breve introdução às tecnologias...
TRANSCRIPT
1Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Breve introdução às Tecnologias PAT
Prof. José Cardoso MenezesProfessor (IST) e CEO 4Tune Engineering Ltd
better processes, better products ©
tune (verb)
adapt, adjust, conform, fix, integrate, modulate, regulate, tighten, bring into harmony
2Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Professional highlights
• Chemical, Petrochemical, Food & Pharma
Project Management in PAT & QbD (1996 - )
• 200+ papers & conference talks, graduated 12 PhDs & 50+ MScs theses
• Active member of ISPE, APV, PDA, ACS, AICHE, IFPAC
• Founder of The Lisbon Pharmaceutical Engineering MSc Program (2006 - )
• Trained “Portuguese FDA” (INFARMED) PAT Teams (2006, 2009, 2012)
• Built PAT Teams at six major pharma and biopharma companies
CV highlights
• Professor at TU Lisbon (2005 - )
• Invited Professor at Faculty of Pharmacy Lisbon (2009 – )
• Chemical Engineer (1985), Chemical and Nuclear Industry (1985-1986)
• MSc Organometallic Chemistry (1988), PhD in Bioengineering (1996)
• Post-Docs and Sabbatical leaves in Pharma Industry (1999, 2004, 2011)
Dr. Jose C. Menezes, 4Tune Engineering
Founder and Senior Partner of 4Tune Engineering
(2004 – )
3Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
4Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
raw-mat process
product
When final-specs depend on
RMs and/or processing conditions
easy to monitor by process NIR
high lot-to-lot variability of RMs
end-product multiple specifications
When should a PAT Strategy be Applied ?
5Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Systems EngineeringProcess & Information Flows
________________________________________________
* production-line, process-step, analytical-instrument
SYSTEM*... ...
INPUTS
operating variablesOUTPUTS
quality specs
• Ask “what-if” questions• Be capable of system redesign
• Ability to understand parts• See interconnections
6Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
PAT: Process Understanding & Control
more than putting probes on a process !
6
7Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
P Felizardo, T Robalo, F Folque
Improving biofuels manufacturing through
NIRS and MIRS quality control.
Biofuels International 2010,9,57-58
PAT in Biodiesel Manufacturing
8Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Process Development & ManufacturingSample, Process-Step, Production Line, Life-Cycle
Food Industry Example
9Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
PAT Implementation Scenarios
Marketed “robust” products
PAT used as IPCs to improve QC efficiency
Cost reductions associated with QC
ROI: 100’s k EUR /Year
Marketed products needing improvement
Step-wise PAT implementations to improve QA
Major process efficiency gains
ROI: 1-5 Mio EUR/Year
New products / processes
PAT tools used throughout development,
industrialization & routine manufacturing
Faster time to market and better product QA
ROI: 100’s Mio EUR /Year
A
B
C
without PAT with PAT
10Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Opening a Window onto the Process
PAT instrumentation
11Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
PAT Monitoring: from A to Z
ABB, Bruker, Fogale, Kaiser, Parsum, Thermo, Yokogawa, Zeiss-Corona
at-line or on-line 2D-FLUO, Acoustics, Dielectrics, PSD, MIR, MRT, NIR, RAMAN
liquids, suspensions, powders, solids
12Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Multivariate Calibration Methods
Ab
sorb
an
ce
(a
.u.)
Wavenumber (cm-1)
Chemical and
physical
information
PCA
PLS
Pro
pe
rty
X p
red
icte
d
Property X measured
Multivariate fingerprint of
sample properties –
understanding
relationships
Multivariate fingerprint for
classification purposes
Multivariate
calibration (e.g.,
moisture, API content)
13Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Good-Modeling Practices
• Know your Process– Dynamics, process phases and how these are represented in the available data
(sampling probs etc)
– Are process variables (PVs) cross-correlated or not ?
– Which PVs affect the CQA of interest and should threfore be included in the model)
• Know the Data acquired on your Proceess– Structure (clusters), quality, outliers, missing data points, to be able to choose which
samples for model calibration and validation
• Choose Model Strategy: MLR – PLS– model structure defined by the calibration data set; model should be able to model
well trends in Y (.e., main CQA features)
• Calibrate and Validate the Model– model accuracy evaluated with a validation set (data not used before)
– Use several figures of merit: (1) predicted x fitted; (2) residual plots; (3) statistical tests
RMSE (root mean square error)
14Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Batch Trajectories & Batch Variability
industrial
bioreactors
15Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
• PCA using batch wise unfolding
• Correlation with relative yield
On-line NIR Fermentation Monitoring
16Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Batch Process
17Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Life-Cycle Analysis
• Product Design / Realizationrisk-assessment tools
• Process Development / Industrializationknowledge, design and operating spaces
• Routine Manufacturingcontrol strategies
• Continuous Improvementcontinued verification and troubleshooting
“Knowledge has temporal spread. Information is not knowledge.”Deming
18Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Process Analytical TechnologyData – Information - Knowledge
DATA INFORMATION
KNOWLEDGE
19Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
DIKI* SolutionsIntelligence for your data
Added value increase
Data Inform ation Knowledge Intelligence
A Systems-Engineering Approach
to PAT Implementations
Unit
operationsProcess Products
Overall
system
Monitor Control QualityContinuous
improvement
20Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
What we at 4Tune Engineering
learned over 10 years ?
