I-nexus ID: 3,031
Right First Time Six Sigma Project
“Improve batch record system for Packaging ”
Start Date: 01 Feb 2008
Black Belt: Marina Suryanto
Sponsor: Sis Mardini (QO Manager)
Process Owner: Raharsih Basrodin (Production)
Team Members: Production: Lily, Yaseph, Lely
QA: S. Wigati, Yodi, Melissa
0
Define
Measure
Analyze
Improve
Control
Problem Statement
The lead time to manufacture to release is too long.
Business Case
Expected business results:
• Reliable supply of product
• Improve quality of records
• Reduce time and efforts needed to complete batch
documentation
1
Define
Measure
Analyze
Improve
Control
Scope
The lead time to manufacture comprises of 2 parts i.e:
1. Raw material receipt to bulk film coated tablet and
final blend release (Project INX 7724 by JTM)
2. Primary packaging to product disposition
Product
START
STOP
Exclude
: Ponstan 500 mg Film Coated Tablet (FCT)
and Terramycin (TM) Oph. Oint.
: Ponstan  Blistering
TM  Filling ointment
: Product disposition by QA
: Batch with deviation and validation
2
Define
Measure
Analyze
Improve
Control
Project Goal
PROJECT GOAL
Reduction of
packaging lead time
(LT)
METRIC
BASELINE*
CURRENT
GOAL
Working Days
Ponstan I:
Average 53
TM Oph II:
Average 26
TBD
Ponstan*:
Max 20 days/
batch
TM Oph*:
Max 25 days/
batch
I
Data collected from lot released in Jul 2007 to Jan 2008.
Data collected from lot released in Feb 2007 to Feb 2008
* Maximum exclude validation batch and deviation
II
3
Define
Measure
Analyze
Improve
Control
Process Map
Packaging Flow of Ponstan 500 mg FCT (As Is)
Printing Multicarton
Folding Leaflet
Printed
multicarton
Folded
leaflet
Released
coated
tablets
Blistering
Pack into Multicarton
Pack into Shipper
Export
product?
Yes
Pack into Export
shipper
No
Inspection on
defects
B
4
Define
Measure
Analyze
Improve
Control
Process Map
Batch Record Process of Ponstan 500 mg FCT (As Is)
B
Completion in MAPS
by TL
TL calculate product
yield & accountability
TL
TL/ Operator/
Inspector
Prod. Admin review
batch record for doc.
error
Disposition in
MAPS
Admin
Record data in the
log book of doc error
Ok?
Yes
No
Ok?
No
Prod. Manager/
QA Spv
Yes
Prod Spv review and
sign off the batch record
QA Manager review
and sign-off the batch
record
Prod Spv
QA Manager
No
Ok?
Create CoA
Yes
Yes
Prod Manager review
and sign-off the batch
record
Ok?
Prod Manager
Ok?
Yes
QA Spv
QA Spv review and
sign-off the batch
record
No
Prod Manager/
Inspector/ Lab
Manager
Quality Assurance
Profiles (QAP)
Review Batch record = Manufacturing + Packaging batch record
5
Define
Measure
Analyze
Improve
Control
Process Map
Packaging Flow of TM Oph. Oint. (As Is)
Sampling for Lab
Test
Final
blend
Filling
Packing for Gamma
radiation
Sampling for
Micro Test
Testing
Irradiated
products
Gamma radiation
Testing
Inspection on
defect
Inspection on
defect
Folding Leaflet
Printing
Multicarton
A
Pack into
Shipper
Shrink wrapping
Printed
multicarton
Folded
leaflet
Pack into
Multicarton
Yes
Market: Korea?
Cartoning
No
Pack into
Shipper
6
Define
Measure
Analyze
Improve
Control
Process Map
Batch Record Process of TM Oph. Oint. (As Is)
B
Completion in MAPS
by TL
TL calculate product
yield & accountability
TL
Prod Spv review and
sign off the batch record
Disposition in
MAPS
Admin
TL/ Operator/
Inspector
Yes
Ok?
Ok?
Yes
Prod. Admin review
batch record for doc.
error
Prod Spv
No
Record data in the
log book of doc error
Prod. Manager/
QA Spv
QA Manager review
and sign-off the batch
record
No
QA Manager
No
Ok?
Create CoA
Yes
Yes
Prod Manager review
and sign-off the batch
record
Ok?
Prod Manager
Ok?
