Media and buffer preparation is a key part of the biopharmaceutical manufacturing process, and improving the powder transfer process can make this step can cleaner, safer and more efficient. ILC Dover’s DoverPac Containment Systems division explains how
Because sterility is not vital at this early stage of manufacturing, powder ingredients for media and buffers have historically been transferred from stock containers using scoops, and weighed and mixed in buckets or open top bags. This process has often been carried out in a separate room from the production line, to contain any airborne contaminants.
Many companies are starting to move to single-use systems as a simpler, cleaner, and safer way to handle ingredients, but this still means that the dry ingredients for buffers and other media need to be transferred into single-use bags in pre-weighed amounts from large-scale storage drums or bags. There are challenges to face in this process, including the generation of airborne particulates, and the overall aim for powder transfer management is to meet these through the optimised handling of raw materials.
While the ingredients used in media and buffer preparation are typically benign, long-term exposure to any airborne particles is not ideal
Handling any powders creates levels of fine particles in the air. While the ingredients used in media and buffer preparation are typically benign and stable, long-term exposure to any airborne particles is not ideal for employees’ health. Even with the most stable of compounds, a fine powder ‘haze’ in the air also comes with a slight risk of ignition, particularly when there is a chance of static build-up.
Because airborne particles eventually settle out onto surfaces, these could contaminate the next batches of media and buffer to be prepared, so the preparation area has to be cleaned between batches.This lengthens the time needed for changeover, and increases staff costs, or takes people away from more vital jobs.
Biopharmaceutical manufacturing is an expensive process, and waste, even of relatively low-cost ingredients has an impact on the overall costs. Potential sources of waste include single-use bags that are:
These issues can also make it harder for users to stick to recipes accurately, which can have an impact on reproducibility all the way through the manufacturing chain.
To provide a practical solution, single-use bags should be:
Many companies have developed powder-handling systems but these are derived from existing liquid containment systems. While powders and liquids do behave in a similar way, their flow and handling characteristics are not the same. Powders also may need to be dispensed in different volumes to liquids or need different flow rates, meaning that a liquid-type system does not quite meet the right criteria.
ILC Dover has been working in flexible films since its inception in 1947, from NASA spacesuits to drug manufacturing. Its DoverPac Containment Systems division specialises in powder containment systems and has purpose-designed systems from scratch specifically for powder handling in the biopharmaceutical industry, with a focus on getting the usability of the system just right. Called the EZ BioPac, it has a true three-dimensional (3D) design, allowing for enhanced flow and control of the powder, unlike conventional 2D counterparts.
Packs with narrow openings are harder and slower to fill and increase the risk of spillage, leading to contamination of the pack surfaces and wasted raw materials. The EZ BioPac is designed with an open funnel-like top so that it can provide easier and quicker filling. A light, non-metallic frame that holds the top open means that no separate funnel is required and there is one less piece of equipment needing cleaning in the filling area. The large target opening also reduces the chance of overfilling, and makes it easier to fine-tune the weight of product, leading to a more accurate fill.
A non-metallic filling stand is designed to provide an easy fill and adjustment for accurate weighing
By reducing uncontrolled powder handling, the EZ BioPac system lessens the amount of powder that disperses into the air, thereby lowering the risk of cross-contamination and the need for such frequent cleaning. This also serves to protect staff from long-term exposure to inhaled particulates. By lowering the amount of powder in the air, the system also reduces any ignition risk.
It is easy for traditional style single-use bags to become contaminated on the outside as product is spilled, overflows, or simply settles from the surrounding air
It is easy for traditional style single-use bags to become contaminated on the outside as product is spilled, overflows, or simply settles from the surrounding air. DoverPac’s system has a protective outer skirt that covers the outside of the bag during filling, reducing surface contamination and making sealing and handling a cleaner process. To make it simple to seal, the pack simply requires a fold in the bag’s upper neck, which is then clamped tightly closed with cable ties.
Some manufacturing processes require large quantities of buffer and media, thus ready supplies of raw materials are needed in various locations. When filled packs are self-supporting, it is easier to move them around and store them before use. This allows the packs to be filled centrally and stored where they are needed, saving time and resources, and ensuring that supplies are always available. A variety of sizes available off-the-shelf or as custom orders mean that the right volume of bagged raw materials is always available, making media and buffer preparation simpler and cutting the waste of time and product caused by using bags that are too large or too small.
Bags filled with raw materials need to be robust to avoid damage during handling and need to be ergonomically designed to protect staff from injury while lifting. Packs with built-in handles or lifting loops, depending on the size, are thus much easier to handle.
All media and buffers used in biopharmaceutical manufacturing must be made up accurately to ensure that the entire manufacturing process is as reliable and reproducible as possible. As well as ensuring that the single-use bags of raw materials are filled as accurately as possible, they also need to be discharged fully into the mixing vessels. For this purpose, packs should have a separate filling inlet and discharge outlet, keeping the flow path for discharge clean until the contents are required.
One of the sources of incomplete emptying and wastage for single-use bags is the static that builds up on the film
One of the sources of incomplete emptying and wastage for single-use bags is the static that builds up on the film, causing particles to cling to the inside of the bag. Use of an antistatic film which meets FDA, USP, and EU regulatory compliance standards helps to prevent such static.
As the needs of the biopharma companies, regulatory authorities, doctors and patients continue to change, biopharma manufacturing approaches must also adapt. For example, the industry is moving towards open suite processing as a way to lower facility costs. Such facilities demand closed processing to prevent cross contamination, which was formerly avoided by the use of segregated rooms and processing suites.
While media and buffer preparation have been notorious contributors to airborne particulates and contamination, improved powder transfer management allows the process to be closed and contained easily to avoid these risks. Companies supplying single-use disposables will have to ensure that their products are compatible and competitive within this new manufacturing paradigm.
The EZ BioPac system was developed as a disposable system to manually fill powders and then discharge while maintaining GMP conditions.
The system includes a strong, lightweight non-metallic frame that is easy to use and minimises the load on the weight scale to enhance accuracy. The empty EZ BioPac is placed in the frame and becomes self supporting with a wide open top. The unique design includes a protective outer skirt to keep the EZ BioPac clean from powder that can cause cross-contamination.
Charging the bag
With this system a powder charge can be filled quickly, the weight can be adjusted easily in the case of an overfill or underfill, and the unit is securely closed and ready for connection to a vessel for discharge.
The use of ArmorFlex 114 film in its make-up delivers permanent static dissipative properties while meeting FDA and 2002/72/EC requirements for food contact and EP 3.1.3 test conditions.
The pack sizes range from 1–100 litre capacities with 1.5–8in sanitary ferrule reactor charge connections. Rinse ports, vent filters and other process features are available. Smaller sizes have a handle for manual lifting, and larger sizes have lifting loops.