Date post: | 30-Jun-2015 |
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FLEXIBLE ASEPTIC MANUFACTURING
TRADITIONAL VS. FLEXIBLE ASEPTIC MANUFACTURING
Steven Walter, Process SystemsTech. SpecialistHargrove LS
Josh RussellPrincipal EngineerAST
Objective / AgendaProvide 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
CNC CNCCNC/Grade D Grade C
Traditional Aseptic Processing
DepyroWash FillComp Prep Capping
Via
lsC
artr
idge
Comp Prep Wash Depyro
Stopper
Lin
e Se
al
Cap
ping
Fill
Inse
rt
Plu
nger
Syri
nges
Comp Prep
De-Bag
Tub Decon
Lid/
Line
r R
emov
al
De-
Tub
Fill
Inse
rt
Plu
nger
Re-
Tub
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
technologies• Simplifies the manufacturing
process • Ability to fill multiple container
formats & sizes• Common facility with reduced
floor space and utilities• Increased asset utilization
Flexibility is the antidote to uncertainty
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
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)
Flexible Aseptic ProcessingCNCGrade 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
RapidDecon
ChamberComp Prep
Lid/
Line
r R
emov
al
De-
Tub
Fill
Stop
per
/ P
lung
er
Re-
Tub
Rea
dy-T
o-Fi
ll C
onta
iner
s
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 8 ISO 8
Air HandlingRoom 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
GowningClass 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 COMPARISONCriteria RABS Isolator Robotic Isolator
Comparison
Material TransferMousehole, 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 SpeedsLimited / # 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 COMPARISONCriteria RABS Isolator Robotic Isolator
Comparison
Criteria Isolator FlexibleGlove 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
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
* 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
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 / 468,594
Cost Impact - Facility
* 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 ModularGeorge Wiker, Principal, SmartFit Modular
Chris Tyree, Ompi North America
Thank You!
Joshua Russell, Principle Engineer – Life SciencesAutomated Systems of Tacoma (AST)4110 South Washington St. Tacoma, WA 98409(253) [email protected]
Steven Walter, Process Systems Tech. Specialist Hargrove Life Sciences1880 JFK Blvd., Suite 700, Philadelphia, PA 19103(215) [email protected]