WIXLIB

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 11 of 32INSPECTION OF:Date:3.0 A: Adequacy#Audit Item1Is the equipmentappropriatelydesigned, constructed and maintained?Are steps taken to prevent anysubstances required for operation, suchas lubricants or coolants, from comingin contact with in-process or finishedproducts?Are equipment surfaces that contactcomponents or products of a noninteractive nature?Are process pipelines or service lineswhose contents come in contact withproducts or product contact surfacessloped to allow proper drainage?234YesNoNAObservations (indicateN.O. if not observed)YesNoNAObservations (indicateN.O. if not observed)3.0 B: Cleaning and Maintenance#Audit Item1Is the equipment suitably located tofacilitate its use, cleaning andmaintenance?Are equipment and utensils cleaned,maintained and sanitized as appropriateto prevent malfunction or crosscontamination?Are piping systems, valves and ventfilters properly designed to facilitatecleaning and sterilization? NOTE:Maintaining closed systems through theuse of “clean in place” and “sterilize inplace” if preferable.Are the valves on primary re non-fiber releasing filters used forfiltration?Are filters used for sterile filtrationintegrity tested before and after use?Are calibrations and validation beingperformed adequately?Are autoclaves and sterilizing ovensfitted with effective, proper air filtersand are these integrity tested? AreHEPA filters used for the ovens?Are supplies and equipment which areexposed to pathogens during processingkept separate from unused items toprevent cross-contamination?23456789

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 12 of 32INSPECTION OF:Date:3.0 C: SOPs and Records#Audit Item1Are there written procedures (SOPs)for cleaning and maintenance ofequipment and utensils and are theyfollowed?Do these SOPs include:Assignment of responsibility forcleaning?Defined schedules for cleaning andmaintenance?Description of methods, equipment andmaterials used?Instruction for protection of cleanequipment from contamination?Inspection of equipment for cleanlinessimmediately before use?Assignment of identification number?Documentation in record books?Are cleaning and sanitizing agentsvalidated and approved for use by QC?Is clean equipment identified as such?Are calibrations and qualificationsproperly recorded?Are all certifications within date?Are there preventive maintenanceprograms and consistent records ofwork performed?2a.b.c.d.e.f.g.34567YesNoNAObservations (indicateN.O. if not observed)

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 13 of 32INSPECTION OF:Date:3.0 D: Automated and Computerized Equipment and Systems#Audit Item1For automatic and computer-controlledsystems:Is there an adequate description of thesystem, the components, and theoperating characteristics including alogic flow diagram?Is there an individual with appropriateexpertise in charge?Is there a procedure for on-goingevaluation and change control?Are there manual overrides forautomated production equipment orfacility systems in case of failure?Are the procedures in writing?Are computer systems such asprogrammable scales, autoclave, etc.controlled in order to preventunauthorized changes?Are back-files of computerized datacreated regularly and maintained?Where computerization eliminatescalculations, is a written record of theprogram filed with the validation data?Are there alternative systems (hardcopy) designed and maintained toensure that back-up data are exact andcomplete and is that system securedfrom alteration, erasure or loss?Validation of hardware and software:Have all systems been validated?Is validation performed in-house or oncontract?If on contract, are records kept of thequalifications of the contractor?Are records maintained?Has a risk assessment of each computersystem been made?It is ns (indicateN.O. if not observed)

