Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying
Continuous manufacturing (CM) is a promising strategy to achieve various benefits in the context of quality, flexibility, safety and cost in pharmaceutical production. One of the main technical challenges of CM is that the process needs to handle transient conditions such as the start-up phase befor...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-01-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/12/1/67 |
| _version_ | 1828275543870537728 |
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| author | Victoria Pauli Peter Kleinebudde Markus Krumme |
| author_facet | Victoria Pauli Peter Kleinebudde Markus Krumme |
| author_sort | Victoria Pauli |
| collection | DOAJ |
| description | Continuous manufacturing (CM) is a promising strategy to achieve various benefits in the context of quality, flexibility, safety and cost in pharmaceutical production. One of the main technical challenges of CM is that the process needs to handle transient conditions such as the start-up phase before state of control operation is reached, which can potentially cause out-of-specification (OOS) material. In this context, the presented paper aims to demonstrate that suitable process control strategies during start-up of a continuous granulation and drying operation can limit or even avoid OOS material production and hence can ensure that the provided benefits of CM are not compromised by poor production yields. In detail, heat-up of the drying chamber prior the start of production can lead to thermal energy being stored inside of the stainless-steel housing, acting as an energy buffer that is known to cause over-dried granules in the first few minutes of the drying process. To compensate this issue, an automatic ramping procedure of dryer rotation speed (and hence drying time) was introduced into the plant’s process control system, which counteracts the excessive drying capacity during start-up. As a result, dry granules exiting the dryer complied with the targeted intermediate critical quality attribute loss-on-drying (LOD) from the very beginning of production. |
| first_indexed | 2024-04-13T06:48:11Z |
| format | Article |
| id | doaj.art-2835c5c9d4c5498e91687c17a71d9980 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T06:48:11Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-2835c5c9d4c5498e91687c17a71d99802022-12-22T02:57:29ZengMDPI AGPharmaceutics1999-49232020-01-011216710.3390/pharmaceutics12010067pharmaceutics12010067Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and DryingVictoria Pauli0Peter Kleinebudde1Markus Krumme2Novartis Pharma AG, Continuous Manufacturing (CM) Unit, Novartis Campus, 4002 Basel, SwitzerlandInstitute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitaetsstr. 1, 40225 Dusseldorf, GermanyNovartis Pharma AG, Continuous Manufacturing (CM) Unit, Novartis Campus, 4002 Basel, SwitzerlandContinuous manufacturing (CM) is a promising strategy to achieve various benefits in the context of quality, flexibility, safety and cost in pharmaceutical production. One of the main technical challenges of CM is that the process needs to handle transient conditions such as the start-up phase before state of control operation is reached, which can potentially cause out-of-specification (OOS) material. In this context, the presented paper aims to demonstrate that suitable process control strategies during start-up of a continuous granulation and drying operation can limit or even avoid OOS material production and hence can ensure that the provided benefits of CM are not compromised by poor production yields. In detail, heat-up of the drying chamber prior the start of production can lead to thermal energy being stored inside of the stainless-steel housing, acting as an energy buffer that is known to cause over-dried granules in the first few minutes of the drying process. To compensate this issue, an automatic ramping procedure of dryer rotation speed (and hence drying time) was introduced into the plant’s process control system, which counteracts the excessive drying capacity during start-up. As a result, dry granules exiting the dryer complied with the targeted intermediate critical quality attribute loss-on-drying (LOD) from the very beginning of production.https://www.mdpi.com/1999-4923/12/1/67continuous manufacturingprocess controlmodel-based controlstart-upshut-downcost reduction |
| spellingShingle | Victoria Pauli Peter Kleinebudde Markus Krumme Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying Pharmaceutics continuous manufacturing process control model-based control start-up shut-down cost reduction |
| title | Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying |
| title_full | Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying |
| title_fullStr | Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying |
| title_full_unstemmed | Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying |
| title_short | Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying |
| title_sort | predictive model based process start up in pharmaceutical continuous granulation and drying |
| topic | continuous manufacturing process control model-based control start-up shut-down cost reduction |
| url | https://www.mdpi.com/1999-4923/12/1/67 |
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