annexure-1 gmp checklist

SOP No.: EP-INS-004

Annexure-1

GMP CHECKLIST(Based on WHO Good Manufacturing Practices (GMP) for active pharmaceutical ingredients stated as per

Annex 2- WHO Technical report Series(TRS), No. 957, 2010; Good Manufacturing Practice guide forActive Pharmaceutical Ingredients ICH Harmonised Triplicate Guideline stated as per ICH Q9; and GMP

requirements as per Directives No. 2001/83/EC latest amended vide Directive 2011/62/EU)

1 Location and surroundings: Self appraisal tobe filled by themanufactureralong with alldetails (yes or notype reply will notbe acceptable)

Observations tobe noted by theinspecting teamat the time ofinspection

Remarks

1.1 How factory building is situated andcontrolled to avoid risk ofcontamination from externalenvironment including open sewage,drain, public lavatory or any otherfactory which produces disagreeableor obnoxious, odors, fumes,excessive soot, dust, and smoke,chemical or biological emissions.Pls specify industries /establishments adjoiningmanufacturing site.

2 Building and premises: -

2.1 How the building has been designedconstructed and maintained to suitthe manufacturing operations so asto produce drugs under hygienicconditions.Pls specify nature of constructionused in the facility in respect of itsmaintenance and hygienicconditions.

2.2 Whether the building confirm to theconditions laid down in the FactoriesAct, 1948Pls attach valid factory certificate/license issued by the competentauthority.

2.3 Specify how the premises used formanufacturing operations andtesting purpose preventscontaminations and crosscontamination is:a) Compatible with other drugmanufacturing operations that maybe carried out in the same oradjacent area.Pls specify any special criteria for

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the product manufacturered. e.g.temperature, humidity, air classrequirements maintained for asepticproducts, etc.

2.4 b) Whether adequate working spaceis provided to allow orderly andlogical placement of equipment,materials and movement ofpersonnel so as to avoid risk of mix-up between different categories ofdrugs and to avoid possibility of thecontamination by suitablemechanism.Pls specify space left around themachines. Pls attach equipment layout, men and material movement,waste movement if applicable.

2.5 c) Describe the pest, insects, birdsand rodents control system followedin the premises.Attach copy of pest / rodent controlschedule along with contractagreement if any.

2.6 d) What measures have been takento make Interior surface of (walls,floors, and ceilings) smooth and freefrom cracks, and to permit easycleaningSpecify material of construction andfinish for walls, ceiling, floor, covingetc. i.e. whether Epoxy or PUcoated, kota / granite stone withepoxy sealed joints, solid / GI /gypsum / cal. Silicate board ceilingwith epoxy, PU or any other pre-fabricated panel (GRP, powdercoated SS or Aluminum etc.) paint.

2.7 e) What measures have been takenso that the production anddispensing areas are well lighted andeffectively ventilated, with aircontrol facilities.Pls specify the lux level maintainedin various parts of the premise.

2.8 Pls specify the air handling systemused in various areas like stores,production, packing, QC areas etc.

SOP No.: EP-INS-004

2.9 f) Specify drainage system whichprevents back flow and entry ofinsects and rodents into thepremises.(pls specify number and location ofdrains installed)

3 Water system: -

3.1 Whether the unit has validatedsystem for treatment of water drawnfrom own or any other source torender it potable in accordance withstandards specified by BIS or localmunicipal norms.Pls specify source of raw water andgive details of treatment processes,sampling points, distribution andstorage system for raw and purifiedwater.

3.2 How bio burden in purified watercontrolled / reduced.

3.3 How water tank are cleanedperiodically and records maintainedthereof. How water distributionsystem is sanitized to controlmicrobial contaminations.

4 Disposal of waste: -4.1 Specify the system of disposal of

sewage, and effluents (solid, liquid,and gas) from the manufacturingsite.(Enclosed the copy of NOC obtainedfrom State Pollution Control Boardin this regard).

4.2 Whether provision for disposal ofbio-medical waste made as per theprovisions of the Bio Medical Waste(Management and Handling) Rules1996.

5 Warehousing Area: -

5.1 Whether adequate areas have beenallocated for warehousing of RawMaterials, intermediates, PackagingMaterial, products in quarantine,finish products, rejected or returnedproducts.How these areas marked orsegregated.Please specify the total areaprovided for warehousing.

5.2 How the warehousing areas beingmaintained to have good storage

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conditions. Are they clean and dryand maintained within acceptabletemperature limits?

5.3 Specify the storage arrangementprovided for materials whichsensitive to temperature, humidityand light and how the parameters aremonitored.Is cold room or deep freezersrequired for storage of goods? If yes,how the temperature is monitored.

5.4 Whether proper racks, bins andplatforms have been provided for thestorage.

5.5 Whether receiving and dispatch baysare maintained to protect in comingand out going materials.

5.6 How incoming materials are treatedand cleaned before entry into theplant.Please specify the cleaning systemfor the outer surface of thecontainer.

