(442a) Framework for Changeover Cleaning in Pharmaceutical Industries

Advances in pharmaceutical manufacturing practices, including continuous manufacturing, distributed manufacturing, campaign optimization, modular facility design, and an emphasis on personalized medicine, have significantly enhanced operational flexibility and production efficiency.¹ However, these innovations introduce new challenges, as shorter campaign durations increase the time and effort required for more frequent cleaning steps while still ensuring that the risk of cross-contamination is minimized.^2-3 Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), place significant emphasis on robust contamination control programs, making effective cleaning strategies essential for ensuring drug product quality, patient safety, and compliance with current Good Manufacturing Practices (cGMP).⁴ Although routine cleaning procedures are an established part of standard operations, there have been limited efforts reported on improving their efficiency or minimizing the related downtime and resource consumption.

This study presents a generalized modeling framework for optimizing the cleaning process in pharmaceutical manufacturing. The cleaning process is analyzed using two common pharmaceutical vessel configurations: uniformly mixed and radially mixed vessels. By modeling these configurations, we quantify as well as observe the impact of varying operating conditions on key performance metrics such as downtime, solvent usage, and cleaning effectiveness. The insights obtained enable the identification of optimal cleaning conditions that achieve regulatory cleanliness standards while minimizing operational costs and environmental impact.

The proposed framework offers a structured approach for the systematic selection of cleaning solvents, optimization of cleaning process parameters, and evaluation of trade-offs between traditional cleaning methods and disposable alternatives. The generalized modeling approach enables the extrapolation of cleaning analyses to a broad pharmaceutical flowsheet, allowing for the estimation of cleaning-related downtimes and associated costs across multiple unit operations. This enables pharmaceutical manufacturers to make informed decisions that enhance efficiency and reduce resource wastage while upholding stringent product safety standards. Furthermore, the methodology aligns with sustainability goals by minimizing solvent usage and reducing the overall environmental footprint of cleaning processes. This integrative approach supports the advancement of greener and more efficient pharmaceutical operations.

In summary, this work highlights the critical role of process modeling and changeover cleaning management in enhancing operational efficiency within the pharmaceutical industry. By integrating process modeling and process analytical technology (PAT) tools with industry best practices, the proposed approach paves the way for more sustainable, cost-effective, and regulatory-compliant pharmaceutical manufacturing practices.

References:

1. Gong, SJ., Kim, H.R., Park, YJ. et al.Recent trends in continuous manufacturing and digitalization in pharmaceutical process development and manufacturing. Journal of Pharmaceutical Investigation, (2025).
2. S. Food and Drug Administration. Code of Federal Regulations—“Equipment cleaning and maintenance.” National Archives and Records Administration, (1993).
3. S. Food and Drug Administration. Code of Federal Regulations— "Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; general.” National Archives and Records Administration, (1993).
4. Haleem, R. M., Salem, M. Y., Fatahallah, F. A., & Abdelfattah, L. E. Quality in the pharmaceutical industry – A literature review. Saudi Pharmaceutical Journal, 23(5), 463-469 (2015).