Slide 1 © PharmOut 2017

Benefits of Modularity and Rapid Bio Decontamination for Processing in Small Scale Aseptic Filling Line

Paolo Liverani, GETINGE LaCalhène

2017 July 25th

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Table of Content

CONTENT:

• NEW TRENDS: CDMO MODEL

• CONVENTIONAL ISOLATOR LINE

• FLEXIBILITY OF MODULAR ISOLATOR LINE

• PRESSURE & BIODECONTAMINATION STRATEGY

• ALTERNATIVE TO CLASSICAL H2O2 PROCESS (NO2)

• RTU TECHNOLOGY

• CONCLUSION

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New Trends CDMO Model

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New Trends: CDMO model

INTRODUCTION:

In response to a more and more competitiveinternational Pharmaceutical Market and to the rising demand of Service Outsourcing, in recent years, Bio-Pharma industry has witnessed an increasing development of the Contract Supplier business model.

CMO (Contract Manufacturing Org.)

CRO (Contract Research Organization)

CDMO (Contract Development and Manufacturing Organization)

Those acronyms identify the ability of the Contract Supplier to provide a comprehensive range of services from early-stage drug development to manufacturing.

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New Trends: CDMO model

• What are the consequences of this emerging business model in terms of technology?

➢ Deliver a flexible and possibly standardized technologicalsolution

➢ Suit a new design Facility with minor cost and lead time impact

➢ Adjust to existant Plant Lay-out (to suit its geometry and constraints)

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New Trends: Isolator or RABS?

Isolator vs Rabs:

FDA, CGMP, PDA, ISPE, EMEA, WHO, are assessing the definitionsand guidelines for Advanced Barrier Technologies defining the regulatory aspects and have identified the Isolator as the Best Practice to minimize the risk of microbial contamination and operator protection for Sterile and Sterile + Toxic Applications as alternative to the traditional « Clean Room Approach» requiringoperator personal protection by gowning.

Cleanroom

ISOLATOR

RABS

-+

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Hierarchy: Contamination Risk

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General Typical Requirements

PROJECT : Isolated Vial Filling Line Small Or Medium Throughput

✓ Filling under aseptic conditions (Grade A)

✓ Isolator surrounding in Grade C

✓ Throughput: ≤ 6.000 pcs / h

✓ Standard Isolator Size and system

✓ Product: Sterile + Cytotoxic

✓ Adapt to the existing Facility

✓ Freeze Dryer to be integrated

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Conventional Isolator Line

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Conventional Filling Line

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Conventional Filling Line

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Conventional Filling Line

• Freeze Dryer Integration

with Loading and Unloading System

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Flexibility of Modular Isolator Line

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Modularity: Variety of Configurations

14

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Modularity – Details: Rapid On-Board Biodecontamination System H2O2

Cleanroom Ceiling: 3m

ISOLATOR

FILLER

AHU

H2O2

GENERATOR

ON-BOARD

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Modular Filling Line Case Study: Bulk Vials

16

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Modularity: Freeze Dryer Integration

17

LYO already existing

Pharma Wall

AdjustableConfiguration to

Plant Layout

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Pressure & Bio-DeconaminationStrategy

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Line Bio-Decontamination Strategy

Buffer

Fill

ing &

Sto

ppering

Freeze DryerLoading and Unloading

External Vial washer B

uffer

Capping

DepyrogenationTunnel

Vial washer

Steritrace™ II

#3Steritrace™ II

#2

Ste

ritr

ace

™ II

#1

Bulk Vials

Mo

du

le #

1M

od

ule

#2

Module #3 Module #4 Module #5

door opened

door closed

Initial condition :

1- The gasket of the inlet door(D1) is sterilized duringsterilization cycle of theDepyrogenation tunnel (byheat).This door is closed.

2- Outlet door (D4) is closed.This door is opened towardsthe outside of Module #5

3- Doors D2 and D3 areopened.

Start of complete line bio-decontamination

D1

D2

D4D3

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Pressure Cascade Strategy

Buffer

+1

0P

aFill

ing &

Sto

ppering

++

+ P

a

Freeze DryerLoading and Unloading

+++ Pa

External Vial washer- Pa B

uffer

+ P

a

Capping+ Pa

DepyrogenationTunnel

++ Pa

Vial washer

Steritrace™ II

#3Steritrace™ II

#2

Ste

ritr

ace

™ II

#1

Bulk Vials

Mo

du

le #

1M

od

ule

#2

Module #3 Module #4 Module #5

door opened

door closed

D1

D2

D4D3

Pressure Cascade :

- The given values are set asan example in case ofCytotoxic Products

- The Pressure can be adjustedfor other applications

- Each module can bebiodecontaminated separatelyin case of need (unforeseenevent, scheduled maintenance,etc) the user can close theintermediate doors; it willseparate module from the restof the line (keeping the rest ofthe line sterile)

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Modularity – Different Formats: Bulk or Batch Feeding

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Modularity – Configuration Possibilities: COMBO LINES

Syringes (RTU) and Vials (Bulk) – Layout Example

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Alternative to Classical Bio-Decontamination Process: NO2

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Time Saving Bio-Decontamination: NO2

RTU Applications: LineBio-decontamination by NO2

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Bio-Decontamination for RTU: NO2

NO2 BIODECONTAMINATION:

- Unique, fast sterilization process, TUBS containing sterilized nested containers are transferred into theModulineTM compact aseptic filling line via the BioDecontamination Module which uses NO2 gas as thesterilizing agent to ensure that no microbes are transferred into the filling line on the tubs.

- Key point: can bio-decontaminate under the Tyvek lip, which is a critical area – as it is contacted by theoperator while removing the Tyvek – any organisms could be transferred off the Tyvek / adhesive into the opencontainers.

>

Does it in 20 minutes

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RTU Fast Decontamination using NO2

• The cycle is composed of 4 phases:

Humidification phase

NO2 Delivery

Dwell

Aeration

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Integrated DPTE® for material transfer

27

• Suitable for DPTE® Alpha Connection to transfer process materials

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Integrated DPTE® for material transfer

28

stoppers caps components

DPTE® Alpha

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Compatible System for Liquid Transfer and Filling

29

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Conclusions

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Conclusions

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CONVENTIONAL LINE MODULAR LINE

Dedicated and busy technicalarea needed above the clean room level: ➢ Piping➢ Cabling➢ AHU➢ Bio-Decon System

All inside the cleanroom

Many utilities needed for Line , HVAC, media

Only power supply and compressed air needed

Longer Project Timeline Shorter Project Timeline

Traditional Concept Filling Line according to the latest trends

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Conclusions

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CONVENTIONAL LINE MODULAR LINE

Applicable for larger scale Ideal for small / medium size process

Larger Footprint and materialmedia consumption

Low energy impact and costimpact

Longer Bio-Decon Cycle (VPHP in technical area) potential problemof condensation

Shorter Cycle and Generatorcloser to the Process (chamberdirect injection). Possibility to apply H2O2 or NO2

Custom Made Modular system to suit the existing lab geometry possibilityof L-shape or U-shapeconfiguration

Dedicated and fix process Multiple Process: to suit differentsizes and container shapes (RTU Syringes, Cartridges, vials)

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ANY QUESTIONS?

• any feedback appreciated!

• paolo.liverani@getinge.com