{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:35:03Z","timestamp":1793370903630,"version":"4.5.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Integral drug-device combinations (iDDCs) are governed in the European Union (EU) under the medicinal products framework, but the medical device part must meet relevant requirements of the medical device framework. This implies increased complexity as actors with different responsibilities, expertise and priorities are involved. Regulation (EU) 2017\/745 on medical devices (MDR) [1] came into effect on 26 May 2021. At the time of the repealed Council Directive 93\/42\/EEC on medical devices (MDD) [2], the European Medicines Agency (EMA) and EU National Competent Authorities (NCAs) were overseeing the evaluation of the quality, safety, efficacy, benefit\/risk of the medicinal product and the relevant Essential Requirements according to the MDD of the integral medical device used in combination. Article 117 of the MDR introduced a fundamental change: notified bodies became responsible for assessing compliance of the integral medical device with the relevant General Safety and Performance Requirements (GSPRs), as set out in MDR Annex I. These GSPRs represent a more stringent set of requirements in comparison with the Essential Requirements in the MDD. One of the objectives of Article 117 and the MDR was to strengthen regulatory oversight of the device component of the iDDC and increase confidence in the regulatory system. Given the interface of the medicinal product and medical device legislations, the regulatory process for initial authorisation and lifecycle management of iDDCs is challenging to operate for pharmaceutical industry, EMA, EU NCAs and notified bodies. In particular, the implementation of Article 117 raised challenges to all stakeholders involved. In order to support implementation for pharmaceutical industry and EU medicines NCAs, EMA published dedicated guidance and engaged in various conferences and stakeholder meetings. EMA also facilitated discussion of issues with different actors and enhance mutual understanding and sharing of experience. Here, we present EMA\u2019s perspective on Article 117 implementation challenges and opportunities to tackle them.<\/jats:p>","DOI":"10.1007\/s43441-026-00983-3","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:26:27Z","timestamp":1785601587000},"page":"1619-1626","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integral Drug-Device Combinations and Medical Device Regulation Article 117: The European Medicines Agency Perspective"],"prefix":"10.1007","volume":"60","author":[{"given":"Pascal","family":"Venneugues","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Bouygues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Girard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Jekerle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"983_CR1","unstructured":"Regulation (EU). 2017\/745 of the European Parliament and of the Council of 5 April 2017 on medical devices. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/?uri=CELEX%3A02017R0745-20250110"},{"key":"983_CR2","unstructured":"Council Directive 93\/42\/EEC of 14. June 1993 concerning medical devices. Available online: https:\/\/eur-lex.europa.eu\/eli\/dir\/1993\/42\/2007-10-11"},{"key":"983_CR3","unstructured":"MDCG 2021-24 Guidance on classification of medical devices. Available online: https:\/\/health.ec.europa.eu\/system\/files\/2021-10\/mdcg_2021-24_en_0.pdf"},{"key":"983_CR4","unstructured":"CHMP Guideline on the sterilisation of the. medicinal product, active substance, excipient and primary container. Available online: www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-sterilisation-medicinal-product-active-substance-excipient-and-primary-container_en.pdf"},{"key":"983_CR5","unstructured":"MDCG 2022-5 Rev. 1 Guidance on borderline between medical devices and medicinal products under Regulation (EU) 2017\/745 on medical devices. Available online: https:\/\/health.ec.europa.eu\/latest-updates\/mdcg-2022-5-rev1-guidance-borderline-between-medical-devices-and-medicinal-products-under-regulation-2024-10-29_en"},{"key":"983_CR6","unstructured":"Questions. & Answers for applicants, marketing authorisation holders of medicinal products and notified bodies with respect to the implementation of the Regulations on medical devices and in vitro diagnostic medical devices (Regulations (EU) 2017\/745 and (EU) 2017\/746). Available online: www.ema.europa.eu\/en\/documents\/regulatory-procedural-guideline\/questions-answers-implementation-medical-devices-vitro-diagnostic-medical-devices-regulations-eu-2017-745-eu-2017-746_en.pdf"},{"key":"983_CR7","unstructured":"European Medicines Agency. 