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 14 of 32INSPECTION OF:Date:4.0 A: Adequacy of starting materials#Audit Item1Are there approved specification for allstarting material or raw material used inthe manufacturing process and are theyreleased by Quality control?To ensure the quality of raw materials:Is there a quarantine and releasesystem?Are the conditions of storageevaluated?Do the contracts with vendors ensurequality and stability,includingreporting of changes in manufacture?For raw material of animal origin:Are the details of source, origin, andmethod of manufacture documented?Are they stored in controlledenvironments?Are expiry dates given and is there aretest policy?Are rejected materials properlysegregated from acceptable material?Have viral removal and inactivationprocedures been validated?Are biological materials that maycontain infectious organisms screenedor tested prior to entry into laboratoriesor manufacturing sites?Do Master / Working Cell Banks andSeed Stocks have detailed records of:History of cells including the numberof generation doublings or passages ofvirus? Is there a maximum limit?Characterization according ot the WHOTRS relevant to the product?Demonstration of purity?Manufacturing procedures?Appropriate storage and security withcontinuous monitoring of temperature,alarms and backup power supply?Inventory log?Adequately segregates storage to avoidmix-up or cross-examination with othermaterial?Storage split into 2 separate locations?Routine monitoring of stability(viability / purity)?Demonstration of esNoNAObservations (indicateN.O. if not observed)

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 15 of 32INSPECTION OF:Date:4.0 B: Processes#Audit Item1a.Master Formula (MF):Does the MF adequately describe thecomplete production process?Is the MF up-to-date and approved byQC/QAIs the Batch Production Record formand adequate representation of the MF?Process validation:Has each phase of the productionprocess been validated according to anapproved validation protocol?Is re-validation done when required,and performed appropriately?Aseptic fill:Are suitable precautions taken tomaintain aseptic conditions during thefilling process?Is each filling process validated by asimulated media fill?Does the simulation use suitablemedium, fill sufficient numbers ofvials, and cover the full complexity ofoperations?Are time and temperature limitsestablished for the completion ofproduction phases?Are viral removal and inactivationprocesses validated, if applicable?Are in-process intermediate materialstested for identity, quality strength andpurity? Alternatively, are there validcertificates of quality issued from thesuppliers?Is there bioburden monitoring ofstarting, raw, and in-process materialsbefore sterilization?Are alert and action limits establishedfor environmental monitoring, and areeffective measures taken when limitsare exceeded?Are criteria for microbial limits,physico-chemical characteristics andendotoxins established for watersystems and are effective measurestaken when limits are exceeded?b.c.2a.b.3a.b.c.456789YesNoNAObservations (indicateN.O. if not observed)

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 16 of 32INSPECTION OF:Date:4.0 C: Sterilization/Depyrogenation#Audit Item1Are all sterilization/depyrogenationprocesses and cycles validated andcurrent?Is there a sufficient supply of puresteam to assure the simultaneous andproper operation of the validatednumber of autoclaves?Are systems for filter sterilizationvalidated and conditions still the sameas when validation was performed?Is an expiry date given to sterilizeditems and is there a maximum timeperiod established between washingand sterilization?Are storage conditions for sterilizeditems specified and appropriate?Are the filters tested immediatelybefore and after use for integrity by anappropriate method such as the bubblepoint test?Are in-line sterilizing filters used forroutine addition of gases, media,solutions, etc. to fermenter?23456YesNoNAObservations (indicateN.O. if not observed)YesNoNAObservations (indicateN.O. if not observed)4.0 D: Identification#Audit Item1If a component/material is transferredto a new container, is the newcontained identified with:Component/material name or itemcode?Receiving or control number?Amount in container?Are dispensing/addition operationsadequately supervised in that eachcomponent /material dispensed isexamined by a second person to ensure:The component/material was releasedby QC?The amount agrees with the batchrecord?The container is properly identified?The components/material are added inthe batch by one person and verified bya second person?Are actual yield and percentages oftheoretical yield determined at theconclusion of each phase of operationwith documentation of any losses?Are the yield calculations verified by asecond person?Are all containers, lines and majorequipment identified at all timesproduction for content and phase ofoperations?a.b.c.2a.b.c.d.345

