project disha intermediate product yield … limited...• kicked off in 2012 at two pilot sites,...
TRANSCRIPT
Project Disha – Intermediate Product yield improvement
Leader: Mr. Pankaj Chaudhari Sponsor: Mr. Pravindan Gadhvi
Coordinator: Mr. Roshan Wanjari
• Kicked off in 2012 at two pilot sites, has completed four waves covering all sites
• Top driven – Steering committee chaired by MD
• Uses Lean Six Sigma approach for continuous process improvement
• A pool of over 48 Black Belts and 72 Green Belts
• Saved over INR 50 Cr since inception of the program
DISHA – Operational Excellence Program at Lupin
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Build a sustainable operating model for improving and sustaining profitability by developing
continuous improvement capabilities within Lupin
Intermediate High Level Process Map
Stage 1 Stage 2
Stage 4
Stage 3
Stage 5 Stage 6 Stage 7
Baseline Yield of Nov-Dec 2013
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Project Charter
Business case: Intermediate yield improvement from 0.2474
to 0.2592, which leads cost saving of 898 lac/annum against the budgeted volume of 239 MT per year.
In Scope : Steps : Stage 4,5,6 & 7 Out of Scope In-between process change shall not be considered. Solvent recovery specific Stage 4 and Stage 5 DCM are not taken into consideration.
Problem Statement: Since last 9 months Intermediate yield variation
is critical problem & variation is observed from 0.241 to 0.254
Goal Statement: Yield improvement Stage 4: From : 0.8137 to 0.819 Stage 7: From 0.3477 to 0.363. Intermediate: From 0.2474 to 0.2592. Variation (standard deviation) reduction : Intermediate: From 0.01517 to 0.00506
Team: 11 Members from Production 1 Member from Engg 1 Member from PD lab 1 Member fro PED 1 Member from QC/QA
DMAIC
Phase Jan-14 Feb-14 Mar-14 Apr-14 May-14 Jun-14
Define 12-Feb
Measure 20-Mar
Analyze 20-Apr
Improve 10-May
Control 15-Jun
Customer & Quality focus
Voice of Process
• Price reduction for the Intermediate
• Sustained quality of the Intermediate
• High variation in yield
• Gap between actual and theoretical yield
• API sales team asking for reduction in Ex factory cost.
• 20 Ton Market share can be increased in 2015-16, if cost of Production is lower. Regulatory
compliance
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DMAIC
SIPOC
Process
Stage 1
Stage 2 In Scope
Out of Scope
Stage 3
Stage 5B
Stage 6
Stage 7
Stage 5A
Stage 4A Stage 4B Stage 4C Stage 4D Stage 4
Stage 5C
Supply Input (Qty)
Input requirement
Process Output
requirement Output (Qty)
Customer
RM suppliers
RM Specification.
of RM
Key Raw material to
Stage 7 Intermediate
Spec. of intermediate
Intermediate
Warehouse
DMAIC
Out of seven stage,
Stage no.4, 5,6 & 7 are in scope of this project &stage 4 & 5 are also
divided into sub steps.
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Targets Validated Through 1 Sample T Test
Stage
Average yield
of April'13-Dec'13
Targeted yield is validated by 1 sample “T”
test
Stage 1 Assuming same as previous for benefit calculation.
(Out of Scope) Stage 2
Stage 3
Stage 4 0.8137 0.8190
Stage 5,6 & 7 0.3477 0.3630
Intermediate 0.2477 0.2592
Total Potential cost saving of 8.98 Cr/ Year Validated by Finance Dept.
Ho: Target is equal to Baseline Ha: Target is greater than Baseline
DMAIC
As P value is less than 0.05 accept Null hypothesis which shows that target is significant.
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Define Phase Activity
Probability of Occurrence
Seve
rity
of
Imp
act
High Medium Low
Hig
h
Med
ium
L
ow
Risk 5
Risk 4 Risk 1
Risk 2 Risk 6
Risk 3
Risk Prioritization Grid
DMAIC
No
Risk Description
Prob.
Impact
Risk Risk Management Plan
(How to Avoid / Transfer / Mitigate / Accept)
1 Experimental and analytical support
2 3 6 Delegation of task by making responsible to concern person.
2 Input RM supplier, quality and analysis
1 3 3 Prior discussion with vendor , raising specific requirement. Avoid new vendor during project.
