In the world of healthcare, many patients benefit from the use of combination products – medical devices that incorporate pharmaceuticals or biologics. These innovative products have the potential to revolutionize patient care by providing integrated solutions for complex medical conditions. To regulate and ensure the safety and efficacy of combination products, the European Union Medical Device Regulation (EU MDR) includes Article 117, which outlines specific requirements for these unique medical innovations. In this article, we'll delve into the details of Article 117 and its significance in the world of combination products.
What Are Combination Products?
Combination products, as defined by the U.S. Food and Drug Administration (FDA), are therapeutic and diagnostic products that combine drugs, devices, and/or biological products. In the context of EU MDR, combination products primarily involve medical devices combined with pharmaceuticals or biologics. These products are designed to treat, diagnose, or prevent a variety of medical conditions.
Types of Combination Products
Before delving into Article 117, it's crucial to understand what combination products are. According to the European Medicines Agency (EMA), combination products can take various forms:
Integral Component: In some cases, the medical device is an integral part of the medicinal product. Think of pre-filled syringes or auto-injectors that are inseparable from the drug they deliver.
Co-Packaged: In other instances, the device and medicinal product are packaged together but remain distinct entities.
Referenced Products: Here, the medicinal product's information references a specific medical device to be used alongside it, but the device is obtained separately by the user.
Defining Primary Mode of Action (PMOA)
Before we dive into the intricacies of Article 117, let's start by understanding the concept of Primary Mode of Action (PMOA). The PMOA is the primary function or purpose of a combination product. It determines which regulatory route the product should follow.
Identify the Regulatory Route
The regulatory route your combination product takes depends on its PMOA:
Medical Device-Driven Combination Product:
Regulated under EU MDR: If the device component is the primary mode of action, it falls under the scope of the European Union Medical Device Regulation (EU MDR).
Conformity Assessment through Notified Body (NB): Manufacturers must undergo a conformity assessment, often involving consultations with European Medicines Agency (EMA) and Competent Authorities.
CE Marking: Once the conformity assessment is successful, the device receives CE marking.
Place in EU Market: The product can then be placed in the EU market, complying with medical device regulations.
Drug-Driven Combination Product:
Governed by Directive 2002/83/EC or Regulation (EC) No 726/2004: If the medicinal product is the primary mode of action, it is regulated as a medicinal product under the relevant directive or regulation.
Article 117 of EU MDR
Article 117 of EU MDR addresses the regulatory framework for combination products and is a significant development in the European regulatory landscape. It clarifies that medicinal products incorporated into a device, which have an action ancillary to that of the device, are subject to the provisions of the EU Regulation on Medicinal Products for Human Use. This means that the evaluation and authorization of the medicinal component of combination products fall under the domain of the European Medicines Agency (EMA).
If the device component of a combination product is integral, non-reusable, and the primary mode of action is attributed to the medicinal product. In such cases, manufacturers must:
Seek a Notified Body Opinion (NBOp): Manufacturers placing drug-device combination products on the market as an integral device and marketing them as a "medicinal product" must obtain an NBOp. This opinion confirms the device's compliance with the relevant General Safety and Performance Requirements (GSPR).
Examples of Products Requiring NBOp:
The device information must be included in the Market Authorization Application (MAA).
For co-packaged products, only CE-marked devices can be used, and device data should be included in the MAA. Referenced products typically involve general group devices or specific devices used alongside the medicinal product.
Significance of Article 117
Article 117 plays a crucial role in ensuring the safety, efficacy, and quality of combination products in the European market. Here's why it's significant:
Primary Mode of Action: Article 117 distinguishes between the primary mode of action of a product. If the primary mode of action of a product is achieved through the device component, the product will be regulated as a medical device under EU MDR.
If the primary mode of action is attributed to the medicinal component, it will be regulated as a medicinal product under the EU Regulation on Medicinal Products for Human Use.
Clear Regulatory Path: Article 117 provides a clear regulatory path for combination products, ensuring that each component is evaluated by the appropriate regulatory authority. This helps avoid regulatory ambiguity and streamlines the approval process.
Patient Safety: By subjecting combination products to rigorous evaluation by both device and medicinal product regulators, Article 117 enhances patient safety. It ensures that these complex products meet the highest standards of quality and performance.
Innovation: Regulatory clarity promotes innovation by providing manufacturers with a predictable and transparent framework for bringing combination products to market. This encourages the development of new and groundbreaking therapies.
Harmonization: Article 117 aligns EU regulations with international standards for combination products, contributing to global harmonization and facilitating access to international markets.
Collaboration between Competent Authorities: Article 117 emphasizes the importance of collaboration between Competent Authorities in the assessment and authorization of combination products. This collaboration ensures that both the device and medicinal components are evaluated comprehensively and in alignment with their respective regulations.
Former Regulatory Framework for CE Marking Combination Products
Before the implementation of EU MDR, combination products had a regulatory framework defined under the Medicinal Product Directive (MPD). This directive mandated evidence of CE marking for these products but did not specify requirements for non-CE marked devices. Essentially, if the device and medicinal product formed a single integral product that was not reusable and where the primary mode of action was attributed to the medicinal product, it fell under the MPD's jurisdiction.
The EU MDR System for CE Marking Combination Products – Article 117
With the introduction of EU MDR, Article 117 significantly impacts the regulation of combination products. It states that manufacturers of drug-device combination products must adhere to MDR regulatory requirements. Specifically, if the device component is integral, non-reusable, and the primary mode of action is attributed to the medicinal product, compliance with the General Safety and Performance Requirements (GSPRs) of MDR Annex I is mandatory.
Role of Notified Bodies (NBs)
For manufacturers of combination products, Article 117 introduces the role of Notified Bodies (NBs) in assessing the safety and performance of device components. Depending on the classification of the device, manufacturers may need to obtain either a CE certificate or seek a Notified Body Opinion (NBOp). The NBOp confirms whether the device complies with relevant GSPRs and is included in the Market Authorization Application (MAA).
Next Steps for Manufacturers
Manufacturers of combination products should take the following steps to implement Article 117:
Identify a Suitable NB: Find an NB designated for your specific technology under EU MDR.
Assess GSPRs: Determine which GSPRs are applicable to your products.
Obtain Scientific Data: Gather scientific data demonstrating conformity to applicable GSPRs.
Prepare Technical Documents: Assemble technical documentation to support the
Article 117 of EU MDR is a significant milestone in the regulation of combination products in the European Union. It offers a clear and structured approach to ensure that these innovative medical solutions meet the highest standards of safety and efficacy. As the regulatory landscape evolves, manufacturers of combination products must stay informed and work collaboratively with regulatory authorities to bring these life-changing therapies to patients in need.
Take Action Today!
Are you a manufacturer or stakeholder involved in combination products under EU MDR? It's crucial to understand and comply with Article 117 to navigate the regulatory landscape effectively. Stay informed, collaborate with regulatory authorities, and ensure your innovative medical solutions meet the highest standards of safety and efficacy.
If you have questions or need assistance with compliance, contact us today to guide you through the complexities of Article 117 and help you bring your combination products to market successfully. Your commitment to patient safety and regulatory compliance is key to the future of healthcare innovation.
Don't wait; act now to make a difference in the world of combination products!