Improving the Performance of your Lyophalization System Giving you the A to Z on the PAT! Improve Your Ability To: Increase the productivity of your Lyophilization system and avoid expensive batch contamination. Improve the performance of your Lyophilization technology and increase stability and shelf life of your product. Communicate effectively with other departments and team members to streamline your workload Handle scale up issues associated with Lyophilization to get your product to market faster Interpret the PAT and know what the FDA will look for when analyzing your Lyophilization system and avoid costly delays. Keep your system running smoothly by updating outdated equipment and understanding the validation requirements Who Should Attend: This course is intended for both new and experienced professionals within the Pharmaceutical and Biologic Industry. Specifically, the following job functions would benefit from taking this course: Process Engineers Formulation Scientists Validation Engineer Validation Scientist Process Supervisor Chemical Engineer Manufacturing Manager Production Manager Course Description: Lyophilization is a complex science, and finding the practical, hands on knowledge you need is difficult. This two day course will provide much needed information to industry professionals dealing with the formulation, processing, and manufacturing of Lyophilized products. From complying with current regulations to developing a more efficient process, Improving the Performance of your Lyophalization System is the perfect opportunity for you to learn more than what is in a textbook. By integrating case studies, interactive, exercises, and lively discussion, participants will return to work with the knowledge you need to increase productivity and be confident in your “fill to finish” approach to Lyophilization. Agenda - Day One I. Examine the Fundamentals of Lyophilization (1.5 hours) a. Explain current state of affairs b. Examine the essential elements of Lyophilization c. Define key stages, terms and definitions Discussion: Review Participants Background with Lyophilization (0.5 hours) II. Examine Regulatory Issues (1.5 hours) a. Product End Test Requirements i. <1> Injections ii. <905> Uniformity of Dosage Units iii. <85> Bacterial Endotoxin iv. <921> Water Determination v. Elegance? vi. Stability b. Machine Requirements i. Sterility ii. Leak tests iii. What cycle variance is tolerable? c. Cleaning i. TOC testing ii. Release criteria d. Event Recovery: Handling issues Exercise: Critique a Case Study and Discuss Preventative measures (0.5 hours) III. Aseptic Processing (1 hour) a. Autoloaders b. c. d. e. SIP & CIP Pizza Doors Isolators General Process Design IV. Use Process Analytic Technology: “Real time measurements determining process control” (3/4 hour) a. Thermocouple Data – Old and still useful b. Pressure Hold methods c. Manometric Temperature Measurement d. Pirani gauge e. Dew point indicator f. Uses for NMR g. Sample thieves V. Optimizing the Process Cycle (1 hour) a. Chemistry i. Analytic techniques ii. Which excipients and why iii. Stability testing b. Mechanics i. Pressure ii. Temperature iii. Time VI. Improve the Throughput of Your Lyophilization System (1 hour) a. Implementing complete cycle optimization b. Reaching maximum capacity/capability Agenda - Day Two VII. Scale Up – From Pilot to Production (1 hour) a. Using the Collapsed Temperature formulation VIII. Design (1 hour) a. Refrigeration b. Vacuum c. Control systems d. Shelf mechanics IX. Validation (2 hour) a. Formulation b. Freeze Drying Cycle c. Freeze Dryer X. Buying a New Lyophilizer (2 hours) Analysis & Discussion of a URS (one can be handed out and this can be a group discussion session). XI. Trouble Shooting (1 to 2 hours) a. Dealing With: i. Proven Acceptable Range XII. Meeting Review and Close Exercise: Examine Key Points from the past two days of training NOTES: I. II. III. IV. V. VI. Regulations: Guide To Inspections of Lyophilization of Parenterals Automation Miniaturization Batch Process Vs. Continuous Process Advances in Technology PAT as a guide for scale up, setting those parameters would reduce time. Examine the Fundamentals of Lyophilization Explain Current Stat of Affairs Examine the essential elements of lyophilization Define Key Stages, Terms and Definitions Discussion: Review Participants Background with Lyophilization Examine the Regulatory Requirements for Lyophilization Improving your Filling Accuracy The Non Contact Check Weigher (NCCW) Exercise: Critique a Case Study and Discuss Preventative measures Communicate with Key Departments Define Roles and Responsibilities Optimize communication among all personnel involved in Lyophilization Optimizing the Process Cycle Improve the Throughput of Your Lyophilization System Implementing Complete Cycle Optimization Reaching Maximum Capacity/Capability Scale Up – From Pilot to Production Use PAT to Develop Understanding your Company’s PAT Program Validation Formulation Freeze Drying Cycle Freeze Dryer Trouble Shooting Dealing With: Proven Acceptable Range Meeting Review and Close Examine Key Points from the past two days of training Implement Best Practices for Lyophilization Techniques Prevent Lost Batches Streamline your Process Accurately Report Your Progress Stopper Selection Assess Your Product’s Stability Analytical Techniques Practical Applications Speed Up Your Process Micro Containers and Stoppers Improving your Cycle Development PAT Process Capability Approach for Lyophilized Proteins and Biologics Each lyophilization cycle is a specific set of PLC set points in time for chamber pressure and shelf temperature. However, lyophilizers are a complex system of heaters, pumps, compressors, and control systems. As such, they do not operate at the specific set points, but rather vary over a finite range around these set points. While it is not possible to test each of the possible combinations, an envelope of upper and lower limits can be defined. David A. Hamilton, M.S. Ch.E., Manager Pharmaceutical Technology Transfer, Schering-Plough Corporation, Singapore