ISPE Aseptic Manufacturing.pdf pharmaceutical manufacturing

Ispe

1. FLEXIBLE ASEPTIC
MANUFACTURING
TRADITIONAL VS. FLEXIBLE ASEPTIC
MANUFACTURING
Steven Walter,
Process Systems
Tech. Specialist
Hargrove LS
Josh Russell
Principal Engineer
AST

2. Objective / Agenda
Provide an overview and comparison between traditional
and flexible aseptic manufacturing, the impact to facility,
operations, and cost.
• Industry Trends & General Requirements
• Traditional Aseptic Processing Overview
• Flexible Aseptic Processing Overview
• Comparison Between Tradition and Flexible
Approaches
• Operational Differences
• Cost & Savings

3. Trends & General Requirements • Small scale, high value, patient
focused
• Fast turnaround time and clinic
responsiveness becoming more
critical
• New products are highly potent
at the filling stage
• Leaner, modular, simpler
• Superior flexibility –multi-format,
multi-product, multiple dosing
options

4. CNC
CNC
CNC/Grade D
Grade C
Traditional Aseptic Processing
Depyro
Wash
Fill
Comp
Prep
Capping
Vials Cartridge
Comp
Prep
Wash
Depyro
Stopper
Line Seal
Capping
Fill
Insert
Plunger
Syringes
Comp
Prep
De-
Bag
Tub
Decon
Lid/Liner
Removal
De-Tub
Fill
Insert
Plunger
Re-Tub

5. Traditional Aseptic Processing
• Dedicated fill-finish capabilities for a specific
container type or “format”
• Adding additional container filling capabilities is a
significant investment in facilities, time and
equipment
• Processing challenges include glass on glass
contact, machine jams, broken containers, etc.
• Very efficient for high volume dedicated products
where flexibility is not necessary

6. Flexible Aseptic Processing
• Integrates best in industry
technologies
• Simplifies the manufacturing
process
• Ability to fill multiple container
formats & sizes
• Common facility with reduced
floor space and utilities
• Increased asset utilization
Flexibilityis the
antidote touncertainty

7. Enabling Technologies • Ready-To-Fill Containers
• Vials, Syringes, Cartridges
and Infusion Bags
• WFI Washed, <1
EU/Container, EtO Sterilized
• Cartridges have line seal &
crimp cap placed, and
oriented like a pre-filled
syringe
• No glass on glass contact
• Ready-To-Use
Components

8. Enabling Technologies
• Single-Use Product Pathway
• Peristaltic & time-pressure
• Minimal product holdup
• Containment of potent compounds

9. Enabling Technologies • Isolator Barrier
Technology + Robotics
• Provides full separation
between the operator and
the process
• Compatible with VHP bio-
decontamination
• Recipe driven operation
• Maximum flexibility and
functionality
• Negligible particle
generation
“Automation of other process steps, including the use of technologies such as robotics, can
further reduce risk to the
product.” Guidance for Industry: Sterile Drug Products
Produced by Aseptic Processing — Current
Good Manufacturing Practice (Pg.10)

10. Flexible Aseptic Processing
CNC
Grade D or C
• Consolidated manufacturing process that allows
multiple container formats to be filled and finished on a
single system.
• Interchangeable robot tooling specific to container
Capping
Rapid
Decon
Chamber
Comp
Prep
Lid/Liner
Removal
De-Tub
Fill
Stopper /
Plunger
Re-Tub
Ready-To-
Fill
Containers

11. Physical Attributes
Hard walls, interlocked 
doors, glove ports, transfer 
ports
Stainless walls, sealed unit, 
glove ports, transfer ports, 
bio‐decon system
Stainless
 
walls,
 
sealed
 
unit,
 
minimal glove ports, 
transfer ports, bio‐decon 
system
Room Classification ISO 7 Min ISO 8ISO 8
Air Handling
Room HVAC or Separate 
AHU
Separate AHU & HVAC, Leak 
Tight, Outside Venting
Separate AHU & HVAC or 
Integrated , Leak Tight, 
Outside Venting
Bio‐Decon Manual, Glove Autoclaving Automatic 
Duration depending on 
components
Environmental 
Monitoring Portable or Built‐In Built‐In Built
‐In / Automated
Gowning
Class 5 or 7 Gowns, Glove 
Port Usage
Class 8 Gowns, Glove Port 
Usage Class 8 Gowns
Glove Testing Visual, Automatic Visual, Automatic If Required
ASEPTIC PROCESSING COMPARISON
Criteria RABS Isolator              Robotic Isolator
Comparison

