validation protocols for the rabies laboratory

RABIES VACCINE UNIT

Validation protocols for the Rabies laboratoryThe following is a comprehensive listing of equipment, systems, processes and procedures which should be validated..A. Waste Systems1. Domestic sanitary sewer systems2. Process drain systems3. Hazardous waste systems4. Solid waste disposal systems5. Hazardous emissions systems

B. Air Handling Systems (IQ/OQ/PQ)1. Heating system2. Ventilation system3. Air conditioning system4. Air filter systems5. Biological safety cabinets6. Laminar flow hoods

C. Water System (IQ/OQ/PQ)1. Purified water2. Water for injection (WFI)3. Source potable water

D. Steam Systems (IQ/OQ/PQ)1. Plant steam (raw steam)2. Clean steam

E. Cooling Systems (IQ/OQ/PQ)1. Chillers2. Cooling towers

F. Gas Systems (IQ/OQ/PQ) CO2

G. Electrical System (IQ/OQ)1. Electrical standard2. Electrical emergency power3. Electrical back-up power

H. Equipment(IQ/OQ)1. Production2. Quality control laboratory

I. Sterilization1. Steam sterilization (autoclaves)(IQ/OQ/PQ)a. Component preparation sterilizerb. Terminal sterilizerc. Laboratory sterilizer2. Dry heat sterilization/depyrogenation (IQ/OQ/PQ)b. Ovens3. Terminal filtration process

J. Cleaning Processes1. CIP (Clean-in-Place) processa. Asepticb. Non-aseptic2. SIP (Sterilize-in-Place) process3. Facility cleaning processesa. Equipmentb. Clean areac. Aseptic aread. Sanitizatione. Garment launderingf. General facility cleaning (janitorial)

K. Component Preparation Equipment1. Container washing equipment (IQ/OQ/PQ)a. Manualb. Semi-automatic (programmable controllers)c. Automatic (computer controlled)2. Closure washing equipment (IQ/OQ/PQ)a. Manualb. Semi-automatic (programmable controllers)c. Automatic (computer controlled)3. Washing/depyrogenation/sterilization processes

L Aseptic Solution Preparation1. Solution manufacture process2. Solution filtration process

M. Sterile Filling (Aseptic or Terminally Sterilized)1. Solution filling a. Manual b. Automatic3. Container sealing a. Manual vial stoppering b. Automatic vial stoppering c. Ampoule sealing4. Container capping

N. Finishing1. Labeling processa. Manualb. Semi-automaticc. Automatic2. Packaging (boxing) process

O. Manufacturing Processes1. Cell separation2. Cell growth

a. Roller bottle3. Buffer preparation

a. Buffer weigh-up. b. Buffer preparation

i. Sterile filtrationii. Sterilizationc. Buffer storage4. ultrafiltrationa. inactivationb. adjuvanisation

P. Storage/Warehouse Operations (Storage, Holding, Distribution)1. Incoming/Receiving2. Warehousing3. In process storage4. Approved finished goods storage5. Outgoing/distribution/shipping

