DRUG-DEVICE COMBINATION PRODUCTS UNDER THE EU LEGAL FRAMEWORK

Step 1: Pre-Evaluation

Defining the Right Regulatory Path: Classifying Your Drug-Device Combination Product

The first and most crucial step in the regulatory pathway is determining the correct classification of your product—whether it qualifies as an integral drug-device combination (iDDC), a co-packaged product, or both. Ideally, this decision should be made early in development and double-checked again for accuracy, as it defines the applicable regulatory route: either the EU Medical Device Regulation (MDR 2017/745) or Directive 2001/83/EC for medicinal products.

In the section that follows, we'll explore key aspects of this classification, including:

• Differentiating between iDDCs and co-packaged products
• Verifying the need for a CE mark
• Understanding the role of Notified Bodies (NBs) in the approval process

These foundational elements are essential for a smooth and compliant development pathway.

iDDC or Co-Packaged: Determining the Right Classification

The EU regulatory framework for drug-device combination products follows a hierarchical approach, making early classification essential for compliance. Below are key distinctions:

• Integral Drug-Device Combinations (iDDC): These are single, combined products—such as pre-filled syringes—where the drug and device are physically integrated and not reusable. Governed primarily by Directive 2001/83/EC, the device component must meet relevant MDR safety and performance requirements.
• Co-Packaged Products: These involve a drug and a device supplied together but as separate items (e.g., a vial of insulin with a reusable injection pen). Such products fall under both the medicinal product and medical device regulations.

Note:

• Pure medical devices (e.g., empty syringes, wound dressings) are not covered here.
• Medical devices with an ancillary medicinal substance (e.g., a heparin-coated catheter) are also outside the scope of this section, though they represent a core area of our expertise.

Borderline cases can present challenges. The MDCG 2022-5 guidance provides clarity by outlining criteria related to physical integration, exclusive use with a specific drug, and reusability.

To support your regulatory strategy, the following decision tree offers step-by-step guidance in identifying the correct classification and regulatory pathway for your combination product.

CE Mark and Notified Body Involvement: Key Steps in the Regulatory Assessment

Once the classification of your combination product is determined, the next step is verifying the regulatory status of the medical device component—particularly its CE marking and the involvement of a Notified Body (NB).

CE Mark Verification

Start by evaluating whether the device component already holds a valid CE mark under the Medical Device Regulation (MDR). It's essential to ensure that its intended purpose aligns with the therapeutic or medical function of the combination product.

• CE-marked and compatible: If alignment is confirmed, proceed confidently to the next step in the regulatory pathway.
• No CE mark or not compatible:
  - For co-packaged products, identify a suitable alternative that meets MDR requirements.
  - For iDDCs, classify the device component per MDR Annex VIII rules as it would be a standalone medical device.

Notified Body (NB) Involvement

The need for NB involvement depends on the device classification, which is determined based on factors such as the intended use, invasiveness, duration of contact, and the potential risk to users or patients—defined in detail in MDR Annex VIII.

• Class I devices (e.g., non-sterile syringes without measurement markings) typically do not require NB review.
• Higher-risk classes (Is, Im, IIa, IIb, III)—including sterile prefilled syringes or syringes with graduation—do require the involvement of a Notified Body seeking for Notified Body opinion (NBOp).

Understanding and fulfilling these requirements early in development ensures smoother regulatory progress and helps avoid costly delays.

Key Considerations for EU Regulatory Compliance of Drug-Device Combination Products

Successfully navigating the EU regulatory pathway for drug-device combination products requires a clear understanding of classification rules, applicable legislation, and the involvement of regulatory bodies.

Integrated vs. Co-Packaged: Choosing the Right Framework

• Integral Drug-Device Combinations (iDDCs) require a single marketing authorization under medicinal product legislation (Directive 2001/83/EC). However, the device component must comply to the applicable general safety & performance requirements (GSPRs) of Annex I MDR 2017/745.
• Co-packaged products, where the drug and device are supplied together but not physically integrated, are subject to dual regulatory frameworks, applying both medicinal and medical device requirements.

