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Open AccessArticle

Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying

1
Novartis Pharma AG, Continuous Manufacturing (CM) Unit, Novartis Campus, 4002 Basel, Switzerland
2
Institute of Pharmaceutics and Biopharmaceutics, Heinrich Heine University, Universitaetsstr. 1, 40225 Dusseldorf, Germany
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(1), 67; https://doi.org/10.3390/pharmaceutics12010067
Received: 29 November 2019 / Revised: 9 January 2020 / Accepted: 10 January 2020 / Published: 15 January 2020
(This article belongs to the Special Issue Continuous Pharmaceutical Manufacturing)
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. View Full-Text
Keywords: continuous manufacturing; process control; model-based control; start-up; shut-down; cost reduction continuous manufacturing; process control; model-based control; start-up; shut-down; cost reduction
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MDPI and ACS Style

Pauli, V.; Kleinebudde, P.; Krumme, M. Predictive Model-Based Process Start-Up in Pharmaceutical Continuous Granulation and Drying. Pharmaceutics 2020, 12, 67.

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