isolator for sterility from the customer needs to the ... · • aeration time and running cost •...

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ISOLATOR For SterilityTesting

From The Customer Needs To The Qualification On Site

Charles Daviau GETINGE La Calhène

2017 July 25th

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Table of Content

CONTENT:

REMINDER

THE ISOLATOR

METHOD OF CHOICE

SOLUTIONS

CONCLUSION

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Sterility Testing Reminder

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What Is The Sterility Testing?

Definition:

• Sterility testing is required for monitoring all products that are manufactured according to GMP and purporting to be sterile.

• Sterility testing is the last test practiced on sterile finished products: antibiotic powders, injectable liquids, ophthalmic products… before giving them the authorization to go on the market.

• Sterility testing is a destructive test.

• Two methods are described with number of samples to use, the 2 culture media to use and the 2 temperatures of incubation:

• 0.45 micron membrane filtration (method of choice)

• Direct inoculation

• Time of incubation and quarantine is 14 days.

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Why?

• Industry perspective:

• No false positive (showing positive test / non sterile drug although it is sterile, i.e. re-contamination of it during testing)

• Efficiency, cost

• Regulation perspective:

• No false negative (showing negative test / sterile drug although it is non-sterile, i.e. usually H2O2 penetration prior or during testing)

• Agree with alternatives methods, with justifications

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Regulations / Guideline

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Why an Isolator?

• A physical barrier between operator and product• To reduce Risks of external contamination

• A working volume with controlled atmosphere

“Isolators are devices that provide for total separation between one environment and another. An

isolator does not directly exchange air with the surrounding environment and all air must enter through a

HEPA or ULPA filtration system. All transfer of material into the isolator must be accomplished while

maintaining complete environmental separation. The interior of the isolator, and all equipment contained

therein, must be sterilizable in a highly reproducible manner”.

James Akers

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Isolator vs LAF Cabinet

• Traditional clean room technology A/B

• RABS in grade B cleanroom

• BSC / LAF in grade B cleanroom

• Downflow booth

• PPE Personnel Protective Equipment

BSC & CLEANROOM

CLOSED BSC

Traditional A/B

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Why Isolator and not LAF Cabinet?

• To be able to test cytotoxic drugs / potent products without any risk for the operator

• To use the safest way for waste disposal

• To ensure reproducible and validated bio decontamination cycles

• A leaktight volume which can be traceable, measurable, « monitor able »

• But it ‘s mainly a reduced area close to the product , easy to clean and easy to bio decontaminate (6 log reduction, ATCC 12980 Bacillus Stearothermophilus).

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THE ISOLATOR

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Isolator Principle

Please draw me an isolator……

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Isolator Principle

VENTILATION &

FILTRATION

• Positive pressure

• Negative pressure

• Turbulent flow (ETF)

• Unidirectional flow (UDF)

BIO DECONTAMINATION

TRANSFER

BatchContinuous

Dynamic output Sterilization tunnel

DPTE® transfer OvenAutoclave

chemical airlock

MANIPULATION

Half-suitGlove/ sleeveDPTE® suit

CONTAINMENT (isolator)

• Flexible wall

• Rigid wall

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The Containment

• 316L base

• Soft wall

• Rigid wall of 316L/glass or PMMA

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Manipulation

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Biodecontamination /Sterilisation

CORE STERILIZATIONCONTACT STERILIZATION

AutoclaveOven

Steam

Vaccuum

Dry heat

Gaz sterilant

Isolator

RESULTS :

S.L.R. 106 spores

S.L.R. = Spore Log Reduction

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Biodecontamination

ClO2

H2O2

NO2

Formaldehyde

Peracetic acid

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Transfer

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Ventilation: Positive Pressure

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METHOD OF CHOICE

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How to Define?

