15.0 Warehousing AreaDuring inspection of warehouse area, there should be adequate areas allocated for warehousing of raw materials, intermediated, products in quarantine, finish products, rejected or returned products and packaging material. The area of separation must be fully specified with specific parameter required for each material such as temperature, humidity and others and should be marked or separated with each other.
These criteria must be followed by the manufacture to avoid cross contamination and safety of the material and product itself.The external auditor will check whether the storage area is maintained in a good condition with clean and dry condition and maintained within acceptable temperature limit of each specified material. This parameter is important during warehouse evaluation to maintain the stability of the product especially for the sensitive type of materials. Specific provision must be provided for the hazardous chemical type and how well the area is safely secured from unexpected accident such as spillage, explosion and others that will protect the workers inside the plant. Proper racks, bins and platforms should be available with correct label for the storage of materials. The auditor will inspect this storage condition whether it is label properly and follow the sequent to avoid confusion to the operator in-charge during manufacture of product. The auditor will evaluate based on the master label record for comparison to the issued label based on GMP guideline.
There should be also specified area available for sampling of raw materials and excipients been provided by the manufacturer. This area will be evaluated by checking the specify sampling method used, the control of personnel allowed to the room, the arrangements of sample taken ,the cleaning and step precaution method used for sampling and the log book for sampling booth.Proper method delivery of incoming materials will be checked whether it is clean and treat well before entering the plant.16.0 Production AreaIn this area, auditor will examine the flow of personnel, materials and logical sequences of operations in the manufacturer plant whether the sequence will prevent mix-up or product contamination. This is important measures to ensure smooth planning of product manufactured. The IPQC lab position in the manufacturing area should also be specified and the room should be restricted to qualified personnel only.If there is any non-storage area used for storage of materials, the manufacturer should inform the auditor for inspection to ensure safety and productivity of the area for approval.
If there is any production of sensitive pharmaceutical product like Penicillin or Biological preparation like microorganism, the auditor will inspect whether separate and self-contained facilities have been provided for the operation. The auditor will ask for the attachment of the copy of the plan of the premises for each of the category of the product manufactured.The area of storage of dirty, washed and cleaned equipment parts must be specified with logical manner .The auditor will evaluate how the manufacturer manage these equipment accordingly as to prevent cross contamination between material and product.The specification of service lines like pipe work, ventilation openings, electrical fittings and others will be examine and identified by colours for nature of the supply and direction of the flow based on provided guideline by the manufacturer. The auditor will inspect whether service line in production are through the service pendants or the placement of lines must not provide accumulation of dust to the environment.17.0 Documentation and RecordsEvaluation of each document will be based on how the documents being designed, developed, reviewed and controlled to provide an audit trail.
Each documents will be checked and must have the approval and signature and dated by appropriate and qualified person with specify title, nature and purpose. If the documents are regularly reviewed, the manufacturer must specify review period of document with attachment of list maintained by the firm for the knowledge of the auditor.The auditor will check whether the records are made at the time of each operation in a way that all significant activities related to the production are traceable and if the data is recorded by electronic data processing system, there should be a method to access the system by the user.The hard copy of the master formula and detailed operating procedures of the operating procedures should be available for an audit trail and there must be personnel who is responsible for maintenance of these records.
All of these documents will be analysed by the auditor and should be organized in a systematic way according to the guideline available.18.0 Sanitation in the Manufacturing AreasThe cleaning procedure that been implemented by the manufacturer must be specified according to the type of production. The auditor will validate the effectiveness of the cleaning method used based on type of production being implied.
The auditor will check whether the area of manufacturing being used as the general route in the plant and the area of the storage materials can be used and not under process of maintenance.Routine sanitation programme must be in place for this type of validation for approval. The manufacturer must specify their detailed sanitation programme in various area, equipment and method used.The auditor must inspect whether the area of production do not affect the cleaning procedure of the equipment used as well as the area itself which they locate and should not cause contamination to the product being manufactured. The area of production will be validate for its lighting source used and the manufacturer should provide the lux level utilize for the production for visual inspection.19. CleaningFor cleaning procedure, the auditor will check whether there is a validation being performed to prove the cleaning effectiveness of the facilities being used. The auditor will inspect whether the protocol utilized by the manufacturer fit the criteria of product for the cleaning validation.
The data produced from the manufacturer must support the conclusion being made on the cleanliness level for evaluation record. The auditor will check the acceptance limit based on the following criteria:The area is visually clean10 ppm for another type of productThe level of the therapeutic dose is 0.1 %There must be person in charge from the manufacturer who is responsible of the sampling for cleaning verification such as the Quality Control officer. The parameter include cleaning validation during surfaces in contact between personnel with the product, after interchange in product and in the middle shift of batches.
The auditor will ask for specification whether the detergent residue had been investigated and degradation of products being verified during validation.There must be validation records available including the Recovery study data, Signature of the Quality Assurance Manager, Analytical methods including Detection Limits and Quantification Limits, employee in charge for the cleaning and the verification from the Production and Quality Control.20. Other Product ManufacturedThe product name should be available for identification during inspection with specific description of the product.
The auditor will check whether there is validated master formula available for reference and specific SOP for product during production.Apart from that, there should be proved of stabilities studies being conducted and the expired date of the product been assigned based on the stability study. The auditor will check whether tend analysis and interpretation of result being carried out for evaluation of quality by the manufacturer to sustain the product quality.There should be annual product review (APR) being conducted by the manufacturer based on the parameter available:Used the critical in-process control and result of critical API test The report on all batches that failed to meet the specification based on GMP guidelinesThe critical deviations and non-conformances investigation and related document Any adjustment been carried out to the operation or analytical methodsThe result of the stability analysis programmeThe quality of the quality-related returns, complaints and recalls on product and reasonable corrective actionsThe auditor must check whether there is any complaint received for the product and there should any report along with ATR available for audit trail.