Q. Analytical Methods1. Raw materials2. In-process product3. Intermediates4. Final product

R. Other2. Vendor validation/supplier audit3. Animalsa. Animal care and handling processesb. Supplier validation (audit)

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RABIES VACCINE UNIT

Validation and Calibration Documents related to Rabies Vaccine

Master Validation Plan for the Vaccine FacilityDesign qualification for the clean roomsInstallation Qualification for Classed and UnClassed RoomsPerformance Qualification for Classed and UnClassed RoomsDesign qualification for the HVACInstallation Qualification for the HVAC SystemsOperational Qualification for the HVAC Systems Performance Qualification for the HVAC SystemsDesign qualification for the cold roomsInstallation Qualification for Classed and UnClassed Cold RoomsOperational Qualification for All Cold RoomsDesign qualifications for the hot roomsInstallation Qualification for IncubatorsOperational Qualification for IncubatorsDesign qualification for the BS 3 hoodInstallation Qualification for the BS 3 hoodOperational Qualification for the BS 3 hoodPerformance Qualification for the BS 3 hoodInstallation Qualification for Class 100 Hoods Operational Qualification for Class 100 Hoods Design qualification for the ultrafilteration systemDesign qualification for the double ended autoclavesDesign qualification for the depyrogenatorsCalibration of Cage Washer ThermocouplesInstallation Qualification of AutoclavesOperation Qualification of AutoclavesCalibration of Humidity RecordersCaliberation of temperature recordersCaliberation of pressure recordersCaliberation of anemometersOperation Qualification of Millipore water SystemPerformance qualification of Millipore water SystemValidation of Millipore water SystemInstallation Qualification of WFI Distribution SystemOperation Qualificationof WFI Distribution SystemInstallation Qualification for Refrigerators and FreezersOperational Qualification for Refrigerators and FreezersInstallation Qualification for the ………………….Environmental Monitoring SystemValidation of Filling Equipment CleaningPQ for Unclassed Cold Rooms Refrigerators, Freezers, and IncubatorsPQ for Biological Safety Cabinets and Laminar Flow HoodsPQ for HVACPerformance Qualification and Process Validation for ……………….Centrifuge Calibration of HydrometersCalibration of Sanitary GaguesCalibration of ………………… Viable Air SamplerValidating & Monitoring of Glassware Prep.Validation Plan for Computerized Systems at ...................OQ of Calibration Manager


RABIES VACCINE UNIT

Process Validation Bulk Transfer to FillingAnnual Standardization of RABIES VACCINEValidation Procedure for the UltraFiltration of culture Validation of Cleaning processes Using SwabsQuarterly Calibration of Cold Rooms, Incubators, and water BathsCalibration of Pressure GaugesRequirements for Validating Assays in QCQC Testing of Trypicase Soy Broth Medium for Broth Fills ValidationGlassware Cleaning and Validation of CleaningValidation of clean room cleaningValidation of surface sterilizationValidation of hydrogen peroxide fumigationStandardization of ThermometersValidation of analytical assays

a. NIH testb. virus


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Validation protocol No. effective dateTitle: MASTER VALIDATION PLAN Written by: Edited by: Revised by: Section: Revision No.: Revision date:

1. INTRODUCTION

2. ORGANIZATIONAL STRUCTURE OF VALIDATION ACTIVITIES

3. PLANT/PROCESS/PRODUCT DESCRIPTION

4. SPECIFIC PROCESS CONSIDERATION

5. LIST OF PRODUCTS/PROCESS/SYSTEMS TO BE VALIDATED

6. KEY ACCEPTANCE CRITERIA

7. DOCUMENTATION FORMAT

8. REQUIRED SOPs

9. PLANNING &SCHEDULING

10. CHANGE CONTROL

Senior Research Officer Quality Control Officer


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Validation protocol No. DESIGN QUALIFICATIONS Effective date:Title: DESIGN QUALIFICATION OF …………………………………….. Written by: Edited by: Revised by: Section: Revision No.: Revision date:

OBJECTIVE

To ensure that the system/equipment installed conforms to the purchase specifications and the manu-facturers

literature, and to document the information that the equipment meets specifications.

SCOPE

To be performed at time of installation, modification, or relocation.

RESPONSIBILITY

Person overseeing the design will perform the qualification and record the information.

The responsible engineer will verify the records and write the report.

Quality Assurance will review and approve the IQ Protocol and Report.

DESIGN INPUTS

System/Equipment _______________________________ Code No. _______________

a Description of the System/Equipment being installed: General description of the function and

the main components.

________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________________b List of the main components1 _____________________________________________ Code # _______________2 _____________________________________________ Code # _______________3 _____________________________________________ Code # _______________4 _____________________________________________ Code # _______________5 _____________________________________________ Code # _______________6 _____________________________________________ Code # _______________c Description of any required supporting utilities (piping, connections, water supply).1 _____________________________________________ Code # _______________2 _____________________________________________ Code # _______________3 _____________________________________________ Code # _______________4 _______________________________

DESIGN BASIS

ACCEPTANCE CRITERIA

SYSTEM DESCRIPTION


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REFERENCE DOCUMENTS

MANUFACTURER’S COMMUNICATION


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Validation protocol No. INSTALLATION QUALIFICATION Title: INSTALLATION QUALIFICATION OF …………………………….. Written by: Edited by: Revised by: Section: Revision No.: Effective date: Revision date:

OBJECTIVE

To ensure that the system/equipment installed conforms to the purchase specifications and the manufacturers

Literature, and to document the information that the equipment meets specifications.

