GMP现场检查Checklist(ENGLISH).doc

6.2 Addendum B：GMP Checklist for Compliance with GMPDIRECTORATE: INSPECTORATE and LAW ENFORCEMENTROUTINE GMP:APPLICANT WITH OWNMANUFACTURING PLANTINSPECTORS CHECKLIST FOR ROUTINE GMP INSPECTION6.3 Addendum C: Cover letter for GMP inspectionsSUB DIRECTORATE: MEDICINES CONTROLROUTINE GMP:APPLICANT WITH OWNMANUFACTURING PLANTINSPECTORS CHECKLIST FOR RROUTINE GMP INSPECTIONTHIS DOCUMENT MAY NOT BE REPRODUCED FOR ANY OTHER PURPOSE THAN FOR THE USE BY AN INSPECTOR TO ASSIST DURING AN INSPECTION. IT REMAINS THE PROPERTY OF THE INSPECTORATE. NO COPY MAY BE PROVIDED TO ANY OTHER PERSON WITHOUT THE PRIOR AUTHORISATION BY THE HEAD OF THE INSPECTORATE.COMPILED BY AJ VAN ZYL2 EDECEMBER 1997File no.: Type of Inspection: Routine GMPCompany name:Company address:(Postal)Company street address:Tel no.:Fax no.:RESPONSIBEL PHARMACIST:QA MANAGERPRUDUCTION MANAGER:ACTIVITIES:APPLICANT:MANUFACTURER:PACKER:DISTRIBUTOR:LABORATORY:DOSAGE FORMS HANDLED:CAPSULES:LIQUIDS:S.V.P:AEROSOLS:LOZENGES:OTHER (SPECIFY):TABLETS:POWDERS:L.V.P:SUPPOSITORIES:CREAM/OINTMENTS:TYPE:CYTOTOXICS:HORMONES:PENICILLINS:BIOLOGICALS:OTHER:HOMEOPATHIC:CEPHALOSPORINS:DENTAL:VETERINARY:Staff Member:Date of contact:Time involvement: (Preparation+Travel+Inspection+Report)GG vehicle no.:KM:File no.: Type of Inspection: Routine GMPCompany name:Company address:(Postal)Company street address:Tel no.:Fax no.:RESPONSIBEL PHARMACIST:QA MANAGERPRUDUCTION MANAGER:ACTIVITIES:APPLICANT:MANUFACTURER:PACKER:DISTRIBUTOR:LABORATORY:DOSAGE FORMS HANDLED:CAPSULES:LIQUIDS:S.V.P:AEROSOLS:LOZENGES:OTHER (SPECIFY):TABLETS:POWDERS:L.V.P:SUPPOSITORIES:CREAM/OINTMENTS:TYPE:CYTOTOXICS:HORMONES:PENICILLINS:BIOLOGICALS:OTHER:HOMEOPATHIC:CEPHALOSPORINS:DENTAL:VETERINARY:Staff Member:Date of contact:Time involvement: (Preparation+Travel+Inspection+Report)GG vehicle no.:KM:OBSERVATIONSA: PLANT WALK-THROUGH1. PREMISES AND EQUIPMENT (general)1.1 Layout/design Minimise: risk of errors, mix-up, cross-contamination, build up of dust or dirt.1.2 Permit effective cleaning, maintenance1.3 SOP: Rodent, insect and pest control. No insects, animals (especiallyrodents) or birds, premises1.4 Building maintained in good order1.5 Waste materials continually removed, check dust bins, labels, products1.6 SOP for sanitation with schedules,methods, materials and equipmentavailable, cleaning and disinfectionon-going on a regular basis and include change rooms, wash rooms, toilets and canteen1.7 Adequate lighting and venitilation, filters, gauges, dust controlled,humidity, pressure and temperatures,(filtration of outside air and airreturned to the atmosphere the minimum requirement).1.8 Environmental conditions monitored regularly and recorded.1.9 Production areas-logical flow, sufficient space1.10 Production of potent products inseparate facilities(penicillins,biologicals, certain antibiotics, certain hormones and certain cytotoxics indedicated facillities)1.11 Technical poisons, (pesticides and herbicides) not in premises used for the manufacture of medicinal products.1.12 Working and in-process storage spacesufficient.1.13 Dust extraction and collection wheredust is generated.1.14 Drains have trapped gullies1.15 Pipes, fittings and the other servicesdo not create places difficult to clean1.16 Fixed pipework labeled to indicate thecontents and direction of flow.1.17 Floors, walls and ceilings: materials that facilitate cleaning1.18 Storage areas: ensure good storageconditions (clean, dry, temperature)1.19 Special storage area for flammable goods/cold rooms/low humidity rooms. Monitored and equipped withalarms to alert in case of failure.2. CHANGE ROOMS2.1 Rest rooms, smoking areas andRefreshment rooms separate fromOther areas2.2 Washing and toilet easily accessibleand appropriate for the number of users.2.3 Toilets not directly communicate withProduction or storage areas, clean andwell ventilated2.4 Soap, towels, toilet paper, (showers where necessary)2.5 No foreign material (labels, medicine)3. RECEIVAL AREA3.1 Acceptance and dispatch bays protect materials/products from the weather.3.2 Each container/grouping of container cleaned, examined for appropriate labeling (including name, batch number, expiry date, supplier)damage and contamination,containerscompared with order document and invoice3.3 In-house nomenclature list3.4 Approved suppliers list (Reg Affairs)3.5 SOPs available: control, purchasing, receipt, storage, handling and issuing of raw materials, packaging material components, intermediate and finished products.3.6 