Advanced Depth Filtration for Biologics Clarification Training Course

Advanced Depth Filtration for Biologics Clarification Training Course

Introduction

The biopharmaceutical industry is undergoing a revolution driven by ever-increasing cell densities and higher product titers for complex molecules like Monoclonal Antibodies, Vaccines, and Gene Therapies. This intensification has rendered traditional separation methods inadequate, positioning Advanced Depth Filtration as the indispensable, front-line unit operation in Downstream Processing. Depth filters, with their high dirt-holding capacity and versatile adsorptive mechanisms, are critical for efficiently removing Host Cell Proteins, DNA, and cell debris from challenging harvest streams. Mastering this technology is no longer optional; it's essential for achieving process robustness, maximizing product yield, and safeguarding the performance of subsequent, high-value chromatography steps. This course provides the cutting-edge knowledge required to develop and optimize next-generation clarification trains.

Advanced Depth Filtration for Biologics Clarification Training Course is meticulously designed to bridge the gap between theoretical principles and real-world manufacturing challenges. It moves beyond basic filtration concepts to delve into Quality by Design principles, filter sizing, and the implementation of Single-Use Depth Filtration Systems the fastest-growing segment in the clarification market. Participants will gain practical expertise in feed stream characterization, predictive fouling analysis, and effective troubleshooting for high-turbidity, high-volume batches. By focusing on process intensification and regulatory compliance, this course equips scientists and engineers to deliver cost-effective, scalable, and fully validated clarification processes that meet stringent cGMP and viral safety requirements, ensuring the accelerated market entry of life-saving biologics.

Course Duration

10 days

Course Objectives

Upon completion of this course, participants will be able to:

1. Evaluate and select optimal Advanced Depth Filter Media based on diverse Feed Stream Characteristics
2. Apply core principles of Quality by Design to design a Robust Filtration Train with documented performance metrics for critical quality attributes.
3. Master the latest techniques in High Cell-Density Clarification and Process Intensification for bioreactors operating at million cells/mL.
4. Perform accurate Filter Sizing and Scale-Up calculations using practical methods like Constant Flux and Constant Pressure tests.
5. Implement and troubleshoot Single-Use Depth Filtration Systems to minimize cleaning validation and reduce cross-contamination risk.
6. Characterize and mitigate the impact of process-related impurities like HCPs, DNA, and colloids using depth filtration's adsorptive mechanisms.
7. Optimize Pre-Treatment strategies, including Flocculation and pH adjustment, to significantly enhance filter throughput and yield.
8. Design and execute effective Filter Flushing and Wetting procedures to ensure Extractables/Leachables compliance and process consistency.
9. Differentiate the roles of depth filtration in Primary Clarification versus Secondary Clarification
10. Analyze and interpret key filtration performance indicators, including Throughput, Flux, and Differential Pressure, for Predictive Fouling Analysis.
11. Develop an effective Troubleshooting protocol for common issues like premature clogging, filter blinding, and product loss.
12. Integrate depth filtration into modern Continuous Bioprocessing workflows and hybrid clarification schemes
13. Ensure regulatory compliance for the clarification step by adhering to cGMP guidelines and demonstrating Viral Safety contribution.

Target Audience

1. Process Development Scientists.
2. Manufacturing & Production Engineers
3. Upstream Processing (USP) & Harvest Specialists
4. Quality Assurance (QA) & Validation Personnel 
5. Technical Services/Support Personnel
6. R&D Bioprocessing Associates
7. Facility & Project Managers.
8. Biotech Consultants & Vendors.

Course Modules

Module 1: Fundamentals of Biologics Clarification

• Role of clarification in the entire Downstream Purification workflow.
• Comparison of primary separation methods.
• Key Impurities in cell culture harvest.
• Introduction to Feed Stream Variability and its impact.
• Case Study: Analyzing a high-titer CHO cell harvest stream to define initial clarification needs.

Module 2: Depth Filtration Mechanisms & Theory

• Detailed mechanisms: Sieving/Straining, Impaction, and crucial Adsorption.
• The role of Zeta Potential and surface chemistry in impurity binding.
• Understanding the Filter Matrix Gradient.
• Filter Media Composition.
• Case Study: Investigating a filter exhibiting early breakthrough due to incorrect electrokinetic adsorption matching.

Module 3: Advanced Filter Media Selection and Characterization

• Selection matrix based on Biologic Type and process stage.
• Bench-Scale Filter Screening using HTS tools for rapid evaluation.
• Assessing the influence of buffer and process fluid pH/Conductivity on filter performance.
• Identifying and mitigating potential Extractables and Leachables risk.
• Case Study: Screening five different depth filter types for a viral vector clarification process to maximize recovery.

Module 4: Process Intensification via Pre-Treatment

• Principles and application of Chemical Flocculation.
• Optimizing Polyelectrolyte Dosing and mixing conditions for aggregate formation.
• The use of Filter Aids to enhance dirt-holding capacity.
• Designing an integrated Flocculation-Depth Filtration train.
• Case Study: Optimizing a polycationic polymer-based flocculation step that reduced filter area by 5-fold.

Module 5: Single-Use Depth Filtration Systems

• Overview of Single-Use filter cartridges, capsules, and integrated assemblies.
• Benefits and challenges of SUTs.
• Practical aspects of SUT set-up, connection, and disposal in a cGMP environment.
• Strategies for maintaining Sterility Assurance and managing supply chain.
• Case Study: Transitioning a 1000L stainless steel clarification process to a fully Single-Use skid to reduce cleaning validation costs.