SCOPE

To be performed at time of installation, modification, or relocation.

RESPONSIBILITY

Person overseeing the installation will perform the qualification and record the information.

The responsible engineer will verify the records and write the report.

Quality Assurance will review and approve the IQ Protocol and Report.

System/Equipment _______________________________ Code No. _______________

A DESCRIPTION OF THE SYSTEM/EQUIPMENT BEING INSTALLED:

Name of system Model Serial No. Manufacture’s address Suppliers address

B LIST OF THE MAIN COMPONENTS

1 _____________________________________________ Code # _______________2 _____________________________________________ Code # _______________3 _____________________________________________ Code # _______________4 _____________________________________________ Code # _______________5 _____________________________________________ Code # _______________6 _____________________________________________ Code # _______________

C DESCRIPTION OF ANY REQUIRED SUPPORTING UTILITIES (PIPING, CONNECTIONS, WATER SUPPLY).

1 _____________________________________________ Code # _______________2 _____________________________________________ Code # _______________3 _____________________________________________ Code # _______________4 _____________________________________________ Code # _______________

Checklist for Component Number _____ Name ________________________ Code # ______

Component Function: _______________________________________________________

SL NO Required/ordered Actual Deviations1 MODEL/SERIAL No.


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2 Specifications3 Manual/booklet4 Drawing5 Wiring/cabling6 Power, fusing7 Operation SOP,

maintenance SOPcalibration SOP

8 Input/output control9 Environmental

requirement10 Test equipment or

instrument11 Utilities and services12 Spare part list, part

No. and supplier13 Others

DEVIATION REPORT

Deviation(s):

Justification for acceptance:

Impact on operation:

PHYSICAL DETAILS

Serial No. Description Particulars1 Overall dimension2 Weight3 Colour code4 Surface finish5 Motor/gear box/pulleys etc6 Electrical rating7 Details of auxiliary equipments

SOP s

FUNCTION SOP No. Date of issue Revision no & date

Title Next revision

CALIBRATION REVIEW


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Process instrument

Location Date of calibration

Calibrated by Checked by Next calibration due on

Test instrument

Location Date of calibration

Calibrated by

Checked by

Next calibration due on

Component to be calibrated

SYSTEM / INSTRUMENT CHECK LIST

Sl. No. Statement YES/NO Observed by DateSpace for installationPowerCompressed airSteamVacuumWater, plumbing, drainageOthers

DRAWINGS

Sl.

No.

Drawing Category Location Drawing No Date Physical

verificationPiping and instrumentationGeneral arrangement/schematic diagramUtilityIsometricOthers

SUPPORT UTILITIES

Utility Facility Capacity required Capacity available Properly connected

&identified(Y/N)

MANUFACTURER’S SUBMISSIONS

1. commissioning report

2. test report

3. calibration certificates

4. others

Report Written by: ______________________________________________ Date ___________

INSTALLATION QUALIFICATION REPORT


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RESULTS:

CONCLUSIONS

Report Written by: ______________________________________________ Date ___________

QA approved by: ________________________________________________ Date ___________


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Validation protocol No. OPERATIONAL QUALIFICATIONTitle: OPERATIONAL QUALIFICATION OF Written by: Edited by: Revised by: Section: Revision No.: Effective date: Revision date:

OBJECTIVE

To determine that the system/equipment operates according to specifications, and to record all relevant

information and data to demonstrate it functions as expected.

SCOPE

To be performed after installation, modification or relocation, after the Installation Qualification has

been completed.

RESPONSIBILITY

Person responsible for operating the system/equipment will perform the qualification and record the

information.

The supervisor will supervise the study, verify the completion of the records, write the deviation report

and the Operational Qualification Report.

Quality Assurance will review and approve the OQ Protocol and Report.

MATERIALS OR SUPPLIES NEEDED TO PERFORM THE OPERATIONAL QUALIFICATION

1 _____________________________________________ Code # _______________2 _____________________________________________ Code # _______________3 _____________________________________________ Code # _______________4 _____________________________________________ Code # _______________5 _____________________________________________ Code # _______________6 _____________________________________________ Code # _______________

CALIBRATING APPARATUS AND INSTRUMENTS.

