Filter Capsule Integrity Testing With a Steamable Sterile Connector

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Solution Overview

Problem

Current pharmaceutical and biopharmaceutical systems face challenges in maintaining sterility during fluid handling, particularly when integrating disposable filter capsules with reusable equipment, as existing methods like steam sterilization can damage non-steel components and lack efficient means for integrity testing without exposing the system to environmental contamination.

Innovation Solution

A fluid transfer device with a non-telescoping plunger mechanism and cam actuator allows for sterile fluid pathway establishment and steam sterilization of filter capsules, enabling integration with both disposable and reusable systems, while providing a pre-sterilized connector that maintains sterility and facilitates easy integrity testing without external piping.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If steam sterilization is used to sterilize filter capsules and connectors, then sterility is achieved, but non-steel components may fail due to high temperature and pressure differentials

Engineering Contradiction:
ImprovesterilityVSAvoidcomponent integrity
Core Design Contradiction:
ReliabilityVSStrength

Solution Approach 1:

The system is divided into separate sterilizable components (connectors) and non-sterilizable components (filter capsules with soft seals). The connectors can withstand steam sterilization and are sterilized separately, while the filter capsules with temperature-sensitive components are handled differently to avoid damage from high temperature and pressure differentials.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

A sterile barrier or intermediary method is used to transfer components without direct contact that would require both components to be steam-sterilized. This allows the filter capsule to remain protected from steam while the connector achieves sterility through alternative means or controlled exposure.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Ease of manufacture

If disposable filter capsules are used to reduce cleaning costs, then cleaning and capital equipment costs are reduced, but integration with non-disposable equipment becomes difficult

Engineering Contradiction:
Improvecleaning costVSAvoidsystem integration
Core Design Contradiction:
Ease of manufactureVSAdaptability or versatility

Solution Approach 1:

The connector design provides universal adaptability by incorporating features that work with both disposable filter capsules and traditional reusable equipment. The connector serves multiple functions: it connects to disposable capsules, interfaces with reusable equipment, and maintains sterility barriers, enabling the system to accommodate different component types.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Solution Approach 2:

The system embraces disposable components (filter capsules) where appropriate to reduce cleaning costs and improve ease of manufacture, while using reusable components (connectors, equipment) where it makes sense. The connector acts as a bridge that enables the economical use of disposable capsules without sacrificing integration capability.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

3Reliability

If pre-sterilized assemblies are used to reduce bioburden, then aseptic assurance is improved, but connections made after steaming must be aseptic to prevent contamination

Engineering Contradiction:
Improveaseptic assuranceVSAvoidconnection procedure
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

Components are pre-sterilized and pre-prepared before assembly to establish sterility barriers in advance. The connector is designed to maintain these pre-established barriers during connection, allowing assemblies to be connected after steaming without compromising aseptic assurance, as the sterility was already established in the pre-sterilized components.

Inventive Principle:
Principle #10Preliminary action

4Reliability

If rigorous testing and validation are performed on reused systems, then sterility is proven to authorities, but costs and time to market increase significantly

Engineering Contradiction:
Improvesterility validationVSAvoidtime to market
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The system uses disposable filter capsules that eliminate the need for rigorous repeated validation of the same physical system. Each disposable capsule is pre-validated by the manufacturer, and once used, it is discarded rather than re-validated. This approach maintains sterility assurance while dramatically reducing the time and cost associated with repeated validation cycles for reused equipment.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

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 solution allows for efficient sterilization and integrity testing of filter capsules within existing systems, reducing contamination risks and costs by enabling the use of pre-sterilized components that can withstand steam sterilization, and simplifying the assembly and validation processes.

Implementation Method 1

A linearly moveable plunger is contained within the bore. The plunger can be moved by rotation of a section provided on the body.

Methodology Applied
Scientific EffectMechanical movement:

Implementation Method 2

Steaming is the most effective means of sterilization. The use of steam in a set system is known as steaming in place or SIP. Saturated steam carries 200 times the BTU heat transfer capacity of heated air because of the latent heat released by the steam as it changes from vapor to liquid.

Methodology Applied
Scientific EffectSteam sterilization:

Implementation Method 3

provide a processing system that is capable of handling fluids in a sterile manner. This is designed to prevent unwanted, often dangerous organisms, such as bacteria as well as environmental contaminants, such as dust, dirt and the like from entering into the process stream

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentEP3495701B1A method of integrity testing filter capsules
Publication Date: 2021.06.16 EMD MILLIPORE CORP
  • EP3495701B1 patent drawingFigure 1~2
  • EP3495701B1 patent drawingFigure 3~4
  • EP3495701B1 patent drawingFigure 4A~5

AI summary

In a method of integrity testing a filter capsule, a manifold assembly unit is used, which comprises a filter capsule having a pressure input port, a feed port and a permeate port, a pair of valves in fluid communication with the feed port and a pair of valves in fluid communication with the permeate port. Each valve comprises a body (4). Contained within a bore of the body is a movable plunger (18) that moves without changing the axial dimensions of the body (4). A first end (6) of the body (4) contains a face designed to be attached to an upstream component. A second end (8) of the body (4) is connected to a downstream component. A first end of the plunger, when it is in the closed position, is in alignment with the face of the body, which combined form a steamable surface and a sterile barrier against the environment to the remainder of the interior of the body (4), the plunger and downstream components. An actuator (50, 50') is rotatable relative to the body (4) and causes the plunger (18) to move axially within the bore from an open to a closed position.