3 Variation in budgeted volume
1 2 2 To be done in second phase
4 Changes in process, equipment and facility
1 3 3 Risk evaluation shall be done
5 Audits (ISRS, Regulatory, vendor)
2 1 2 Rescheduling according to audit period.
6 Documentation delay
2 3 6 Escalating the issue to seniors and arranging all concern to meet and approve the same.
Risk Identification
DMAIC
• Value stream Mapping • Issue tree • Data Collection Plan • Measurement System Analysis • Process capability • Quick Wins
MEASURE
Value Stream Mapping Summary of VSM Exercise (12 Feb to 4th Mar 14 )
Step Important Insights & Quick
Wins Status
Stage 4
In process Recovery stage – Temp control up to NMT 40 C against NMT 50 C
Implemented since 15th Feb 2014,Significant improvement of 2.1% observed in Stage 4 yield.
Stage 5
Stage 5 ML Treatment - Increased caustic lye quantity from 82 lit to 98 lit per batch
Implemented Since 2nd March 2014.Significant improvement observed in yield 3.3% in IBA.
Lower temp during Stage 4 addition is favorable.
Evaluated & fixed.
Stage 6 & 7
Drying output of Stage 5 and Stage 6 to evaluate stage wise yield
Implemented on 15th March-2014. Drying done-Significant improvement observed in yield of Stage 5 (Refer insert file)
Quality of Sodium hydro sulfite on yield – As per data observations higher % LOD gives better yield
Evaluated.
DMAIC
Value stream mapping activity performed at • Shop floor (on 30 Meter chart paper) • With 18 members including PD lab
production. ( 40 hrs. activity) • Identify all hidden factors & key parameters
impacting the process
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Issue tree
Intermediate
wt.
Reaction efficiency
Unreacted Stage 4
Unreacted Stage 4 , Unreacted Stage 5
Unreacted in Stage 5 input
Physical
Loss
Stage 4 in ANF
Stage 5 in ANF
Stage 6 and Stage 7 Intermediate in CF
Out going stream
Intermediate in Stage 6 ML
Intermediate Stage 7 ML
Stage 4 in ML/ wml
Intermediate in spent carbon
Stage 5 output in ml
Output Area
DMAIC
*ANF- Agitated Nutch Filter *ML- Mother Liquor
Significant losses were identified in the Reaction efficiency. (highlighted in red color) Loss at other areas were also identified & regularly monitored.
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Data Collection Plan
Sub steps Performance
Measure Operational Definition
Data Source and Location How Will
Data Be
Collected
Who Will
Collect
Data
When Will
Data Be
Collected Operation Equipment
What to
measure
with unit
Stage 4
Quantity (DCM)
Monitoring of Initial level and final level, and
deriving quantity from calibration.
Charged 2014 lit.±14 lit Pre-chilled Washed
Methylene Stage 5oride in the R-3401D/R-3401F.
Before charging check the analysis.
V-3401A Quantity in
ltrs Physically/Manually
Team member
Befor /After bx charging
Time (DCM Charging)
Charging start time and end time
V-3401A Start time and
end time in min
Manually. Team
member Befor /After
DCM charging
Analysis(DCM) Withdrawal of sample for analysis from column pot
4401A/4401B V-3401A
%Methanol and % MECL2
Analysis Team
member Before bx charging
DMAIC
204 225 150 180 120 140
0
500
Stage 4 Stage 5 Stage 6 & 7
No of Parameters/ Batch No of Batches
Detailed data collection plan prepared with 580 data point in each batch. With the team of 17 members in the plant and 5 members in Analysis development Lab, 84720 data points collected.
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Measurement System Validation
Purpose:
To validate that our Project Y or critical X’s does not have measurement system error
All our project Y is measured on HPLC ( High pressure liquid chromatography) which is highly
précised instrument with regular calibration & less manual intervention.
In few X’s were we found the manual intervention during measurement ,we performed Gage
Reproducibility & Repeatability study with two operators for measurement system validation
Sr. no Key parameter Activity Inference
1 Weighment of
Bromine at Stage 4 Gage R&R and done with two operator
GRR is 14.81% Measurement found OK
2 MEG addition Gage R&R and done with two operator GRR is 3.87%
Measurement found OK
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Gage Repeatability & Reproducibility
The measurement systems are acceptable % GRR is < 30
The data is considered to not have potential for significant error.
