Pharmaceutical Guidelines Page 1 73 SELF INSPECTION CHECK …

Pharmaceutical Guidelines

SELF INSPECTION CHECK LIST

Page 1 of 73

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Sr.No Requirements Compliance Comments

I. PERSONNEL Y N NA

1 Is up-dated organization chart showing arrangement for quality assurance including production and quality control available

.is up dated technical staff list is available with following information

Name, qualification and years of relevant experience of responsible pharmacists, Chemist in Production,

Quality Assurance, Quality Control

2 Are production and Quality Assurance/ Quality control functions independent of each other?

3 Are all unit areas adequately staffed?

4 Is there proper supervision in every unit?

5 Is hiring of an employee proceeded by a medical examination?

6 Is this examination done periodically ?

who is responsible for reporting/checking health of employee

7 Is an employee whose states of health is doubtful immediately removed from the work site until she/he has recovered?

8 Is there system of reporting back after illness?

9 Is medical assistance available during the normal working hours?

10 Are there suitable washing, changing and rest areas?



Page 2 of 73



I. PERSONNEL Y N NA

11 Is the clothing suitable for the activity undertaken? Briefly describe the clothing.

12 Are there clear instructions on how protective clothing should be used and when it should be changed?

13 Is in-house or external laundry used?

14 Have all personnel received GMP training?

A. Induction

B. Continuous

15 Is training manual/syllabus of GMP available and enclosed?

16 Do all personnel receive up-dated GMP training?

How often?………

17 Is record of training details (induction/continuous) provided to each staff in-house available and enclosed?

18 Is efficacy of training assessed by questionnaire?



Page 3 of 73


Sr.no Requirements Compliance Comments

II. PREMISES Y N NA

1 Are there any sources of pollution (industrial or other) in the neighborhood of the building?

2 Is well-labeled plant lay-out of suitable size, design and construction for each areas of production and control available/enclosed?

3 Is the plant so constructed and maintained to protect against.

a) Weather, flood, ground seepage?

b) Access and harboring of vermin, rodents, birds, insects and other animals?

4 Is there an adequate working space for

a) Orderly and logical placement of equipment and materials?

b) Efficient flow of work?

c) Effective communication?

5 Are buildings and facilities properly constructed to facilitate smooth operation and adequate cleaning?

6 Are room arrangements adequate, to prevent mix-up and/or cross-contamination of products?

7 Are lighting and ventilation adequately designed and installed?

8 Is schematic drawings/data on design criteria (specification of the air supply, temperature, humidity, pressure differential and air change rate, re-circulation percentage), filter design/efficiency, limits for changing filters, validation, re-validation frequency provided?



Page 4 of 73


Sr.no Requirements Compliance Comments

II. PREMISES Y N NA

9 Are toilets:

a) not open directly to production areas?

b) well ventilated?

10 Are sewage, trash and other effluent disposal adequate?

11 Are floors, walls and ceilings constructed of materials which will facilitate easy cleaning and if necessary Disinfections?

.

12 Are products of other highly toxic/hazardous products, cephalosporins, steroids/hermones, cytotoxics well segregated?

13 Is schematic description of water system including sanitation provided?

( Indicate city supply, capacity, vessel materials/pipework, filters specification, store/circulating temperature, specification of water produced, sampling points, frequency testing, procedure and frequency of sanitation)

14 Are there preventative maintenance and servicing programme/procedure/reporting available?

( Indicate the frequency of services /checks, details of services/repairs/modification, critical maintenance that could affect product quality, access/use of maintenance records)



Page 5 of 73



III. EQUIPMENT Y N NA

1 Is brief description of major production and quality control lab. Equipment indicating construction, validation and suitability of other materials (polypropylene, chrome plated brass, PVC, non-reactive plastic materials) provided?

2 Are the equipment of appropriate design, construction and adequate size suitably located?

3 Are the equipment surfaces coming into contact with any raw material, intermediate bulk or finished product made of inert materials (e.g. stainless steel)

4 Are the equipment properly maintained and easily cleaned?

5 Are there procedures for cleaning and maintenance available? ( Indicate responsibility, contractual details, maintenance routines which could affect product quality)

6 Are all equipment for cleaning and maintenance recorded? ( Indicate type, frequency, details of reports/modification, use of report)

7 Are all equipment properly grounded where required?

8 Is there any program for calibration of measuring equipment?

Is the result of the calibration documented?

