Media and Buffer Preparation
When considering the design of a large-scale manufacturing facility, support functions such as media and buffer preparation are critical. There are many factors to consider when designing the support spaces for these critically central operations. If large-scale vessels are to be used, their size and number will depend greatly on the number of required solutions. If the facility is multi-product, a greater number of different mixtures are likely to be required than for a single product facility.
Additionally, in a multi-product facility, there are likely to be many different permutations of the production schedule creating variable demand for these services. The media and buffer support functions cannot be a bottleneck for continued facility operation, and must be designed with flexibility in mind. An adequate number of vessels must be available at all times for solution preparation, sterile filtration, and storage, allowing for adequate turnaround time to clean and sterilize between batches. Solutions cannot be stored indefinitely, and the media/buffer preparation schedules must be coordinated so that sterile solutions are used before they expire.
Small-scale production facilities may choose to purchase ready-to-use media and/or buffers in bags in lieu of the capital investment. This approach is only practical when the number of different solutions required is few. The capital equipment expenditure on stainless steel vessels and filters is eliminated; however, the facility operating and raw material costs are increased. Rather than space for cleaning, storage, and operation of support vessels, cold room space must be designed for long-term storage of media and buffer bags. Parsons' staff has experience in the design for both the permanent buffer/media preparation systems and the bag systems.
Filling
Many biotech facilities produce only bulk materials, and ship the product to another facility for formulation and dosage form preparation. Due to the high cost of filling equipment and the high value of the product, special care must be taken when designing a filling suite. Operations are carried out under laminar flow, in Class 100, fully HEPA-filtered processing suites. Access to the room is limited during filling operations to minimize disturbance in the air flow patterns. Protein products are heat and shear sensitive and cannot be terminally heat sterilized; therefore, they must be sterile filtered. All components including tanks, lines, filters and filling equipment must be separately heat sterilized. The components that are exposed to the product are assembled under laminar flow. The product is filled in vials in filling machine and partially stoppered with special stoppers, ready for lyophilization.
Lyophilizer
Most biologics are unstable in aqueous solutions. To extend shelf life, they are freeze-dried. In this process, water is selectively removed from frozen product ice matrix via sublimation, leaving behind solids locked into the matrix. After filling and partial stoppering, vials have to be loaded in pre-washed and pre-sterilized lyophilizers under laminar flow. The product is at risk because of partial stoppering. For larger operations, vials can be automatically trayed and stacked in a cart with shelves and a laminar flow unit. When the cart is full, it can be moved to the lyophilizer and trays loaded in the lyophilizer. The cart travel path and the loading area of the lyophilizer need to be under laminar flow to protect the product. Equipment is available to tray and load the lyophilizer directly from the filling machine.
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