High-temperature, short-time (HTST) pasteurization and ultra-high temperature (UHT) sterilization are continuous-flow thermal processes that have been established and highly refined in other industries for many years. Their precision and minimal impact enable the manufacture of products that cannot be made using batch technologies. HTST and UHT are traditionally used for heat-sensitive products. As continuous-flow processes, they are effective against vegetative cells, viruses, and heat-stable endospores. These characteristics and their continuous-flow nature make them potentially useful as part of the trend toward methods of continuous manufacturing of bio/pharmaceuticals.
Photo courtesy of MicroThermics, Inc.
Technologies frequently evolve separately, often independently, in unrelated industries and transfer between them. This transfer is often how industries and technologies advance and take significant steps forward. Identifying a technology that is proven, highly refined, and fully supported industrially and regulatorily, however, is less common. This is the case for high-temperature, short-time (HTST) pasteurization and ultra-high temperature (UHT) sterilization. HTST and UHT are continuous flow, thermal processes that have been used to pasteurize and sterilize liquids (e.g., foods) for more than 60 years. The processes have been developed as tightly controlled systems and refined to reliably produce high quality products at low cost. HTST and UHT have been optimized to reach high assurance levels for inactivation of vegetative cells, viruses, and heat-stable endospores, all while retaining quality that could not be maintained using batch processes, such as autoclaving.
HTST and UHT in the Food Industry
It seems somehow concerning to use a process that has evolved for food products, such as milk and juices, and use it for highly refined pharmaceuticals, but let's consider the fundamentals. The chemical-reaction kinetics that describe how and why these processes inactivate bacteria but retain the quality in a biological fluid (e.g., milk) are the same as in any other biological fluid. Commercially, these processes are well established and used for products ranging from juices to baby food and even products as sensitive as liquid whole egg. These processes have annual capacities measured in hundreds of billions of packages per year. Commercial equipment for HTST and UHT processes commonly operate at flow rates ranging from roughly 5 gallons to more than 100 gallons per minute. Commercial capacities, however, do not lend themselves to the batch sizes and rapid cycles of research and development. The need to conduct thorough research and to optimize treatments (e.g., hold time, temperature, and heat transfer) for different products has triggered the development of miniaturized research equipment and experimental methods for this purpose. These tools have enabled R&D professionals to address potential manufacturing issues early and avoid losses and costly problems while also helping these processes to become better understood. Optimization of these processes has led to development of a wide assortment of time and temperature treatments as well as highly refined tools to test products and deliver these treatments. As a consequence, small-capacity systems have been developed for lower flow rates, bringing the benefits of HTST pasteurization and UHT sterilization to the high-value, low-volume materials of pharmaceuticals.