Downstream Process Development
Generally speaking, bioprocess development can divided into upstream process and downstream process. Upstream processes focus on cell amplification and cell culture, while downstream processes focus on purification. During the downstream process development, scientists will perform a number of unit operations. In order to remove process impurities and isolate and purify the target protein, the clarified feedstock will then undergo a variety of required subsequent processing steps. With years of experience in providing satisfactory downstream process development solutions to each of our customers, BOC Sciences has demonstrated unparalleled expertise and capabilities by employing a variety of protein purification and preparation platforms. We will continue to provide the same high quality and reliable service to all of our existing and new customers.
Platform features
- Powerful and complete platform: Supports research and development of a range of processes
- Fast turnaround time
- High recovery rate of product: Residual impurities amountof process and product is significantly below quality standards
- Protein drug development
- Customized services
Figure 1. Schematic illustration of an integrated biopharmaceutical process development for up- and downstream applications based on combinatorial approaches. (Pascal, B.; Jürgen, H. 2016)
Our Services
To make it easier and better for researchers, BOC Sciences provides downstream process development service in a competitive fashion. We have provided a more efficient way to increase the number of new drugs, greatly shorten the R&D cycle, and reduce the development costs.
- Chromatography development and optimization: Selection for initial capturing (affinity chromatography, etc.) and polishing chromatography (ion exchange chromatography; hydrophobic chromatography, multimodal chromatography); high throughput screening of chromatography resins; chromatography resin lifetime studies; resin and buffer screening
- Filtration (TFF and depth filters) development and sizing: Filter sizing and flux studies
- Process scale-up, scale-down and characterizationand tech transfer
- Bulk formulation development
- Viral clearance and inactivation steps development (pH and detergent)
- QbD driven downstream process characterization
- In-process hold studies
- Process verification at scale, using AKTA Ready and AKTA Pilot
- Chromatography capabilities include all modalities (affinity, IEX, HIC, multimodal)
- Ultrafiltration and diafiltration
- Development and optimization of customized purification process
- Clarification process development
- Process characterization, process optimization, and process validation of late-stage clinical projects
- Harvesting (centrifugation, depth-filtration) and cell disruption
- Isolation and solubilization of inclusion bodies followed by refolding of target protein
Figure 2. Schematic illustration of different tools for downstream process development. (Pascal, B.; Jürgen, H. 2016)
Development workflow
- First, we thoroughly assess the risks that may arise during process development and obtain as much information as possible about the product properties. During the evaluation phase, our experts identify product critical quality indicators (CQAs) and critical process parameters (CPPs)
- Next, we develop a series of experimental designs to obtain the process design space
- Finally, we will confirm the operating range of the critical process parameters through experimentation and risk assessment. Our goal is to ensure that once the process is scaled-up, and product quality factors can always be maintained within a controlled range
Downstream Process Platform
- Affinity chromatography: Removal of media components, HCP, DNA
- Cation or Anion exchange chromatography (CEX/AEX chromatography): Removal of contaminants (DNA, virus) and product related impurities (HMWs & LMWs)
- Hydrophobic chromatography
- Mixed mode chromatography
- Depth filtration system: Clarification of cell culture, and removal of cells and cell debris
- Nanofiltration
- Ultra-filtration and diafiltration
- Virus inactivation system
- Membrane chromatography
- Periodic counter-current chromatography (PCC)
- Akta Avant, Akta Pure, Crossflow
- Akta Pilot
- Akta Ready, Akta Process
- Automatic UFDF system
- Scale up tool and tech transfer tools
- Acid treatment: Inactivation of enveloped viruses
- Secondary deep filtration: Removal of contaminants (turbidities, HCP, DNA, virus)
- TFF: Concentration & diafiltration
- Formulation: Excipient addition
Figure 3. Overview of different commercial miniaturized systems in downstream process development and their applications. (Pascal, B.; Jürgen, H. 2016)
Why choose BOC Sciences?
Our dedicated CMC team has provided tailored solutions to our clients from engagement to launch. With many years of industry experience, we provide clients with the following:
- Comprehensive, integrated CMC services with a flexible service model that grows with your programs
- Knowledgeable industry experts who deliver scalable, actionable insights
- World-class facilities and equipment that remain at the forefront of the global pharmaceutical research, analytical and development standards
- Our comprehensive services support products at every stage of the product lifecycle, from early-stage discovery to full commercial cGMP manufacture
- A focus on risk management that is designed to ensure completion of your technical goals
BOC Sciences provides professional, rapid and high-quality services of downstream process development at competitive prices for global customers. Personalized and customized services of downstream process development can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Pascal, B.; Jürgen, H. Downstream process development strategies for effective bioprocesses: Trends, progress, and combinatorial approaches. Engineering in Life Sciences. 2016. 17(11): 1142-1158
