Classification Rules for Drug-Device Combinations: The PMOA Decision Framework

The audit finding arrived on a Thursday afternoon. Three words highlighted in red: "Classification inadequately justified."

His team had spent eighteen months preparing the dossier.
The device incorporated a well-known anticoagulant coating—nothing exotic, nothing novel.

What the auditor found: the PMOA determination was based on assumptions, not documented analysis. Was the anticoagulant action principal or ancillary? The dossier didn't definitively answer.

The framework that follows prevents exactly this scenario—by grounding classification in the regulatory logic that auditors and assessors expect to see.

The Foundation: Principal Mode of Action (PMOA)

Why this matters: PMOA isn't just a technical determination—it's the single decision that routes your product into either the pharmaceutical or device regulatory framework. Everything else follows from this.

The demarcation between MDR and pharmaceutical legislation is built on one question: What is the principal intended action of the product?

This isn't an arbitrary distinction. Pharmaceutical legislation exists because pharmacological actions carry specific safety considerations—dose-response relationships, metabolic interactions, immunological reactions—that device regulations weren't designed to address. MDR exists because mechanical and physical actions carry their own safety considerations—biocompatibility, sterility, mechanical failure modes.

When Is Action "Principal" vs "Ancillary"?

The regulations don't define a precise threshold. Instead, the determination requires clinical and scientific judgment:

MDR Classification Rules That Apply to DDCs

Why this matters: When the device function is principal, specific MDR Annex VIII rules trigger mandatory Notified Body involvement and scientific consultation with medicinal product authorities.

Rule 14: Devices Incorporating Ancillary Medicinal Substances

Rule 14 of MDR Annex VIII applies when a medical device incorporates, as an integral part, a substance which—if used separately—would be considered a medicinal product. The critical word is "ancillary": the medicinal action supports rather than drives the device's purpose.

The consultation requirement exists because Notified Bodies have expertise in device conformity assessment but not in pharmaceutical quality and safety. A scientific opinion from a medicinal products authority ensures the ancillary substance is evaluated appropriately.

Rule 22: Devices with Integrated Diagnostic Functions

Rule 22 addresses devices that include an integrated diagnostic function—for instance, a drug delivery device with a sensor that monitors patient response. While not strictly about drug-device combinations, this rule becomes relevant when combination products include monitoring or feedback mechanisms.

How Pharmaceutical Legislation Interacts with Device Classification

Why this matters: When PMOA is pharmacological, the product falls under pharmaceutical legislation—but device aspects don't disappear. Understanding this interaction prevents gaps in your regulatory strategy.

MDR Article 117 creates the bridge between frameworks. When a medicinal product incorporates a device component (like a pre-filled syringe), the marketing authorization dossier must address both pharmaceutical and device requirements.

The critical insight: The General Safety and Performance Requirements (GSPRs) of MDR Annex I apply to the device part of integral drug-device combinations, even when the product is regulated primarily as a medicinal product. You don't escape device requirements—they're integrated into the pharmaceutical assessment.

Classification Scenarios: Which Rules Apply?

Why this matters: Theory is helpful, but regulatory decisions happen in specific product contexts. These scenarios illustrate how classification logic applies in practice.

IVDR Considerations for Combination Products

Why this matters: If your combination product includes an IVD component, IVDR adds another regulatory dimension. Understanding this prevents pathway confusion.

IVDR (EU) 2017/746 governs in vitro diagnostic devices. When a combination product includes an IVD element—for instance, a drug with an accompanying diagnostic test—the classification analysis becomes multi-dimensional.

This means companion diagnostics—IVDs essential for safe and effective use of corresponding medicinal products—remain separate products under IVDR, even when closely linked to specific therapies. The classification frameworks don't merge; they coordinate.

Consequences of Misclassification

Why this matters: Classification errors aren't correctable with minor amendments. They can invalidate entire regulatory strategies and require starting over.

The documents are clear: correct qualification and classification of a product is crucial for applying the appropriate set of requirements. Misclassification doesn't trigger a minor correction—it triggers the wrong framework entirely.

Dispute Resolution: If a manufacturer and Notified Body disagree on device classification, the dispute is referred to the national competent authority for medical devices in the Member State where the manufacturer is registered. This provides a formal mechanism—but it's far better to resolve classification questions before submission.

A Practical Classification Framework