Gmp Checklist

GMP Checklist Company Name: Address Phone Number: Date: Contact Person: Title: Phone Number:

Questions 1.1. GENERAL 1.1.1. 1.1.1.1.

Response 1

General information Is there evidence of registration of the key persons responsible by the Regulatory Authority?

1.1.1.2.

Is the qualified person responsible, according to company's organization chart, present at the time of the inspection?

1.1.1.3.

Is there evidence of a license to operate issued by the Regulatory Authority?

1.1.1.4.

is there a complete separation between beta-Lactam (penicillin /cephalosporin), hormones or cytotoxic products or any hazard material with other area& Lines in the scope of inspection incase the line not for one of this products?

1

2 3

1.1.1.5.

Is there a GMP related recalls from the market in last 2 years?

1.1.2. 1.1.2.1.

Premises Are there any sources of environmental contamination in the area surrounding the building? 1.1.2.2. If "YES", are protective measures undertaken? 1.1.2.3. Are there approved and up to date layouts for the area? 1.1.2.4. Are toilets located before change rooms? 1.1.2.5. Are there physically separated areas for each production step? 1.1.2.6. Is the flow of personnel and materials shown such that they are unidirectional& prevent product contamination &mix up? 1.1.2.7. Is there a distinct and separate area for washing 1.1.2.8. Do the flow of cleaned equipment through the washing room don’t allow re contamination? 1.1.2.9. Is there packaging area completely physically separated from processing area? 1.1.2.10. Are drained equipped to prevent back flow? 1.1.2.11. Are the visible electrical installations maintained in good condition? 1.1.2.12. Does the company comply with the national legislation on fire control and prevention? 1.1.2.13. Is waste treatment program covering the entire factory? 1.1.2.14. Is there a special lighting system in the sampling, weighing, processing area in case those photosensitive raw materials are being handled? 1.1.3. Ancillary area 1.1.3.1. Are there SOP’s for washing uniforms separately depending on the type of area (sterile, non sterile, maintenance, special products)? 1.1.3.2. Is there a laundry area for uniforms which is separate from production areas? 1.1.3.3. If an outside laundry facility is used, are personnel and the person responsible instructed about the corresponding SOP? 1.1.3.4. Is this outside laundry facility periodically audited & the audit recorded? 1.1.3.5. Is there a pure steam generator, if necessary? 1.1.3.6. Is there a compressed air generator free of oil, if necessary? 1.1.3.7. Is there an electricity generator for the maintenance of critical systems and processes to be used in case of problems with the electricity supply occur? 1.1.3.8. IS it connected to critical equipment as autoclave, lyophilizer …etc? 1.1.3.9. Do its performance tested &the time it starts work after electricity drop is suitable? 2

1.2. VALIDATION 1.2.1. 1.2.1.1. 1.2.1.2. 1.2.1.3. 1.2.1.4. 1.2.1.5.

1.2.1.6. 1.2.1.7. 1.2.1.8. 1.2.1.9. 1.2.1.10.

1.2.1.11. 1.2.2. 1.2.2.1.

1.2.2.2. 1.2.2.3. 1.2.2.4. 1.2.2.5. 1.2.2.6. 1.2.2.7. 1.2.2.8.

General aspects: Is there a validation master plan? Is there a validation and re-validation program, and under the responsibility of quality assurance for approval and follow-up of its activities? Are critically important processes validated? Are the validations performed and documented? Is every important modification to the manufacturing process validated, including any change in equipment, manufacturing area, materials, changes in raw materials, packing materials, changes in critical support systems processes and methods that may affect the quality of the product or reproducibility of the process? In case electronic data processing systems are used, are these validated? If the system automated is a safety back-up kept? Are safety passwords used for system access? Are these passwords only assigned to authorize personnel? Are the validation studies performed according to pre-defined protocols &there is a report? Are trend analyses performed to assess the need to re-validate in order to assure the processes and procedures continued to obtain the desired results? CLEANING Is a validation performed to confirm major& minor cleaning effectiveness? Is the quality of the water used in the final rinse of the same quality of the water used in production? Does the Validation Protocol include Cleaning SOP’s to be used& clearly defined sampling points? Is the work of the Operating Personnel effectively supervised? Have acceptance limits been set according worst case? Are detergent residues within limits? Are there Validation Records? Is the Final Validation Report is supported by the signature of all those involved, the verification by Production and the signature of Quality Assurance?

1.3. WATER SYSTEM 1.3.1. GENERAL 3

1.3.1.1.

Is the source of water used in the company allowing suitable continuous supply?

1.3.1.2.

Are the system schematics shown?

1.3.1.3.

Does the company have potable, purified water tanks?

1.3.1.4.

Is the cleaning and disinfecting record for cistern (if present) & potable water tanks documented, is it maintained in good condition?

1.3.1.5.

Does the procedure include a justifiable frequency and sampling points?

1.3.1.6.

Is there a SOP for sampling of all types of produced water?

1.3.1.7. Are physicochemical& microbiological tests&, (endotoxin for WFI) tests of all types of produced water recorded&analysis established by current editions of official pharmacopoeias? 1.3.1.8.

Does it include identification of pathogenic micro organism?

1.3.1.9.

Are the sampling points rotated to cover all points adjacent to treatment stages in the station & all point of use?

1.3.1.10.

Is the frequency of sampling justifiable &validated?

1.3.1.11.

Is the action limit of purified water is no more than 100 cfu / mL& 10 cfu / 100mL for WFI?

1.3.1.12.

When the action limit is exceeded, is an investigation always undertaken to ensure quality of the batches of product made with that water according OOS plan?

1.3.1.13.

Is the documentation shown?

1.3.1.14.

Is there a preventive maintenance program that includes the water system?

1.3.1.15.

Is there an automatic system to prevent use of the water; if it is out of specifications if not is there another system?

1.3.1.16.

If there is an automatic system, is this checked to verify that it is functioning properly? 4

1.3.1.17.

Are gauges in the station calibrated?

1.3.1.18.

Is there a record for monitoring pressure difference?

1.3.1.19.

Are there dead legs in the water system?

1.3.1.20.

Is there a trend analysis?

1.3.2.

PURIFIED WATER

1.3.2.1.

Is the system used to obtain purified water satisfiable?

1.3.2.2.

Are there written procedures for the operation of the system?

1.3.2.3.

Is there a tank for purified water storage; is it of sanitary type material?

1.3.2.4.

Is it having a hydrophobic vent filter?

1.3.2.5.

Are records periodic integrity tests kept?