Device Classification: Why It Matters

The classification of the device component is critical and depends on: intended use, sterility, and functional features (e.g., presence of graduation markings).

For example, a prefilled syringe containing a medicinal product is considered an iDDC and regulated primarily as a medicinal product. However, its device component (the syringe) must still comply with MDR. If it is sterile or includes graduations, Notified Body (NB) involvement is mandatory.

Essential References:

• MDR 2017/745
• EMA Guideline www.ema.europa.eu/en/quality-documentation-medicinal-products-when-used-medical-device-scientific-guideline
• EMA FAQ DDC www.ema.europa.eu/en/documents/regulatory-procedural-guideline/...
• MDCG 2021-24 www.health.ec.europa.eu/system/files/2021-10/mdcg_2021-24_en_0.pdf
• MDCG 2022-5 www.health.ec.europa.eu/document/download/...mdcg_2022-5_en.pdf

Step 2: Data Creation & Documentation

From top to bottom the tasks of step 2 and the substeps 2.1 and 2.2 are evaluated separately for the following products:
1. iDDC with and without NB
2. iDDC with CE-marked device component
3. Co-packed/ referenced

iDDC with and without NB

Step 2.1
Objective: For the iDDCs with and without a NB compliance to the applicable GSPRs, Annex I, MDR is to be demonstrated.

The GSPRs – the General Safety & Performance requirements are a set of requirements covering the whole range of medical devices. Annex I is divided into three main chapters:

• Chapter I general requirements
• Chapter II requirements regarding design and manufacture
• Chapter III requirements regarding the information supplied with the device

Table 1 GSPR overview

CHAPTER I GENERAL REQUIREMENTS	CHAPTER II REQUIREMENTS REGARDING DESIGN AND MANUFACTURE	CHAPTER III REQUIREMENTS REGARDING THE INFORMATION SUPPLIED WITH THE DEVICE
1 Safe; perform as intended	10 Chemical, physical and biological properties	23 Label and instructions for use
2 Risk reduction, risk-benefit ratio	11 Infection and microbial contamination
3 Risk Management System	12 Devices incorporating a substance considered to be a medicinal product
4 Risk control measures	13 Devices incorporating materials of biological origin
5 Eliminating & reducing risks related to use error	14 Construction of devices and interaction with their environment
6 Lifetime	15 Devices with a diagnostic or measuring function
7 Transport & Storage	16 Protection against radiation
8 Minimising foreseeable risks, and any undesirable side-effects	17 Electronic programmable systems
9 Devices without a medical purpose	18 Active devices and devices connected to them
	19 Particular requirements for active implantable devices
	20 Protection against mechanical and thermal risks
	21 Protection against the risks posed to the patient or user by devices supplying energy or substances
	22 Protection against the risks posed by medical devices intended by the manufacturer for use by lay persons

Documenting the tasks in a tabulated form results in the so-called GSPR Checklist (see annex II MDR, 4), see example below.

In line with the latest EMA Q&A, the outcome of this assessment must be a conclusion of full compliance with all relevant GSPRs for the intended purpose of the device component used in the iDDC. Partial compliance conclusions or opinions that leave relevant GSPRs unaddressed are no longer acceptable. This applies both to Notified Body Opinions (NBOp) and, for eligible class I devices, to MAH GSPR compliance statements, which must clearly list the applicable GSPRs and confirm full conformity.

EMA FAQ: https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/...

Step 2.2
While Annex I defines the WHAT (safety and performance requirements), Annex II specifies the HOW (documentation structure and data organization), detailing the technical documentation requirements necessary to demonstrate compliance to the applicable GSPRs.

For non‑sterile, non‑measuring, non‑reusable class I devices, the EMA Q&A allows the MAH to provide a MAH's statement of compliance with the relevant GSPRs of MDR Annex I as an alternative, where a Declaration of Conformity is not available.