Yes
QA Spv
QA Spv review and
sign-off the batch
record
No
Prod Manager/
Inspector/ Lab
Manager
Quality Assurance
Profiles (QAP)
Review Batch record = Manufacturing + Packaging batch record
7
Define
Measure
Analyze
Improve
Control
DATA PLOT PONSTAN 500 MG FCT
Time Series Plot of Production LT, Packaging LT, and Total Manufacturing LT
100
Variable
Production LT
Pack aging LT
Total Manufacturing LT
90
80
Med: 77
Days
70
60
A v g: 52
50
40
30
Med: 25
20
10
38 45
99
12
23
29
37
46
52
58
64
00 300 3 00 301 3 01 30 1 301 3 01 301 3 01 30 1
3
9- 9- 299- 29 - 29- 2 9- 299- 29 - 2972 72
7
72
7
7
7
7
72
7
7
Lot No
Total Manufacturing LT = Production LT + Packaging to disposition LT
Total manufacturing lead time ranges from 59 to 99 days with median of 77 days.
Production process LT ranges from 17 to 37 days with median of 25 days.
Packaging to disposition LT ranges from 38 to 77 days with average of 52 days
8
which contributes 68% to the total LT.
Define
Measure
Analyze
Improve
Control
DATA PLOT PONSTAN 500 MG FCT
Time Series Plot of Packaging, Final Review, and Total LT (Pack - Disposition)
80
Variable
Pack aging Lead Time
Final Rev iew Lead Time
Total LT (Pack -Disposition)
Lead Time (Working Days)
70
60
Av g: 53
Av g: 50
50
40
30
20
10
Med: 2
0
38
45
99
12
23
29
37
46
52
58
64
00 300
00
01
01
01
01
01
01
01
01
3
3
3
3
3
3
3
3
3
3
9- 2999999999972
7
72
72
72
72
72
72
72
72
72
Lot No
LT (Pack – Disposition) = Packaging LT + Final review LT
Total lead time ranges from 38 to 77 days with average of 53 days.
Packaging process LT ranges from 1 to 12 days with median of 2 days.
Final review LT ranges from 35 to 75 days with average of 50 days
which contributes 94% to the total LT.
9
Define
Measure
Analyze
Improve
Control
DATA PLOT PONSTAN 500 MG FCT
Boxplot of Production Review LT and QA Review LT
80
70
60
Days
50
40
49.5
38.8333
30
20
10
10.4833
0
Production Review LT
QA Review LT
Total Final Review LT
79% of the total review LT is contributed by the production review time.
Production review LT ranges from 26 – 58 days with average of 39 days.
QA review LT ranges from 1 – 28 days with average of 10 days.
10
Define
Measure
Analyze
Improve
Control
DATA PLOT TM Oph. Oint.
Time Series Plot of Production LT, Packaging LT, Total Manufacturing LT
50
Variable
Production LT
Pack aging LT
Total Manufacturing LT
40
Days
30
A v g: 30
A v g: 27
20
10
Med: 3
0
05
10
20
23
26
30
34
42
50
01
20 52 0 52 0 52 0 52 0 52 0 52 0 52 0 52 0 52 0
5
7777777778-
Lot No
Total Manufacturing LT = Production LT + Packaging to disposition LT
Total manufacturing lead time ranges from 2 to 7 days with average of 30 days.
Production process LT ranges from 14 to 45 days with median of 3 days.
Packaging to disposition LT ranges from 17 to 48 days with average of 27 days
which contributes 90% to the total LT.
11
Define
Measure
Analyze
Improve
Control
DATA PLOT TM Oph. Oint.
Time Series Plot of Packaging, Final Review, and Total LT (Pack - Disposition)
50
V ariable
P ackaging LT_1
F inal Rev iew LT_1
Total LT (P ack - Disposition)_1
Lead Time (Working Days)
40
30
Av g: 26
20
Av g: 16
10
Med: 10
0
05
10
20
23
26
30
34
42
50
01
20 520 520 520 520 520 520 520 520 520
5
7777777778-
Lot No
LT (Pack – Disposition) = Packaging LT + Final review LT
Total LT ranges from 14 to 45 days with average of 26 days.
Packaging LT ranges from 6 to 21 days with median of 10 days.
Final review lead time ranges from 5 to 30 days with average of 16 days
which contributes 62% to the total LT.
12
Define
Measure
Analyze
Improve
Control
DATA PLOT TM Oph. Oint.