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MEG Addition by Level Indicator GRR 3.87 %
Weighment of Bromine GRR 14.81 %
Baseline Process Capability : Stage 7 Yield
Current process is not capable to meet the target specification . (Capability Analysis was carried out with target yield and with data of 150 batches)
DMAIC
Ppk -0.34
Implementation of Quick wins
• Ideas identified in the VSM is discussed & Few Quick wins were identified.
• Few ideas were also validated with the historical data wherever available .
• Those data points where historical data are not available are introduced in data collection plan.
• Quick win identified through VSM is implemented which give the lift in yield up to 40 % of targeted. ( from 0.350 to 0.356)
DMAIC
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I-MR chart after implementation of Quick wins DMAIC
Caustic lye quantity increased in treatment of Rec DCM
VSM Ideas evaluated with data
Rotary Vacuum paddle dryer (RVPD) wise variation observed in the yield
Variation in yield observed in Thin Layer Chromatography
pass batches
DMAIC
Analyze
DMAIC
• X’s Funnel • Hypothesis testing • Regression Analysis
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Overall process Flow
Stage 5 Stage 4 Stage 6 & 7
Process Steps
In process Ys used are : • Yield at each stage, • % product formed & • % Unreacted raw material at each stage
DMAIC
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Stage 4 – Process Steps for Regression Analysis (Y’s chosen at each step to increase the reaction conversion)
Stage 4B Stage 4A Stage 4C Stage 4D Stage 4
Process Steps
% Stage 4B Product
Conversion
% Stage 4A Product
Conversion
% Stage 4C Product
Conversion
% Stage 4D Product
Conversion Stage 4 yield
Y variables
Y variables at each steps are showed in box below each stage. In coming slides Reducing X’s Funnel analysis method for Stage 4A demonstrated , Similar methodology used in other stages to reach critical X’s at each step. (Total 204 X’s at Stage 4 Stage – A to D sub stage)
DMAIC
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All Possible Variables (X’s)
Critical Input Variables
• VSM • Brainstorming
• Cause and Effect Matrix
• Graphical analysis • Cp/Cpk
• Hypothesis testing • Regression
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52
30
18 5
X’s Funnel at the end of Analyze- Stage 4A DMAIC
Similar Analysis was carried out for B to D stages also
Stage X’s from I-O
Worksheet Cause & Effect Matrix Process Capability Statistical Test
Multiple
Regression
Stage
4A
Rec DCM Qty. Rec DCM Qty. No variation in Qty.
%M/C- DCM %M/C- DCM %M/C- DCM Only 4 values of M/c
Removed by ANNOVA test
Temp Before AEN Lower CE matrix score
PTSCL %M/C NMT 2.% PTSCL %M/C NMT
2.% PTSCL %M/C NMT 2.% PTSCL %M/C NMT 2.%
PTSCL %M/C
NMT 2.%
%MeOH-DCM %MeOH-DCM Remove due to higher
CpK>4
%DCM-CHS %DCM-CHS Remove due to higher
CpK>4
Reactor A & B of -Tosyl Reactor A & B of -Tosyl Reactor A & B of -Tosyl Removed by 2 Sample T
Test
Melting Point-AEN Lower CE matrix score
NH3 addition rate NH3 addition rate NH3 addition rate NH3 addition rate NH3 addition rate
NH3 addn temp at 60min NH3 addn temp at 60
min NH3 addn temp at 60 min NH3 addn temp at 60 min NH3 addn temp-60
Final PH - at TLC-
Tosysyl
Final PH - at TLC-
Tosysyl Final PH - at TLC- Tosysyl Final PH - at TLC- Tosysyl
Final PH - at TLC-
Tosysyl
TLC observation Ok/Not
Ok
TLC observation Ok/Not
Ok
TLC observation Ok/Not
Ok 2 Sample T test TLC OK is
found significantly better.
Total
X's 71 52 30 18 5
X’s in Stage 4A is reduced by using the funnel
Finally 5 Critical parameters were identified in Stage 4 A through regression.