Table 2 Summary of Annex II MDR

CH.	Description	Main Content	Key Points/Examples
1	Device description and specification, including variants and accessories	- General description - Intended purpose and users - Risk class and justification - Principles of operation - Novel features - Accessories and variants - Reference to previous generations	- General description - Intended purpose and users - Risk class and justification - Principles of operation - Novel features
2	Information supplied by the manufacturer	- Labels - Instructions for Use (IFU) - Other information	- All labeling and IFU as supplied to users
3	Design and manufacturing information	- Design and manufacturing processes - Manufacturing environment controls - Suppliers and subcontractors	- Design drawings - Manufacturing process details - List of critical suppliers
4	General safety and performance requirements	- Evidence of conformity with GSPRs (Annex I) - Declaration of conformity - Applicable standards	- How the device meets safety/performance requirements - Applied harmonized standards
5	Risk management	- Benefit-risk analysis - Risk management process and results - Compliance with ISO 14971	Risk Management file including Plan, report, analysis
6	Product verification and validation	- Pre-clinical and clinical data - Biocompatibility, electrical safety, software validation - Sterilization, stability, packaging	Test reports/test summaries; Biocompatibility plan & report, clinical evaluation, transport, packaging, sterilization…

Why is that information about Annex II, I helpful?
Some examples from Module 3.2.:

P.2 Pharmaceutical Development
This section of the dossier should summarise the information relevant to development of the specific medical device (part) integrated into the medicinal product, including the rationale for its selection in the specific sections of 3.2.P.2.

P.3.5 Process validation and/or evaluation
Process validation for the integral medicinal product manufacturing process should be performed, as appropriate, in line with relevant European guidelines, including the assembly and sterilisation of the device (part) (if applicable) and any filling steps.

P.8 Stability
Stability studies for the integral medicinal product (or variant, where justified) should include functionality tests determined as stability-indicating CQAs for the medicinal product (refer to P.2.4).

Table 3 Correlation between Annex II, I, & EMA guideline (excerpt)

Annex II MDR sections	Annex I MDR	Dossier / CTD
3 Summary of development 3a) information to allow the design stages applied to the device to be understood;	1 "… devices shall be designed & manufactured…" See also, e.g. 7, 10	3.2.P.2 This section of the dossier should summarise the information relevant to development of the specific medical device (part) integrated into the medicinal product,
3 Process verification & validation ("3b (…) complete information and specifications, including the manufacturing processes and their validation")	e.g. 1, 7, 10	3.2.P.3.5
6 Stability testing ("detailed information regarding test design, complete test or study protocols (…) for stability, including shelf life;"	6, 11.3, 11.4	3.2.P.8

Even if it is considered as a single integral product, it will be unavoidable to divide the data in principle into three buckets, as these are used for different purposes.

• Part 1 and 2 for the Notified Body Opinion (NBOp) or the MAHs declaration of conformity.
• The MAHs declaration of conformity or NBOp plus bucket 3 and 2 for approval by the authorities.

Redundancies cannot be avoided, but can be reduced through a clever structure, which ultimately can also simplify data maintenance.

iDDC with CE-marked device component

Step 2.1
Objective: Demonstrate compatibility and reconfirm the suitability of the device for use with the drug.

Data Assessment/Creation Steps:

1. Reconfirm the scope of the CE-marked device for the combination product, including its intended use (indications, limitations), manufacturing processes, assembly requirements, and other relevant parameters.
2. Evaluate existing data to determine its adequacy in addressing the requirements outlined in the EMA Guideline.
3. Address potential gaps: While the CE mark provides a presumption of conformity with relevant requirements, additional data may still be necessary to fully demonstrate compliance with the GSPRs for the particular combination.

Step 2.2
Objective: Drug-device compatibility data

1. Include a valid CE certificate or Declaration of Conformity (DoC) for the device to demonstrate compliance with applicable GSPRs.
2. Embed evidence documentation (e.g., supplier data, internal test reports, risk assessments) in the dossier to confirm compatibility between the device and medicinal product.
3. Structure the data in line with CTD requirements provided in the EMA guideline

Key Considerations:

• Supplier Data: If relying on supplier-provided evidence (e.g., biocompatibility, sterilization validation), ensure it is traceable and referenced in the dossier.
• Own Data: Include in-house compatibility studies (e.g., leachables/extractables, dose accuracy) to address gaps not covered by the CE mark or supplier documentation.
• Risk Assessment: Align with ICH Q9/ISO 14971 principles to justify compatibility and mitigate interaction risks.

