Thursday, March 28, 2024
July 28, 2023
Biopharmaceutical products are valuable and often highly sensitive substances. Their active pharmaceutical ingredients (APIs) must be maintained at the highest-possible quality at all times during their production, transport, and storage. This requires sophisticated freezing and fill technologies.
Freeze-drying, also known as lyophilization, is a common process used to preserve certain biopharmaceutical products. However, not all biopharmaceuticals are suitable for freeze-drying. Some products may have specific stability requirements that are better met by alternative preservation methods such as refrigeration or formulation in a liquid state. The decision to use freeze-drying as a preservation method should be made based on the specific characteristics and stability needs of the biopharmaceutical in question.
There are ongoing studies into the possibility of freeze-drying lipid nanoparticle (LNP)-based mRNA vaccines, although they are not typically freeze-dried . These vaccines are formulated as LNP complexes that protect and deliver the messenger RNA (mRNA) to cells so that they can carry out protein synthesis. The LNPs play a crucial role in stabilizing the mRNA and facilitating its entry into cells. Maintaining the stability and activity of mRNA vaccines can be achieved through freezing and cold storage at very low or ultra-low temperatures, e.g. between -20°C and -70°C.
Cell-based therapies, which involve the use of living cells as therapeutic agents, are also generally not freeze-dried. These therapies often require the cells to be in a viable state to retain their biological activity and therapeutic potential. Freeze-drying typically involves the removal of water from a product, which can be detrimental to the survival and functionality of living cells. While freeze-drying can be used for certain types of cells, such as bacterial cells and cells of some yeast strains, it is not a commonly used preservation method for living mammalian cells in biopharmaceutical manufacturing due to the potential for cell damage and loss of viability during the process. Cryopreservation remains the preferred method for preserving living cells for biopharmaceutical applications.
The freezing of biopharmaceutical compounds has generally relied on one of two methods: Lyophilization (also known as freeze-drying) and freezing. Lyophilization involves the removal of water from a product by lowering its temperature and then lowering the pressure so that any water present, now in the form of ice, can be removed by sublimation, i.e. the ice passes directly from the solid to the gas phase . The frozen liquid is pulverized for shipment and storage, before being returned to its original liquid form. During this process step, known as reconstitution, a suitable solvent, usually sterile water or a buffer solution, is added to the lyophilized product.
Although lyophilization is a commonly used method for freezing biopharmaceuticals such as proteins, the lyophilization process itself also exerts stresses on protein molecules that can lead to a reduction in their stability, affecting a product’s quality and safety .
With lyophilization, on the other hand, product losses can range from a few percentage points to more considerable losses of 10% or more. These numbers can vary considerably depending on the specific circumstances. What undoubtably has a major impact on product viability is the open handling of freeze-dried biopharmaceuticals until their reconstitution.
Plate-freezers offer scalability, from small to large volumes of bulk drug substances, and are therefore suitable for a wide variety of applications, including the laboratory freezing of a few milliliters to the commercial production of hundreds of liters. Compared with other freezing technologies it involves a lower total cost of ownership and an early return on investment.