All materials handled and stored in a manner to prevent contamination, deterioration and intermixing.3.7 Only taken into stock if all relevant documentation (eg. Delivery note and COA) accompanied.3.8 Materials subject to QC quarantined and ithheld from use, until tested and released by quality control.3.9 Status clear, appropriately labeled manually or validated computer systems.3.10 Purchase, handling and control ofprimary and printed packaging materials.3.11 Receipt of starting material, and PPMrecorded, (GRV), include: date of receipt,name of material, supplier, suppliersbatch number, total quantity and numberof containers, AR number assigned.4 WAREHOUSES4.1 If not computer controlled-separate demarcated areas, preferably physically separated for: sampling, quarantine, raw materials, packaging material, intermediate and finished products, rejected, recalled and returned goods.4.2 Access restricted, safe and secure conditions.4.3 Quarantined, approved or rejected goods segregated byl Physically segregated areasl Clear and easily distinguishableStatus labeling, (Labels applied tocontainers, equipment adhere well, areclear, unambiguous, completed,)l A system of control, e.g. byComputers, (validated)4.4 Conditions, SOP for control and monitoring of: l Storage temperaturel Huminityl No direct lightl No exposure to air4.5 Off the floor, suitably spaced from other materials and walls4.6 Batch integrity maintained4.7 Sampled Bulk containers can be identified4.8 FIDO4.9 Re-test dates adequate system for monitoring the storage period5 SAMPLING AREA5.1 Separate area, lighting, ventilation, dust extraction5.2 Sops, equipment5.3 SOP and records for cleaning5.4 Prevent cross-contamination5.5 Samples are representative of the batch5.6 SOP include: method. Equipment to be used, amount of sample, instructions for any required sub-division, type and condition of sample container, special precautions to be observed (sterile or noxious material), cleaning and storage of sampling equipment.5.7 Sample label indicating: contents, batch no date of sampling, sampler initial, link from which container the sample was taken.5.8 Care: avoid contamination, or deterioration during and after sampling, containers resealed6 RELEASED MATERIAL STORE6.1 Only QC released material6.2 Status clear6.3 Issuing of material performed by suitably trained and responsible persons, properly released, batch integrity maintained.6.4 Records for quantities received, issued and returned6.5 Discrepancies investigated.6.6 Appropriately labeled (status clear, not too many labels): name, internal code reference, batch number given at receipt, status, expiry/re-test date.6.7 FIFO6.8 No expired stock7 REJECTED GOODS AREA7.1 Dedicated area, access controlled7.2 SOP: label, responsibility7.3 Reasons for rejecting documented8 RETURNED GOODS AREA8.1 Dedicated area, access controlled8.2 Returned from the market: destroyed unless without doubt their quality is satisfactory8.3 SOP: 9 PRINTED PACKAGING MATERIAL STORE9.1 Access controlled9.2 Separate locked areas with each component stored separately with suitable identification9.3 Supervision of a suitably trained and responsible person9.4 Issuing strict and careful control, order9.5 Avoid mix-ups: transport in sealed containers excess components destroyed if intermixing could have occurred returned components batch integrity maintained9.6 Foil: temp and humidity10 DISPENSARY10.1 Material released by QC, within shelf-life10.2 Dispensed by designated persons.10.3 Correct materials accurately weighed into clean, properly labeled containers10.4 No foreign material present10.5 Each dispensed material ID and mass/volume independently checked andsigned by pharmacist/other legallyauthorized person.10.6 Materials dispensed for each batch kept together, conspicuously labelled 10.7 SOPs and records for cleaning10.8 SOP and records for calibration and maintenance of balances10.9 Lighting and ventilation, dust extraction11 PRODUCTION AREAS11.1 Flow, walls, floors, temp, cross- contamination11.2 Addition to the mix checked and signed for by a pharmacist11.3 One product at a time per area or no risk of mix-up or cross-contamination11.4 Materials per batch kept together11.5 Areas and equipment checked for cleanliness prior to starting production.11.6 Products and materials protected from microbial and other contamination11.7 Materials, bulk containers, major itemsof equipment, rooms used labeled/identified with product or material being processed, its strength and