Boxplot of Production Review LT and QA Review LT
30
25
Days
20
16.0938
15
10
7.84375
8.125
5
0
Production Review LT
QA Review LT
Total Final Review LT
Production review time ranges from 1 – 18 days with average of 8 days.
QA review lead time ranges from 1 – 25 days with average of 8 days.
13
Define
Measure
Analyze
Improve
Control
CAPABILITY ANALYSIS
Process Capability of Packaging Lead Time of Ponstan 500 mg FCT
USL
O v erall C apability
*
Pp
*
PPL
P P U -1.56
-1.56
P pk
*
C pm
P rocess D ata
*
LS L
*
Target
20
USL
52.3
S ample M ean
60
S ample N
S tD ev (O v erall) 6.89461
20
O bserv ed P erformance
*
% < LS L
% > U S L 100.00
100.00
% Total
30
40
50
60
70
E xp. O v erall P erformance
*
% < LS L
% > U S L 100.00
100.00
% Total
100% of the batches cannot meet the lead time of max 20 days.
Data is approx. normal
14
Define
Measure
Analyze
Improve
Control
CAPABILITY ANALYSIS
Process Capability of Packaging Lead Time of TM Oph Oint
USL
P rocess D ata
LS L
*
Target
*
USL
25
S ample M ean
26.6875
S ample N
32
S tD ev (O v erall) 8.05801
O v erall C apability
Pp
*
PPL
*
P P U -0.07
P pk
-0.07
C pm
*
8
O bserv ed P erformance
% < LS L
*
% > U S L 50.00
% Total
50.00
16
24
32
40
E xp. O v erall P erformance
% < LS L
*
% > U S L 58.29
% Total
58.29
58% of the batches cannot meet the lead time of max 25 days.
Data is approx. normal
15
Define
Measure
Analyze
Improve
Control
Value Stream Map Analysis (Ponstan 500 mg FCT)
Production Process
Warehouse
Warehouse
I
Blistering
PT: 1.5 - 2 hours
PT: 0.5 hours
Printing
Multicarton
Folding Leaflet
I
Secondary
0
Packing
I
Completion
by TL
0 – 1 WD
0 WD
I
Review by
Production
2 WD
I
Review &
Disposition by QA
1 - 4 WD
PT: 8 – 9 hours
PT: 6 – 8 hours
PT: 0.5 hours
PT: 4 – 7 hours
PT: 1 – 2 hours
LT: 1 WD
LT: 1 WD
LT: 1 WD
LT: 17 - 21 WD
LT: 2 - 3 WD
Total Packaging Lead Time ranges from 24 – 29 days.
Total processing time (P/T) ranges from 3 – 3.5 days (23 – 26 hours)
Total delay time ranges from 21 – 26 days. Delay time was 89% of total LT
Processing time in batch record review ranges from 6 – 8 hours per batch with delay time
19 - 24 days. Delay time in review process needs to be minimized.
Note: Data taken from measurement of 3 batches
16
Define
Measure
Analyze
Improve
Control
Value Stream Map Analysis (TM Oph Oint)
Warehouse
Production Process
I
PT: 2 hours
PT: 14.3 hours
Lab Testing
(Chemical)
Lab Testing
(Chem&Micro)
2
5
Filling & Packing
for Radiation
Gamma
Radiation
I
I
0-2
LT: 3 WD
PT: 4.5 – 7 hours
LT: 1 - 2 WD
LT: 2 WD
Printing
carton
Folding
Leaflet
2
1
I
6I
8
PT: 22.5 – 25 hours
Inspection on
defects
PT: 7.5 – 8.5 hours
1-2
Secondary
Packing
I
8
Warehouse
Completion
by TL
1
1-2
0
I
Review by
Production
I
Review &
Disposition by
QA
2
3
0-5
0-1
PT: 2 – 3 WD
PT: 2 WD
PT: 4 - 5 WD
PT: 3.5 – 6 WH
PT: 6 - 9 WH
PT: 1.5 WH
LT: 3 - 4 WD
LT: 2 – 5 WD
LT: 4 – 5 WD
LT: 1 - 2 WD
LT: 1 - 8 WD
LT: 5 – 6 WD
Total Packaging Lead Time ranges from 22 - 33 days.
Total processing time (P/T) ranges from 15 – 18 days (113 – 134 hours )
Total delay time ranges from 6 - 15 days (45 – 113 hours). Delay time was 37% of total LT.
Processing time in batch record review ranges from 7 – 10 hours per batch with delay time
2 – 10 working days. Delay time in review process needs to be minimized.
