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

Johannes Khinast, Michael Leane, Kendal Pitt, Gavin K. Reynolds, Neil Dawson, Iris Ziegler, Aniko Szepes, Abina M. Crean, Rafaela Dall Agnol, Bianca Broegmann, Stuart Charlton, Conrad Davies, John Gamble, Michael Gamlen, Wen Kai Hsiao, Yaroslav Khimyak, Peter Kleinebudde, Chris Moreton, Mira Oswald, Susanne Page & 5 Sonstige Amrit Paudel, Ranjita Sahoo, Stephen Sheehan, Howard Stamato, Elaine Stone

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

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.
Originalspracheenglisch
Seiten (von - bis)964-977
Seitenumfang13
FachzeitschriftPharmaceutical development and technology
DOIs
PublikationsstatusVeröffentlicht - 2018

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Industry
Particle Size
Pharmaceutical Preparations
Proxy
Drug Compounding
Excipients
Tablets

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    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. / Khinast, Johannes; Leane, Michael; Pitt, Kendal ; Reynolds, Gavin K.; Dawson, Neil; Ziegler, Iris; Szepes, Aniko; Crean, Abina M.; Agnol, Rafaela Dall; Broegmann, Bianca; Charlton, Stuart; Davies, Conrad; Gamble, John; Gamlen, Michael; Hsiao, Wen Kai; Khimyak, Yaroslav; Kleinebudde, Peter; Moreton, Chris; Oswald, Mira; Page, Susanne; Paudel, Amrit; Sahoo, Ranjita; Sheehan, Stephen ; Stamato, Howard; Stone, Elaine.

    in: Pharmaceutical development and technology, 2018, S. 964-977.

    Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

    Khinast, J, Leane, M, Pitt, K, Reynolds, GK, Dawson, N, Ziegler, I, Szepes, A, Crean, AM, Agnol, RD, Broegmann, B, Charlton, S, Davies, C, Gamble, J, Gamlen, M, Hsiao, WK, Khimyak, Y, Kleinebudde, P, Moreton, C, Oswald, M, Page, S, Paudel, A, Sahoo, R, Sheehan, S, Stamato, H & Stone, E 2018, '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' Pharmaceutical development and technology, S. 964-977. https://doi.org/10.1080/10837450.2018.1534863
    Khinast, Johannes ; Leane, Michael ; Pitt, Kendal ; Reynolds, Gavin K. ; Dawson, Neil ; Ziegler, Iris ; Szepes, Aniko ; Crean, Abina M. ; Agnol, Rafaela Dall ; Broegmann, Bianca ; Charlton, Stuart ; Davies, Conrad ; Gamble, John ; Gamlen, Michael ; Hsiao, Wen Kai ; Khimyak, Yaroslav ; Kleinebudde, Peter ; Moreton, Chris ; Oswald, Mira ; Page, Susanne ; Paudel, Amrit ; Sahoo, Ranjita ; Sheehan, Stephen ; Stamato, Howard ; Stone, Elaine. / 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. in: Pharmaceutical development and technology. 2018 ; S. 964-977.
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    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.",
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    AU - Reynolds, Gavin K.

    AU - Dawson, Neil

    AU - Ziegler, Iris

    AU - Szepes, Aniko

    AU - Crean, Abina M.

    AU - Agnol, Rafaela Dall

    AU - Broegmann, Bianca

    AU - Charlton, Stuart

    AU - Davies, Conrad

    AU - Gamble, John

    AU - Gamlen, Michael

    AU - Hsiao, Wen Kai

    AU - Khimyak, Yaroslav

    AU - Kleinebudde, Peter

    AU - Moreton, Chris

    AU - Oswald, Mira

    AU - Page, Susanne

    AU - Paudel, Amrit

    AU - Sahoo, Ranjita

    AU - Sheehan, Stephen

    AU - Stamato, Howard

    AU - Stone, Elaine

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