Co-packed/referenced

Step 2.1
Target: Demonstration of compatibility of the device with the drug.

Data Assessment/Creation:

• Request and assess device supplier data, including the CE certificate, scope of certification, and additional documentation such as the Instructions for Use (IFU) and any other relevant technical or regulatory documents.
  
  Avoid assuming device manufacturer obligations under MDR Article 16 by ensuring:
  - The device's intended use remains unchanged.
  - No modifications are made to the device that could void its CE mark
• Follow EMA Guideline requirements to ensure alignment with regulatory expectations for a co packed/ referenced product

Step 2.2
Target: Drug-device compatibility data.

• Include a valid CE certificate or Declaration of Conformity (DoC) for the device to confirm compliance with applicable regulations.
• Embed evidence documentation (e.g., supplier-provided data, internal test reports, risk assessments) within the dossier to substantiate compatibility and safety of the device-drug combination.

Key Considerations

1. Regulatory Compliance and CE Marking

• CE Mark Validity: Ensure the co-packaged device has a valid CE mark under MDR. Verify the device's intended use aligns with its original certification when paired with the medicinal product
• MDR Transition Challenges: If the device is transitioning from MDD to MDR, confirm the manufacturer's compliance timeline to avoid market disruptions
• Unique Device Identification (UDI): Include the device's UDI in documentation (if applicable) and ensure traceability

2. Documentation and Dossier Integration

• EMA Guidelines: Follow EMA's quality documentation requirements for co-packaged products, focusing on:
  - Container Closure System (Module 3.2.P.7): Detail device specifications, sterility, and compatibility with the drug
  - Pharmaceutical Development (Module 3.2.P.2): Describe how the device impacts drug safety, efficacy, and usability (e.g., dosing accuracy)
  - Stability Data: Provide in-use stability data if the device affects drug integrity
• Supplier Agreements: Secure contracts ensuring the device manufacturer remains responsible for MDR compliance (e.g., post-market surveillance)

Summary
Depending of the product, the following should be available:

	iDDC with NB	iDDC without NB	iDDC with CE marked device	Co-packed/ referenced
Deliverable	GSPR Checklist Technical documentation acc. Annex II CTD	GSPR Checklist Technical documentation acc. Annex II MAH's statement of compliance with the relevant GSPRs of the MDR Annex I (only for class I devices) CTD	GSPR Checklist (part of CE certificate/ Declaration of conformity for the device component, in a best case scenario) Suitability & compatibility data for the device component CE certificate/ Declaration of conformity for the device component CTD	Suitability & compatibility data for the device component CE certificate/ Declaration of conformity for the device component CTD
Next step	NBOp	Authority approval

Step 3: NBOp Process and Approval

NBOp Process

For the iDDC requiring an Notified Body, Art 117 MDR mandates that manufacturer of the drug product (Marketing Authorization holder – MAH) must obtain a Notified Body Opinion (NBOp) on the device component before submitting their Marketing Authorization Application (MAA) to the competent authority, such as the European Medicines Agency (EMA). The NBOp process is not a certification or CE marking procedure; rather, the Notified Body conducts an independent assessment of the provided data demonstrating compliance to the applicable GSPRs. After this review, the Notified Body issues a Notified Body Opinion report, which must be included in the MAA.

The EMA Q&A now makes clear that the NBOp must confirm full compliance with the relevant GSPRs for the device component as used in the specific iDDC, including its intended purpose, user population and use setting. Opinions that only conclude on partial GSPR compliance or explicitly exclude relevant GSPRs are not acceptable to the medicines authorities.

The steps leading up to the submission may include the following:

a) Identifying a suitable Notified Body;
b) Submitting an application to the selected Notified Body;
c) Receiving and approving a quotation;
d) Planning the submission process.