9 Are all open mechanical belts, pulley, etc equipped with safety guards?

10 Are major equipment clearly marked with identifying numbers?



Page 6 of 73


11 Are qualification, validation and calibration programs available for equipment used for production, quality control heating ventilation, air conditioning (HVAC), water system, steam, compressed air, gasses etc.?

( indicate policy/protocols for qualification and validation, revalidation, calibration and their recording)


IV. SANITATION AND HYGIENE Y N NA

1 Is high level of sanitation and hygiene implemented in every aspect of manufacturing of drug product?

2 Are protective measures taken to avoid direct contact of operators and materials (raw materials and drug products) and assuring protection of product from contamination as well as the safety of personnel?

3 Is there any regulation for personnel entering the building and facility designated as limited access area?

4 Are smoking, eating, drinking, chewing or keeping plant, food, drink, smoking material and personal medicines restricted to specific areas and not permitted in production, laboratory, storage areas and other area where they might adversely influence product quality?

5 Are employee's washing and toilet facilities adequate and in sufficient quantity?

6 Are there any procedure of qualification and validation of sanitation and hygiene available?

7 Is there a program for control of pest, rodents, insects or birds?

8 Is the program appropriately designed so that the rodenticides, insecticides, fumigating agents and sanitizing material do not contaminate equipment, raw materials, packaging materials, in-process materials or finished products?

9 Are cleaning agents changed from time to time?



Page 7 of 73


10 Are cleaning method monitored routinely by chemical and or microbiological method?

11 What are the cleaning methods/frequency for the water supply system, air handling system and dust extraction system?

Sr.

No.

Requirements Compliance Comments

V STORAGE OF STARTING MATERIALS Y N NA

1 Are there physically separated storage areas for,

a. raw materials?

b. Packaging materials

2 Are storage areas enclosed and locked, where required?

3 Is storage available for

a. solvent?

b. Inflammable material?

4 Is there a quarantine for raw materials and packaging materials and finished products before release?

5 Is there a segregated area for rejected materials?

6 Are there separated areas for toxic substances, psychotropic agents and the like?

7 Is the area for storage of materials of adequate size?

8 Are warehouse lighting and ventilation adequate?



Page 8 of 73


Sr.

No.



9 If there is a need for humidity and temperature control, are these regulated?

10 If so, are there humidity and temperature measuring instruments? .

11 Are there written records for these data?

12 Is the possibility of entering insects, rodents, birds in the building completely avoided?

13 Is the warehouse adequately staffed?

14 Is there a proper supervision?

15 Have the personnel receive appropriate GMP training?

16 Do the personnel receive up-date GMP training?

How often ?

17 Is each delivery visually checked on receipt for

a. General condition?

b. Integrity of containers?

c. Spillage?

d. Possible deterioration?

18 Are there standard operating instructions and procedures available for handling of starting materials, packaging materials, finished product, sampling, quarantine release/storage etc.



Page 9 of 73


Sr.

No.



19 Is there a record on incoming goods, which includes the following information on,

a. Receiving document number?

b. date of receipt?

c. date of releasing?

d. date of expiry, if any?

e. Supplier?

f. Manufacturer?

g. Manufacturer's batch number?

h. Internal identification number?

i. type and size of containers?

j. Number of containers and their conditions?

20 Is there similar record for outgoing goods including delivering document number?

21 Is stock record maintained so that stock reconciliation can be made?

22 Are the starting materials labeled, including the name designated in the specification?



Page 10 of 73


Sr. no Requirements Compliance Comments

Y N NA

23 Is the disposition of the stock adequate to preserve the integrity and identity of the materials?

24 Quality Control Labels

a. Are there different labels each for quarantine, release and rejected?

b. Are those of different colors?

c. Are there the following information on the labels:

- Name of materials?

- batch number?

- Analysis number?

- date released/rejected?

- Retest date/expiration date?

25 Are quality control labels attached only by persons approved quality control?



Page 11 of 73



Y N NA

26 Sampling

a. Are they performed by Quality Control or staff approved by Quality Control?

b. Are there sampling plan and procedures?

c. Are there the following information on each sample taken:

- Name of person who performed the sampling.

