factores de sucesso na implementação de tecnologias...
TRANSCRIPT
1Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Factores de Sucesso na Implementação de Tecnologias PAT
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
Originating from our own track-record
Large Multinational Companies
World-class CMO Companies
Innovator SMEs
Regulatory Agencies
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
5Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
The PAT Team
Diverse knowledgeable people (diverse team)
QA, QC and Production Management on-board
upper management support
control engineers – sensor, sampling, DAQ
statisticians and computer-nerds are to be avoided
put together a team of good, competent, hard-working people
don’t underestimate the importance of having expertise in
chemometrics and multivariate process control on board
A PAT-champion in upper management
6Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Goals Activities Team &
Hierarchy Project Management &
Work Flow Financing & BudgetClients & Internal Dependencies Action
Plan Short & Long-Term
PAT Team Governance
7Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Before you Start
Check the quality and quantity of your process operating data
and the associated lab (QC) data
Check again that your QC has their protocols validated
Ensure good comunication among all involved
clear understanding of gools by all parties involved
good comunication: QA – QC – Production
Have and enforce all the time realistic expectations
reduce expectations of your “end-users” when necessary
8Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Equipment
Type of AnalysisAt-line
in-line
on-line (in-situ)
Multiple Instruments vs Centralized EquipmentMultiple probes in one instrument
Dedicated instrument
SamplingMay become more complex than all the rest
Make sure you design and then measure your sampling system withyour process dynamics in mind (sample transport delays).
9Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Project Development
Define project comprehensively
start-small (less ambitious)
don’t fancy people with your PAT/QbD tools(viz., chemometrics)
Don’t believe in your first results ever
Check & double-check – keep a critical attitude all the time
Use proper statistics in calibration development & validation
Don’t throw away “outliers” (abhnormal data)
Keep as close as possible to the industrial people
don’t get to attached to scaled-down or lab experiments
move ASAP to or even start right away at the industrial problem
Don’t underestimate the time (or effort) needed to get things working (1sttime) and then to keep things running after that.
10Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Adapted from A.Hussain (FDA) Presentation at Pittcon 2002
Marketed “robust” products.
PAT to improve efficiency (minimal
improvement in quality assurance).
Cost reductions associated with QC.
Marketed products needing improvement.
Step wise PAT approach: first improve product
quality, then concentrate on process efficiency !
QC cost reductions, but major profit increases.
New products
same PATs used throughout development,
scale-up & full scale production.
Faster process and product R&D cycles.
A
B
C
without PAT with PAT
PAT Implementation Scenarios
11Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
PAT “Clients”
Quality Control Labs
Production Plants
Process Development Labs
12Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Governance
A
B
C
without PAT with PAT
Quality Control
Production
Process Development
13Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Quality Control
PAT Team
QC Labin a specific
site
– Supplier – Client
Risk VERY LOW
Investment LOW
Return MEDIUM/LOW, might not even justify computation of ROI
Goal QC cost reduction
Example faster & cheaper IPCs and guided sampling towards end-point QC
14Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Production
PAT Team
Production Linein a specific
site
– Supplier – Client – Solution Owner
Risk LOW/MEDIUM
Investment MEDIUM
Return HIGH
Goal Significant Productivity & Consistency Increases
Example Yield optimization, cycle time reduction, variability reduction, etc
15Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Process Development
– Supplier – Client
PAT TeamR&D
Risk MEDIUM
Investment MEDIUM/HIGH
Return VERY HIGH
Goal Faster-Better-(Cheaper) Time-to-Market
Example Quality by Process Design
16Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Implementation & ROI
Building a QbD/PAT Cultureestablishing in-house programs, teams and implementation issues
Business Incentives of QbD & PAT Implementationreturn on investment (ROI)
17Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Typical ROI of PAT Implementations
For Type-A implementations ca. € 50 000 / parameter / year.
For Type-B implementations half of the optimization margin istipically within reach of PAT for improvement (€ 0.5 – 5million/year) depending on type of industry (pharma /biopharma), product unit value, market, regulatory status,.
ROI of Type C implementations is 1 to 2 orders of magnitude hiherthan Type B.
These figures have been obtained by us on several (> 50) industrialPAT projects and also reported by others.
18Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
PERSPECTIVE
FRAMEWORK
THINKING
PROCESS
DISCIPLINE VOCABULARY
SET OF
TOOLS
AN ABILITY WAY
OF
THINKING
CIRCULAR
PAT is about Systems Thinking
being systemic, strategic and holisticPAT must be in place early in process development and throughout process &
product life-cycle
19Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
©J.C
. M
enezes,
2000
Monitoring
Control
Supervision
Diagnosis
PAT Multiple Benefits
20Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
better process characterization & process understanding,
potentialy shorter development & scale-up cycles,
consistent process operation, reducing product variability,
increased productivity with faster monitoring techniques,
increased frequency of analysis for each critical step (product)
achieving higher safety & quality levels for whole process (end-
product),
better use of available production equipment, reduction of
inventory of in-processing products
Process Analytical Technologies
21Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
©J.C
. M
enezes,
2000
Monitoring
Control
Supervision
Diagnosis
Processing Industries: Strong in Control
22Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
A
B
C
process with PAT
process without PAT
QC efficiency gains through cheaper and simpler on-line or
at-line measurements by shift-personnel. Minimal QA
improvements.
Gains in QA with significant reduction in off-spec products
and product reworks, major productivity improvements.
Significantly faster process and product R&D cycles (“time
to market”), very efficient and creative process designs
(“near real-time product release”) and process operation
paradigms.
PAT Implementation Scenarios
23Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Scenario A: PAT as QC Tools
24Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Near-Infrared & Mid-Infrared EquipmentDiffuse Reflectance, Transmittance, Transflectance, Attenuated Total Reflectance
Process Analytical Chemistry
In-Process QC
25Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
FASTER more rapidly (secs) for equal accuracy
BETTER simpler sample presentation
no sample preparation, automatic analysis & reporting
CHEAPER no reagents, no dedicated CQ personel
shift personel handle analysis and measurement feedback
to the process
NIR analyses are generally, 5 to 20 times cheaper and/or faster than reference
methods, for the same accuracy & precision
exact figures depend on type of analysis (identification or quantification) and the
replaced analytical reference method.
NIR Analytical Benefits
26Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Cost x Investment
Profit x Value
27Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Scenario B: PAT in Process Improvement
28Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
A Batch Process
29Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Direct Benefits - COST REDUCTIONS
In-Process Quality Control ………. > € 40,000 / y
Raw-Mat Qualification ………. > € 6,000 / y____________________
TOTAL ca. € 50,000 / y
Indirect Benefits - PRODUCTIVITY INCREASES
ca. 20 times greater : ca. € 1,000,000 / year
1. Improved process understanding
2. Improved process operation
3. Improved QA (following FDA’s tendency)
4. Freeing QC for end-product certification
Economic Evaluation for one PAT Implementation
30Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Scenario C: PAT and Time-to Market
31Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Faster Time to Market
32Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Batches - Samples - Parameters
Transferring from #1 to #2
PAT – Analysis with multi-parametric sensors– On-line processing of data obtained– re-evaluation of transfer criteria
#1
#2
33Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Time 0
industrial
lab
Scaled-Down Experiments (1:1000)
after ensuring comparability of scale-down results
different operating recipes
were used in designed (DOE)
LAB experiments
INCREASING
PROCESS
UNDERSTANDING
OPTIMAL
PROCESS
RECIPES
34Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
QbD/PAT: Faster PD & MAN
Improve Process & Product Target
Compliance
Prototype New Processes Faster
Design More Robust Product Formulations
35Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
QbD/PAT Implementation Scenarios
Adapted from A.Hussain (FDA) Presentation at Pittcon 2002
Marketed “robust” products.
PAT to improve efficiency (minimal
improvement in quality assurance).
Cost reductions associated with QC.
Marketed products needing improvement.
Step wise PAT approach: first improve product
quality, then concentrate on process efficiency !
QC cost reductions, but major profit increases.
New products
same PATs used throughout development,
scale-up & full scale production.
Faster process and product R&D cycles.
A
B
C
without PAT with PAT
36Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
QbD/PAT: The value proposition
Half of the quality losses are within reach of PAT for improvement.
These can amount to € 0.5 – 5 million/year depending on type of
industry, product unit value, market, regulatory status, etc
These figures have been reported and have been obtained by us on
several (> 20) industrial PAT applications already deployed.
Typical figures for the optimization margin captured by PAT are in the
range € 1-2 million / year per PAT application.
37Aplicações NIR na Indústria Agroalimentar | Seminário CATAA| Castelo Branco| Maio. 28, 2015 | © 4Tune Engineering 2015
Summing Up
QbD & PATs were born in the 21st century for this century’s
industries
QbD & PATs are changing process validation, regulatory
submission & inspection (QC & QA)
QbD & PATs are an important economic opportunity at times
of increased competition (e.g., time to the market &
competitive processes)
38Aplicações 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 ©