The complexity of biologics drugs in development continues to increase as the capability in discovery and recombinant technology improves. Numerous commercially-approved products are manufactured by freeze-drying, thus lyophilization represents the gold standard to which novel drying methods must be compared. There are, however, a number of drawbacks to lyophilization, including the lengthy process time required for drying, low energy efficiency, high cost of purchasing and maintaining the equipment, and sensitivity of the product to freezing and various other processing-related stresses.
An alternative drying process evaluated is the vacuum-foam drying (VFD), which compared to other drying techniques, dry static foams have been reported to provide significant stabilization to biotherapeutics. Vacuum-foam drying is a modified freeze-drying process that challenges the conventional processing conditions utilized in lyophilization
Vacuum-foam drying is a drying process, whereby the solution is converted to a dried foam structure in a single step. The overall method involves boiling, or foaming, of the solution under reduced vapor pressure followed by rapid evaporation, leaving a solidified expanded foam structure. The temperature is carefully controlled to avoid freezing due to evaporative cooling. The process can be thought of as a freeze-drying method conducted under a cake collapse condition. Vacuum-foam drying enables removal of water at low temperatures, which is required for heat labile biotherapeutics, through the use of a strong vacuum. For pharmaceutical applications.
Excellent vacuum control is crucial for foam drying. For processing methods in which the system pressure is decreased too quickly, the solution has a greater tendency to freeze and will not foam effectively. Conversely, foaming will be inhibited by decreasing the pressure too slowly, as the concentration and viscosity of the remaining solution will increase. By decreasing the chamber pressure stepwise, while allowing for a short equilibration period, the process-associated loss can be minimized significantly.
Benefits of vacuum-foam drying include the ability to operate at near-ambient temperature. This reduces energy consumption compared to the processes that require either low or high temperature for drying, allowing for a more economical process and reduced stress on the material. Foam drying avoids the formation of ice, which may lead to protein aggregation.
With respect to aseptic processing, the challenges encountered in foam drying are similar to those in freeze-drying. Foam drying does introduce its own unique set of stresses not encountered in lyophilization, namely the surface tension stress associated with cavitation. In addition, the rate of water desorption is expected to be slower for foam dried material compared with a similar formulation processed by freeze-drying, due to the lower specific surface area of the former. Thus, a longer secondary drying process may be required to reduce the residual water content to similar levels as that achieved by freeze-drying, which may potentially negate the energy and time savings associated with foam drying.
Furthermore, vacuum levels must be optimized so that foaming is effective. Freezing of the solution or rapid boiling, which may cause material to escape from the vial, must be avoided through the choice of appropriate vacuum conditions that may be challenging at scale. The potential for boil over could also negatively impact container closure, leading to sterility concerns.
Finally, the appearance of foam dried materials is inherently more heterogeneous than that of lyophilized cakes, which may make product characterization and quality control difficult, let alone acceptance by patients and health care professionals. Hence, foam drying faces a number of significant barriers that may be difficult to overcome prior to its implementation for manufacturing a drug product.