News
PUPSIT Uncovered | Ensuring Sterile Filtration Integrity in Monoclonal Antibody Processing
2026-01-27
In the sterile battlefield of biopharmaceuticals, final sterilizing filters act as silent guardians, intercepting all microorganisms to ensure every drop of medicine is safe and sterile.But did you know? Before this guardian starts its job, it needs to undergo a rigorous "checkup" — the Pre-Use Post-Sterilization Integrity Test (PUPSIT).Today, let's discuss this critical test and how it becomes the "strongest insurance" for the sterility of pharmaceuticals.
🔍 What is PUPSIT? Why is it so important?
Imagine this: the filter has been sterilized and is about to be put to use. If there’s a tiny defect (like a pinhole or improper installation) during sterilization or installation, regular post-use tests might not detect it. This is because the drug components could "seal" the defect during the filtration process (known as "defect masking").
PUPSIT serves as a "pre-service checkup" for the filter, right after sterilization and before coming into contact with the drug. It can identify "imperfections" before problems arise, preventing contamination risks and avoiding the waste of an entire batch of products due to filter failure.
In a nutshell: PUPSIT = Early risk detection, safeguarding drug safety + reducing production loss.
🧪 Two mainstream "checkup" methods, how to choose?
1️⃣ Bubble Point Test
This test is like checking when a balloon pops: gas is used to push the liquid out of the filter’s wet membrane pores, and the pressure at breakthrough is recorded.
-
✅ Suitable for: Small filters (Area < 0.03 m²)
-
🛠️ Features: Intuitive, sensitive, suitable for small area precision testing.
2️⃣ Diffusion Flow/Forward Flow Test
This is like measuring the "breathing rate" of a filter’s wet membrane: the gas diffusion flow rate through the membrane pores is measured under fixed pressure.
-
✅ Suitable for: Medium to large filters (Area > 0.03 m²)
-
🛠️ Features: Stable, automatable, suitable for mass production.
💧 Pre-test “preparation work”: Choose "water" or "drug"?
Before testing, the filter must be fully wetted. The choice of wetting liquid is crucial:
| Option | Advantages | Considerations |
|---|---|---|
| Water or buffer solution | Low cost, standardized, no product loss | May dilute the drug solution, requiring subsequent drying or rinsing |
| The drug solution itself | No dilution, easier operation | Requires product-specific testing standards, some drug solutions may interfere with test results |
Tips: For high-value products or those prone to foaming, water/buffer solution is more reliable; if aiming for simplified processes and stable drug properties, using the product's own liquid is also a good choice.
🧼 Implementing PUPSIT: Key points to remember!
-
✅ When operating within isolators/RABS
High-pressure tests and manual operations can pose contamination risks. It's recommended to place the filter outside the isolator or significantly simplify the process to maintain sterile conditions. -
✅ Exhaust design considerations
Two common approaches:-
Exhaust bags: Simple and economical, suitable for small volumes.
-
Mixed barrier filters: Handle large gas and liquid volumes but require additional testing.
-
-
✅ Temperature control is key
The temperature of the wetting liquid and test gas must be stable. Temperature fluctuations can directly affect test results and may lead to "false readings." -
✅ Sterility maintenance is non-negotiable
Minimize manual operations, keep systems under positive pressure whenever possible, and automate where possible to avoid manual handling.
🏭 Two classic application scenarios:
Scenario 1️⃣: Fully automated system with hard pipes (e.g., downstream of large bioreactors)
-
Wetting liquid: Water
-
Features: Fully automated operation with air drying, suitable for continuous production, stable and reliable.
-
Steps: System exhaust → Wet filter (water) → PUPSIT → Air purge/drying → Offline integrity test for downstream exhaust liquid filters → Product filtration pre-exhaust
Scenario 2️⃣: Disposable manual system (e.g., clinical samples or small batch production)
-
Wetting liquid: Product itself
-
Features: Flexible and portable, disposable without the need for drying, suitable for multiple product line switching.
-
Steps: System exhaust → Wet filter (process fluid) → PUPSIT → Offline integrity test for downstream exhaust liquid filters → Product filtration pre-exhaust
Note: Steps 1.1–2.5 are cited from PDA Guidelines - Points to Consider for Implementation of Pre-Use Post-Sterilization Integrity Testing (PUPSIT).
🌟 Conclusion: PUPSIT is not just a test, but trust
In the pharmaceutical industry, safety and sterility are not just standards; they are lifelines.
PUPSIT, as the final confirmation before filter use, is not just a technical process but a solemn commitment to patient drug safety.
As a filter manufacturer, we are dedicated to providing high-performance, easy-to-integrate filtration products and systems that meet PUPSIT requirements, working alongside pharmaceutical companies to safeguard the purity and safety of every pharmaceutical product.
References:
PDA Guidelines - Points to Consider for Implementation of Pre-Use Post-Sterilization Integrity Testing (PUPSIT)
📩 For more information on PUPSIT implementation plans or product selection, feel free to contact us for professional support!
Feature-Tec is a global leader in advanced filtration solutions for the biopharmaceutical industry. Specializing in monoclonal antibody (mAb) production, vaccine purification, ADC drug processing, and fermentation purification, we provide cutting-edge technologies including depth filtration, filter integrity testing, sterile filtration, and sterilizing gas filtration. Our comprehensive services also include filter validation, bacterial challenge testing, and chemical compatibility testing, ensuring the highest quality standards.
Feature-Tec’s filtration and separation technologies empower clients to enhance compliance in testing and validation. we support critical stages in drug and vaccine production, including clarification and bioburden reduction. By adhering to stringent global standards such as GMP, USP, ICH, ISO 17025, EMA Annex 1 (EU GMP), and PIC/S, We help our clients meet the highest standards of quality, safety, and regulatory compliance with our solutions.
For partnership inquiries or more information, Email us at marketing@feature-tec.com
Contact
Hotline: (+86)400-820-6150
Email: marketing@feature-tec.com
Address: 8/F, Block A, Building 3, Tianhua Information Technology Park, 299 Longcao Road, Xuhui District, Shanghai
