Biologics Process Development & Optimization - Abzena

Biologics Process Development

Seamless upstream and downstream biologics process development, optimization and manufacturing from cell line development (CLD) to patient.

Minimize risk, timelines and costs.

Developing biologic therapeutics presents unique challenges due to the intricate nature of large biomolecules and the variability inherent in biological systems. Optimizing production processes to ensure consistent product quality, scalability, and regulatory compliance requires specialized expertise and advanced technologies. Abzena have expertise across multiple modalities, which means we can successfully transfer your existing process, or develop new, innovative processes to meet your objectives. Our strategy minimizes risk, timelines and costs.

At Abzena, we offer comprehensive upstream and downstream process development services tailored to the specific needs of your biologic therapeutics. Our integrated approach combines advanced cell culture and purification techniques to deliver scalable solutions as you progress your program onwards toward GMP manufacturing.

By utilizing our established cell line and platform process we rapidly develop and streamline your program development and commercial timelines. Our process development, optimization and manufacturing teams work together to develop quality, commercially viable processes, that ensure a seamless scale up directly from bench scale to final manufacturing through to commercialization.

Our state-of-the-art locations have a range of capabilities supporting the development, scale-up, optimization and stability of your process.

Our Process Development Capabilities

Advance your biologic with confidence:

  • Experience with multiple mammalian cell types including CHO, ABZ-CHO K-1, sp2/0, yp2/0, and NSO
  • Experience beyond mAbs including fabs, ADCs, oligonucleotides, nanoparticles, bispecifics, fusion proteins, vaccines, virus-like particles, enzymes, and bioconjugates
  • Transfer verification optimization of your process
  • Design of statistical experiments to optimize media feeds and growth conditions
  • Scale down fed batch and perfusion production models
  • Robotic systems from 250ml to manufacturing scale at 2K
  • High cell density and titer optimization
  • Bench scale process characterization and validation
  • Coordination with Analytical Method Development (AMD) to determine quality attributes

Our team brings extensive process development for biologics capabilities and expertise in the following areas:

Cell Culture Process Development

We optimize upstream processes to enhance cell growth, productivity, and product quality.

  • Clone Selection and Media Screening: Utilizing high throughput screening platforms to identify optimal cell clones and media formulations that maximize protein expression and maintain desired quality attributes. Detailed analyses of cell line stability, growth kinetics, and metabolite profiles guide the selection of the best production clone.
  • Seed Train Development: Establishing robust seed train protocols to ensure consistent inoculum quality and viability for large-scale bioreactor runs. Optimization of cryopreservation methods, numbers of passages, and seeding densities maintains cell health and performance.
  • High-Throughput Bioreactor Parameter Screening: Employing scale-down bioreactor systems to rapidly optimize critical process parameters such as dissolved oxygen (DO), pH, temperature profiles, agitation rates, and feed strategies. This accelerates process development and identifies optimal conditions for large-scale production.
  • Centrifugation Development: Optimizing cell harvest techniques by evaluating centrifugation conditions (e.g., g-force, flow rates) to maximize cell removal efficiency while minimizing shear stress and product loss.
  • Production Scale Bioreactors: Our capabilities range from benchtop (250 mL) to pilot and GMP manufacturing scales (2L, 50L, 200L, 500L, 2000L) using single-use bioreactor systems. We ensure seamless scale-up by maintaining geometric and kinematic similarity across scales.
  • Cell Culture Parameter Optimization: Fine-tuning culture conditions, including nutrient feed compositions, feeding strategies (fed-batch, perfusion), culture duration, and metabolic control to enhance titre and product quality.
  • Toxicology Production: Producing GLP preclinical batches for toxicology studies, ensuring material consistency with future GMP batches regarding glycosylation patterns, charge variants, and impurity profiles.
  • Pilot Scale Confirmation Batches: Executing pilot-scale runs to confirm process scalability and reproducibility, assessing mixing times, oxygen transfer rates (kLa), and shear effects on cell culture performance.
  • Scale-Down Model Development: Creating and qualifying representative models to facilitate process characterization, optimization, and troubleshooting. These models are essential for risk mitigation and efficient process validation.
  • Process Characterization: Performing statistical design of experiments (DoE) to identify critical process parameters (CPPs) to maintain critical quality attributes (CQAs) and develop in-process controls (IPCs), establishing a robust design space and control strategy.
  • Process Transfer: Managing seamless technology transfer of processes into and out of process development to manufacturing facilities. We prepare comprehensive process descriptions, and transfer protocols to ensure efficient and accurate knowledge transfer.

Purification Process Development

Our downstream processing expertise ensures high purity and yield while maintaining critical quality attributes.

