Manufacturing classification system in the real world: factors influencing manufacturing process choices for filed commercial oral solid dosage formulations, case studies from industry and considerations for continuous processing. (26th November 2018)

• Record Type: Journal Article
• Authors: Leane, Michael; Pitt, Kendal; Reynolds, Gavin K.; Dawson, Neil; Ziegler, Iris; Szepes, Aniko; Crean, Abina M.; Dall Agnol, Rafaela; The Manufacturing Classification System (MCS) Working Group,
• Is Part Of: Pharmaceutical development and technology. Volume 23:Number 10(2018)
• Page Start: 964
• Page End: 977
• Publication Date: 2018-11-26
• Subjects: Drug product manufacturing processes -- oral solid dosage forms -- pharmaceutical development -- quality by design -- drug substance -- continuous processing; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.1080/10837450.2018.1534863
• Languages: English
• ISSNs: 1083-7450

Abstract

Abstract: Following the first Manufacturing Classification System (MCS) paper, the team conducted surveys to establish which active pharmaceutical ingredient (API) properties were important when selecting or modifying materials to enable an efficient and robust pharmaceutical manufacturing process. The most commonly identified factors were (1) API particle size: small particle sizes are known to increase risk of processing issues; (2) Drug loading in the formulation: high drug loadings allow less opportunity to mitigate poor API properties through the use of excipients. The next step was to establish linkages with process decisions by identifying publicly-available proxies for these important parameters: dose (in place of drug loading) and BCS class (in place of particle size). Poorly-soluble API were seen as more likely to have controlled (smaller) particle size than more highly soluble API. Analysis of 435 regulatory filings revealed that higher doses and more poorly-soluble API was associated with more complex processing routes. Replacing the proxy factors with the original parameters should give the opportunity to demonstrate stronger trends. This assumption was tested by accessing a dataset relating to commercial tablet products. This showed that, for dry processes, a larger particle size was associated with higher achievable drug loading as determined by percolation threshold.