2024. The evaluation of medicines, step-by-step. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/marketing-authorisation\/evaluation-medicines-step-step"},{"key":"983_CR8","unstructured":"MDCG 2022-14 Position Paper on Transition to the MDR and IVDR, Notified body capacity and availability of medical devices and IVDs. (2022). Available online: https:\/\/health.ec.europa.eu\/system\/files\/2022-08\/mdcg_2022-14_en.pdf"},{"key":"983_CR9","unstructured":"TEAM-NB Position Paper New MDR Transition Timelines and Notified Body Capacity. 2023. Available online: https:\/\/www.team-nb.org\/wp-content\/uploads\/2023\/08\/Team-NB-PositionPaper-MDRTransitionTimelines-NotifiedBodyCapacity-V1.pdf"},{"key":"983_CR10","unstructured":"Article. 117 - Documentation submission best practice guidelines (BSI). Available online: www.bsigroup.com\/en-GB\/insights-and-media\/insights\/brochures\/article-117-documentation-submission-guidelines\/"},{"key":"983_CR11","unstructured":"Position Paper on Navigating EU MDR Article 117, Industry Experience EFPIA. June 2025. Available online: https:\/\/www.efpia.eu\/media\/jv0e1w5u\/efpia-publication-draft-art-117_final-june-2025.pdf"},{"key":"983_CR12","unstructured":"CHMP guideline on quality documentation for medicinal products when used with a medical device. Available online: www.ema.europa.eu\/en\/documents\/scientific-guideline\/guideline-quality-documentation-medicinal-products-when-used-medical-device-first-version_en.pdf"},{"key":"983_CR13","unstructured":"MDCG 2020-3. Guidance on significant changes regarding the transitional provision under Article 120 of the MDR with regard to devices covered by certificates according to MDD or AIMDD Rev.1 Available online: https:\/\/health.ec.europa.eu\/system\/files\/2023-09\/mdcg_2020-3_en_1.pdf"},{"key":"983_CR14","unstructured":"TEAM-NB Position paper for the interpretation of. device related changes in relation to a Notified Body Opinion as required under Article 117 of Medical Device Regulation (EU)2017\/745. Available online: www.team-nb.org\/wp-content\/uploads\/2020\/12\/Team-NBPosition-Paper-Art117SubChangeLifeCycleMngt-202012.pdf"},{"key":"983_CR15","unstructured":"EMA post-authorisation guidance. Available online: www.ema.europa.eu\/en\/human-regulatory-overview\/post-authorisation\/contacting-ema-post-authorisation"},{"key":"983_CR16","unstructured":"EMA Regulatory Science. to 2025 - Strategic reflection. Available online: www.ema.europa.eu\/en\/documents\/regulatory-procedural-guideline\/ema-regulatory-science-2025-strategic-reflection_en.pdf"},{"key":"983_CR17","unstructured":"European medicines agencies network strategy to 2028. Available online: https:\/\/www.ema.europa.eu\/en\/about-us\/how-we-work\/european-medicines-regulatory-network\/european-medicines-agencies-network-strategy"},{"key":"983_CR18","unstructured":"Combination Products Operational Group (COMBO) \u2013 Terms of reference. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/other\/combination-products-operational-group-combo-terms-reference_en.pdf"},{"key":"983_CR19","unstructured":"Regulation (EC). No 1394\/2007 of the European Parliament and of the Council of 13 November 2007 on advanced therapy medicinal products. Available online: https:\/\/eur-lex.europa.eu\/legal-content\/EN\/TXT\/PDF\/?uri=CELEX:32007R1394"},{"key":"983_CR20","unstructured":"EU rules on medical devices and in vitro diagnostics \u2013 targeted evaluation. Available online: https:\/\/ec.europa.eu\/info\/law\/better-regulation\/have-your-say\/initiatives\/14155-EU-rules-on-medical-devices-and-in-vitro-diagnostics-targeted-evaluation_en"},{"key":"983_CR21","unstructured":"Proposal for a Regulation of the European Parliament and the Council amending Regulations (EU) 2017\/745 and 2017\/746. Available online: https:\/\/health.ec.europa.eu\/medical-devices-sector\/new-regulations_en"},{"key":"983_CR22","unstructured":"A pharmaceutical strategy for Europe. Available online: https:\/\/health.ec.europa.eu\/medicinal-products\/pharmaceutical-strategy-europe_en"}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-00983-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-026-00983-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-026-00983-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T14:07:11Z","timestamp":1793369231000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-026-00983-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["983"],"URL":"https:\/\/doi.org\/10.1007\/s43441-026-00983-3","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"value":"2168-4790","type":"print"},{"value":"2168-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]},"assertion":[{"value":"22 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}