Mass Balance in Pharmaceutical Stress Testing: A Review of Principles and Practical Applications.

Autor: Marden S; Advanced Drug Delivery, Pharmaceutical Sciences, R&D, Astrazeneca, Boston, 35 Gatehouse Dr., Waltham, Massachusetts, 02451, USA. stacey.marden@astrazeneca.com., Campbell JM; Analytical Development, GSK, 1250 South Collegeville Rd, Mail Stop UP1400, Upper Providence, Pennsylvania, 19426, USA. john.m.campbell@gsk.com., Adams N; Scientific and Laboratory Services-Analytical Sciences, Pfizer Inc, Kalamazoo, Michigan, USA., Coelho R; Regulatory Affairs, Eurofarma Laboratórios SA, Itapevi, São Paulo, Brazil., Foti C; Analytical Development and Operations, Gilead Sciences Inc., Foster City, California, USA., Franca JR; Brazilian Health Regulatory Agency (ANVISA), Brasilia, DF, Brazil., Hostyn S; Janssen Research & Development, LLC, a Johnson & Johnson Company, Predictive Analytics & Stability Sciences Coe, Beerse, Belgium., Huang Z; Drug Product Development, Bristol-Myers Squibb Co., New Brunswick, New Jersey, USA., Ultramari M; Spektra Soluções Científico-Regulatórias Ltda, São Paulo, Brazil., Zelesky T; Analytical Research & Development, Pfizer Inc., Groton, Connecticut, USA., Baertschi SW; Baertschi Consulting LLC, Carmel, Indiana, USA.
Jazyk: angličtina
Zdroj: The AAPS journal [AAPS J] 2024 Aug 22; Vol. 26 (5), pp. 96. Date of Electronic Publication: 2024 Aug 22.
DOI: 10.1208/s12248-024-00961-3
Abstrakt: Stress testing (also known as forced degradation) of pharmaceutical drug substances and products is a critical part of the drug development process, providing insight into the degradation pathways of drug substances and drug products. This information is used to support the development of stability-indicating methods (SIMs) capable of detecting pharmaceutically relevant degradation products that might potentially be observed during manufacturing, long-term storage, distribution, and use. Assessing mass balance of stressed samples is a key aspect of developing SIMs and is a regulatory expectation. However, the approaches to measure, calculate, and interpret mass balance can vary among different pharmaceutical companies. Such disparities also pose difficulties for health authorities when reviewing mass balance assessments, which may result in the potential delay of drug application approvals. The authors have gathered input from 10 pharma companies to map out a practical review of science-based approaches and technical details to assess and interpret mass balance results. Key concepts of mass balance are introduced, various mass balance calculations are demonstrated, and recommendations on how to investigate poor mass balance results are presented using real-world case studies. Herein we provide a single source reference on the topic of mass balance in pharmaceutical forced degradation for small molecule drug substances and drug products in support of regulatory submissions with the goal of facilitating a shared understanding among pharmaceutical scientists and health authorities.
(© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
Databáze: MEDLINE
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