Khalil Essani, product line manager sterile products at Single Use Support explains how process intensification advances bioprocessing.
Single Use Support
Optimising production processes has become essential in the rapidly changing biopharmaceutical manufacturing market, in order to remain competitive and satisfy needs for healthcare around the world. Traditional bioprocessing techniques frequently struggle with high costs due to inefficiencies and risk reduction measurements, which restricts the availability of essential medications to larger populations.
What makes a bioprocess more intense?
The primary goal of (bio)process intensification is to increase productivity, lower costs, and shorten the time to market to develop and manufacture pharmaceuticals safely and efficiently. Manufacturers can minimise facility footprints, enhance throughput, and accelerate drug development timelines by applying novel technologies and tactics. This technique is especially important as the sector confronts increasing demand to boost output while cutting production costs.
The benefits make process intensification an appealing option for biopharmaceutical businesses and CDMOs looking to optimise their operations and remain competitive in a continuously changing market.
Process intensification aligned with market dynamics
While monoclonal antibodies (mAbs) continue to be a cornerstone of biologics development, there is growing interest in viral vectors for gene treatments and vaccinations. This trend has prompted businesses to investigate new production methods, such as partially and totally continuous upstream procedures that use perfusion cell culture for intensification.
Process intensification technologies must be adaptable to many modalities and scales, ranging from research and development to large-scale commercial production. The major goal is to move away from traditional bioprocessing and toward more modern and versatile systems that improve economic efficiency, productivity, and sustainability in different areas of applications.
Intensified processes boost upstream productivity by targeting high cell densities to allow smaller modern bioreactors to provide equivalent or higher throughput than large classic bioreactors. Furthermore, process intensification promotes sustainable manufacturing by lowering waste and energy consumption, which is becoming increasingly crucial as businesses strive to fulfil environmental targets and respond to regulatory requirements for greener practices.
So, in particular, what processes might be enhanced?
High-density cell banks
One important strategy to process intensification in drug development is the utilisation of increased cell densities and functional cell banks. In other words, a certain start (inoculation) cell concentration is required to cultivate the cells and efficiently achieve the exponential growth phase.
There are essentially two ways to intensify the process: Either increase the volume of the initial inoculum or raise its concentration.
- Starting with a larger initial cell mass cuts down the time needed to build up enough biomass for seeding an N-stage bioreactor.
- The approach of increasing concentration entails growing cells to high densities in fed-batch or perfusion bioreactors, then storing them in many single-use bags. This way the seed train time can be reduced.
High-density (HD) cell banking has several benefits that improve production procedures when used in the biopharmaceutical industry. The decrease in seed train steps is one of the main advantages. Manufacturers can significantly reduce production timelines by avoiding many expansion phases by beginning with a higher cell density. For innovative treatments to reach the market sooner, this acceleration is essential.
Additionally, HD cell banking improves operational effectiveness. A smaller chance of contamination results from fewer expansion processes, which is essential for preserving product quality. Reliability and reproducibility are critical components in the biopharmaceutical sector, and this step reduction encourages higher process homogeneity.
High-density working cell banks also maximise the use of facility space. Manufacturers can obtain higher output with fewer bioreactors thanks to higher density cultures, which significantly lowers infrastructure costs. This efficient use of space can lower capital expenditure and contribute to ongoing operational savings.
Modular single-use technologies providing process flexibility
The utilisation of modular, single-use technologies has revolutionised the process flexibility and intensification. These technologies provide various advantages, including scalability to suit fluctuating production numbers, decreased contamination concerns, faster turnaround times due to no additional washing and sterilising, and enhanced flexibility. Modular systems simply enable quick alterations to manufacturing lines based on products and procedures.
Modular and automated filling systems for single-use bags, for example, show how these technologies can be integrated into more complex operations. They allow for the standardisation of process stages, which improves reproducibility and reduces contamination hazards associated with manual handling.
Automation in fluid and cold chain management
Automation is critical for process intensification, especially in fluid and cold chain management. Advanced automated technologies are transforming the way large volumes, such as cell material, are handled, stored, and transported during the manufacturing process.
Key advantages of automation in this field include:
- Precision: Automated fluid management systems provide accurate fill quantities and consistent processes. It enables high accuracy of low-volume applications in an aseptically closed system.
- Traceability: Automated cold chain processes ensure regulatory compliance and quality assurance.
- Productivity: Minimising manual handling reduces the risk of error and contamination.
Automated filling, freezing, and thawing methods push the sector closer to the Pharma 4.0 idea, which envisions digital transformation enabling more efficient and dependable pharmaceutical processes.
Continuous bioprocessing
Unlike typical batch processing, continuous bioprocessing entails conducting production operations without interruption. This technique has various advantages over batch procedures, including higher cell densities, more consistent product quality, a smaller facility footprint, and greater flexibility. It’s another piece of the productivity puzzle.
While the traditional cell expansion process using durable steel bioreactors tends to be associated with single-product manufacturing facilities, single-use technologies facilitate the option of continuous upstream expansion processes to produce multiple products. The added flexibility is what makes it on demand for CMOs and CDMOs manufacturing multiple products.
Driving the evolution of the biopharmaceutical industry
Process intensification is redefining biopharmaceutical manufacturing by tackling critical issues such as efficiency, quality enhancement, and flexibility. It’s an opportunity for manufacturers to considerably improve their production capabilities. All of these mentioned approaches – the implementation of high-density cell banks, modular single-use technologies, automated fluid and cold chain management, and continuous bioprocessing – are driving process intensification.
Single Use Support’s vendor-independent fluid and cold chain process solutions are focused on helping biopharmaceutical manufacturers aspire to evolve. The Austrian process solution provider’s approach is to holistically assess and optimise the end-to-end process, while some other life science providers offer solutions for very siloed process steps.
Process intensification will play an increasingly important role in the industry’s evolution, ensuring the timely and cost-effective delivery of life-saving biopharmaceuticals to patients around the world.