Vaisala PR-23 Instructions Manual

IM-EN-PR23AC-VACC-A

Appendix

to PR-23 Instruction Manual for Vaisala K-PATENTS®

Products Intended for Use in Vaccine Production

Vaisala K-PATENTS® Pharma Refractometer PR-23-AC

Appendix to the Instructions Manual PR-23

Do not underestimate or neglect the laboratory and factory safety rules:

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Before you start, assess the workplace to determine if hazards are present, or are likely to be present, which necessitate the use of personal protective equipment, e.g.:

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protective clothing and shoes

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safety goggles

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protective gloves

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respiratory shields and devices

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Locate the nearest safety equipment, extinguishers, eyewash, and emergency shower

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

Contents

Section 1 Vaisala K-PATENTS® products for vaccine production and sucrose gradient

ultracentrifugation ............................................................................................................... 5

1.1 Designqualication........................................................................................................ 6

Section 2 The Pharma Refractometer PR-23-AC ................................................................................ 7

2.1 System description ........................................................................................................ 7

2.2 System components ...................................................................................................... 8

2.2.1 Checklist of components .................................................................................... 8

2.3 Pharma Refractometer Sensor PR-23-AC- 62-HSS-SC ............................................. 10

2.3.1 Sensor model code .......................................................................................... 10

2.3.2 Pharma Mini Flow Cell model code ................................................................. 10

2.4 Indicating Transmitter DTR-GP-SC ............................................................................. 12

2.4.1 Indicating Transmitter model code ................................................................... 12

2.5 Pharma vaccines accessories ..................................................................................... 13

Section 3 Installation of PR-23 Pharma Refractometer ................................................................... 15

3.1 Hardware and software requirements ......................................................................... 15

3.2 Mechanical and electrical requirements ...................................................................... 15

3.3 Sensor installation for use in pharmaceutical batch manufacturing ............................ 15

3.4 Indicating Transmitter installation for use in table top ................................................. 19

3.5 Wiring transmitter connections to sensor, power cable and computer ....................... 20

3.6 Refractometerinstrumentverication .......................................................................... 21

Section 4 Electronic data capture and storage ................................................................................ 23

4.1 Ethernet connection ..................................................................................................... 23

Section 5 Complying with documentation and validation regulations ......................................... 25

5.1 Documentation ............................................................................................................. 25

5.2 Qualication ................................................................................................................. 25

5.3 Protocol acceptance by customer and list of tests performed .................................... 25

5.4 Electronic data management and data storage ........................................................... 26

5.5 Electronic signatures/audit trail .................................................................................... 26

5.6 Record keeping ............................................................................................................ 26

5.7 Security ........................................................................................................................ 26

5.8 System validation ......................................................................................................... 26

5.9 Vaisala K-PATENTS

Section 6 Onsitequalicationprotocolsandrecords:InstallationQualication ....................... 29

6.1 Authorization and responsibilities ................................................................................ 29

6.1.1 Documents and procedures ............................................................................ 29

6.1.2 Authorizedofciator ......................................................................................... 30

6.1.3 Execution ......................................................................................................... 30

6.2 System ......................................................................................................................... 30

refractometer system adherence to Part 11 ............................. 27

Appendix to the Instructions Manual PR-23

6.2.1 Qualifying the system ...................................................................................... 30

6.2.2 Manufacturers and suppliers ........................................................................... 31

6.3 IQ protocol ................................................................................................................... 31

6.3.1 Scope of delivery ............................................................................................. 31

6.3.2 Damage ............................................................................................................ 32

6.4 Documentation ............................................................................................................. 32

6.5 Operating environment ................................................................................................ 33

6.6 Installation .................................................................................................................... 33

6.7 Setting up the system components and devices ......................................................... 34

6.8 Electrical connections and wiring ................................................................................ 35

6.9 Ethernet connection ..................................................................................................... 36

6.10 Initial check and switching the device on ................................................................... 36

6.11 InstallationQualicationsummaryreport .................................................................... 37

Section 7 Onsitequalicationprotocolsandrecords:OperationalQualication ...................... 39

7.1 Individual module and system components check ...................................................... 39

7.2 InstallationQualicationhasbeenperformedsuccessfully ........................................ 39

7.3 Test procedure ............................................................................................................. 40

7.4 Authorizedofciator ..................................................................................................... 40

7.5 Systemqualication ..................................................................................................... 41

7.6 Setting up the system components and devices ......................................................... 41

7.7 Instrumentvericationwithsampleholderandrefractiveindexliquids ...................... 42

7.8 OperationalQualicationsummaryreport .................................................................. 43

Section 8 Routine operation phase ................................................................................................... 45

