From good to great: Innovative biopharmaceutical manufacturing is key
The recent past has strongly demonstrated the true potential of biopharmaceuticals, and the coming years promise to further strengthen their global position and reputation. This growth, for the short- and long-term, can best be sustained by advancing innovations in process development and manufacturing.
In pursuit of better treatments to alleviate suffering and improve human lives, biopharmaceuticals have proved to be a game-changer. Fueled by the transition from small molecules to formats with increasing complexity- be it proteins or nucleic acids, and an increase in druggable targets, these
biopharmaceuticals are here to stay.
Today, biopharmaceuticals and the manufacturing processes that make them possible, contribute immensely to treating and improving the lives of innumerable patients across the globe. The recent past has shown us how advanced manufacturing can be leveraged to produce new technology like mRNA within cGMP requirements and demanding timelines. Join us in taking a closer look at what this means for scalability and continuous manufacturing.
Solving scalability challenges with innovative approaches
To tackle manufacturing challenges in scalability, the following innovations will play a central role in the next few years. The continuous increase in on-line and in-line monitoring capabilities (E.g., RAMAN, MIR) in combination with computational modeling is essential. This will lead to a better understanding of the interplay between technical limitations and desired product quality. Furthermore, new cell line development platforms, also in combination with new process formats such as intensified fed-batch or continuous manufacturing via perfusion will be key for consistently increasing product titers. For further optimization, an increasing number of materials in ready to process format will be applied. This will enable upscaling within material design, with the use of prepacked columns and scalable functionalized filter capsules.
From a drug development perspective, there could be a tendency towards a higher number of active pharmaceutical ingredients (APIs) enhanced by the trend towards personalized medicine in lower doses. This in turn will shift manufacturing towards lower batch sizes. Modalities like mRNA or viral-based biologics could further reduce the overall demand for manufacturing as they are administered in lower doses and are targeted at enabling cure instead of long-term treatment. Moreover, growing and learning database technologies could help in fostering the creation and sharing of knowledge. This in turn would assist in foreseeing potential offsets or limited
comparability, for specific process unit operations or techniques. In addition to that, mechanistic modeling approaches (standalone or in combination with statistical models) will allow for enabling precision in predictions, by including the variable scale with reduced experimental effort.
Enabling efficient production with continuous manufacturing
Generally speaking, continuous processes generate a better space-time yield resulting in production facilities with a lower footprint. Hence, by combining continuous processes with the application of modular single-use equipment, such production set-ups can be established faster at different sites (outscaling). For cell-free production systems, such as those used in mRNA synthesis, “enzymatic reactors” can also be run in a continuous mode. In subsequent steps, simple and streamlined purification processes such as filtration can be used to continuously purify the relevant mRNA construct. With regards to viral vector prototypes in tubular reactors, we witness the development of purification techniques, that in combination with known classical continuous chromatography techniques, could successfully serve continuous bioreactor virus production. In general, both viral vector and mRNA constructs are very suitable for a streamlined production platform and allow for the rapid production of large amounts. This is independent of the format, i.e., if performed in batch, semi-continuous or continuous mode.
To sustain this development, the evolution of technology and innovation must go hand in hand with advancements in manufacturing. This will be key to ensuring that promising biopharmaceuticals successfully make the journey from concept to market, and ultimately to the patient.
Dr. Latika Bhonsle-Deeng
Senior Manager Corporate Communication
Rentschler Biopharma SE