Integral DDC Labeling: The CE Mark Trap Nobody Warns You About

A colleague forwards him a marked-up draft of the package leaflet. Seven annotations in red, all in the same section—the device instructions.

The comments are from the quality reviewer, and they all say variations of the same thing: this reads like a device IFU, not like a section of a medicinal product leaflet. The formatting is wrong. The symbols are wrong. And there's a CE mark on the mock-up that shouldn't be there at all.

He's been working on medical devices for eight years. He knows MDR Annex I labeling requirements in his sleep—every symbol, every mandatory element, every placement rule. And that's precisely the problem. Because integral DDCs don't follow those rules. They follow pharmaceutical labeling rules, and the instincts he's built over a decade are now working against him.

EMA's Q&A Questions 3 and 4 explain why—and what integral DDC labeling actually requires. The logic is clear once you see it. The challenge is unlearning what you already know about device labeling.

What Q3 and Q4 Actually Address

Why this matters: Q3 and Q4 resolve a tension that exists at the heart of integral DDCs—a product with device components that must follow pharmaceutical labeling rules. Understanding the EMA's position prevents labeling deficiencies that create review cycles and delay authorization.

The EMA Q&A addresses labeling for integral DDCs within a broader section on labeling requirements. The core principle is straightforward: integral DDCs form a single integral product governed by pharmaceutical legislation—either Directive 2001/83/EC or Regulation (EC) No 726/2004. Because the product is regulated as a medicinal product, the labeling framework is pharmaceutical, not device.

This has several practical consequences that catch teams off guard, particularly those with device backgrounds. MDR obligations like CE marking are not required and should not appear on the iDDC packaging. The Quality Review of Documents (QRD) templates—not MDR Annex I—govern the labeling structure. And device administrative information (manufacturer name, notified body number, device symbols) stays off the medicinal product labeling entirely.

For integral DDCs, the product labelling should follow the requirements for medicinal products, as outlined in the QRD templates. MDR obligations such as the CE mark are not required and should not be applied to the package of such an iDDC.

Why Pharmaceutical Labeling Takes Precedence

Why this matters: The rationale behind this rule isn't arbitrary—it follows directly from how integral DDCs are classified. Understanding the logic prevents the instinct to "add device info just to be safe."

The reasoning follows a chain that starts with classification under Q1. An integral DDC is a single product where the drug and device form an inseparable unit. When the principal mode of action is pharmacological (the majority of integral DDCs), the product is regulated as a medicinal product under pharmaceutical legislation.

Labeling follows regulation. If the product is regulated as a medicinal product, its labeling must conform to medicinal product rules. Applying MDR labeling elements—CE marks, device manufacturer details, MDR symbols—would misrepresent the product's regulatory status. It would suggest to healthcare professionals and patients that the product has undergone conformity assessment as a medical device, when in reality the product as a whole has been assessed and authorized as a medicinal product.

This doesn't mean the device component is unregulated. The device part must still meet relevant General Safety and Performance Requirements (GSPRs) from MDR Annex I. It's assessed through the Article 117 consultation, where a Notified Body evaluates the device component's conformity. But that assessment happens within the pharmaceutical authorization process—and the labeling reflects the pharmaceutical authorization, not the device conformity assessment.

The CE Mark and UDI Rules for Integral DDCs

Why this matters: This is where the most common labeling errors occur. Teams with device experience instinctively add CE marks and UDI carriers—both of which should be absent from iDDC packaging.

The Q&A is explicit on this point: CE marks should not be applied to the package of an integral DDC. The reasoning is simple—CE marking signifies that a product has undergone conformity assessment as a medical device under MDR. An integral DDC has not. It has undergone marketing authorization as a medicinal product, and its regulatory status is represented by the marketing authorization number, not a CE mark.

The practical summary: What's physically on the device component can stay. What appears on the product's labeling, packaging, and product information must follow pharmaceutical rules exclusively. The distinction is between the device itself and the product as a whole—and for labeling purposes, only the product-level regulatory status matters.

Instructions for Use: Where Device Meets Drug

Why this matters: This is where the two regulatory worlds genuinely overlap. The device IFU can't be ignored—it must be translated into the pharmaceutical labeling framework. Getting this wrong creates medication error risks that assessors take very seriously.

The device component of an integral DDC has Instructions for Use—information about how to handle, prepare, and operate the delivery mechanism. For a pre-filled syringe, that's injection technique. For an autoinjector, that's activation sequence. For a transdermal patch, that's application and removal. This information is essential for patient safety, and the EMA's position is clear: it must be incorporated into the medicinal product's SmPC and Package Leaflet.

The key phrase from the Q&A is "clear and simple instructions for the intended use of the DDC, aimed at patients and/or healthcare professionals, written in such a way as to prevent medication errors." This isn't a suggestion—it's a requirement that reviewers actively check during assessment.

The Integral DDC Labeling Checklist

Why this matters: Labeling deficiencies are among the most common reasons for Day 120 questions in centralized procedures. This checklist covers the elements assessors verify.

Labeling Traps That Delay Submissions

Why this matters: These aren't theoretical risks—they're the patterns that generate Day 120 questions, List of Questions, and labeling-related review cycles in real submissions.