LyoHUB efforts drive first consensus standard for lyophilization

Recommended best practices in monitoring of product status during pharmaceutical freeze drying are presented focusing on methods that apply to both laboratory and production scale.

In 2021, the American Society for Testing and Materials (ASTM) issued a new standard, ASTM E3250-21, Standard Practice for Product Temperature and Equipment Pressure Instrumentation in Pharmaceutical Freeze Drying. Much of the standard incorporated findings are laid out in a paper Alexeenko co-authored, a collaborative effort among members of Purdue University’s Advanced Lyophilization Technology Hub (LyoHUB), which was aided in its consortium development with support from the National Institute of Standards and Technology (NIST).

The paper, Recommended Best Practices for Pharmaceutical Freeze-Drying Process Instrumentation, while recognizing the need to protect intellectual property, emphasizes that there are areas where industry can benefit from information sharing and standards — in this case, for pharmaceutical freeze-drying. The paper sets out recommendations for measuring and monitoring product temperature and pressure within the freeze dryer, along with equipment capability testing. Temperature and pressure are vital variables that affect things like heat transfer, process efficiency and product quality.

The ASTM standard, taking the paper’s lead, focuses on best practices for freeze dryer instrumentation, with emphasis on monitoring the status of product for temperature and pressure. It examines and clarifies sources of uncertainty around measurement probes, and the differences between temperature-measuring instruments like thermocouples and resistance temperature detectors. On the pressure side, it considers and issues recommendations for pressure transducers — specifically, thermal conductivity type gauges and capacitance manometers for the dryer’s product chamber and condenser.

LyoHUB led the multi-year effort to deliberate the details of this first recognized consensus standard for pharmaceutical lyophilization. The participants’ collegial, cooperative approach was vital to forging agreement on the best practices that would constitute key elements of the standard. “The consensus-building process took time, to carefully review and consider all aspects of the process across the extended value chain of stakeholders, through a series of workshops and collaborative events with ASTM at Purdue,” said Arnab Ganguly, principal engineer for pivotal drug product technologies at Amgen, chair of ASTM subcommittee E55.05.

LyoHUB also worked to establish an ongoing ASTM subcommittee on lyophilization. This subcommittee’s mission is to develop, disseminate and educate standard practices and guidance relevant to lyophilization of parenterals and other pharmaceutics and biologics for the manufacture of pharmaceutical and biopharmaceutical products. ASTM E55.05 is currently working on establishing best-practice guidance on equipment performance validation and commercial scale-up, and will be looking to convert these best practices into standards very soon as well.

“ASTM E3250-21 is a significant accomplishment,” Alexeenko said. “In 1996, U.S. Congress enacted the National Technology Transfer and Advancement Act, which requires the federal agencies and departments to utilize technical standards developed by voluntary consensus standards organizations whenever possible. Purdue is proud of its faculty involvement in such an important pharmaceutical standard, which may help to combat the pandemic.”