5.7 How quarantined materials aresegregated from other materials.How access to quarantined area isrestricted.

5.8 Whether separate sampling area foractive Raw Materials and Excipientsis provided and maintained.If yes, what is the control on entry ofmaterial and men into the samplingarea. Whether reverse LAF havebeen provided for sampling.Whether log book for samplingbooth maintained.If not what provision has been madefor sampling so as to preventcontamination, cross contaminationand mix-ups at a time of sampling.

5.9 Specify the arrangementsprovided to sample the primarypackaging materials foils, bottles,etc which are used as such.

5.10 Pls specify sampling plan used.Which type of sampling tools areused and how they are cleaned, driedand maintained.

SOP No.: EP-INS-004

5.11 How containers are cleaned beforeand after sampling. Who carries outthe sampling?(Pls specify whether the sampling iscarried out as per the current SOP).

5.12 What precautions are taken duringsampling of photosensitive,hygroscopic materials?

5.13 What provisions have been made forsegregated storage of rejected,recalled or returned materials orproducts.How is the access to these areasrestricted.

5.14 How highly hazardous, poisonousand explosive materials, narcotics,and psychotropic drugs are handledand stored.How these areas are safe and secure.Is there certification from competentauthority for handling of explosivesetc. If any. Pls attach the certificateissued by the competent authority.

5.15 How printed secondary packagingmaterials are stored in safe, separateand secure manner.

5.16 Specify the arrangement providedfor dispensing of starting materials.What is the control on entry ofmaterial and men into the dispensingarea? Whether reverse LAF havebeen provided for dispensing withback ground clean air supply.Whether pressure differential ismaintained between the dispensingand adjacent areas.

5.17 Which type of dispensing tools areused and how they are cleaned, driedand maintained.How containers are cleaned beforeand after dispensing. Who carriesout the dispensing?(Pls specify whether the dispensingis carried out as per the currentSOP).

5.18 How and where sampling of sterilematerials carried out.

5.19 What steps are taken againstspillage, breakage and leakage ofcontainers?

5.20 What provisions have been made toprevent the entry of rodents, insects,

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birds.Which substance is used for pestcontrol and how it is handled.(Pls specify whether the pest controlis carried out as per the SOP).

5.21 Whether record of master labels ismaintained for comparision toissued labels?

6 Production Area: -6.1 Please specify the design of the

manufacturing area which allow uni-flow and logical sequence ofoperations so as to prevent productcontamination/ mix ups.Is there any criss cross of flow ofmaterials and men.Specify the position of IPQC lab inthe manufacturing area .Please specify whether non storageareas used for storage of anymaterial.

6.2 Whether separate dedicated and self-contained facilities have beenprovided for the production ofsensitive pharmaceutical productlike Penicillin, Biologicalpreparation with like micro-organism, Beta lactam, SexHormones and Cytotoxic substances.If yes pls explain how and attachcopy of plan of premises of eachcategory of drug.

6.3 Please specify the provisions ofstorage of dirty, washed and cleanedequipment parts, tool room, inprocess storage areasetc. Which provide sequential /logical manner so as to preventcontamination and crosscontamination?

6.4 Please specify how service lines likepipe work, electrical fittings,ventilation openings etc. areidentified by colors for nature ofsupply and direction of the flow.Whether service lines in productionareas are through service pendants.If not, how they are placed so as toavoid accumulation of dust.

7 Ancillary areas: -

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7.1 Please specify the position of restand refreshment rooms and mentionwhether they are separate and notleading directly to the manufacturingand warehouse areas.

7.2 Are there general change rooms inplant?Are toilets, change room separatefrom mfg. Area? Pls specify numberof washing station & toiletsprovided for number of users.Whether change facilities separatedfor both sexes.How many sets of protectivegarments provided for eachpersonnel entering production area.Is there in house general laundry forgarment washing / cleaning? If nothow garments washing are carriedout and monitored

7.3 Whether maintenance workshop isseparate and away from production.

7.4 Whether animals for production ortesting are housed in the facility if sowhether areas housing animals areisolated from other areas.Please specify the provision of airconditioned and ventilation systemfor the animal house.How quarantined, under test andtested animals housed andcontrolled.How animal carcass are disposed of.Pls attach copy of CPCSEA.

8 Quality Control Area: -

8.1 Whether QC area is independent ofproduction area.Whether QC carries out its own: physico-chemical testing, biological testing, microbiological testing & sterilitytesting and Instrumental testing.Whether firm is outsourcing testing.If yes names of the testinglaboratories contacted or approved.Pls give list of test currentlyoutsourced.In case of contractual testing whatare the responsibilities of contractgiver and contract acceptor. (Copyof the contract should be enclosed)

SOP No.: EP-INS-004

Are there safety installation such asshower, eye washer, fireextinguisher etc in the laboratory.Is there separate area for humiditychambers for stability studies. Howmany humidity chambers have beenprovided. Pls attach stabilitycalendar.

