Overcome development and manufacturing obstacles for gene therapy commercial success
Gene therapy brings life-changing medicines to patients and even the hope of a cure to those with chronic illness, but the patient-specific nature and different operational requirements compared to traditional biologics create challenges in the transition to commercial viability. Process development and commercialization obstacles must be overcome quickly. Fast optimization of scalable viral vector processes to meet the demands of clinical approvals and commercial cGMP manufacturing is needed to keep pace with rapid movement in the clinical landscape.
At Pall, we understand the uphill battle you are facing to deliver a robust, reproducible and scalable gene therapy viral vector process. We have the proven scalable technology, end-to-end integrated platforms, knowledge and services to help you get your gene therapy to market. Work with us to increase your speed to commercialization or to improve process productivity and deliver therapies to transform lives.
Partner with us to accelerate and optimize your viral vector process
The journey to industrialization is exciting and can be challenging at times but development and optimization obstacles can be overcome with support from our experts. Our Accelerator℠ process development services, specialize in designing, optimizing and transferring scalable processes from pre‐clinical to cGMP commercial manufacturing, reducing time to market. Our team can draw on experience from multiple gene therapy viral vector projects to collaborate with you.
In 2019, Zolgensma, an AAV-based viral vector gene therapy used in the treatment of spinal muscular atrophy was approved by the FDA and our iCELLis® fixed-bed bioreactor was used in the production. Zolgensma’s journey began at the Center for Gene Therapy at The Abigail Wexner Research Institute of Nationwide Children’s Hospital and eventually made its way to Novartis.
Together, we can rapidly optimize your process, whether to prove readiness for industrial scale production or to increase capacity.
Cell Expansion and Virus Production
Efficient transfection and scalable cell culture are two of the upstream hurdles to overcome. Our solutions support you to design a robust, reproducible and scalable process for generating viral vectors.
Get the Guide:
Master Large-Scale Transfection
Purification of Viral Vectors
The ratio of impurity to protein, the charge and size of viral vectors, and the risk of generating empty capsids create purification challenges. Optimized filtration and chromatography solutions maximize yield.
Read the Article:
Optimize Clarification of Industrial Scale Viral Vector Culture for Gene Therapy
End-to-End Integrated Systems
An integrated system where all the unit operations are harmonized is the key to getting your process to run optimally to set performance criteria every time. Our keystone technologies combine to create robust but flexible integrated bioprocessing platforms. These preconfigured platforms can also be provided in a flexible POD® cleanroom from G-CON to further accelerate a compliant manufacturing process.
Read the Article:
End-to-End Integrated Manufacturing Solutions Enable Gene Therapy Commercialization
Process Workflows for Adeno-Associated Virus (AAV) Production
Process Workflows for Adenovirus (AV) Production
Process Workflows for Lentivirus (LV) Production
Single-use, scalable cell culture options support suspension and adherent producer cell lines, cell expansion, viral transfection and virus production. All production systems are designed to maintain a sterile closed manufacturing environment and are automated to assure consistent operation and assure product quality.
Podcast: Evolution of Culture Systems for Viral Vector Production: Advantages, Challenges and Cost Considerations
Published: March 10, 2020
Listen to this podcast interview featured on BioInsights with Emmanuelle Cameau, Cell and Gene Therapy Technical Manager within our Scientific Laboratory Services team, and Joseph Capone, Senior Global Product Manager.
Adherent Cells
One of the greatest challenges facing adherent cell processes is the scale-up to an industrial scale. Our unique fixed-bed bioreactors are capable of simple scale-up maintaining closed system production with a small footprint across all scales.
iCELLis® 500+ System for manufacturing scale production (66 m2 to 500 m2)
iCELLis Nano for feasibility and small-scale production (0.5 m2 to 4 m2)
Xpansion® Multiplate Bioreactor System is well suited for seed train operations for the iCELLis bioreactor range (0.6 m2 to 12 m2)
Suspension Cells
For suspension cultures, a range of single-use, scalable stirred-tank bioreactors and a bi-axial rocking system are available to support cell expansion and vector production at all scales.
