Wednesday 15th November 2006 Design of isolators and glove boxes/codes and design guidance

Emilio Moia

Contents 1. Introduction 2. Development of isolator concept 3. Containment Isolator Standard 4. Containment Isolator Design Criteria 5. Testing 6. Example of isolator

Contents 1. Introduction 2. Development of isolator concept 3. Containment Isolator Standard 4. Containment Isolator Design Criteria 5. Testing 6. Example of isolator

The Isolation continuum

Block flow diagram for development of isolator

Identify operation that require containment

Determine worker Exposure Limit

Review process operation

Select concept for design

Develop concepts for isolators that perform operations

Preliminary design drawing

Build Mock-up

Final Design based on mockup changes

Contents 1. Introduction 2. Development of isolator concept 3. Containment Isolator Standard 4. Containment Isolator Design Criteria 5. Testing 6. Example of isolator

Identification of operation that require containment

Concepts of isolator that perform operations

li ia er at M n

Manipulation

Clea ning

Extraction of material through plastic bag or through the RTP port

Detail of material exhaust

Select concept for design

Raw Material

IBC FILTER DRYER

Substance 3 OEL g/m H-Group Characteristic Quantity Time (Short:< 30') Control Strategy

XXX 1 D polvere >1 Kg ---L M Long CS4

BLENDER

Operation description Filter dryer discharge

Tablet packing

substance 3 OEL g/m H-Group characteristic quanity time (Short:< 30') Control Strategy

IBC
XXX 1 D polvere >1 Kg ---L M Long CS 3 CS 3

IBC

Operation description

Tabletting

10

Select concept for design

Raw Material

IBC FILTER DRYER

BLENDER

Tablet packing Containment Isolator with RP

IBC
11

IBC

RABS

Isolator for dispensing: U.R.

Exhaust fan Single push push filter with flap Double push push filter with flap Full size door always open during production

Chamber

Battery Limits Door

Battery Limits Interlocked doors Weighing scale BIN BIN lift Tapped ZA NCHETTA density ISO valve Thermo- tester balance Particle size for LOD distribution testing equipment

12

Isolator for dispensing: U.R.

Interlocked doors Electrical supply for weighing scale Electrical supply and print signal for thermo-balance for LOD testing Full size door always open during production Electrical supply for tapped density tester Electrical supply for particle size distribution equipment Door

Pre.chamber

Waste continuous film bagging and sealing system Hot water Cold water Battery Limits Distribution piping for hot/cold water to spray guns Weighing scale Connection for hot/cold water supply to spray guns Connection to BIN Thermobalance for LOD testing Tapped density tester Particle size distribution equipment

Chamber

13

Isolator Design Cycle

T R SE MEN U E IR QU RE

Mock-up Testing Detail Design

Preliminary Design

Isolator design cycle

FAT & SAT IQ & OQ

Realization & installation

14

Contents 1. Introduction 2. Development of isolator concept 3. Containment Isolator Standard 4. Containment Isolator Design Criteria 5. Testing 6. Example of isolator

15

Containment Isolator Standard

ISO 14644-7: Separative devices (clean air hoods, gloveboxes, isolators and minienvironments) ISO 10648-1, Containment enclosures Part 1: Design principles ISO 10648-2, Containment enclosures Part 2: Classification according to leak tightness and associated checking method AGS-G001-1998

EN 12469, Biotechnology Performance criteria for microbiological safety cabinets

16

ISO 14644-7
1 Scope 2 Normative references 3 Terms and definitions 4 Specification of requirements 5 Design and construction 6 Access Devices 7 Transfer Devices 8 Siting and Installing 9 Testing and Approval Annex A (informative) Separation continuum concept Annex B (informative) Air handling and gas systems Annex C (informative) Access devices Annex D (informative) Transfer device examples Annex E (informative) Leak testing Annex F (informative) Parjo leak test method Bibliography

17

ISO 14644-7: Terms and Definitions

access device: device for manipulation of processes, tools or products within the

separative device action level:level set by the user in the context of controlled environments, when exceeded immediate follow-up is required as well as investigation with subsequent corrective action alert level :level set by the user for controlled environments giving early warning of a potential drift from normal conditions, when exceeded an investigation is required to ensure that the process and environment are under control. breach velocity :velocity through an aperture sufficient to prevent movement of matter in the opposite direction to the flow containment :state achieved by separative devices with high degree of separation between operator and operation leak (of separative devices) :defect revealed by testing under a pressure differential after corrections for atmospheric conditions pressure integrity :capability to provide a quantifiable pressure leakage rate repeatable under test conditions separative device :equipment utilizing constructional and dynamic means to create assured levels of separation between the inside and outside of a defined volume

18

ISO 14644-7: Requirements

The following information shall be defined, agreed and documented between customer and supplier: reliability and availability; when appropriate, any applicable hazard analysis if devices depend on differential pressure, the differential pressure shall be continuously monitored and alarmed in some applications; where appropriate, a specified hourly leak rate (for an example of methodology, see Annex E); other operational parameters, including 1) test points,2) alert and action levels to be measured to ensure compliance,3) test methods; required methods of measurement, sample locations, control, monitoring and documentation; mode of entry or exit of separative devices and related equipment, apparatus, supplies and personnel into the controlled environment required during 1) installation, 2) commissioning, 3) operation, 4) maintenance;

19

ISO 14644-7: Requirements

layout and configuration of the installation; critical dimensions and mass restrictions, including those related to available space; process requirements that affect the installation; installation process equipment list with utility requirements; requirements maintenance requirements of the installation; responsibilities for the preparation, approval, execution, supervision, documentation, statement of criteria, basis of design, construction, testing, training, commissioning and qualification, including performance, witnessing, and reporting of tests; identification and assessment of external environmental influences; es compliance with local regulations.