Note: Data taken from measurement of 3 batches
17
Define
Measure
Analyze
Improve
Control
Brainstorming
Why batch record review lead time is too long?
1.
2.
3.
4.
5.
Structure and content of batch record is not user friendly/
complicated
Effort and time needed for correcting documentation errors
Flow of batch record review process is not efficient. Review level
that is labor intensive involving several personnel. The overall
documents of the batch record from manufacturing to packaging
is reviewed at the end of the process.
Standard lead time for batch record review and product release is
not clearly defined. Delay time during final review is high.
Batch record is accumulated waiting for review and sent to QA
including waiting time for approved QAP for TM Oph. Oint.
18
Define
Measure
Analyze
Improve
Control
Batch record is accumulated waiting for review and sent to QA
Time Series Plot of No of Batch Records to QA per day
25
No of Batch Records
20
15
10
5
Med=5
0
3-
8
-0
n
Ja
17
8
-0
n
Ja
8
8
-0
-0
b
b
e
e
-F
-F
1
1
1
2
-M
10
8
-0
r
a
8
-0
r
a
-M
6
2
9-
8
-0
r
Ap
21
8
-0
r
Ap
ay
M
7-
08
ay
M
23
08
Date
Numbers of Batch Record sent to QA per month was variable
ranges from 1 – 23 batch records per receiving day with median of 5/ day.
19
Define
Measure
Analyze
Improve
Control
Waiting time for QAP Availability
Time Series Plot of QAP LT & QA Review LT
30
Variable
QAP LT
QA rev iew LT
20
Days
10
0
-10
-20
7
5
00
2
-5
01
52
7
0
0
52
7-
21
7
4
02
2
-5
7-
8
02
52
A
(M
L)
7
1
03
2
-5
7-
5
03
2
5
7
9
04
2
-5
05
52
7
6
0
52
8-
04
Lot No
QAP LT = Batch record receive date – QAP receive date
The QA review lead time, which ranges from 1 – 25 days, includes the waiting
lead time for QAP from lab. QAP LT ranges from -19 to 11 days.
Minus value means that the QAP has been received prior to the batch records sent to QA.
20
Define
Measure
Analyze
Improve
Control
Improvement Matrix
Potential X’s
Proposed Solution
Structure and content of batch
record is not user friendly/
complicated: Excessive data
entries, excessive signatures,
Many separate forms are linked
to the batch record for data
recording.
Excessive data verification
during IPC between Production
and QA
Re-structure of batch record both
contents and format. The content is
also analyzed and some
improvements are made to comply
with PQS & regulatory
requirements.
Some of IPC activities and data
verification will be transferred from
QA to Production as per risk
assessment.
Supporting Data
QA Risk assessment:
New IPC matrix:
Numbers of signatures for the
new format of batch packaging
records are reduced by approx.
50% (Ponstan FCT: 52%; TM
Oph: 58%)
21
Define
Measure
Analyze
Improve
Control
Improvement Matrix
Potential X’s
Proposed Solution
Supporting Data
Documentation error
- Re-structure batch record as above.
- Training Operator on documentation
practice for the new batch record
-
Flow of batch record review
process is not efficient. Review
level that is labor intensive
involving several personnel. The
overall documents of the batch
record from manufacturing to
packaging is reviewed at the end
of the process
New flow of packaging process
including IPC and batch record review
process:
- Batch record will be reviewed at each
defined stage.
- Reviewers include Prod Spv, Prod
Manager, QA Spv, QA Manager 
Delete non-value-added activity i.e.,
Prod Admin function to check and
record doc error. These functions will
be integrated to all reviewers.
See proposal of new flow
in the next slides.
22
Define
Measure
Analyze
Improve
Control
Improvement Matrix
Potential X’s
Proposed Solution
Supporting Data
Waiting time for approved QAP of
TM Oph Oint
The Lab Spv will also sign off the
batch record at each stage (Before
radiation & after radiation) to confirm
whether the test result meet or
doesn’t meet spec. The QAP will be
inserted into the batch record after the
Lab Spv sign off the BR at the after
radiation stage, then the batch record
will be circulated to the Prod and QA
Manager for final approval. This avoid
the delay due to QAP documentation.
-
Batch record is accumulated waiting
for review and sent to QA.
Define standard lead time for review:
1) Review at each stage: Max 1
business day per reviewer per batch.
2) Final review: : Max 2 business day
per reviewer per batch.
