Moisture content is one of the major output parameters for freeze-dried product. The presentation first reviews sorption and desorption isotherm. An evaluation and validation of moisture limit for a freeze-dried product is then proposed. The different available tools to analyze moisture content inside freeze-died product are described. An evaluation of different lyoprotectors is done. Their evolution during shelf life using non destructive methods is performed. The relevant factors influencing final moisture content during secondary drying of the freeze-drying cycle are evaluated. Finally a simple theoretical model to explain the different results obtained will be described. Attendees will learn:

• A Better understanding of key parameters influencing the freeze-drying process
• A realistic expectation in terms of moisture content in regard of the formulation
• The different tools allowing to follow moisture content for freeze-dried product

The risk of failure and sensitivity to events such as abhorrent conditions, process excursions and differences in dried product attributes sometimes occur in routine manufacturing is high for lyophilized products. Such events warrant an analysis of the root cause and evaluation of any impact on the final product attributes and suitability in releasing a batch. Knowledge of the process and product through appropriate development activities and the ability to assess the impact of such events are critical in evaluating their impact on final product quality.

• Resources and approaches for proper analysis and impact assessment will be highlighted, and encompass

• Evaluating data and a scientific rational for critical product characteristics and attributes
• Identifying and understanding critical and key parameters and their effect on the process
• Use of real-world examples of root causes and impact on process and product
• Impact of new indications and dosage forms in "energizing" sales
• Reallocate resources between internal and external development groups to maximize asset

A lyophilization process is usually only specified in terms of a 乪recipe乫 (shelf temperature and chamber pressure vs. time). This, however, may not guarantee repeatable conditions for the freezing and sublimation steps. According to the recent PAT guidelines, there is the need to study in depth the process in order to develop on-line tools to enable better monitoring and control. It is necessary to move from intensive property (independent of mass) measurements (such as temperature, pressure -partial or total-) to parameters which are scalable and in so doing implement the necessary tools to control the parameters and hence the cycle; thus permitting real-time feedback control actions. Two variables are key to monitoring the lyophilization process: sublimation interface temperature (during the whole of primary drying this has to be maintained below the collapse temperature) and sublimation mass flow (which has to be maximized to achieve the most cost effective cycle). With classical monitoring tools these key goals are not achievable. This is an important issue because:

• Traditional lyophilization process needs a serious qualitative step to adapt to this emerging PAT guidelines initiative and in depth analysis helps to gain process knowledge
• From simpler steady state models up to more complex transient ones, they open a window into the process assisting to assess important lyophilization parameters
• Process can be optimized from the initial R&D
• R&D stage of process development tremendously simplified (time saving)
• Industrial processes can be monitored
• In-line closed loop control possible

Key learning objectives:

• Hear about new and developing technologies for Process Control
• Understand how to control product consistency from lab scale to full scale production
• Discover areas for potential process and operational optimization