Apparatus/Instrument Calibration method Calibration date

Performed by: ______________________________________________ Date _______________

Deviations:

Verified by: ________________________________________________ Date

________________

DOCUMENT CHECK


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SOP Title Number File Location QA/QC approval date

TRAINING RECORDS

Course on SOP # Staff name Date

Equipment Make Model Manual Available (Y/N)


Deviations:

Verified by: ________________________________________________ Date ________________

Results

CONTROL PANEL FUNCTIONALITY

Purpose

Testing

Functionality test results

Equipment

No

Make Serial no. Location of

equipment

Control panel

sl.no

Location of

control

pannel

Component of control panel Described function Description matches function

(Y/N)

Results


Deviations

Verified by: ________________________________________________ Date ________________

SAFETY FEATURES REVIEW

Safety features Description Applicable/not applicable(Y/N)


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extreme temperature Hot line/equipment insulatedPersonal protection availableHeat source identified and shieldedSign post to alert operations

Pressure considerations All piping properly aligned

Pressure ratings of piping components is compatible with operating conditionsPressure release devices provided where applicableCompressed air / gas lines can be isolated and blended to zero energy stateASME stampsVessel registered with site services for insurance registrationCalculations for pressure release devices

Hazardous materials of fluid

natureMaterial safety data sheet (MSDS) locationIf required, SOP for handling available

Spill retention providedToxic and flammable chemical risks controlled

Biohazards information provided

Electrical hazardsAll wiring properly placedAll systems properly groundedLock-outs available on all equipment emitting ionizing radiationsProper shielding provided

Moving parts

Guards provided are in place at pinch pointsLock nut on shaftBelt tension properly adjusted

Noise leval Noise level is dB on scale Ambient noise level is

Noise reduction equipment /devices in place, if required

Physical environmental factors Sharp edges removed or protected

Trip/fall hazards eliminated or protected againstLow clearance head space clearly indicated or eliminatedEquipment properly anchored

Eye hazards eliminated

Adequate lighting provided in the areaWarning and precautionary signs provided wherever required


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Ergonomic design Ergonomic risks evaluated, operators can safely and conveniently access allareas of equipmentAdequate operator visibilityEmergency stop buttons visible, accessible, labeled, and operationalWarning bells and lights audible, visible and functionalBelt/conveyor/table width appropriate for manual operationsHazardous equipment not operational without safety guardExcessive reaching, body bending, weight lifting, pushing and pullingeliminated or minimizedPersonnel protective equipment to be worn when operating is indicated

Dust level Particulate matter concentrationRespiratory equipment / device in place if required.

CONTROL POINTS AND ALARMS.

Control point/Alarm Results Date


Deviations

Verified by: ________________________________________________ Date ________________

Results

OUTPUTS

Outputs Results Date


Deviations:

____________________________________________________________________________________________Verified by: ________________________________________________ Date ________________

CALIBRATION OF EQUIPMENT/SYSTEM

Calibration SOP Result Date

Performed by: ______________________________________________ Date _______________Deviations:

Verified by: ________________________________________________ Date ________________


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SPECIFIC CHALLENGE OF THE EQUIPMENT OR SYSTEM

Test in normal conditions:

Test of worst case situation:

(e.g. start-up after shutdown, temperature recovery time, centrifuge imbalance)


Deviations:

Verified by: ________________________________________________ Date ________________

DEVIATION REPORT

Deviation(s):

Justification for acceptance:

Impact on operation:

Written by: ______________________________________________________ Date ___________

OPERATIONAL QUALIFICATION REPORT

Results:

CONCLUSIONS:

Written by: __________________________________________________ Date ___________QA approved by: _____________________________________________ Date ___________

DEFINITIONS AND ABBREVIATIONS

REFERENCE DOCUMENTS


RABIES VACCINE UNIT

Validation protocol No. 1 PERFORMANCE QUALIFICATIONTitle: PERFORMANCE QUALIFICATION OF ……………………… Written by: Edited by: Revised by: Section: Revision No.: Effective date: Revision date:

OBJECTIVE

To determine that the systems/equipment perform as intended by repeatedly running the system on

its intended schedules and recording all relevant information and data. Results must demonstrate

that performance consistently meets pre-determined specifications under normal conditions, and

where appropriate for worst case situations.