-
Standard lead time for batch record
review and product release is not
clearly defined. Delay time during
final review is high.
23
Define
Measure
Analyze
Improve
Control
Proposal for New Process Flow
Off-Line Printing
Warehouse
Packaging
Multicarton
Printed
Multicarton
Line clearance
Printing
PM Reconciliation
Review dan approval
printing process by Prod
Spv
Batch packaging
records – Printing
stage
Examination & approval
of printed multicarton
sample
Printing Inspection
Verification by QA
Inspector
24
Define
Measure
Analyze
Improve
Control
Proposal for New Process Flow
Folding Leaflet
Warehouse
Packaging
Folded
leaflet
Leaflet
Line clearance
Folding
PM reconciliation
Examination & approval
of folded leaflet sample
Review dan approval
folding process by Prod
Spv
Batch packaging
records – Folding
stage
25
Define
Measure
Analyze
Improve
Control
Proposal for New Process Flow
Filling & Packaging of TM Oph Oint 3.5 g Korea
Compounding
PPIC
Inspection on filled
weight, foreign matter,
blend homogeneity,
and leak test
Verification by QA
Inspector
Final
blend
Examination &
approval of sample of
embossed empty tube
Inspection on
defects
Inspection on
embossed lot no &
exp date
Start-Up
Lab Testing
(Chemical & Micro)
End of Run
Check
A
Finished
Products
Batch record review
and approval (Filling
stage)
Sampling
Line Clearance
Inspection on defect
of filled alutubes
Filling
Packing for radiation
Radiated
products
Gamma Radiation
I
Lab Testing
(Chemical)
Sampling
B
Inspection on
defect
Examination &
approval of
embossed carton
Verification by QA
Inspector
Folded
leaflet
Printed
Multicarton
Packing into carton
Packing into
Multicarton
Examination &
approval of shipper
label
Batch record review
& disposition
Shrink wrapping
Packing into export
shipper
End of Run Check
(30 carton)
Weight monitoring
of carton,
multicarton, shipper
Start up (30 carton)
Reconciliation
Inspection on
embossed lot no &
exp date
Inspection on
cartoning results
Inspection on product
& packaging defects
(ROI)
26
Define
Measure
Analyze
Improve
Control
Proposal for New Process Flow
TM Oph Oint 3.5 g Batch Record Review Process
A
TL/ Operator/
Inspector
Prod Spv
No
No
Lab Spv
Prod Spv
Prod. Spv review and
sign-off the batch
record
Ok?
QA Spv
QA Spv review and
sign-off the batch
record
Lab Spv sign off the
batch record
Yes
Ok?
Yes
Approved batch
packaging record
(filling stage)
B
TL/ Operator/
Inspector
No
TL/ Prod Spv
Prod Spv
Prod. Spv review and
sign-off the batch
record
Ok?
Yes
Lab Spv
Completion in
MAPS
Lab Spv sign off the
batch record
Prod Manager
Production Manager
review and sign-off
the batch record
Ok?
No
Prod Spv
Yes
Approved batch
packaging record
Disposition in MAPS
Yes
Ok?
QA Manager review
and sign off the batch
record
No
27
Prod Manager
QA Manager
Define
Measure
Analyze
Improve
Control
Proposal for New Process Flow
Blistering & Packaging of Ponstan 500 mg FCT
Coating
PPIC
Verification by QA
Inspector
Coated
Tablet
Examination &
approval of sample of
embossed empty
blister
Leak Test
Inspection on
embossed lot no and
exp date
Inspection on
blister defects
Printed
Multicarton
Folded
leaflet
Finished
Products
A
Line Clearance
Packing into
multicarton
Blistering
Packing into export
shipper
Reconciliation
Examination &
approval of shipper
label
Batch record review
and disposition
End of Run Check
Start-Up
Weight monitoring of
multicarton
Inspection on product
and packing defect
(ROI)
28
Define
Measure
Analyze
Improve
Control
Proposal for New Process Flow
Ponstan 500 mg FCT Batch Record Review Process
A
TL/ Operator/
Inspector
Prod Spv
No
No
Prod Spv
Prod. Spv review and
sign-off the batch
record
Ok?
Yes
TL/ Prod Spv
Prod Manager
Completion in
MAPS
Production Manager
review and sign-off the
batch record
Ok?
Yes
Approved batch
packaging record
Disposition in MAPS
Yes
Ok?
QA Manager review
and sign off the batch
record
No
Prod Manager
QA Manager
29