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Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study.
J Pharm Biomed Anal. 2020 Feb 05; 179:112971.JP

Abstract

Continuous Manufacturing (CM) of pharmaceutical drug products is a rather new approach within the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line used for clinical production of solid dosage forms was investigated with a thorough monitoring strategy regarding process performance and robustness. The line was composed of the subsequent continuous unit operations feeding - twin-screw wet-granulation - fluid-bed drying - sieving and tableting; the formulation of a new pharmaceutical entity in development was selected for this study. In detail, a Design of Experiments (DoE) was used to evaluate the impact of the three main factors (amount of water, filling rate, and shear force in twin-screw granulator) on the tablet quality. The process was monitored via in-process control (IPC) tests (e.g. weight, hardness, disintegration, and loss-on-drying), Process Analytical Technologies (PAT), and through the analysis of the process parameters (multivariate process control). The tested formulation was very robust to the large process variation of the DoE: all IPC results were in specification, the PAT probes provided stable results for the content uniformity and no critical variations can be detected in the process parameters. An adequate monitoring strategy was presented and the robustness of the process with one formulation has been demonstrated. In summary, this continuous process in combination with smart formulation development allows the robust production of constant quality tablets. The synergy between PAT, process data science and IPC creates an adequate monitoring framework of the continuous manufacturing line.

Authors+Show Affiliations

Novartis Pharma AG, Continuous Manufacturing (CM) Unit, CH-4002, Basel, Switzerland. Electronic address: yves.roggo@novartis.com.Novartis Pharma AG, Continuous Manufacturing (CM) Unit, CH-4002, Basel, Switzerland.Novartis Pharma AG, Continuous Manufacturing (CM) Unit, CH-4002, Basel, Switzerland.Novartis Pharma AG, Continuous Manufacturing (CM) Unit, CH-4002, Basel, Switzerland.Novartis Pharma AG, Continuous Manufacturing (CM) Unit, CH-4002, Basel, Switzerland.Novartis Pharma AG, Continuous Manufacturing (CM) Unit, CH-4002, Basel, Switzerland.Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitaetsstr. 1, 40225, Dusseldorf, Germany.Novartis Pharma AG, Continuous Manufacturing (CM) Unit, CH-4002, Basel, Switzerland.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31771809

Citation

Roggo, Yves, et al. "Continuous Manufacturing Process Monitoring of Pharmaceutical Solid Dosage Form: a Case Study." Journal of Pharmaceutical and Biomedical Analysis, vol. 179, 2020, p. 112971.
Roggo Y, Pauli V, Jelsch M, et al. Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study. J Pharm Biomed Anal. 2020;179:112971.
Roggo, Y., Pauli, V., Jelsch, M., Pellegatti, L., Elbaz, F., Ensslin, S., Kleinebudde, P., & Krumme, M. (2020). Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study. Journal of Pharmaceutical and Biomedical Analysis, 179, 112971. https://doi.org/10.1016/j.jpba.2019.112971
Roggo Y, et al. Continuous Manufacturing Process Monitoring of Pharmaceutical Solid Dosage Form: a Case Study. J Pharm Biomed Anal. 2020 Feb 5;179:112971. PubMed PMID: 31771809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Continuous manufacturing process monitoring of pharmaceutical solid dosage form: A case study. AU - Roggo,Yves, AU - Pauli,Victoria, AU - Jelsch,Morgane, AU - Pellegatti,Laurent, AU - Elbaz,Frantz, AU - Ensslin,Simon, AU - Kleinebudde,Peter, AU - Krumme,Markus, Y1 - 2019/11/09/ PY - 2019/08/20/received PY - 2019/11/01/revised PY - 2019/11/01/accepted PY - 2019/11/28/pubmed PY - 2020/11/13/medline PY - 2019/11/28/entrez KW - Continuous manufacturing KW - Multivariate data analysis KW - Process analytical technology KW - Process data analytics KW - Process data science KW - Process monitoring KW - Solid dosage form SP - 112971 EP - 112971 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 179 N2 - Continuous Manufacturing (CM) of pharmaceutical drug products is a rather new approach within the pharmaceutical industry. In the presented paper, a GMP continuous wet granulation line used for clinical production of solid dosage forms was investigated with a thorough monitoring strategy regarding process performance and robustness. The line was composed of the subsequent continuous unit operations feeding - twin-screw wet-granulation - fluid-bed drying - sieving and tableting; the formulation of a new pharmaceutical entity in development was selected for this study. In detail, a Design of Experiments (DoE) was used to evaluate the impact of the three main factors (amount of water, filling rate, and shear force in twin-screw granulator) on the tablet quality. The process was monitored via in-process control (IPC) tests (e.g. weight, hardness, disintegration, and loss-on-drying), Process Analytical Technologies (PAT), and through the analysis of the process parameters (multivariate process control). The tested formulation was very robust to the large process variation of the DoE: all IPC results were in specification, the PAT probes provided stable results for the content uniformity and no critical variations can be detected in the process parameters. An adequate monitoring strategy was presented and the robustness of the process with one formulation has been demonstrated. In summary, this continuous process in combination with smart formulation development allows the robust production of constant quality tablets. The synergy between PAT, process data science and IPC creates an adequate monitoring framework of the continuous manufacturing line. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/31771809/Continuous_manufacturing_process_monitoring_of_pharmaceutical_solid_dosage_form:_A_case_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(19)32037-0 DB - PRIME DP - Unbound Medicine ER -