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 17 of 32INSPECTION OF:Date:4.0 D: Identification, continued#Audit Item6Is major equipment identified with anidentification number, which isrecorded in the batch processingrecords (BPR) during production?Are all deviations from SOPsdocumented and subject to review byQA/QC for approval or hed to specify action taken withregard to the identification anddisposition of material in theenvironmentally controlled rooms andin the autoclave if the automatic systemfails or malfunctions?Are records made of the mode, date,duration, temperature and otherconditions relating to each sterilizationcycle of equipment and supplies used inproduction? Are they maintained in amanner that permits identification ofthe product with the particularmanufacturingandsterilizationprocess?Are sterilized items identified by asterilization reference number?Are inspections of areas undertakenimmediately prior to use to ensure thatall materials from previous operationhave been removed and are theseprocedures?Are all autoclaved and dry heatsterilized items marked with heatsensitive indicators?789101112YesNoNAObservations (indicateN.O. if not observed)

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 18 of 32INSPECTION OF:Date:5.0 A: Adequacy#Audit Item1Are specifications, standards, samplingplans, test procedures or otherlaboratorycontrolmechanismsincluding any revision, reviewed andapproved by Quality Assurance?Are any deviations from these specs,standards, etc. recorded and justified?Do laboratory controls include theestablishment of scientifically ng plans,testprocedures and reference substances,designed to assure that tested materialsconform to appropriate standards ofidentify, strength, quality and purity?Do these laboratory controls include:Determination of compliance withwritten specifications for acceptance ofeach lot within each shipment ofmaterials or holding or products?Description of sampling and testingprocedures for in-process materials?Retest policy, indentifying the rationaleand criteria for retests, number ofsamples, and the documentationrequired?A comprehensive calibration programthat includes calibration/certificationintervals, acceptance criteria andprovisions for remedial action?Are reagents, culture media, etc.properly labeled, preparation recordedin lab books and expiry dates given?Is appropriate testing done on eachbatch of product required to be free ofobjectionable microorganisms?Are there written sampling and testingplans for raw materials, intermediates,and final products that include methodof sampling and the number of unitsper batch to be tested and are thefollowed?234a.b.c.d.567YesNoNAObservations (indicateN.O. if not observed)

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 19 of 32INSPECTION OF:Date:5.0 B: Reference Reagents#Audit Item1Are all reference reagents kept secure,properly stored, identified and theirintegrity maintained?Are the tests results of all reference andstandards analyzed at appropriateintervals for statistical variation fromthe expected value?2YesNoNAObservations (indicateN.O. if not observed)NoNAObservations (indicateN.O. if not observed)5.0 C: Validation, Calibration and Stability Programme#Audit Item1Aretheaccuracy,sensitivity,specificity and reproducibility of testmethods established, documented,validated and subject to regular reviewand updating?Is there a written testing programmedesignated to assess the stabilitycharacteristics of each product todetermine the appropriate storageconditions and expiration dates?Is there a retention sampling system?Does the retention sample quantityconsist of at least twice the quantityneeded to perform all required tests(except for sterility and pyrogens)?Any retention samples of each lot offinal product stored under conditionsconsistent with product labeling?Are these samples at least visuallyexamined annually for evidence ofdeterioration? Is this recorded?23456Yes

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 20 of 32INSPECTION OF:Date:6.0 A: General#Audit Item1a.b.c.Are there records for:All materials used?All standard operating procedures?Each lot and/or batch processing anddistribution?All complaints and their investigation?All equipment, including cleaning,maintenance and validation?Cleaning,maintenanceandenvironmental control of the premises?Are all records:Dated?Signed by the person performing thetask (and, for all critical steps, by theperson checking it)?Kept at the workstation during theentire operation?Retained and available for inspection atleast 2 years after the expiry date of thelot/batch?d.e.f.2a.b.c.d.YesNoNAObservations (indicateN.O. if not observed)YesNoNAObservations (indicateN.O. if not observed)6.0 B: Lot/Batch Processing Records (BPR)#Audit Item1a.Does the BPR indicate:The name, strength and dosage of theproduct?The date of manufacture?The lot and batch identification no.?Assurance that the copy of the masterprocessing record is accurate?Changes in the master processingrecord approved by QA prior to startingthe operation?The complete formulation of thelot/batch?The batch number of each componentor other in-process materials and, whenapplicable, the sterilization number?The SOPs used?The yield obtained a different stage ofmanufacture, both actual measuredvalues and as a percentage of theexpectation?A record of each step followed?A record of all major equipment used?A record of all in-process controlsamples taken and of the resultsobtained?A sample of the label on the finalcontainer?Identification of packaging materials,containers, closures used?b.c.d.e.f.g.h.i.j.k.l.m.n.