SCOPE

To be performed after the Installation and Operational Qualification have been completed and approved.

To be performed after installation, modification or relocation and for re-validation at appropriate intervals.

Each piece of equipment must be validated before it serves another piece of equipment/system during

validation of the latter (e.g. water system before steam generator; steam generator before autoclave).

RESPONSIBILITY

Person responsible for operating the system or equipment will perform the qualification and record

the information.

The supervisor will supervise the study, verify the completion of the records and write the Deviation

Report and the Performance Qualification Report.

Quality Assurance will review and approve the Performance Qualification Protocol and Report.

MATERIALS, EQUIPMENT, DOCUMENTS

SOPs for normal operations of the equipment or system under test (including data record forms,

charts, diagrams materials and equipment needed). Attach copies.

SOP LIST:

SOPs specific for performance tests (including data record forms, charts, diagrams, materials and

equipment needed, calculations and statistical analyses to be performed, and pre-determined specifications

and acceptance criteria). Attach copies.

SOP LIST:

PROCEDURE

Equipment: Run normal procedure three times for each use (configuration or load) and record all


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required data and any deviations to the procedure.

Systems: Run for 20 consecutive working days, recording all required data and any deviations to the

procedure.

Attach all completed, signed data record forms.

SUMMARY DATA RECORD (TO BE PREPARED FOR THE SPECIFIC PROCEDURE ON TEST)

Performed by: _____________________________________________ Date ___________

Verified by: ________________________________________________ Date ___________

CALCULATIONS AND STATISTICAL ANALYSES


Verified by: ________________________________________________ Date ___________

ACCEPTANCE CRITERIA VS. PERFORMANCE TEST RESULTS

Criteria Results Pass/Fail


Verified by: ________________________________________________ Date ___________

DEVIATION REPORT

Deviation(s):

JUSTIFICATION FOR ACCEPTANCE:

Impact on operation, function or process:

Written by: _________________________________________________ Date ___________

Verified by: _________________________________________________ Date ___________

PERFORMANCE QUALIFICATION REPORT

Results:

Conclusions:

Written by: _________________________________________________Date ___________

Verified by: ________________________________________________ Date ___________


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Validation protocol No. 1 PROCESS VALIDATION

Title: Written by: Edited by: Revised by: Section: Revision No.: Effective date: Revision date:OBJECTIVE:

To determine that process consistently performs as intended by repeatedly running the system

on its intended schedules and recording all relevant information and data. Results must demonstrate

that the process meets pre-determined specifications under normal conditions, and where

appropriate worst case conditions.

SCOPE

To be performed with validated equipment in the specified location in validated premises. If

equipment or systems or the facility are modified or the premises where the process takes place

is changed, or the process is relocated, the process must be re-validated after the systems,

equipment and facility qualifications, as appropriate, have been performed and approved.

RESPONSIBILITY

The persons responsible for the process will perform the validation and record the information.

The responsible person will supervise the study, verify the completion of the records and write the

report.

Quality Assurance will review and approve the Process Validation Protocol and Report.


Master Formula or SOPs for normal operations of the process under test. (including data record

forms, batch record forms, materials and equipment needed).

MF/SOP LIST:

SOPs for in-process and quality control tests performed during process (validated tests) (including

data record forms, materials and equipment needed).

SOP LIST:

SOPs for test specific to the validation study performed (validated tests) (including data record

forms, materials and equipment needed).

SOP LIST:

PERFORMANCE

Process: Run full process according to SOP three times and record all required data.


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Deviations to the procedures must be recorded on the data record forms.

Analytical tests: Perform the routine tests associated with the process according to

the SOP. Test results must be approved by QC.

EVALUATION

ATTACH ALL DATA RECORD FORMS AND CHARTS.

