Processing of double chamber syringe and cartridges
Thomas Bühler, Sales Manager
Bausch + Ströbel Maschinenfabrik GmbH & Co. KG
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Speaker profile
Thomas Bühler started in September 2000 at Bausch+Stroebel
Ilshofen for an apprenticeship program for business
administration.
After two years he started in the international sales and project
managing department and was involved in many high tech
project for the pharmaceutical industry.
He has a excellence experience on projects of filling liquid and
powder products into primary packaging.
As sales and project manager he is
responsible for the north and central
American market.
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New Filling Technologies and Techniques
Agenda
1. Disposable Product Path
- Peristaltic dosing system
- Disposables
2. Bulk manufacturing of cartridges and syringes vs. nested processing
- Nested processing
- Processing of double chamber cartridge
- Status Quo and trends of double chamber container
3. Track and Trace
- Track and Trace for primary packaging
- Coded primary packaging
- Example at a bulk syringe processing line with Isolator
3
Disposable Product Path
Peristaltic dosing system
Fully integrated peristaltic dosing system
4
Disposable Product Path – Dosing system
Peristaltic dosing system – Function
Self-priming system using the filling hose as pump chamber
Only the hose gets in contact with the product.
Advantages:
• Easy cleaning / No cleaning
• No pressurization in the dosing vessel
• Low shear stress
(thus gentle product handling)
handling)
• Product carrying system free of dead space
• Fast product change as only hoses
and manifold have to be exchanged
• No product contacting mechanical parts
• Servo technology provides high flexibility
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Disposable Product Path
Peristaltic dosing system – Changing filling hoses
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Disposable Product Path
Peristaltic dosing system with disposables
Peristaltic dosing system on separate base
with product bag and weighing system
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Disposable Product Path
Peristaltic dosing system with disposables
Filling hoses and needle bag ready for beeing
connected to the filling machine enclosure
(RABS or isolator) via RTP ports
Filling hoses and needles ready for installation
inside the filling machine enclosures
8
Disposable Product Path
Peristaltic dosing system with disposables
Dosing size parts with filling hoses and
needles in inner bag with RTP port
Set of pre-sterilized dosing size parts in outer bag
9
New Filling Technologies and Techniques
Agenda
1. Disposable Product Path
- Peristaltic dosing system
- Disposables
2. Bulk manufacturing of cartridges and syringes vs. nested processing
- Nested processing
- Processing of double chamber cartridge
- Status Quo and trends of double chamber container
3. Track and Trace
- Track and Trace for primary packaging
- Coded primary packaging
- Example at a bulk syringe processing line with Isolator
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Bulk lines (syringes / cartridges) vs. pre-sterilized container
Advantages of the processing in bulk
controlled silicone process
controlled deeply process in house
not related to single source
cheaper for productions > ~ 10 Mio container / year
track and trace through the complete line possible
customer is independent from the glass supplier
11
Bulk lines (syringes / cartridges) vs. pre-sterilized container
Advantages of the nested processing
lower investment cost
less space requirement
preparation of container outsourced
higher processing output
safe handling – Lower risk of contamination
number of suppliers is increasing
12
Nested processing – Layout example
Output up to 60.000 /h.
Tub debagging
Sterilization of tubs
(E-beam)
Removal of foil lid
and liner
Filling and stopper insertion
13
Case study – High speed lines < 300 / min –
Double-chamber-cartridges / syringes with powder-product
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1.
2.
3.
4.
1
4
2
3
5.
Cartridge unpacking
Washing and siliconizing
Sterilizing and silicone baking
- Stopper insertion I
- Filling of liquid product
- Stopper insertion II
- Filling second chamber (only
for Media-Fill-Tests)
- Dosing of powder product
- Stopper insertion III
- Crimping station
- Air rinsing, checking and
reject discharge
Cartridge insertion
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SAM8062 – Cartridge unpacking machine
Cartridge unpacking
Tray infeed
Tray outfeed
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FAU8000 – Cartridge washing and siliconizing machine
Thorough cleaning inside and outside at
various stations (WFI, recycled water, air)
Infeed area with individual transport
scroll and segment wheel
16
FAU8000 – Cartridge washing and siliconizing machine
Silicone treatment station
and silicone checking
17
QTS – Transverse conveyor for cartridges
Loading of cartridges row by row into
the transport pockets of the sterilization
tunnel by a robot
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DHT – Sterilization tunnel
Transport pockets,
stress-free
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KFM8012 – Filling and closing machine for cartridges
1. Stopper insertion station I
2. Pump dosing station with CIP/SIP
and In-Process Control „IPC“
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KFM8012 – Filling and closing machine for cartridges
Rotary piston pumps
Pump consisting
of only two parts
Piston
Cylinder
Advantages:
High dosing accuracy: ± 0,5 % (dosing volume > 0,5 ml)
no valves, no seals
solid precision machine part
minimal „dead“ quantity
flexible with different dosing quantities
easy and fast cleaning
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KFM8012 – Filling and closing machine for cartridges
4. Checking station with
reject discharge
3. Stopper insertion station II
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KFM8012 – Filling and closing machine for cartridges
5. Peristaltic dosing
system with disposables
for Media-Fill-Tests
6. Powder dosing system with IPC
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KFM8012 – Filling and closing machine for cartridges
8. Crimp cap placement
and crimping
7. Stopper insertion station III
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SEM8062 – Syringe tray loading
Cartridge insertion into trays
Infeed of empty trays
Outfeed of filled trays
Post-pressing of cartridges
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Pharmaceutical market – Status quo Trend to double chamber cartridges/syringes
Lyo + Syringes
Powder + Syringes
Cartridge + Cartridge / Vial + Vial
i.e. Vaccines
i.e. Therapeutic / Long-Acting
i.e. Two-component drug
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Disadvantages of two-component container
Multiple
production
Logistics
Bigger
packaging
Marketing
Risk of
contamination
Difficult
handling
Difficult selfmedication
production
space, labour,
machinery, ...