20

ISO 14644-7: Design and Construction

Separative-device design shall provide the process, the operator or third party with protection against contamination appropriate to the operation being performed. Consideration shall be given to malfunction, procedures and ancillary systems involved with the separative-device application (see Annex B). Consideration shall be given to access devices and transfer devices (see Annexes C and D). Separative devices shall be ergonomically designed for easy access to all internal surfaces and work: areas, and with respect to the process undertaken. Access devices shall be of the minimum size and number consistent with operation, cleaning and maintenance. Consideration shall be given to differential operating pressure, including excursions. excursions External influences, such as air flow, vibration and pressure differences, shall be flow considered to avoid adverse effects on integrity and function. Provision for cleaning or decontamination, including possible disposal of the device or its components, shall form part of the design criteria.

21

ISO 14644-7: Design and Construction

Built-in test facilities and appropriate alarms shall be included. Transfer device(s) shall be appropriate to process and routine operation. Filtration shall be appropriate for application. application Whenever possible, items requiring maintenance shall be external to the separative device. Materials used in the construction of separative devices, including sealing materials, fans, ventilation systems, piping and associated fittings, shall be chemically and mechanically compatible with the intended processes, process materials, application processes and decontamination methods. Protection against corrosion and degradation during prolonged use shall be considered. Heat and fire resistant construction materials shall be considered when appropriate (see Annex B). Where appropriate, materials used shall be checked for thermal characteristics, sorption and out gassing properties. Materials selected for viewing panels shall be tested and proven to remain transparent and resistant to changes that would prevent clear visibility.

22

ISO 14644-7 Access Devices

Gauntlets, glove systems, half-suits When using gauntlets, glove systems and half-suits, these types of flexible-membrane access device systems shall be designed and constructed to allow for glove change without breaching the separative device (see Annex C). These systems are unlikely to maintain molecular containment, therefore alternative systems should be considered for applications requiring molecular containment. Glove ports and glove cuff rings devices shall be designed for ease of change, integrity change testing and security of operation. The following selection criteria shall be considered in choosing gauntlet, glove sleeve and halfsuit system materials that are vital in maintaining separation: a) materials and tools to be handled within the separative device; b) temperature limitations of the glove materials; c) acceptable permeability; d) chemical resistance or mechanical strength, or both; e) sorption and desorption of chemicals; f) known shelf and service lives of glove material; g) differential pressures, including transient excursions (operating and abnormal pressures); h) operations to be performed.
23

ISO 14644-7 Access Devices Glove Material

a) Latex, natural rubber or cis-1,4-polyisoprene
Latex, natural rubber or cis-1,4-polyisoprene is suitable in cases where great flexibility and good mechanical properties are necessary. However, latex articles are not impermeable to gas, perish in ozone, offer no resistance to flame, hydrocarbons and oxidising salts and poor resistance to esters, acids and bases. The potential of life-threatening allergic reactions should be considered. b) Polychloroprene or 2-chloro-1,3-butadiene Polychloroprene or 2-chloro-1,3-butadiene is especially recommended when good resistance to oils and greases is needed. This chloroprene is self extinguishing, i.e. when the source of ignition is removed it no longer continues to burn. Polychloroprene is highly resistant to ozone, ultraviolet light, concentrated acids and bases, and strong oxidising agents. Polychloroprene articles are unsuitable for work with hydrocarbons, halogens and esters. c) Nitrile or copolymer of butadiene and acrylonitrile Nitrile or copolymer of butadiene and acrylonitrile is recommended when good resistance to solvents is required. Nitrile articles stand up well to aliphatic hydrocarbons and hydroxyl compounds. d) Polyvinyl chloride Although plastic, polyvinyl chloride has a certain elasticity and is recommended for its good electrical properties and resistance to chemical agents. e) Chlorosulfonated polyethylene Chlorosulfonated polyethylene offers very good resistance to H2O2, and its white colour allows good visual inspection. Other materials are resistant to H2O2, as well.

24

ISO 14644-7 Transfer Devices

Transfer devices Use :Transfer devices shall not diminish the performance of separative devices. In
specific applications, transfer devices become critical in maintaining integrity of the device or process. Some transfer devices are used as independent separative devices. Selection :Selection of a transfer device shall be based on the level of separation required by the application. The hourly leak rate of the transfer device shall not be greater than the hourly leak rate of the separative device which the transfer device serves. Transfer devices shall minimize the transfer of unwanted matter. Outline diagrams and descriptions of possible types of transfer device are included in Annex D. These diagrams are only illustrative examples of possible configurations. Fail-safe design :In the event of power failure, transfer devices that have electrical interlocking mechanisms shall prevent access via the transfer device. vice

25

ISO 14644-7 Testing and Approval

Glove breach test:
When appropriate, the airflow through one open glove port shall be measured by placing an anemometer at the centre of the glove port. The velocity shall be agreed between customer and supplier (guidance value: 0,5 m/s).