1.3.2.6.

If purified water kept circulating?

1.3.2.7.

Are the pipes and valves used to distribute purified water made of sanitary material?

1.3.2.8.

Is there a record for the sanitation of purified water storage and distribution system?

1.3.2.9.

In case of using u.v lamp is there a record of its working hours?

1.3.2.10.

In the case of chemical sanitation, or ozone treatment are there record?

1.3.2.11.

In the case that filters exist, are there filter sanitation records?

1.3.2.12.

Are the filter replacement records shown?

1.3.2.13.

If the water that feeds the system is chlorinated, is there a system to remove the chlorine? 5

residues testing

1.3.2.14.

In case of presence of carbon filter is there a record of sanitization of it with validated frequency?

1.3.2.15.

In case ionic exchange resins used, is there a SOP that considers the criteria to follow for the regeneration of resins and the frequency of regeneration?

1.3.2.16.

Are records kept?

1.3.2.17.

If a reverse osmosis system is used, is there a record for system sanitization with satisfiable frequency?

1.3.2.18.

In case that chemical sanizatation is undertaken, are sanitizing agent residues investigated& Are records kept?

1.3.3.

WATER FOR INJECTION

1.3.3.1.

Is distillation system is used to get Water for Injection?

1.3.3.2.

Is there a storage tank for the Water used for injection?

1.3.3.3.

Is the tank made of sanitary material?

1.3.3.4.

Does it have a hydrophobic vent absolute filter?

1.3.3.5.

Are periodic integrity tests records kept?

1.3.3.6.

Are pipes used in the distribution of Water for Injection up to the point of use?

1.3.3.7.

Are pipes made of sanitary material?

1.3.3.8.

If there any type of heat exchanger are there guarantees that the heat exchanger is not a source of contamination?

1.3.3.9.

Is the water maintained circulating at 70-80 °C?

1.3.3.10.

Is there a system to guarantee that temp maintained 70-80°C? 6

1.3.4.

VALIDATION:

1.3.4.1.

Have the water system installation been qualified? Is a protocol and report been produced?

1.3.4.2.

Is pipes &tanks been passivated?

1.3.4.3.

Have the system operation qualification been produced? is protocol and report been produced?

1.3.4.4.

Are there daily sampling records for every pretreatment &treatment point and usage point for a period of 2 to 4 weeks in phase one validation?

1.3.4.5.

Are there daily sampling records for every pretreatment&treatment point and usage point for a period of 4 to 5 weeks after Phase 1 for phase two validation?

1.3.4.6.

Are the reports summarizing the results of phases 1 and 2 of the validation available?

1.3.4.7.

Are the weekly sampling records available of every usage point for a one-year period continuously in phase three validation?

1.3.4.8.

Is the validation summary report for phase three validation available? Is the result of these records show the system is under control?

1.3.4.9.

Is Sampling point rotation program included in the performance qualification protocol& report?

1.3.4.10.

Is Physical-chemical and microbiological analysis programme &system release parameter produced in it?

1.3.4.11.

Are the cleaning and sanitation procedures and frequencies been defined in it?

1.3.4.12.

Are SOPs have been initiated during the validation phase?

1.3.4.13.

Is any deviation from the designed criteria in qualifications &validation investigated &action is taken&invetigation recorded in the report?

1.4. STORAGE AREA 7

1.4.1. 1.4.1.1. 1.4.1.2. 1.4.1.3. 1.4.1.4. 1.4.1.5. 1.4.1.6. 1.4.1.7. 1.4.1.8. 1.4.1.9. 1.4.2. 1.4.2.1. 1.4.2.2. 1.4.2.3. 1.4.2.4. 1.4.2.5. 1.4.2.6. 1.4.2.7. 1.4.2.8. 1.4.2.9. 1.4.2.10. 1.4.2.11. 1.4.2.12. 1.4.2.13. 1.4.2.14.

Sampling area Is there a physically separated area for sampling? Does the sampling area have sanitary finishes? Does the sampling area has LAF unit ? Does it have change room? Is there a SOP for the cleaning of the sampling area? Is there a place to keep the sampling utensils in an orderly fashion to protect it from contamination? Is there a washing area, which is separated, for the sampling utensils? Incase no washing room for sampling area; is there a SOP for the handlig&storage of those sampling utensils to their washing area? Is there a SOP for the incoming of raw materials to sample and their transfer to the quarantine area after sampling? Weighing Area Is there a physically separated weighing area? Is there a SOP for the cleaning of the weighing area? Are the area have LAF unit? Is there an area for the cleaning and sanitation of the containers? Is there a ventilation system in the room with pressure differentials, and the raw materials handled with controlled temperature, humidity, and air filtration, if required? Does it have change room? If orders which are already dispensed are not transferred to the plant immediately, is there a place or system that prevents mix-ups? Is there a SOP for cleaning the tools/utensils & containers used in weighing and/or measuring? Is there an area for washing the tools/utensils & containers used in weighing and/or measuring? Are these tools/utensils& containers kept clean and labeled in a safe place? Are the scales calibrated periodically, is there arecord? Are there records that scales checked on a defined scheduled basis? Is protective equipment used when necessary? Are the materials, after being weighed or measured, immediately labeled in order to 8

1.4.2.15.

1.4.2.16. 1.4.3. 1.4.3.1. 1.4.3.2. 1.4.3.3. 1.4.3.4. 1.4.3.5. 1.4.3.6. 1.4.3.7. 1.4.3.8. 1.4.3.9. 1.4.3.10. 1.4.3.11. 1.4.3.12. 1.4.3.13. 1.4.3.14. 1.4.3.15. 1.4.3.16. 1.4.3.17. 1.4.3.18.

prevent mix-ups? On the label, does it state: Name or code and batch of the item , Name or code of the product to which the item is destined , Product Batch number, Quantity that was weighed or measured, Signature and date of the worker who carried out the operation , Signature and date of weight verification? Is there a SOP that describes all the operations of this sector/area? Warehouse Is there a receiving area? Is the receipt of materials documented and recorded? Is a visual inspection done at receipt, to verify damages or integrity of seal and containers, which could affect product quality? Is each received container labeled upon receipt& label attached to the container body and not to its removable parts? Does the label contain the following information: Item name and code Supplier name Supplier's lot number , Total Number of Manufacture date , Expiry date , Internal lot number , Special storage conditions , Test Date , Retest date ? Are the premises of adequate size according to the needs of the company? Is the quarantine& release area properly identified? Do the storage environmental conditions (including lighting, temperature and humidity) comply with the established storage requirements? Are there records for the temperature, humidity? Are there temperature records for the cold room if present? Is there an alert system to indicate deviations from the established temperature in the cold room? Is there a SOP to handle such deviations? Are necessary precautions undertaken for the packaging of finished products that require cold chain? Are the scales calibrated& checked on a scheduled basis? Are there areas physically separated or systems in place to prevent mix-ups of different materials and products? Are there procedures for all the operations of this area receipt of goods, movement of containers, load conditions, dispatches, etc?) Is there Stock control system of materials and products? Are the FIFO /FEFO followed for the use of starting materials? 9

1.4.3.19.