LIST OF ATTACHED DATA RECORD FORMS

Verified by: ______________________________________________Date ___________


Performed by: _________________________________________ Date ______________

Verified by: ___________________________________________ Date ______________

ACCEPTANCE CRITERIA VS. TEST RESULTS


Recorded by: ___________________________________________ Date _____________

Verified by: ____________________________________________ Date _____________

DEVIATION REPORT

Deviation(s):


Impact on process:

Supervisor: _____________________________________________________ Date

_________

PROCESS VALIDATION REPORT

Results:

Conclusions:

Written by: _____________________________________________ Date _____________

QA approved by: ________________________________________ Date ____________


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Validation protocol No. ANLYTICAL ASSAY VALIDATION

Title: Effective date:

Written by: Edited by:

Revised by: Section:

Revision No.: Revision date:

OBJECTIVE

To demonstrate in a laboratory study that the performance characteristics of an assay make it fit

for the intended analytical application.

To record the information and data needed to establish the performance specifications for the

assay.

SCOPE

To be performed for new assays, or for current assays when any changes are made to the

equipment, procedure, laboratory conditions, technical staff, reagents and starting materials,

references/standards/ controls, etc.

All equipment must be validated before being used for the validation of an analytical assay.

RESPONSIBILITY

Person trained and responsible for performing the analytical test will perform the validation study

and record the information.

The supervisor will plan the study, write the protocol, supervise the performance, and verify the

completion of the records.

QA will review and approve the protocol before the validation study, and review and approve the

data in validation report.


SOP AND DATA RECORD FORMS FOR THE ASSAY UNDER TEST.

MATERIALS AND EQUIPMENT AS DESCRIBED IN THE SOP.

REFERENCE TO DOCUMENTS


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PROCEDURE

PERFORMANCE

CONDITIONS FOR THE PERFORMANCE OF THE TEST,

EVALUATION

ATTACH ALL DATA RECORD FORMS AND CHARTS.


Performed by: __________________________________________ Date _____________

Verified by: ____________________________________________ Date ______________

ACCEPTANCE CRITERIA VS. TEST RESULTS


Recorded by: __________________________________________ Date ___________

Verified by: ____________________________________________ Date ______________

DEVIATION REPORT

Deviation(s):


IMPACT ON PROCESS:


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Written by: ________________________________________________ Date _________

ASSAY VALIDATION REPORT

Results:

CONCLUSIONS:

Written by: _____________________________________________ Date _____________

QA approved by: _________________________________________


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Format for a standard operating procedure (SOP)

SOP Number ________ Title_________________________________________________Revision number ________Written by _________________________Edited by__________________________Authorization signature ________________________ Department _______ Date___________Effective date ____________________________________ Replaces ___________________

Purpose:

Scope

Responsibility

Materials and equipment

Procedure

Reporting

Reference documents:


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DATA RECORD FORM

Name of facility.........................................page....... of .......

Data Record Form #....... rev #....... SOP reference number....................Title _________________________________

PreparationMaterials checklist (buffers, glassware, supplies, QC approved dates if required)Equipment checklist (including specific numbers if there is a choice)Buffer, media, cleaning solution, etc preparation if necessary. Reference to SOP

Step by step InstructionsPresented in the order in which the work is routinely performed.Brief instructions with blanks for all data to be filled in.Dates and times for all operations, especially if procedure takes several days, or if there areSpecification limits to be met.Blank for verification signature for critical steps where necessary.Blanks for calculations as required and in order performed.Instructions for sending intermediate samples for testing, if appropriate.Instructions for storage during any waiting periods.Criteria for repeating test or procedure.Instructions for reporting any deviations, or problems.Instructions for correcting mistakes (no erasures, cross-out, add correct information andInitials)

Signatures Operator (technician) _____________________________ Date ____________Verification (supervisor)___________________________ Date ____________

Instructions for filing and approvalState where completed data sheet is to be delivered, copied, and filed.Submit to QC or QA for review and approval of the data.


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MASTER FORMULA RECORD

Master Formula: Revision number 2Product Name _______________ Product Code _______________ Batch Size _____Written by _________________ Edited by _____________________________Production Approval Signature _________________ Date ____________Authorization Signature _________________ Department (QA/QC) ________ Date ___________Effective date_________________ Replaces Rev 1 .

