In recent decades, sensor-less cars that rely on human decision-making have evolved into self-driving taxis that arrive on demand. Beate Mueller-Tiemann, PhD, CTO of the global life sciences company Cytiva, points to these autonomous vehicles as an analogy for the digitization of the biomanufacturing industry, which has recently culminated in a new era known as “Bioprocess 5.0.” This latest generation integrates advanced digital technologies, automation, and sustainability principles to streamline the production of biological products, such as pharmaceuticals, vaccines, and enzymes.
“Pharma companies like to use the term ‘smart manufacturing,’ in which operations are driven not only by serendipity and diligent work, but by data-driven insights and adaptive process control,” explained Mueller-Tiemann in an interview with GEN.
5.0 pillars
The hallmarks of Bioprocess 5.0 include the incorporation of artificial intelligence (AI) tools to optimize and control of bioprocess parameters in real-time to support improved quality and standardization. For example, virtual replicas that simulate processes, known as “digital twins,” can test scenarios while minimizing risk to actual production runs, thereby increasing process consistency, limiting error, and increasing speed-to-clinic.
“Successful bioprocessing pipelines will maintain a focused approach, in which upstream and downstream efforts are connected with a focus on yield, robustness, and reproducibility,” Sebastián Arana, head of process solutions life science business of Merck KGaA, Darmstadt, Germany. told GEN. He emphasizes that data should be leveraged at every stage for faster decisions and fewer batch failures.
Arana also notes that sustainability goals remain at the forefront of Bioprocess 5.0, with the use of renewable energy being one of the most impactful movements to decrease the footprint of bioprocessing production. MilliporeSigma is the U.S. and Canada Life Science business of Merck KGaA, Darmstadt, Germany. It currently operates with 78% renewable electricity and is aiming to increase that value to over 90% in Q1 of 2026.
“The next chapter is the transition to focusing on reducing the footprints of the individual products and increasing the intensification of bioprocessing,” explained Arana. Aligned with this goal, MilliporeSigma is driving a Design for Sustainability program into the company’s R&D pipelines. The program develops eco-friendly and disposable products.
Sigma Mostafa, PhD, CSO at KBI Biopharma, highlights the incorporation of human-centric automation within Bioprocess 5.0, in which digital tools are designed to work with humans to enhance manufacturing capabilities. She says the emphasis remains on scientists working with software as opposed to machines replacing humans.
“You can come up with the best automation or machine-learning solution, but it may not take into account new sustainability solutions or how the industry and market are changing. 5.0 brings that holistic perspective,” Mostafa said. She lists particle characterization as an example process that bridges the balance between human decision-making and digital tools.
While machine-learning models can improve the precision of comprehensive analyses of the physical and chemical properties in a drug formulation, effectively evaluating the safety, efficacy, stability, and manufacturability of a drug requires living scientists to leverage existing knowledge from the literature to assist interpreting model results.
Scaling personal therapies
Mueller-Tiemann looks to CAR T manufacturing for autologous cancer cell therapy as a prime example of the need for autonomous systems. Specifically, as many CAR T therapeutics are moving toward autoimmune diseases with larger patient populations, manufacturers and technology providers will need to develop solutions that scale to that expanded reach.
Aligned with this goal, Cytiva announced a partnership in January that combines the company’s manufacturing technologies with the robotic platform of Cellular Origins, a cell therapy-focused manufacturing company, to enable production of cell and gene therapies for larger populations.
The recent story of Baby KJ, an infant who became the first patient to receive a bespoke gene editing therapy to treat his severe metabolic disorder, has also added new hope for scaling personalized therapies.
KJ was diagnosed with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, an often fatal urea cycle disorder with an estimated 50% mortality in early infancy. Given these urgent timelines, the FDA granted accelerated approval for his experimental bespoke base-editing therapy manufactured by Danaher-owned companies, Aldevron and Integrated DNA Technologies.
According to Kiran Musunuru, MD, PhD, one of the lead physicians overseeing KJ’s case and professor of translational research at Perelman School of Medicine at the University of Pennsylvania, the therapy’s cost was “not as expensive as you might think.” While the traditional approval route for gene editing therapies requires years of rigorous studies to demonstrate safety and effectiveness, the fast timelines to address KJ’s urgent health status significantly lowered costs compared to standard drug development. However, the bioprocessing industry is still wrestling with establishing a reproducible scalability blueprint that would support similar cases beyond KJ’s treatment.
When reflecting on the broader impact of single patient cases, Peter Marks, MD, PhD, former director of the Center for Biologics Evaluation and Research (CBER) at the FDA, urged regulatory approaches to leverage the information that is used repeatedly from product to product, while allowing for the required customization, such as guide RNA in the case of CRISPR constructs.
“Facilitating such a process could transform N-of-1 therapy into N-of-many therapies, thus leading to commercial viability of these products for rare diseases—a development that would ultimately benefit many persons with great unmet medical need,” Marks wrote earlier this year in an editorial in The New England Journal of Medicine.1
Complex molecules
The complexity of biomolecules has greatly evolved from the advent of monoclonal antibodies nearly half a century ago. Modalities such as antibody drug conjugate (ADC)-based drugs, a class of cancer therapies that combine the targeting ability of antibodies with the cell-killing power of cytotoxic drugs, require additional regulatory and manufacturing considerations, which can slow uptake. Despite adoption challenges, Mueller-Tiemann emphasizes that evolving therapies will mature and are here to stay.
“Complex new biologics, like ADCs, now mean we have a need for our scientists who have both a biologics and chemistry understanding because you have to be able to conjugate, purify, and analyze these materials to get the right product,” explained Mueller-Tiemann.
Aligned with this trajectory, Enhertu, an ADC-based blockbuster drug that first received FDA approval in December 2019 for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer, achieved global sales exceeding $1.6 billion in 2022.
Back at Millipore Sigma, the manufacturing of ADCs has advanced thanks to an alliance for Antibody Drug Conjugate Drug Substance and Drug Product Manufacturing Services with Simtra Biopharma Solutions. Announced in June, the partnership creates a turnkey offering for biopharmaceutical companies seeking ADC and bioconjugation, linker/payload manufacturing, drug product formulation development, and fill-finish capabilities.
“Connecting the bioconjugation and fill-finish steps will be a value-add for our clients, meeting their ambitious timelines and allowing the broadest number of patients to benefit in the fastest and safest possible way,” Benjamin Hein, head of life science services, life science business of Merck KGaA, Darmstadt, Germany, told GEN.
Taken together, Mostafa emphasizes that Bioprocess 5.0 is not being applied to “local optima” that focus on a specific facility or equipment, but is aimed at broader solutions.
“Have we improved our sustainability metrics and overall human experience? Is there a clear definition of the value proposition for humans? When we can articulate these points and people’s roles evolve, that’s where 5.0 truly will kick in,” says Mostafa.