adapted to meet the specific requirements of a doctor of medicine, a dental practitioner or any other professional user and devices which are mass-produced by means of industrial manufacturing processes in accordance with the written prescriptions of doctors of medicine, dental practitioners or any other authorised person shall not be considered to be custom-made devices;”
Indeed, in the EU regulatory logic such devices are customizable ‘standard’ medical devices. The question is whether this excludes individualised 3D printed devices or not. That will really depend on whether 3D printing is considered an “industrial manufacturing processes in accordance with […] written prescriptions”. There are good arguments to say that it is. The available EU guidance on custom-made products says that mass-production according to individual specifications can still constitute a non-custom made medical device. In the field of other regulated life sciences products such as ATMPs authorities have been very quick to find without almost no exception that the cells or tissues have been produced with an industrial manufacturing process, purely because the perceived risk profile invariably prompts them into a precautionary regulatory approach and shelter under the heaviest regulatory regime so they can never be wrong – at least, that is my personal experience with authorities in the field. You could also argue that 3D printing is customisation of a standard virtual device defined in a software model rather than custom production according to a production process that is not already fully determined in advance, which would be the case for a true traditional custom-made device.
At present, we don’t know yet where this will land, but it would be a good idea for the Commission to provide guidance on how it sees this. To me, an industrial manufacturing process is characterised by a standardised production method, which intends to ensure that each device is produced in the exact same way, using the same materials and the same manufacturing template, taking into account customization features that are implemented in the production process. This seems to fit manufacturing of individualised devices by means of 3D printing pretty well – and fits 3D printing of non-individualised devices without any doubt. Basically, 3D printing of custom devices is mass-production of devices that are customized in the production process, rather than producing ‘custom conceived and built devices one at a time’. The current custom-made devices regime assumes that the prescription specifics and the expertise of the custom device manufacturer are sufficient safeguard for the safety and performance of the device. This may be true for many of the traditional custom made devices, but will arguably not be sufficient for higher risk devices produced with a production process that the prescription cannot really change anything about, except provide for customization specifics.
Production quality requirements
A way to deal with the regulatory insufficiency is to require that manufacturers of higher risk 3D custom printed devices (e.g. implantable and/or invasive custom-made devices) shall be subject to a conformity assessment based on product conformity verification as specified in Section 7 of Part A of Annex X (see our consolidated text). This would provide for initial and regular follow-up notified body control of the production process, and an ex ante and continuing audit of whether the production process is capable of producing devices that meet the Annex I requirements as required. This solution has my own personal preference, because it does exactly what is needed in solving the production quality dilemma and can be inserted in the current text of the proposal with such minimal invasiveness that it should not even be controversial.
Input material medical device?
Yet another (or complimentary) way to control quality of 3D custom printed devices would be to require CE marking of the input material. This approach would require taking the view that the printing material is equal to, for example, CE marked filling materials that are used for creating a dental filling. That would fit current policy in the EU Guidance Note For Manufacturers Of Custom Made Medical Devices , which sets out specifically in this regard:
“Intermediate products specifically intended for manufacture of custom-made devices may also be considered as medical devices. This applies essentially to dental alloys, dental ceramics, modular components for prosthesis, if the intended purpose of such products is specifically related to medical devices.”
Since it is the intended purpose of the input material that counts, manufacturers could be required to use CE marked input material. This would apply even if the input material is completely generic material, just like completely generic industrial gasses like oxygen must be licensed as medicinal products in a number of member states if they are to be used for medical purposes.
Regulate lower risk like home brew IVDs?
If 3D printing of all types of devices remains within the custom-made devices regime, I think the EU should consider some revisions to the custom-made devices regime. Characteristic for 3D printing is that it concentrates manufacturing in one place, and limits reliance on suppliers (except for the raw materials input for the printer). On the other hand, because anybody that can obtain the software models for devices can print them anywhere you can install a 3D printer (like in my own garage) quality systems become very very important. More so even if you would come to the conclusion that individualised 3D printed devices do not consitute devices fully subject to medical devices regulation. Yet, quality system requirements are precisely what is lacking in the new rules with respect to custom-made devices. As a result, 3D printing regulation in the medical devices field in the EU is not really scalable, unless you would bring 3D printing out of the scope of the custom made devices scope alltogether by taking the policy decision that 3D printing using software defined models consitutes manufacturing using an industrial process. Especially for higher risk 3D printed devices this seems a way to go, because it would involve certification of the quality system and production process by a notified body, ensuring a degree of ex ante controls on production and quality system.
A way to solve this for lower risk custom devices would be to include a regime analogous to the home brew IVDs regime set out in article 4 (5) of the IVD regulation proposal. This regime focuses on quality system requirements for the production of home brew IVD devices and makes sure that lab developed tests have at least been developed in an accredited laboratory, with the other requirements (e.g. ex-post notification to member state) being remarkably similar. This approach would help ensure that at least the production environment is controlled, which would be important for higher risk devices.
Several ways to Rome
As I have shown, there are several ways to Rome in this case, and it’s important that we take one. Proverbially speaking, your life is not complete if you’ve never visited Rome. I have pointed to a lot of instances of not very well-considered over-regulatution in the medical devices regulation proposal on this blog, but regulation of custom 3D printed devices is one area that is definitely stuck in the past given the developments in this field. If this technology delivers on its promises – and all the signs point to that it will – it will very soon be an important regulatory item the medical devices regulation cannot afford to not have seriously considered, especially because adaptation of regulation to new technologies (like nanotech) is one of the important drivers for the new regulation proposal.
The mode of manufacture does not change the definition of ‘custom made’.
It should not, but that’s not how competent authorities see it at the moment.
As Mr Hyde already comments; 3D printing is just a method of manufacturing. Admittedly, “Custom-made devices” require more clear regulations, regardless of how they are manufactured. 3D printing just happens to be very suitable for customization, but can also be used to mass-produce standard devices (e.g. porous spinal cages) which require CE marking. I am always baffled to read that 3D printing is almost always associated with custom-made devices and somehow “3D printed devices” are a device category of their own, whereas CNC-milled devices are not (although custom-made devices can also be milled).
I think the challenge is to regulate custom-made devices appropriately (for example enforce a quality system as you propose) and in parallel validate the 3D printing process (for example by CE marking input material and assessing production quality as you also propose).