Leak testing
When appropriate, a leak test shall be performed. Guidance is given in Annexes E and F. NOTE Integrity testing on some separative devices that operate close to atmosphere pressure (less than 1 000 Pa) requires detailed procedures and sensitive test equipment to establish a quantifiable leak rate. The resulting leak determines acceptability for the intended application (see Annex A). When appropriate, an induction leak test shall be performed. Guidance is given in Annex E. NOTE Induction leaks can occur when the velocity across an orifice creates a pressure depression and induces a reverse flow through the orifice (Venturi effect). Devices that operate at low differential pressures may be compromised by induction leakage. Similarly, devices that utilise over pressure or flow to minimise or prevent the transfer of unwanted matter may be at risk from induction leakage when operating under transient volume changes such as glove entry or withdrawal.

26

ISO 14644-7 Testing and Approval

Periodic testing
The tests and checks are a function of the application and instrumentation/detection systems. Routine tests shall be established and recorded for comparison preventative maintenance requirements. The following recommendations for testing are given: a) half-suit/glove testing 1) on commissioning, 2) prior to and after completion of work, 3) after glove/glove sleeve changes; b) pressure testing 1) on commissioning, 2) after any airflow or filter-pressure parameter changes, 3) after maintenance affecting the separative device envelope or pressure control devices; c) induction testing on commissioning; d) instrumentation and alarm system testing 1) on commissioning, 2) after maintenance affecting the control system, 3) at the frequency dictated by the instrumentation manufacturer, 4) at predetermined periods consistent with use and operational requirements.

27

ISO 14644-7 Annex D

A1 transfer device
When operated in accordance with a validated transfer procedure, air can flow freely through the A1 transfer device (see Figure D.1) between the background environment and the separative-device environment when the door is open. EXAMPLES Doors, access panels, zips, hook and loop tape, poppers and jam pot covers, bag-in-bag-out.

1 separative-device environment 2 background environment 3 ingress 4 egress 5 sealed door 6 work surface of controlled workspace Figure D.1 A1 transfer device

28

ISO 14644-7 Annex D

A2 transfer device
When operated in accordance with a validated transfer procedure in a dynamic state, air flows freely through the A2 transfer device (see Figure D.2) out of the separative device environment. EXAMPLES Dynamic holes, mouse holes.

1 separative-device environment 2 background environment 3 ingress 4 egress 5 airflow 6 work surface of controlled workspace Figure D.2 A2 transfer device

29

ISO 14644-7 Annex D

D.4 B1 transfer device
The B1 transfer device (see Figure D.3), when operated in accordance with a correct sequence or interlocked transfer procedure, does not permit the direct passage of air between the background environment and separative-device environment. However, air from the background environment can be trapped and then released into the separative-device environment, and air from the separative-device environment can be trapped and released into the background environment. EXAMPLES Double-door sealed transfer chambers, bagging ports, telescopic waste ports and simple docking devices.

1 separative-device environment 2 background environment 3 ingress 4 egress 5 sealed door 6 work surface of controlled workspace

Figure D.3 B1 transfer device

30

ISO 14644-7 Annex D

D.5 B2 transfer device The B2 transfer device (see Figure D.4) has double sealed doors and facilities that permit the purging and evacuation of the transfer device to ensure compatibility of environments before breaching the interconnection to the separative-device environment. Evacuation gases require safe disposal. NOTE Evacuation may not be possible with liquid transfer, depending on the liquid boiling point/pressure relationship. 1 separative-device environment 2 background environment 3 ingress 4 egress 5 sealed door 6 work surface of controlled workspace 7 valve Figure D.4 B2 transfer device

31

ISO 14644-7 Annex D

D.6 C1 transfer device The C1 transfer device (see Figure D.5) has doors and HEPA filters which, when used in a positivepressure separative device and operated in the correct sequence, do not allow unfiltered air from the background environment to reach the separative-device environment but which may allow unfiltered air from the separative-device environment to reach the background environment. Such transfer devices are not suitable for negative-pressure separative devices because unfiltered air from the background environment would be allowed to reach the separative-device environment. C1 transfer devices are not recommended where operator and third-party protection is required in positivepressure separative devices. EXAMPLE Single-filtered transfer chambers. 1 separative-device environment 2 airflow 3 background environment 4 HEPA filter 5 positive pressure 6 ingress 7 egress 8 sealed door 9 work surface of controlled workspace Figure D.5 C1 transfer device
32

ISO 14644-7 Annex D

D.7 C2 transfer device The C2 transfer device (see Figure D.6) has doors and HEPA filters which, when used in a negative-pressure separative device and operated in the correct sequence or interlocked transfer procedure, do not allow unfiltered air from the background environment to reach the separativedevice environment (such air passes straight into the space below the work surface of the separative-device environment and then exits through an exhaust) or unfiltered air from the separative-device environment to reach the background environment with the separative device in an operational state. Such transfer devices are not appropriate for use with a positivepressure separative device. EXAMPLE Single-filtered transfer chambers. 1 separative-device environment 2 airflow 3 background environment 4 HEPA filter 5 negative pressure 6 ingress 7 egress 8 sealed door 9 work surface in controlled workspace 10 exhaust Figure D.6 C2 transfer device
33

ISO 14644-7 Annex D

D.8 D1 transfer device The D1 transfer device (see Figure D.7) has doors and HEPA filters which, when operated in the correct sequence or interlocked transfer procedure, do not permit unfiltered air from the background environment to reach the separative-device environment or unfiltered air from the separative-device environment to reach the background environment. EXAMPLES Double-filter transfer chambers, or separative devices used as a transfer device. 1 separative device environment 2 valve 3 background environment 4 HEPA filter 5 ingress 6 egress 7 sealed door 8 work surface of controlled workspace Figure D.7 D1 transfer device

34

ISO 14644-7 Annex D

D.10 E transfer device The E transfer device (see Figure D.8) is subject to sanitation together with its contents, if any, before being opened into other areas which have been subject to sanitation. EXAMPLES Gassable/autoclavable transfer devices, including certain transfer separative devices and docking devices, permanently connected autoclaves and similar devices.

