Flexible Aseptic Manufacturing

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FLEXIBLE ASEPTIC MANUFACTURING TRADITIONAL VS. FLEXIBLE ASEPTIC MANUFACTURING Steve Walter, GMP Technology Specialist CDI Life Sciences Josh Russell Principal Engineer AST

description

An overview of flexible aseptic manufacturing of syringes, vials, cartridges and IV bags in ready-to-use (RTU) formats.

Transcript of Flexible Aseptic Manufacturing

Page 1: Flexible Aseptic Manufacturing

FLEXIBLE ASEPTIC MANUFACTURINGTRADITIONAL VS. FLEXIBLE ASEPTIC MANUFACTURING

Steve Walter, GMP Technology SpecialistCDI Life Sciences

Josh RussellPrincipal EngineerAST

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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

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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

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CNC CNCCNC/Grade D Grade C

Traditional Aseptic Processing

Depyro

Wash FillComp Prep

Capping

Comp Prep

WashDepyr

o

Stopper

Comp Prep

De-Bag

Tub Decon

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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

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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

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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

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Enabling Technologies• Single-Use Product Pathway

• Peristaltic & time-pressure• Minimal product holdup• Containment of potent compounds

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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)

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Flexible Aseptic Processing

CNCGrade 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

Chamber

Comp Prep

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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

Automatic, Shorter 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 COMPARISON

Criteria RABS Isolator Robotic Isolator

Comparison

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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

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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

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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

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* 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

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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.

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Flexible, Multi-Format Facility

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Flexible, Multi-Format Facility

Fill Suite Size:3600 SF / 335 SM

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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

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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

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Acknowledgements:

Andrew Scherer, President, SmartFit Modular

George Wiker, Principal, SmartFit Modular

Chris Tyree, Ompi North America

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Thank You!

Joshua Russell, Principle Engineer – Life SciencesAutomated Systems of Tacoma (AST)4110 South Washington St. Tacoma, WA 98409(253) [email protected]

Steven Walter, GMP Technology SpecialistCDI Life Sciences1801 Market Street, Ste. 1300, Philadelphia, PA 19103(215) [email protected]