The European Medicines Agency (EMA) has adopted a guideline on the quality information that manufacturers of combination products should submit in marketing authorization applications (MAA).
It also incorporates the recent revision of the EU’s Medical Devices Regulations (MDR) in requiring makers of these products to obtain the results of conformity testing of the device part from a notified body. The MDR regulation went into effect in May 2021. The guideline gives general and specific considerations on how to comply with the amendment to Annex 1 to Directive 2001/83/EC, introduced by Article 117 of the MDR, that requires such testing.
The guideline focuses on product-specific quality aspects of a medical device that may have an impact on the quality, safety and efficacy of a medicinal product, and outlines where this information should be placed in the Common Technical Document. The guideline should be read in conjunction with the Q&A on the implementation of the MDR.
EMA said that the guidance is meant to address “inconsistent” submissions for drug-device combination products and “provide guidance to quality assessors and the applicant/[marketing authorization holder] of a medicinal product on the type of information that should be provided in a submission.”
Three types of combination products covered
The guideline covers three types of combination products: drug-device combination products where the medical device is integral to the product; medical devices co-packaged with medicinal products; and medical devices that are obtained separately by the user for use with medicinal products.
Examples of integral products include single-use pre-filled syringes; single-use pre-filled pens and single-use pre-filled injectors (including autoinjectors); pre-assembled, non-reusable applicators for vaginal tablets; dry powder inhalers and pressurized metered dose inhalers that are preassembled with the medicinal product and ready for use with single or multiple doses that cannot be refilled when all doses are exhausted.
Examples of medical devices co-packaged with medicinal products include oral administration devices such as spoons and syringes; injection needles; and refillable/reusable pens and injectors, including autoinjectors.
For integral products, the guideline outlines the information that should be submitted in the CTD’s Module 1 section on product information, Module P.2.3 on manufacturing process developments and Module P.2.F on microbiological attributes.
Makers of integral combination products should also “include evidence demonstrating the conformity of the device (part) with the relevant GSPRs [General Safety and Performance Requirements], set out in Annex I of Regulation (EU) 2017/745.” It directs manufacturers to consult the EMA Q&A on Implementation of the Medical Devices and In Vitro Diagnostic Medical Devices Regulations (EU) 207/745 and EU 2017 2017/746 for further details.
This information is similar for medicinal products with co-packaged or reference devices. The guidance addresses the inclusion of the quality information in the CTD, and address product information, microbiological attributes and comparability.
Final revisions
The guidance revises the former draft by eliminating the term “non-integral” and replacing it with devices that are co-packaged with medicinal products. The Parenteral Drug Association wrote in comments on the draft that the term “non-integral” was confusing and needed refinement.
The revision also clarifies that advanced therapy medicinal produces (ATMPs) are not covered by the guideline, eliminates reference to the use of platform technology and eliminates a template cover sheet for the Notified Body opinion.
The guideline takes effect on 1 January 2022.
To continue reading this article please go to RAPS .