Identification of a NB (if not done yet)

The identification and selection of the Notified Body is the responsibility of the Marketing Authorization Holder (MAH). You can find a complete and regularly updated list of all Notified Bodies in the EU on the NANDO (New Approach Notified and Designated Organisations) website maintained by the European Commission. Art 117 is not in scope of each notified body – early engagement is highly advisable.

NBOp Application

Each Notified Body does have a more or less similar application process – completion of forms by the MAH or representative followed by an offer related to the requested services.

Prior proceeding with the next step, it is highly recommended engaging with your NB early and aligning on expectations, if not yet done, like submission format, timelines, etc.

Submission & Evaluation

The specific details on what data to provide and how to structure it are outlined in Step 2 ("Data Creation & Documentation").

The Notified Body (NB) conducts its review and may issue questions or requests for clarification. If, after three rounds of questions, unresolved gaps remain, the procedure is concluded with a negative outcome. Conversely, if all questions are satisfactorily addressed, the NB issues a positive NBOp report to the applicant.

Timelines (might vary due to complexity/ resources etc.):
- From identification to submission: 1-3m
- Submission to NBOp report: 3-6m

For the other combination product types:

• iDDC without need for a NBOp
• iDDC with an already CE marked device
• Co-packed/ referenced (presuming the device is already CE marked)

There's no need for an additional review by a Notified body. The data relevant to the device component is to be provided with the submission to the authorities, see step 2 for further details.

When and Why?

• Products approved prior to the date of application (DoA) of the MDR (26 May 2021) are not re‑opened solely because of Article 117. However, as soon as there is a major change to the device part that may significantly affect the safety, performance or intended use of the device, or when a new device/device part is added or replaces the existing one, a new or updated EU Declaration of Conformity, EU certificate or NBOp/MAH GSPR statement in line with MDR and Article 117 must be submitted within the appropriate post‑authorisation procedure.
• New marketing authorisations submitted on or after the MDR DoA must comply with Article 117 at the time of MAA submission (see MDR, EMA Guideline & FAQ).

Approval New Drug-device Combination Product

Legal basis of an EU MAA
Marketing Authorisation Applications (MAA) in the EU/EEA are submitted in accordance with the relevant legal basis specified in Directive 2001/83/EC, as amended:

• Article 8.3 – "full" application supported by full clinical, non-clinical and quality documentation;
• Article 10(a) – "well established use" application;
• Article 10(b) – "fixed combination" application;
• Article 10(c) – "informed consent" application;
• Article 10.1 – "generic" application;
• Article 10.3 – "hybrid" application;
• Article 10.4 – "biosimilar" application.

Regulatory Procedures
Within the EU/EEA there are four regulatory procedures for MAA:

• Centralised Procedure (CP) – a single marketing authorisation granted in all EU/EAA countries at the same time;
• Mutual-Recognition Procedure (MRP) – a marketing authorisation granted in one EU/EEA Member State can be recognised in other EU countries;
• Decentralised Procedure (DP) – a medicine not yet authorised in the EU can be simultaneously authorised in several EU/EEA Member States;
• National Procedure (NP) – a marketing authorisation granted in one EU/EEA Member State.

Key Determinants of the Regulatory Roadmap

• Scientific Advice & Structured Dialogue: Proactive consultation with the authorities and/or notified body is critical to align on non-clinical, clinical, and manufacturing requirements.
• Regulatory marketing planning: early considerations for market access strategies
• Exclusivity & patent research

Re‑use of Existing Device Evidence in MRP/DCP and Line Extensions

For mutual recognition, decentralised procedures and line extensions of existing iDDCs, the need for updated device documentation depends on whether the device part has undergone significant change. If the same device is used without major changes to its design, performance or intended use, existing MDD‑based certificates and earlier device evidence may still be acceptable under the MDR transitional provisions.

Further Links

• Authorisation of medicines | European Medicines Agency (EMA)
• Obtaining an EU marketing authorisation, step-by-step | EMA
• National competent authorities (human) | EMA
• Medical devices | EMA
• Quality documentation for medicinal products when used with a medical device | EMA
• Heads of Medicines Agencies: Application for MA

Step 4: Maintenance

Same Same, But Different

Drug-device combination products—whether integral (iDDC) or non-integral/co-packaged—are fundamentally composed of three elements: the drug component, the device component, and the combination product as a whole.