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 21 of 32INSPECTION OF:Date:6.0 B: Lot/Batch Processing Records (BPR), contd .#Audit Itemo.Inspection of the processing area beforeand after use?Precautions taken and special orunusual observations made throughoutthe manufacture of the lot?Investigationofallunusualobservations for the batch and whererelevant, from samples of other batchesof the product?For rejected lots/batches, a record ofdisposal or reprocessing?Are all batch processing recordsreviewed and signed appropriately asindicated by:A BPR review document or checklistdescribing the review process?A dated signature of the personresponsibleforapprovingthemanufacturing operations?An analytical report, dated and signedby the responsible person, showingwhether the lot/batch complies with thespecifications?Decision on release or rejection of thelot/batch by the quality controldepartment?Are the BPRs maintained on file for 2years past the expiry date?p.q.r.2a.b.c.d.3YesNoNAObservations (indicateN.O. if not observed)YesNoNAObservations (indicateN.O. if not observed)6.0 C: Documentation of Equipment Used#Audit Item1Are records on the use, cleaning,sterilization and maintenance ofequipment kept in individual logs foreach piece of equipment?Are these records dated and signed inchronological order?Do the records include information ofthe lot/batch including identificationnumbers and dates?23

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 22 of 32INSPECTION OF:Date:7.0 A: Procurement#Audit Item1ArethereSOPsforanimalprocurement?Is a specific individual in department,authorized to order animals?Do contracts with supplies assure thequality and consistency of the animalsprovided?If the animals come from themanufacturer’s own breeding colony,are there SOPs for the maintenance andtesting of the colony?234YesNoNAObservations (indicateN.O. if not observed)YesNoNAObservations (indicateN.O. if not observed)YesNoNAObservations (indicateN.O. if not observed)YesNoNAObservations (indicateN.O. if not observed)7.0 B: Receipt and Evaluation#Audit Item1Are there SOPs covering the receipt ofanimals, including identification of theresponsible person and requireddocumentation?Are the newly received animals placedin quarantine?Are there SOPs for evaluating thehealth status of animals prior to use?237.0 C: Care#Audit Item1Are there SOPs covering housing,feeding, handling and care of theanimals?Are there SOPs for identification andisolation of any sick animal?Are any sicknesses of animals,treatment and preventive measuresrecorded?237.0 D: Allocation of Animals to Use#Audit Item1Are the specifications for animals usedin production or quality control testswritten in the respective SOPs?Is there a clear system of identificationof animals allocated for each test oruse?2

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES)Page 23 of 32INSPECTION OF:Date:7.0 E: Facilities#Audit Item1Are there enough animal rooms ofappropriate design to allow separatehousing of:The breeding colony?Different animal species?Animals in quarantine?Sick animals?Animals on-test including tests withhazardous infectious and non-infectiousmaterials?Are there facilities and SOPs forcollection and disposal of animal wasteand of dead animals, to minimizedisease hazards and environmentalcontamination?Are there facilities and SOPs forcleaning, sanitizing, sterilizing a

GMP AUDIT CHECKLIST (AS PER WHO GUIDELINES) Page 10 of 32 INSPECTION OF: Date: 2.0 C: Sterile Processing, continued # Audit Item Yes No NA Observations (indicate N.O. if not observed) e. Environmental monitoring system, e.g. temperature, humidity and particulates? f.