Before release by quality control, are all items and finished products properly identified as such and maintained in quarantine, either physically or by a system? 1.4.3.20. Are rejected materials properly identified and stored separately in restricted areas? 1.4.3.21. Is there procedure for materials destruction? 1.4.3.22. Are shelves and/or platforms separated from floors and walls to allow cleaning? 1.4.3.23. Is there a SOP&record for cleaning ware house? 1.4.3.24. Are packages and containers with items (drums, , boxes, etc.) adequately closed? 1.4.3.25. Is there an area which is secure or with restricted access which is used to store labels? 1.4.3.26. Are all outdated printed materials destroyed? 1.4.3.27. Within the storage room, are there distinct areas which are physically separated and with restricted access for psychotropic and narcotic substances? 1.4.3.28. Is there a SOP dealing with spills of corrosive or toxic and active substances? 1.4.3.29. Are there areas specific for the storage of flammable and explosive Products ,is its temperature &humidity record comply with the stated on the drums? 1.4.3.30. Is there an area for Finished Product Release? 1.4.3.31. Is there a suitable fire fighting system with record of regular check on it? 1.4.4. Rodent & pest control 1.4.4.1. Is there control for rodent & insects? 1.4.4.2. Is there a map& monitoring record for the rodent and pest control? 1.4.5. Returned/ Recall Product 1.4.5.1. Is there an area that is physically separated and has restricted access for the storage of returned or recalled products until their fate is determined? 1.4.5.2. Are the products properly identified as such? 1.4.5.3. Are all actions and decision taken recorded? 1.5. DOCUMENTATION 1.5.1. Master formula 1.5.1.1. Is there an updated master formula for each product and size of lot to be manufactured? Do the Technical Director and/or Quality Control/Assurance Director authorize all master formulas? 1.5.1.2. If it is necessary to modify the master formula, are there written procedures on how to do this? 1.5.1.3. Is authorization from the Health Authority expected before undertaking the change? 1.5.1.4. Do all products have a master formula containing Product name, code and product 10

1.5.1.5. 1.5.1.6. 1.5.1.7. 1.5.1.8. 1.5.1.9. 1.5.1.10. 1.5.1.11. 1.5.1.12. 1.5.1.13. 1.5.1.14. 1.5.1.15. 1.5.1.16. 1.5.2. 1.5.2.1. 1.5.2.2.

number? Do all products have a master formula containing Description of pharmaceutical dosage form, concentration and/or strength of the active ingredients, Product shelf life? Do all products have a master formula containing Theoretical intermediate yield and theoretical final yields with their correspondent limits? Indication of the areas in which each one of the process steps occur and equipment used? Do all products have a master formula containing Names and signatures of the qualified people involved in the issuance, review, and approval (at least two)? Do all products have a master formula containing detailed instructions of the steps to follow for each stage of the process? Do all products have a master formula containing Instructions concerning controls during the process, of intermediate products and operational variations, indicating specifications? Do all products have a master formula containing In the master formula, are there references to the SOPs related to different stages of manufacturing, equipment operation, etc. when they correspond? Do all products have a master formula containing Special precautions that should be taken during the different stages of the process due to the characteristics of the starting materials handled and equipment? Do all products have a master formula containing The standards for the storage of the intermediate or bulks, including the container, the labeling and any other storage condition when the product requires it? Do all products have a master formula containing Formula review date? Do all products have a master formula containing Forms for record keeping of product specifications during manufacture process (weight, hardness, friability, closure of capsules, disintegration, viscosity, etc.) performed by production and quality control? Is a production order issued for each batch of processed product? Batch process record Does the batch process record contain the Product name, Issue date, Batch number, Expiry date of finished product? Does the batch process record contain the list of raw materials involved (including the ones that are used up during processing) with their code numbers, lot, and/or analysis, theoretical and real quantities utilized for each of them? 11

1.5.2.3. 1.5.2.4. 1.5.2.5. 1.5.2.6. 1.5.2.7. 1.5.2.8. 1.5.2.9. 1.5.2.10. 1.5.2.11. 1.5.2.12. 1.5.2.13. 1.5.2.14. 1.5.2.15. 1.5.2.16. 1.5.2.17. 1.5.2.18.

1.5.3. 1.5.3.1. 1.5.3.2. 1.5.3.3.

1.5.3.4. 1.5.3.5.

If it is necessary to adjust the concentration of raw materials, is the modification signed by a qualified person? Are the labels of the raw materials separated, attached? Is the detailed description of each one of the steps included in the processed lot record? Are the areas and equipment/lines released recorded? Is the date, the starting and ending time of every step recorded? Are the values of operational deviations to be controlled during process (Ex.: temperature, pH, times, agitation speeds, etc.) recorded and the acceptance limit indicated? If there are process deviations with regard to the master formula, are they recorded? Whenever there is an IPC in some step of the process, are they recorded? Are the real yields of the intermediate and end stage recorded? Are the yields within the acceptable limits? In case of a deviation, is the cause of the deviation investigated according to the SOP & the findings documented? Are the signatures/ initials of the people who carry out the different operations and of those who supervise them recorded? It is verified that the data that should appear on the batch process record are completed at the time in which each action is undertaken during the process? Are reprocessing and reworking previously authorized by Control/Quality Assurance & done in accordance with a SOP? After the manufacture process is ended, is all the documentation that is part of the batch record, including the certificate of analysis of the Finished Product, filed? Is the file maintained for at least one year after the Expiry date of the lot? Batch packaging record Is a packaging order for every batch or part batch processed issued? Is the release of areas and equipment/ lines recorded? Does the batch packaging record contain the name of the product, the batch number, the expiry date of the finished product and the quantity of bulk product to be packed, as well as the batch number and the planned quantity of the finished product that will be obtained, the quantity actually obtained, and the reconciliation? Does the batch packaging record contain the date (s) and time(s) of the packaging operations? Does the batch packaging record contain the initials of the operators of each one of the 12

1.5.3.6. 1.5.3.7. 1.5.3.8. 1.5.3.9. 1.5.3.10. 1.5.3.11.

