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Flexibility and process intensification are advantages of continuous biopharmaceutical manufacturing, but some challenges remain.
Continuous manufacturing that integrates upstream and downstream biopharmaceutical production may offer cost and speed-to-market advantages, but technology requirements and regulatory uncertainty, as well as business risk, are ongoing challenges (1). BioPharm International asked José Castillo, chief technology officer and co-founder of Univercells, which manufactures an automated and integrated continuous platform, to comment on the drivers for and limitations of continuous biopharmaceutical manufacturing.
BioPharm: What do you see as the current state of end-to-end continuous manufacturing process for biopharmaceuticals?
Univercells: Significant progress has already been accomplished in continuous bioprocessing, in particular in upstream manufacturing, with the increasing uptake of cell culture operated in perfusion mode. Continuous renewal of culture medium and harvesting of the product have proven successful in improving cell viability and reducing equipment footprint. In this light, progresses in perfusion culture permitted the uptake of another manufacturing technology: the use of single-use bioprocess equipment. Downstream manufacturing processes are now following the same path, with efforts put in developing continuous harvesting, clarification, and multi-column or simulated-moving bed chromatography.
Designing complete end-to-end continuous processes, from perfusion culture to novel multi-column capture and polishing, aims at optimizing equipment and space utilization, reducing process footprint for a positive impact on facility design and related costs. Such entirely continuous processes, when fully automated, reduce unit steps for simplified operations, reducing associated risk.
The technology developed at Univercells combines process intensification and chaining for an end-to-end manufacturing process that is fully automated. With a drastic reduction of equipment footprint, the platform reduces the capital expenditure needed to enable rapid market entry.
BioPharm:What industry trends have made manufacturing flexibility increasingly important?
Univercells:Blockbusters from previous decades have reached their full potential and are now giving way to highly specific drugs targeting reduced patient subsets. The shift towards precision and niche medicines has resulted in a multiplication of biopharmaceutical players and segmentation of the market, where the market volume per drug will decrease. The ability to supply small amounts of biological drugs is a major increasing stake of the biopharmaceutical industry, causing unprecedent challenges in manufacturing.
Apart from precision medicines, the industry is seeing an increasing willingness from local players, especially in emerging economies, to develop and distribute their own biologics, which is yet another argument for scaling-down biomanufacturing processes.
The need for flexibility in manufacture is essential, with increasing requests of multi-product platforms to supply a variety of product from one product line as a way to diversify one’s portfolio while limiting facility investment.
But the need for flexibility is noticeable not only on the manufacture process itself, but also a flexibility in the decision: new players demonstrate a certain willingness to dedicate their investment in the product itself and less on the building, which still represents the major entry barrier to the biomanufacturing market.
BioPharm:What are the major technology hurdles inhibiting the uptake of continuous manufacturing technology in biopharma, and how can these challenges be addressed?
Univercells: One of the challenges to consider in the development of continuous bioprocessing technologies is their acceptability by regulatory agencies to ensure approval of the corresponding manufactured products. Fully continuous processes, in particular in the biopharmaceutical industry, still come with a high level of perceived risk, with particular concerns regarding product quality and consistency.
Required efforts should target the development of appropriate quality control and analytical methods, along with the manufacturing process itself, accompanied by open dialogue to increase awareness and educate stakeholders about the benefits of continuous manufacturing for the market. Efforts in development and collaboration with regulatory agencies will help decrease the perceived risk associated with continuous manufacturing and aid in bringing such innovation to the market.
1. C. Challener, BioPharm Int. 3 (5) 12-17 (2018).