8.2 Please specify the arrangementprovided for handling and storage oftest samples, retained samples,reference standards / cultures,reagents.Whether retained samples are storedfor a period of 1 year after expiry or3 years after distribution whicheveris earlier?Whether separate area for storage ofreagents and glassware provided.Whether separate records room isprovided.

8.3 How hazardous or poisonousmaterials are stored and handled.

8.4 How environmental conditions aremet during the course of storage andtesting of samples.

8.5 Which grade of glassware are usedin assay procedures.

8.6 Whether separate AHU's areprovided for biological,microbiological and radio iso-topestesting areas withHEPA filter arrangement.

8.7 Whether separate areas provided forsterility testing within microbiologylab.Whether support areas are underAHU.Whether double door autoclaveprovided for sterilization ofmaterials.

8.8 Whether entry to the sterility area isthrough three air lock systems.What is the air class of these testingareas and whether pressuredifference is maintained in theseareas?

8.9 Which types of workbenches areprovided in these areas for testing?When was the last filter integritytests performed on HEPA filters

SOP No.: EP-INS-004

8.10 How waste (cultures etc) disposedof.Whether in case of antibioticpotency testing, statistical proof ofthe determination of potency andvalidity of the test carried out.

9 Personnel: -9.1 Whether the manufacturing and

testing of drugs is conducted underapproved technical staffNames of Technical Staff alongwithqualification & experienceFor Manufacturing: -For Analysis:

9.2 Please specify whether head of Q.C.is independent of manufacturing unit

9.3 Name, qualification and experienceof the personnel responsible forQuality Assurance function.

9.4 Whether responsibilities forproduction and QC laid down andfollowed.

9.5 Whether adequate number ofpersonnel employed in directproportion to the work load.

9.6 What is the firm‟s policy on trainingof personnel at various levels?

9.7 How is Periodic assessment of thetraining checked?

10 Health, clothing and sanitation ofworkers: -

10.1 Whether personnel handling Betalactam antibiotics are tested forpenicillin sensitivity beforeemployment.

10.2 Whether personnel involved inhandling of sex hormones, cytotoxicand other portent drugs areperiodically examined for adverseeffect.(Pls specify whether the current SOPis followed or not).

10.3 Whether all personnel prior toemployment have undergonemedical examination including eyeexamination and all free fromTuberculosis, skin and othercommunicable or contagiousdiseases

10.4 Whether there is a SOP for medicalexamination.

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10.5 Pls give name and qualification ofcontracted medical officer formedical examination.

10.6 Whether investigational reports,films of X rays etc. preserved.Whether records of such medicalexamination are maintained thereof

10.7 Whether all personnel are trained toensure high level of personalhygiene.Pls attach training calendar of lasttwo years.

10.8 Whether proper uniforms andadequate facilities for personalcleanliness are provided.Pls specify nature and type of dressused by the personnel invarious areas of operation.How many dress/footwear have beenprovided to each personnel.Please specify whether cross overbench is in place in the change roomand if so whether it rule out thepossibility of entering dust particleto the clean side.Whether arrangements provided forcleaning of outside dust and dirtfrom footPlease specify whether hands aredisinfected before entering theproduction areaWhether for sterile garments inhouse clean laundry has beenprovided.

11 Manufacturing Operations andControls: -

11.1 Whether the contents of all vesselsand containers used in manufactureand storage is conspicuously labeledwith the name of the products. Batchno, Batch Size, and stage ofmanufacture along with signature oftechnical staff.

11.2 Whether the products not preparedunder aseptic conditions are freefrom pathogens like Salmonella,Escherichia coli, Pyocyanea etc.

11.3 If yes, pls give brief account ofmeasures taken to assure freedomfrom pathogens.

11.4 Precautions against mix-up andcross-contamination: -

SOP No.: EP-INS-004

11.4.1 Whether proper AHU, pressuredifferential, segregation, statuslabeling have been provided toprevent mix-up and cross-contamination in manufacturing area

11.4.2 Pls specify the areas of dustgeneration and mechanism involvedin controlling the dust.

11.4.3 Do all the areas have their ownindependent air locks separately formen and material entry.

11.4.4 What criteria of pressure differentialhave been set for production v/sadjoining areas.

11.4.5 Whether various operations arecarried out in segregated areas.

11.4.6 Whether processing of sensitivedrugs like Beta lactum Antibioticsand Sex Hormones is done insegregated areas with independentAHU and proper pressuredifferentials alongwithdemonstration of effectivesegregation of these areas withrecords.