Maintenance represents just one aspect of comprehensive lifecycle management. Market feedback (such as complaints), evolving regulatory requirements, or supplier changes may trigger a formal change management process, typically involving the following steps:

• Definition of the change
• Identification and assessment of potential impacts
• Planning and execution of the change
• Final evaluation to ensure objectives are met

The EMA Q&A now explicitly links such change assessments to Article 117 in the post‑approval phase. For all authorised iDDCs, major changes to the device part that may significantly impact its safety, performance or intended use trigger the need for a new or updated EU Declaration of Conformity, EU certificate or NBOp/MAH GSPR statement.

Changes to an Approved Drug-device Combination Product

During the lifecycle of an approved drug‑device combination product, the device component may need to be changed, replaced or newly added. The MAH is responsible for evaluating whether such changes could affect the delivery, quality, safety or efficacy of the combination product.

As a general rule, a new or revised NBOp or MAH GSPR compliance statement is:

• required when a new device or device part is introduced with a line extension or variation;
• expected when major changes are introduced to an existing device, such as changes to design, key performance characteristics, intended purpose (including new patient population, different user such as home vs hospital, or significantly different instructions for use/usability);
• expected when changes to the medicinal product (for example a new formulation with markedly different viscosity) may impact device performance or safety.^[1]

Depending on the type of change either a Variation or an Extension application becomes applicable.

Variation
Variations to the dossier should be submitted in accordance with Regulation (EC) No 1234/2008 (Variation Regulation), as amended. In general, the Variation Regulation defines variations as minor (Type IA, Type IB) or major (Type II).

Extension
Certain changes to an approved marketing authorisation have to be considered to fundamentally alter the terms of this authorisation and therefore cannot be granted following a variation procedure. The three main categories of 'changes requiring an extension of marketing authorisation' are:

• changes to the active substance;
• changes to the strength, pharmaceutical form and route of administration;
• other changes specific to veterinary medicinal products.

iDDC - Example 1
Let's assume the following. For an iDDC (e.g. prefilled syringe), the patient population is to be extended covering children. According to the TEAM NB Guidance, a change of the device component of the medicinal product is understood to be substantial or significant if it may affect the device conformity with the General Safety and Performance Requirements.

Example 2:
A material modification required for a device component, such as the outer shell of an autoinjector. Although this outer shell typically does not come into direct contact with the drug substance, from a device perspective, it maintains direct contact with the patient or user. Consequently, this change could impact compliance with the applicable GSPRs and should therefore be evaluated as a substantial change.

Examples for Co-packed Products
For a co-packed product, the pivotal question will be if the new patient population is covered by the certificate/declaration of conformity of the device or not.

Co-packed Example 2
In case of a material change of the co-packed device, the impact on the drug/ medicinal substance is also to be evaluated.

Summary

In a nutshell, the 4 steps are key to obtaining regulatory compliance of drug-device combination products.

Step 1: Pre-Evaluation

• Systematically review your product portfolio to identify all drug-device combination products.
• Classify each product accurately as either an iDDC or a co-packaged product.
• Verify if a Notified Body (NB) involvement is required.
• Document the regulatory pathway for each product.

Step 2: Data Creation & Documentation

• Assess and update technical documentation for each combination product.
• Review and compile all supporting data (clinical, technical, quality) to identify any gaps.
• Ensure traceability and consistency between drug and device documentation.

Step 3: Notified Body Opinion (NBOp) & Approval

• Engage with Notified Bodies early if required.
• Prepare and submit robust NBOp dossiers or other regulatory submissions as needed.
• Monitor approval progress and be ready to respond to regulatory queries.

Step 4: Maintenance

• Implement a continuous lifecycle management process for all combination products.
• Monitor evolving EU regulations and assess their impact on your product portfolio.
• Plan and execute timely variations to ensure ongoing compliance.
• Regularly review and update product data and documentation.