PAT MonitoringMeasure whole samples to assess process, not sample parameters
Batch Processing1st sample is not just one more sample
Consecutive Batch StepsEnd-to-End Analysis
PAT SolutionsSupport Quality over the life-cycle, not just process-understanding
21Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Industry Challenges
What drives Food companies to become
“operationally excellent” is …
Global competition
Price pressure from Competitors
Regulatory initiatives for Process Innovation
Customer expectations
Shareholder expectations
Manufacturing costs
Increasing standards and regulatory requirements
22Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Lean-Six Sigma vs PAT & QbDfor already existing processes/products
Six Sigma
• Minimizes process variation
• Stable and predictable process results.
• Improves process understanding
• Identify & control causes of defects
Focus on Accuracy
Lean Manufacturing
• Eliminates Waste
• Standardizes work
• Continuous Flow
• Pull strategy
Focus on Productivity
Lean Six Sigma (LSS)
23Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
PAT-Based Manufacturing
Assessing Raw-Materials' Variability
– Complex raw-materials (RM): fast qualification schemes (QC)
– Opportunity for RMs supervisory systems (QA)
– Formulating mixed lots of RMs for targeted specifications
Handling RM Variability During Processing
– Monitoring quality attributes in-process (IPCs) at-line or on-line
– Process supervision (e.g., multivariate trajectories)
– Controlling critical to quality parameters (MPC, feed-forward)
End-Product Quality Control
– Multiparametric QC (e.g., conformity index)
– Blending operations for targeted specifications (when allowed)
24Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Publically Available
References and Credentials
of 4Tune Engineering Ltd
better processes, better products ©
tune (verb)adapt, adjust, conform, fix, integrate, modulate, regulate, tighten,
bring into harmony
25Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
• Felizardo P, Folque F, Machado JE, Menezes JC (2012), Process Analytical Technology: a common
approach across different industries. NIRNEWS 23(10),10-13.
• Alcalà, M., Blanco, M., Menezes, J. C., Felizardo, P. M., Garrido, A., Pérez, D., Zamora, E., Pasquini,
C. and Romañach, R. J. (2012). Near-Infrared Spectroscopy in Laboratory and Process Analysis.
Encyclopedia of Analytical Chemistry, pp. 1-46, John Wiley & Sons, Ltd.
• Menezes, J.C. Correia J.N., The Use of PAT Tools in Biodiesel Production., IFPAC - 21st Int. Process
Analytical Chemistry & Technology Forum, January 27-30, 2008 Baltimore, Maryland (USA)
• Jaumot J, Menezes JC, Tauler R (2006), Quality assessment of the results obtained by multivariate
curve resolution analysis of multiple runs of gasoline blending processes. J. Chemom. 20,54-67 (doi:
10.1002/cem.985).
• Brás LP, Bernardino SA, Lopes JA, Menezes JC (2005), Multiblock PLS as an approach to compare
and combine NIR and MIR spectra in calibrations of soybean flour. Chemom. & Intell. Lab Syst. 75(1),
91-99.
• Felício CC, Brás LP, Lopes JA, Cabrita L, Menezes JC (2005), Comparison of PLS algorithms in
gasoline and gas oil parameter monitoring with MIR and NIR, Chemom. Intell. Lab Syst. 78(1-2),74-
80.
General References
26Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
• Canha N, Felizardo P, Menezes JC, Neiva Correia MJ (2012), Multivariate near infrared spectroscopy models for predicting the
oxidative stability of biodiesel: Effect of antioxidants addition. Fuel 97, 352–357.
• Felizardo P, Menezes JC, Neiva-Correia MJ, PAT Use in Biofuels Manufacturing, chpt 11, pp 201-221, in PAT Applied in
Biopharmaceutical Process Development and Manufacturing An Enabling Tool for Quality-by-Design. Eds Cenk Undey,
Duncan Low, Jose C. Menezes, Mel Koch CRC Press (2011).
• Folque F, Lewis I, Menezes JC (2011), Use of RAMAN as a PAT Tool in Biodiesel Analysis., IFPAC – 25th Int. Process
Analytical Technology Forum, January 17-21, 2011, Baltimore, Maryland (USA).
• Baptista P, Felizardo P, Menezes JC, Neiva-Correia MJ (2008), Multivariate near infrared spectroscopy models for predicting
the iodine value, CFPP, kinematic viscosity at 40ºC and density at 15ºC of biodiesel. Talanta 77(1),144-151.
• Baptista P, Felizardo P, Menezes JC, Neiva-Correia MJ (2008) Monitoring the quality of oils for biodiesel production using
multivariate near-infrared spectroscopy models. J. Near Infrared Spectrosc. 16(5), 445–454.
• Baptista P, Felizardo P, Menezes JC, Neiva-Correia MJ (2008), Multivariate near infrared spectroscopy models for predicting
the methyl esters content in biodiesel. Anal. Chim. Acta 607,153–159.
• Menezes JC, Felizardo P, Neiva-Correia MJ (2008), The Use of Process Analytical Technology in Biofuels Production.
Spectroscopy 23(9),30-33.
• Felizardo P, Baptista P, Menezes JC, Neiva-Correia MJ (2007), Multivariate near infrared spectroscopy models for predicting
methanol and water content in biodiesel. Anal. Chim. Acta 595(1-2),107-113.
• Felizardo P, Baptista P, Sousa-Uva M, Menezes JC, Neiva-Correia MJ (2007) Monitoring biodiesel fuel quality by near infrared
spectroscopy, J. Near Infrared Spectrosc. 15(2), 97–105.
Biofuels
27Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
THANK YOU, any questions ?
Chief Business Development ManagerJoão E Machado, 4Tune Engineering Ltd
4Tune Engineering LtdAv. Antonio Augusto Aguiar 108, 4th floor1050-019 Lisbon, Portugalwww.4TuneEngineering.com
Tel. (+351) 21 606 2788 Fax (+351) 21 606 2790
better processes, better products ©