- Quantity of samples taken.

- Number of containers sampled.

- date of sampling.

27 Are different batches within one delivery recorded as separate batches for sampling testing and release purpose?

28 Is each starting material used only after release for use?

29 Is there a stock rotation program?

(First Expiry First out-FEFO) or (First Approved First Out )FAFO

30 a. Are samples taken for identification from every container to provide assurance that all containers in a delivery contain the correct starting materials and are not mislabeled by the supplier?

31 Are deliveries of starting materials held in quarantine until approved and released for use?



Page 12 of 73



Y N NA

32 Are stocks of starting materials

a. Inspected at intervals to ensure that the containers are properly closed and labeled and are in a good condition?

b. reported in writing to quality control for sampling and retesting after a definite storage period of after exposure to air, heat or other conditions that may adversely affect their quality?

33 Are materials stored off the floor?

34 Are the materials stored under suitable environmental conditions?

35 Are inventory cards periodically reconciliated?

36 If a discrepancy is found, is it recorded and justified?

37 Is the discrepancy and justification documented with a explanation?



Page 13 of 73



Y N NA

38 Raw materials and packaging materials,

a. If the identity or condition of a container of raw materials or packaging materials is suspicious or does not comply with requirements,

- is the container delivered to the quarantine area?

- is the disposition of the material determined by the Quality Control unit?

b. Are rejected materials consciously identified, segregated from approved materials and stored in the restricted and assigned area for rejects?

c. Are rejected materials destroyed or immediately returned to the supplier?

( Describe arrangement for disposal and destruction record)

d. Are printed packaging materials,

- stored in a restrictive storage area?

- dispensed under strict supervision?



Page 14 of 73


Sr.no Requirements Compliance Auditors Comments

V PROCESS VALIDATION

1

. Is validation, properly done to all critical production procedures?

(Indicate all critical production procedures for which validation is done?

a. conducted in accordance with previously defined procedures?

b. result maintained?

c. extension and degree dependable on the value and complexity of the product and process?

2 Do the validation program and documentation provide

a. evidence of suitability of equipment and systems?

b. the performance and reliability of equipment and systems?

c. the competency of personnel?

3 Are the adopted Master Processing Procedures based on the process validation?

4 Are further validation steps done if significant change occurred in

a. Process, Equipment & Materials?

5 Are routine critical appraisals (e.g. annual product review) performed to ensure that the process and the procedure remain capable of achieving the intended results?



Page 15 of 73


Sr.

No


VI. BATCH AND LOT NUMBERING SYSTEMS Y N NA

1 Is there a system or SOP describing the details of batch and lot numbering set-up including for identification of

a. raw materials? b packaging materials? c intermediate products?

d bulk products? efinished products?

2 Is the batch and/or lot numbering system applied to a processing stage and to the respective packaging stage related to each other?

3 Is the numbering system applied to assure that the same batch or lot number will not be repeatedly used for the same product for at least 10 years?

4 Is the allocation of the batch or lot numbers immediately recorded?

5 Does the record of the allocation include

a. the date of allocation?

b. the product identity?

c. the size of the batch or lot?

VII. WEIGHING AND DISPENSING

1 Is the area equipped to avoid cross-contamination and physically separated from the other rooms by walls or other type of separation?

2 Are lighting and ventilation adequate?

3 Is there temperature and humidity control, where required?



Page 16 of 73


Sr. No Requirements Compliance Comments

VII. WEIGHING AND DISPENSING Y N NA

4 Are weighing and dispensing area maintained in a clean condition?

5 Are sterile raw materials weighed and dispensed in the sterile area?

6 Is the area adequately staffed?

7 Is there proper supervision in the area?

8 Have the personnel received GMP training?

9 Do the personnel receive up-dated training?

10 Are personnel wearing appropriate clothing?

11 Is protective clothing (gloves, caps, masks etc.) used during the weighing operations?

12 Are the utensils used for weighing (receptacles, scales, hoppers, spatulas, pipettes etc.) properly cleaned after each use?