11.4.7 Please specify what measures hasbeen taken to prevent contaminationof products with Beta LactumAntibiotics, Sex harmons and cytotoxic substances

11.4.8 What measures has been taken toprevent mix-ups during variousstages of production.

11.4.9 Whether equipments use forproduction are labeled with theircurrent status.

11.4.10 What is the policy for the use ofRecovery material?

11.4.11 Whether packaging lines areindependent and adequatelysegregated.

11.4.12 How line clearance is performed.Whether records of line clearance ismaintained according to appropriatechecklist

11.4.13 Whether separate coding area hasbeen provided or online coding isperformedHow coding procedure is controlled.

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11.4.14 Please specify how temperature,humidity and air filtration arecontrolled in the areas where rawmaterial and/or products are exposedand handled.

11.4.15 How access of authorized persons tomanufacturing areas includingpackaging is controlled.

11.4.16 Whether separate gowning provisionis follows before entering into theprocedure.

11.4.17 Whether segregated secured areasfor recall or rejected materials or forsuch material which are to beprocessed or recovered are provided.Please specify the room No. of suchareas in the plant.

11.5 Sanitation in the Manufacturingareas:-

11.5.1 Specify the cleaning procedure ofthe manufacturing areas.Whether cleaning procedure isvalidated.Please specify validation protocolNo. of the same.

11.5.2 Whether the manufacturing areas areused as the general thoroughfare andstorage of materials not underprocess.

11.5.3 Whether a routine sanitationprogram is in place.Please specify detailed account ofsanitation proramme specific tovarious areas, equipment.

11.5.3 Dose the location facilitate cleaningof equipment as well as the cleaningof the areas in which they areinstalled.

11.5.4 Whether production area isadequately lit. If yes.Please give lux levels provided inproduction, visual inspect

12 Raw Materials: -

12.1 Whether the hard copies of recordsof Raw Materials are maintained asper schedule-U.

12.2 Please specify the proceduresfollowed receiving and processing ofin-coming materials (Startingmaterials and packing material).

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12.3 Whether first in / first out or firstexpiry principal has been adopted.

12.4 How they are labeled and stored asper their status – Under Test,Approved and Rejected

12.5 Whether incoming materials arepurchased from approved sources.

12.6 What is the procedure for approvingthe source for incoming materials.

12.7 Whether the raw materials aredirectly purchased from themanufacturers.

12.8 Whether list of approved vendors isavailable to the user.

12.9 How damaged containers areidentified recorded and segregated.

12.10 How damaged containers areidentified recorded and segregated.

12.11 Whether all the containers of eachbatch of starting materials issampled for identification test.

12.12 Whether labels of raw material inthe storage area have informationlike(a) designated name of the productand the internal code reference,where applicable, and analyticalreference number;(b) manufacturer‘s name, addressand batch number;(c) the status of the contents (e.g.quarantine, under test, released,approved, rejected); and(d) the manufacturing date, expirydate and re-test date.

12.13 Whether separate areas are providedfor under test, approved and rejectedmaterials.

12.14 How control on temperature andhumidity conditions, wherevernecessary, maintained in thesestorage areas.

12.15 How the containers from whichsamples have been drawn labeled.

12.16 Please specify the procedures bywhich it is ensured that the rawmaterials which hasbeen released by the Quality ControlDepartment and which are withintheir shelf life are going to be usedin the product.

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12.17 How materials are stacked in theStores i.e on Pallets, racks etc.

13 Equipment: -13.1 Whether the equipments are

designed aiming to minimize risk oferror and permit effective cleaningin order to avoid crosscontamination, build up of dust

13.2 Whether all equipment are providedwith log book.

13.3 Please specify the procedures toclean the equipment after each batchproduction.

13.4 Whether validity period for use afterthe cleaning of equipment isspecified.

13.5 Whether separate area is providedfor storage of machine parts etc.

13.6 Whether balances and othermeasuring equipments withappropriate range are available inthe Raw Material stores &production areas and they arecalibrated in accordance with SOPmaintained.Specify the calibration schedule ofthe balances.

13.7 Please specify material ofconstruction of contact parts of theproduction equipments.

13.8 Which types of lubricants are usedin the equipment.Specify the quality and controlreference No. of these lubricants.

13.9 Specify the procedures to removedefective equipments fromproduction areas.

14 Documentation and Records: -14.1 How the documents are designed,

prepared, reviewed and controlled toprovide an audit trail.Whether documents are approvedsigned and dated by appropriate andauthorized person.Whether documents are approvedsigned and dated by appropriate andauthorized person.Whether documents specify title,nature and purpose.Whether documents are regularlyreviewed and kept up to date. If yes.

SOP No.: EP-INS-004

Please specify review period.Please attached the list of documentsmaintained by the firm

14.2 Whether the records are made at thetime of each operation in such a waythat all significant activitiesconcerning to the production aretraceable.

14.3 Whether data is recorded byelectronic data processing system orby other means. If by electronic dataprocessing system then how accessis controlled to enter, modify etc. thedata.