Module 6: Filter Sizing and Scale-Up Methodology

• Principles of Filter Scaling using Flux and Mass Throughput ratios.
• Practical implementation of Constant Flux and Constant Pressure sizing studies.
• Predictive modeling for determining the required Filter Area (A) using A VspecΓÇïVBatchΓÇïΓÇï.
• Evaluating the impact of Cell Viability and Packed Cell Volume (PCV) on sizing.
• Case Study: Scaling a 50L development batch to a 2000L commercial batch while maintaining the critical throughput per area

Module 7: Filter Flushing and Process Start-Up

• Purpose and necessity of pre-use Filter Flushing and wetting.
• Defining and validating the Flushing Volume and duration for conductivity/turbidity targets.
• Minimizing Product Hold-up Volume and maximizing product recovery.
• Best practices for Equilibration to match the feed stream's environment.
• Case Study: Developing a validated flushing protocol to minimize leachable silicates from a DE-based filter.

Module 8: Performance Monitoring and Predictive Fouling Analysis

• Monitoring key parameters: Differential Pressure, Flow Rate, and Turbidity.
• Interpreting the Filter Performance Curve to identify fouling mechanism.
• Applying models for Predictive End-Point Determination.
• Using Process Analytical Technology tools for real-time monitoring.
• Case Study: Employing an in-line PAT system to predict filter clogging 2 hours in advance, allowing for proactive changeout.

Module 9: Two-Stage and Multi-Stage Filtration Trains

• Rationale for a Graded Filtration Strategy using coarse and fine filters.
• Designing effective Pre-Filtration to protect final sterilizing filters and chromatography.
• Optimizing the inter-stage Buffer Composition and process timing.
• Techniques for integrating Depth Filters with sterile Membrane Filters.
• Case Study: Designing a 3-stage clarification train to protect a Protein A chromatography column from high residual solids and haze.

Module 10: Regulatory Compliance and QbD in Clarification

• Integrating the clarification step into the overall Control Strategy.
• Applying Quality by Design.
• Documentation requirements for Filter Validation and change control.
• Addressing Annex 1 and current cGMP expectations for process control.
• Case Study: Creating a QbD submission package demonstrating the relationship between feed quality and filter

Module 11: Troubleshooting Common Depth Filtration Issues

• Identifying root causes for Premature Clogging
• Strategies for mitigating Filter Blinding and flow rate decay.
• Investigating Product Loss due to non-specific adsorption.
• Analytical techniques for post-use filter examination
• Case Study: Root cause analysis for a batch failure traced back to an un-optimized low pH hold step causing precipitation before clarification.

Module 12: Depth Filtration for Advanced Biologics

• Specific clarification challenges for Vaccine and Recombinant Protein production.
• Depth filtration strategies for high-viscosity and high-turbidity Cell & Gene Therapy vectors.
• Handling Microbial vs. Mammalian cell harvest streams.
• Integrating depth filters into Perfusion and Continuous Manufacturing systems.
• Case Study: Developing a depth filtration process for a high-titer Adeno-Associated Virus harvest, focusing on viral vector recovery.

Module 13: Economic and Environmental Aspects

• Calculating the Total Cost of Ownership for depth filtration options.
• Evaluating the Sustainability impact of single-use vs. stainless steel systems.
• Strategies for effective Waste Stream Management and plastic disposal.
• Optimizing Buffer Consumption and utility usage in the filtration step.
• Case Study: A cost-benefit analysis comparing a regenerated/reused depth filter system versus a standard single-use disposable process.

Module 14: Practical Workshop: Sizing Simulation

• Step-by-step practical exercise in analysing vs. Volume data.
• Interactive session on calculating the required and total filter Cost.
• Hands-on review of vendor sizing tools and software.
• Peer review and critique of simulated Scale-Up Reports.
• Focus on data integrity and documentation for Validation.

Module 15: Future Trends and Regulatory Horizons

• Emerging filter media technologies
• The rise of Hybrid Clarification trains for ultimate optimization.
• Advancements in Automated and In-line Control of filtration skids.
• Future Regulatory Focus areas
• Case Study: Evaluating the potential of a novel electrostatic filter to improve HCP removal after a standard clarification step.

Training Methodology

This course employs a participatory and hands-on approach to ensure practical learning, including:

• Interactive lectures and presentations.
• Group discussions and brainstorming sessions.
• Hands-on exercises using real-world datasets.
• Role-playing and scenario-based simulations.
• Analysis of case studies to bridge theory and practice.
• Peer-to-peer learning and networking.
• Expert-led Q&A sessions.
• Continuous feedback and personalized guidance.

Register as a group from 3 participants for a Discount

Send us an email: info@datastatresearch.org or call +254724527104 

Certification

Upon successful completion of this training, participants will be issued with a globally- recognized certificate.

Tailor-Made Course

 We also offer tailor-made courses based on your needs.

Key Notes

a. The participant must be conversant with English.

b. Upon completion of training the participant will be issued with an Authorized Training Certificate

c. Course duration is flexible and the contents can be modified to fit any number of days.

d. The course fee includes facilitation training materials, 2 coffee breaks, buffet lunch and A Certificate upon successful completion of Training.

e. One-year post-training support Consultation and Coaching provided after the course.

f. Payment should be done at least a week before commence of the training, to DATASTAT CONSULTANCY LTD account, as indicated in the invoice so as to enable us prepare better for you.