title: Recommended Best Practices for Process Monitoring Instrumentation in Pharmaceutical Freeze Drying-2017.
abstract: 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. With respect to product temperature measurement, sources of uncertainty associated with any type of measurement probe are discussed, as well as important differences between the two most common types of temperature-measuring instruments-thermocouples and resistance temperature detectors (RTD). Two types of pressure transducers are discussed-thermal conductivity-type gauges and capacitance manometers, with the Pirani gauge being the thermal conductivity-type gauge of choice. It is recommended that both types of pressure gauge be used on both the product chamber and the condenser for freeze dryers with an external condenser, and the reasoning for this recommendation is discussed. Developing technology for process monitoring worthy of further investigation is also briefly reviewed, including wireless product temperature monitoring, tunable diode laser absorption spectroscopy at manufacturing scale, heat flux measurement, and mass spectrometry as process monitoring tools.
authors.affiliation: Baxter Medical Products R&D, LLC\ 927 S. Curry Pike, Bloomington, Indiana, 47403, USA. steven_nail@baxter.com.
authors.forename: Steven
authors.initials: S
authors.lastname: Nail
authors.affiliation: Pfizer Global Research, Andover, Massachusetts, USA.
authors.forename: Serguei
authors.initials: S
authors.lastname: Tchessalov
authors.affiliation: Allergan, Inc., Palo Alto, California, USA.
authors.forename: Evgenyi
authors.initials: E
authors.lastname: Shalaev
authors.affiliation: IMA Life, Inc., Tonawanda, New York, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Ganguly
authors.affiliation: IMA Life, Inc., Tonawanda, New York, USA.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Renzi
authors.affiliation: IMA Life, Inc., Tonawanda, New York, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Dimarco
authors.affiliation: Baxter Medical Products R&D, LLC\ 927 S. Curry Pike, Bloomington, Indiana, 47403, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Wegiel
authors.affiliation: Baxter Medical Products R&D, LLC\ 927 S. Curry Pike, Bloomington, Indiana, 47403, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Ferris
authors.affiliation: Physical Sciences, Inc., Andover, Massachusetts, USA.
authors.forename: William
authors.initials: W
authors.lastname: Kessler
authors.affiliation: University of Connecticut, Storrs, Connecticut, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Pikal
authors.affiliation: Baxter Medical Products R&D, LLC\ 927 S. Curry Pike, Bloomington, Indiana, 47403, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Sacha
authors.affiliation: Department of Aeronautical Engineering, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Alina
authors.initials: A
authors.lastname: Alexeenko
authors.affiliation: Millrock Technology, Kingston, New York, USA.
authors.forename: T N
authors.initials: TN
authors.lastname: Thompson
authors.affiliation: Millrock Technology, Kingston, New York, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Reiter
authors.affiliation: Injectable Drug Product Technology Services, Pfizer, Inc., McPherson, Kansas, USA.
authors.forename: James
authors.initials: J
authors.lastname: Searles
authors.affiliation: SP Scientific, Gardiner, New York, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Coiteux
mesh_terms: D005612:Freeze Drying / Q000295:instrumentation* / Q000379:methods; D011312:Pressure; D013057:Spectrum Analysis; D013678:Technology, Pharmaceutical / Q000295:instrumentation* / Q000379:methods; D013696:Temperature
keywords: heat flux measurement; mass spectrometry; pressure measurement; process analytical technology; temperature measurement; tunable diode laser absorption spectroscopy