14.4 Whether master formula anddetailed operating procedures aremaintained as hard copy.

14.5 Who is responsible for maintenanceof these records.

15 Labels and Other PrintedMaterials:

15.1 Whether the printing is in brightcolour and legible on labels andother printed materials.

15.2 How printed labels (art work) areapproved. Is there any SOP for thisif yes please give current SOP No.

15.3 Which colour coding system is usedto indicate the status of a productand equipment.

15.4 How printed packaging materials,product leaflets etc. are storedseparately to avoid chances of mix-up.

15.5 How labels cartons boxes circularsinserts and leaflets are controlled.

15.6 Whether the samples from the bulkare drawn tested, approved andreleased prior to packaging andlabeling.How carryout the sampling

15.7 How records of receipt of alllabeling and packaging materials aremaintained.

15.8 Whether re-conciliation of usedpackaging materials is maintained.Whether unused packaging materialsreturn to the store or destroyed.

15.9 How returned/unused packagingmaterial like foils is controlled so asto prevent contamination and cross-contamination.

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15.10 How the labels of reference standardand culture maintained.

16 Quality Assurance: -16.1 Specify the comprehensive quality

assurance system maintained by thefirm Inter-alia to cover deviation,reporting, investigation and changecontrol.How the products are designed anddeveloped in accordance with GMP.

16.2 Please specify the arrangementsprovided to ensure that correctstarting and packaging materials areused for manufacture.

16.3 Please specify the mechanism bywhich all control like IP QCCalibration, Validation etc. areensured.

16.4 Please specify the mechanisms toensure that the finished product hasbeen correctly processed andchecked in accordance with theestablished procedures.

16.5 Please specify the mechanisms toensure that Pharmaceuticalsproducts are released for sale byauthorization person.

17 Self Inspection and Quality Audit: -17.1 Whether the firm has constituted a

self inspection team supplementedwith a quality audit procedure toevaluate that GMP is beingfollowed. If no. How internal auditsare carried out.

17.2 What is the system of monitoring,evaluation of self inspection.

17.3 How conclusion and recommendedcorrecting actions are followed andadopted.

17.4 What is the frequency of self-inspection.

17.5 Is there any proforma for carryingout the self-inspection.Please indicate the date of last self-inspection.

18 Quality Control System: -18.1 Please specify the details of quality

control system of the unit.

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18.2 How the reference standards arestored, evaluated and maintained.Please provide list of referencestandard and reference impuritiesprocured from the authentic sources.

18.3 Please specify the procedures ofpreparation of working standardfrom the reference standards.

18.4 Whether SOPs for sampling,inspecting, testing of Raw Materials,Finish products, Packing Materialsand for monitoring environmentalconditions are available.

18.5 Whether approved specifications fordifferent materials, products,reagents, solvents including test ofidentity content, purity and qualityavailable.

18.6 How reference samples from eachbatch of the products are maintained.

18.7 Who releases batch of the productsfor sale

18.8 Whether there is check list forrelease of a batch. Please specifycurrent SOP No. for batch release.

18.9 Please specify the samplingprocedures from various stages ofproduction.

18.10 How it is ensured that the samplecollected are representative of thewhole batch.

18.11 Please specify the procedures forcarrying out the stability studies.

18.12 Under what condition stabilitystudies of the products are tested.How many stability chambers havebeen provided.

18.13 How self life is assigned to aproduct. Please give current stabilityprotocol No.

18.14 Whether records of stability studiesare maintained.

18.15 Please attach stability calendar oflast year.

18.16 How complaints are investigated.18.17 How instruments are calibrated and

at which interval.18.18 How testing procedure validated

before they are adopted for routinetesting.

18.19 Specify the validation procedure isresponsible for validation of

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procedures.18.20 How validation procedures are

documented (Please indicate variousprotocols/ recoding system appliedduring validation).

18.21 Whether specifications for rawmaterials intermediates finalproducts and packaging materialsare available.

18.22 Whether periodic revision of thesespecifications are carried out.Please specify No. of STPs beingmaintained by the firm.

18.23 Which pharmacopoeias in originalare available in the plant.

19 Specifications: -

19.1 Whether specification of rawmaterial include.(a) the designated name and internalcode reference;(b) reference, if any, to apharmacopoeial monograph;(c) qualitative and quantitativerequirements with acceptance limits;(d) name and address ofmanufacturer or supplier andoriginal manufacturer of thematerial;(e) specimen of printed material;(f) directions for sampling andtesting or reference to procedures;(g) storage conditions; and(h) Maximum period of storagebefore re-testing.Whether specification of finishedproduct include(a) the designated name of theproduct and the code reference;(b) the formula or a reference to theformula and the pharmacopoeialreference;(c) directions for sampling andtesting or a reference to procedures;(d) a description of the dosage formand package details;(e) the qualitative and quantitativerequirements, with the acceptancelimits for release;(f) the storage conditions andprecautions, where applicable, and(g) the shelf-life.