13 Are these utensils kept in appropriate place which is free from contamination?

14 Are the scales and balances used for weighing calibrated regularly?

15 Are these recorded?

16 Are records for these calibrations maintained?

17 Are the containers of the raw materials to be weighed cleaned before being opened?

18 After weighing, are these containers well sealed?

19 Are raw materials or components for each batch properly identified and segregated after weighing?



Page 17 of 73


Sr.No Requirements Compliance Auditors Comments


20 Does this identification include

a. the name of the raw materials or component?

b. the batch and other control number of the raw material or component?

c. the batch number of the drug product to be manufactured?

d. the quantity that was weighed?

e. the signature/initial of the weigher and the checker?

22 Is a control system governing issuance of starting materials, intermediate products and bulk products available?

23 Are there written procedures for handling, weighing, counting and dispensing

a. raw materials? b packaging materials?

24 Are only the relevant raw materials, intermediate products and bulk products located within the dispensing area?

25 After weighing, dispensing and labeling, are raw materials, intermediate products and bulk products transported and stored in a manner that will preserve its integrity until further processing?

26 Is only one particular printed packaging material permitted in a single coding station at a time?

27 Is adequate segregation provided between coding stations?



Page 18 of 73


Sr.

No



28 Prior to weighing and dispensing, is each container of raw materials checked for proper labeling, including the approval label from quality control?

29 Are capacity, accuracy and precision of weighing and measuring equipment used appropriate to the amount of materials to be weighed or measured?

30 For any weighing or measuring operation do at least two persons independently verify the correctness of the identity and amount of weighed or measured material?

31 Are dispensed raw materials intermediate and bulk products rechecked for accuracy and signed by the production supervisor prior to delivery to the production area?

32 Are all raw materials, packaging materials, intermediate and bulk products returned to storage areas properly documented and reconciliated?

33 Is return of raw materials, packaging materials, intermediate and bulk products prohibited unless they meet their defined specification?

A .PERSONNEL

1 Are there adequate number of personnel and adequate supervision for all processing operations?

2 Are they adequately trained and qualified for operations performed?

3 Are they restricted to work, if medical reasons dictate?

4 Are they properly clothed for the operations performed?

5 Have personnel received GMP training?

6 Do the personnel receive up-date training?...



Page 19 of 73



B PREMISES Y N NA

7 Is the area properly constructed to facilitate proper operation, cleaning and maintenance?

8 Is adequate lighting provided?

9 Is temperature and humidity controlled, where necessary?

10 Is dust control provided, where needed?

11 Is the environment of processing areas monitored and controlled to the degree required for the operation performed?

12 Are processing areas clean and properly maintained according to specified procedures?

13 Is the air supply system for all processing areas adequate to eliminate cross-contamination of drug products?

14 Are effective air extraction system in the dust producing locations and equipment installed with discharge points situated so to avoid contamination?

15 Are effective air filtration or other appropriate system installed to retain dust?

16 Are steps taken, before any processing operation begins, to ensure the work area and equipment free from any materials, products or document not required for the current operation?

C EQUIPMENT

17 Is the equipment adequate for intended use? size? capacity?

- made of non reactive, non absorbtive, non additive material?

18 Is it constructed as such that lubricants or coolants cannot contact drug products?



Page 20 of 73



C EQUIPMENT Y N NA

19 Does the equipment facilitate adequate cleaning and maintenance?

20 Is the equipment identified as to its status (e.g. clean, under cleaning, to be cleaned, product/batch controls)?

21 Are all equipment in processing checked before use?

22 Is the equipment certified in writing as clean before use?

23 Are written procedures available for cleaning, maintenance and sanitizing?

24 Are records for cleaning, maintenance, sanitation and inspection maintained?

25 Are containers and closures used for materials awaiting processing for intermediate and for bulk products made of a material and type which prevent contamination and deterioration of the products or materials?

26 Are all containers and equipment holding intermediate products properly labeled as to identify the stage of processing?

27 Are all inappropriate labels or marks previously used completely removed?

28 Are all intermediate and bulk products properly labeled and quarantined until approved and released by quality control unit?

29 Are all required in-process controls accurately recorded at the time of the performance?

30 Is the actual yield of each processing step of a production batch recorded and checked against the theoretical yield?

31 Is particular attention paid to the problem of cross-contamination of processing?

32 Are special care taken to protect against contamination of the product by fragments of metal, glass and wood?



Page 21 of 73



C EQUIPMENT Y N NA

36 Are critical operating parameters (e.g. time, speed and temperature) for each mixing, operation monitored during processing?