1 separative-device environment 2 three-way valve 3 quick-connect coupling 4 background environment 5 HEPA filter 6 ingress 7 egress 8 sealed door 9 work surface of controlled workspace Figure D.8 E transfer device
35

ISO 14644-7 Annex D

D.11 F transfer device The F transfer device (see Figure D.9) docks and seals onto a separative device. The transfer device is commonly used as a transport container. Some devices may have disconnects for air bleed. EXAMPLES Rapid transfer systems, standard mechanical interfaces, and split valve connections.

1 separative-device environment 2 background environment 3 quick-connect coupling 4 double interlocked doors or valves 5 work surface or controlled workspace Figure D.9 F transfer device

36

ISO 14644-7 Leak Detection

E.3.1.6 Classification The classification of separative devices according to hourly leakage rate is shown in Table E.1.
Table .1 Classification of separative devices and appropriate test methods Class Hourly Leak Rate Tf h-1 5 x 10 -4 < 2,5 x 10 -3 < 10-2 <10-1 Pressure Integrity Test Methods

1 2 3 4

High Medium Low

Oxygen method, pressure change method or Parjo method Oxygen method, pressure change method or Parjo method Oxygen method, pressure change method or constant pressure method Constant pressure method

NOTES 1 The classification and specified test methods in ISO 10648-2 were combined with pressure integrity levels to allow comparison to the separation continuum in annex A. 2 Parjo method was included where appropriate. 3 ISO 10648-2 test methods are for negative pressure separative devices and can be modified for positive pressure separative devices with the exception of the oxygen method.

37

AGS-G001-1998
Example of single-sided glovebox with gloveports through window

38

AGS-G001-1998
Example of double-sided glovebox with gloveports through window

39

AGS-G001-1998
Detail of glove port attachment, glove port and working plane elevation

40

ISO 10648-1: Dimension

41

ISO 10648-1: Dimension

42

Access Device: Glove System

Glove port and glove cuff rings shall be designed for easy change #6

43

ISO 14644-7 & AGS-G001-1998

Description

ISO 14644-7
The velocity should be agreed between customer and supplier (guidance value: 0,5 m/s).

ASG-G001-1998
V= 125 25 ft/min For some facility v= 150 ft/min

Air velocity into open port

Glove box negative pressure Class1 : Tf 5 x 10 -4 Class 2: Tf < 2,5 x 10 -3 Class 3: Tf < 10-2 Class 4: Tf <10-1 Tf=(60/T)*(P2T1/ P1T2-1)

- 0,5 < pressure < -1,5 inches

Leak rate

Leak rate < 0,5% of the glove box volume % of box volume =Q/V Q/V=(60/T)*(P2T1/ P1T2-1)

44

Contents 1. Introduction 2. Development of isolator concept 3. Containment Isolator Standard 4. Containment Isolator Design Criteria 5. Testing 6. Example of isolator

45

Isolator for dispensing: Detail design and Mock-up

Ergonomic Study for easy access #5

46

Isolator for dispensing: P&ID

GLOVE PORT
3072001
TO EXHAUST HVAC PLAN 1) CONNECTION FOR SPRAY GUN 2) CONNECTION FOR SPRAY BALL 3) CONNECTION FOR WASTE DRAIN 4) CONNECTION FOR ELECTRICAL SUPPLY (85 m3/h) 5) CONNECTION FOR LINE DRAIN 6) FLEXIBLE FLOOR SECTION FOR WEIGH-SCALE 7) CONNECTION FOR CLEANING VACUUM

NOTES

167

AREA PORT= 0.033 m2

Air-break: identification of external influences #4

INV-0110
INVERTER -

DWG N

250

GLOVE BREACH TEST GUIDANCE VALUE: 0,7 m/s

CLIENT
THIMBLE DIAM. 200 mm

STERIL

Q = 0.033x0.7x3600 = 83.16 m3/h

BATTERY LIMIT

DN80

0110

DN80
DPI DPI 0105

(0.3 m3/h) CLEANING WATER

DPT

DN20 DN20

SLOPE

0103

VME-1005

PUSH-PUSH

0110 DPI

PUSH-PUSH

DN20

SLOPE

DN20 (NOTE 5)
DPI

VME-1001

DPI 0101

VME-1002
DN20
DPI 0102

F-0103 F-0102 L-1002

0110

VME-1003
DN20
DPI 0104

F-0105 F-0104 L-1003

LIGHTING

VME-1004
DN20

0106

VFA-1002 F-0106
CANISTER BAG-IN BAG-OUT

VFA-1001
DN80 CANISTER BAG-IN BAG-OUT

LIGHTING

LIGHTING (NOTE 1) DN50 (NOTE 2) DN20

L-1001
(NOTE 2) DN20

(NOTE 1) DN50
DIV ID

CAB-1002 CAB-1001 D-1003

D10
DO

D1

SE CT

OR

d. 4/6mm

F-0101

W-1001

W-1002

IN

W-1003

(NOTE 2) DN20

00

NEGATIVE PRESSURE -75 Pa (NOTE 7) DN25

01

D1

00

OR

G-1001

G-1002

DO OR

G-1003
(NOTE 4)

