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IMA SpA

Advancements in Isolation

Technology for Aseptic Filling

Marco Preus, 11-12 July 2016

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Agenda

• Isolation technology advantages

• Isolation technology cost saving

• Air flow circuits

• Case study: vials filling under 100% Nitrogen atmosphere

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Isolation technologies advantages

• Increased product safety

(that results in an increased product quality)

• Increased operator protection (in case of toxic product)

• Possibility to frequently perform cleaning and

decontamination cycles

• Surrounding area in class C (FDA; EU-GMP) or D (EU-

GMP only)

• Controlled atmosphere (see case study)

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Isolation technologies cost saving

• The surrounding area in class C or D

allows the following cost saving:

• Less time for personnel gowning

• Lower personnel gowning

(material)

• Less ambient monitoring

(viable/non-viable)

• Less air to be conditioned

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Filling Line with 2 FD: different protection solutions

Production Area 68 m2

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Solution A: All production room in class A

Traditional solution: production room completely in class A (68 m2 with LAF)

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Solution B: Open Active RABS

Solution with Open Active RABS: Class A: 20,6 m2; LAF 20,4 m2 (Total LAF41m2)

Class B 27 m2 (Total 68 m2)

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Solution C: Isolation Technology

Solution with Isolator: Class A: 20,6 m2, Class C 47,4 m2 (Total 68 m2)

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Clean Room vs RABS vs Isolator

SOLUTION A

CLEAN ROOM

SOLUTION B

OPEN RABS

SOLUTION C

ISOLATOR

filling sorrounding filling sorrounding filling sorrounding

CLASS A B A B A C

Clean room area m2 68 41 27 20,6 47,4

Air changes per hour

(considering the ceiling at 3m) 60 40

Total air per hour 110.160 66.420 4.860 33.372 5.688

Total air per day (24 hours) 2.643.840 1.594.080 116.640 800.928 136.512

TOTAL AIR PER DAY (24 hours) in

m3 2.643.840 1.710.720 937.440

Saving with respect to solution A -35,29% -64,54%

Saving with respect to solution B -45,20%

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• IMA Life isolators for filling lines are equipped with a

sophisticated air flow circuit that can be subdivided in three

main section:

• Re-circulated air flow to create the unidirectional air flow

(LAF)

• “Make-up” air flow, to ensure an adequate amount of

“new” air in the loop

• Extraction air flow, to have a fine pressure adjustment

inside each isolator chamber

Isolator Air Flow Circuits

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Re-circulation Air Flow

LAF Fan

LAF Filter

Air recirculation ducts

Recirculation Fan

Machine base

It is a closed loopcomposed by inlet fans and inlet filters (HEPA H14) in charge of the generation of the unidirectional air flow (LAF) inside the isolator.

At the bottom of each isolator section, all air is extracted by the fans in charge of the recirculation, and reintroduced in the isolator chamber via the filtration stage.

Hepa filter

with

Bag-in

Bag-out

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Make-up Air Flow

EXTRACTION UNIT

HVAC

We just need to extract and make-up approx. 20% of the total amount of air, to keep the right Humidity and Temperature levels.

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Extraction Air Flow

Exhaust

This circuit is in charge of the “fine pressure control”.Large HVACs have a high response time when a modification in the air flow (pressure, speed,…) is required, due to its size and related inertia. Through this extraction pipe, the main control system is able to ensure a very fast and precise pressure control for each single section.

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Case study: vials filling under 100% Nitrogen atmosphere

Filling Line specification:• Small batches: 12.000 vials per batch• Filling speed: 70 VPM• Single format: 5 ml• Multiple filling volumes: 1.5, 3, 5 ml• Extremely expensive products• 100% IPC• Aseptic, NON-toxic product

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Case study: vials filling under 100% Nitrogen atmosphere

Filling Line specification:• Small batches: 12.000 vials per batch• Filling speed: 70 VPM• Single format: 5 ml• Multiple filling volumes: 1.5, 3, 5 ml• Extremely expensive products• 100% IPC• Aseptic, NON-toxic product

Customer requirements:• Isolation technology with CLASS C background• Oxygen residual inside the vials close to

0%

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Case study: vials filling under 100% Nitrogen atmosphere

1. Nitrogen

purging

station

2. Nitrogen

flushing of

the complete

isolator

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1. Nitrogen purging

1st step:Vials are purged with nitrogen before and after filling

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1. Nitrogen purging

2nd step:Filled vials are flushed with nitrogen up to the capping station

Tunnel to flush the filled vials with nitrogen

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1. Nitrogen purging

3rd step:A concentrated nitrogen cloud is created around the capping area

Nr. 2 nitrogen ejectors

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2. Complete filling isolator is pressurized with nitrogen

Accumulation table areaStandard air flow

Capping areaStandard air flow

Filling & Stoppering area100% Nitrogen flow

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Isolator pressure cascade

Tunnel cooling zone+ 45 Pa

Accumulation Table+ 55 Pa

Filling & Stoppering+ 60 Pa N2

Capping+ 45 Pa

Room + 30 Pa Room + 15 Pa

Air trap+ 0 Pa

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Isolator pressure cascade

+ 45 PaTunnel cooling zone

+ 55 PaAccumulation Table

+ 60 PaFilling & Stoppering

+ 45 PaCapping

+ 0 PaAir trap

N2AIR AIR

N2 N2AIR +N2 AIR +N2

AIR

AIR

N2 recyclingExhaustExhaust Exhaust

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Residual O2 results

Nitrogen vial flushing (only):Approx. 1% of residual O2

Difficult validation procedure: O2 analysis on samples

Nitrogen vial flushing + Complete isolator nitrogen flushing:

<1% forwarding to 0% of residual O2

Easier validation approach, due to the possibility to monitor the O2 level inside the isolator

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IMA portfolio for aseptic filling

……single stop shopping…………..

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ANY QUESTIONS?

Marco Preus

Isolation technology

Product manager

preusm@ima.it

Shane Sipthorp

Selpak

shane@selpak.com.au