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Borderline & combination products

Regulatory basis

Borderline product guidance is primarily in MDCG 2022-5. Drug-device combinations are addressed in MDR Art. 1(8)–(9), MDR Annex I §12.2, and relevant EMA guidance. ATMP combination products are governed by Regulation (EC) No 1394/2007.

Disclaimer

This site provides general information only and does not constitute legal or regulatory advice. Borderline determinations can be highly product-specific — always seek qualified regulatory advice.

What is a borderline product?​

A borderline product sits at the regulatory boundary between two or more frameworks — most commonly between:

  • Medical device (MDR) and medicinal product (Directive 2001/83/EC)
  • Medical device (MDR) and IVD (IVDR)
  • Medical device and cosmetic (Regulation 1223/2009)
  • Medical device and food (Regulation 178/2002)
  • Medical device and biocide (Regulation 528/2012)
  • Medical device and ATMP (Regulation 1394/2007)

The determination matters enormously — each regulatory framework has different requirements, timelines, and costs. Incorrect classification can result in non-compliant products on the market or unnecessary regulatory burden.

Device vs medicinal product — the principal mode of action test​

This is the most commercially significant borderline. The rule is:

A product is a medical device if its principal intended action is achieved by physical, mechanical, thermal, or other non-pharmacological/immunological/metabolic means.

A product is a medicinal product if its principal intended action is achieved pharmacologically, immunologically, or metabolically.

A product may be assisted by the other mechanism without changing its primary classification.

Drug-device combinations — integral products​

When a drug and device are combined into a single integral product and cannot be used separately, the primary mode of action determines which regulation governs:

Principal actionGoverning regulationOther regulation involvement
Device action is principalMDR (device governs)EMA or NCA consulted on drug component
Drug action is principalDirective 2001/83/EC (drug governs)MDR requirements apply to device component

Device-led integral combinations (MDR Art. 1(8))​

Where the device is principal:

  • The product is regulated as a Class III medical device under MDR Rule 14
  • The notified body must consult EMA or a national medicines authority for an opinion on the quality, safety, and usefulness of the incorporated substance
  • The drug substance must meet applicable pharmaceutical requirements in parallel

Examples: drug-eluting coronary stents (heparin or sirolimus-eluting), antibiotic-coated bone cement, chlorhexidine-impregnated central venous catheters.

Drug-led integral combinations (MDR Art. 1(9))​

Where the drug action is principal:

  • The product is regulated as a medicinal product under pharmaceutical legislation
  • The device component must nevertheless meet the relevant MDR general safety and performance requirements (GSPR, specifically those in Annex I applicable to devices)
  • EMA or the NCA assesses the whole product; they seek input from the notified body on the device component

Examples: pre-filled syringes with a proprietary needle system (drug + device), auto-injectors with active drug.

Device vs IVDR — in vitro or in vivo?​

The MDR/IVDR split is covered fully in MDR vs IVDR — which applies?. The main borderline:

  • A continuous glucose monitor (CGM) worn on the body: measures interstitially in vivo → MDR
  • A blood glucose test strip examining a blood drop extracted from the body: in vitro → IVDR

Device vs cosmetic — intended purpose and claims​

Products become medical devices when manufacturers make claims that imply a medical purpose (diagnosis, treatment, alleviation, or prevention of a disease or disability). Cosmetic claims relating to appearance, odour, or cleansing do not trigger MDR. But:

  • "Reduces appearance of wrinkles" → cosmetic
  • "Treats dermatitis or eczema" → likely medical device
  • Dermal fillers for aesthetic augmentation → MDR Annex XVI (non-medical-purpose device)

Device vs biocide — what the product is used on​

Biocidal products are intended for non-living surfaces and environments. A product used to disinfect medical devices (e.g. endoscope reprocessing chemicals) may itself be an accessory to a medical device → MDR. A product used to disinfect floors or surfaces → biocide.

Device vs ATMP — tissue engineering and cell therapy​

ATMPs (gene therapies, somatic cell therapies, tissue-engineered products) are governed by Regulation (EC) No 1394/2007. Borderlines arise with:

  • Scaffolds seeded with cells: if the scaffold's function is inextricably linked to the cells → likely ATMP combined product
  • Acellular scaffolds: the scaffold alone, with no living cells → may be an MDR device (e.g. decellularised collagen matrices)

ATMP combined products (Art. 2(1)(d) of Regulation 1394/2007): the device component must still meet relevant MDR requirements, but EMA governs the combined product.

The MDCG borderline manual​

MDCG 2022-5 is the primary EU resource for borderline and classification questions. It covers:

  • Borderline with medicinal products
  • Borderline with cosmetics
  • Borderline between MDR and IVDR
  • Software borderline (cross-referenced to MDCG 2021-24)
  • Specific product category worked examples

The MDCG updates this guidance as new borderline questions arise. National competent authority opinions are collected and referenced, though they are not binding outside their member state.

Seeking a formal borderline opinion​

If uncertainty remains after applying the guidance:

  1. Compile a product dossier — intended purpose, mechanism of action, relevant claims, composition
  2. Contact the relevant NCA — in the member state where you intend to first place the product
  3. Request a formal opinion — most NCAs offer a borderline query process; timelines vary (weeks to months)
  4. For drug-device combinations: consider pre-submission meetings with both EMA (for the drug aspect) and a notified body (for the device aspect)

NCA opinions are country-specific and not binding EU-wide, but they provide documented regulatory certainty for that market and are generally respected by other NCAs.

Official references​

ReferenceDescription
MDR Art. 1(8)Device-led drug-device integral combinations
MDR Art. 1(9)Drug-led drug-device integral combinations
MDR Annex VIII Rule 14Classification of device-drug combinations
MDCG 2022-5Borderline and classification manual
MDCG 2021-24Software borderline and classification
Regulation (EC) 1394/2007ATMPs
EMA guidance on borderline medicinal productsVarious product-specific opinions