Allegro™ STR Stirred Tank Bioreactors for culture volumes of 10 L to 2000 L
Allegro XRS 25 Bioreactor (rocking) system for cultures of 2 L to 25 L
The range of robust, scalable purification technologies effectively combine to reduce impurities such as residual plasmid DNA, host cell DNA and empty or partially filled vectors, to deliver the high purity, concentration and potency that you need.
Flexible, automated systems for chromatography and ultrafiltration permit the re-use of non-product wetted components and use single-use systems that are quick to install and eliminate the risk of batch to batch contamination. They can be applied to multiple stages within the process to eliminate cleaning and cleaning validation, minimize capital investment and accelerate batch turnaround times.
Podcast: Empty/Full Separation: Gene Therapy’s Hidden Challenge
Published: January, 2021
Listen to this podcast interview featured on BioInsights with Mark Schofield, Senior R&D Manager. With over 15 years of experience in R&D and new product development in biopharma related industries, Mark discusses how you can overcome the obstacle of AAV full capsid enrichment in your viral vector process.
Clarification of Harvested Vectors
The removal of cells and cellular debris requires the careful application of filters with structures that can retain both large and fine debris while maintaining high yields. The combination of optimized depth filtration and sterilizing-grade filtration assures low particle feed to downstream purification and high virus transmission.
- Supracap™ capsules with V100P; small-scale depth filtration capsules (0.05 to 0.3 m2)
- Stax™ Disposable Depth Filter Systems with V100P; (0.5 m2 to 20 m2)
- Kleenpak Nova capsules with Supor EKV sterilizing-grade media (0.6 m2 to 1.8 m2)
- Kleenpak capsules with Supor EKV sterilizing-grade media (0.04 m2 to 0.15 m2)
Chromatography
Membrane based ion exchange chromatography delivers high capacity, high purity and can work with single-use, automated platforms for simplified operation and improved process agility.
- Mustang Q anion exchange membrane chromatography capsules for the reduction of DNA, and empty capsids.
Ultrafiltration
The diafiltration and concentration of intermediates and final product can be achieved using single-use cassettes and systems to simplify processing.
Worried about the impact of shear on your sensitive product? Try our range of single-pass concentration and discover how these could revolutionize these operations.
Sterile Filtration of Purified Vectors
The sterile filtration of viral vectors provides a unique challenge and yields can be significantly impacted without careful selection. Our Supor® sterilizing-grade filter capsules balance the assurance of sterility with the high transmission of virions and can be supplied presterilized and as part of a multicomponent system designed to simplify your manufacturing process.
- Mini Kleenpak™ capsules with Supor EKV sterilizing-grade media (0.02 m2)
- Kleenpak capsules with Supor EKV sterilizing-grade media (0.04 m2 to 0.15 m2)
- Kleenpak™ Nova Capsules with Supor EKV sterilizing-grade media (0.6 m2 to 1.8 m2)
The preparation, storage and transfer of media, buffers, intermediates and final drug product requires careful control to prevent contamination and to comply with cGMP. The efficiencies that can be gained by using single-use solutions are well documented and their use can accelerate process development, simplify manufacturing processes and safeguard quality.
Our range of fluid handling technologies can be used as part of a pre-assembled, sterilized system or as components added to existing processes. They support single-use manufacturing platforms to reduce bottlenecks and are simple to use, reducing process deviations and assuring quality.
Sterile Connection and Disconnection
The addition of fluids to the producer cell culture at all stages of the process including transfection and production as well as secure disconnection of the final product containers demands absolute cleanliness. Supplied ready for integration with existing process components or supplied as part of a single-use system, Kleenpak® sterile connectors and disconnectors provide an easy to use, secure method of connection and disconnection in flexible tubing assemblies.
Fluid Handling
Single-use technology can simplify the assurance of cleanliness and remove process bottlenecks. From simple fluid transfer sets to mixing solutions that deliver sterile cell culture media or buffer to your process, these solutions streamline production, safeguard cleanliness and simplify operation to support a rapid development of processes.
Automation and Control
Process control, either through manual adjustments, or with the help of automated systems, helps assure final product quality and simplifies production. Our range of control systems and process flow components are designed to integrate with a single-use process to streamline production through the application of optimal design and automation.