Why shift from batch to continuous manufacturing
The traditional batch mode is more complex
Complexity in the manufacturing and composition of essential drugs adopted by biopharmaceutical companies is one of the reasons for high drug prices. Unlike regular pharmaceutical drugs, biopharma drugs are synthesized using living cells, necessitating various purification steps. This is time-consuming and demands stringent quality standards.
The industry norm is to manufacture biopharma drugs in batch mode. Despite its flaws, the batch production of biopharma drugs is widely adopted due to its familiarity, lower equipment cost, and relatively lower failure rates. However, the need to stop at the end of each step results in increased hold-up times. This increases the overall cost and production cycle time, making the process inefficient. Moreover, manual intervention induces errors that are expensive to bear. There is, therefore, an increasing push to switch to continuous biopharma manufacturing.
The continuous manufacturing process
Toward a seamless workflow where unit operations are uninterrupted
In continuous manufacturing, all unit operations work in an uninterrupted mode – from the entry of raw materials to the output of final products, all happens seamlessly. The product is manufactured at a single location end-to-end, with no hold-up times. As a result, most unit operations occur in parallel, with maximum utilization of equipment and space.
Continuous biopharma manufacturing involves upstream and downstream processing steps. In upstream processing, the biomolecules are generated and consist of harvesting and clarification steps. In downstream activity, purification separates the desired drug from a host of impurities.
End-to-end unit operations in a continuous biopharma manufacturing process encompass perfusion bioreactors, acoustic wave separation for clarification, multi-column chromatography units, viral inactivation, and single-pass tangential flow filtration.
Achieving complete operational integration
Integrating all operating units in parallel is feasible and results attainable
Biopharma companies are now moving toward adopting the continuous process. The maximum these companies have achieved is operating one or two units at a given time in a continuous mode. Operationalizing all the units in tandem is yet to be realized.
The first step to attain this objective would be to make individual constituent unit operations continuous. Each unit is represented with accurate mechanistic models with optimization and control strategies via digital twins of the processes. The final step is integrating and connecting these individual units with a plant-wide simulation, optimization, and centralized control system.
Advantages in terms of time, money, productivity
A continuous process improves yield, turnaround time, and cost reduction
The continuous process depends less on human intervention, requires a smaller facility footprint, and is open to scaling, automation, and adaptation. Transitioning between different unit operations is also relatively smooth.
Process automation and control systems with integrated physics-based models can help achieve stable critical quality attributes by adjusting critical process parameters in real time. This helps improve process robustness, efficiency, and utilization, as well as quick detection and correction of anomalies, if any.
Continuous manufacturing is gaining traction because of its ability to improve product quality, production consistency at lower costs, flexibility, and shorter time-to-market. By integrating single-use technology into the process line, the initial capital investment could come down, too.
Moreover, acceptance of continuous manufacturing by the pharma sector is likely to grow with the demand of low-cost lifesaving drugs, and vaccines from unforeseen events such as the COVID-19 pandemic. The increasing approval of biologics by food and drug administrations and capacity expansion plans by manufacturers to meet the uneven demand for affordable drugs further strengthens the need for the shift.