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Cause & Effect Matrix with Plant & PD lab
X’s with scores in excess of 38 were carried forward for graphical/regression analysis
DMAIC
Sr No Stage Xs from I-O Worksheet
C&E Matrix
C & E Score Yield Quality Total
10 8
1
Stage 4A
Rec DCM Qty 4 3 64 Rec DCM Qty.
2 %M/C- DCM 5 5 90 %M/C- DCM
3 %MeOH-DCM 5 5 90 %MeOH -DCM
4 %DCM-Stage 4 5 5 90 %DCM-Stage 4
5 %IMP-DCM 5 5 90 %IMP-DCM
6 Water Qty-Stage 4 Total 7 6 118 Water Qty.- Stage 4A Total
7 Conc NH3 -Stage 4A 7 6 118 Conc .NH3 - Stage 4A
8 Reactor No-Stage 4A 5 5 90 Reactor No-Stage 4A
9 Centrifuging time 1 2 26
10 Wet Stage 3 Input 7 5 110 Wet Stage 3 Input
11 %Assay-Stage 3 8 6 128 %Assay-Stage 3
12 Melting Point-Stage 3 3 1 38
13 PTSCL
14 PTSCl Qty 7 7 126 PTSCl Qty.
15 Total PTScl 7 7 126 Total PTSCL
Process Step total Scores, Prioritized steps highlighted.
Capability analysis for Xs
Process Capability of % DCM is 2 Process Capability of dry Stage 4 1.26
Process Capability of Impurity in Cryo is 3.12 Process Capability of % M/c in DCM is 1.16
DMAIC
Hypothesis testing - PTSCL source 2-sample t-test indicates significant difference in fresh PTSCL and Rec PTSCL on Stage 4A reaction. Action: Planning to minimize the use of Rec. PTSCL in Stage 4A
DMAIC
Stage 4 Conversion
PTSCL Source
Two Sample T test of PTSCL in Stage 4A
Null Hypothesis : Conversion is same for both the sources of PTSCL Alternate Hypothesis: The conversion in fresh PTSCL is higher than recovered.
As P value is less than 0.05 we are rejecting the null hypothesis & accepting the alternate hypothesis
Annova Test for Bromine source
On the basis of this test we are preferring supplier Y for all the future requirement.
DMAIC
Null Hypothesis : % conversion is same for all the suppliers. Alternate Hypothesis % conversion is different for at least any one of the supplier.
Though the P value is 0.076 we reject the null hypothesis after discussing the case with PD lab & accept that the yield in supplier y is statically different.
Best Subset Regression
Best Subset Regression : %Product 4A
• Best Subset with higher R-Sq. Adjacent & lower Mallows Cp with minimum parameters. Regression was carried out after 2 T test and ANOVA with 18 X’s
• 5 X’s – selected – NH3 addition temp at 60 min, NH3 addition rate, impurity in stage 4A, Final PH & PTSCL M/C
DMAIC
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List of Critical X’s prioritized at the end of Analyze
Phase of Tosylation reaction
DMAIC Critical Parameter Through Regression Final Regression Equation obtained with R-sq.
Adjacent as 64.82% i.e. 64.82 % of the variation
in % Product stage 4A is defined these 5
parameters.
Detail Unit Desired Min Max Mean
NH3 Addition Temp at 60 min. Degree C 1.5 6 1.3317
NH3 addition rate Lit/Min 4.028 7.7267 6.4699
Impurity in Stage 4A % 0 1.6 0.2742
Final Ph at Satge 4A (8.9-9.0) 8.81 9.1 8.88
PTSCL M/C % 7.59 9.2 8.8657
% product in stage 4A
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Critical parameter at other stages are identified by implementing the similar exercise.
Sr Stage 5 1 Maximum temp Stage 4 Addition
2 Stage 4 disso. Maint. Time (min)
3 After 1st lot DMA maintaining time and quantity
4 Extra PCL-5 Qty. in Kgs 5 %IBC Rec DCM,%IMP in cryo.
Sr Stage 6 & Stage 7
1 Soda charging temp
2 Maintaining Time 30 min instead of 15 min after soda
3 pH of reaction mass after soda addition.