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19.2 Whether the container and closuresmeet the pharmacopialspecifications.Whether second hand or usedcontainers and closures used.

20 Master Formula Records: -20.1 How master formula records are

prepared, authorized and controlled.20.2 Whether head of production, quality

control and quality assurance unitendorse this documents. Whethermaster formula is batch size specific.

20.3 Whether all products have masterformula containing.(a) the name of the product togetherwith product reference code relatingto its specifications;(b) the patent or proprietary name ofthe product along with the genericname, a description of the dosageform, strength, composition of theproduct and batch size;(c) name, quantity, and referencenumber of all the starting materialsto be used. Mentionshall be made of any substance thatmay „disappear‟ in the course ofprocessing.(d) a statement of the expected finalyield with the acceptable limits, andof relevant intermediate yields,where applicable.(e) a statement of the processinglocation and the principal equipmentto be used.(f) the methods, or reference to themethods, to be usedfor preparing the critical equipmentsincluding cleaning, assembling,calibrating, sterilizing;(g) detailed stepwise processinginstructions and the time taken foreach step;(h) the instructions for in-processcontrol with their limits;(i) the requirements for storageconditions of the products, includingthe container, labeling and specialstorage conditions where applicable;(j) any special precautions to beobserved;(k) packing details and specimenlabels.

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21 Packaging Records: -21.1 Whether authorized packaging

instructions for each products, packsize and type are maintained andcomplied with.Whether following are included inthe packaging instructions.(a) Name of the product;(b) the pack size expressed in termsof the weight or volume of theproduct in the final container;(d) complete list of allthe packaging materials required fora standard batch size, includingquantities, sizes and types with thecode or reference number relating tothe specifications of each packagingmaterial.;(e) reproduction of the relevantprinted packaging materials andspecimens indicating where batchnumber and expiry date of theproduct have been applied;(f) special precautions to beobserved, including a carefulexamination of the area andequipment in order to ascertain theline clearance before the operationsbegin.(g) description of the packagingoperation, including any significantsubsidiary operations and equipmentto be used;(h) details of in-process controlswith instructions for sampling andacceptance; and(i) Re-conciliation after completionof the packing and labelingoperation.(j) Whether line clearance recordsare part of batch packing records.

22 Batch Processing Records(BPR)

22.1 Whether BPR are based on currentmaster formula record.

22.2 How BPR are designed to avoidtranscription errors.Whether the Batch ProcessingRecords for each product on thebasis of currently approved masterformula is being maintained.Whether following information arerecorded in BPR

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(a) the name of the product,(b) the number of the batch beingmanufactured,(c) dates and time ofcommencement, significantintermediate stages and completionof production.(d) initials of the operator ofdifferent significant steps ofproduction and where appropriate,of the person who checked each ofthese operations,(e) the batch number and/oranalytical control number as well asthe quantities of each startingmaterial actually weighed,(f) any relevant processing operationor event and major equipment used,(g) a record of the in-processcontrols and the initials of theperson(s) carrying them out,and theresults obtained,(h) the amount of product obtainedafter different and critical stages ofmanufacture (yield),(i) comments or explanations forsignificant deviations from theexpected yield limits shall be given,(j) notes on special problemsincluding details, with signedauthorization, for any deviation fromthe Master Formula,(k) Addition of any recovered orreprocessed material with referenceto recovery or reprocessing stages.Specify the procedures for all theentries made in BPR‟s.

23 Standard Operating Procedureand Records: -Whether SOPs and records are beingmaintained and complied for thefollowing.SOP for receipt of in comingmaterial(a) SOP for Internal labelling,quarantine, storage, packagingmaterial and other materials(b) SOP for each instrument andEquipment(c) SOP for sampling(d) SOP for batch numbering(e) SOP for testing(f) SOP for equipment assembly and

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validation(g) SOP for Analyticalapparatus and calibration(h) SOP for maintenance, cleaningand sanitation(i) SOP for training and hygiene forthe personal(j) SOP for retaining referenceSamples(k) SOP for handling, re-processingand recoveries(l) SOP for distribution of theproduct(m) SOP for warehousing ofproducts.Whether applicable SOPs areavailable in each area where they arerequired.Whether recording formats arereferred in SOP.Is there SOP for writing an SOP.

24 Reference Samples24.1 Specify the procedures for collection

of reference samples of activeingredients and finishedformulations and how they arestored and maintained.

25 Reprocessing and Recoveries25.1 Is appropriate Validation of

recoveries and reprocessing done isbeing performed?

26 Distribution records26.1 Whether pre dispatch inspections are

carried out before release.26.2 Whether periodic audits of

distribution center are carried out toaccess warehousing practices

26.3 Whether distribution records are partof the batch record. If not how batchwise distribution record up to retaillevels are maintained.

