Combination Products in EU
As we all know, the US FDA handles Combination products according to their Primary Mode of Action (PMOA). For example, If the device PMOA is through chemical interaction, its approval process is handled through Center of Drug Evaluation and Research (CDER). In EU, the term combination product does not exist. Products are either considered a Medical Device or a Medicinal Product. Notified bodies usually face challenges when reviewing technical dossiers for combination products because they do not have a specific guideline to follow when reviewing these kinds of products. One example that I have seen notified bodies struggle with is prefilled syringes. These are considered combination products according to the FDA, but they are considered as just Medical Devices according to MDD.
Do you have experience with filing Combination products in EU? what is the major hurdles that you anticipate facing when filing for approval in EU?
I do not have experience with filing for combination products within the EU but I believe what helps in distinguishing if your product falls under the MDD 93/42/EEC or the MDP 2001/83/EEC is to choose a Notified Body with the experience in assessing combination products. Also if you are a company from outisde the EU, help can also be provided by choosing an Authorized Representative that is competent in dealing with combination products as they will be a point of contact with the competent authorities and notified body.
I personally do not have any experience working in any industry. But from my understanding, I would imagine the company I work for would have either fall under FDA or EU. So under EU, the notified bodies will be filing the paperwork as they are experts and actually have power to inspect manufactures and audit the devices. They will be the best source of filing paper work for combination products. It would be unreasonable to rely on a single person to file paperwork for combination product without an expert's opinion on classifying the product.
Great question, Fady!
I have some experience with filing combination drug product in the EU. One instance, in particular, that comes to mind is a topical gel for scarring that was accompanied by a massaging applicator. The purpose of the applicator was to penetrate the scar tissue with the gel in order to achieve the greatest effect to minimize scarring. It was difficult to choose a directive because it fell into two categories: a class one, non-sterile device and a gel with active product. Since the applicator was not the primary mode of action, it could not be filed as a medical device.
I do not have any experience, but I found an article about the regulatory pathways of drug-device and device-drug combination products on the EU from the NSF. In the key points, they clearly state that it is critical to understand the main mode of action of the product since that will determine whether it will be regulated as a medical device or as a medicinal product in the EU. If it is a Drug-Device Combination, then medicinal product has the primary mode of action and the design dossier is evaluated by the European Medicines Agency (EMA) which is an expensive regulatory process. If it is a device-drug combination the main authority is the Notified Body and they are usually classifies as class III MD, if the device-drug combination involves blood then EMA consultation is mandatory and if unfavorable opinion is given by EMA to the notified body, then the notified body cannot issue a CE mark. There is more information that can be useful so the link for this document is: http://www.nsf.org/newsroom_pdf/md_regulatory_pathways_j31.pdf
I do not have experience with filing combination products in the EU. However, in my opinion, it seems like a major hurdle would be choosing a Notified Body that is capable of evaluating combination products and completing paperwork associated with the conformity of the product before being placed on the market. The evaluation by a Notified Body of combination products needs to include an opinion of a competent authority. The regulatory review and approval process for combination products is certainly complex because it can take several months to achieve.
This is an interesting article. It also points out that a medical device is actually faster and less expensive than a medicinal product. But if the combination product has both a medical device and a medicinal component, that it is automatically considered a high risk and the notified body along with the competent authority evaluate the safety, quality, and usefulness the drug portion. Lastly, a key component that the EU will enforce more strictly any new regulations created while keeping the existing ones set in place since they are currently in use. Would this mean that the EU has the potential to be as highly regulated as the FDA and if not stricter?
Hey so what did you end up filing it as? This is interesting as I didn't know you chose the notified body unless you work in regulatory then that makes sense. Even still I believe there are checklist involved and guidance to see where your product fits best, no?
Although, I personally have never dealt with the European Union regulations for medical devices, from what I understand medical devices adhere to three directives: the active implantable medical device directive, medical device directive and in vitro diagnostic device directive. But as Fady mentioned earlier, notified bodies review devices, but do not set a guideline for the reviewing of these products.
i dont have experience with this, and since a lot of student have answer i want to add some information about the Authorisation procedure. it said that the Full copies of the marketing authorisation application file are sent to a rapporteur and a co-rapporteur designated by the competent EMA scientific committee. They co-ordinate the EMA's assessment of the medicinal product and prepare draft reports.
Once the draft reports are prepared (other experts might be called upon for this purpose), they are sent to the CHMP or CVMP, whose comments or objections are communicated to the applicant. The rapporteur is therefore the privileged interlocutor of the applicant and continues to play this role, even after the marketing authorisation has been granted.
As mentioned be other fellow commentators, combinational medical device are much difficult to classify for those in the Notified Bodies, this is because according to the directives, the device would fall under either of the three categories, MDD, IVDD, and AIMDD. I currently do not have experience with comdinational medical devices but from what i have read and researched is that such device must first be investigated and identified what is the main objective of the product and how it is used. For example, for products such as a syringe with pre-filled solution such as collagen infused with antibiotics for 3D printing, the medical product would essentially be the collagen infused with antibiotics. The syringe and the printer would be in a way considered accessories.
I do not personally have experience with getting combination devices approved in the EU, but I did some research on this topic and I found an interesting article explaining that the EMA is considering developing a new guideline on quality requirements for combination products. In the EU, CE marked medical devices are provided separately but may be co-packaged with the medicinal product, and the assessment performed by the notified body may not fully take into account the characteristics of the specific medicinal product that the device is to be used with. The proposed guidelines would show that the combination has been appropriately designed and controlled and can be used correctly in the intended clinical situations.
I agree with opinions stated above. I believe the major challenge facing medical device regulators as well as manufacturer comes down to differentiating between combination devices that are primarily devices and those that are medicinal. This will even get harders with the adoption of new technologies such as bioelectronics because they could both diagnose and treat diseases and/or in combiation with other pharmaceutical components. Similar to what @srg36 has found, I also found the news about a new regulation being referenced in many different posts/journals to create consistency and uniformity in the assessment of medical devices. To me, it doesn't seem like they want to create a product "filter type", instead focus on the quality requirement of "Drug-Device-Combination".
This is the link to the concept paper by EMA http://europa.eu/rapid/press-release_MEMO-17-848_en
Absolutely. The revisions that have taken place under the Medical Device Directives are meant to be on par or if not more stringent then the US FDA. Notified bodies showing up unannounced and greater scrutiny, which wasn't existent at this level before, is forcing companies to take higher consideration into introducing their products to market whether its combination product or not.