4 Qty. of soda in kg.
5 Sodium hydrosulphite temp at 10 min
6 Fresh water charging end temp
7 pH after hydrosulphite and maintaining
DMAIC
Sr. Stage 4A 1 NH3 addition rate
2 Final Ph at Tosyl (8.9-9.0) 3 PTSCL source
4 PTSCL M/C
5 Impurity Tosyl
Sr. Stage 4B 1 Final temp Ennamine
2 Water washing Qty-Enamine
Sr. Stage 4C 1 Final Temp-Bromine
2 R-3402 Dry dip
3 Stirring time 30 after morpholine
4 Bromine supplier
Sr. Stage 4D 1 PH-cyclize
2 Total Cyclize maintaining time
3 Imp Cyclize
4 Unreacted Ennamine-Bromo stage
5 End Temp of Maintaining
Sr. Stage 4
1 Final temperature during recovery-Max
2 Qty . of Rec DCM +Methanol
3 Stage 4 Dryer RVPD (Higher temp)
Critical Parameter After Regression
IMPROVE
DMAIC
• Brainstorming • DOE • FMEA
Stage 4 stage Critical X’s under control
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Stage Detail Unit Before After
Remarks Mean
Std. dev .
Mean Std. dev.
Stage 4A Avg. NH3 rate Lit/mi
n 6.5 0.7 5.5 0.24
Orifice applied (5mm and 6mm respectively) to control NH3 addition rate, cleaning frequency 10 days.
Stage 4A Final PH - at TLC- Tosyl
7.86 0.19 7.89 0.08 Presently Manually controlled, future plan of application of on line ph meter with addition pump.
Stage 4C
Morpholine addition
stirring time Min 31.7 14.6 40 -
Morpholine stirring time maintained 40 min instead of 25 min
Bromine addition time
min 8.85 2.14 - - Charging time should not increase above 7-8 min. Possibility to work out for fast addition of bromine in future.
In this data we can see that the mean is shifted & variation is also reduced
DMAIC
Stage 6 : Critical X’s under control
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Detail Unit Before After
Remarks Mean Std. dev. Mean Std. dev.
Soda charging temp 0C 43 2.7 48 0.87 Presently charging started at 45°C ,by applying hot water if required
pH of reaction mass after soda addition
5.22 0.09 5.22 0.1 ph is maintained NLT 5.0
Maintaining Time after soda
Min 10.2 6.7 30 Maintaining time of 30 min started
Qty. of soda in kg Kg 55.2 2.1 55.6 1.3 Qty. of soda charged is NLT35 KG
Sodium hydrosulphite temp at 10 min
0C 30.8 1.8 34.3 1.12 Sodium hydrosulphite charging started at 40°C and 150 kg sodium hydrosulphite charged within 10min
Fresh water charging end temp
0C 33.7 2.2 30.7 1.05 Fresh water charging started after bringing temp of mass up to 48°C
ph after Hydrosulphite and maintaining
- 4.53 0.16 4.71 0.08 ph is maintained NMT 4.8
DMAIC
In all the critical X’s mean were shifted & standard deviation reduced. And to maintain the parameters within the desired limit auto system like online PH
meter & peristaltic pump were installed in few areas.
7 Critical parameters were identified in Stage 6, where the Theoretical yield is lowest out of all the stages.
DOE to be planned to further optimize the critical parameters to get the maximum yield with complete control.
Out of Seven, 3 parameters i.e. PH of reaction mass after soda, sodium hydrosulphite temp at 10 min & PH after hydrosulphite & maintaining is not under direct control.
Screening DOE done with 4 parameters & 2 Leveled at pilot plant.
On the basis of screening DOE , Optimization DOE planned with 2 factors & 2 Level Full factorial DOE with 2 replicates & 1center point.
Stage 6 : DOE Planning
Experiment performed in Pilot lab as per the Run order.
DMAIC
DOE on Stage 6 parameters
Implementation of DOE learnings leads to major improvement in the yield.
DMAIC
In Intermediate after implementation of the
critical parameter identified through
regression further scope observed for which Full factorial DOE planned
with 2 Factors at 2 Levels including center point.