G-1004

G-1005
(NOTE 4)

G-1006

G-1007

(NOTE 4)

Pre-chamber @ -45 Pa Main Chamber @ - 75 Pa Consideration shall be given to differential operating pressure, including excursions : #5
TO SERVICES INSTRUM COMPR AIR (TYPICALS 1)

G-1008

CB-0101

CONTROL BOARD

(NOTE 6)

SLOPE
DN50

SLOPE

SLOPE

SLOPE

DN32

ZSL 0101

XY 0101

(NOTE 3) (SEE TYP 1)

ZSL 0102

XY 0102

(SEE TYP 1)

VFA-1003

ZSL 0103

XY 0103

ZANCHETTA ISO VALVE (SEE TYP 1)

LOCAL PRESSURE +/- 0 Pa

I I I I

PLC

PLC

PLC

PLC

PLC

PLC
D C 08.02.05 10.01.05 08.11.04 08.10.04
DATE

AS BUILT UPDATED ACCORDING TO CONSTRUCTION UPDATED AFTER CLIENT VISIT ON 18.10.04 AND 28.10.04 FIRST ISSUE
DESCRIPTION

COMPRESS AIR

(5-7 bar)

DP: continuous monitoring and Alarm #4

ELECTRICAL SUPPLY 400V 3PH+N+PE 1 Kw

DPA

DN80

Transfer Device: Mode of entry/exit #4

FAN-1001
PLC H

DF DF DF DF
BY

SC SC SC SC
CHD

PB PB PB PB
APP.

TYPICAL 1
PLC
I

KY TO ATMOSPHERE
S

COMPRESS AIR (5-7 bar)

XY

Interlocking system that prevent access via transfer device in the event of power failure #7

B A
LETTER

REVISIONS
APPROVED FOR CONSTRUCTION

DISPENSING ISOLATOR IS-1500 P&ID

cod.=
THIS DRAWINGIS THE PROPERTY OF STERILANDIS LENT WITHOUT CONSIDERATION OTHERTHANTHE BORROWER'S AGREEMENT THAT IT SHALLNOT BE REPRODUCED COPIED LENT OR DISPOSEDOF DIRECTLY ORINDIRECTLY , NORUSEDFORANY PURPOSE OTHER THAN THAT FOR WHICH IT IS SPECIFICALLY FURNISHED. THE APPARATUS SHOWNINTHE DRAWINGIS COVEREDBY PATENTS .

DWG. REV. SIGNATURE

DATE

NOT SPECIFIED TOLLERANCE : rif. SP.TEC. TOLL-001 PAINTING: rif. SP.TEC. PAINT-001 THIS DWG.SUPERSEDED BY THIS DWG. SUPERSEDES DWG. N REV. SCALE

3072001

47

Isolator for dispensing: Equipment Lay-out

NOTES
1) CONNECTION FOR SPRAY GUN

3072.000

2) CONNECTION FOR SPRAY BALL

PLANT
EXHAUST FAN DOUBLE PUSH-PUSH FILTER WALL STABILITY SUPPORT 600

3) CONNECTION FOR WASTE DRAIN 4) CONNECTION FOR ELECTRICAL SUPPLY 5) CONNECTION FOR LINE DRAIN

DWG N

Operational ergonomics: glove port position # 8

CONNECTION FOR HOT WATER VALVE DN15 VALVE DN15 (NOTE 5)

6) FLEXIBLE FLOOR SECTION FOR WEIGH-SCALE

FLAP DN80

LIGHTING

LIGHTING

LIGHTING

VALVE DN20

VALVE DN20

VALVE DN20

(NOTE 1, 2)

(NOTE 1, 2)

(NOTE 1, 2)

maintenance requirements of the installation #4

7) CONNECTION FOR CLEANING VACUUM

220

310

220

245

380

380

220

220

280

280

220

CANISTER FILTER BAG-IN/BAG-OUT

OVAL GLOVE PORT

A
4590 DOUBLE PUSH-PUSH FILTER EXHAUST FAN 470 600 DOUBLE PUSH-PUSH FILTER EXHAUST FAN 1250 1000 220 575 750 2250 DOUBLE PUSH-PUSH FILTER 575 220 400 MINIMUN FOR MAINTENANCE

600

470

DIVIDING SECTOR OPEN DIVIDING SECTOR CLOSE

WALL STABILITY SUPPORT VALVE DN20 VALVE DN15 LIGHTING

OPERATOR CONTROL PANEL

WALL STABILITY SUPPORT VALVE DN20

OPERATOR CONTROL PANEL

LIGHTING FLAP DN80

SLOPE

CONNECTION FOR SPRY BALL CANISTER FILTER BAG-IN/BAG-OUT (NOTE 5) FLAP DN80

Alarms
VALVE DN20 FLAP DN80 WALL FAN SUPPORT WALL STABILITY SUPPORT 80 350

(NOTE 1, 2) 350 80 CONNECTION FOR SPRY GUN OVAL GLOVE PORT

(NOTE 1, 2) CONNECTION FOR SPRY GUN

SLOPE

600

INTERLOCKED DOOR DIM. HOLE D.280mm

(NOTE 7)