26.4 Whether instruction for warehousingand stocking of products like LVPs,Heat sensitive etc are available instore.

26.5 Whether Good DistributionPractices followed

27 Validation and ProcessValidation: -

27.1 Specify the validation policy of thecompany.Whether validation master plan has

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been prepared.27.2 Whether validation studies of

processing, testing and cleaningprocedures are conducted as per predefined protocol.

27.3 How records and conclusion of suchvalidation studies are prepared andmaintained.

27.4 Whether master formula is based onapproved process validation.

27.5 Specify how significant changes tothe manufacturing processequipments material etc arecontrolled.

27.6 Whether DQ,IQ,OQ & PQ are inplace for all major equipment andfacility.

27.7 Whether validation records of allutilities and major equipments areavailable.

28 Product Recalls: -28.1 Specify the product recall system

followed by the firm.How promptly recall operation at thelevel of each distribution channelup-to the retail level can be carriedout.Whether there is a SOP for recall ofproducts clearly definingresponsibility, procedure, reporting,re-conciliation etc.

29 Complaints and Adverse Reactions:29.1 Specify the review system for

complaints concerning the quality ofproducts.

29.2 How records of complaint andadverse reactions maintained.

29.3 Whether reports of serious drugsreaction with comments anddocuments immediately sent toLicensing Authority

29.4 Is there any criteria for action to betaken on the basis of nature ofcomplaint / adverse reaction.

30 Site Master file: -30.1 Whether all the relevant information

have been included in the site masterfile.

30.2 Whether quality policy has beenincluded in the site master file.Please attach the current version

30.3 Is there a master plan (Master

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validation plan) covering:30.4 Resources and those responsible for

its implementation.30.5 Identification of the systems and

processes to be validated30.6 Documentation and standard

operating procedures (SOPs), WorkInstructions and Standards(applicable national andinternational standards)

30.7 Validation list: facilities, processes(e.g. aseptic filling), products

30.8 Key approval criteria30.9 Protocol format30.10 Each validation activity, including

re-validation and reasonableunforeseen events (power failures,system crash and recovery, filterintegrity failurer. Please attachvalidation calendar.

30.11 Pls specify whether the criticalprocesses validated Prospectively,retrospectively or concurrently.

30.12 Whether validation of followingperformed and documented:Analytical methods, Production andassay equipment, Sterile productionprocesses, Non-sterile productionprocesses, Cleaning procedures,Critical support systems (purifiedwater, water for injections, air,vapor, etc.), Facilities

30.13 Please list reasons consideredimportant for validation or re-validation.

30.14 In case electronic data processingsystems are used, are thesevalidated?Please specify whether periodicalchallenge tests performed on thesystem to verify reliability.

30.15 Are the validation studies performedaccording to pre-defined protocols?Is a written report summarized,results and conclusions prepared andmaintained? Is the validity of thecritical processes and proceduresestablished based on a validationstudy?

30.16 Are criteria established to assess thechanges originating a revalidation?Are trend analyses performed to

SOP No.: EP-INS-004

assess the need to re-validate inorder to assure the processes andprocedures continue to obtain thedesired results?

31 WATER SYSTEMPURIFIED WATERWATER FOR INJECTIONS

31.1 Please specify whether wastersystem qualification (IQ, OQ andPQ) has been carried out as perprotocol and repots have beenprepared and maintained.

31.2 Whether IQ protocol include at leastfacility review, equipmentspecification vs. design, weldingroughness testing on pipelines,absence of dead points / section inthe pipelines, pipe and tankpassivation, drawings, SOP foroperations, cleaning, sanitation,maintenance and calibration ofgadgets. Whether its report includesConclusion / Summary, descriptionof the performed assay, Data tables,Results, Conclusions, Protocolreference, Revision and approvalsignatures.

31.3 Whether OQ protocol include atleast System production capacity(L/min), Flow type and water rate,Valve operation, Alarm systemoperation and Controls operation?

31.4 Whether its report includesConclusion / Summary, descriptionof the performed assay, Data tables,Results, Conclusions, Protocolreference, Revision and approvalsignatures.

31.5 Please specify the water whetherPhase 1, Phase 2 and Phase 3 studiescarried out in at PQ stages?

31.5.1 Phase 1 : Whether the operationsparameters, cleaning and sanitationprocedures & frequencies defined.Whether daily sampling records forevery pretreatment point and usagepoint for a period of 2 to 4 weeksmaintained and SOP‘s prepared.

31.5.2 PHASE 2 : Whether daily samplingrecords for every pretreatment pointand usage point for a period of 4 to 5weeks after Phase 1 maintained andreviewed.

SOP No.: EP-INS-004

31.5.3 PHASE 3 : Whether weeklysampling records available of everyusage point for a one-year period.In the case of water for injectionssystems, are the daily samplingrecords of at least one usage pointavailable, with all the usage pointssampled weekly?Whether results of these recordssummarized to show suitability.Are there personnel trainingrecords?