0.3677 yield can be obtained by optimizing this two parameters
CONTROL
DMAIC
• Control Limit • Control Plan for Sustenance • Before/After Process Capability
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Control limits
Control Action Responsible Individual
Lower Control Limit
Target Value Upper
Control Limit
Current
Avg. NH3 rate in stage 4A
Operating officers
4.9 5.5 6.1 5.5
Final PH - at TLC- Stage 4A 7.68 7.87 8.06 7.87
Stage 4B final temperature 19.57 20.36 21.15 20.36
Final temp Stage 4B 20 20.6 27.2 20.6
Final Temp-Bromine -9.7 -6.85 -4.2 -6.85
Bromine supplier
PH- Stage 4D 0.53 0.68 0.84 0.68
Total Stage 4D maintaining 180 180 540 188
End Temp of Maintaining 35.4 40.85 45 40.85
Final temperature during recovery-Max 36 42.8 49 43
Stage 4 disso. Maint. Time (min)
Operating officers
10 15 30 12.84
After 1st lot DMA maintaining time 15 30 400 53.41
Maximum temp Stage 4 ADDTN -15 -12 -8.2 -11.03
%IBC Rec DCM 0 0.06 0.5 0.06
%IMP in Cryo. 0.06 0.4 0.84 0.354
DMAIC
Control limits established for all critical parameters & tracking through Dashboard in Plant
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Process Control Plan Monitoring
Step Actions Frequency Responsibility
Stage 4 1. Cleaning of Orifice at Dil. Ammonia addition
Stage 4 A 10 Days
Section in charge/Executive
Stage 4 Water washing at Stage 4B :-Water meter
calibration to be done and if any error replace it with new one.
Weekly Section in
charge/Executive
Stage 4 End Temp Of Maintaining :- Orifice at Stage 4
maint. Reactor to be cleaned.
15 days Section incharge/Executive
Stage 4 Recovery Time & Temp :-Vacuum drop checking of
Stage 4 recovery system 15 days
Section in charge/Executive
Stage 4 RVPD Vacuum & temp :- Vacuum line filter
cleaning. 15 days Section incharge/Executive
Stage 5 Stage 5 ANF bag replacement Plant incharge
Stage 6 HCL charging time at Stage 6 :-Cleaning of Orifice in
HCL line 15 days Section incharge/Executive
Stage 6 Stage 6 Methanol quality :- Re distillation After 40 Batch Plant incharge
Stage 7 HCL charging time at Stage 7 :-Cleaning of Orifice in
HCL line 15 days
Section in charge/Executive
DMAIC
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Yield after Implementation
Overall yield Stage 4 Stage 5, 6 & 7
Baseline 0.2474 0.8137 0.3477
Target 0.2592 0.8193 0.3630
July 0.264 0.8298 0.3687
0.2474
0.8137
0.3477 0.2592
0.8193
0.3630 0.264
0.8298
0.3687
0
0.4
0.8
1.2
DMAIC
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Before & After Process capability DMAIC
For the specific customer requirement we are using IBA / MEG solvent for isolation of product in Stage 5. In IBA stage with the implementation of solution theme yield improvement of 0.363 & above
obtained , at the same time similar improvement was not observed in the MEG batches. Due to which the yield after improvement is also observed below 0.363 which impact the
Process capability
People involvement: At all stages of project and primarily for the following activities
1. Creation of VSM
2. Data collection
3. Brainstorming
4. DOE & Pilots
5. Sustenance.
• Learning from the project:
• This is statistical data base approach where critical X’s responsible for output is identified in systematic way started with hundreds of X’s and further drill down to manageable level by using different LSS tools to get maximum benefit with minimum efforts.
• Team understood the power of DMAIC. This was an eye opener in a product where yield was almost stable for last 5 years
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People involvement and Learning
Project leader & Team appreciated by Plant head
DMAIC
Innovative Methodology
Quantification of impact of multiple X’s on Y
Statistically determine the relationship of Y = f(X1, X2, X3…..)
Interaction effect of multiple parameters in multi-stage and complex process.
Challenging the “Status quo”.
In Wave 4 we got financial saving of 9 Cr validated by our finance team & in Wave
5 We are again taking a stretch target of 10 Cr potential saving. ( 5% improvement
in the yield)
Similar Methdology adopted for improvement in yield, solvent, Engineering and also in
Administration & HR departments.
DMAIC
Way Ahead
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Thank You Never doubt that a small group of thoughtful committed
people can change the world:
Indeed it’s the only thing that ever has !
Disha Team- Lupin, Ankleshwar Yes I Can...Yes I Can... Yes We Can...Yes LUPIN Can.