batchnumber, and stage of production.11.8 Pipelines are connected correct11.9 Access controlled11.10 Deviations controlled11.11 Yields and reconciliation of quantitiescarried out, discrepancies investigatedand explained.11.12 Critical steps signed for.11.13 In-process laboratory tests done11.14 Inappropriate labels removed fromcontainers or equipment before enteringthe manufacturing area11.15 Environmental control done11.16 Cross-contamination avoided and effectiveness checked periodically(SOP).11.17Prevent generation,dissemination of dust11.18 Authorization of start of manufacture in area11.19 Intermediate and bulk products: storage conditions, controlled periods, labels.11.20 SOP reworks11.21 Specific for oral solid dosage forms11.22 Specific for Sterile products11.23 Specific for LCO, aerosols11.24 Fixed pipework clearly labeled to indicate contents and direction of flow.11.25 No eating, drinking, chewing andsmoking, or the storage of food, drink,smoking materials and personal medicationin manufacturing areas11.26 No direct contact between the operators hands and starting materials, intermediates and products11.27 Protective clothing apply to all (including visitors, maintenance personnel, senior management and inspectors) entering production areas, regularly and frequently cleaned, not worn outside the factory premises11.28 Defective equipment removed or at least clearly labeled as defective11.29 Cleaning: SOP,11.30 Equipment stored in a clean and dry condition.11.31 Adequate cleaning records indicating previous product made11.32 Entries in clear legible writing, with confirmation by adding initials, no sticking, in ink or other indelible medium11.33 Records completed at the time of action11.34 Errors corrected, such a manner, original entry is not lost-initialed and dated, plus reason for correction. No correction fluid12 PACKAGING12.1 Area suitable (space, light, ventilation)12.2 SOPs12.3 Packaging documents,legal requirements, labels and labeling12.4Obsolete PPM destroyed and recorded.12.5 Packaging lines well separated or physical barriers to prevent mix-ups12.6 Line-clearance/opening: check-list and signed for (eg PPM, printing operations, bulk identity) signed by pharmacist.12.7 Name and batch number displayed at packaging station or line12.8 Checked on delivery to the packaging department: quantity, identity and conformity with the packaging instructions12.9 Filling and sealing followed by labeling as quickly as possible.12.10 Printing operation (eg, code numbers, expiry dates) checked and recorded.12.11 Hand packing operations increased vigilance to prevent inadvertent mix-ups. 12.13 In process: procedures and tabulated checks signed at regular intervals for:l General appearance of the packagel Fill masses/volumes or quantity complyl Whether the packages are completel Whether the correct products and pack- Aging materials are usedl Whether any over-printing is correctl Seal integrityl Correct functioning of line monitors.12.14 Automated controls and monitors checked regularly during production run and validated from time to time.12.15 Samples taken away from packaging line not returned12.16 Completion of a packaging run: reconciliation.12.17 Special care to control return of unused packaging materials12.18 Line closing: clean, removal of material, labels and unused batch-coded packagingmaterials-destroyed and destruction recorded13 FINISHED PRODUCT RELEASE13.1 Finished products quarantined until released.13.2 Documentation reconciled, complete/and sent for complete documentation audit by quality assurance: SOP.13.3 Released for sale by a pharmacist.14 QUALITY CONTROL LABORATORY (Good Laboratory Practice)1 Premises: separated from production areas, Independent from Production1 Clean: floors, walls, ceilings, extraction/ ventilation, lighting, pipes, wires. Records/logs1 Special requirements for biological/ radioactive samples/penicillin adhered to1 Properly trained, managed and motivated staff, dress code cmplies1 Sufficient space to avoid mix-ups and cross-contamination Adequate suitable storage space for samples and records1 Organogram (authorized, names) linked to job descriptions, experience1 Equipment: location, condition, logs to be kept: SOPs for each piece of equipment (operation, cleaning, calibration/checks), maintenance records1 Documentation: SOPs: sampling, retention samples and records,stability,investigation of complaints related to quality, testing and supervision of the testing of all materials and products, control over labeling