Barrier Systems & Requirements for Sterile Manufacturing Annex … · 2020. 7. 13. · HEPA...

Barrier Systems & Requirements

for Sterile Manufacturing –

Annex 1 Draft

Date : 14th July 2020

▪ Senior Consultant

Aseptic Processing & Containment @ SKAN AG

▪ PDA: Preventing Contamination and

Cross Contamination

▪ PDA Isolator Expert Group

▪ PDA Program Committee for the EU ATMP

and Bio Conference

▪ ISPE Chair CoP Containment and Chair Robotics

▪ ISPE CoP SPP Sterile Product Processing

▪ ISPE Chair Containment Guide

▪ PICs/Annex 2 – 2A ISPE Comments Team

▪ ISO TC 198 Aseptic Processing and Isolators

Your Presenter: Richard Denk

• Under Revision

• 6400 Comments back from the Industry.

• Complete new write of the document.

• Annex 1 is an European Document but with

global involvement.

Version 7 Publish Dec. 2017

Regulatory Annex 1 Draft 2017- 2020

• New Round of Comments to stakeholders

like ISPE, PDA to specific chapters.

• Lessons learned from the first draft.

Version 12 Draft Febr. 2020

PDA Points to Consider Published June 2020

• Contamination Control Strategy CCS

• Quality Risk Management QRM

• Keep Operators out of critical Aseptic

Operations

• Barrier Solutions the preferred technology.

What are the :major driver for the

new Annex 1

Conventional

Aseptic

Processing

Highest risk of

intervention

RABS «Restricted

Access Barrier

System»

Reduced risk of

human intervention

Isolators

Lowest risk of

human intervention

Conventional

Aseptic

Processing

Highest risk of

intervention

Conventional Solution

▪ Operator have access to critical areas

▪ No Barrier

▪ Contamination Risk on the Curtain.

▪ Intensive Training and Monitoring

▪ Technology should be replaced to Barrier Solutions.

RABS «Restricted

Access Barrier

System»

Reduced risk of

human intervention

RABS “ Restricted Access Barrier

System”

▪ Operator have access to critical areas

▪ Barrier but doors can be opened

▪ Decontamination inside of the door before closing.

▪ Intensive Training and Monitoring

▪ More and more poor designed RABS on the market.

Isolators

▪ Operator have no direct access to critical areas

▪ Surrounding Class C/D

▪ Validated and integrated decontamination system

with vH2O2

▪ Suitable for high potent products

▪ Operator have direct access to critical areas

▪ Surrounding Class B

▪ Decontamination together with the room

▪ Not suitable for high potent products

Isolators

Lowest risk of

human intervention

Isolators

▪ Operator have no direct access to critical areas

▪ Validated and accepted decontamination system

▪ Reduced Clean Room requirements outside of the

Isolator (ISO 7/8 Class C/D)

▪ Less Gowning of the Operator

▪ More and more poor designed Isolators on the

market.

High risk to the product

The Olympic Rings for Annex1 Compliance in Isolators

Contamination Control Strategy

Stainless steel not polished Aluminium

Influence of Cleaning and Decontamination on different surfaces

Grade A - Air Supply and Surface Decontamination

Service covers

Vaporizer plate for H2O2Intake air from air handling unit

Recirculation fan

Unidirectional air flow

Differential pressure indicator

HEPA filter

Diffusor membrane

Return air

through double door

Critical zone

“Classified working zone”

Critical Zone for Surface Decontamination

dosing unit

vaporizer plate

Surface Decontamination

with vH2O2

H2O2 SolutionFlash

Vaporizer

H2O2 vapour

Carrier gas

HEPA filter

Isolator chamber

Surface Decontamination

with vH2O2

0 1 2 3 4

Leak Test Pre-Conditioning Conditioning Decontamination Aeration

Decontamination effect

Cycle phases

Surface Decontamination with vH2O2

Fastest H2O2 cycles with state-of-the-art SKANFOG® decontamination

technology

▪ Micro-nebulization of H2O2

▪ Fastest decontamination process

Cycle phases

Surface Decontamination with atomized H2O2

Proof of Surface Decontamination with Biological Indicators

• Defined test organism

• Defined initial population

• Carrier material

• Primary packaging

• Inactivation method

• e.g. Geobacillus

stearothermophilus

• e.g. 1.0 x 106 [spores/carrier]

• e.g. stainless steel

• e.g. Tyvek

• e.g. gaseous H2O2

Worst Case Study with Biological Indicators

Sterility Test

There will be a PDA Paper about Quality Risk Management for Isolator Gloves together with the BPOG.

Isolator Glove Test

Visual Test Physical Test Glove Quality Risk Management

GMP Cleaning and Operator SafetyContamination Control Strategy

Validation of the cleanliness of

non-product-contact surfaces

has increased in popularity

since the EMA proposed the

following measures in order to

demonstrate effective

management of the cross-

contamination risk (in Chapter

5.21 of Part 1 of its GMP

guidelines): “Depending on

the contamination risk,

verification of cleaning of non-

product contact surfaces and

monitoring of air within the

manufacturing area [...] in

order to demonstrate

effectiveness of control

measures against airborne

contamination or

contamination by mechanical

transfer.”

Automation with Robotics

▪ Human intervention only possible with

the Robot

▪ New Requirements for Viable

Monitoring needed based on automation

and real time release.

▪ Automated Transfer of Stoppers, Caps

▪ Ready to Use (RTU) End to End design

( Sustainability)

▪ ISPE DACH SIG Robotic

Questions?

Thank you!

richard.denk@skan.ch

Barrier Systems & Requirements for Sterile Manufacturing Annex … · 2020. 7. 13. · HEPA...

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