Siemens Nederland N.V. 2001 FDA13April2004 1 Presented by Troy Logan at the Advisory Committee for...
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Siemens Nederland N.V. 2001 FDA13April2004 1 Presented by Troy Logan at the Advisory Committee for Pharmaceutical Science meeting on April 13, 2004
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Transcript of Siemens Nederland N.V. 2001 FDA13April2004 1 Presented by Troy Logan at the Advisory Committee for...
Siemens Nederland N.V. 2001
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Presented by Troy Logan at the
Advisory Committee for Pharmaceutical Science meeting on April 13, 2004
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Siemens – PAT solution in pharmaceutical industry
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• Reducing production cycle times
• Right first time quality (RFT)Preventing rejects, scrap, re-processing
• Managing variability (improving energy and material use and increasing capacity)
• Facilitating continuous processing (improve efficiency)
• Increasing automation to improve operator safety and reduce human errors
• Real time release
PAT opportunities (FDA’s PAT Draft Guidance)
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Ultimate step – Real Time Product Release
• Production and release of pharmaceuticals, without final tests
• Quality is based only on review of process characteristics
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Standardized over the complete unit
Bioreactor Harvest &separation
PurificationBuffer + Medium
Formulation Finishing Packaging
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Multidisciplinary approach
ProcessAnalyticsProcessAnalytics
Chemometrics/ MVDA
Chemometrics/ MVDA
Process under-standin
g
Process under-standin
g
(advanced)Controls
(advanced)Controls
Process development
Process development
ModellingModelling
MESMESregulatory
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7PROCESS
Control
Process
Monitorin
g
PAT concept
IT / MES INFRASTRUCTURE 110100100110010001001001011111001110101
Process Analytics
process Specif. verification
real-timeproduct release
monitoring
iterative learningcontrol
(process) knowledge
optimization
control modules
electronic batch record
equipment modules
pharma modules
batch
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Real Time Product Release
Process output
Temperature,
pH, pO2pressure
Close loop control Close loop control (physical / chemical(physical / chemical parameters only)parameters only)
Close loop control Close loop control (physical / chemical(physical / chemical parameters only)parameters only)
Process feed
Off lineOn line
Required Required Process informationProcess information
PAT
Iterative Learning Iterative Learning ControlControl
Iterative Learning Iterative Learning ControlControl
QualitativeQualitativeQuantitativeQuantitativeFingerprintFingerprint
Transform to quality data
Transform to quality data
Product
M
Bio-reactor
MonitoringMonitoringMonitoringMonitoring
Temperature, pH, pO2, pressure
Lab based review of product quality
Lab based review of product quality
hold
rele
as
e
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Infection detection with PAT
B. subtilis, C. albicans, S. aureus, E. coli, Ps. Aeruginosa, A. niger and L. Brevis
Infected (102 CFU/ml) Non infected
on yeast based fermentation and substrate samples:
Biological contamination
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Bioreactor process monitoring
In-situ NIR Probe
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Use of PAT as qualitative tool
Example vaccine production
Process track monitoring and early detection of disturbances
Scores plot for the two main principal components on collected spectra during the batch process
Process pattern : process fingerprint / signature (multidimensional profile)
Comparing “fingerprints” of different batches
Change in process status
Disturbance
Start
End
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Process Path definition
Data analysis
PAT implementation Road Map
Product Q assessment
Process assessment
analyzer assessement
Risk assessment
1. Measure (Monitoring + Process understanding)
Process control definition (ideal process runs)
Process control for process corrections
Knowledge + Change management
Continuous optimization & improvement
2. Control
3. Optimization
Time
Validation Plan
People & organizatio-nal Managm.
