Integrated process equipment into high containment system

Presented by

Stefano Butti

Technical Sales Manager

Mobile: +39 331 6819414

F.P.S. Food and Pharma Systems Srl

Via Vandelli 20

I-22100 Como (Italy)

e-mail: butti@foodpharmasystems.com

website: www.foodpharmasystems.com

Containment system Localsuction arms

Cleanroom

LAF

Downcross booth

Charging system

Packing –off system

flexibleisolator

Rigid isolator

– Glove-boxes

– Half-Suite boxes

RABS

Process

Reactor

Filters

Dryers

Milling

Micronisation

Blending

Tablet pressing

Capsule filling

Final packaging

Dispensing and IPC test

CLEAN ROOM

JETMILL

ISOLATOR

LAF QMILL

Containment in the pharmaceutical industry: Overview

On-site preliminary discussion

Front-end design

Detail engineering

Manufacturing

Document review

FAT

Transport & installation

SAT

validation (IQ/OQ)

Maintenance and operator training

Containment performance verification

Containment in the pharmaceutical industry: Project activities

1. EN 14175 Biosafety cabinet (Part 1,2,3 and 6)

2. ISO 14644-7 Separative devices (clean air hoods, glove boxes, isolators, and minienvironments)

3. ISO 10648-1 Containment enclosure – Part 1 Design principles

4. ISO 10648-2 Containment enclosure – Part 2 Classification according to leak tightness and associated checking method

5. AGS-G001-2007

6. Containment Systems a design guide (IchemE editor)

Containment in the pharmaceutical industry: applicable standard and literature

Hazard group definition: Nomenclature

OEL (Occupational Exposure Limit) mg/m3 8h TWA

Referred to a chemical substance in dry form is an upper limit on the

acceptable concentration of a hazardous substance in workplace air

for a particular material or class of materials

TLV (Threshold Limit Value) ppm or mg/m3 8h TWA

Referred to a chemical substance in gas form, is a level to which it is

believed a worker can be exposed day after day for a working lifetime

without adverse health effects

OEL Example:

Citric Acid OEL 2500 mg/m3 8h TWA

Salbutamol OEL 0.1 mg/m3 8h TWA

TLV Example:

Starch TLV 10’000 mg/m3 8h TWA

Testosterone (ormon) TLV 4 mg/m3 8h TWA

Dexamethone (steroid) TLV 0.02 mg/m3 8h TWA

Hazard group definition: OEL Example….

OEL (Occupational Exposure Limit)

1 mg of lactose in a volume of 1m3

correspondent to…

Empire State Building NY, approx. volume:

1’000’000 m3

N° 2 Casinò dice compared to…

F.P.S. Food and Pharma Systems

Hazard group definition:

Table from: Containment Systems a design guide (IchemE editor)

Containment in the pharmaceutical industry : Occupational Exposure Band (OEB) definition

OEB Range of OEL (µg/m3) Toxicological/Pharmacological

proprieties

OEB 1 > 1.000 Harmful, and/or low

pharmacological activity

OEB 2 100 – 1.000 Harmful, and/or moderate

pharmacological activity

OEB 3 10 - 100 Moderate toxic and/or high

pharmacological activity

OEB 4 1 - 10 Toxic and/or very high

pharmacological activity

OEB 5 < 1 Extremely toxic and/or extremely

high pharmacological activity

F.P.S. Food and Pharma Systems

Containment strategy description:

Strategy 1: Controlled general ventilation

Strategy 2: Local exhaust ventilation

Strategy 3: Local exhaust ventilation with barriers

Strategy 4: Open handling within simple isolator (also flexible) or

high-integrity coupling between closed containers

Strategy 5: Open handling within high containment isolator or

closed handling within isolator

Strategy 1:

CLEAN ROOM installation

Strategy 1 : Controlled

general ventilation

No special engineering requirements; adequate control is achieved by

general ventilation of the process area.

Strategy 2:

Downcross booth LAF booth

Strategy 2 : Local exhaust

ventilation

A Local Exhaust Ventilation (LEV) system is used to contain the

contaminants within a defined area and draw airborne contaminants

away from the operator breathing zone. This can involve either:

• a good point exhaust ventilation

• a unidirectional air-flow booth

This can achieve significant reduction in operator exposures to the

concentration of airborne dusts and vapours generated

Biosafety Cabinet

Strategy 3:

+

Strategy 3 : Local exhaust

ventilation with barriers

A down-cross booth or unidirectional air-flow booth system is used

in combination with an extra barrier to contain the contaminants

within a defined area, this could typically involve:

• Glove tent

• Glove bag with flexible isolators

• Continuous liner systems

Class II Biosafety cabinet for small

Laboratory activities

Strategy 4:

Isolator with cont. liner technology

Split valve with rigid containers

Strategy 4 : Open handling

within isolator

Open transfer or handling of hazardous materials takes place within

an isolator.

Typically this might involve surrounding the transfer operation with

a fixed or flexible air-tight barrier. Containers of process material

may be placed in or removed from the isolator only in a way that

does not compromise the integrity of the containment it provides.

The operator uses glove ports for transfer and cleaning operations.

This containment strategy can also cover transfers effected by high

integrity coupling systems within closed containers.

High-integrity closed

coupling without external

containment

Strategy 5:

+

RTP technology isolators and rescricted access barrier system, “double containment”

Strategy 5 : Closed handling

within isolator

Closed transfer or handling of hazardous materials takes place within

an isolator.

This is similar to previous strategy with exception that open transfer

is not permitted even within the enclosure. The operator using glove

ports attaches the closed container directly to the access port for the

process and then opens the valve to effect the transfer of material.