450

280

1000

CANISTER FILTER BAGIN-BAGOUT 493 WASTE MATERIAL SY STEM 300 INTERLOCKED DOOR DIM. HOLE 350x450mm REMOVABLE COARSE GRID 5mm 1780 340 380 (NOTE 4) 150 650 400
T ENSI O NE EQ UI PM ENT AL L ARM E ACUST I CO AL L ARM E VI SI VO O FF O N CO M ANDO O FF L UCE CABI NA O N RESET PRO G RAM M A PRESENZ A T ENSI O NE

250

167

CAMERA CAB- 1 0 0 2 NTERRUTTORE GENERAL E I

(NOTE 4)

250

SLOPE

SLOPE

SLOPE

SLOPE

750

200

594

INTERLOCKED DOOR DIM. HOLE 350x450mm

200 (NOTE 3) REMOVABLE COARSE GRID 5mm 350 327 CONNECTION TO BIN ZANCHETTA ISOVALVE
FIL TROEXP F- 0 1 0 2 FIL TROEXP F- 0 1 0 4 FIL TROCANIS TERF- 0 1 0 1

ELETTRICAL BOX STAINLESS STEEL

3379

1350

327

1100

BUTTERFLY VALVE CLAMP 1 1/2 "

FLEXIBLE FLOOR SECTION FOR WEIGH-SCALE INDEPENDENT SUPPORT FOR WEIGH-SCALE SLIDING TABLE FOR DISLAY WEIGHING SCALE

450

780

ELECTRIC DEVICE FOR ISOVALVE (BY ZANCHETTA) TO BE FIXED ON ISOLATOR SLIDING TABLE FOR DISPLAY WEIGHING SCALE

857

3379

80

201

250

FIL TROEXP F- 0 1 0 3

FIL TROEXP F- 0 1 0 5

FIL TROCANIS TERF- 0 1 0 6

450

150

250

150

200

600

630

SUPPORT TO BE FIXED ON THE FLOOR

1884

FLOOR

SECTION A-A

Access devices shall be of the minimum size and number consistent with operation, cleaning and maintenance #4
1350 PLATFORM (BY OTHERS) BIN ZANCHETTA 1700 900 1200

BIN ZANCHETTA 1350

1834

1884

PLATFORM (BY OTHERS)

1027

SUPPORT TO BE FIXED ON THE FLOOR

LIFTING TABLE

Balance with independent support: process requirements that affect the installation #4
200

FLOOR

900

FRONT VIEW

LIFTING TABLE

1450

ELECTRIC DEVICE FOR ISOVALVE (BY ZANCHETTA) TO BE FIXED ON ISOLATOR

750

2250

LIFTING TABLE

600

320

WASTE MATERIAL SY STEM

45 BIN ZANCHETTA 594

Process equipment list with utility requirements (piping connection, electrical sockest, bin charging.. ) #4
627 653 600 300 PARTICLE SIZE DISTRIBUTION EQUIPMENT DIM. 300x350 h750 TAPPED DENSITY TESTER DIM. 330x450 h700 ELETTRICAL BOX STAINLESS STEEL

FLOOR

SIDE VIEW
576

INTERLOCKED DOOR DIM. HOLE D.280mm INTERLOCKED DOOR DIM. HOLE 350x450mm INTERLOCKED DOOR DIM. HOLE 350x450mm WEIGHING SCALE DIM. 350x350 h150 (NOTE 3)

DIVIDING SECTOR OPEN

200

F
30 0

08-02-05 19-11-04 02-11-04 26-10-04 12-10-04 08-10-04 DATE

AS BUILT ISSUED FOR CONSTRUCTION ISSUED FOR APPOVAL - WHITH CLIENT COMMENT ON 28.10.04 UPDATED AFTER CLIENT VISIT ON 18.10.04 CHANGING SUPPORT TYPE FIRST ISSUE DESCRIPTION

DF DF DF DF DF DF BY

SC SC SC SC SC SC CHD

PB PB PB PB PB PB APP.

630

E D C B A LETTER

DIVIDING SECTOR CLOSE (NOTE 6)

REVISIONS
APPROVED FOR CONSTRUCTION

VIEW H2300
SLIDING SUPPORT FOR VISUAL WEIGHING SCALE DISPLAY WEIGHING SCALE DIM. 345x190 h145

1040

DISPENSING ISOLATOR IS-1500 ASSEMBLY OVERALL DIMENSION

cod.=

DWG. REV. SIGNATURE

DATE

NOT SPECIFIED T OLLERANCE : rif. SP.TEC. TOLL-001 PAINT ING:

SI131530720
THIS DRAWING IS THE PROPERTY OF STERILAND IS LENT WITHOUT CONSIDERATION OTHER THAN THE BORROWER 'S AGREEMENT THAT IT SHALLNOT BE REPRODUCED COPIED LENT OR DISPOSED OF DIRECTLY OR INDIRECTLY , NOR USED FOR ANY PURPOSE OTHER THAN THAT FOR WHICH IT IS SPECIFICALLY FURNISHED. THE APPARATUS SHOWN IN THE DRAWING IS COVERED BY PATENTS .

rif. SP.TEC. PAINT-001 THIS DWG.SUPERSEDED BY THIS DWG. SUPERSEDES DWG. N SCALE 1:10 REV.

3072.000

48

Isolator for Compounding: Equipment lay-ou

2300 2240 CARTER 1000 CARTER COPRI CAVI
FI LTR O E X P F- 0104 FI LTR O E X P F- 0102

1240

3080.000

FI LTR O E X P F- 0103

FI LTR O E X P F- 0101

1"1/2 T.C. 1" T.C.

