May 18, 2021
The pandemic has driven the pharmaceutical industry to dramatically accelerate their drug development programs and the processes associated with manufacturing billions of doses of drugs. The importance of lyophilization is coming to the fore as manufacturers seek to develop formulations that are stable at higher temperatures.
Lyophilization is a freeze-drying process in which ice is sublimated from a frozen drug product under high vacuum and low heat conditions. It is the same process that was used to develop the famous “astronaut ice cream” from the ’60s for NASA’s Apollo mission. For biological drugs, a gentler drying process is used so that it is suitable for heat-sensitive active ingredients. The benefits of a lyophilized drug formulation include longer shelflife for actives that are unstable in aqueous solutions, low particle contamination and compatibility with aseptic (sterile) processing. However, there are certain engineering challenges inherent in the process.
Lyophilization chamber operation requires tight control of pressure, temperature and other process conditions. Manufacturers start by establishing the equipment capability of a given chamber because this information helps to determine the ability of a given chamber to remove water for a range of chamber pressures. Therefore, it is necessary to also have insights on the sublimation process occurring in the drug vial and the equipment capability curve to achieve a successful lyophilization process for a given set of operating conditions.
Computational modeling provides a de-risking option for pharmaceutical manufacturers because finished drug product is required for testing the lyophilization process, which represents a significant investment. Modeling also offers a quick and inexpensive option to gain detailed physical insights into process operations. Taken together, modeling helps to optimize operating conditions and equipment design and reduce cost by eliminating product loss.
Ansys has developed two solutions that provide detailed insights regarding equipment capability and the sublimation process. For equipment capability, Ansys engineers have developed a validated methodology to simulate ice slab experiments. This methodology provides information about maximum chamber pressure as well as details about flow velocity, pressure and temperature distributions inside the lyophilization chamber (Figure 1). For sublimation, Ansys has developed a solution that is up to an order-of-magnitude faster to compute compared to traditional physical testing (Figure 2). These two simulations provide detailed information regarding the temperature distribution in a vial and the variation of ice and rate of sublimation as a function of time.
Building on the above work, Ansys is developing a solution that predicts chamber conditions when one of the lyophilization chamber’s shelves is filled with vials. We look forward to sharing this solution with you in a future blog once it is available.