Change management considerations for orally inhaled and nasal drug products and other drug device combination products in the European Union

Abstract

In this paper, the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS), discusses the current regulatory landscape associated with change management of orally inhaled and nasal drug products (OINDP) and other drug device combination products in the European Union.

The paper also describes current challenges related to alignment of regulatory expectations, particularly for integral drug device combination products, and proposes topics for further discussion with regulatory agencies and stakeholders to help advance alignment. To further illustrate current challenges and industry approaches to meeting change management requirements, we also present results of an IPAC-RS benchmarking survey and case studies, and outcome from interactions with notified bodies and regulatory agencies. This document is intended to be used as a guideline for industry alignment.

Introduction

The European Union Medical Devices Regulations (EU MDR) 2017/745¹ Article 117 states, in summary, that the manufacturer of a product (in this case an integral drug device combination, or iDDC) governed under the Medicinal Products Directive 2001/83/EC,² shall provide a conformity assessment of the device part to Annex I of the regulation. Should the device utilized not have a Conformité Européene Mark (CE Mark), then a notified body opinion (NBOp) must be included in the marketing authorization or variation application. In addition, a change that could affect the performance and safety characteristics of the device will require an NBOp as part of the variation process.

The scope of the IPAC-RS Change Management Working Group (WG) is on how industry is navigating post-marketing change management expectations within the EU, with a focus on assessing what should, or should not, constitute a major/significant change and a new NBOp or an amendment to an existing NBOp, based on a review of current change examples, case studies assessments and interactions with notified bodies (NBs) and regulatory agencies.

The main reason for creating this WGwas due to many questions and issues related to the NBOp process, such as the lack of understanding and alignment on what constitutes a major/significant change and the NBOp approach; guidance and alignment among NBs; the expectations for pharmaceutical companies and contract development and manufacturing organizations (CDMOs); and understanding timelines for NBs to develop their assessment/opinions.

The WG developed a survey across the IPAC-RS membership to gather additional data to assess whether a proposed change should prompt an NBOp or not for orally inhaled and nasal drug products (OINDPs) and drug device combination products (DDCPs). The team also reached out to NBs and discussed their expectations with a list of questions. This paper presents the results of the survey as well as responses from NBs. The paper is intended as a guideline for industry, aiming for industry alignment where NBOps are concerned. The ultimate goal is to ensure that quality, efficacy and safety are maintained throughout the product lifecycle benefiting the needs of patients and healthcare professionals.

Continue reading here

Marielle Calderini, Beatrice Grand-Demars, Lee Nagao, Change management considerations for orally inhaled and nasal drug products and other drug device combination products in the European Union, Journal of Pharmaceutical Sciences, 2026, 104357, ISSN 0022-3549, https://doi.org/10.1016/j.xphs.2026.104357.

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