EMA’s updated guideline on pharmaceutical quality of inhalation and nasal products put to a peak flow test

This blog is part of The Regulatory Navigator series, where we explore the evolving regulatory landscape with actionable insight from Parexel's experts, sharing their experience to maximize success for clinical development and patient access.

The European Medicines Agency (EMA) published the final, legally binding update to its guideline on quality standards for inhalation and nasal products, in February 2026.¹ The revision combines earlier 2006² guidance, the Medical Device Regulation (MDR)³, and recent technical advances and common practice. As a regional guideline, and not an International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use (ICH) standard, European requirements for pharmaceutical development and quality control may differ from United States (US) Food and Drug Administration (FDA) guidance.  

In this blog it is discussed how these changes may impact your inhalation or nasal product development, specifically in the context of Marketing Authorization Application (MAA) and Chemistry, Manufacturing and Controls (CMC) data generation.  

Five key takeaways for CMC data generation and MAA submissions  

Applicants may now need to generate more development data than before. Specifically, developers of inhalation products will need to ensure that production scale and validation data are included in the MAA or provided during the MAA assessment period – otherwise a major objection will be raised. This and other requirements for CMC data require careful pre-planning to avoid delays or rejections from European regulatory authorities.  

1. Provision of full commercial scale process validation data as part of the MAA submission for inhalation products (but not all nasal products) that are specialized dosage forms with non-standard manufacture. This is a key difference from the US Abbreviated New Drug Application (ANDA)/ New Drug Application (NDA) for which Process Performance Qualification (PPQ) batches are to be executed before commercialization, but a protocol is sufficient for the marketing application submission.  
2. Additional technical and regulatory information needed for container closure system in 3.2.P.7 and 3.2.R, as well as user acceptance testing, as the impact of the recent MDR and EMA Guideline on Combination Products.⁶ 
3. New (and updated) pharmaceutical development studies for inhalation products, including a spray pattern / plume geometry characterization test, reflecting the contemporary technological and analytical advancements that have been made since the initial guideline was issued. Batch requirements are also refined. 
4. Better integration with linked ’TE guideline’ for generics, with information relating to demonstrating equivalence to the reference products being removed and instead a cross reference to this complementary guideline being provided. 
5. Revised requirements for clinical batches with conduct of testing not expected on all clinical trial batches; however, extensive characterization of the active substance and finished medicinal product batches used in pivotal clinical trials is necessary to qualify the medicinal product proposed for marketing. 

What’s new in the final updated EMA guidance?  

The guideline's structural layout has been reorganized, separating inhalation and nasal medicinal products into distinct sections following M3 CTD format for improved usability. Three new subsections—therapeutic equivalence, product information, and lifecycle management—have been added, with updates reflecting ICH Q8⁷ which came into effect subsequent to the original 2006 guidance. 

While inhalation and nasal products share similarities in quality attributes and most inhalation requirements apply to nasal products, key distinctions exist. Inhalation products require respirable particles (<5 µm), whereas nasal products must avoid small particles that could reach the lungs causing unwanted effects. Manufacturing also differs with nasal products typically using standard processes (versus specialized inhalation dosage forms), though some may be complex (e.g., suspensions, low active content) per the EMA PV Guideline.⁸ Additionally, companion guidelines CPMP/EWP/239/95⁹ (clinical requirements for locally applied products) and CPMP/EWP/QWP/1401/98¹⁰ (bioequivalence investigation) are referenced for nasal products. 

Key updated EMA requirements for inhalation products are described in the table below. 

Table 1. Comparison of EMA’s original vs. updated requirements on inhalation products.   

Conclusion 

This updated EMA guideline on pharmaceutical quality of inhalation and nasal products – the first revision in 20 years – reflects recent EU/ICH guideline changes, EU regulations, and technical/regulatory updates (development studies, batch requirements). The revision greatly enhances developers’ understanding of required studies and data, and clarifies the EMA expectations for information to be included in the MAA.   

EMA and EU national competent authority quality reviewers will use this guidance for Module 3 assessments, therefore developers who do not adhere to the stated principles and requirements risk multiple queries and major objections during the MAA procedure — particularly for process validation data or co-packaged device information. Additionally, generating required data post-factum (during assessment procedures) is extremely challenging and may cause application rejection. As such, for inhalation/nasal product developers planning European MAAs or NDA-to-MAA conversions, applying the guideline requirements is essential.  

Preparing for MAA submission should include conducting gap analysis of the available CMC/quality data, comparing this against this guidance and relevant ICH/EMA requirements.  We strongly recommend pursuing EU scientific advice when deviations/uncertainties exist. 

Parexel Regulatory Consulting experts have deep nasal/inhalation product expertise across global markets, from clinical development to CMC requirements, and are ready to support with assessment of development impacts, conducting gap analyses, and scientific advice procedures navigation. While NDA-to-MAA conversions may be complex due to regional guidance differences and varying ICH implementation, our experts understand all regional requirements and are available for consultation. Please get in touch.  

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References  

1. EMA/CHMP/20607/2024: Guideline on the pharmaceutical quality of inhalation and nasal medicinal products, 14 July 2025 

2. EMEA/CHMP/QWP/49313/2005 Corr: Guideline on the Pharmaceutical Quality of Inhalation and Nasal products, 21 June 2006  

3. Regulation (EU) 2017/745 of the European Parliament and of the Council of 5 April 2017  

4. CPMP/EWP/4151/00 Rev. 1: Guideline on the requirements for clinical documentation for orally inhaled products (oip) including the requirements for demonstration of therapeutic equivalence between two inhaled products for use in the treatment of asthma and chronic obstructive pulmonary disease (COPD) in adults and for use in the treatment of asthma in children and adolescents, 22 January 2009  

5. EMA/CHMP/101453/2024: Guideline on the requirements for demonstrating therapeutic equivalence between orally inhaled products (OIP) for asthma and chronic obstructive pulmonary disease (COPD), 16 March 2024 

6. EMA/CHMP/QWP/BWP/259165/2019: Guideline on quality documentation for medicinal products when used with a medical device, 22 July 2021 

7. ICH, Pharmaceutical Development Q8(R2), August 2009 

8. EMA/CHMP/CVMP/QWP/BWP/70278/2012-Rev1,Corr.1, Guideline on process validation for finished products - information and data to be provided in regulatory submissions, 21 November 2016 

9. CPMP/EWP/239/95 Rev. 1, Corr.1*: Guideline on equivalence studies for the demonstration of therapeutic equivalence for locally applied, locally acting products in the gastrointestinal tract, 18 October 2018  

10. CPMP/EWP/QWP/1401/98 Rev. 1, Corr**: Guideline on the investigation of bioequivalence, 20 January 2010  

11. ICH, Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances Q6A, 6 October 1999 

12.EMA, Product-information (QRD) templates - Human, January 2025 

13. Official Journal of the European Union, Volume 56, 2 August 2013 

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