LAPSE:2023.1480
Published Article

LAPSE:2023.1480
A Feedback Control Strategy for a Fed-Batch Monoclonal Antibody Production Process Utilising Infrequent and Irregular Sampled Measurements
February 21, 2023
Abstract
The ability to take non-invasive Raman measurements presents a unique opportunity to use one Raman probe across multiple vessels in parallel, reducing costs but making measurements infrequent. Under these conditions, infrequent and irregular feedback signals can result in poor closed-loop control performance. This study addressed the issue of infrequent and irregular Raman measurements using a linear dynamic model developed from interpolated data to predict more frequent measurements of the controlled variable. The simulated monoclonal antibody production was sampled hourly with white noise added to the simulated glucose concentration to replicate real Raman measurements. The hourly samples were interpolated into 15 min intervals and a linear dynamic model was developed to predict the glucose concentration at 15 min intervals. These predicted values were then used in a feedback control loop by using model predictive control or a conventional proportional and integral controller to control the glucose concentration at 15 min sampling intervals. For setpoint tracking, the model predictive control reduced the integral of absolute errors to 14,600 from 15,900 (with a 1 h sampling time) or 8.2% reduction. With adaptive model predictive control, the integral of absolute errors was reduced from 14,500 (1 h sampling time) to 14,200 for setpoint tracking and from 13,500 (1 h sampling time) to 13,300 for disturbance rejection. A final comparison demonstrated that the proposed method can also cope with random variations in the sampling time.
The ability to take non-invasive Raman measurements presents a unique opportunity to use one Raman probe across multiple vessels in parallel, reducing costs but making measurements infrequent. Under these conditions, infrequent and irregular feedback signals can result in poor closed-loop control performance. This study addressed the issue of infrequent and irregular Raman measurements using a linear dynamic model developed from interpolated data to predict more frequent measurements of the controlled variable. The simulated monoclonal antibody production was sampled hourly with white noise added to the simulated glucose concentration to replicate real Raman measurements. The hourly samples were interpolated into 15 min intervals and a linear dynamic model was developed to predict the glucose concentration at 15 min intervals. These predicted values were then used in a feedback control loop by using model predictive control or a conventional proportional and integral controller to control the glucose concentration at 15 min sampling intervals. For setpoint tracking, the model predictive control reduced the integral of absolute errors to 14,600 from 15,900 (with a 1 h sampling time) or 8.2% reduction. With adaptive model predictive control, the integral of absolute errors was reduced from 14,500 (1 h sampling time) to 14,200 for setpoint tracking and from 13,500 (1 h sampling time) to 13,300 for disturbance rejection. A final comparison demonstrated that the proposed method can also cope with random variations in the sampling time.
Record ID
Keywords
adaptive modelling, batch processes, infrequent measurement, Model Predictive Control, process analytical technologies
Subject
Suggested Citation
Joynes L, Zhang J. A Feedback Control Strategy for a Fed-Batch Monoclonal Antibody Production Process Utilising Infrequent and Irregular Sampled Measurements. (2023). LAPSE:2023.1480
Author Affiliations
Joynes L: School of Engineering, Merz Court, Newcastle University, Newcastle upon Tyne NE1 7RU, UK
Zhang J: School of Engineering, Merz Court, Newcastle University, Newcastle upon Tyne NE1 7RU, UK [ORCID]
Zhang J: School of Engineering, Merz Court, Newcastle University, Newcastle upon Tyne NE1 7RU, UK [ORCID]
Journal Name
Processes
Volume
10
Issue
8
First Page
1448
Year
2022
Publication Date
2022-07-24
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr10081448, Publication Type: Journal Article
Record Map
Published Article

LAPSE:2023.1480
This Record
External Link

https://doi.org/10.3390/pr10081448
Publisher Version
Download
Meta
Record Statistics
Record Views
440
Version History
[v1] (Original Submission)
Feb 21, 2023
Verified by curator on
Feb 21, 2023
This Version Number
v1
Citations
Most Recent
This Version
URL Here
https://psecommunity.org/LAPSE:2023.1480
Record Owner
Auto Uploader for LAPSE
Links to Related Works
