Mass Spectrometry in Freeze Drying, Over 25 Years since the First Installation: How Far have we Come?

Mass Spectrometry in Freeze Drying, Over 25 Years since the First Installation: How Far have we Come?

04/18/2018, 1:15 PM - 2:00 PM

Technical Conference Stage 3, Booth 1376, Exhibit Hall

Language:
English

Mass Spectrometers have commonly been used in the semi-conductor industry where maintaining a clean environment with minimum contaminants under high vacuum is crucial for successful manufacturing batches. Since its early usage for pharmaceutical manufacturing, particularly in the freeze drying environment, a lot has changed. Do we see a growing demand for installations in the production environment? The focus of the current work is aimed at testing developments in mass spectrometers for residual gas analysis and addressing frequently asked questions about the need for, and usage of the same in application to the freeze drying environment. Service life of freeze dryers can sometimes exceed three decades. A simple preventative maintenance operation of the shelf hoses can risk batch contamination unless materials and connections are carefully chosen. A typical freeze dryer cycles through large local thermal stresses with operating temperatures ranging from -50 ˚C to 121˚C and pressures ranging from 10 Pa to 0.2 MPa. Moreover, the shelves of a freeze dryer move during Clean in Place/Sterilize in Place cycles, loading/unloading and stoppering of vials. Although rare, the thermal and mechanical stresses can ultimately lead to micro cracks that eventually leak silicone oil. Initially, these cracks are too small to be observed during preventative maintenance or by the human eye. Coupled with the value of the products manufactured in each batch of a freeze drying cycle, testing product integrity is of paramount importance. Mass spectrometry (MS) is a powerful detection technique that allows sensing species concentrations down to ppm levels of contaminants in a closed environment. The final presentation will compare the use of MS in early installations in the late 80's with recent experiences of the technology in the production environment, its advancement and installation and operation techniques. Further, we will compare data from different MS technologies and cover broad application of the technology towards silicone oil detection, and then explore the option of using MS in detecting water vapor and nitrogen concentration not just in primary drying, but also in secondary drying to better understand the potential of the technology in use as a robust tool not just for silicone oil detection, but also as a PAT tool for moisture measurement and helium detection for system leaks (Mockus et al., 2011; Nail et al., 2017; Patel et al., 2017). Acknowledgements The authors gratefully acknowledge the work and support of the MS group and the PAT and Lyo group from Pfizer for the continuous involvement, feedback and insightful discussions in this on-going research and development initiative. References • Mockus, Linas N., Timothy W. Paul, Nathan A. Pease, Nancy J. Harper et al. "Quality by design in formulation and process development for a freeze-dried, small molecule parenteral product: a case study." Pharmaceutical development and technology 16(6): 549-576. 2011. • Nail, S., Tchessalov, S., Shalaev, E. Ganguly, A. et al. "Recommended Best Practices for Process Monitoring Instrumentation in Pharmaceutical Freeze Drying-2017", AAPS PharmSciTech. doi:10.1208/s12249-017-0733-1. 2017 • Patel, S. M., & Pikal, M. Process analytical technologies (PAT) in freeze-drying of parenteral products. Pharmaceutical Development and Technology, 14(6), 567-587. 2009.

Contributors

  • Arnab Ganguly

    Speaker

    Technology Manager

    IMA Life

    Arnab received a PhD in the School of Aeronautics & Astronautics at Purdue University in 2014 with a focus on modeling low-pressure water-vapor flows...

Type of Session

  1. Type of Session
    Session

Learning Objectives

  1. Learning Objectives 1. Learn about Mass spectroscopy 2. How Mass spectroscopy can help in your manufacturing process 3. Application of Mass spectroscopy to freeze drying for silicone oil detection, water vapor, nitrogen and Helium.

Categories

  1. Track
    Manufacturing Efficiencies & Improvements

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