Product description
Custom single-use PUPSIT assemblies are preassembled disposable fluid paths designed to support Pre-Use Post-Sterilization Integrity Testing of sterilizing-grade filters in pharmaceutical and biopharmaceutical processes.
The assemblies combine sterilizing-grade liquid filters, gas filters, tubing, storage bags, aseptic connectors and optional pressure-monitoring components into a defined sterile filtration fluid path.
Standard configurations are available for single filtration and redundant filtration arrangements, while custom assemblies can be engineered around the required filter train, wetting strategy, process connections and final filling process.
Technical overview
PUPSIT is used to verify the integrity of a sterilized sterilizing-grade filter assembly before process filtration begins. The test is performed after sterilization and before the filter is exposed to the product filtration step.
A PUPSIT assembly provides the tubing, filters, containers and process interfaces required to wet, test and subsequently use the sterilizing-grade filter within a controlled single-use fluid path.
Depending on the filtration strategy, the assembly can contain a single sterilizing-grade filter, serial filtration stages or a redundant sterilizing-filter arrangement.
Operating principle
The sterilizing-grade filter is first prepared using an appropriate wetting liquid and then connected to an integrity-testing system.
A validated non-destructive integrity test is performed before product filtration. Suitable test methods can include:
- Diffusive-flow testing
- Bubble-point testing
- Pressure-hold testing where appropriate
- Other validated integrity-test methods suitable for the selected filter
The applicable integrity-test method and acceptance criteria must correlate with the microbial-retention capability established during filter validation.
After a successful pre-use integrity test, the filtration fluid path can be prepared for process filtration according to the validated operating procedure.
Following product filtration, the sterilizing-grade filter is normally integrity tested again using the validated post-use integrity-test method.
PUPSIT and EU GMP Annex 1
EU GMP Annex 1 states that the integrity of the sterilized filter assembly should be verified by integrity testing before use to check for damage or loss of integrity caused during filter preparation and sterilization.
Annex 1 also requires a non-destructive integrity test after use for a sterilizing-grade filter used to sterilize a fluid.
The guidance recognizes that PUPSIT may not always be possible because of process constraints. Where an alternative approach is used, this should be supported by a thorough risk assessment and appropriate controls.
Material options
Standard PUPSIT configurations combine several fluid-contact materials, each selected according to its function within the filtration assembly.
Typical standard components include:
- PES membrane for the sterilizing-grade liquid filter
- PTFE membrane for hydrophobic gas filtration
- Platinum-cured silicone tubing
- Single-use process bags selected according to the required fluid volume
- Polymer aseptic connectors, fittings and instrumentation components
Reinforced silicone tubing can also be incorporated where a section of the assembly requires increased pressure capability.
Alternative filter membranes, tubing materials, bag constructions and connection technologies can be evaluated for custom assemblies.
Available micron ratings
Standard PUPSIT configurations use:
- 0.2 µm PES sterilizing-grade liquid filter
- 0.2 µm hydrophobic PTFE gas filter
A standard sterilizing-grade capsule configuration is available with an effective filtration area of approximately 660 cm².
A standard hydrophobic gas-filter configuration is available with an effective filtration area of approximately 640 cm².
Other filter sizes, filtration areas and membrane materials can be selected for custom PUPSIT assemblies according to required batch volume, flow rate, product compatibility and validated filtration parameters.
Design and construction
Single-filter PUPSIT assemblies
A single-filter configuration is designed around one sterilizing-grade process filter together with the required wetting, testing, venting and process-transfer fluid paths.
This configuration can be used where the validated sterile-filtration process contains a single final sterilizing-grade filter.
Serial filtration assemblies
Serial filtration configurations can incorporate a bioburden-reduction or prefiltration stage upstream of the final sterilizing-grade filter.
Filter selection and integrity-testing requirements must be defined according to the function of each filtration stage and the validated process.
Redundant sterilizing-filter assemblies
Redundant filtration configurations use two sterilizing-grade filters within the filtration train.
Where both filters form part of the validated sterilizing filtration strategy, the integrity-testing arrangement must allow the applicable filters to be tested according to the validated PUPSIT procedure.
Single-use bag integration
Standard PUPSIT configurations are available with:
- 500 mL single-use bag
- 5 L single-use bag
Other bag volumes can be incorporated into custom assemblies according to the required wetting-liquid volume, flushing procedure and filtration process.
Pressure monitoring
Single-use pressure sensors, pressure gauges or instrumentation tees can be incorporated at suitable positions within the assembly.
