Disposable Technologies for Aseptic Filling

8/13/2019 Disposable Technologies for Aseptic Filling

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Integrated Process Solutions

for Aseptic Processing

Alain Rachon

Europ ean Field Marketing Manager


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Aseptic Process

The product and all of its contact parts are

sterilized separately and brought together under

exposed conditions where, if not properly

controlled, could result in contamination.

John W. Levchuk, Ph.D CBER, FDA


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Risk mitigation

Project design phase

Begin with the end in mind

- Process transfer

- Process scaling-up- Licenced process

- Validated process

Not just building the project right

But building the right project !!!

Quality

Schedule

Cost

Project

risk


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Assembly andCleaning area

Class A

Mixing tank

API solubilization

under isolator

Class B

Class C

Autoclave


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Regulatory View Point
http://www.fda.gov/default.htm


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Regulatory point of view

Aseptic design

The design of equipment used in aseptic processing should limit the numberand complexity of aseptic interventions by personnel. Rather than performing

an aseptic connection, sterilizing the preassembled connection using sterilize-

in-place (SIP) technology also can eliminate a significant aseptic manipulation

- Easy to clean, sterilize & dry process line

- Avoid manual aseptic connection

- Use pre-assembled components

- Use pre-sterilized assemblies


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Sterile Disposable Fluid Path


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No crosscontamination

Keep sterility

No CIP validation

Protect operator

Flexible

Easy to use

Or

???

API preparation & transfer

What do you need?


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Sterilizing filter

0,2 m filter capsule

Disconnection tool

Inlet silicone tubing

+ Novaseal pipe

2 D Sterile Holding

100 ml/50 l bag

Transfersolution

Outlet Lynx S2Sconnector

API preparation & transfer

How does it solve your pain?


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Improve process economics

- Reduce capital investments

- Eliminate cleaning validation

- Labor cost savings

Increase flexibility

- Lower floor space vs SST

- Shortened cycle times

Safety & quality- Disposable container

- No cross contamination

- Self contained system

Disposable mixing system

Why does it adress your challenges?


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Disposable fluid path

Sterile filter & tubingGamma irradiated

Formulation tank

500 l mixing bag

(Gamma irradiated)

Sterile holding500 l bag + SS carrier

WFI Inlet

1 inch inlet port


Formulation & sterile holding


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m: Foot print for Mix 500

rpm: Maximum rotation speed

min: Bag set-up time

liters: Minimum working volume

sec: Mixing starting time

ml: Hold-up volume

< 1.5

550

< 1

5

< 1

30


What does it make for you?


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Stainless Steel

11 components

Cleaning and validation

Autoclaving/SIP and validation

Assembly operation

Sterilizing grade filtration

Hardware vs disposable

Disposable

1 disposable filter

Not needed

Not Needed

Not


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Various aseptic processing operation call for different environmental class

ISO 8:

Components handling & washing

ISO 7:

Formulation & bioburden filtration

ISO 6/5:

Aseptic preparation & filling

Sterile transfer solution

Barrier technology


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1.Secured design

Independant from operator

2.Bidirectional transfer

Loading & unloading

3.Validated system

For bio & particules

4.World wide compatible

To any RABs, Isolator, filling

machine manufacturers


Rapid Transfert Port technology


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RTP application for fluid transfer

Rigid passtrought

Allow connexion of the

inner tubing

RTP Flange Beta port

To be connected to the

supported Alpha port

PE bag

Bottom welded after theassembly being built

Inside tubing

Sterile Disposable fluid

path


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Disposable sterile fluid transfer


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RTP application for fluid transfer

Flushing bag

Pureflex 20 L

Bioburden filter

10 capsule 0.2 m

WFI Inlet

Flushing & Integrity testing

DPTE Beta bag

for sterile fluid

transfer

Outlet

Inlet

ISO 6/5

Inlet

Sterilizing filter

4 caspule, 0,2 m

ISO 7
http://www.colder.com/asp_main/FeaturesBenefits/MPCFBBio.asphttp://www.colder.com/asp_main/FeaturesBenefits/MPCFBBio.asp


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Sterile Connector LynxTM S2S

What does it do & how does it work?

Female

coupling

Male

coupling


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Sec: To perform the connexion

Actuation: Single use & secured

ml: Hold-up volume

bar: No pressure leak below

Degrees: Max. autoclaving temp.

