As per the requirements of EU MDR, the medical devices being marketed in the EU should have a UDI (Unique Device Identification) system. For those medical devices which are known as “combination products”, the European Medical Association (EMA) has issued draft guidelines. These guidelines cover quality and regulatory requirements required for combination medicinal products and drug-medical device combination products.
Understanding the Dynamics of Medical Devices & Combination Products
What are Combination Products?
Combination products are the products that combine many regulations. A combination product can contain a medical device along with a drug or a drug along with a cosmetic product.
Types of Combination Products with Drugs
There are two main types of medical device combinations with drugs:
- Integral Combination Products and
- Co-packaged Combination Products.
Integral Combination Products
Integral combination products constitute a medicinal item and medical device combined as a unitary integrated medical product. For example transdermal drug supply, pre-filled pens and syringes, and pre-filled inhalers.
Co-packaged Combination Products
In co-packaged combination products, both the medicinal products and device are two distinct units kept inside the same parcel. For example surgical tray with surgical instruments and drug or vaccine vial which is packaged with delivery service.
Is UDI Necessary for Combination Products?
UDI requirements are necessary for those combination products which are the combination of a medical device and medical product. The products which come under this category are regulated by MDCG 2019-2. Their examples include:
- Heparin or antibiotic coated catheters;
- Soft tissue fillers which contain local anaesthetics;
- Bone void filler with an antibiotic;
- Implantable infusion pump;
- Metered-dose inhalers required to be used with spacer devices and
- Bone void fillers which come with animal growth factors; where actions of growth factors provide additional support to physical fillers etc.
In contrast to these, UDI is not mandatory for the combination products that are regulated by Medicinal Directive 2001/83/EC. Devices that fall under this category are:
- Non-reusable auto-injectors which have a medicinal product as their integral part;
- Pre-charged nebulizers containing a specific medicinal product;
- Transdermal patches used for drug delivery;
- Wound dressings that contain an antibiotic; the primary intended use of such wound dressings is the antibiotic administration to wound and
- Those bone void fillers which contain animal growth factors; where actions of growth factors do not provide additional support to the physical fillers.
Roles of EMA & Notified Body as per EU MDR-Article 117
In one of its Question and Answer documents which it released in 2019, EMA identifies a requirement set by Article 117 of EU MDR. This article requires manufacturers and makers of drug-device combination products to get market approval from Notified Bodies.
However, this requirement will only apply to medicinal products that form an integrated product with a medical device, and the primary action of such products is related to the medicinal product.
Article 117 of EU MDR also require that a medical product’s device and medicinal parts must constitute a “Unitary Integral Product.” This product must only be utilized in a drug-device combination. Also, this product should be designed in such a way that it cannot be reused.
Solutions to Major Issues
The Question/Answer document of EMA also provides solutions to some of the major problems being faced regarding medicinal drug-device combination products such as:
1. Notified Bodies & Medicinal Drug-Device Combination Products’ Compliance
- Devices and their Parts with CE Mark
Marketing approval dossiers of medicinal drug-device combination products shall contain results of conformity assessment or CE mark allotted by Notified Bodies.
- Devices and their Parts Devoid of CE Mark
Manufacturers of such parts must provide views from Notified Bodies. These views will concern conformity of such device part against EU MDR’s requirements.
2. Market Approval for New Applicants
Those applicants who are new in the industry and want market approval for their combination products shall either obtain a CE mark or a Declaration of Conformity.
This will help in determining whether the device meets the MDR requirements given in Annexure I or not. An alternate option for such candidates is that they must offer related views from Notified Bodies which proves conformity of their products to rules of Annexure I.
Documentation for Drug-Device Combinations (DDCs)
According to the EMA draft guideline, the documentation for approval of marketing application for DDC shall be anticipated in the quality section of the dossier. These DDCs are those devices that are either:
- Integral to the medicinal product
- Co-packaged with the medicinal product or
- Identified in the medicinal product information and are purchased separately.
Classification of DDCs
According to the EMA guideline, the DDCs are classified as integral and non-integral DDCs. The guideline also contains details about the incorporation of various components and approval for a marketing application.
For Integral DDCs
For an integral DDC, the marketing application shall incorporate proof of compliance of device part with General Safety and Performance Requirements (GSPRs).
According to MDR, any non-integral DDC shall be CE marked.
General Guidelines for Data Submission, Scientific Advice, and Platform Technology:
With the guidelines it has issued regarding data submission, scientific advice, and platform technology, EMA hopes to make transparency and information consistency more prevalent. These factors will be helpful while submitting data to regulatory authorities. The ultimate outcome of these guidelines will be improved work productivity and patient safety.
Alysidia can help in compliance of Combination Products
All those companies, who are facing compliance issues for their combination products specially for UDI and EUDAMED related queries related to EU MDR, can immediately contact Alysidia team for support for various regulatory compliance solutions.