1.5.3.12. 1.5.3.13. 1.5.4. 1.5.4.1. 1.5.4.2. 1.5.4.3. 1.5.4.4. 1.5.4.5. 1.5.4.6. 1.5.4.7. 1.5.4.8.

different steps? Does the batch packaging record contain the controls undertaken with the outcome of verifying the identity and conforming to the packaging instructions, including the results of the inprocess controls? Does the batch packaging record contain Details of the packaging operations carried out, including references to equipment and the packaging lines used, cleaning records? Does the batch packaging record contain if necessary, the instructions for keeping the product unpackaged or a record of returning product that has not been packaged to the storage areas? Does the batch packaging record contain whenever possible, samples of the printed packaging materials used, including samples bearing the batch number, expiry date signed? Does the batch packaging record contain Notes on any special problems, including details of any deviation from the packaging instructions, with written authorization by the qualified person responsible? Does the batch packaging record contain the quantities and reference numbers or identification of all the printed packaging materials and bulk product issued, used, destroyed or returned to stock and the quantities of product obtained to permit an adequate reconciliation? Are the reprocessing and reworking of products controlled in a SOP for deviations? After the packaging process is ended, is all the documentation that is part of the batch packaging record, including the analytical protocol of the Finished Product, filed? General documentation For each procedure, are the purpose, scope, references, issuing& effective date and responsibilities clearly defined? Is there the detailed and precise description, in order of the routine operations? Are the procedures available, current? Are the signatures of the personnel that issue, review, and approve the document indicated? Are the records indicated within the procedures available? Does the use of correction fluid or eraser remain clearly prohibited in the documentation? If there are amendments/changes, are the date and signature recorded? Is there a SOP for the handling of changes and deviations? 13

1.6. NON-STERILE PRODUCTS 1.6.1. 1.6.1.1. 1.6.1.2. 1.6.1.3. 1.6.1.4. 1.6.1.5.

1.6.1.6. 1.6.1.7. 1.6.1.8. 1.6.1.9. 1.6.1.10. 1.6.1.11. 1.6.1.12. 1.6.1.13. 1.6.1.14. 1.6.2. 1.6.2.1. 1.6.2.2. 1.6.2.3. 1.6.2.4. 1.6.2.5. 1.6.2.6. 1.6.2.7.

Area: Are there adequate changing stages before entering the areas? Is there written instruction with that? Are changing rooms having the same class as the area they lead to? Are the change rooms designed with air locks? Is a bench of sanitary conditions available? Is the area for washing with a supply of purified water &filtered air? Is a validity period established for cleaned objects? Are personnel responsible for clean toilets &there tools different from who clean manufacturing area? Are there gauges to detect pressure differentials? Is there a record? Are the walls, floors and ceiling surfaces smooth and easy to clean? Are fixed pipes identified and do they indicate the direction of flow, whenever necessary? If raw materials or the handled products which require it, are the temperature and relative humidity measured and recorded? Is the IPC room with calibrated needed instruments? Is the area cleaned, as per established Requirements in the cleaning SOP? Is it documented? Equipment Are the materials used in the construction of the equipment, non reactive with the active ingredients handled? Are the labels adhered to the containers, equipment, and other auxiliary elements of production and areas unambiguous &indicate its condition? Are the records of use and maintenance of equipment kept? Are the instruments correctly labeled indicating the validity of calibration? Is the equipment not in use identified as such and removed from the production areas according to the SOP? Are all the containers, equipment and auxiliary elements cleaned after their use, is it documented? For fluid bed dryers: is there a set of sleeves for each product, or is there a cleaning validation process that guarantees no cross-contamination? 14

1.6.2.8. 1.6.2.9. 1.6.2.10. 1.6.2.11. 1.6.3.

Are the integrity, measurements, and identity of the punches confirmed? Are records kept? Is the access to them restricted? Is the air injected in the coating equipment filtered? Is it included in the preventive maintenance plan? Are the filters used in filtration of liquid disposable? Are the changes recorded? Operation

1.6.3.1. 1.6.3.2.

Is there a confirmation that only one product processed in each processing room? Do personnel in production carry out the verification of the weight of the raw materials used in the manufacturing of each lot? 1.6.3.3. Are the parameters of the drying operations measured and recorded? 1.6.3.4. Is there assurance that the drying ovens do not receive lots of different products or different lots from a single product at the same time? 1.6.3.5. Is the transfer of semi manufactured/bulks products between one step of the process and another carried out in a manner to prevent their contamination? 1.6.3.6. Is there confirmation that the suspensions and/or emulsions are maintained uniform throughout the bottling process? 1.6.3.7. Do bottles receive some type of cleaning &on line with before filling? 1.6.3.8. In the case of the automatic system, are discarded units which are returned to the line, previously inspected and approved by authorized personnel? 1.6.3.9. Are process controls performed at each production step? 1.6.4. Validation 1.6.4.1. Is installation of equipment been qualification (IQ)? Is protocols &report produced? 1.6.4.2. Is operation of equipment been qualification (OQ)? Is protocols &report produced? 1.6.4.3. Is performance of equipment been qualification (PQ)? Is protocols &report produced? 1.6.4.4. Is any deviation in the report of qualification investigated &action is taken? 1.7. STERILE PRODUCTS 1.7.1. Premises, Area Design And Layout: 1.7.1.1. Does the design of the areas, grade A and B, permit a visual view of all the operations from the outside? 1.7.1.2. Is the preparation environment where a solution is subject to terminal sterilization a grade D at least? 1.7.1.3. Are sterile products that are to be terminally sterilized, filled in a workstation with 15

1.7.1.4. 1.7.1.5. 1.7.1.6. 1.7.1.7. 1.7.1.8. 1.7.1.9. 1.7.1.10. 1.7.1.11. 1.7.2.

