The COVID-19 pandemic has highlighted the need for high-quality therapies to be manufactured efficiently at scale, with particular focus on the need for multiple vaccines to be developed, produced, and distributed globally. Liposomes, among several other promising drug-delivery systems, represent an advanced technology to deliver active molecules to the site of action. Currently, there are several formulations in clinical use.
One of our customers, Basic Pharma in Geleen, is a contract drug manufacturing organization (CDMO). Basic Pharma produces semi solid and liquid preparations for pharmaceutical purposes, including liposomes. Liposomes can present difficulties during bioprocessing at the sterilizing-grade filtration step. Sterilizing-grade filtration is an essential operation for biomanufacturing. It ensures that drug substances are free from microorganisms at the end of downstream processing (DSP). One of the challenges in this process when using liposomes is that they are often much larger than conventional biologics such as monoclonal antibodies (MAbs). These antibodies are, on average, around 12nm long, while liposomes have diameters from 40nm up to 500nm. This can be problematic when a liposome particle’s size is reasonably close to or even larger than the nominal pore size of sterilizing-grade membranes, which is typically 200nm (0.2µm). Liposomes are shear sensitive, and thus could deform during filtration, which could explain unconventional filtration and folding behavior.
The case of Basic Pharma
Basic Pharma was using a peristaltic pump for filtration of the liposome solution. However, the liposomes eventually clogged the filter in the pump, thereby halting the flow. This caused significant problems in the production process. When I spoke to them about this problem, I recommended them the Quattroflow 150 pump (QF150SU). This is pump, with a single-use pump chamber, is great for processes like liposome filtration, because it's very gentle with the product. These pumps minimize friction and shear stress as the continuous flow generated by the four diaphragms mimics the pumping of the blood through the four chambers of the human heart. The video below illustrates this method.
Because these pumps are very gentle, a relatively high flow rate can be achieved, creating a high differential pressure over the following filter. As differential pressure increases, relative contact time of the liposomes with the filter will decrease, lowering absorption opportunities. By using the Quattroflow pump, Basic Pharma was able to increase the yield and throughput of the liposome solution and the filtration process now goes smoothly.
Quattroflow pumps minimize friction and shear stress and increase efficiency
At Hitma, we offer a range of Quattroflow pumps, both multiple-use pumps or pumps with single-use pump chambers. Single-use pump chambers can be easily and quickly replaced between batches, resulting in little to no downtime. They have been proven highly suitable for live cell solutions as well as sensitive drug products and other vulnerable biologic products. This is due to their low-shear pumping method. With the Q-control, the controller integrated in every Quattroflow pump, the desired differential pressure across the filter can be maintained throughout the process to protect the product and the system itself.
Do you want to know more about pump technology and the best solution for your specific process? Feel free to contact me.