Continuous Therapeutic Protein Purification via TFF and TFVF Circuit Integration

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Solution Overview

Problem

Current biomanufacturing methods for recombinant proteins are not flexible or cost-effective enough to meet the demands of diverse product pipelines, particularly in terms of continuous and efficient processing and purification of therapeutic proteins.

Innovation Solution

The use of circuit systems incorporating tangential flow filtration (TFF) and tangential flow virus filtration (TFVF) units for continuous ultrafiltration/diafiltration and virus filtration, respectively, integrated with multi-column chromatography systems for the continuous manufacturing of therapeutic protein drug substances.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional batch processing methods are used for recombinant protein manufacturing, then process simplicity is maintained, but productivity and flexibility are insufficient

Engineering Contradiction:

Improvemanufacturing efficiencyVSAvoidsystem complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent implements continuous processing systems where feedstock continuously flows through multiple unit operations including TFF, TFVF, and chromatography columns. This eliminates batch-to-batch interruptions and maintains continuous productive action throughout the manufacturing process, significantly improving productivity compared to traditional batch methods.

Inventive Principle:

Principle #20Continuity of useful action

Solution Approach 2:

The continuous manufacturing system is divided into distinct functional modules: TFF unit for concentration, TFVF unit for virus removal, and multiple chromatography columns for purification. Each module operates independently but continuously, allowing the system to achieve high productivity while managing complexity through functional segmentation.

Inventive Principle:

Principle #1Segmentation

2Productivity

If continuous processing systems with multiple units are implemented, then productivity improves, but device complexity increases

Engineering Contradiction:

Improveprocessing throughputVSAvoidnumber of units

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent combines multiple filtration and purification functions into an integrated continuous system where TFF, TFVF, and chromatography operations are coupled through continuous flow. This merging of functions into a unified continuous process achieves high throughput while managing complexity through systematic integration rather than separate batch operations.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The continuous processing system is designed to handle multiple unit operations (filtration, concentration, virus removal, purification) within a unified platform. The system can process different recombinant proteins through the same continuous workflow, providing multi-functionality that improves productivity without proportionally increasing complexity.

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Adaptability or versatility

If traditional processing methods are used, then equipment cost is lower, but manufacturing flexibility is insufficient for diverse product pipelines

Engineering Contradiction:

Improveproduct pipeline flexibilityVSAvoidmanufacturing cost

Core Design Contradiction:

Adaptability or versatilityVSEase of manufacture

Solution Approach 1:

The continuous processing system is designed with adjustable operating parameters including flow rates, pressure differentials, and residence times that can be dynamically optimized for different recombinant proteins. This dynamic adjustability provides manufacturing flexibility for diverse product pipelines while the standardized continuous platform helps control overall manufacturing costs.

Inventive Principle:

Principle #15Dynamics

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach enables flexible and cost-effective continuous processing and purification of recombinant therapeutic proteins, improving efficiency and reducing costs by allowing for the continuous flow of fluids through the system and efficient separation and collection of desired proteins.

Implementation Method 1

circuit system including a tangential flow filtration (TFF) unit... where the system is configured such that fluid can be flowed through the conduit and the TFF unit, and filtrate not including the recombinant therapeutic protein can be collected from the TFF unit

Methodology Applied

Scientific EffectUltrafiltration: Semipermeable Membrane

Implementation Method 2

circuit system including a tangential flow filtration (TFF) unit having first and second inlets, and (ii) a conduit in fluid communication between the first and second inlets

Methodology Applied

Scientific EffectTangential flow:

Data Source

PatentUS11884703B2Methods of processing a fluid including a recombinant therapeutic protein and use thereof

Publication Date: 2024.01.30 GENZYME CORP

AI summary

Provided herein are methods of processing a fluid that include the use of one or both of a circuit system including a tangential flow filtration (TFF) unit and a circuit system including a tangential flow virus filtration (TFVF) unit. Also provided are integrated and continuous processes for manufacturing a therapeutic protein drug substance that include a step of processing a fluid including the recombinant therapeutic protein using any of the methods provided herein.