IgG Purification Yield via Depth Filtration and pH Control

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Solution Overview

Problem

Current processes for purifying IgG from plasma have limited yields, achieving only up to 55% recovery, which is a constraint given the increasing demand for IgG products while maintaining product quality.

Innovation Solution

A modified purification process involving octanoic acid fractionation, low pH incubation, pH-shift, depth filtration, anion exchange chromatography, virus filtration, and ultra/diafiltration, with specific adjustments in pH and conductivity using multi-hydroxylated amine compounds to enhance IgG yield without compromising quality.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If traditional purification processes (Cohn fractionation, caprylate precipitation) are used, then IgG can be purified from plasma, but the yield is limited to up to 55% recovery

Engineering Contradiction:
ImproveIgG yieldVSAvoidIgG loss
Core Design Contradiction:
ProductivityVSLoss of substance

Solution Approach 1:

The patent applies parameter changes by carefully controlling pH (adjusting to pH 5.2-6.2), conductivity (maintaining below 1.5 mS/cm), temperature (20-25°C), and incubation time (30-120 minutes) during the depth filtration step to optimize IgG recovery while removing impurities, achieving yields exceeding 55%

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent uses an intermediary depth filtration step between caprylate precipitation and anion exchange chromatography. This intermediate filtration using specific filter media (cellulose, diatomaceous earth, or polypropylene) serves as a bridge to remove precipitated impurities while preserving IgG in solution, thereby increasing overall yield

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If multiple purification steps are performed to ensure product quality, then purity is improved, but process complexity increases

Engineering Contradiction:
Improveproduct purityVSAvoidprocess complexity
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent merges multiple functions into the depth filtration step: it simultaneously removes precipitated impurities (proteins, lipids, caprylate complexes), clarifies the solution, and prepares the filtrate for chromatography. This consolidation of filtration and clarification functions reduces the number of separate unit operations required

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent performs preliminary depth filtration to remove bulk impurities and clarify the solution before subjecting it to anion exchange chromatography. This preliminary action reduces the load on subsequent chromatographic steps, allowing them to focus on fine purification rather than bulk impurity removal

Inventive Principle:
Principle #10Preliminary action

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

The modified process increases IgG yield by at least 5% compared to traditional methods without affecting the purity of the final product, addressing the yield limitations of existing processes.

Implementation Method 1

short fatty acids (C6-C12) form insoluble complexes with α- and β-globulins whereas γ-globulins are not as readily precipitated

Methodology Applied
Scientific EffectPrecipitation: Precipitation

Implementation Method 2

steatocrit value, which is a measure of the extent of caprylate complex formation with plasma proteins and lipoproteins

Methodology Applied
Scientific EffectComplex formation:

Implementation Method 3

Batch adsorption of the supernatant on DEAE-cellulose was used to clear additional impurities from the isolated IgG fraction

Methodology Applied
Scientific EffectIon exchange: Ion Exchange

Implementation Method 4

adjusting the solution to a pH of 5.2 to 6.2... removing any precipitate

Methodology Applied
Scientific EffectpH-dependent precipitation: Precipitation

Data Source

PatentEP3016976B1process
Publication Date: 2020.09.09 CSL BEHRING AG
  • EP3016976B1 patent drawingFigure 1
  • EP3016976B1 patent drawingFigure 2(a)~2(b)
  • EP3016976B1 patent drawingFigure 2(c)

AI summary

The invention relates to a modified process for the purification of IgG, improving the yield of IgG per litre of starting material without compromising the quality of the product.