SOPs, maintenance records, specifications, master documents, log books, test results, COAs, labels, trend analysis, self audit, authorization, archiving Text books ( Pharmacopoeia) Testing: retesting if fail (SOP), re-sampling,no averaging of results, master documentationreadily available and include: specifications,sampling procedures, testing procedures andrecords (including analytical worksheets and/or laboratory notebooks),analytical reportsand/or certificates, data from environmentalmonitoring, validation records of test methods,SOP and records of calibration and maintenance Test records: name, quantity of product, codereference, date of receipt,sampling and testing,manufacturer and/or supplier of product, supp-liers batch no., test performed, reference to the relevant specifications and test methods used and to any COA, test results including observations and calculations, initials of analyst and supervisor, decision statement regarding release, rejection or other status.Analysts laboratory records available: sourcedata (eg. weighings, readings, recorder charts,etc.), results and calculations documented and critically examined/checkedTesting (starting material) recorded, (master specifications) and include: Date of sampling, date of testing, name and quantity of materials, batch identifying no., results of tests, analyst, cross reference to COA, analysts signature, status decision.BMR, AR retained for at least one year afterthe expiry date of batch.Testing of packaging materials recorded(muster specifications) and include:date of sampling, date of testing, name ofmaterials, batch number, results, analyst,analysts signature, statusReagents: purchased or prepared to SOP,records, label, storage, expiry date, discardVolumetric solutions: Purchase, storage,labeling (identity, factorization, date ofstandardization, BN, date of preparation,signature, storage condition, expiry date),calculations, log books, date for re-standardization, signed, datedComputers: URS, qualification (IQ, OQ, PQ), security (change) and historical data, data data entries not deleted tamperproof database printer as specified Poisons and hazardous substances: Cupboard, list, register (receival and issue), SOP for accidentsSOP: waste collection and disposalSampling SOP: method, equipment, amount, composite, containers, labeling (name, BN, date, number of container ,sample container nr), status label control, who, where, what, sampling points in container, precautions, storage, cleaning of equipment (cross-contamination), tests, results, specifications.SOP for retest if fails specificationGlassware: SOP safe use and storage, no cracked/chipped/broken volumetric glassware e.g. pipettes.SOP for cleaningReference standards: Primary vs. secondary, temperature, humidity,Light, label for secondary(name, BN, potency,date of preparation, date of assay, date ofreceipt, date of opening, retest date, containernumber of total), COACalibration: SOP for calibration for each piece of equipment:external calibration (contract acceptor: frequencywhat to do, methods,personnel, reports,changecontrol), and in-house: what,(selection criteria,instrument), who (training, responsibility,expertise), method (where, how, using what),standards (precision, accuracy, traceability,certified), frequency (justification, scheduling,flagging), limits, (justification, validation,approval, action if limits exceeded), record(instrument, date, SOP, what to record, review(frequency acceptance criteria (tolerance),labeling (instrument nr, date, due date, signature)Dissolution apparatus:SOP for use (sampling, volume, media, degassing),Maintenance recordSOP for calibration: RPM, whobble, belttension, temperatureCleaning of waterbathSOP: System suitability (USP) plus recordsPH meter:SOP operation, cleaning, calibrationPreparation of buffer solution (tablets-expirydate, discarding of solution, if poured from original container-period of use), labeling,record, temperature vs. reading, maintenancerecordBalances:Shockproof bench, (attached to wall or floor),air flow, no foreign material, not in walk way/passage, no heaters, no plastic containers forweighing, calibration record, range, masspieces,maintenance recordHPLC:SOPs for use, calibration, cleaningLog for use of columns (date, column nr,product, batch nr)Storage of columnsSOP for washing/rinsing of columnsPH of rinse, type of methanol usedDedicated columns, determination of nr ofPlates and frequencySystem suitabilityMaintenance recordViscometer:SOP use, cleaning,Maintena