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An Overview and Discussion of N-nitrosamine Considerations for Orally Inhaled Drug Products and Relevance to Other Dosage Forms

AAPS PharmSciTech volume 24, Article number: 37 (2023) Cite this article

Abstract

The presence of N-nitrosamines in drug products are currently an area of high regulatory and industry scrutiny, having been detected above acceptable regulatory levels in several solid oral drug products. For over 20 years, there has been an expectation that N-nitrosamines be eliminated or controlled to acceptable levels in orally inhaled and nasal drug products (OINDP). As a result, the OINDP industry has developed and implemented risk management processes and considerations to address N-nitrosamines in final drug product, including management and understanding of upstream supply particularly for OINDP device and container closure systems. We provide an overview of N-nitrosamine formation, discuss key current regulatory expectations worldwide for N-nitrosamines in drug products, discuss risk management approaches relevant for drug device combination products, and share analytical “tips” with respect to handling N-nitrosamines chemical assessments.

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Data availability

This is a review work, and original data was therefore not generated. Any data noted in the paper is cited and referenced to the published source material.

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All authors declare that there are no sources of study funding related to this publication.

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Authors and Affiliations

  1. Vectura Delivery Services, Cambridge, UK

    Hera Shams Khan

  2. Aptar Pharma, Le Vaudreuil, France

    Fabienne Despres-Gnis

  3. C&M Technical Consulting, LLC, San Mateo, California, USA

    Cheryl L. M. Stults

  4. PPD, Part of Thermo Fisher Scientific, Middleton, WI, USA

    James Mullis

  5. Merck, Rahway, New Jersey, USA

    Niran Nugara

  6. AstraZeneca, Research Triangle Park, North Carolina, USA

    Atish Sen

  7. Faegre Drinker Biddle & Reath LLP, 1500 K Street, NW, Suite 1100, Washington, DC, 20002, USA

    Lee Nagao

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  1. Hera Shams Khan
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Khan, H.S., Despres-Gnis, F., Stults, C.L.M. et al. An Overview and Discussion of N-nitrosamine Considerations for Orally Inhaled Drug Products and Relevance to Other Dosage Forms. AAPS PharmSciTech 24, 37 (2023). https://doi.org/10.1208/s12249-022-02491-7

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