By Mark Durivage, Quality Systems Compliance LLC
On July 22, 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted for publication the guideline on quality documentation for medicinal products when used with a medical device (similar to “combination products” referred to by the US FDA), which will become effective January 1, 2022.
This guideline focuses on product-specific quality aspects of a medical device and/or part of a medical device that may have an impact on the quality, safety, and/or efficacy of a medicinal product. It describes the information that should be presented in the quality part of a marketing authorization dossier for a medicinal product when it is used with a medical device and/or as part of a medical device and submitted in accordance with Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use and/or Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004, which lays out Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishes the EMA. Additionally, this guidance considers Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017 on medical devices, amending Directive 2001/83/EC, Regulation (EC) No 178/2002, and Regulation (EC) No 1223/2009 and repealing Council Directives 90/385/EEC and 93/42/EEC and Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use.
This guideline applies to medicinal products in the following instances:
- When the medical device and/or part of a medical device and the medicinal product form a complete single-use product that is not reusable, and the primary mode of action is from the medicinal product (referred to as integral)
- When the marketing authorization holder (MAH) places the medicinal product on the market and the medical device is packed together with the medicinal product (referred to as co-packaged)
- When the product information refers to a specific medical device that is to be used with the medicinal product, and the medical device is obtained separately by the user of the medicinal product (referred to as referenced).
This guideline does not apply to:
- Veterinary products
- In vitro diagnostic devices (including companion diagnostics)
- System and procedure packs (MDR Article 22)
- Devices where reference is directly made, or inferred, in the product information
- Products falling under the first sub-paragraph of MDR Article 1(8).
This guideline explains the documents that should be submitted to demonstrate control of manufacturing and quality of the medicinal product in order to comply with applicable regulations. The medical device and/or part of a medical device (integral, co-packaged, or referenced) must comply with the General Safety and Performance Requirements (GSPRs) as set out in Annex I of the MDR.
Common Technical Document (CTD)
This guideline provides additional support for the electronic Common Technical Document (eCTD) format (Volume 2B Notice to Applicants Medicinal Products for Human Use – Presentation and Format of the Dossier). Relevant information pertaining to the medical device and/or part of a medical device should be plainly structured and cross-referencing between sections is encouraged to avoid unnecessary duplication. Presentation and format of the dossier includes the following modules:
Module 1 European Union (EU) Administrative Information and Prescribing Information
Module 2 Common Technical Document Summaries
Module 3 Quality
Module 4 Nonclinical Study Reports
Module 5 Clinical Study Reports
The MAH must ensure that when changes occur to a medical device and/or part of a medical device that is integral or co-packaged medicinal product, they are aware of any changes and determine whether updates to the eCTD are required. Variations to the dossier related to a medical device and/or part of a medical device should be submitted in accordance with Commission Regulation (EC) No 1234/2008 of 24 November 2008 concerning the examination of variations to the terms of marketing authorizations for medicinal products for human use and veterinary medicinal products.
When a change impacts a critical quality attribute (CQA) of a medicinal product and/or any element of the overall medicinal product control strategy, you should assess the impact of the change when determining the variation category and its reportability. You may consult the Competent Authority that issued the marketing authorization when the category of the variation is not clear prior to submission of the variation. The MAH should also consider whether changes to the medicinal product may impact the performance of the medical device and/or part of a medical device in such a way that its use may require further verification, validation, or an additional usability study.
When submitting a variation application to change, replace, or add a medical device and/or part of a medical device or other aspect of the user interface, consider whether there is an impact on the product information that may affect the potential risk of medication errors. The overall risk assessment of the medicinal product should consider the need for communication with patients and/or healthcare professionals and the risks of potential medication errors. You may need to update your risk management plan (RMP) based on the risk assessment, especially if there is a potential risk of a medication error because of the change.
This guidance, which is applicable to medicinal products when the medical device and/or part of a medical device is single use and is integral, co-packaged, or referenced, will become effective Jan. 1, 2022. Begin planning and updating your eCTD now to ensure compliance.
About The Author:
Mark Allen Durivage has worked as a practitioner, educator, consultant, and author. He is managing principal consultant at Quality Systems Compliance LLC, an ASQ Fellow and SRE Fellow. Durivage primarily works with companies in the FDA regulated industries (medical devices, human tissue, animal tissue, and pharmaceuticals), focusing on quality management system implementation, integration, updates, and training. Additionally, he assists companies by providing internal and external audit support as well as FDA 483 and warning letter response and remediation services. He earned a BAS in computer aided machining from Siena Heights University and an MS in quality management from Eastern Michigan University. He holds several certifications, including CRE, CQE, CQA, CSSBB, RAC (Global), and CTBS. He has written several books available through ASQ Quality Press, published articles in Quality Progress, and is a frequent contributor to Life Science Connect. You can reach him at email@example.com with any questions or comments.