Next Article in Journal
Green Synthesis of Potent Antimicrobial Silver Nanoparticles Using Different Plant Extracts and Their Mixtures
Previous Article in Journal
Formation and Evolution Mechanism for Carbonaceous Deposits on the Surface of a Coking Chamber
Previous Article in Special Issue
Online Decision-Support Tool “TECHoice” for the Equipment Technology Choice in Sterile Filling Processes of Biopharmaceuticals
Open AccessFeature PaperArticle

Robust Process Design in Pharmaceutical Manufacturing under Batch-to-Batch Variation

1
Institute of Energy and Process Systems Engineering, Technische Universität Braunschweig, Franz-Liszt-Straße 35, 38106 Braunschweig, Germany
2
Center of Pharmaceutical Engineering (PVZ), Technische Universität Braunschweig, Franz-Liszt-Straße 35a, 38106 Braunschweig, Germany
*
Author to whom correspondence should be addressed.
Processes 2019, 7(8), 509; https://doi.org/10.3390/pr7080509
Received: 7 June 2019 / Revised: 28 July 2019 / Accepted: 30 July 2019 / Published: 3 August 2019
(This article belongs to the Special Issue Model-Based Tools for Pharmaceutical Manufacturing Processes)
  |  
PDF [803 KB, uploaded 3 August 2019]
  |  

Abstract

Model-based concepts have been proven to be beneficial in pharmaceutical manufacturing, thus contributing to low costs and high quality standards. However, model parameters are derived from imperfect, noisy measurement data, which result in uncertain parameter estimates and sub-optimal process design concepts. In the last two decades, various methods have been proposed for dealing with parameter uncertainties in model-based process design. Most concepts for robustification, however, ignore the batch-to-batch variations that are common in pharmaceutical manufacturing processes. In this work, a probability-box robust process design concept is proposed. Batch-to-batch variations were considered to be imprecise parameter uncertainties, and modeled as probability-boxes accordingly. The point estimate method was combined with the back-off approach for efficient uncertainty propagation and robust process design. The novel robustification concept was applied to a freeze-drying process. Optimal shelf temperature and chamber pressure profiles are presented for the robust process design under batch-to-batch variation. View Full-Text
Keywords: robust process design; batch-to-batch variation; parametric probability-box; point estimate method; pharmaceutical manufacturing; freeze-drying robust process design; batch-to-batch variation; parametric probability-box; point estimate method; pharmaceutical manufacturing; freeze-drying
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Xie, X.; Schenkendorf, R. Robust Process Design in Pharmaceutical Manufacturing under Batch-to-Batch Variation. Processes 2019, 7, 509.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Processes EISSN 2227-9717 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top