32 EQUIPMENT32.1 Are the equipment installation

Qualification (IQ) protocols containsfollowings: Introduction, Installationdescription, Responsibilities,Performed tests/assays,Qualification acceptance criteria andData recording and reporting?

32.2 Whether report contains Summary,Description of performedtests/assays, Obtained data tables,Results, Conclusions, Installationdiagrams, Revision and approvalsignatures.

32.3 Whether the equipment operationqualification (OQ) protocolscontains following: Introduction,Equipment description, Descriptionof the equipment operation steps(SOP‘s), Responsibilities,Qualification acceptance criteria,Data recording and reporting.Whether report contains Summary,Description of performedtests/assays, Obtained data tables,Results, Conclusions, Revision andapproval signatures.

32.4 Whether equipment performancequalification (PQ) protocols containsfollowings: Introduction,Responsibilities, Performed assays,Qualification acceptance criteria,Data recording and reporting.

32.5 Whether report contains Summary,Description of performedtests/assays, Obtained data tables,Results, Conclusions, Revision andapproval signatures.

32.6 Whether Preventive MaintenanceSchedule of the equipments isfollowed and records available?

SOP No.: EP-INS-004

33 Analytical Method Validation33.1 Please specify whether following

Characteristics are consideredduring validation of analyticalmethods:— specificity— linearity— range— accuracy— precision— detection limit— quantitation limit— Robustness.

33.2 Whether Paharmocopial methods arealso validated. If yes, how.

33.3 Whether system suitable testing isincluded in testing protocols e.g.HPLC, GC etc.

33.4 Whether the procedure covers allaspects of impurity profilingrequired

33.5 Whether procedure covers allaspects of Organic VolatileImpurities detection andquantification

34 CLEANING34.1 Is a validation performed to confirm

cleaning effectiveness?34.2 Does the protocol define the

selection criteria for products orgroups of products subject tocleaning validation?

34.3 Is data produced supporting theconclusion that residues wereremoved to an acceptable level?

34.4 Please specify whether thevalidation is implemented to verifycleaning of:Surfaces in contact with the product,After a change in product, Betweenshift batches.

34.5 Please specify whether theValidation Strategy includecontamination risks, equipmentstorage time, the need to storeequipment dry and sterilize and freeof pyrogens if necessary?

34.6 Whether the cleaning ValidationProtocol include:a. Interval between the end ofproduction and the beginning of thecleaning SOP‘s.

SOP No.: EP-INS-004

b. Cleaning SOP‘s to be used.c. Any monitoring equipment to beused.d. Number of consecutive cleaningcycles performed?e. Clearly defined sampling points.

34.7 Whether Quality Control responsibleof the sampling for cleaningverification?

34.8 Whether personnel engaged incleaning, sampling etc. trained.

34.9 Please specify whether acceptancelimits been set for cleaningverification and are based onfollowing criteria:a. Visually clean.b. 10 ppm in another productc. 0.1% of the therapeutic dose?

34.10 Please specify whether detergentresidues investigated anddegradation products verified duringvalidation.

34.11 Whether validation records includeRecovery study data, Analyticalmethods including Detection Limitsand Quantification Limits,Acceptance Criteria, Signatures ofthe Quality Assurance Manager,employee in charge of cleaning andthe verification from Production andQuality Control.

35 HVAC35.1 Please specify whether following

parameters have been qualified:— temperature— relative humidity— supply air quantities for alldiffusers— return air or exhaust air quantities— room air change rates— room pressures (pressuredifferentials)— room airflow patterns— unidirectional flow velocities— containment system velocities—filter penetration tests (HEPA)— room particle counts— room clean-up rates— microbiological air and surfacecounts where appropriate— operation of de-dusting— warning/alarm systems whereapplicable.

SOP No.: EP-INS-004

35.2 Whether strategic tests like Particlecount, air pressure differential, airflow volume, air flow velocity etc.included in HVAC qualification.

36 Media fill test36.1 Whether medial fill tests carried out

twice in a year during normalworking conditions.

36.2 Pls give date of last such test.36.3 How many units are filled and

tested.36.4 What is the criterion for

qualification of this test?36.5 In case of failure of media fill test,

what precautions or actions aretaken.

37 Product Information37.1 Name of product

(i) Generic Name(ii) Brand Name

37.2 Whether validated master formula isavailable?

37.3 Whether specific SOP for productprocessing is available?

37.4 Comments on the above SOP37.5 Process Validation performed for the

product covers all aspects and theapproach is Risk Based

37.6 No. of Batches Produced37.7 Stability studies

(i) Accelerated(ii) Real Time(iii) Whether the expiry dateassigned on the basis of stabilitystudy?

37.8 Whether trend analysis was carriedout and interpretation thereof?

37.9 Whether Annual product review(APR) is carried out?

37.10 Is there any complaint received forthe product and If any, whether theinvestigation report along with ATRis maintained?

annexure-1 gmp checklist

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