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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: [email protected]
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.
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: 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: [email protected]
website: www.foodpharmasystems.com