Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative
1. Introduction: Where Are We Now
1.1. Critical Views on Current Practices
1.2. Academic Engagements Supporting the Advancement
2. What Is Creating This Disjoint
2.1. Are Costs or Regulators to Blame
2.2. Realization of Flexible and Intensified Manufacturing
2.3. The Dilemma of Technology Evolution—Continuous Stainless Steel vs. Single-Use
2.4. Organisational Readiness
3. What Can Be Done to Improve the Situation
3.1. Need for More PSE Case Studies to Build Confidence
3.2. PAT Solutions and Robotics for Better Control
3.3. Modeling and Simulation
3.4. The Clarity in Regulation for Continuous Biologics Manufacturing
4. Sustainability Considerations of Continuous Manufacturing of Biopharmaceuticals: Process Integration and Automation
5.1. From Smart Sensors to Big Data
5.2. Digital Twins
5.3. Application of Modeling in Regulatory Decision
5.4. Leveraging Process Data
5.5. Hybrid Facilities: Acknowledging the Best of Both Worlds
6. Summary and Outlook
- Improvement in automation to allow flexibility in the design and control of continuous processes;
- Adoption of a “digital twin” of processes to reduce the costs and risks linked with a decision made based on a limited set of experimental results;
- Application of detailed modeling and expert systems to support the development and regulatory requirements, such as scale-down modeling;
- Working on hybrid approaches such as single-use and multi-use to obtain best-of-all outcomes, thus enabling continuous manufacturing;
- Application of “big data” to support process development, control, and regulatory filing of a project.
- Training on realistic situations highlighting risks and benefits of continuous manufacturing will allow removing the barrier caused by preexisting perceptions;
- Acquisition of trained staff who can support the adoption of new technology;
- Identifying key stakeholders from across the organization and getting them involved in the migration processes;
- Early alignment of R&D and commercial manufacturing business drivers to realize the extensive benefits of continuous biologics manufacturing.
- Clarity on the regulation of continuous vs. batch definitions under newer integrated and hybrid biomanufacturing process designs will be very useful;
- Increase in acceptability of digital twins as evidence for regulatory clearance;
- A joint effort by regulatory agencies and industries to develop a possible roadmap for the integrated continuous manufacturing will be highly beneficial for the biologics sector;
- Harmonization of continuous manufacturing standards and regulations.
Conflicts of Interest
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|Biomanufacturing consortium (BioMAN)||Industry–academia collaboration lead by Massachusetts Institute of Technology (MIT)||Several stakeholders work together to develop new knowledge, science, technologies, and strategies to improve biomanufacturing .|
|BioPhorum consortium||Cross-industry collaboration||Connecting most big biopharmaceutical manufacturers and suppliers collaboratively to produce technical documents to explore, propose, and define industry best practices on the topics mentioned earlier .|
|National Institute for Innovation in Manufacturing Biopharmaceuticals (NIIMBL)||Public–private partnership, manufacturing innovation institutes funded through a cooperative agreement with the National Institute of Standards and Technology (NIST)||To achieve a public–private partnership to enable more efficient and rapid manufacturing capabilities and biopharmaceutical manufacturing workforce to accelerate biopharmaceutical innovation.|
|BIOPRO cluster||Industry–academia collaboration lead by Technical University of Denmark (DTU)||Developing new ways of making bio-based production more efficient and sustainable by reducing the consumption of energy and raw materials while improving yields .|
|Multi-Use Stainless Steel Systems||Single-Use Systems|
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Kumar, A.; Udugama, I.A.; Gargalo, C.L.; Gernaey, K.V. Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative. Processes 2020, 8, 1641. https://doi.org/10.3390/pr8121641
Kumar A, Udugama IA, Gargalo CL, Gernaey KV. Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative. Processes. 2020; 8(12):1641. https://doi.org/10.3390/pr8121641Chicago/Turabian Style
Kumar, Ashish, Isuru A. Udugama, Carina L. Gargalo, and Krist V. Gernaey. 2020. "Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative" Processes 8, no. 12: 1641. https://doi.org/10.3390/pr8121641