Learn More:

• Drug-Device Combination Product Regulatory Landscape FAQ

Roles and Responsibilities

Roles and Responsibilities under the MDR

Under the EU Medical Device Regulation (MDR), a "manufacturer" isn't always the one physically making the product. MDR changes the way roles and responsibilities are defined — and these distinctions have real compliance consequences.

Why This Matters

Knowing exactly who is responsible for what is essential for meeting regulatory requirements, avoiding delays, and ensuring product safety. This is especially true for integral and co-packaged drug-device combination products, where different parties may carry overlapping duties.

Key Economic Operators (MDR)

Manufacturer
A person or company that manufactures, refurbishes, or has a device manufactured/refurbished and markets it under their name or trademark (MDR Art. 2(30)).

• Legal manufacturer: Legally responsible for the device, even if a contract manufacturer (CMO) actually makes it.
• Comparable to the Marketing Authorisation Holder (MAH) for medicinal products.
• Often misunderstood: in pharma, "manufacturer" usually means the physical maker; in MDR terms, this is about legal responsibility, not production activity.
• Identified on packaging next to the manufacturer symbol.

Bringing a Device to the EU Market: The Process

1. Placing on the market – First making the device available in the EU (MDR Art. 2(28)).
2. Making available on the market – Any commercial supply of the device (MDR Art. 2(27)).
3. Putting into service – When the device is ready for first use by the final user for its intended purpose.

Considerations for iDDCs and Device Component Choice

For iDDCs, the overall legal responsibility lies with the Marketing Authorisation Holder (MAH) of the medicinal product.

• The legal manufacturer need not be the physical manufacturer of the device (part).
• The legal manufacturer assumes full responsibility for MDR compliance of the device, irrespective of who physically manufactures it.

Using a CE-Marked Device Part

• The iDDC's regulatory status remains that of a medicinal product; the complete iDDC will not carry its own CE mark.
• Using a CE-marked device part may reduce compliance efforts with GSPR if the device's certified intended purpose aligns with the combined product's intended purpose.

Using a non–CE-Marked Device Part

• Selecting a non-CE-marked device part offers flexibility to define or adapt the intended purpose but imposes significant regulatory challenges.
• The supplier of such a device part is considered only a supplier under MDR and assumes no legal responsibility for the device part.

Importance of the Intended Purpose

• Determines device classification which defines the conformity assessment procedure needed for CE marking
• Defines the applicable GSPRs and the design of the device

Considerations for Co-packed Drug–Device Combination Products

Co‑packed drug–device combination products consist of a medicinal product and a medical device packaged together but remaining separate components. Each component retains its own regulatory framework.

Using a CE Marked Device in a Co-pack

Case 1 MAH as Distributor
If the device part is already CE marked, the CE mark remains valid, the intended purpose is unchanged, and no modifications affecting compliance are made, then according to EMA guidance, the MAH's obligations for the device part are those of a distributor (MDR Art. 14).

Distributor obligations include:

• Verifying CE marking, Declaration of Conformity, and required documentation.
• Ensuring the device is supplied with appropriate information and IFU in the correct language(s).
• Storing and transporting the device to maintain compliance.
• Maintaining traceability of the device (UDI requirements).
• Communicating incidents and recalls to the manufacturer and authorities.

Case 2 MAH as Legal Manufacturer
A MAH may choose to designate itself as the legal manufacturer for the device part. This means taking on full MDR manufacturer responsibilities under Art. 10.

Using a Non CE Marked Device in a Co-pack
If the device lacks CE marking, it must undergo full MDR conformity assessment before using as in co-packed device. The MAH bears the compliance burden.

Documentation, Traceability & Post Market Responsibilities

• The device must have a UDI in accordance with MDR.
• The MAH is responsible for post market surveillance of the co packed product as a whole.
• Unless manufacturer status shifts under Art. 16(1), the device manufacturer retains its own MDR vigilance duties.
• The MAH's MAA must include adequate information on the device to demonstrate safe and effective combined use.