Detection of silicone oil via mass spectrometry
Detection of silicone oil via mass
spectrometry inside a freeze dryer
April 2, 2013 / Jens Gemmecker
11-Apr-13 / S. 1
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Content
ƒ
ƒ
ƒ
ƒ
ƒ
ƒ
ƒ
ƒ
Purpose of silicone oil detection
Silicone oil
Technical approach on detection
Mass spectrometer: configuration and measuring principle
Integration in freeze dryer (FD)
Worst case scenario
Conclusion
Further options
02/04/2013 / p. 2
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Purpose of silicone oil detection
Primary:
ƒ Securing of product quality during the drying process
ƒ Reliable detection of silicone oil emission within the FD
ƒ Permanent or mobile application under pharmaceutical conditions
ƒ Integration in the plant control system
ƒ Controlled prevention of silicone oil back flow into the FD when
using oil-sealed vacuum pumps
Secondary:
ƒ Process development – reliable detection of steam to determine
the limit point of main and second drying phase
ƒ Maintenance – helium leak testing
ƒ Proof of cleanliness – detection of other gases and fluids (oil,
grease, etc.)
02/04/2013 / p. 3
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Silicon oil: characteristics
Partial pressure of saturated steam:
ƒ ~ 1 mbar at 80 °C
ƒ ~ 10-3 mbar at 0 °C
shelves
cooling coils
x l / s, good
ƒ In case of leaks
creep behaviour leads to emission of oil
even clearly below the detection limit
<10-3 mbar
ƒ In a worst case, emitting particles can
vaporise immediately and cannot be
detected in the process
chamber
02/04/2013 / p. 4
condenser
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Silicon oil: leakage problems
ƒ Silicone oil leaks are not indicated by
regular tests – no obvious loss of silicone
oil, no visible indication on the machine‘s
leak test
shelves
cooling coils
ƒ Silicone oil will be collected at the ice
condenser
ƒ Silicone oil tubes of the shelves are
under the highest stress of the entire
system
chamber
02/04/2013 / p. 5
condenser
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Silicon oil: mechanic strain of the system
ƒ Thermically:
-70…+125 °C
ƒ Mechanically: -1.00…2.45 barü
shelves
cooling coils
chamber
02/04/2013 / p. 6
condenser
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Technical approach on oil detection
Common method:
ƒ Sample taking and analysis in a mass spectrometer (MS)
− Standardised technology
− many possible applications
− „border“ between aseptic area and measuring device
required
− theoretical and technical feasibility of the system has
been proven at the plant
Further options:
ƒ MIR-Adsorption (Medium Infrared Adsorption)
ƒ Photo-acoustic effects in the MIR range
ƒ Laser technologies offer additional chances but the required
development effort is also much higher
02/04/2013 / p. 7
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Mass spectrometer: configuration and measuring principle
ƒ A gas probe is taken out of the process
and ionised, single atoms (mostly vapour)
are separated.
ƒ Taking of the gas probe is done at a much
lower vacuum in order to minimise back
flow into the aseptic area.
02/04/2013 / p. 8
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Mass spectrometer: configuration and measuring principle
ƒ The ionised molecule parts (radicals) are
accelerated and shot into an electric field
(deflection depends on the field strength
and molecule mass)
ƒ A mass spectrum of the radical masses is
captured
ƒ This mass spectrum provides a reliable
conclusion on the different gas particles
02/04/2013 / p. 9
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Mass spectrometer: analysis via Quadera (Pfeiffer Vakuum)
ƒ Inspection of raw data
ƒ Direct analysis of gas
molecules via
determinate matrix
(requires additional PC)
02/04/2013 / p. 10
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Comparison of measuring systems
MKS Vision 2000-P
Pfeiffer Hi Cube RGA
Residual gas analyzer (RGA)
Residual gas analyzer (RGA)
System structure
QUADRUPOLE MASS
SPECTROMETER
PrismaPlus mass spectrometer +
dry-run vacuum pumpstand
System control
Software: Process Eye
Professional
Software: Quadera
System
System denomination
Mass range spectrometer
(atom mass unit / unified atomic mass
unit)
02/04/2013 / p. 11
1-100 amu
1-200/1-300 amu (optional)
1-100/1-200/1-300 amu
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Advantages of mass spectrometry
ƒ Qualitative and quantitative gas analysis
ƒ Low detection limit (< 1 ppm)
ƒ Compact and easy to use analysing unit
ƒ Reliable identification of unknown gases via spectral library
ƒ Monitoring of up to 128 masses (intensities) over time
ƒ Mass range 1 to 100 amu, 1 to 200 amu and 1 to 300 amu
ƒ Application in pressure range from vacuum up to atmospheric pressure
ƒ Gas analysis at variable inlet pressure with pressure-regulated gas inlet
ƒ Measurement of non-polar inert gases
02/04/2013 / p. 12
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Advantages of analysing software
Pfeiffer Vacuum / Quadera:
ƒ User-friendly, intuitive handling
ƒ Customised surface
ƒ Automated measuring processes, programmable via integrated
Microsoft© VSTA© script editor
ƒ Exchange of measuring data via I/O module
ƒ Simple definition of measuring recipes
ƒ Interconnection of the spectrometer data with external signals
02/04/2013 / p. 13
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Integration in freeze dryer
ƒ New machines
ƒ Retrofit
SPS and
visualisation
system
Result
Control
Data transfer
Rack-PC with analysing
software (21 CFR 11
conformity)
Chamber
Mass spectrometer
Condenser
Vacuum unit
02/04/2013 / p. 14
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Integration in freeze dryer
ƒ Different connection points possible
ƒ Connection to the chamber has proven very convenient (sensitivity
measurement)
ƒ Connection to the condenser is rather disadvantageous since the
condenser produces a cold trap and falsifies the measured results
Chamber
Mass spectrometer
Condenser
Vacuum unit
02/04/2013 / p. 15
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Assumption of a worst case scenario
Large system volume:
~24 m³
Small leak of the silicone oil system in an
air bubble above the silicone oil level:
~5 x 10-5 mbar * l / s
Leak rate measuring capacity of the
machine test:
10-2 mbar * l / s
ƒ 2 ppm / s at 1 µbar system vacuum: such a leak can be detected!
02/04/2013 / p. 16
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Conclusion
ƒ Quantitative evaluation of silicone oil contamination has proven
robust and useable in pharmaceutical environments
ƒ Reasonable measuring limit is approx. 10 ppm (theoretically 1 ppm)
ƒ Use of mass spectrometry during production processes is technically
possible; aseptic consequences must be evaluated on an individual
basis.
02/04/2013 / p. 17
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Further possibilities
ƒ All gases (e.g. helium, vapour or evaporated lubricants) can be
detected
ƒ The precise inline measurement of all gas particles allows for onlineassessment of the process development PAT
02/04/2013 / p. 18
© OPTIMA packaging group GmbH
Detection of silicone oil via mass spectrometry
Jens Gemmecker
Technical support by Sebastian Orth
OPTIMA pharma GmbH
35075 Mornshausen
Telefon +49 6462 91576-0
www.optima-pharma.com
02/04/2013 / p. 19
© OPTIMA packaging group GmbH