  • Chromatography Resin Screening: Evaluating various chromatography resins (e.g., Protein A, ion exchange [IEX], hydrophobic interaction chromatography [HIC], mixed-mode [MMC]) for binding capacity, selectivity, and scalability. This identifies optimal purification strategies tailored to your molecule.
  • Filter Screening and Sizing: Determining optimal filtration strategies, including depth filtration (e.g., diatomaceous earth, cellulose-based filters) and standard flow filtration (NFF) membranes. We aim to achieve the desired purity and clarity while maximizing product recovery.
  • Virus Filter Sizing: Selecting virus filtration membranes (e.g., Planova™ filters, Viresolve® Pro) to ensure robust viral clearance, meeting regulatory requirements for product safety.
  • Tangential Flow Filtration (TFF) Development: Optimizing ultrafiltration/diafiltration processes for concentration and buffer exchange. We select appropriate membrane materials (e.g., polyethersulfone, regenerated cellulose), molecular weight cut-offs (MWCO), and operating parameters such as transmembrane pressure (TMP) and crossflow rates.
  • Chromatography Parameter Screening and Optimization: Fine-tuning chromatographic conditions such as pH, conductivity, gradient elution profiles, isocratic elution profiles, and flow rates. This improves separation efficiency, resolution, and product purity while minimizing process related impurities and aggregates.
  • Toxicology Production: Purifying bulk drug substance for preclinical evaluations, ensuring that material represents
    clinical-grade product in terms of purity, potency, and impurity profiles.
  • Pilot Scale Confirmation Batches: Conduct purification runs at pilot scale to verify scalability, assess impurity profiles, confirm viral clearance steps, and verify process performance under GMP-like conditions.
  • Scale-Down Model Development: Establishing and qualifying laboratory-scale models of downstream processes that replicate large-scale performance. This enables process optimization, and characterization with reduced material requirements.
  • Process Transfer: Providing comprehensive documentation, including process descriptions, and detailed protocols to support the efficient transfer of purification processes to manufacturing facilities.
  • Support for Viral Clearance Studies: Collaborating with Contract Research Organizations (CROs) to design and execute viral clearance validation studies. This includes small-scale spiking studies, scale-down model qualification, and preparation of regulatory documentation.

Advanced Analytical Support

Our state-of-the-art analytical capabilities support every stage of process development:

→ Analytical Method Development and Validation: Developing and validating robust, phase-appropriate analytical methods for product characterization, including:

  • Purity and Impurity Analysis: High-performance liquid chromatography (HPLC), capillary electrophoresis sodium dodecyl sulfate (CE-SDS), size-exclusion chromatography (SEC), and reverse-phase (RP) HPLC.
  • Identity and Structural Analysis: Peptide mapping, intact mass analysis, N-terminal sequencing, and mass spectrometry (MS).
  • Potency Assays: Cell-based bioassays, binding assays (e.g., ELISA, surface plasmon resonance [SPR]), and enzymatic activity assays.
  • Safety Testing: Quantification of residual host cell proteins (HCPs) via ELISA, host cell DNA using quantitative PCR (qPCR), endotoxins through Limulus Amebocyte Lysate (LAL) assays.

→ Product Characterization: Comprehensive analysis of biologic products, including:

  • Glycosylation Profiling: Analysis of glycan structures using techniques such as hydrophilic interaction liquid chromatography (HILIC)-UPLC-FLR-MS.
  • Charge Variant Analysis: Isoelectric focusing (IEF), imaged capillary isoelectric focusing (icIEF), and ion exchange chromatography
  • Post-Translational Modifications: Identifying and quantifying oxidation, deamidation, glycation, and other modifications that may affect product efficacy and stability.

Regulatory Compliance and Quality Assurance

Abzena adheres to the highest standards of regulatory compliance and quality assurance:

  • cGMP Compliance: Our facilities and processes comply with current Good Manufacturing Practices, ensuring that all materials produced meet regulatory requirements for clinical use.
  • Quality Management Systems: Robust quality management systems are in place, including SOPs, deviation management, change control, document control, and comprehensive training programs to ensure compliance and data integrity.
  • Regulatory Support: Providing support for regulatory submissions, including preparation and review of Chemistry, Manufacturing, and Controls (CMC) sections for Investigational New Drug (IND) applications, Biologics License Applications (BLA), and Marketing Authorization Applications (MAA).
  • Auditing and Inspections: Experience with regulatory audits and inspections from agencies such as the FDA and EMA, ensuring readiness and compliance throughout the development process.

Optimizing your downstream processes

Material generated from the upstream process is used to develop your downstream process as well as provide early stage material for analytical and formulation development. We optimize your downstream processes to remove impurities and increase yields with minimal steps and optimal recovery.

Our capabilities include:

  • Harvest optimization through depth filtration or combined with continuous centrifugation
  • Chromatography steps utilizing all models e.g., affinity, ion-exchange, hydrophobic interaction, metal affinity, etc.
  • Column chromatography from 1 ml through 10 L of bed volume
  • Filter sizing studies
  • Viral filtration determination and viral clearance validation
  • Stability on process intermediates and process hold steps
  • Critical Quality Attributes (CQAs) and Critical Process Parameter (CPPs) validation

Stability

Offering a full spectrum of services, we support stability for drug substance and in-use testing per ICH guidelines. Stability indicating assays are identified early on via forced degradation studies performed during process development.

Following completion of stability time point testing, a final stability summary report is provided to support your clinical studies and market authorization applications.

Preclinical Analytical Development Support

Robust analytical methods inform critical decisions.

Upstream Process Development
Our team applies real-time monitoring strategies to optimize cell culture performance. Using targeted analytical assays, we evaluate parameters such as nutrient utilization, metabolite accumulation, product yield, and process consistency.

 

Downstream Process Development
We design analytical methods to assess purification efficiency (e.g., host cell protein quantification, aggregation analysis) and product purity at each downstream step. This ensures that any process adaptations—such as changes in chromatography conditions—are supported by reliable and actionable data.

Advance your biologic therapeutics with confidence

Abzena San Diego

Partnering with Abzena accelerates your biologic therapeutic programs by delivering optimized, scalable, high-quality processes. Our specialized expertise reduces development and manufacturing risks, enhances efficiency, and positions your biologic for successful clinical and commercial outcomes. We navigate the complexities of biologic process development so you can focus on bringing innovative therapies to patients faster.

Let’s move medicine forward - Abzena

Let’s move medicine forward.

The treatments you’re developing right now can make a real difference for human health. Let us support your work by successfully transferring an existing process—or developing a new one designed around your exact needs.