Combination products, which combine drugs and devices into a single entity play an important role in enhancing healthcare solutions. However, their unique nature presents regulatory challenges, particularly in classification and compliance. The primary obstacle is determining the primary mode of action (PMOA), which dictates whether a product adheres to drug or device regulations.
Regulatory requirements can differ significantly between regions, such as the FDA in the U.S. and the EU MDR. Developing a clear regulatory strategy that addresses these differences is crucial for maintaining compliance and avoiding costly setbacks. For those seeking assistance in navigating these complexities, Drug Device Combination Product Consulting offers expert guidance on managing regulatory pathways confidently.
Staying updated on regulatory changes is also essential. The Medical Devices Industry Regulatory Updates from October 2024 provide timely insights to help align product development with evolving standards.
Understanding Combination Products
Combination products merge elements from both drugs and devices into a single unit. They offer unique advantages, such as targeted therapy delivery and enhanced patient convenience. However, their hybrid nature complicates regulatory oversight. To effectively manage these complexities, it's important to understand what combination products are and how regulatory bodies classify them based on their core function.
Definition and Examples of Combination Products
A combination product consists of two or more regulated components, typically a drug and a medical device, that work together. These components can be combined physically, co-packaged, or linked by labeling, and they interact to create a combined therapeutic effect.
Common examples include:
Each of these examples illustrates how drug and device functions merge to improve treatment outcomes and ease of use.
Combination products are classified into integral, where the components are physically, chemically, or otherwise combined, and non-integral, where the components maintain separate identities.
| Type of combination | Illustration | Conformity assessment of device |
|---|---|---|
| Integral | ||
| Co-packaged or obtained separately |
Please refer to : Medical devices | European Medicines Agency (EMA)
Please refer to : MDCG 2022 – 5 Rev. 1 Guidance on borderline between medical devices and medicinal products under Regulation (EU) 2017/745 on medical devices October 2024
Regulatory Classification of Combination Products
The classification of combination products is based on their primary mode of action (PMOA), which is the main function providing the intended therapeutic effect. Regulatory authorities like the FDA and EU MDR utilize this principle to determine which set of rules applies - either drug or device regulations.
Three common scenarios include:
The challenge arises in borderline cases where the contributions of the drug and device are closely intertwined. For instance, drug-eluting stents involve a device structure delivering a drug, but the regulatory pathway often relies on which effect is dominant.
Regulatory bodies may require collaboration between drug and device centers or specific opinions, such as the Notified Body Opinion under MDR, to clarify classification in the EU. The FDA’s Office of Combination Products provides guidance and assigns lead reviewers to ensure consistent enforcement.
Understanding this classification is crucial as it influences compliance requirements, submission types, and testing protocols. Companies should create a regulatory strategy tailored to the PMOA and jurisdiction-specific rules to avoid costly delays.
For more information on regulatory pathways and maintaining compliance, Global Medical Device Registration offers detailed support for various markets. Additionally, keeping abreast of the latest rule changes through resources like the Medical Devices Industry Regulatory Updates from April 2025 can help anticipate shifts in classification approaches.
This foundational understanding of combination products sets the stage for developing an effective regulatory strategy. Next, we will explore how to address the challenges in defining the primary mode of action and the differences between FDA and EU approaches.
Challenges in Defining the Primary Mode of Action
Defining the primary mode of action (PMOA) is central to any regulatory strategy for combination products. This step determines the regulatory framework governing the product and shapes submission requirements, testing protocols, and compliance pathways. However, the process is often complex, as the blend of drug and device elements can lead to overlapping functionalities, making it challenging to identify a dominant therapeutic effect. This section highlights the significance of PMOA and discusses common challenges, along with practical strategies to overcome them
Importance of Primary Mode of Action
The PMOA is the dominant therapeutic effect through which a combination product fulfils its intended purpose.
Common Challenges and Solutions
Challenges in defining the PMOA stem from the overlapping functionalities of combination products, where both drug and device components significantly contribute. Some common scenarios include:
Addressing these challenges requires a strategic approach:
Reference:
https://eur-lex.europa.eu/eli/reg/2017/745/oj
https://www.fda.gov/combination-products
Please refer to : Harmonized Notified Body Opinion Template for Drug-Device Combination Products under EU MDR Article 117
Team NB position paper on Template for NBOp_V4
When submitting a drug-device combination product for market authorization, and the device component lacks CE marking or a valid EU Declaration of Conformity, the manufacturer is required to obtain a Notified Body Opinion. This opinion serves to confirm that the device component complies with the applicable requirements of the EU Medical Device Regulation (MDR).
Examples of such products include:
Final Thought
By proactively addressing these challenges with a well-supported regulatory strategy, companies can minimize the risk of review delays. For those looking to market combination products efficiently, understanding PMOA nuances and effectively demonstrating it is essential.
For additional insights on medical device regulations and compliance requirements, the Latest Medical Devices Compliance Updates newsletter offers timely information that can support your regulatory preparations.
This foundational understanding of PMOA allows for confident submission planning, whether under FDA rules or the EU MDR framework, each of which treats combination products slightly differently regarding classification and compliance. Grasping these nuances early in the process can facilitate a smoother path to approval and market access.
Need Further Guidance?
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