EU Regulation 2021/2226 and 2025/1234: The Foundation of the eIFU System Framework

EU Regulation 2021/2226 and 2025/1234 together define when medical device manufacturers may provide eIFU — electronic Instructions for Use — under MDR 2017/745. The original regulation (2021/2226) established the eligibility conditions, URL requirements, and paper-on-request obligation. The 2025 amendment (2025/1234) widened the eIFU application range, strengthened the persistent URL requirement and connected the framework explicitly to EUDAMED registration. Understanding these changes is required before any manufacturer can confirm their eIFU strategy is compliant.

How the eIFU Regulatory Framework Evolved

Understanding 2021/2226 and 2025/1234 requires knowing where they came from. This timeline traces the regulatory lineage — why each regulation was created and what gap it filled.

Manufacturers who implemented eIFU under 207/2012 (MDD era) should conduct a compliance review when transitioning from MDD to MDR.

EU Regulation 2021/2226: The MDR eIFU Framework

What the Regulation Covers

Regulation (EU) 2021/2226 establishes the conditions under which manufacturers of medical devices may provide instructions for use in electronic form. It applies to all devices subject to MDR Regulation (EU) 2017/745 where the manufacturer wishes to use eIFU as the primary format or as a supplementary format alongside paper.

Article 2(1) defines eIFU as instructions provided in electronic form made available via a publicly accessible website, portable storage media (USB, optical disc), or a display integrated into the device. Only website-hosted eIFU triggers the EUDAMED URL registration requirement.

Article 3 — Supplementary eIFU: No Eligibility Conditions Required

Any manufacturer may provide eIFU as a supplement to a paper IFU without meeting any eligibility criteria. The paper IFU remains the primary format; the eIFU provides additional or equivalent access. Article 3 imposes no conditions on device class, user type, or professional status. This is the lowest-risk eIFU pathway.

Article 4 — Primary eIFU: The Conditions for Going Paperless

The more demanding pathway — providing eIFU as the only format, with no paper IFU supplied — requires all of the following conditions to be met simultaneously :

Condition 1: Professional use only. The device must be intended exclusively for use by healthcare professionals. Devices intended for self-use, home use, or use by lay persons cannot use eIFU-only under Article 4.

Condition 2: Device category. The device must be an implant, an implant accessory, or a software. This condition was removed by the amendment 2025/1234.

Condition 3: Digital access is expected. The device must be one where users would normally be expected to have access to digital resources at the point of use.

Condition 4: Demonstrated access. The manufacturer must demonstrate that professional users can access and read the eIFU before using the device.

Condition 5: EUDAMED registration (from 28 May 2026). From the date EUDAMED's UDI/Devices module becomes mandatory, the eIFU URL must be registered in EUDAMED's Part B, Point 22 data field . New registrations that lack a valid URL will be rejected.

Condition 6: Paper-on-request. The manufacturer must supply a paper copy of the IFU to any user who requests one, free of charge, within 7 calendar days.

Articles 5–8: Operational Requirements

Article 5 — Languages. eIFU must be available in the official language(s) of each EU Member State where the device is placed on the market. A single URL may host all language versions. Manufacturers selling into all EU Member States must accommodate up to 24 official EU languages.

Article 6 — URL Requirements. The URL registered in EUDAMED and shown on device packaging must be persistent, publicly accessible without authentication or payment, stable, and HTTPS. The URL or QR code on device packaging must resolve to the device-specific eIFU or an accessible portal.

Article 7 — Paper-on-Request. Any user may request a paper copy. The 7-calendar day clock starts from the moment of the request. The paper copy must be identical to the currently approved eIFU version and must be provided free of charge. This obligation runs for the entire period the device is on the market, plus the post-market surveillance period.

Article 8 — Informing Users. The eIFU URL or QR code must appear on device labelling or packaging.

EU Regulation 2025/1234: What the Amendment Changed

Regulation (EU) 2025/1234, published June 2025, amends 2021/2226 in three key areas.

Expansion of the application range for eIFU

Devices that are intended to be used exclusively by healthcare professionals can now be provided with eIFU as a replacement for the paper IFU, provided that quality assurance requirements, such as a validated computer system and a risk analysis are documented. 

Persistent URL — Strengthened and Extended

The amendment clarified and strengthened the Article 6 URL obligation:

• The URL must remain accessible for a minimum of 3 years after the device is discontinued from the EU market, covering the post-market surveillance period per MDR Article 87(1)

• Manufacturers who migrate website infrastructure must update EUDAMED with the new URL immediately

• The amendment confirmed that registering a generic portal URL (one per manufacturer account, not one per product) satisfies the persistent URL requirement — consistent with the practical recommendation to use a single stable portal address. This means device additions and discontinuations never invalidate the registered EUDAMED address.