37 Are they recorded in the batch processing record?

38 Are filter pad use for filtration for different products washed between use?

39 Are filters pad specific to one products only used for certain highly potent or sensitizing products?

40 Is air used for manufacturing is of suitable quality and filtered through air filter?

44 Are the preparation of the solution and their use documented?

49 Are rejected or discarded bottles placed in containers and clearly identified as such?

50 Are their quantities recorded in the batch processing record?

53 Are liquids produced so as to protect the products form microbial and other contamination?

54 Are closed systems employed for production and transfer of liquids or creams and ointments?

55 Is water used for production of liquids tested for quality and microbial count?

56 Where pipelines are used for delivery of ingredients or supply of bulk products, is

a. care taken to ensure that such systems is easy to clean?

b. designed and installed so that it may be readily dismantled and cleaned?

57 Are measuring system verified as accurate?

58 Are measuring dipsticks used only with the particular vessel for which they have been calibrated?



Page 22 of 73


Sr.

No


WATER SUPPLY SYSTEM Y N NA

60 To ensure the reliable production of water of the required quality are water treatment plants -

a. designed and constructed? B maintained? operated?.

61 Are water sources, water treatment equipment and treated water checked for contamination and maintained regularly for

a. chemical? b Microbial?

62 Does the monitoring system cover

a. sample size?

b. location where samples are taken form?

c. frequency of sampling?

d. test and specifications including chemical, microbiological and Pyrogen tests?

63 Are records of the result of the monitoring and any of remedial action maintained?

64 Is the water produced, stored and distributed in such a way to discourage microbial growth?

65 Are pressure relief outlets of water storage protected by hydrophobic microbial air filters?

66 Method of water for production;

a. by distillation ? by other means(mention the method)? ... ...

67 Is purified /Distilled water stored

a. in clean, , non-reactive, non-absorptive, non-additive containers?

b. protected from contamination?



Page 23 of 73


Sr.

No


WATER SUPPLY SYSTEM Y N NA

68 If it is not recirculated, is it discarded after 24 hours?

69 Is there a sampling procedure covering

a. location where samples taken?

b. sample size?

c. frequency of sampling?

d. test and specification including chemical and microbiological and perogen tests?



Page 24 of 73


Sr.

No


FILLING AND PACKAGING Y N NA

1 Are there procedures describing

a. receipt and identification of bulk ,packaging components?

b. proper control to assure the correct, printed and unprinted packaging component used?

c. the required in-process control?

d. the reconciliation of bulk products and printed packaging materials?

e. final package examination?

2 Do the packaging operations proceed following the instructions and using the specified materials described in the Master Packaging Procedure?

3 Are the details of the operation recorded on the Batch Packaging Record?

4 Is only one product batch and packaging size on a line at any given time?

5 Are all deliveries of bulk product and packaging components checked and verified for their correctness against the Master Packaging Procedure of other specific order?



Page 25 of 73


Sr.

No


Pre- coding of components Y N NA

6 Is the first precoded packaging compound checked on the correctness of the printed codes?

7 Are components allocated for pre-coding stored in sealed containers within an appropriate area for proper security and segregation?

8 Does pre-coding of components take place in an area isolated form other packaging operations?

9 Are all pre-coded components checked against the correctness before transfer to packaging?

Line clearance

10 Before a packaging operation starts, are checks carried out to ensure that work area and equipment are clean and free form

a. any products?

b. product residues? Or

c. documents not required for that operation?

11 Is an inspection conducted of each line prior to packaging to ensure

a. removal of all previous drug product and labeling materials?

b. general cleanliness of the line and the immediate area?

c. cleanliness of the equipment to be used? Employed

12 Is there inspection verified by Quality Control?

In-process control



Page 26 of 73


Sr.

No


Line clearance Y N NA

13 Are there procedures for in-process control describing,

a. the point of sampling?

b. the frequency of sampling?

c. number of samples to be taken?

d. specification to be checked?

e. the limit of acceptability for each specification?

14 Does the in-process control include;

a. checking of the product till or count at the start of the packaging run?

b. checking of the finished products through-out the run at regular intervals for their full compliance with specifications?

c. checking of batch identity through-out the packaging operation?

15 Are the results of in-process tests and inspection

a. recorded?

b. included in the Batch Packaging Record?

