Experts reflect on 3 topics that reinforce Annex 1 compliance
PUPSIT
Amanda Hawkins, Director of Manufacturing
Grand River Aseptic Manufacturing (“GRAM”) performs pre-use integrity testing of sterilizing grade filters before sterilization, pre-use/post-sterilization (PUPSIT), and traditional post-use. We are experienced with using both pre-sterilized (gamma irradiated) assemblies or assembling and sterilizing in-house through qualified steam sterilization cycles.
Regardless of how materials are received and prepared, GRAM implements PUPSIT to accommodate your process. We incorporate client preferences and product-specific needs within the risk assessments for you. GRAM also performs in-line filtration pressure monitoring utilizing single-use disposable pressure sensing to capture data for monitoring and controlling the overall performance of the filtration process. We adapt our process to the phase of your process, from engineering batches through commercial launch.
These options and all other process parameters and controls are standard topics during technical transfer and project life-cycle management to ensure the process remains robust and compliant.
Facility Design
Jennifer Leale, Director of Quality Assurance and Regulatory Affairs
At GRAM, we designed our facilities from the ground up with Annex 1 top of mind. By choosing a similar platform technology for all four of our B+S filling lines with SKAN isolators, aseptic manufacturing operators knowledgeably move between machines with a deep understanding of all GRAM’s filling equipment. Operator training is robust to ensure up-to-date aseptic practices plus right first time, reducing batch record error, and improving the release time of client products.
Furthermore, GRAM facilities prevent cross-contamination with wide corridors that allow for easy movement and airlocks that separate personnel and material flow. Our Grade C formulation environment incorporates localized Grade A air supply over open the mixing tank during active formulation.
Clients are welcomed to GRAM facilities with a dedicated space to comfortably view their product during the manufacturing process with windows into the formulation suites or camera feeds inside equipment.
Lyophilization
David Belanger, Sr. Validation Manager
Modern CDMO equipment reduces the need for operator interventions and minimizes the risk of contamination. Here at Grand River Aseptic Manufacturing, we have isolator technology with integrated decontamination systems that make the process faster and more efficient. Our SKAN isolators use SKANFOG technology, an advanced decontamination system that reduces process time by several hours. Isolators are considered the safest method for maintaining high sterility levels and reducing the risk of impurity.
Within our isolator Grade A environment, we have an IMA lyophilizer CLU automatic load and unload unit that reduces the need for operator intervention or dealing with a HEPA cart. The lyophilizer chamber is steam sterilized before each use.
The equipment design of our capper includes a camera system to monitor stopper presence and raised stopper detection for 100% of vials that come from the lyophilizer. Every single glove on the isolator is tested no less than once per month, used or not, and all critical gloves are tested after each campaign or batch.
