Innovations in Closed System

Sterile Powder Transfer

Problem

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Need a reliable and innovative solution to move material…

Reliable solution but…

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Innovative Alternative

Sterile Drug Product

Multi-Chamber Drug Cartridge

Closed System Sterile

Powder Transfer

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Presentation Overview

Closed System Sterile Powder Transfer

Purpose:•Maintain a high level of sterility assurance while moving drug product and materials through different room classifications into the filling environment. •Eliminate the need for repeated sanitization / sterilization treatments.

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Presentation Overview

Key Objectives:•To define the requirements and risks involved in transferring drug product (powder) to the filling line•To describe the sterilization steps for the powder transfer components•To describe how alpha / beta and aseptic connections can be employed for a powder transfer system•To demonstrate how sterility assurance is maintained throughout the process of transferring sterile powder to the filling line

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Presentation Overview

Take Home Benefits:•Introduction to closed system powder transfer•Practical knowledge of rapid transfer port (alpha / beta) connections•Use of established GMP methods in a novel manner•Introduction to use of these concepts for transfer of other materials (stoppers, aluminium caps) to the filling line

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Closed System Sterile Powder Transfer

Powder Sifter

Mobile Storage / Transfer Vessel

Docked Vessel

Isolator Filling Line

Automated Rapid Transfer Port

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Closed System Sterile Powder Transfer

Transfer Chute

Flexible Bellow Connection

Powder Distribution

Filling System

Multi-Chamber Drug Cartridge

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Within Grade

A

Quality By Design

Material of Construction:•All product contact surfaces 316L stainless steel •Electropolished•Surface roughness Ra < 0.5µm (20 µinches)•Steam sterilizable components•Vapor Phase Hydrogen Peroxide compatible materials•Flexible materials silicone

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It Starts Here

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Closed System Sterile Powder Transfer

Powder Sifter

Mobile Storage / Transfer Vessel

Docked Vessel

Isolator Filling Line

Automated Rapid Transfer Port

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Powder Sifter / Transfer Vessel

Existing equipment New equipment

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Sifter / Transfer Vessel

Transfer Vessel:•Sterilizable (steam-in-place and autoclave)•Nitrogen pressurized to protect contents•Variable sizes (10 – 300 liter volumes)•Compatible with lift system

Sifter:•Raw material filtered to sifter under positive pressure, Grade A environment•Connected to transfer vessel with sterile flex boot

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Vessel Features

Filter connection for pressurization

Butterfly valve for

powder dosing to isolator

Beta port for RTP connection

Pressure gauge

Butterfly valve for

powder dosing from sifter

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Powder Transfer: Sifter to Vessel

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Problem

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Reliable solution but…

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Closed System Sterile Powder Transfer

Powder Sifter

Mobile Storage / Transfer Vessel

Docked Vessel

Isolator Filling Line

Automated Rapid Transfer Port

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Lifting Device

• Automated lift system• Programmable paths for

vessel docking• Ergonomic

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Vessel and Lifting Device

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Docked Vessel

• Alpha / beta connection• Automated rapid transfer

port (RTP)

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Vessel Docking to Isolator

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Problem

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Reliable solution but…

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Closed System Sterile Powder Transfer

Powder Sifter

Mobile Storage / Transfer Vessel

Docked Vessel

Isolator Filling Line

Automated Rapid Transfer Port

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Rapid Transfer Port

• Alpha door mounted in isolator wall

• Beta cap mounted on vessel

• False beta cap installed during isolator VPHP

• Non-sterile surfaces mate and door opens

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Transfer Chute, Beta Port, Ring of Concern

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Transfer Chute, Beta Port, Ring of Concern

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Transfer Chute, Beta Port, Ring of Concern

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Automated Rapid Transfer Port

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Problem

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Reliable solution but…

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Closed System Sterile Powder Transfer

Transfer Chute

Flexible Bellow Connection

Powder Distribution

Filling System

Multi-Chamber Drug Cartridge

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Within Grade

A

Transfer Chute

Preparation/protection of sterile product contact surfaces:•Sterilize chute inside autoclave bag with end caps installed•Unwrap and install chute assembly on support arm prior to isolator VPHP decontamination•Aseptically remove end caps using isolator glove ports after isolator decontamination

•Powder discharge angle optimized at 50 degrees•Tested to confirm no bridging during powder flow

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Isolator: Transfer Chute Insertion

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Isolator: Transfer Chute Insertion

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Flexible Bellow

Preparation/protection of sterile product contact surfaces:•Autoclave bellow inside sterilizable stainless steel container•Place container in isolator and seal prior to isolator VPHP decontamination cycle•Aseptically remove and install bellow using isolator glove ports after isolator decontamination

•Bellow maintains contained system, while allowing for powder bunker movement

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Flexible Bellow Connection

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Flexible Bellow Connection

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Flexible Bellow Connection

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Powder Transfer: Vessel through Chute / Bellow

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Vessel Docking, RTP, Chute, Bunker

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Closed System Sterile Powder Transfer

Transfer Chute

Flexible Bellow Connection

Powder Distribution

Filling System

Multi-Chamber Drug Cartridge

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Within Grade

A

Transfer Chute / Flexible Bellow / Powder Bunker

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Powder Bunker / Distribution System

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Transfer Chute / Flexible Bellow / Powder Bunker

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Distribution System

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Problem Solved

Closed System Sterile

Powder Transfer

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Other Applications

This concept is effective for processing and transfer of other materials (stoppers, aluminium caps) to the filling line

Plungers and Disk Seals

Aluminum SealsNeedle Shields

Serum and Lyo StoppersTip Caps

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Component Processing System

UnclassifedCleanroom D or C

Isolator

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Component Processor

Purpose:•Washing, siliconization, sterilization, drying and cooling of pharmaceutical closures.•Contained system from component loading until use at the filling line.•Maintain a high level of sterility assurance materials through different room classifications into the filling environment.

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Presentation Conclusion

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Take Home Benefits:•Introduction to closed system powder transfer•Practical knowledge of rapid transfer port (alpha / beta) connections•Use of established GMP methods in a novel manner•Introduction to use of these concepts for transfer of other materials (stoppers, aluminium caps) to the filling line

Acknowledgements

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Bausch and Ströbel

SKAN AG

Beckman Machine

Thank you for your attention!

*These are not tools for the pharmaceutical industry and should not be used in a clean room environment.

Aaron MertensUS Technical Support

+1-440-530-0060mertens@atecgroup.de

Atec PharmatechnikSörup, Germany

www.atecgroup.de

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