DWG N

SPRY BALL

2" T.C.
CARTER 900 600 260 LAMPADA LAMPADA

1/2" T.C.

1/2" T.C. 1" T.C. 1"1/2 T.C.

220

460

460

460

460

240

AIR INLET

1" T.C.
CB-0102 VANO TECNICO CONTROSOFFITTO 60

CARTER

1500

I N TE R R U TTO R E G E N E R A LE

1/4" G 1/4" G
VENTILATORE 300 240 460 460 460 460 220

CB-0101 QUADRO ELETTRICO dim.450x600x300 300

VISTA ALTO SX
HOUSING PUSH-PUSH FILTER 1240

TERMINALE OPERATORE CONNECTION FOR ELECTRICAL SUPPLY (FORO D.22mm)

60

80

60

60

3/4" T.C.

60

60

60

VISTA RETRO
656.4

250

2240 CARTER 1000

DX

600

CONTROSOFFITTO PEDONABILE

+3000
CB-0102 SPRY BALL CARTER CB-0102 322 DISLAY PH-METRO dim. HOLD DISLAY BILANCIA dim. HOLD
AL L ARME ACUSTICO AL L ARME VIS V O I

C A B I N A D I S P E N S I N G I S - 1400

2" T.C.
TENSIONE EQUIP MENT OFF ON COMANDOL UCE CABINA OFF ON RESET PROGRAMMA

495

P R E S E N ZA TE N S I O N E

10%% d

I N TE R R U TTO R E G E N E R A LE

250

339

167

GOLFARE CARTER COPRI CAVI

TERMINALE OPERATORE

1" T.C.

VISIVA FRONTALE APRIBILE CON VETRI STRATIFICATI DI SICUREZZA FILTER AIR DISPOSABLE

240

460

460

460

220

1/2" T.C. 1" T.C. 1"1/2 T.C.

RTP PORT DPTE-S 270 (FORO D.350mm)

770

339

250

167

3/4" T.C.
2239

MIN 1900 MAX 2000

RTP PORT 2076 DPTE-S 270

3/4" T.C. 1/2" T.C. 3/4" T.C.

770

RTP PORT DPTE-S 270

3/4" T.C.
CONNECTION FOR SPRY GUN

SCARICO

R-911
TANK 1350 300 1300

1"1/2 T.C.
1350 STAFFA DI SUPPORTO CELLE DI CARICO TANK 1300 STAFFA DI SUPPORTO CELLE DI CARICO

1116

974

1116

SEZIONE FLESSIBILE

R-911

250

450

974

250

200

CORRIPIEDE

CORRIPIEDE

PEDANA

Transfer device VISTA LATO DX appropriate for operation #5

840 715 650 540 50

+924

2273

SX

VISTA FRONTE
CONNECTION FOR ELECTRICAL SUPPLY (FORO D.22mm) 1050 250 1250 450

DX

Vessel supported on weighing device: ProcessVISTA LATO SX requirements #4

900

132

CARTER COPRI CAVI

CONNECTION FOR COMPRESS AIR

250

56

1" T.C. 1"1/2 T.C.

MANICOTTO RTP PORT DPTE-S 270 (FORO D.350mm)

450

1/2" T.C.

1/4" G 1/4" G 1/4" G

MIN.

18.02.05 26.01.05
DATE

EMESSO PER APPROVAZIONE

D.F.

S.C.

1790

P.B.

A
LETTER
900

EMESSO PER COMMENTI

DESCRIPTION

D.F.
BY

S.C.
CHD

P.B.
APP.

1/2" T.C. 3/4" T.C.

PH-METRO dim.230x390 h100

REVISIONS
APPROVED FOR CONSTRUCTION

3/4" T.C.
SPRY GUN

1/4" G
576 BAGNO TERMOSTATICO dim.240X330 h220 CORPO BILANCIA dim.120x330 h110

256

50

3/4" T.C.
126

1/2" T.C.
140

RTP PORT DPTE-S 270

DISPENSING COMPOUNDING REPARTO SCHF - GSK (PARMA)

450

DWG. REV. SIGNATURE

DATE

3/4" T.C.
SPRY GUN

ISOLATORE IS-1400-DF DIMENSIONI D'INGOMBRO

cod.= SI131430802
THIS DRAWINGIS THE PROPERTY OF STERILANDIS LENT WITHOUT CONSIDERATION OTHERTHANTHE BORROWER'S AGREEMENT THAT IT SHALLNOT BE REPRODUCED COPIED LENT OR DISPOSEDOF DIRECTLY ORINDIRECTLY , NORUSEDFORANY PURPOSE OTHER THAN THAT FOR WHICH IT IS SPECIFICALLY FURNISHED. THE APPARATUS SHOWNINTHE DRAWINGIS COVEREDBY PATENTS .

NOT SPECIFIED TOLLERANCE : ref. TEC.SP. TOLL-001 PAINTING: ref. TEC.SP. PAINT-001 THIS DWG.SUPERSEDED BY SCALE 1:10

200 465 540 900 50 50 125 CONNECTION FOR COMPRESS AIR

300

3/4" T.C.
1400 SPRY GUN 900

THIS DWG. SUPERSEDES DWG. N

VISTA LATO DX

VISTA H=1200

REV.