Enhanced
efforts for
storage and
transport
Enhanced
efforts for
storage and
transport
Disadvantage of
marketing
Using to
components for
application
can only be
carried out by
specialized
staff
not suitable for
inexperienced
users
Disadvantages
Increased cost
expenditure
Disadvantages
for patients
Solution
Double chamber syringes and cartridges
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Example of a double-chamber container: GENOTROPIN MiniQuick® by Pfizer
Screwing the needle with
needle guard into syringe
Putting the outer protective
cap on the needle
Removing protective caps
Turning the plunger rod
clockwise until it stops
(Mixing of powder and liquid)
Pushing the needle into
skin and injecting the drug
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Example of insulin pens
Source: Homepage Diabetes-News
Source: Homepage Sanofi-aventis
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Benefits of processing of double-chamber container in a single transport system
Track and Trace through the complete line
All data applied per container
Low risk of cosmetic defects
First in First out process
Various checking stations
for „track and trace“
Example of coding packaging
material for „track and trace“
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Challenges of processing of double-chamber container
Single transport system necessary
Multiple process operations necessary
i.e. multiple filling and sealing
High level of automation
Only single format line economical
Individual transport
2 filling stations
2-3 stopper stations
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Challenges to equipment of double-chamber container
No accumulation / limited accumulation in the process
Fragile sections on container, i.e. Bypass
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Thought about future for the injection products
powder replace lyo
increase of cartridges because
of pen applications
Single transport systems due to
the demand of Track and Trace
Cosmetic quality more important
on injection containers
Customized drugs with multiple
active ingredients
Long-acting therapeutic products
i.e. Insulin for Diabetes
Conclusion
Double chamber containers for a convenient use of patients
33
New Filling Technologies and Techniques
Agenda
1. Disposable Product Path
- Peristaltic dosing system
- Disposables
2. Bulk manufacturing of cartridges and syringes vs. nested processing
- Nested processing
- Processing of double chamber cartridge
- Status Quo and trends of double chamber container
3. Track and Trace
- Track and Trace for primary packaging
- Coded primary packaging
- Example at a bulk syringe processing line with Isolator
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Track and Trace / Individual Container Transport
1.1 Batch documentation to date
Contents:
Product data
Size data
Monitoring of viable and non-viable particles
Fault messages with time stamp
Statistic evaluations
.
.
.
Batch in relation to: product, machines, clean room, operator ...
Disadvantage
difficult to represent the time sequence
of the production steps
manual tracking procedure
no item-level traceability
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Track and Trace / Individual Container Transport
1.2 Track and Trace
Revision of 2001/83 EG
Article 54
outer packaging
Introduction of particulars on
immediate packaging
Target
Identification, authenticity, traceability
Approach: unambiguous labeling of the primary packaging
Identification
Fault finding
Sortability
Protection against counterfeiting
Traceability of manufacturing parameters to individual primary packaging units
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Track and Trace / Individual Container Transport
1.3 Data structure
MES
Ethernet
Scada
Document
database
PC
SDV
Ethernet
PLC
Machine A
HMI
PLC
Machine B
HMI
PLC
Machine C
HMI
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Track and Trace / Individual Container Transport
2.1 Primary packaging coded by the supplier
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Track and Trace / Individual Container Transport
2.2 Individual coding – Examples
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Track and Trace / Individual Container Transport
2.3 Data matrix code
Code pattern
Figures
Characters*
Combinations
using figures
Combinations
using characters*
10 x 10
6
3
106
363
12 x 12
12
6
1012
366
16 x 16
24
16
1024
3616
20 x 20
44
31
1044
3631
* Characters =
Capital letters + figures
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Track and Trace / Individual Container Transport
2.4 Data matrix code for primary packaging
Coding by the packaging manufacturer:
Advantages: + Low investment costs per line (read only)
+ No safety problems (CO2 / Nd:YAG lasers)
+ Stress in the glass can be eliminated during manufacture
Disadvantages: - Close cooperation with the packaging suppliers
- Alignment of the containers to read the code?