Section 9 Preventive maintenance .................................................................................................... 47

Section 10 Other documentation ......................................................................................................... 49

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

Vaisala K-PATENTS® products for

vaccine production and sucrose gradient ultracentrifugation

This instruction manual appendix covers Vaisala K-PATENTS® Pharma Refractometer PR-23-AC when used in the production of viral vaccines. The vaccines are either produced

by inoculating viruses into specic pathogen-free eggs or in animal cell culture based process. The allantoic uid of these processes is harvested and puried by centrifugation

and stabilised with buffer containing sucrose. The centrifugation process typically uses

density gradient continuous ow ultracentrifuge for the purication of the virus particles.

The internal subviral core of the virus is separated and fractionated on the basis of its’ sedimentation rate, and the buoyant sucrose density. Pharma Refractometer PR-23-AC is used for accurate measurement of these sucrose densities. The measurement signal is used for reliable and timely determination of the product peak in the density gradient (0 to 60% w/w sucrose), and the subsequent collection of the virus rich fraction (Figure 1.1.).

Pharma Refractometer PR-23-AC can be installed in the vaccines fractionation unit for in-line process control. The output of the transmitter is a 4 to 20mA DC output signal proportional to sucrose solution density or Brix. Process data can also be downloaded to a computer via an Ethernet cable.

High Density Solution

• Inoculation egg with virus

• Incubation

• Inoculation preparation

• Cell expansion

• Virus propagation

Figure 1.1 Ultracentrifugation density gradient purication process steps.

Inactivation of virus

Low Density Solution

Sucrose gradient purication by zonal centrifugation

Fractionation and separation

Chart Recorder

Filling

Low Density High Density

Rotor unloading

Appendix to the Instructions Manual PR-23

1.1 Design qualication

Design Qualication (DQ) typically consists of manufacturer’s documentation to verify

that the proposed design of the Vaisala K-PATENTS intended purpose.

Pharma Refractometer PR-23-AC is an in-line real-time instrument that is designed to meet the pharmaceutical industry standards and guidelines including PAT, GMP, CIP/SIP and validation. Pharma Refractometer PR-23-AC wetted parts materials comply with the contactcompatibility of a substance with pharmaceutical materials. Gasket materials conform to the FDA requirements 21 CFR 177.2600 and to biocompatibility standards according to USP Class VI. Meeting the FDA and USP criteria guarantees that the seal material is acceptable for sanitary process applications and the material, or extracts from the material will not be harmful to human health. No animal derived ingredients (ADI) have been used in the machining and polishing processes. The PR-23-AC also meets the 3-A Sanitary Standard and is tested for in-place-cleanability according to the Euopean Hygienic Engineering Design Group (EHEDG) test.

The refractometer has an Ethernet communications solution. The transmitter uses the IP protocol to communicate over the Ethernet to any type of computer. This eliminates human error and allows for easy capture of the refractometer generated measurement and diagnostic data for storage, analysis and reporting. Access to the refractometer

and the generated data can be restricted to authorized personnel using password and

padlock protection.

Refractometer is suitable for the

Vaisala K-PATENTS refractometers are designed, manufactured and serviced under ISO 9001 quality system and procedures that guarantee the accuracy and repeatability of the measurement results. Each refractometer sensor is provided with a calibration

certicate comparing a set of standard liquids to the actual sensor output. Vaisala veries

the calibration of all delivered instruments according to the procedure similar to the one described in the PROCESS REFRACTOMETER PR-23 INSTRUCTION MANUAL, Section 13.

The quality system is ISO 9001 certied by Det Norske Veritas. The quality performance

is improved by critical self-assessment, internal auditing and feedback system. The chain of quality starts from the subcontractors with whom Vaisala maintains a quality contracting

and regular auditing system. The internal quality functions, from verication of incoming products to packing and delivery, are based on dened procedures. Vaisala provides full traceability of the wetted parts materials. Certicates of Origin, and any other required

quality documentation is available upon request at time of order.

Vaisala K-PATENTS process refractometers and support services are available to customers anywhere in the world. Application, installation and technical assistance are provided both locally by the representatives and by the headquarters in Finland and a branch in the U.S.

Vaisala warrants that all products made by Vaisala shall be free of defects in material and workmanship. Vaisala agrees either to replace or repair free of charge any such product or

part thereof which shall be returned to the nearest authorized Vaisala K-PATENTS repair

facility within two (2) years from the date of delivery.

