17 November 2025
As sterile manufacturing standards continue to evolve, so do the expectations for filtration performance. One process that has received renewed attention is pre-use post-sterilization integrity testing, or PUPSIT. At Atlas Copco, we work with pharmaceutical manufacturers to deliver process filtration solutions that support compliance and help maintain product safety at every stage. This article outlines key practices for implementing PUPSIT, regulatory expectations, and how to navigate common challenges in pharmaceutical environments.
The role of PUPSIT in sterile pharmaceutical processes
Pre-use post-sterilization integrity testing (PUPSIT) is a method used to confirm that a sterilizing-grade filter remains intact after sterilization and before it is used in production. It is designed to detect damage that might compromise the filter’s performance once the process begins, helping support seamless pharmaceutical filtration processes.
PUPSIT involves testing a sterilizing filter after it has been installed and sterilized but before it is used in production. The goal is to confirm that the filter remains intact and fully functional following sterilization. This step becomes especially important if damage occurs during sterilization and is later obstructed by the product during filtration. In such cases, the post-use integrity test may still indicate a pass, even though the filter did not perform as intended. To minimize this risk, many regulators now require integrity testing before use.
Filter integrity testing methods used in PUPSIT
A range of non-destructive testing methods are available to verify filter integrity before use. These methods help ensure that sterilizing filters remain intact and fully functional after installation and sterilization. Each method has advantages depending on the filter material, configuration, and application. In some cases, combining methods can offer additional validation confidence. Below are some of the most commonly applied techniques in PUPSIT.
Regulatory perspectives on filter integrity testing
The most explicit requirement for PUPSIT is found in the EU’s Good Manufacturing Practice (GMP) guidelines. Annex 1 states that sterilizing filters should be tested before and after use using a validated method. While the US FDA does not mandate PUPSIT specifically, it expects manufacturers to ensure filter performance is controlled and appropriately verified. Regulatory agencies across regions are moving toward harmonized approaches, but in Europe, pre-use testing continues to be strongly emphasized.
Risk assessment-based alternatives to PUPSIT
Not all processes or batch sizes may be suitable for PUPSIT. In such cases, regulators may allow alternatives if risks are well controlled. Research by PDA and BioPhorum notes that while filter damage can be masked under certain conditions, this is rare in well-managed production. Annex 1 now provides guidance for exceptions, such as small-batch use, provided there’s a formal risk assessment and mitigation plan. Assessments should consider filter design, product traits, microbial load, and fouling risk. Supporting documentation must include validation data, justification, and a clear record of process controls.
Implementation challenges in pharmaceutical environments
Successfully incorporating PUPSIT into a sterile production process can be complex. These risks highlight the importance of designing systems that are optimized for PUPSIT from the beginning. Common challenges include:
System complexity
Supporting PUPSIT may require extra components like vent filters, test ports, or drainage systems. These additions must be carefully integrated to maintain sterility while enabling reliable testing.
Contamination risk
Manual interventions or added parts can increase bioburden, especially downstream of the filter. Any compromise here can directly affect product safety.
Operator handling
Errors in valve operation, improper wetting, or incomplete evacuation may lead to inaccurate test results. This puts both sterility and data integrity at risk.
Time and validation impact
Additional setup and test steps can extend batch processing timelines. These changes also require more extensive validation, particularly in high-throughput facilities.
Atlas Copco solutions for PUPSIT and filter integrity
A structured approach is essential for teams tasked with integrating PUPSIT into sterile production. This ensures the testing is efficient, compliant, and does not disrupt routine operations. Some of the key best practices include:
- Designing filtration systems for compatibility: Installing valve configurations and testing access points that allow inline testing without compromising sterility. Additional filters, such as our SMT-G Hydrophobic PTFE membrane for sterilizing grade air, should be placed between the integrity test device and the filter to be tested. This helps to avoid increased bioburden.
- Using validated filters and housings: Atlas Copco provides sterile-grade filters that are fully compatible with forward flow and bubble point testing methods. Our range of SLH-P housings is designed for in situ integrity testing, and the SME⁺ pharma-grade filter is suited for sterilizing-grade liquid applications.
- Incorporating sterile air and steam filtration: Our sterile air filters, such as SMT-G, and steam filter systems, such as MSS, maintain clean conditions during testing and production, reducing the contamination risk.
- Automating where practical: Automation minimizes manual handling errors and supports repeatable testing. Our filters and housings integrate easily into automated skids and cleanroom processes.
- Standardizing training and procedures: Clear SOPs and hands-on training help ensure consistent execution during critical phases like filter preparation and drying.
- Maintaining complete documentation: All testing results, validation protocols, and exceptions should be recorded and traceable to support audits and inspections.
Atlas Copco experts can also support the development of filtration strategies tailored to PUPSIT requirements, from equipment setup to documentation guidance.
Tailored filtration strategies for PUPSIT integration
PUPSIT plays a critical role in assuring sterility and product safety. While it can introduce complexity, it also enhances confidence in process integrity. When equipment and workflows are designed with PUPSIT in mind, compliance becomes much easier to achieve. Atlas Copco offers filtration solutions that simplify PUPSIT implementation across stainless steel, hybrid, and single-use systems. From validated filter elements and housings to sterile air and steam filtration, our products help streamline testing and meet regulatory expectations. If your operations are preparing for Annex 1 compliance or require a filtration strategy that supports integrity testing, contact us to learn how our experts can help you build a compliant and audit-ready solution.