CONFIDENTIAL - SEMINAR -April 2016

Inventory of the load

Check the feasibility

Load study

Validation on site

Sterility test method

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Regulations / Guideline

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Inventory

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Load Study

• To perform the “worst case” load(s) bio-decontamination

• Use CAD drawings, real units in ourshowroom or mock-ups

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Trial Synoptic

LOAD FOR EACH TEST

Description TEST#1 TEST#2

Glass Screw Vials 100 ml 20 20

Glass Screw Vials 50 ml 20 20

Plastic Syringe 2 ml 40 40

Plastic Syringe 5ml 4 4

2ml Pipettes 40 40

Rack of 40 Vials XXml 1 1

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Installation Assistance

Need:

• Close relationship early in the process

• Customer/supplier involvement

• Building constraints

• Very important :

• Air exhaust design

• Air exhaust location on roof (dangerous H2O2 reject)

• Alternative : catalytic converter option

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Installation Assistance

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Installation Assistance

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Cycle Development

The cycle development and validation must be done by isolator experts or approved / certified team in order to optimize:

• H2O2 consumption

• aeration time and running cost

• Cycle time

… and to avoid:

✓ The “non specialist” mistakes

✓ Avoid waste of time, searching the right / best bio decontamination parameters

✓ Direct explanations / training on site by the expert

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SOLUTION ?

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Successful Solution?

Flexible in use

Upgradeable /Modular

Workable

Traceable

Complete validated solution

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The State Of The Art

➢Our perspective: • Propose a very standard state-of-the-art

solution for a very standard application• Strong La Calhène expertise since 80’s, with

more than 900 references only for sterility testing

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Different Configurations/Units

< ISOFLEX-S with

small bio decon hatch

ISOFLEX-R with

bio decon hatch >

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ISOTEST –Up To 40 Tests Per Shift

• Integrated Steritrace II

• 316L stainless steel and glass, Siemens PLC control and touch panel

• Composed of 1 workstation (suitable for 2 operators) and 1 bio decontamination transfer hatch

• High throughput / productivity, one-way product flow using DPTE® transfer systems (option)

• Ideal for cytotoxic drugs (with waste management system)

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ISOFLEX R with Hatch

• ISOFLEX-R ™ with bio decontamination hatch and integrated Steritrace II

• 316L stainless steel and glass• Composed of 1 workstation (with 3

or 4 gloves for one operator) and 1 bio decontamination transfer hatch with front loading

• Smaller footprint than ISOTEST• Both chambers can be bio

decontaminated separately• High throughput / productivity,

one-way product flow using DPTE® transfer systems (option)

• Ideal for cytotoxic drugs (with waste management system)

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ISOFLEX R

• 3 or 4-glove ISOFLEX–R with integrated Steritrace II

• Batch concept isolator: • front window opening• Loading and closing• bio decontamination• sterility testing• opening for removal of

waste and canisters• Minimum useful surface:

<2,5mx1,5m• Ergonomics and visibility• Bio decontamination hatch can

be added • Easily upgradable

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Modularity

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Easy To Install And Maintain

Sensors and transmitters are located on the internal

face of the openable upper ventilation doors

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Tracability

InTouch® software as standard• 21 CFR part 11 & GAMP 5

compliant as standard.

• No extra cost for integration with SCADA.

• Trending data storage on Panel PC.

• Recorded in SQL data base:

• Audit trail

• Alarms *

• Reports *

• Recipes *

• Trends

• *Can be printed or stored in PDF

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Eliminate The Risks

• Glove leak tester

• Safe and secure Wastemanagement with DPTE ® system

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Conclusions

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Conclusions

• THE ISOLATOR FOR STERILITY IS NOT A SIMPLE GLOVE BOX :IT IS A «TOOL « .

• IT MUST BE DESIGNED

• TO BE FULLY QUALIFIED AND DOCUMENTED

• TO ENSURE THE FULL TRACABILITY

• TO BE EASY TO INSTALL/MAINTAIN /OPERATE

• TO ENSURE « PRODUCTIVITY «

• TO NOT CORRUPT THE TEST

• FOR THE FUTURE (RAPID METHOD….)

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ANY QUESTIONS?

Charles.daviau@getinge.com