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

The Pharma Refractometer PR-23-AC

2.1 System description

The recommended system for the vaccines production process comprises of a Pharma Refractometer PR-23-AC unit and a Pharma Mini Flow Cell PMFC-HSS that allows the sensor connection to the zonal ultracentrifuge rotor unloading and fractionation phase.

The standard Ethernet communication solution allows for simultaneous data logging and continuous monitoring of the measurement values and diagnostic data from the Indicating Transmitter DTR to a computer via an Ethernet connection.

Appendix to the Instructions Manual PR-23

2.2 System components

2.2.1 Checklist of components

Pharma Refractometer Sensor PR-23-AC-62-HSS-SC- EP calibrated with raw

measurement data refractive index (n

Indicating Transmitter DTR-M/U-GP-SC that calculates and displays the process liquid

concentration based on the refractive index and temperature, installed in a stainless steel

enclosure that contains a key

Table top stand PR-7603-SS for Indicating Transmitter,

contains a set of two M5x10 A2 DIN 912 screws

Wall mounting screws kit for mounting the Indicating Transmitter DTR on the wall

Interconnecting cable between transmitter and sensor PR-8230

PR-8820 Crossover cable for Ethernet connection between Indicating Transmitter and

computer, length 5 m (16 inch), contains cable gland for enclosure connection

Table top stand PR-7605 -SS with an integral support rod and

2.5” Sanitary Clamp for the Pharma Refractometer Sensor PR-23-AC-62-HSS

contains a M5x16 A4 DIN 912 screw

Pharma Mini Flow Cell PMFC-HSS

PR-9244-USP O-ring for the Pharma Mini Flow Cell, 22.2x3.0 EPDM

Two sets of PR-9235 0.5” Sanitary Clamp for the Pharma Mini Flow Cell connection

Two sets of PR-9236 -USP Sanitary gasket EPDM for the 0.5” Sanitary Clamps

Two sets of PR-9237 0.5” Sanitary ferrule (lenght 1.5 cm) for the inlet and outlet hose

connections and Pharma Mini Flow Cell

Universal sample holder PR-1012

R.I. Liquid set PR-2300, consists of Cargille Cer ticate for the liquids

) and temperature (T)

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

The Pharma Refractometer PR-23-AC

Figure 2.1 System components provided by Vaisala.

Appendix to the Instructions Manual PR-23

2.3 Pharma Refractometer Sensor PR-23-AC-62-HSS-SC

2.3.1 Sensor model code

Model and Description Model

PR-23 = Sensor PR-23

Sensor model

-A = 3A approved -A

Sensor type

C = Compact type for pipe line installation C

Refractive Index range limits

-62 = R.I. 1.320....1.530 ( 0-100 Brix ) -62

Process connection -SC

-H = Sanitary 3A-clamp, 2 ½ inch -H

Sensor wetted parts material

SS = AISI 316 L SS

Electrical classication

-GP = General purpose -GP

-AX = ATEX certied EX II 3 G Eex nA II T4 (up to Zone 2) -AX

-IA = ATEX and IECEx certied EX II 1 G Ex ia II C T4 Ga (up to Zone 0) (A) -IA

Sensor housing

-SC = Stainless steel -SC

Sensor wetted parts surface treatment option

-EP = Electropolished process wetted parts (Ra 0.4µm, 15 µ inch ) -EP

(A) Available with STR- Indicating Transmitter and IS Isolator only

2.3.2 Pharma Mini Flow Cell model code

The wetted parts materials for the Pharma Mini Flow Cell are AISI 316 stainless steel standard Ra 0.4µm, 15 µ inch and EPDM (ethylene propylene diene monomer) for the O-ring sealing.

Model and Description Model

PMFC = Pharma Mini Flow Cell PMFC

Sensor connection

-H = Sanitary 3A-clamp, 2 ½ inch -H

Material of Construction

SS = AISI 316 SS

Process connection

-H = Sanitary mini tting -H

Pipe section diameter

04 = 4 mm 04

05 = 5 mm 05

06 = 6 mm 06

Options

-EP = Electropolished process wetted parts (Ra 0.4µm, 15 µ inch ) -EP

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

The Pharma Refractometer PR-23-AC

Figure 2.2 Pharma Refractometer PR-23-AC-62-HSS-EP sensor and Pharma Mini Flow Cell

Figure 2.3 Pharma Mini Flow Cell PMFC-HSS-EP.

PMFC-HSS-EP with PR-7605 -SS table top stand.

Appendix to the Instructions Manual PR-23

2.4 Indicating Transmitter DTR-GP-SC

Indicating Transmitter DTR is a specialized computer designed to process data received from the refractometer sensor. Indicating Transmitter (Figure 2.4) contains a front panel with a backlit Liquid Crystal Display (LCD) and a keyboard. A lock and a key are included in the enclosure’s door to prevent unauthorized access. Please note that neither any power cables nor any external power switches are included in the standard delivery.