EUDAMED Registration — Made Explicit

Prior to 2025/1234, the requirement to register the eIFU URL in EUDAMED was derived from MDR Annex VI via cross-reference. The amendment made this an explicit condition within the eIFU regulation itself. A device using primary eIFU must have its URL registered in EUDAMED from 28 May 2026 as a direct requirement of the eIFU framework.

What Did Not Change

Knowing what 2025/1234 did not alter is equally important:

• Eligibility conditions (Article 4): professional-use-only remains the baseline; device classes were removed

• 7-calendar-day paper-on-request free of charge (Article 7): unchanged

• Language requirements (Article 5): unchanged

• Supplementary eIFU (Article 3): still available to all manufacturers with defined requirements regarding the computer system and software

• Labelling requirements (Article 8): URL on packaging remains mandatory for devices with eIFU

Primary vs. Supplementary eIFU: A Decision Framework

Most manufacturers begin with Article 3 (supplementary) to test eIFU operationally before committing to packaging changes — this is an implementation strategy, not a regulatory requirement. Moving to Article 4 (primary) requires confirming eligibility for target markets and device classes.

Practical Impact: What the Combined Regulation Requires

For a manufacturer selling MDR-regulated Class II devices into all EU Member States, professional-use only:

1. eIFU via website is permitted under Article 4 if the device is professional-use only and digital access can be demonstrated.

2. EUDAMED URL registration is mandatory from 28 May 2026 — Part B, Point 22 must contain a valid, accessible URL

3. The URL strategy should use a generic portal URL — one address per manufacturer account is more resilient than per-product document URLs and keeps the registered EUDAMED address stable as the catalogue changes. Matrix eIFU uses this architecture by default: one persistent portal URL per manufacturer account, so the EUDAMED-registered address never needs to change regardless of catalogue size or product lifecycle events

4. Paper-on-request must be operational before the device launches with eIFU-only

5. All applicable EU languages must be accessible from the registered URL if selling across Member States

6. The URL must remain accessible through the post-market surveillance period (minimum 3 years post-discontinuation per MDR Article 87(1))

For Class I devices or devices intended for lay users: primary eIFU under Article 4 is not available. Article 3 supplementary eIFU is the only compliant pathway.

Frequently Asked Questions

What is EU Regulation 2021/2226 and what does it cover?

Commission Implementing Regulation (EU) 2021/2226 is the EU regulation that defines when medical device manufacturers may provide electronic Instructions for Use (eIFU) under MDR 2017/745. It establishes two pathways: supplementary eIFU (alongside paper, Article 3, no eligibility conditions) and primary eIFU (replacing paper, Article 4, professional-use-only with five conditions). Published 14 December 2021, amended by Regulation (EU) 2025/1234.

What did Regulation 2025/1234 change compared to 2021/2226?

Regulation (EU) 2025/1234 made four changes: it widened the application range for eIFU as a replacement of paper IFU, it strengthened the persistent URL requirement by requiring the URL to remain accessible for 3 years after device discontinuation (per MDR Article 87(1)); it made EUDAMED URL registration an explicit condition of the eIFU framework. The eligibility conditions, 7-calendar-day paper-on-request obligation, and language requirements were not changed.

Under which conditions can a manufacturer provide eIFU without a paper IFU?

Under Article 4 of Regulation (EU) 2021/2226 (as amended), all five conditions must be met: (1) the device is intended exclusively for professional use; (2) users would normally be expected to have digital access at the point of use; (3) the manufacturer demonstrates users can access the eIFU; (4) the eIFU URL is registered in EUDAMED from 28 May 2026; and (5) paper copies are supplied on request within 7 days. Implantable devices and emergency-use devices are excluded.

What is the difference between primary and supplementary eIFU?

Primary eIFU means eIFU is the only format supplied — no paper IFU is included with the device. Available only for professional-use devices meeting all regulatory conditions. Supplementary eIFU means eIFU is provided in addition to a paper IFU. Any manufacturer may provide supplementary eIFU under the conditions defined in Article 9 of Regulation (EU) 2021/2226..

Related Reading

• EUDAMED and eIFU: How to Register Your URL Before the May 2026 Mandatory Deadline — How to complete the EUDAMED Part B, Point 22 registration required by 2025/1234.

Sources

• Regulation (EU) 2021/2226

• Regulation (EU) 2025/1234

• Regulation (EU) 2017/745 (Medical Devices Regulation)

• Commission Decision 2025/2371