Essential Strategies for Scaling Up Biologics
Read the essential strategies and considerations for scaling up biologics and our run down of the top 10 companies supporting biologic scale up.
Biologics are revolutionising healthcare. Characterised as pharmaceutical drugs that are produced from biological systems, biologics such as therapeutic proteins, monoclonal antibodies (mAbs), and vaccines are providing highly targeted and effective treatments for conditions where patients have historically had few effective options. Recent research by Nova One Adviser values the global biologics market at $511 billion, projected to reach $1,375 billion by 2033. The ability for biopharma companies to efficiently scale the manufacturing of this type of therapeutic is paramount to realising this market value. Predictably though, scaling up is complex, and requires the implementation of critical strategies and considerations to ensure the process is efficient, cost-effective, and compliant with regulatory standards. Here, we take a look at the essential strategies for biologic scale-up, and provide a run-down of the top 10 premier companies specializing in biologic scale-up solutions.
Scale up strategies and considerations
Process Development and Optimisation
A critical step in scale up is developing and refining media and feed strategies to maximize yield, titers, and cell density. It is also important to consider how the media and feed strategy translates to large-scale bioreactors. Ensuring bioreactor processes can maintain consistency from lab to pilot and production scales is imperative to achieving succesful scale up.
Using optimized cell lines to enhance productivity and product quality is vital to ensure successful scale up. Cell lines are cultures of animal cells that can be propagated repeatedly, and in some cases indefinitely. Mammalian systems have higher levels of native folding, post-translational modifications, and more functional activity than other systems meaning they are more closely representative of a physiologically relevant environment for producing proteins for human use. Chinese hamster ovary cells (CHO) are the gold standard for protein production due to high productivity, the ability to allow for post-translational modifications, and low virus susceptibility. Additionally, they can grow in serum-free and chemically defined media, which helps ensure reproducibility between different batches, and they can also easily grow in large-scale cell culture.
Quality Control and Assurance
Developing robust analytical methods to ensure product quality and consistency, and ensuring all processes comply with regulatory requirements, including Good Manufacturing Practice (GMP) standards is paramount. Validation processes should be conducted to demonstrate that the process consistently produces a product meeting its predetermined specifications and quality attributes.
Technology Transfer
It is important to have a thorough, well-planned technology transfer program that features detailed product information, process-related documentation, material transfer agreements, facility fit assessments, training requirements, and regulatory considerations. This will help protect against unwanted surprises and instead facilitate a seamless transfer between development and manufacturing stages.
Scale-Up Equipment and Infrastructure
Deciding between single-use bioreactors and traditional stainless steel systems is a key decision that biopharmaceutical manufacturers must make. The decision involves a myriad of different factors that should be considered across areas such as sustainability, flexibility, scale, quality, and cost/speed. In recent times, single-use technologies (SUT) has become more widely adopted, contributing to increasing process intensification due to SUT’s advantage of being more flexible, cost-effective, sustainable, and possessing lower risk of cross-contamination when compared to more traditional stainless steel systems. An additional consideration for equipment and infrastructure is the implementation of automation and advanced control systems in order to maintain optimal and harmonized conditions during production. Real-time monitoring of the bioprocessing workflow allows for precise control of process parameters, which is critical for success.
Supply Chain Management
Reliable sourcing of high-quality raw materials is a vital component of scaling up because any impurities in the raw materials, when scaling up to large bioreactors, can be amplified, in doing so influencing performance parameters and causing lot-to-lot inconsistencies.
It is important when choosing a manufacturing supplier to ensure they have global redundancy in manufacturing supply as pauses in the manufacturing process are highly costly. In recent times, the unprecedented demand for bioproduction materials, combined with significant disruption to global supply chains, has placed an increasing importance on ensuring a robust raw material supply to meet timelines and avoid costly delays.
Risk Management
Developing contingency plans for potential risks, such as equipment failure or supply chain disruptions is crucial as is the use of scale-down models to identify and mitigate risks before full-scale production
The Top 10 Companies Supporting Biologic Scale-Up
Lonza has a strong reputation in the industry. It offers comprehensive biologics development and manufacturing services, including cell line development; process development; commercial manufacturing; mammalian and microbial production; cell and gene therapy manufacturing, drug production services including formulation, fill and finish.
With an extensive global footprint, Thermo Fisher Scientific provides comprehensive services for biologics development and manufacturing, including cell line development, process optimisation, cell culture media, bioreactors, purification systems, fill/finish, analytical testing services, and large-scale production.
WuXi AppTec provides end-to-end solutions for biologics development, including cell line development, process optimization, GMP manufacturing, and analytical development services. It has a strong global presence, rapid turnaround times, and extensive capabilities in cell and gene therapies.
A relatively new player compared to others, Samsung Biologics offers a full-service CDMO for biologics, with process, development, clinical and commercial manufacturing services, as well as drug product services including aseptic fill/finish and lyophilization.
Fujifilm Diosynth Biotechnologies
Located in the United States and Europe, Fujifilm Diosynth Biotechnologies specialises in the development and manufacturing of biologics, with expertise in process development, analytical development, and GMP manufacturing.
With a focus on speed and flexibility, Catalent Biologics offers integrated biologics development and manufacturing solutions, including cell line development, process development, fill/finish, packaging, clinical supply services, analytical services, and commercial manufacturing.
Boehringer Ingelheim BioXcellence
Boehringer Ingelheim BioXcellence has a long history of experience in biopharmaceutical manufacturing. It provides a comprehensive, premium service offering for biologics manufacturing.
With strong expertise in bioprocessing technologies and a focus on innovation, Millipore Sigma services include cell culture media, filtration, purification systems, analytical testing and validation, and manufacturing services.
Cytiva has a strong legacy in bioprocessing and an extensive product and technology service offering. This includes cell culture, filtration, and purification solutions as well as automation and digital solutions for biomanufacturing.
Sartorious is one of the leading providers of single-use bioprocessing technologies and has a strong focus on innovation and process efficiency. It has a comprehensive product portfolio for biologic manufacturing
Conclusion
Scaling up the production of a biologic requires many considerations and optimization strategies. Choosing the right company to partner with can significantly streamline this process, ensuring the biologic is produced efficiently and meets regulatory standards.
Author
BioFocus Newsroom