Materials for the Pharma Indicating Transmitter Enclosure DTR-M/U-GP-SC are: Stainless steel enclosure and polycarbonate window.

2.4.1 Indicating Transmitter model code

Model and Description Model

DTR = Indicating Transmitter (connectivity for two sensors) STR = Indicating Transmitter (connectivity for one –IA/-IE sensor)

Cable connection

-U = ½ inch NPT-type conduit hubs -U

-M = M20x1,5 metric cable glands -M

Electrical classication

-GP = General purpose -GP

Enclosure

-SC = Stainless Steel enclosure with window -SC

Transmitter options (A) (leave this section blank, if AC supply is specied)

-AC = Power supply 100-240 VAC 50/60 Hz -AC

-DC = Power supply 24 V DC -DC

(A) Note standard power supply is 100-240 VAC 50/60 Hz

DTR STR

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

The Pharma Refractometer PR-23-AC

Front view Back view

186 mm

(7.32”)

281 mm (11.06”)

153 mm

(6.04”)

304 mm (11.95”)

254 mm

(9.99”)

50 mm (1.97”)

45 mm

(1.77”)

Figure 2.4 Indicating Transmitter DTR-GP-SC with Stainless steel enclosure; dimensions (mm/in).

2.5 Pharma vaccines accessories

Vaisala recommended accessories for the vaccines production application contain Ethernet crossover cable, IQ and OQ documentation (this document) and parts for

verication and usage of Pharma Refractometer sensor and Indicating Transmitter

mounted on a table top or a trolley via metal support stands. The recommended accessories and corresponding part numbers are:

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PR-7603-SS Table top stand for Indicating Transmitter (contains a set of two M5x10 A2 DIN screws)

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PR-7605-SS Table top stand with the intregral support rod and 2.5” Sanitary Clamp for the Pharma Refractometer Sensor PR-23-AC (contains a screw)

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PR-8820 Crossover cable for Ethernet connection between Indicating Transmitter and computer, length 5 m (16 feet)

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Parts for off-line instrument verification: PR-1012 Sample holder PR-2300 R.I. liquid set 5 x ¼ .oz.; Including: 1.33; 1.37; 1.42; 1.47; 1.52

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IM-EN-PR23AC-VACC IQ and OQ Documentation for Equipment qualification

Appendix to the Instructions Manual PR-23

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

Installation of PR-23 Pharma Refractometer

3.1 Hardware and software requirements

PR-23 software is included in the Indicating Transmitter DTR and it comprises the following functions:

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Automatic temperature compensation

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Ethernet connection for data download

●

Sensor diagnostics and verication

3.2 Mechanical and electrical requirements

Power supply for the refractometer is AC input 100-240 VAC/50-60 Hz, optional 24 VDC, 30 VA.

3.3 Sensor installation for use in pharmaceutical batch manufacturing

Laboratory table top or trolley installation and key considerations for the site preparation

1. Physical dimensions of the instrument and accessories: make sure there is enough space to accommodate them.

2. Suitable recommended operational environment for the instrument and for the Cargille Refractive Index Liquids should be maintained between 20 – 30 °C (68 – 86°F).

3. Utilities: 100-240 VAC/50-60 Hz (optional 24 VDC, 30 VA) electrical power supply and computer network connection.

Appendix to the Instructions Manual PR-23

Attaching table top stand PR-7605-SS for Sensor and Mini Flow cell

Attach the 2.5” Sanitary clamp and the support rod to the base plate. The supplied screw (M5x16 A4 DIN 912) for attaching the stand is inserted from the bottom of the base plate

through the bottom hole (Figure 3.1). To assemble the Pharma Mini Flow Cell rst locate the

PR-9244-USP O-ring 22.2x3.0 EPDM inside the Mini Flow Cell (Figure 3.2). Then insert the

2.5” Sanitary clamp for the sensor and Mini Flow Cell.

Finally insert the two PR-9236-USP Sanitary EPDM gaskets and the two PR-9237

0.5” Sanitary ferrules for the inlet and outlet connectios using the two PR-9235 0.5” Sanitary Clamps.

Sensor can now be connected to exible hoses and used as a free standing tabletop unit,

see Figure 3.3.

Sanitary clamp and support

Base plate

Retaining screw

Sensor stand assembly

Figure 3.1 Sensor stand assembly: Attaching the clamp and support rod to the base plate.

Document/Revision No. IM-EN-PR23AC-VACC/A Effective: March 1, 2020

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