3080.000

CARTER

322

49

Types of Containment Isolator

Variable Airflow rate: N2 inertization system Supply cartridge filter Push-Push exhaust hepa filter Variable Airflow rate: Supply cartridge filter Push-Push exhaust hepa filter Constant Airflow rate: Supply Bag-in/Bag-out Hepa filter Push-Push exhaust hepa filter

N2

CA 18 v/h 2 v/h

P P
P PDT

I
P P P PDT

I
P P

I
P P PDT

I
Kg10g

50

Variable exhaust airflow: reaction to glove break

Pressure / Velocity

Glove break

Dp= -75 Pa

breach velocity =0,7 m/s

Dp= 0 Pa Time ~ 30 seconds

51

Constant exhaust airflow: reaction to glove break

Pressure / Velocity

Glove break

Dp= -75 Pa

breach velocity =0,7 m/s

Dp= 0 Pa Time (min)

Instantaneous

52

Contents 1. Introduction 2. Development of isolator concept 3. Containment Isolator Standard 4. Containment Isolator Design Criteria 5. Testing 6. Example of isolator

53

Isolator testing
Forms List Form 1 Form 2 Form 3 Form 4 Form 5 Form 6 Form 7 Form 8 Form 9 Description Push-Push Integrity Test Isolator Leak Pressure test Pressure Gauges Control Response Time To glove break Smoke Test Light Intensity Test Noise Pressure Level Alarms Operator Panel Check

54

Example: Response Time To glove break

Test description - Record the test instrument Manufacturer, Model, serial/number, calibration Date and due Date. - During the normal isolator working, remove a glove and measure the time to reach a minimum velocity value of 0.7 m/s in the center of the glove port. The time should be less than 30 s. - Once the airflow is stable, record the air velocity in the center of the glove port. - Record the value on the following table. - Verify also the alarms turn on and that the instruments work correctly. (see Form N.11 Alarms)

Acceptance Criteria

- Minimum air velocity value 0.7m/s in the glove port center (CIRCULAR d=167 mm) - Response time < 30 sec Anemometer DESCRIPTION ITEM RESPONSE TIME sec FINAL VELOCITY m/s NOTE

Test instrument Result

Working Chamber Attachments Test Result is acceptable Notes / Deviation N

YES

NO

55

Control System and Alarms

Control System and Alarms

Negative pressure value control by means of PLC regulation of the revolution velocity of the motor blower. The control system modifies the motorfan speed in such way to maintain the set pressure value (-75 Pa) inside the working chamber.. Alarm device optical (red signal light visible from working position) and acoustic (buzzer) type, activated with indication of type of alarm activate, showed on the digital display. Monitoring with alarms/indications of the following parameters: Negative pressure value inside the isolator; Doors opening; Chamber bonification; Operator terminal/control panel showing: Working chamber negative pressure Cycle steps Error messages Indication of soft key to be pushed for proceeding to the next step Inlet filter clogging Exhaust push-push filters clogging Voltage presence
56

Leak Pressure Test

Verifica della tenuta dellisolatore Predisposizione dellisolatore per la prova Misura della temperatura della camera Misura della pressione iniziale e finale della camera
TI PI

Risultato finale: Tf< 2,5 x 10-3 (h-3)

(Tf: Hourly Leak Rate) (ref.: ISO 19648 2

57

Placebo Containment Performance test

Verifica della concentrazione placebo nellaria : Segregazione della zona di campionamento Posizionamento della sonda di campionamento Simulazione delle operazioni utilizzando un placebo (Lattosio)
100 cm2

di

1,0 m

Validazione del metodo di analisi Presentazione dei risultati

1,7 m

Risultato finale: #ambiente< 1g/m3 #Superficie< 10g/100cm2

58

Check of isolator performance

alarm 100 Pa

Set-point - 75 Pa

Alarm - 35 Pa

Start and check of isolator function

Check of High Pressure Alarm

Normal running and check of pressure stability

Check of Low Pressure Alarm

Normal running and check of pressure stability

Check of air velocity into glove port

59

Contents 1. Introduction 2. Development of isolator concept 3. Containment Isolator Standard 4. Containment Isolator Design Criteria 5. Testing 6. Example of isolator

60

Isolator for Compounding of Cytotoxic compound

RTP door: La Calhene DPTE 270 S

Vessel placed over the Cell Weighing and connected to the isolator throu a membrane

61

Isolator for dispensing and Bin Charging

Independent Balance support

Isolator to bin Connection

Bag-out sytem

62

Isolator for Quality Control

63

Isolator for Filter Dryer Discharge

64

Isolator for containment:technical characteristics

A C

Housing in AISI 316, thick 3 mm, continuos welding, bend radius 30 mm(A) extraction of material through barrier bag (B) exhaust system through double Hepa filter, Push-Push type (C) supply system completed of 2 Hepa cartridge filter DP measurements of supply and exhaust filter hinged front window (D) predisposition for WIP

C B D

65

Isolator for containment: technical characteristics

A C

PLC control system (A) Mirror finishing (B) exhaust system able to increase the fan speed in case of serious damage on the glove (break of the glove): the safety inflow velocity throught the glove-hole is 0,7 m/s (C) pressure control of the cabinet @ -75 Pa regulating the fan speed (D)

/s 0 ,7 m

-75 Pa

66

Exhaust filtration: push-push system

67

Some construction datails

Plastic Bag connection

68

Some construction datails

Electrical socket

Gloves

Pass-box

69

Isolator for movable lab

70

Isolator for Dispensing

Isolator with Nitrogen inertisation system

71

Isolator for dispensing and bin charging: ATEX execution

72