Dual Container System for Sterile Pharmaceutical Reconstitution

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Solution Overview

Problem

Current methods for reconstituting and sterilizing pharmaceutical concentrates are costly, time-consuming, and pose risks of contamination due to the need for aseptic filling and sterilization, especially for heat-sensitive drugs, and existing systems do not adequately ensure sterility throughout the process.

Innovation Solution

A dual container system comprising a mixing container with an inlet and outlet port, coupled with a filtration device having a filter membrane with a nominal pore size of 0.1 µm to 0.5 µm, which allows for the reconstitution and sterilization of non-sterile concentrates by introducing a pharmaceutical fluid into the mixing chamber, mixing with the concentrate, and passing the mixture through the filtration device to produce a sterile and reconstituted product.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If aseptic filling and sterilization methods are used to ensure sterility of pharmaceutical concentrates, then product sterility is improved, but process complexity and cost increase significantly

Engineering Contradiction:
Improveproduct sterilityVSAvoidprocess complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The system pre-sterilizes the diluent in a sterile container before use, while the concentrate container can be non-sterile. This preliminary sterilization of the diluent (rather than requiring both components to be sterile) simplifies the overall process while ensuring final product sterility through the sterile barrier during mixing.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

A sterile barrier (sterile filter or sterile membrane) is introduced as an intermediary between the non-sterile concentrate and the sterile diluent. This barrier allows mixing to occur while maintaining sterility, eliminating the need for complex aseptic filling procedures and expensive sterilization of all components.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If steam sterilization is applied to pharmaceutical concentrates, then sterilization effectiveness is improved, but heat-sensitive drugs are damaged

Engineering Contradiction:
Improvesterilization effectivenessVSAvoiddrug degradation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

A sterile barrier (filter or membrane) serves as an intermediary that enables sterilization without direct thermal contact. The barrier allows the concentrate to be protected from heat while still achieving sterilization of the final mixture through the diluent side, preventing drug degradation while maintaining sterilization effectiveness.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The system changes the sterilization approach from direct thermal sterilization of the concentrate to indirect sterilization through a sterile barrier. This parameter change (from direct heat application to barrier-based sterilization) allows heat-sensitive drugs to remain intact while still achieving the required sterility level.

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If pre-sterilized containers and materials are used throughout the reconstitution process, then contamination risk is reduced, but material costs and management complexity increase

Engineering Contradiction:
Improvecontamination riskVSAvoidcost of sterile materials
Core Design Contradiction:
Object-affected harmful factorsVSQuantity of substance

Solution Approach 1:

Instead of making all containers and materials sterile throughout the system, the invention applies sterility locally only where necessary - specifically in the diluent container and the mixing interface. The concentrate container can be non-sterile, reducing material costs while maintaining adequate contamination protection through targeted sterile barriers.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The system uses a disposable sterile barrier (filter or membrane) that is inexpensive compared to pre-sterilized containers. This single-use sterile component provides the necessary contamination protection without requiring expensive pre-sterilized containers and complex sterilization logistics.

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

4Reliability

If reconstitution is performed in a laminar flow hood, then sterility is improved, but the process time and operational complexity increase

Engineering Contradiction:
Improvesterility maintenanceVSAvoidreconstitution time
Core Design Contradiction:
ReliabilityVSLoss of time

Solution Approach 1:

The mixing container is designed with built-in sterile barriers (filters or membranes) that automatically maintain sterility during the mixing process without requiring external laminar flow hood equipment. The system self-regulates contamination protection through its design, eliminating the need for time-consuming setup and operation of laminar flow hoods.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

A sterile barrier (filter or membrane) acts as an intermediary that maintains sterility during mixing without requiring a laminar flow environment. This barrier allows the mixing process to occur in ordinary conditions while still preventing contamination, significantly reducing process time and operational complexity compared to hood-based methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

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 system reduces the risk of contamination, decreases the cost of managing sterile materials, and allows for on-demand reconstitution at healthcare facilities, ensuring the production of sterile products ready for patient administration.

Implementation Method 1

a filtration device having a filter membrane with a nominal pore size of 0.1 µm to 0.5 µm... passing the mixture through the filtration device to produce a sterile and reconstituted product

Methodology Applied
Scientific EffectFiltration: Filter (physical)

Data Source

PatentEP3654919B1Dual container system for product reconstitution
Publication Date: 2024.05.01 BAXTER INT INC
  • EP3654919B1 patent drawingFigure 1
  • EP3654919B1 patent drawingFigure 1A~1D
  • EP3654919B1 patent drawingFigure 2

AI summary

A system for reconstituting and sterilizing a concentrate includes a mixing container, a filtration device, and a product bag. The a mixing container has an inlet port and outlet port in fluid communication with a mixing chamber disposed between the inlet port and the outlet port. The mixing chamber is adapted to contain a product concentrate. The filtration device has an inlet and an outlet, the inlet of the filtration device coupled to the outlet port of the mixing container. The filtration device includes a filter membrane with a nominal pore size in a range of approximately 0.1 μιη to approximately 0.5 μιη. The product bag has an inlet port coupled to the outlet of the filtration device, and has a bladder defining an empty sterile chamber for receiving sterilized and reconstituted product resulting from mixing a diluent with a product concentrate in the mixing chamber to obtain a mixture then introduced through the filtration device to obtain the reconstituted and sterilized product.