Pressure monitoring can support integrity testing and process control while helping confirm that the assembly remains within the validated operating limits of the selected filters and tubing.
Tubing
Platinum-cured silicone tubing is used in standard configurations.
Reinforced silicone tubing can be incorporated where higher pressure resistance is required. Tubing dimensions and lengths can be configured around the required flow, filter connections, integrity tester and filling equipment.
Connection technology
PUPSIT assemblies can incorporate:
- Aseptic and sterile connectors
- Sanitary Tri-Clamp connections
- Hose barb fittings
- Tee, cross and Y fittings
- Instrumentation tees
- Tubing clamps
- Pressure-sensor interfaces
- Connections to integrity-testing equipment
- Custom process interfaces
Wetting strategy
The integrity-test procedure can be designed around a suitable validated wetting liquid.
Depending on the filter and process, this can include WFI or the process liquid itself.
Wetting-fluid selection affects the integrity-test procedure, acceptance criteria, flushing requirements and potential product dilution and should therefore be defined as part of process validation.
Sterilisation and supply condition
Standard PUPSIT assemblies are supplied sterile and ready for integration into the filtration process.
Standard configurations are gamma irradiated using an irradiation range of 25–45 kGy.
Assemblies are individually protected using double-layer PE packaging.
For custom assemblies, gamma compatibility must be confirmed for every component incorporated into the final fluid path.
Production and documentation
Suitable PUPSIT assemblies are produced and assembled in controlled cleanroom environments, with ISO Class 4.8 production available for PUPSIT assemblies.
Each finished assembly is integrity tested prior to release.
Available documentation can include:
- Certificate of Analysis or Certificate of Quality
- Batch traceability
- Filter validation documentation
- Extractables data where applicable
- System design information
- Application and operating documentation
- USP <788> Particulate Matter information
- USP <87> Cytotoxicity information
- USP <88> Biological Reactivity information
- USP <85> bacterial endotoxin information
- FDA 21 CFR 177–182 material conformity information where applicable
- Animal-derived component statements
- TSE / BSE documentation
- Gamma sterilisation documentation
Exact conformity, validation and integrity-test documentation depends on the filters and components selected for the final assembly.
Typical applications
- Final sterile filtration
- Sterilizing-grade filtration prior to aseptic filling
- Pre-Use Post-Sterilization Integrity Testing
- Final filling filtration systems
- Biopharmaceutical manufacturing
- Monoclonal antibody processing
- Vaccine manufacturing
- Recombinant protein processing
- Cell and gene therapy manufacturing
- Small-molecule sterile pharmaceutical processing
- Single-use sterile filtration trains
Key benefits
- Designed for PUPSIT: the fluid path is configured specifically for integrity testing of sterilized sterilizing-grade filters before use.
- Standard and custom configurations: single-filter, serial and redundant filtration strategies can be supported.
- Integrated filtration: sterilizing-grade liquid filters and hydrophobic gas filters can be incorporated within one assembly.
- Pressure monitoring: pressure sensors and instrumentation interfaces can be incorporated where required.
- Closed single-use fluid path: bags, tubing, filters and aseptic connections can be supplied as one preassembled filtration system.
- Pre-sterilised supply: standard assemblies are gamma irradiated and supplied ready for use.
- Flexible process integration: tubing, filter size, bag volume and connection technology can be configured around the existing integrity tester and filtration process.
- EU GMP Annex 1 support: the assembly architecture can support implementation of a validated PUPSIT strategy for sterilizing-grade filtration.
Configuration and quotation
PUPSIT assemblies should be configured around the complete sterile filtration process rather than the filter alone.
For technical configuration and quotation, provide the following information where available:
- Single, serial or redundant filtration strategy
- Process application
- Process fluid
- Required sterilizing-grade membrane
- Required micron rating
- Required filtration area
- Expected batch volume
- Required process flow rate
- Maximum operating pressure
- Integrity-test method
- Integrity tester manufacturer and model
- Wetting liquid
- Required wetting or flush volume
- Single-use bag volume
- Tubing ID and OD
- Required tubing lengths
- Process connection types
- Pressure-sensor requirement
- Final filling equipment connection
- Sterilisation requirement
- Required validation documentation
- Existing filtration drawing or process sketch where available
- Prototype or qualification quantity
- Estimated annual demand
If the complete assembly has not yet been defined, the filtration strategy, filter specification, integrity-test method and existing process connections provide a suitable starting point for technical design.