1.7.2.1. 1.7.2.2. 1.7.2.3. 1.7.2.4. 1.7.2.5. 1.7.2.6. 1.7.2.7. 1.7.2.8. 1.7.2.9. 1.7.3. 1.7.3.1. 1.7.3.2. 1.7.3.3. 1.7.3.4.

laminar airflow grade A surrounded by class C area? Are products that are sterilized by filtration, is the preparation of the solution in closed tanks carried out in a grade D environment at least? Are products that are sterilized by filtration; is the preparation of the solution in opened tanks carried out in a grade C environment? Are sterile filtered products, after the sterilizing filtration process is the product handled and filled under local grade A conditions within a grade B or C background environment? Is the whole manufacturing process of products prepared with aseptic raw materials, carried out under local grade A within a grade B environment? Are the wall surfaces, floors, doors and ceilings smooth and impervious, minimizing the shedding and the accumulation of particles and microorganisms? Are they easy to clean and maintain sanitary? Are the pipes, lighting fixtures, points of ventilation and other services designed in such a way to permit their easy cleaning and sanitation? Are pipes of dangerous liquids or gases identified and indicate the direction of flow, whenever necessary? Changing Rooms: Are there adequate changing stages before entering the sterile areas? Is the entry of the personnel into the clean rooms with watches, jewelry, or cosmetics prohibited? Is there written instruction with that? Are there change rooms exclusive for the controlled environment areas? Are changing rooms having the same class as the area they lead to? Are the change rooms designed with air locks& interlocking? If no is there any type of alarm to prevent opening of more than one door in a time? Is a bench of sanitary conditions available? If no is there any alternative measure to separate the dirty zone from the clean one? Sterile Gowning: Is there an area for the conditioning of the clothes for use in the controlled environments after its sterilization? Is there a validity period for the gown after sterilization? Is the clothing used appropriate for the areas and tasks that are carried out? Are the uniforms used for work in aseptic areas, clean, in good condition and sterilized 16

1.7.3.5. 1.7.3.6. 1.7.3.7. 1.7.3.8. 1.7.3.9. 1.7.4. 1.7.4.1. 1.7.4.2. 1.7.4.3. 1.7.5.

1.7.5.1. 1.7.5.2. 1.7.5.3. 1.7.5.4. 1.7.5.5. 1.7.5.6. 1.7.5.7. 1.7.5.8. 1.7.6.

1.7.6.1. 1.7.6.2. 1.7.6.3. 1.7.6.4. 1.7.6.5. 1.7.6.6. 1.7.6.7.

prior to their use? Is there validity time period established for the sterilization of the uniforms? Are protection elements utilized for the operations that require them? If no does this compromise product quality? Is there an exclusive laundry for the sterile area separated from laundry of other department? Are the gloves free of lubricants? Washing Area Is there an area or sector for the washing of containers and/or tools? Is label attached to cleaned objects showing its status? Is a validity period established for cleaned objects? Ampoules and Vial Washing Area: Is there a separate area for the washing and for the depyrogenation of empty bottles and ampoules? Is the operation of washing of empty bottles and ampoules done at the least in a grade D area? Do the cleaning machines of empty bottles and ampoules use water for injection, for at least the last rinse? Do the compressed air used in these washing machines adequately filtered? Are depyrogenation ovens used are validated? Are depyrogenation tunnels used are validated? Are depyrogenation cycles validated? Are depyrogenation cycles recorded? Cleaning, Sanitization and Hygiene: Are the materials and equipment sterilized and their containers sanitized? Are there instructions in the SOP for the cleaning and disinfection of every area? Is the area cleaned, within 24 hours after ending the process activities? Is a validity period established for area cleaning? Are records for cleaning kept? Is there SOP of disinfection showing show type, conc& contact time of disinfectants used? is there a record? Is there SOP & record for disinfectant preparation and sterilization? 17

1.7.6.8. 1.7.6.9. 1.7.6.10. 1.7.7. 1.7.7.1. 1.7.7.2. 1.7.7.3. 1.7.7.4. 1.7.7.5. 1.7.7.6. 1.7.7.7. 1.7.7.8. 1.7.7.9. 1.7.7.10. 1.7.7.11. 1.7.8. 1.7.8.1. 1.7.8.2. 1.7.8.3. 1.7.8.4. 1.7.8.5. 1.7.8.6. 1.7.8.7. 1.7.8.8. 1.7.8.9. 1.7.8.10. 1.7.8.11.

Are disinfectant used in alternative basis to prevent resistant strains? Are containers for waste collection identified as such? Are the materials used in containers construction compatible with the active ingredients handled? Equipments: Does the location of the equipment facilitate their cleaning, as well as, the cleaning of the area in which are found? Do the cleaning procedure validated? Is there a log book for every equipment usage? Are there calibration records of the equipment/instruments available? Is the unused equipment removed from the production areas? Is the equipment in repair identified as such? Are all equipment and auxiliary elements cleaned after their use? Is a validity period for the cleaning of the equipment established? Are all the hoses, tubes and pipes used in the transfer of fluids identified? When they are not dedicated, is the cleaning validated? Are the connections and valves used of sanitary conditions? Operations Are there flow charts showing the production steps and identify critical points? Are process controls undertaken at the different steps of production? Are records kept? Is there adequate control on maximum number of personnel present in clean and aseptic area? If sterilizing filtration systems utilized is the integrity of the filters confirmed before filtration? If the filters used are not disposable, is their usage period established,are the sterilization number recorded? (NO. of sterilization cycles)? Are the changes recorded? Are the filters dedicated by active raw material? Is the integrity of the filters confirmed after filtration? Are records kept? For each product, is the maximum time between the starting of the preparation of a solution and its sterilization or filtration through absolute filters established? 18

1.7.8.12. 1.7.8.13. 1.7.8.14. 1.7.8.15. 1.7.8.16. 1.7.8.17. 1.7.8.18. 1.7.8.19. 1.7.8.20. 1.7.8.21. 1.7.8.22. 1.7.8.23. 1.7.8.24. 1.7.9. 1.7.9.1. 1.7.9.2. 1.7.9.3. 1.7.9.4. 1.7.10. 1.7.10.1. 1.7.10.2. 1.7.10.3. 1.7.10.4. 1.7.10.5.