Part 1: CELL CULTUREBatch size _________________ Roller bottle Lot No. _______Theoretical Yield ____________Date Started: ______________ Operators ________________________________Date Finished: ______________ ________________________________Day 1: Preparation:This section should list all the preparative work and checks which are required before beginningthe procedure. A checklist for: facility preparation; production location; equipment preparation;reagent preparation; and for preparation and entry of incoming supplies needed for the days operationsis found in this section of the record. The checklist should give reference to the SOPnumbers followed during the preparation, expiry dates of reagents where applicable, QC approvaldates for starting materials, raw materials, supplies and reagents, and dates of cleaning and calibrationof equipment.Day 1: Manufacturing InstructionsThis section contains the step by step instructions for the process performed on Day 1 in sequentialorder. There should be blanks for all information and data to be entered and spaces forsignatures, initials and dates. All steps including sampling for QC tests should be indicated. Manyoperations will be recorded by checking a box to indicate the step was performed. Timed operationsshould have a space to fill in the beginning time and the finishing time. Weighings should


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have a space to record the tared weight and final weight. Any calculations should be presented asa formula with blanks to fill in. All critical steps and blanks for times and weights and all calculationsshould have an additional blank space for the initials of second operator who verifies thereading or calculation. If an item of measuring equipment has a printed readout, the verificationsignature is not necessary, but the printout must be attached to the record as well as the valueentered in the appropriate blank on the record.Day 1: CleanupA checklist of the step-by-step instructions for the procedure for cleaning up after the days productionis completed including: waste disposal, removal of reagents, storage of intermediates if appropriate,status of equipment, cleaning procedures performed before leaving. Blanks andcheckboxes and spaces for signatures, initials and dates are on the checklist.Day 1: ReportingThe days record is delivered to the Production manager at the end of the day.Day 2: PreparationPreparation information for the steps for the continuation of the fermentation process performedon the second day are to be provided in a checklist with all the appropriate information (see day 1).Supplies and reagents brought in for day 2, and any calibrations, cleaning or preparation of equipmentdone on day 2 must be entered on the checklist.Day 2: Manufacturing InstructionsContinued step-by-step instructions for all the steps of the process performed on day 2, blanksand checkboxes for entering data, and spaces for signatures, initials and dates.Day 2: CleanupA checklist of the step-by-step instructions for the procedure for cleaning up after the days productionis completed including: waste disposal, removal of reagents, storage of intermediates if appropriate,status of equipment, cleaning procedures performed before leaving Blanks andcheckboxes and spaces for signatures, initials and dates are on the checklist.Day 2: ReportingThe day’s record is delivered to the Production Manager at the end of the day.


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The Production Manager reviews and signs each page of the record in the appropriate blanks.This format continues for the full number of days for this fermentation part of theproduction process. The batch for fermentation will end with the storage of the singleor pooled harvests, depending on the manufacturing process.Preparation information for the steps for the continuation of the fermentation process performedon the last day are to be provided.Supplies and reagents brought in for the last day, and any calibrations, cleaning or preparation ofequipment done on the last day must be entered on a checklist.Day X: Manufacturing InstructionsSimilar step-by-step instructions for the procedure for the final day’s processing, blanks andcheckboxes for entering data, and spaces for signatures, initials and dates.The final step will be the sampling of the batch to send to the QC department for testing and theinstructions for labelling and quarantine storage of the finished fermentation batch (single or pooledharvests).Day X: CleanupA checklist of the step-by-step instructions for the procedure for cleaning up after the days productionis completed including waste disposal, removal of reagents, storage of intermediates if appropriate,status of equipment, cleaning procedures performed before leaving. There should be blanksand checkboxes for entering data, and spaces for signatures, initials and dates.Day X: ReportingThe day’s record is delivered to the Production Manager at the end of the day. The ProductionManager reviews and signs each page of the record.PART 2 . INFECTION

PART 3 INACTIVATION

PART 4 CONCENTARTION

PART 5 ADJUVANISATION

PART 6 TITARTION

PART 7 FILLING AND LABELLING


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SOP FOR THE CALIBRATION OF FOLLOWING EQUIPMENTS

PH meters

Pressure gauges

Thermometers

Anemometers

Humidity meters

Vacuum pumps

Time controllers

Filling machine

Automatic pipetting devices

Water conductivity meters
