FLEXIBLE ASEPTIC

MANUFACTURING
TRADITIONAL VS. FLEXIBLE ASEPTIC
MANUFACTURING
Steven Walter,
Process Systems Josh Russell
Tech. Specialist Principal Engineer
Hargrove LS AST
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
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
 Traditional Aseptic Processing
CNC CNC/Grade D Grade C CNC

Comp
Vials

Wash Depyro Fill Stopper Capping

Prep
Cartridge

Line Seal

Capping

Plunger
Insert
Comp

Fill
Wash Depyro
Prep

Lid/Liner
Removal
Syringes

Plunger
De-Tub

Re-Tub
Insert
Comp De- Tub

Fill
Prep Bag Decon
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
Flexible Aseptic Processing
• Integrates best in industry Flexibility is the
technologies antidote to uncertainty
• Simplifies the manufacturing
process
• Ability to fill multiple container
formats & sizes
• Common facility with reduced
floor space and utilities
• Increased asset utilization
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
Enabling Technologies
• Single-Use Product Pathway
• Peristaltic & time-pressure
• Minimal product holdup
• Containment of potent compounds
Enabling Technologies
• Isolator Barrier
“Automation of other
Technology + Robotics process steps, including
• Provides full separation the use of technologies
between the operator and such as robotics, can
the process further reduce risk to the
• Compatible with VHP bio- product.”
decontamination Guidance for Industry: Sterile Drug Products
Produced by Aseptic Processing — Current
• Recipe driven operation Good Manufacturing Practice (Pg.10)

• Maximum flexibility and

functionality
• Negligible particle
generation
 Flexible Aseptic Processing
Grade D or C CNC
Containers
Ready-To-

Stopper /
Rapid

Lid/Liner
Removal

Plunger
De-Tub

Re-Tub
Comp Decon
Fill

Fill
Capping
Prep Chamber

• Consolidated manufacturing process that allows

multiple container formats to be filled and finished on a
single system.
• Interchangeable robot tooling specific to container
Comparison
ASEPTIC PROCESSING COMPARISON
Criteria RABS Isolator Robotic Isolator
Stainless walls, sealed unit,
Hard walls, interlocked Stainless walls, sealed unit, minimal glove ports,
doors, glove ports, transfer glove ports, transfer ports, transfer ports, bio‐decon
Physical Attributes ports bio‐decon system system
Room Classification ISO 7 Min ISO 8 ISO 8
Separate AHU & HVAC or
Room HVAC or Separate Separate AHU & HVAC, Leak Integrated , Leak Tight,
Air Handling AHU Tight, Outside Venting Outside Venting
Duration depending on
Bio‐Decon Manual, Glove Autoclaving Automatic components
Environmental
Monitoring Portable or Built‐In Built‐In Built‐In / Automated
Class 5 or 7 Gowns, Glove Class 8 Gowns, Glove Port
Gowning Port Usage Usage Class 8 Gowns
Glove Testing Visual, Automatic Visual, Automatic If Required
Comparison
ASEPTIC PROCESSING COMPARISON
Criteria RABS Isolator Robotic Isolator
Mousehole, Load Lock, Mousehole, RTP, Transfer RTP, Transfer Isolator,
Material Transfer RTPs, DRAWERS Isolator Staging Isolator
Gowning, Aseptic Barrier Control System,
Technique, Barrier Cleaning, Transfer Methods, Glove Barrier Control System,
Emphasis of Training Transfer Methods, Glove Inspection & Testing, Bio‐ Transfer Methods, Bio‐
SOPs Inspection & Testing Decontamination Decontamination
Limited / # Of Modules or
Capacity All Speeds All Speeds filling heads
Minimized: Gowning
functions, Minimal
Minimized: Minimal Component Prep, Support
gowning functions, equipment: A/C, Depyro
Floor Space Component Prep Varies and Wash not required
Minimal: Automatic ‐
Machine settings are stored
Access for Change Easy with Open Doors / as recipe. Some pieces of
Over Gowned with open doors Manual tooling
Operating Costs High Medium Low
Low ‐ Repeatability of
Moderate ‐ Risk with Medium ‐ Utilizing FAT/SAT Robots and no
Validation Complexity Airflows results interventions
Operational Differences
Criteria Isolator Flexible
Glove Testing Visual / Automatic Visual / Automatic –
(Qty) (Qty - Minimal)
Training / SOPs Aseptic Technique / Limited Operator
Transfer interface during set up
Component Prep Varies No Wash / Depyro
Change Over Operator Set Up Programmed with
integrated tooling
Utilization Depends on Set Up, Reduced process steps
Change Out and – Increased Up Time
Product Path Cleaning / Steam In Single Use Assembly
Place
Operational Differences
Criteria Isolator Flexible

Receipt of Packed Glass Tub / Tray RTU

Materials
Component Prep Unwrap / Wash Unwrap / Stage

Waste Packaging Trays / Tubs utilized

Discarded through capping

Sterilization / Low Driven lower with smaller

Decontamination environment and isolated
Time decontamination

Operators Required for setup, Automated – setup,

changeover changeover
Impact to Layout
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 Note * 300 / 28

Staging
Total Area 2400 / 223 1500 / 140

35 – 40% Decrease in required functional areas

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

* Component prep area is included in the overall area of

vial filling & capping.
Flexible, Multi-Format Facility
Flexible, Multi-Format Facility

Fill Suite Size:

3600 SF / 335 SM
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
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
 Acknowledgements:

Andrew Scherer, President, SmartFit Modular

George Wiker, Principal, SmartFit Modular
Chris Tyree, Ompi North America
 Thank You!

Joshua Russell, Principle Engineer – Life Sciences

Automated Systems of Tacoma (AST)
4110 South Washington St. Tacoma, WA 98409
(253) 475-0200
jrussell@ast-inc.com

Steven Walter, Process Systems Tech. Specialist

Hargrove Life Sciences
1880 JFK Blvd., Suite 700, Philadelphia, PA 19103
(215) 789-9665
swalter@hargrove-epc.com