- No standard primary packaging sourcing
First pass read rate 99 – 99,xx %
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Track and Trace / Individual Container Transport
3.0 Example: bulk syringe line with isolator
SAM8061
SEM8062
SWS / FAU
SFM5101
SPE8100
DHT5732
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Layout
Track and Trace / Individual Container Transport
3.1 SAM8061 – Unpacking syringes from trays
1. Registration of the pallet number
using a handhand-held scanner
Release from SCADA system
- Pallet number
2. Detection of container number
Registration in the shift register
2
- Container number
1
4
Ts *
3
Ts
3. Reject discharge with verification
Ts
4. Individual transport to the
rinsing machine
Ts
* Ts = Time stamp
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Layout
Track and Trace / Individual Container Transport
3.2 FAU8000 – Rinsing machine
5. Rinsing with WFI
5
6
WFI
Air
- position 3, pressure, temperature
Ts
Drying with air
- position 3, pressure, temperature
Ts
Steam
7
6. Reject discharge
Silicone
"Cleaning not correct"
- Verification
Ts
7. Coating with silicone
8
- position 5, pressure, silicone detection Ts
8. Individual transport to the sterilizing tunnel
Ts
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Layout
Track and Trace / Individual Container Transport
3.3 DHT5732 – Sterilizing tunnel
9. Transfer to the sterilizing tunnel
- Position 19,, rail 87
9
10
11
Ts
10. Entry into the sterilizing zone
- Air temperature
Ts
11. Discharge from the sterilizing zone
- Air temperature
Ts
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Layout
Track and Trace / Individual Container Transport
3.4 SFM5101 – Filling and closing machine
12. Transfer to zone I
- Position 124
13. DHT reject discharge
- Verification
14. Transfer to zone II
Ts
Ts
Ts
15. Cap application
- Position 3
Ts
16. Flushing with gas before filling
17 19
II
12
I
13
14 15
21
III
16 18
20
- position 3, pressure
Ts
- Position 6
Ts
- Position 6, net weight
Ts
17. Filling
18. IPC
19. Transport into zone III
20. Vacuum‐
Vacuum‐assisted stopper insertion
- Position 6, vacuum
Ts
Ts
21. Stopper height check
- Height
Ts
22. Reject discharge
- Verification
Ts
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Layout
Track and Trace / Individual Container Transport
3.5 SPE8100 – FiFo syringe buffer
VIVI-6060-S Inspection machine ((Seidenader
Seidenader))
28 29 30
24. Entry into the buffer
Ts
25. Creation of a gap
for rere-inspection
Ts
26. Finger flange inspection
- Inspection result
Ts
- Inspection result
Ts
27. Code scanning
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28. Stopper inspection
24
31 32 33 34
25
26
- Inspection result
Ts
29. Particle inspection
- Inspection result
Ts
30. Cosmetic inspection
- Inspection result
Ts
31
31--34. Syringe discharge
- Verification
Ts
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Layout
Track and Trace / Individual Container Transport
3.6 SEM8062 – Syringe packer (into trays)
35. Entry from inspection machine
Ts
36. Elimination of empty spaces
Ts
37. Insertion into tray
Ts
38. Label printing
Ts
37
39
38
36
39. Inspection of label on tray
- Code check
Ts
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Traceability of trays to the individual packaging units
48
Track and Trace / Individual Container Transport
3.7 Data of the individual container
Container number
(2D code)
Container number /
Status
Registered
FAU
Cleaned
FAU – WFI
FAU – air
Coated with silicone
Batch
Sterilized
Date
Reject discharge
Time
SAM – 2D code scanner
Transfer
shift register number
Value
Station
FAU
Silicone detection
-
Date
Time
Assessment
09-01-20 10:13:15
OK
09-01-20 10:14:12
OK
80°C, 2.1 bar, position 3
4.2 bar, position 3
09-01-20 10:15:12
OK
2.3 bar, position 5
287
09-01-20 10:16:04
09-01-20 10:16:06
OK
OK
Rail 87, position 19
09-01-20 10:18:04
OK
Infeed to sterilizing zone
279°C
09-01-20 10:26:03
OK
Exit from sterilizing zone
280°C
09-01-20 11:48:02
-
09-01-20 12:16:09
Reject
-
09-01-20 12:16:10
Yes
DHT infeed
SFM
Verification
Reject
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Thank You!
Thomas Bühler, Sales Manager
Bausch + Ströbel Maschinenfabrik GmbH & Co. KG
Parkstrasse 1
74532 Ilshofen / Germany
+49 7904 701 956
Thomas.buehler@bausch-stroebel.de
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