Are gases used to purge solutions adequately filtered? Is the batch sterilization in more than one cycle, Is it divided to different identified lots for sterility testing? Are records of time, temperature, and/or pressure of the autoclave and depyrogenation oven maintained? Are records of sterilization and depyrogenation of the container for the filtrate product reception available? Is the transfer of intermediate/bulks between one step and another carried out in a manner which prevents their contamination? Is the maximum time elapsed between the filtration and the product filling determined for products without terminal sterilization? Are mix-ups avoided between the sterile and non-sterile material? Is clean steam used in the sterilization cycles monitored to assure suitable quality? Is a validation program for moist heat sterilization cycles performed and recorded? Are indicators used at each cycle of sterilization? Are records kept? Is the product 100% visually inspected? Incase inspected by operators do they a record for periodical medical examination ? Materials and Components: Do they enter to the aseptic area by air lock? Is there a validity time period established for the sterilization of components, containers of products in bulk and other equipment? Do the sterilized material and components transferred in a manner to prevent its contamination or cross contamination? Do leak test is done for ampoules? Aseptic Process Validation: Is media fill conducted with culture medium, in the working conditions, at least on a semiannual frequency? Are these tests carried out in such away to most accurately reproduce the normal working conditions in the area? Are they carried out in a minimum of 3600 units? Are there records of these tests? Are the causes of any detected contamination investigated? 19

1.7.10.6. Are there records of this investigation? 1.7.10.7. Are there records of the corrective actions taken in those cases? 1.8. QUALITY CONTROL 1.8.1. Laboratory equipment 1.8.1.1. Does the Quality Control laboratory carry out its own Physicochemical, Microbiological, and Biological controls? 1.8.1.2. Is a clearly defined flow of samples and documentation established? 1.8.1.3. Are the physicochemical and microbiological controls sector physically separated? 1.8.1.4. Are the physicochemical and microbiological controls sector physically separated from the production? 1.8.1.5. Is the Quality Control Department responsible for approving or rejecting the raw materials, packaging materials, intermediate products, and finished products? 1.8.1.6. Are the installations and the equipment as appropriate with the type of manufacture & active ingredients handled? 1.8.1.7. Is there a defined area for the washing and conditioning of materials exclusively destined for the physicochemical laboratory? 1.8.1.8. Are there safety installations such as shower, eye washer, fire extinguisher, and protection elements? 1.8.1.9. Is there the necessary equipment for the analytical controls required for the material & products? 1.8.2. Stability 1.8.2.1. Does stability study program include a complete description of the product studied? 1.8.2.2. Does stability study program include the controlled parameters and validated analytical methods that demonstrate the stability of the product in concordance with the established specifications? 1.8.2.3. Does stability study program include a sufficient number of lots (no less than three)? 1.8.2.4. Does stability study program include timetable of the analytical tests to carry out for every product? 1.8.2.5. Does stability study program include the accelerated &real time stability? 1.8.2.6. Does stability study program include sufficient quantities of samples in order to fulfill with the program? 1.8.2.7. Is there a summary and obtained data including the evaluations and study conclusions? 1.8.2.8. IS there a record of monitoring of the marketed products that makes it possible to confirm that, if the conditions of storage are met, the product maintains its quality 20

during its validity period? Validation Does the Validation Master Plan include the Quality Control laboratory? Does the laboratory have equipment qualification protocol&report? If there is deviation in the qualification is it investigated &corrective action taken? is that recorded ? 1.8.3.4. Is there a validation program for those analytical methods not published by internationally recognized pharmacopoeias? 1.8.3.5. Are there documents supporting compliance with this procedure? 1.8.3.6. Are analytical methods verified when despite being coded by internationally recognized pharmacopoeias, these are performed differently to the coding? 1.8.4. Sampling procedure 1.8.4.1. Are there SOPs with the detailed description for the sampling of Raw materials, Packaging materials, intermediate, finished product? 1.8.4.2. Are there sampling plan for raw,packging,intermediate &finished product ? 1.8.4.3. Are all incoming packaging materials, without exception, sampled by Quality Control in accordance with the established standard& sampling plan? 1.8.4.4. Are the sampling elements duly stored and labeled? 1.8.4.5. Is there a written procedure for the cleaning, use, and conservation of the sampling eleme 1.8.5. Analytical method 1.8.5.1. Are the analytical methods utilized authorized by the one responsible of Quality Control? 1.8.5.2. Are there specifications for Raw materials, Packaging materials, Intermediate, finished,? 1.8.5.3. Are there records that Quality control checks if each manufactured lot meets the established specifications? 1.8.5.4. Is there SOP for out of specification? 1.8.5.5. Are there records of this investigation &action taken? 1.8.5.6. Do the records of the tests contain Sample identification, Date, Name of the analyst, Identification of the reference standard, Parameters and conditions that correspond? 1.8.5.7. Do the analysts have a serial logbook in which are recorded the laboratory results? 1.8.5.8. Are the calculations dated and signed by the analyst? 1.8.5.9. If there are observed modifications of data, is the amendment carried out dated and 1.8.3. 1.8.3.1. 1.8.3.2. 1.8.3.3.

21

1.8.5.10. 1.8.5.11.

1.8.6. 1.8.6.1. 1.8.6.2. 1.8.6.3. 1.8.7. 1.8.7.1. 1.8.7.2. 1.8.7.3. 1.8.7.4. 1.8.7.5. 1.8.7.6. 1.8.7.7. 1.8.7.8. 1.8.7.9. 1.8.7.10. 1.8.8. 1.8.8.1. 1.8.8.2. 1.8.8.3.

signed? Does the amendment make possible to visualize the original datum? In the records of the analyses, it is indicated: Name of the analyzed material, Lot number , Analysis number ,Obtained results , Date , Utilized methods and specifications , Signs/ initials of the people who carried out the test , Sign/initials of the person that verified the tests and calculations ? Retained samples Are samples of retention of the active raw materials and finished products, in enough quantity to carry out all the tests by duplicate, kept in accordance to a SOP? Are the retention samples of finished products kept until a year after the expiry date of the product? Are the samples of retention of raw materials kept until a year after the expiry date of the last lot of product prepared with them? Reference standard Are there standards and reference materials? Is a record of the primary standards kept? Is a record of the secondary standards kept? Is a record of the reference materials kept? Does the company have primary standards, coded by Pharmacopoeias or internationally recognized agencies, for each active ingredient? Do all the secondary standards and reference materials have current analytical certificate? Are there SOPs for the preparation, use and conservation of standards and reference materials? Are those procedures fulfilled? Are the records shown? Does the company have impurities and related substances standards, officials or nonofficials, especially for those considered toxic? Reagents Are the reagents correctly labeled? Are volumetric solutions used? Is there a standard operating procedure for the preparation, use, and conservation of volumetric solutions? 22

1.8.8.4. 1.8.8.5. 1.8.8.6. 1.8.9. 1.8.9.1. 1.8.9.2. 1.8.9.3. 1.8.9.4.

1.8.9.5. 1.8.9.6. 1.8.9.7.

1.8.9.8. 1.8.9.9. 1.8.9.10. 1.8.9.11. 1.8.9.12. 1.8.9.13. 1.8.9.14. 1.8.9.15. 1.8.9.16. 1.8.9.17. 1.8.9.18. 1.8.9.19. 1.8.9.20. 1.8.9.21. 1.8.9.22.

