Elizma Parry - director, Global Clinical Practice at Maetrics explains what pharmaceutical manufacturers should be doing to prepare for new and important regulations surrounding medical devices.
Untangling web
Some pharmaceutical manufacturers are simply unaware of their entanglement within the EU Medical Device Regulation (MDR) or EU In Vitro Diagnostic Regulation (IVDR) web. Yet, businesses manufacturing combination products or companion diagnostics will inevitably be affected by the new regulations that are coming into effect in May 2020 and 2022 respectively. With little time on their hands, it is vital that pharmaceutical manufacturers commence the preparatory steps towards compliance now.
As such, some pharmaceutical manufacturers may have assumed exemption from the new regulations that target medical device products. They are, however, mistaken. From here on, pharmaceutical companies will undergo oversight for both the device and medicinal components of their combination products. This represents a big change, given that liaising with a national Competent Authority (CA) was the only thing required of them until recently. Indeed, the EU MDR asks that all medical devices have a CE mark in order to continue circulating on European markets. Under the new EU MDR and EU IVDR, no medical device can evade regulatory scrutiny, regardless of its size or function. Previously immune to such strict requirements, it is understandable that pharmaceutical manufacturers producing combination products or companion diagnostics may not realise the obligation they now have under the new medical device and/or in vitro diagnostic regulations for the European market.
Given this unprecedented change in regulation, pharmaceutical manufacturers are most likely going to be unfamiliar with the process of liaising with a notified body and gathering the clinical data necessary to achieving compliance. If any given business fails to meet the deadline for compliance, their products may effectively be required to be removed from the market, causing unwanted repercussions on market access and company reputation. With such severe consequences at stake, pharmaceutical businesses are advised to take the issue of compliance seriously and get an early start on preparing for the imminent deadlines.
Combination products, which can be composed of any combination of an ancillary drug, a device or biologically active product, will fall under the scope of the EU MDR. Some examples of such products are insulin injector pens and metered dose inhalers, in which the device serves as the delivery system of the integral drug component. This type of combination product, where the medical device has an ancillary function, is currently regulated as a medicinal product under the EU Medicinal Product Directive 2001/83/EC (MPD) but will now also fall under Article 117 of the EU MDR, which serves as an amendment to Annex I of the EU MPD. Their inclusion under the EU MDR regulation stems from the increasing complexity of combination products and the need to regulate ancillary device components with the equivalent scrutiny as stand-alone medical devices.
Lacking the data required to submit a compliant clinical evaluation report, most pharmaceutical companies may need to plan for gathering additional clinical data. This will be costly and timely. It is therefore crucial that manufacturers start sooner rather than later with their initial assessments of what data they are missing. Investing resources in this process can only be beneficial for businesses, helping to ensure a smooth and timely transition as well as facilitating the task of keeping clinical data up-to-date and easily accessible for the future. Manufacturers should be aware that products holding a CE mark under the current Medical Device Directive 93/41/EEC are granted a two years grace period for the completion of this transition – although they will need to be recertified under the EU MDR if any changes are applied to the products in question.
In the same vein, pharmaceutical manufacturers will presumably be reaching out to a notified body for the first time and may not be aware of the current shortage of designated organisations in Europe. Presently, there are only 11 notified bodies available to review technical documentation under the EU MDR. Given these limited resources, it is expected that designated notified bodies will find themselves at over-capacity and delays will most likely ensue. Such circumstances should further prompt manufacturers to submit their documentation as early as possible to make sure they receive their approval under the MDR before the applicable cut-off dates.
Regarding companion diagnostics, these will now fall under the remit of the EU IVDR. Companion diagnostics are IVD devices which help strengthen the safety and efficacy of a medicinal product by assessing which patients would most benefit from treatment, and which may experience adverse effects from it. The IVDR has established a new risk-based classification, where Class A is the lowest risk and Class D, the highest. Falling under Class C, companion diagnostics will be subject to a high level of clinical requirements and scrutiny from notified bodies. The IVDR sphere is worst affected by the notified body shortage, as there is currently no designated notified body to review documentation. Manufacturers should be smart about this. It is encouraged that manufacturers begin to investigate, and approach notified bodies awaiting designation from their national competent authority for their specific product area in order to secure a place in line.
Companies solely manufacturing medical devices may be aware of what the EU MDR and IVDR entail, but pharmaceutical manufacturers producing products that contain an ancillary device component may not be so fortunate. Considering the EU MDR and IVDR’s stricter regulatory requirements for combination products and companion diagnostics, in comparison to the current directives, pharmaceutical manufacturers will find themselves equally affected as medical device companies. On the other hand, pharmaceutical companies will be treading into unchartered waters when collating the necessary documentation and liaising with a notified body and should therefore allow for extra time to do so. Companies must give the compliance process its due importance or be prepared to deal with the negative outcomes of non-compliance.