Extra containment level:

FPS containment strategy selection chart : C

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Low

H

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Containment in the pharmaceutical industry:

Rigid isolators (Design Criteria & Working principle)

Technical Features

Full StainlessSteel construction

following cGMP requirements

FDA approved materials for not

Stainless Steel parts

Configuration for HAPI or Sterile

products activities

Constant negative (positive)

pressure working condition

Transfer system available :

Airlock / RTP / Endless Liner /

Split Valve

Full CIP / SIP available

ATEX configuration

Internal class below to ISO5 /

Class A / Class 100 / Class M3.5

OEL < 0.1μg/m3 8h TWA (OEB5)

Leak test following ISO10648-2

below to class 1 or AGS-2007

with 0.5% of Volume leakrate

Sterility level below to 6log (SAL

10-6) by VHP generator

Containment in the pharmaceutical industry: material inlet pass-box

Containment in the pharmaceutical industry: RTP’s

Containment in the pharmaceutical industry: Split Valves

Containment in the pharmaceutical industry: Continuous liner

Containment in the pharmaceutical industry: transfer system - Hicoflex®

Containment in the pharmaceutical industry: transfer system – Ezi-DockTM

Containment in the pharmaceutical industry: Design phase– project development

Project development

Individuate the requirements and create

3D models of the final design following

provided URS

Ergonomic test with moke up and design

review

Manufacture

FAT and installation

Containment in the pharmaceutical industry: Design phase– ergonomic evaluation & manufacture

Dott. Bonapace tablet press and

capsule filling machine

integration

Containment in the pharmaceutical industry: Flexible containment

FPS flexible containment

Flexible isolator with integrated gloves

Glove Bags for maintenance activities

Glove bag for cleaning activities

Glove bag for process operations

Seal tight zip for safe access

Antistatic materials for flexible media

Taylor made solution to meet specific

requirements

Containment in the pharmaceutical industry: barrier isolators

Stainless Steel isolators for

laboratory activities of:

weighting, IPC, sampling,

dispensing, charging,

discharging, sieving….

Containment in the pharmaceutical industry: integrated system – reactors charging (pilot plant)

Different size and type of pilot

reactors in glass or SS could be

integrated in different way to

respect process step

Containment in the pharmaceutical industry: integrated system – reactors charging (production plant)

Small and large production

reactors could be interfaced with

isolator for safe charging by gravity

or by VTS

Containment in the pharmaceutical industry: integrated system – filter and tray dryers (pilot plant)

Filter and tray dryer for pilot plant

are fully integrated with complete

automation control

Containment in the pharmaceutical industry: integrated system – filter dryers and tray dryers (pilot plant)

ANFD for pilot plant with milling

and dispensing isolator are fully

integrated with complete

automation control

Containment in the pharmaceutical industry: integrated system – filter dryers (production)

ANFD for production plant are fully

integrated with sampling, heel push

product discharging and packing-

off contained system

Containment in the pharmaceutical industry: integrated system – Milling & micronisation (pilot plant)

FPS Multi-milling patform

Cone-mill

Pin-mill

Q-mill

Spiral Jet-mill

Cryo-milling

Containment in the pharmaceutical industry: integrated system – Milling & micronisation (production plant)

Milling & Micronisation production Half suit isolators (8”-12” Jetmills)

Containment in the pharmaceutical industry: integrated system – packaging pilot plant

Weighting chamber

Sieving and multi-

blending chamber

Capsule-filling and capsule-

orienting chamber

Semi-automatic counting

machine

Semi-automatic capping

machine

Dispensing

Pan Coating machine

In Process Control

Containment in the pharmaceutical industry Integrated Systems: Oral Solid Forms processing

Capsule filling machine Overview Tablet press machine

Containment in the pharmaceutical industry Integrated Systems: Oral Solid Forms processing

Capsule filling machine – Internal View

OEB4 Marchesini Blistering machine

OEB5 Marchesini Blistering machine

Containment in the pharmaceutical industry Integrated Systems: Oral Solid Forms processing

Containment in the pharmaceutical industry: integrated system – ISPE SMEPAC Test

Containment performance

verification following ISPE

guideline during FAT and at end

user site from approved third

party

Restricted Access Barrier System – ISPE definition (August 2005)

A Restricted Access Barrier System (RABS) is an advanced aseptic processing system that can be utilized in many applications in a fill-finish area. RABS provides an enclosed

environment to reduce the risk of contamination to product, containers, closures, and product contact surfaces compared to the risks associated with conventional clean

room operations.

F.P.S. Food and Pharma Systems

Isolation and containment systems: R.A.B.S.

40

Integrated air treatment system

Horizontal air flow in the dosing machine area

Vertical air flow on the transportation belt and an horizontal air flow for the docking station

Air recirculation and de-humidifier system

PLC control

F.P.S. Food and Pharma Systems

Isolation and containment systems: R.A.B.S.

41

Active open RABS for dosing machine

F.P.S. Food and Pharma Systems

Isolation and containment systems: R.A.B.S.

42

Upgrading of existing filling lines

Barrier with glove ports where needed

Packing materials introduction devices

Integration with existing filling line control system

Glove tester

Passive open RABS application for filling line

Containment in the pharmaceutical industry Integrated Systems: Glove tester

Automatic / Manual Glove tester:

Efficient

Fast response

Easy to use

Available for different flange size/shape

Thank you very much for you attention !

Stefano Butti

Technical Sales Manager

Mobile: +39 331 6819414

e-mail: butti@foodpharmasystems.com

website: www.foodpharmasystems.com