Sterile Submicron Oil-in-Water Emulsion Filtration

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Solution Overview

Problem

Existing methods for producing sterile submicron oil in water emulsions, used as vaccine adjuvants, are insufficient as they rely on a single sterile grade filtration, which does not guarantee sterility, and can lead to clogging and failure in bacterial challenge tests.

Innovation Solution

A process involving the preparation of submicron oil in water emulsions, followed by pre-filtration through a sterile grade filter and subsequent filtration through a separate sterile grade filter, with optional additional filtration steps using filters with varying pore sizes and materials, to ensure sterility and meet bacterial challenge test requirements.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a single sterile grade filtration is used, then the process is simple, but sterility cannot be guaranteed and clogging occurs

Engineering Contradiction:
Improvesterility guaranteeVSAvoidfiltration process complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The single filtration step is segmented into multiple sequential filtration steps using different filter types. A depth filter is used first to remove larger particles, followed by a sterile filter to ensure sterility. This segmentation allows each filter to perform its specialized function, preventing clogging of the sterile filter while guaranteeing sterility of the final product.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The depth filtration is performed as a preliminary action before sterile filtration. By removing larger particles and debris in advance, the depth filter prepares the emulsion for subsequent sterile filtration, preventing clogging and ensuring the sterile filter operates efficiently without being overwhelmed by particulate matter.

Inventive Principle:
Principle #10Preliminary action

2Reliability

If submicron emulsion droplets are used, then sterility can be achieved through filtration, but filtration efficiency decreases and clogging increases

Engineering Contradiction:
ImprovesterilityVSAvoidfiltration efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The filtration process is segmented into two stages: first, depth filtration removes larger particles that would cause clogging, allowing the submicron emulsion droplets to pass through. Second, sterile filtration captures any remaining microorganisms. This segmentation maintains filtration efficiency by preventing premature clogging while ensuring sterility.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The depth filter acts as an intermediary between the submicron emulsion and the sterile filter. It mediates by removing larger particles that would otherwise clog the sterile filter, allowing the submicron droplets to reach the sterile filter without obstruction, thus maintaining both efficiency and sterility.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If multiple filtration steps are used, then sterility is ensured, but retention volume decreases and process time increases

Engineering Contradiction:
Improvesterility assuranceVSAvoidretention volume
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

Each filter is designed with local quality appropriate to its function. The depth filter has larger pores optimized for removing particles in the micrometer range, while the sterile filter has smaller pores optimized for capturing microorganisms. This local quality optimization ensures that each filter operates at peak efficiency for its specific purpose, maximizing retention volume while ensuring sterility.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The filtration process utilizes parameter changes by transitioning from a filter with larger pore size (depth filter) to a filter with smaller pore size (sterile filter). This gradual parameter change allows progressive removal of particles without sudden pressure drops or excessive retention losses, maintaining optimal flow rates and retention volumes throughout the process.

Inventive Principle:
Principle #35Parameter changes

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 process significantly increases the retention volume and ensures the production of sterile submicron oil in water emulsions, meeting the bacterial challenge test conditions and ensuring the emulsions are suitable for human administration.

Implementation Method 1

pre-filtering the oil in water emulsion through sterile grade filter

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentUS10406101B2Process for the production of a submicron oil in water emulsion
Publication Date: 2019.09.10 GLAXOSMITHKLINE BIOLOGICALS SA

AI summary

The present invention provides processes for the production of a submicron oil in water emulsion comprising the steps:a. preparing a submicron oil in water emulsion;b. pre-filtering the oil in water emulsion;c. filtering the oil in water emulsion filtered according to step b) through a sterile grade filter;d. filtering the oil in water emulsion filtered according to step c) through a filter separate to that of step b) or step c); ande. filtering the oil in water emulsion filtered according to step d) through a sterile grade filter separate to that of steps b), c) and/or d).