The Biomanufacturing Paradigm Shift: Why Process Intensification Is Gaining Traction

As drug cost pressures and biosimilar competition accelerate, biopharma stakeholders recognize that now is the time to shift toward future-focused manufacturing. While fed-batch processes have long been the standard, intensified and continuous processes offer opportunities to increase productivity, reduce COGS, and achieve sustainability targets. Process intensification (PI), supported by automation, innovation, and single use technology, enables more efficient use of time, facility space, and equipment. In turn, CDMOs can offer sponsors competitive pricing and multi-modal manufacturing capabilities.

In a recent panel discussion on real-world PI strategies for biomanufacturing success, industry experts explored the factors driving the industry toward continuous processing, strategies for stepwise implementation, and strong use cases. The post-panel Q&A offered insights into which technologies are crucial to continuous process success and how regulators are responding to this shift.

Q: How do you determine if you should use resin or membrane technology to achieve your targets in terms of efficiency, cost-effectiveness, and other PI goals?

Tiago Matos, Associate Principal Scientist, Bioprocess Drug Substance and Commercialization, Merck:

Whether you’re using resins or membranes, the priority is always product quality. We have had situations where membranes operate more efficiently, but once you move to vaccines or large molecules, that makes a lot more sense. In the protein space, resins are still applicable. Sponsors must keep the quality of the final product in mind.

Kevin Brower, Global Head, Purification Development, Sanofi: In the end, it's about utilization, which includes total cost of ownership [TOC] for a large column, a small column, and a membrane for product purification. Manufacturers must carefully estimate costs and be wary of assumptions with Protein A, for example. Blockbuster drugs will cycle 200 times every six weeks and then move to a new column. However, medium and low volume drugs may not. The assumption that you will fully utilize the resin in a large column may be incorrect. Thus, even in a commercial setting, a multimembrane approach may be more important for TOC and changeover.

Geert Lissens, Head of Product Management, Sartorius: Cost modeling tools can be employed to find out what is the best choice in such a scenario.

Q: What technologies need improvements to increase continuous process adoption?

Matos: We need to expand the scope to understand what Industry 4.0 entails beyond automation and plug-and-play technologies. The digital infrastructure needs to be optimized for existing facilities. Digital twins, machine learning, AI algorithms, data analysis, and real-time testing release could all have a significant impact on platforms. AI is not going to replace everything, but it will accelerate the way we build models or soft sensors throughout production campaigns, providing notifications on whether a CQA is changing or pressure is rising in the next cycle. This information is critical to ensure process-optimized outcomes reduce overall cost and accelerate processing.

Brower: Another critical improvement is cell retention technology. One of the single largest barriers to widespread adoption of continuous or perfusion reactors is the lack of scalable, low-fouling cell retention devices. If the industry solves that, adoption will increase overnight. The second is the availability of off-the-shelf PI skids for downstream applications. Most current adopters have done a mix of custom and suboptimal, off-the-shelf skids. Sartorius’ upcoming Pionic® platform is meant to address this.

David Garcia Münzer, Director, Scientific Office, Drug Substance Development, Novartis Pharma AG: To move from connected to truly continuous processing, process analytical technology [PAT] will be critical. A key difference between fed-batch and continuous manufacturing is the need to define a diversion strategy. PAT will play a key role in materializing that.

Q: Can you elaborate on what PAT innovation entails? Are there any specific technologies which are absolutely needed for adopting PI?

Garcia Münzer: If you want to understand a disturbance or deviation in your process and divert material based on CQAs, you need advanced, real-time PAT to efficiently generate a result and divert as your process is running. If you're not able to quantify that deviation or disturbance, how can you divert it? These are important elements to consider when moving to Level 4 adoption of PI — a truly continuous process.

Q: At what point in the Biologics License Application (BLA) filing process should you notify regulators that you are moving to continuous manufacturing?

Abijar Bhori, Associate Vice President, Head of Purification Process Development, Enzene: Many companies are moving forward with a continuous process approach, at least for FIH studies, which can then inform subsequent regulatory campaigns. Regulatory agencies are open to sponsors using continuous processes for biologic filings and are even willing to provide suggestions on PI strategy during different stages of development. There is no bottleneck in this regard.

About Sartorius

At Sartorius, we empower scientists and engineers to simplify and accelerate progress in life science and bioprocessing, enabling the development of new and better therapies and more affordable medicine.

About The Panelists

Geert Lissens, Head of Product Management at Sartorius since 2016, drives innovation and strategic development for downstream systems and instruments. He has more than 20 years of experience in bioprocessing spanning technical, sales, marketing, and product leadership roles.

Abijar Bhori leads the Purification Process Development and Drug Product Development teams at Enzene. His expertise includes purification process development of both small and large biomolecules, process characterization, scale-up, and technology transfer to manufacturing sites.

Kevin Brower is Global Head of Purification Development in the Mammalian Platform at Sanofi. His team performs process development for antibodies, multi-specifics, enzymes, and antibody drug conjugates, as well as technology development in continuous manufacturing, high throughput, PAT, and modeling.

Tiago Matos is an Associate Principal Scientist in Bioprocess Drug Substance and Commercialization at Merck with over a decade of experience in the pharmaceutical industry. At Merck, he drives innovation in process development, smart processing, and advanced control strategies.

David Garcia Münzer is Director of the Scientific Office in Drug Substance Development at Novartis Pharma AG. Since joining Novartis in 2015, David has focused on the development of innovative technologies for portfolio projects like integrated continuous biomanufacturing.