Is there log book for the preparations of the reagent preparation include Name of the analyst, Name of the reagent, Calculations, Date of the preparation & expiration? Do every container of analytical solution have a label where there is indicated: Name of the solution Concentration - standardization factor Preparation date, Responsible, Retest date, expired date, Storage conditions, Safety category, Reference to the SOP? Are the unstable reagents labeled with reception date, opening date and Expiry date? Microbiology laboratory Does the company have separated areas for sterility test and other microbiological controls ? Is there any change room before entering the microbiology laboratory? Is there any change room before entering the areas for sterility test? Is there sop for the cleaning & disinfectant of the change room? Are there proper areas and laminar flow for carry out the sterility tests? Are the filters of the laminar flow periodically checked? Are the materials, culture media and reagents within the validity period? Are the dehydrated culture media stored in the conditions of humidity and temperature indicated by the manufacturer? Are the parameters of every sterilization cycle of culture Is there separated LAF cabinet to perform growth promotion test? Is the growth promotion test carried out whenever new lots of culture media are utilized? Is negative control test done in accordance with every sterility test? Is a standard operating procedure for the preparation of culture media? Are there microbial reference strains? If there are reference strains, are they certified by an internationally recognized agency? Is there a record of identification and use of strains? Are sterility tests carried out? For sterility tests, are coded methods utilized? If the lot fails the sterility test, is it follow OOS ? Are antibiotic potency assays carried out? Does the company have areas or sectors assigned for the sample Preparation? Does the company have areas or sectors assigned for the washing and Conditioning of 23

materials? Does the company have areas or sectors assigned for the preparation of culture media? Does microbiology sector have equipment for bacterial decontamination? Is there a procedure for the handling and disposal of chemical and microbial waste? Does the procedure indicate that should not be permitted the accumulation of discarded materials? 1.8.9.27. Does Quality control carries out environmental microbiological controls? 1.8.9.28. Are there records? 1.8.9.29. Are tests of bacterial endotoxins carried out in raw materials and goods declared as pyrogen-free by the supplier, to be used in the injection manufacture? 1.8.9.30. Are tests of pyrogens or bacterial endotoxins carried out in the finished products for injection? 1.8.9.31. Is an official method utilized for bacterial endotoxin control? 1.8.9.32. Is the method validated? 1.8.10. Animal house 1.8.10.1. Are pyrogen tests carried out in animals? 1.8.10.2. If "YES" Does the company has its animal house or uses a contracted animal house? 1.8.10.3. In any of both cases, does animal house fulfills with the current regulations on animal operation and management? 1.8.10.4. If the company have animal house, is this separated from the other installations with separate AHU? 1.9. QUALITY ASSURANCE 1.9.1. General 1.9.1.1. Is there in the company a quality assurance system? 1.9.1.2. If the documentation is carried out through electronic data processing methods does the company kept a reserve copy of the documentation? 1.9.1.3. Is the admission of new data or modifying of the existing data in the computer system done only by the people authorized? 1.9.1.4. Is a record of the data modifications and/or elimination kept? 1.9.1.5. Are the records of lots electronically filed protected? 1.9.1.6. Is there a program of control of the SOPs? 1.9.1.7. Does Quality assurance is responsible of release of every batch is that indicated in a SOP ? 1.8.9.23. 1.8.9.24. 1.8.9.25. 1.8.9.26.

24

1.9.1.8.

If in the review of the production records are detected bypasses of the established procedures, is quality assurance responsible for ensuring a complete investigation of the bypasses and that the final conclusions are justified? 1.9.1.9. If a lot does not meet specifications, does the investigation is extended to other lots of the same product and of other products that could have had some relation with the defect or the discrepancy? 1.9.1.10. Does the company kept originals of all procedures and records of distribution of the authorized copies? 1.9.1.11. If a procedure is modified, is there a system by which the accidental use of a previous version is prevented? 1.9.1.12. IS there a SOP for change control? is it fullfield? 1.9.1.13. Is there a SOP for annual product review? Is that FULFILED? 1.9.1.14. Is there a SOP for corrective &preventive action? 1.9.2. Preventative maintenance& calibration program 1.9.2.1. 1.9.2.2. 1.9.2.3. 1.9.2.4. 1.9.2.5. 1.9.2.6. 1.9.2.7. 1.9.2.8. 1.9.2.9. 1.9.2.10. 1.9.3. 1.9.3.1. 1.9.3.2. 1.9.3.3. 1.9.3.4. 1.9.3.5. 1.9.3.6.

Is there a program for preventive maintenance for all the equipment, premises ,utilities? Are there records that shown preventive maintenance program compliance? Is there a program of equipment calibration? In the equipment calibration program is indicated, which operations are performed internally and which by contracted services? Is the frequency of calibration indicated in the equipment calibration program? Are records of calibration of each equipment that shown program Compliance? Are there written procedures to perform the calibration of each equipment? Is the equipment correctly labeled indicating the calibration validity? In case of internal calibrations, does the laboratory have certified standards? Are the corresponding certificates shown? QUALITY AUDITS/ SELF-INSPECTIONS Are quality self-inspections and/or audits carried out? Is Quality assurance responsible for the coordination of quality self-inspections and/or audits? Are the self-inspections/audits carried out with a pre-established plan? Are the necessary corrective taken with in the time limit specified? Do the written instructions of quality self-inspection/ audits include the entire factory? Are the Results of previous self-inspections and adopted corrective measures 25

1.9.3.7. 1.9.3.8. 1.9.3.9. 1.9.3.10. 1.9.4. 1.9.4.1. 1.9.4.2. 1.9.4.3. 1.9.5. 1.9.5.1. 1.9.5.2. 1.9.5.3. 1.9.5.4. 1.9.5.5. 1.9.5.6. 1.9.5.7. 1.9.5.8. 1.9.6. 1.9.6.1. 1.9.6.2. 1.9.6.3. 1.9.6.4. 1.9.6.5.

documented? Does the report issued once finished the self-inspection contain the Results of the selfinspection? Does the report issued once finished the self-inspection contain evaluation and conclusions? Does the report issued once finished the self-inspection contain corrective measures recommended? Is the monitoring of the corrective measures carried out? SUPPLIERS QUALIFICATION Is there a record of approved suppliers available for the areas that require it? Is there a program for evaluation and audits to suppliers? Is it fulfilled? RECALL Is there A sop to recall products from the local and international market, if necessary? Is there a responsible person (independent from the marketing department) designated by or in accordance with the qualified person responsible for the coordination and execution of the recall procedure? Is Quality control/Quality assurance/Regulatory Affairs notified of undertaken recall operations? Does the procedure indicate the mandatory requirement of notifying the Health Authority immediately in the event that the cause is for health reasons? In the case of having distributed products to other countries, is the Health Authority of the recipient country and the recipient of these products informed immediately? Are distribution records available for a prompt recall of products from the market? Is there a classification of recall? Is there an updated list of contact persons of the distributors? COMPLAIN Is Quality assurance responsible for coordinating the reception and the monitoring of the received complain? Is there a responsible person assigned? Are there written procedures for the reception and investigation of the complain? Is record of the complain kept? If necessary, is analytical control made? 26

1.9.6.6. 1.10.