12. Material Transfer
Mousehole, Load Lock, 
RTPs, DRAWERS
Mousehole, RTP, Transfer 
Isolator
RTP, Transfer Isolator, 
Staging Isolator 
Emphasis of Training 
SOPs
Gowning, Aseptic 
Technique, Barrier Cleaning, 
Transfer Methods, Glove 
Inspection & Testing
Barrier Control System, 
Transfer Methods, Glove 
Inspection & Testing, Bio‐
Decontamination
Barrier Control System, 
Transfer Methods,  Bio‐
Decontamination
Capacity All Speeds All Speeds
Limited / #
 Of Modules or 
filling heads
Floor Space
Minimized: Minimal 
gowning functions, 
Component Prep Varies
Minimized:  Gowning 
functions, Minimal 
Component Prep, Support 
equipment: A/C, Depyro 
and Wash not required
Access for Change 
Over Gowned with open doors
Easy with Open Doors / 
Manual
Minimal:  Automatic ‐
Machine settings are stored 
as recipe.  Some pieces of 
tooling
Operating
 Costs High Medium Low
Validation Complexity
 Moderate ‐ Risk with 
Airflows
Medium ‐ Utilizing FAT/SAT 
results
Low ‐ Repeatability of 
Robots and no 
interventions 
ASEPTIC PROCESSING COMPARISON
Criteria RABS Isolator              Robotic Isolator
Comparison

13. Criteria Isolator Flexible
Glove Testing Visual / Automatic
(Qty)
Visual / Automatic –
(Qty - Minimal)
Training / SOPs Aseptic Technique /
Transfer
Limited Operator
interface during set up
Component Prep Varies No Wash / Depyro
Change Over Operator Set Up Programmed with
integrated tooling
Utilization Depends on Set Up,
Change Out and
Reduced process steps
– Increased Up Time
Product Path Cleaning / Steam In
Place
Single Use Assembly
Operational Differences

14. Criteria Isolator Flexible
Receipt of
Materials
Packed Glass Tub / Tray RTU
Component Prep Unwrap / Wash Unwrap / Stage
Waste Packaging
Discarded
Trays / Tubs utilized
through capping
Sterilization /
Decontamination
Time
Low Driven lower with smaller
environment and isolated
decontamination
Operators Required for setup,
changeover
Automated – setup,
changeover
Operational Differences

15. * Component prep area is included in the overall area of
vial filling & capping.
Area Isolator (SF/SM) Flexible (SF/SM)
Vial Filling & Capping 2100 / 195 900 / 84
Gowning 120 / 11 120 / 11
Degowning 80 / 8 80 / 8
Material Air Lock (MAL) 100 / 9 100 / 9
Comp Prep / Material
Staging
Note * 300 / 28
Total Area 2400 / 223 1500 / 140
35 – 40% Decrease in required functional areas
Impact to Layout

16. Space /Area Gr $/SF
(US / €)
Isolator
(SF/SM)
$Isolator
(US / €)
Flexible
(SF/SM)
$ Flex
(US / €)
Vial Filling &
Capping
C 425 /
316
2100 /
195
892,500 /
663,840
900 / 84 405,000 /
301,240
Gowning C 425 /
316
120 / 11 54,000 /
40,165
120 / 11 54,000 /
40,165
Degowning C 425 /
316
80 / 8 36,000 /
26,775
80 / 8 36,000 /
26,775
MAL C 425 /
316
100 / 9 45,000 /
33,475
100 / 9 45,000 /
33,475
Comp Prep /
Matl Staging
D 300 /
223
Note * 0 300 / 28 90,000 /
66,942
Totals 2400 /
223
1,027,500 /
764,254
1,500 /
140
630,000 /
468,594Cost Impact -Facility
* Component prep area is included in the overall area of
vial filling & capping.

17. Flexible, Multi-Format Facility

18. Flexible, Multi-Format Facility
Fill Suite Size:
3600 SF / 335 SM

19. Size, Cost & Equipment
• Facility Size
• Reduce operating areas by 30-40%
• Facility Cost
• Reduced engineering / design & construction costs
• Reduced construction / constructability challenges
• Reduced capital equipment investment
• Equipment Operations
• Eliminate washing and depryogenation operations from the
manufacturing site
• Increase equipment utilization
• Single fill line has the ability to process multiple container
formats
• Eliminates some of the most common routine interventions

20. Conclusions
• Flexible aseptic processing simplifies the traditional
aseptic manufacturing process
• Flexible aseptic processing leverages the strengths of
best in industry technologies to:
• Focus on core aseptic manufacturing processes
• Provide an adaptable platform capable of multi-
container format filling
• Minimize routine operator interventions
• Reduce facility size, utilities, cost, and validation
• Increase operational efficiency

21. Acknowledgements:
Andrew Scherer, President, SmartFit Modular
George Wiker, Principal, SmartFit Modular
Chris Tyree, Ompi North America

22. Thank You!
Joshua Russell, Principle Engineer – Life Sciences
Automated Systems of Tacoma (AST)
4110 South Washington St. Tacoma, WA 98409
[phone]
[email protected]
Steven Walter, Process Systems Tech. Specialist Hargrove Life Sciences 1880 JFK Blvd., Suite 700, Philadelphia, PA 19103 [phone] [email protected]