< 10

1

< 1

13

130

Sterile Connector LynxTM S2S

Key figures


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Disposable sterile holding

Stainless steel totes

1.Broad range of sizes

200 to 2000 liters

2.Autoclavable

To be used in ISO 6/7

3.Optional

- Jacketed for T

control- Caster or dollies

- Load cells

- Custom design for shipping


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High purity (Class VI/USP 661/21 CFR)

. Low product adsorption

. Low extractable level

High flex cracking resistance

High gas barrier propertiesFree of animal-derived components

Sampling Pilot Mixing & holding Filling

Disposable sterile holding

Universal Pureflex film


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Optical

Sensors

Pinch

Valves

Reservoir

Holder

Capacitance

Sensor

Handheld

Computer

Dosing & filling with AcertaDS

How does it work?
http://f/Acerta/Acerta2.rm


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Reduce capital & running cost No CIP, No SIP validation

Increase productivity

< 10 min set-up

Increase flexibility

Batch sizes, products, shift

Eliminate risk cross contaminations

Single use, pre-assembled &sterile

Increase operator safety

Close system


What does it bring to you?


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Programming of Acerta System (by PLC) Automatic feed of rubber stopper


Integrated & automated mode


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Validation documents

&

Support services to qualifications


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Type of

COQCOQ Shelf Life

Claim

Sterility Claim LAL &

Particulate

Leak Testing Class VI

USP

Gold

(Drug)

YES, in

each box

YES,

2 years

Sterile, Qrtly

Validation

Lot Release 100% of lot on

full assembly &Bag

Post-gamma,

componentfamily

Silver

(Bulk)

YES, in

each box

YES,

2 years

Sterile, Qrtly

Validation

Quarterly on

representative

sample

In-Process leak

testing

Post-gamma,

component

family

Bronze

(Buffer,

CIP)

YES, in

each box

NONE Gamma Irradiated

>25 kGy, not

validated sterile

No testing

performed

No Testing

performed

Pre-gamma

resin only

MobiusTMDisposable Assembly

Quality Certificate Levels


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USP88 class VI for either film & components (Meet)

USP661 (heavy metals) (Meet)

ISO 10993-4 (Hemolysis) (Meet)

EP 3.2.2.1 (aqueous solution for Parenteral Injections)(Meet)

USP788 (particles for injection forms) (Meet)

ALL TESTS PERFORMED AFTER GAMMA IRRADIATION >45kGy

MobiusTMDisposable Assembly

Validation Guide for PureFlexTMfilm

0.000

0.005

0.010

0.015

0.020

0.025

0.030

0.035

0.040

0.045

0.050

012345678910111213141


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1. Process line design optimization

2. Disposable mixer qualification (IQ/OQ)

3. Assembly performances qualifications Adsorption studies

Chemical compatibility

Leachables

Bacterial retention test

Integrity testing procedures

4. Operator training

5. Maintenance contract

Millipore services offering

Global approach

C l i


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Mixing bag

Assembly

areaClass C

Class A

Autoclave

pH holder kit

Connection inclass C

Sterile connection

in class B/A

Millipak Millibarrier to

perform pre-use int. test

API solubilization

under isolator

Conclusion

Impact of disposables on the process line

V lid ti M t Pl


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Validation Master Plan

Hardware vs disposable Aseptic Processing

Traditional aseptic processing

- Filter retention

- Filter extractables

- Integrity testing

Pre-use Post-use

- Steam sterilization

- Adsorption

- Media fills

- Fills accuracy- Bioburden & sterility testing

- Stability testing

- Others (CIP)

Disposable aseptic processing

- Filter retention

- Disposable assemblyextractables

- Integrity testing

Pre-use may require new SOP Post-use

- Gamma irradiation sterilization

- Adsorption

- Media fills

- Fills accuracy- Bioburden & sterility testing

- Stability testing

- Elimination by incineration

C l i


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Controlled area / Class 100 000

Transition zoneClean area / Class 10 000

Compounding and filtration zone

Critical area

Class 100

Aseptic Filling

area

People

Raw materials

Process Components

Filters, vessels, pumps

Gowning

Sterile filtration

Container Components

Stoppers, vials

Utilities

Gas, Water, Steam, CIP

SIP / CIP

Sterile product

Waste

Clothing, materials

Waste

CIP effluents

Components

CleaningSIP, autoclave

Sterilization tunnel

Conclusion

Impact of disposables on the facility layou

C l i


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Conclusion

A new age is rising

Obvious benefits: - Increase sterility assurance leveI- Improve productivity

- Increase flexibility

But: - New sterilization mode (gamma-irradiation)

- New extended validations datas needed

- Supply chain

Evolution toward a new relationship End user/Supplier

- Collaboration

- Innovation

Transparence

Disposable Technologies for Aseptic Filling

Documents

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