Single-Use System Integrity (SUSI) Assurance
Built-in Integrity Control Strategy All Along the SUS Life Cycle
With the growing implementation of single-use bags into commercial production and critical process steps, SUS Integrity (SUSI) has become a critical quality attribute for both end-users, regulatory authorities, and suppliers of SUS, as an integrity failure can significantly impact drug safety, availability, and costs. The ASTM E3244-20 standard practice on SUSI assurance recommends Quality Risk Management (QRM) and life-cycle approach. This is in-line with the EU GMP Annex 1 for manufacturing sterile medicinal products, proposing a risk assessment for QRM and Contamination Control Strategy (CCS). Thus, depending on customer application and criticality of a SUSI breach, specific integrity and leak tests may be needed.
In addition to the high-quality standard manufacturing process and control, Sartorius offers additional Supplier Integrity Testing (SIT) performed at our manufacturing sites as well as point-of-use leak test (PoU-LT) at end-user’s site. These can be implemented upon request to ensure the relevant level of SUSI in critical process steps.
Supplier Integrity Testing (SIT)
Supplier Integrity Testing With 2µm Sensitivity for Higher Integrity Assurance
The assurance of single-use system integrity (SUSI) is the result of QbD, process validation, process controls, and integrity testing along the entire product life cycle. For critical process steps, a supplier integrity test (SIT) using helium as a tracer gas can be performed. SIT is available upon request on 2D Flexboy and Flexsafe assemblies, 3D Flexsafe assemblies up to 500L, and Flexsafe Mixers up to 650 L. In addition, the new generation of freeze and thaw containers Celsius FFT/FFTp with Safecore Technology are available in some standard configurations tested by SIT. The test is validated to detect defects as small as 2 µm and is performed in-line on 100% of the SUS during manufacturing to ensure the absence of microbial ingress and liquid leak in the intented use-case conditions, such as during storage and shipment of liquid or frozen drug substances or drug products.
2D Supplier Integrity Testing (SIT)
Flexboy® 2D bags for Storage | Shipping: 50mL to 50L
Flexsafe® 2D bags for Storage | Shipping: 50mL to 50L
Freeze and thaw containers Celsius® FFT /FFTp with Safecore Technology
3D Supplier Integrity Testing (SIT)
Flexsafe® 3D for Storage | Shipping: 100, 200 and 500L
Flexsafe® for Mixing: 50L, 100L, 200L, 400L, 650L
Point-of-Use Integrity|Leak Test
Point-Of-Use Integrity Test (PoU-IT) For Flexsafe® and Flexboy® 2D Bags
In a fast, easy and reliable way, an additional 100% PoU-IT reduces the risk of losing high-value product and protects patient and operator by ensuring that no damage would have occurred during shipping, storage, handling or installation of the Flexsafe® or Flexboy® 2D bags. PoU-IT using the FlexAct BT (Bag Tester) Solution with the Sartocheck® 4 Plus Bag Tester, has a validated detection limit of 10 µm.
Point-of-Use Leak Test for Flexsafe® 3D bags for Storage and for Mixing
The well-established Sartocheck® 4 plus Bag tester technology provides a non-destructive leak test for Flexsafe® 3D storage and mixing bags already installed in the Palletank. The unique patented porous spacers perfectly fit the Palletank shape and avoid any masking effect due to direct contact between the bag and its container, assuring the test reliability. Robust validation with a 6-sigma confidence level applied to pressure decay leak test allows to guarantee the absence of leaks with sizes greater than the detection limit post-installation and just prior to filling.
Point-of-Use Leak Test for Flexsafe® STR Bioreactor
Flexsafe® STR Bioreactors used in cell culture can also be tested at their point of use, following the same test method principles as for 3D bags and Mixers point of use leak test.
Single-Use System Integrity (SUSI) Assurance
Proven integrity of SUS in drug processing steps improves production costs, drug quality and availability.
- Prevents the risk of high value product loss at commercial phase
- Speeds up drug product manufacturing capacity and market availability with SU-proven process integrity
- Protects operator exposure to hazardous substances
- Meets cGMP regulatory expectations for single-use system integrity
Confidence® Validation Services
Sartorius, through its Confidence® Validation Services, performs process-specific validation studies considering the SUS application and the impacts of an integrity breach on the drug quality, operator safety, or business continuity.