Do the decisions &corrective action made concerning the complaints remain documented, in the lot records? PACKAGING:

1.10.1. 1.10.1.1. 1.10.1.2. 1.10.1.3. 1.10.1.4. 1.10.1.5. 1.10.1.6. 1.10.1.7. 1.10.1.8.

1.10.1.9. 1.10.1.10.

OPERATION: Is the mix-up of different products or different lots of same product avoided by having physical separation among the packaging lines? Do all finished products have a printed batch number and an expiry date on their primary container? Is the printed information resistant to fading or erasing? If automatic machines are used to control dimensions, weights, labels, prospects, bar code, etc., is their proper performance verified? If the review/verification of product done visually, Is there a changeover of staff? If it is done automatically is it challenged for its performance ? Are conditions of lighting and contrast for the review/verification controlled? Are the containers that contain the already inspected material labeled as such? Are the right batch number and expiry date confirmed by authorized personnel? Are precautions taken on dispensing labels to prevent mix-ups?

1.10.2. 1.10.2.1.

1.11.

DOCUMENTS: Does the company have packaging orders with A full list of all packaging material required for a normal size batch, including quantities, sizes and types, with the lot number, code or reference number related to specifications for every packaging material? 1.10.2.2. Does the company have packaging orders with Details concerning process control with instructions for the sampling and acceptable limits? 1.10.2.3. Is there a SOP available for the process of the return of unused non-coded printed material to the warehouse? HVAC SYSTEM 1.11.1. GENERAL 1.11.1.1. Do they have an air supply filtered by HEPA terminal filter in the areas grade A, B and C? 1.11.1.2. Is the filters efficiency is adequate for such classes? 1.11.1.3. Do grade D areas have high efficiency filters? 27

1.11.1.4. 1.11.1.5.

1.11.1.15.

Is the filters efficiency is adequate for such classes? In the areas of controlled environment (grade B, C and D), is the number of air Changes by hour is sufficient for such areas? Are the integrity and the sealing of the filters confirmed? Is there a SOP for the review and changing of filters? Are there records? Do the areas have instruments with current calibration, which make it possible to confirm a cascade of pressure differential? Are there records? Do the air flow patterns prevent contamination? Is there an alarm system that indicates a deviation in the air supply to the aseptic areas? Is there a SOP for how to proceed in the event that this occurs? Is there a measure in place to avoid a conveyor belt going from a grade B area to one of lower air quality? Are the actual results complying with the designed criteria?

1.11.1.16.

Are there air locks between different classes?

1.11.1.17.

Is there a reasonable upgrading of area cleanliness from black, grey, clean area?

1.11.1.18.

Are the toilets air not returned or mixed with production air?

1.11.1.19.

Is there ventilation with adequate temperature, humidity, and air filtration, if the raw materials and/or handled products require it? Are the temperature and relative humidity measured and recorded? Are pressure differential values in the different areas measured and recorded? Are records kept? Are particulate counts conducted in the controlled environments? Are records kept? Is the frequency for performing the test in different classes suitable? Are microbiological controls conducted in the controlled environments? Are records kept? Is the frequency for performing the test in different classes suitable? Are air conditioning and/or ventilation systems for each area in accordance with the operation to be carried out?

1.11.1.6. 1.11.1.7. 1.11.1.8. 1.11.1.9. 1.11.1.10. 1.11.1.11. 1.11.1.12. 1.11.1.13. 1.11.1.14.

1.11.1.20. 1.11.1.21. 1.11.1.22. 1.11.1.23. 1.11.1.24. 1.11.1.25. 1.11.1.26. 1.11.1.27. 1.11.1.28. 1.11.1.29.

28

1.11.2.

1.12.

Validation:

1.11.2.1.

Is the system installation has been qualified & a protocol with a report has been produced?

1.11.2.2.

Is the system operation has been qualified &a protocol with a report has been produced?

1.11.2.3.

Is the system performance has been qualified &a protocol with a report has been produced?

1.11.2.4.

Does DOP test done in the performance qualification?

1.11.2.5.

Is the air velocity in grade A has been measured?

1.11.2.6.

Is a preventive maintenance program has been produced from the qualification?

1.11.2.7.

Is any deviation during qualification investigated &a corrective action taken to close the case?

PERSONNEL 1.12.1. 1.12.1.1. 1.12.1.2.

General Is there an updated organization chart of the company? Is there a description of the responsibilities and functions of production and quality control personnel? 1.12.1.3. Are the responsibilities of production and quality control personnel independent of each other? 1.12.2. Training 1.12.2.1. Is there a program for on job training & GMP, including specific training appropriate to the duties assigned to them? 1.12.2.2. Is there a program for refreshment training on GMP, including specific training appropriate to the duties assigned to them? 1.12.2.3. Are the training records for the personnel in charge of cleaning, if in-house personnel, shown? 1.12.2.4. Is the Operating Personnel trained by Quality Control on sampling methods (swabs, 29

1.12.2.5. 1.12.3. 1.12.3.1. 1.12.3.2. 1.12.4. 1.12.4.1. 1.12.4.2. 1.12.4.3.

piece of fabric, rinsing, placebo)? Is there documented evaluation for the training? Gowning Are the personnel using the appropriate uniform for the specified area? Is there a SOP dealing with the use of proper clothing for other persons who enter production areas (technical service/maintenance, cleaning personnel, quality control inspectors, quality assurance inspectors, and visitors)? Medical check Are the personnel required to undergo a medical examination prior to being employed? Is there a procedure to prevent any person who has an apparent illness from entering areas in which they may adversely affect the quality of the product or affect their own health? Are frequent ophthalmologic examinations conducted on the workers in charge of the review/verification?

30