Although bulk filtration of a product prior to shipping was one of the first bioprocessing steps to benefit from single-use technology, it has been one of the last to benefit from single-use automation.
Indeed, for many biopharmaceutical manufacturers, the process has changed very little from the days before single-use technology was adopted: the main differences have been the replacement of the stainless steel tank with a bag and the steam cross with aseptic connectors.
Parker Bioscience Filtration was approached by a customer to develop a solution that would address concerns around the bulk filtration unit operation.
What were the customer's concerns?
Protection - As the customer was filling high potency active pharmaceutical ingredients (HPAPIs), it needed to eliminate open processing to protect the operator and the product.
Standardization and simplification - The customer needed to standardize the filling platform in order to create a standard operating procedure (SOP); this would simplify training and eliminate process variation.
Hygiene -The customer wanted to reduce the number of people involved directly in the filling.
How Parker helped
Working closely with the customer, Parker Bioscience Filtration developed the Generation One SciLog® Filter and Dispense System. This enabled fully enclosed automated bulk filling of the HPAPI into bottles in preparation for transportation to a filling site.
Parker was able to identify several benefits of automated closed filling:
No more false positives - The elimination of false positives meant that the customer would not be exposed to the costs (and lost time) of the quarantine and investigation process related to a false positive. Nor would it be exposed to the risk of a batch being rejected.
Saving time - Comparing manual filling and automated filling, data was generated on time savings based on two filling volumes and a set batch size. If these time savings were applied to a facility producing 35 batches per year, the cost reductions generation could run into €100,000s.
Reduction in clean room personnel required - As the process is fully enclosed and automated, the need for QC sampling and QA oversight was reduced - this meant fewer staff were required in the clean room.
Standardization driving simplification - Training and SOP became simpler as a result of standardization. The risk of deviation and human error was also reduced, and the supply chain and handling process was simplified.
The development of the generation two system
Although we had developed a solution for a fully enclosed and automated filling process, collaboration with the customer did not stop there. The safe arrival of the bottles at a filling site was the customer's priority - and taking into account their feedback, we developed the generation two SciLog® Filter and Dispense System.
How did Parker do it?
Increasing the filling accuracy
The filling accuracy of the generation one system was +/- 10 percent - initially deemed acceptable.
However, the filling accuracy was increased to a much higher level of +/- 100 mg following feedback from the customer's QA team and our knowledge of how many bottles they needed to fill, as well as product and consumable reconciliation.
With the generation one system, based on a 20 L and a 500 ml fill, anywhere between 36 and 44 bottles were required. With the generation two system, the maximum number of bottles required is 40 and the minimum is 39.
Improving the filling process
As the generation two system allows a rapid fill to 90 percent of target volume, the process can be run at a slower rate to ensure accuracy. This balances the requirement for product quality and process efficiency.
Parker also introduced a J-tube system which diverts the flow of liquid to the side of the bottle. This was developed to prevent the foaming that would occur if liquid was dropped into a bottle vertically.
Component selection driven by process facility knowledge
It is essential to choose materials that can support the process - and this can only be done if the full extent of the storage conditions is known. A solution may be filled following cold storage at 4°C, for instance, but may then be stored in dry ice at -78.5°C. This will have a critical impact on the choice of materials. In addition, not all products will be compatible with all of the materials used in a single-use assembly. Again, knowledge is key.
Validating the system
While the system was validated to perform the fully automated and contained filtration and dispense of bulk APIs, this was not the end of the validation process.
Shipping of the product to the final destination was also part of the solution Parker needed to provide for the customer and, therefore, this also needed to be validated. To do this, Parker subjected the bottles to further testing to demonstrate their post-shipping integrity — a crucial final step in validating the entire process.
Our work in developing the generation two SciLog® Filter and Dispense System underlined the importance of truly understanding what matters to a customer — and in this case, that went beyond the system's functionality.
This post was contributed by Guy Matthews, division marketing manager, Parker Bioscience Filtration, United Kingdom
Parker Bioscience Filtration specializes in automating and controlling single-use bioprocesses. By integrating sensory and automation technology into a process, a manufacturer can control the fluid more effectively, ensuring the quality of the final product. Visit www.parker.com/bioscience to find out more.