Biopharmaceutical Pouch Integrity Testing via Pressure Drop

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Solution Overview

Problem

Current methods for checking the integrity of biopharmaceutical fluid bags are complex, time-consuming, and cannot test filled bags without risking contamination or requiring lengthy bacteriological challenge tests.

Innovation Solution

A method using external pressure to detect pressure drops and combining it with electrical current measurement through porous layers to determine bag integrity without internal gas or liquid invasion, allowing for quick and reliable testing of filled bags.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If sterile gas is injected into the bag to test integrity, then leak detection is enabled, but contamination risk increases and test complexity increases

Engineering Contradiction:
Improveintegrity test reliabilityVSAvoidcontamination risk
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses the biopharmaceutical fluid already present in the bag as an intermediary medium to transmit and equalize pressure during the integrity test, eliminating the need to introduce external sterile gas. The fluid itself serves as the pressure transmission medium, thereby avoiding contamination risks while maintaining test reliability through pressure differential measurement across the weld lines.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If sterile gas injection method is used, then integrity can be tested, but test time increases and sterilizing air filter testing is required

Engineering Contradiction:
Improveintegrity test capabilityVSAvoidtest duration
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent extracts and eliminates the time-consuming steps of sterile gas injection, sterilizing air filter testing, and complex setup procedures from the integrity test process. By using the biopharmaceutical fluid already present in the bag as the pressure medium, the method reduces the test to essential operations: applying pressure differential and measuring it, thereby significantly reducing test duration while maintaining integrity detection capability.

Inventive Principle:
Principle #2Taking out (Extraction)

3Reliability

If bacteriological challenge method is used, then integrity can be tested on filled bags, but test duration extends to 14 days and product storage is required

Engineering Contradiction:
Improveintegrity test accuracyVSAvoidtest duration
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The patent replaces the biological/bacteriological testing system with a mechanical pressure differential measurement system. Instead of using bacterial challenges that require 14 days for growth observation, the method applies mechanical pressure to the biopharmaceutical fluid and measures pressure changes across weld lines, providing immediate integrity results without lengthy incubation periods or product storage requirements.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

4Reliability

If external pressure is applied to the bag, then leak detection is enabled, but bag deformation may occur

Engineering Contradiction:
Improveleak detection capabilityVSAvoidbag shape stability
Core Design Contradiction:
ReliabilityVSShape

Solution Approach 1:

The patent applies pressure locally and differentially across specific regions of the bag, particularly focusing pressure application on areas with weld lines where leaks are most likely to occur. By using the biopharmaceutical fluid already inside the bag as the pressure medium and applying pressure through the port, the method achieves effective leak detection at critical locations while minimizing overall bag deformation compared to uniform external pressure application.

Inventive Principle:
Principle #3Local quality

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

Enables simple, rapid, and reliable integrity testing of biopharmaceutical fluid bags without contamination risks, capable of detecting leaks and defects efficiently.

Implementation Method 1

measuring the pressure inside the bag... A decrease in pressure indicates that there is a leak in the bag

Methodology Applied
Scientific EffectPressure drop detection: Pressure Drop

Implementation Method 2

the intermediate layer being electrically non-conductive when it is dry... measuring an electrical value representative of an electrical current passing through the intermediate layer

Methodology Applied
Scientific EffectElectrical conduction through porous material: Conduction (electrical)

Data Source

PatentEP3775825B1Method and device for checking the integrity of a pouch for biopharmaceutical fluid
Publication Date: 2024.07.31 SARTORIUS STEDIM FMT SAS
  • EP3775825B1 patent drawingFigure 1A~1C
  • EP3775825B1 patent drawingFigure 2~3
  • EP3775825B1 patent drawingFigure 4~5

AI summary

A method for checking the integrity of a pouch (3) containing a biopharmaceutical fluid, using a device (7) comprising at least one pressure sensor (6; 16), a control unit (5) and two plates (1, 2) having porous front surfaces (SF1, SF2) between which the pouch (3) to be checked is placed, the method comprising: s1- applying a predetermined test pressure (Ptest) by bringing the two plates towards one another, thus sandwiching the pouch to be checked, s2- then maintaining the position of the plates for the remainder of the test, s3- measuring a pressure value representative of the pressure prevailing in the pouch (3) using the pressure sensor (6; 16), and determining the characteristics of a pressure drop over time, s4- deducing from this, by way of the control unit, a faulty state of the pouch if the pressure drop exceeds a predefined criterion.