Operating practices

16 Is there adequate separation of packaging lines to prevent any mix-up?

17 Is each packaging line identified with product name, pack, size and batch number?



Page 27 of 73


Sr.

No


Operating practices Y N NA

18 Are storage containers for a bulk product, partly packed product or sub-batch labeled and marked with;

a. product identity? b quantity? C batch number? d status?

19 Are the empty containers to be filled supplied to packaging line or station in a clean condition?

20 Are printed packaging materials found during clean-up

a. turned over to the supervisor in the packaging area?

b. placed in special designated containers (for reconciliation and destruction at the end of packaging run)?

21 Are finished or semi-finished packages observed off the packaging

a. given to the supervisor of the packaging?

b. never returned directly to the packaging line?

c. scrapped and the amount recorded, if the package cannot be identified for the same batch or lot number?

22 Are products filled into their final containers and awaiting labeling and final packaging segregated and marked with the;

a. product identification?

b. batch number?

c. status?



Page 28 of 73


Sr.

No



23 Are measures taken to control the spread of dust during packaging especially of dry products by;

a. using dust collecting device?

b. discouraging use of compressed air?

24 Is a segregated area provided for filling and packaging of potent low dose or toxic products or sensitizing agents?

25 Is use of brushes discouraged?

26 Is bringing personal medicament into the packaging area prohibited?

27

Is placing of packaging components or products in the pocket of the personnel prohibited?

28 Are supplies like lubricants, adhesive, inks, cleaning fluids etc. kept in

a. a container different form the use for drug containers?

b. clearly labeled as to their contents?

Completion of the packaging operation

29 Is the last production package carefully checked to confirm with specification on completion of the packaging operation?

30 Is only finished products form a single packaging operation placed in a pallet?

31 Is the quantity of the partly filled carton indicated accordingly?



Page 29 of 73


Sr.

No



32 Is inspection performed on each line after the packaging operations, to ensure that

a. all excess packaging components

b. remaining bulk product, or

c. rejected packaging components

are removed, and after reconciliation closely supervised to ensure that only save and properly identified packaging components and bulk products are permitted to be returned to the warehouse?

33 Are all excess or rejected coded packaging materials

a. counted? b destroyed under control of the supervisor?

34 Are quantities destroyed recorded on the Batch Packaging Record?

35 Is the net used packaging components and bulk products calculated and recorded by the supervisor?

36 Is any significant unexplainable yield discrepancy or failure to comply with specification thoroughly investigated?

37 Is the investigation extended to other batches or other products which might also be affected?

38 Are finished products quarantined until final release by Quality Control?

39 Is the removal of excess packaging component and bulk products after reconciliation closely supervised?

H. RECOVERED MATERIAL

1 Is there a procedure available for reprocessing a batch of product?

2 Has the procedure been checked and authorized by appropriate qualified persons?



Page 30 of 73


Sr.

No



3 Does the resultant batch after reprocessing meet the product quality specification as indicated by the laboratory test results?

4 Does the batch processing document precisely record the reprocessing procedure applied to the batch?

Product residues

5 Is there a procedure available for making use of a product residue?

6 Does the SOP specify the quality requirements of the product residue to make it possible for use in subsequent batch?

7 Is the inclusion of a product residue in subsequent batch specifically authorized and documented in the batch record?

8 Is there an established limit for the quantity of product residue to be added to a subsequent batch that has been approved by the Quality Control unit?

9 Has the batch from which the product residue originates been evaluated and judged suitable for use before the batch incorporation that residue is released by the Quality Control unit?

Returned goods

10 Is there a procedure for reprocessing returned goods from the manufacturer’s own warehouse or other store rooms and/or from the market?

11 Does the procedure specify that reprocessing work such as redressing of soiled packaging material or incorporation in subsequent batches, may be considered only after critical assessment of the product’s quality, have been made by the Quality Control unit?

12 Does the assessment also include such parameters as the product’s physical condition and its history (outside the manufacturer’s control) and the age of the product?



Page 31 of 73


Sr. Requirements Compliance Comments


13 Is the reprocessing work specifically authorized by a qualified person and documented?

14 Are special precaution taken for the repackaging work especially relabeling to prevent mix-up or mislabeling?

I. FINISHED PRODUCT QUARANTINE AND DELIVERY TO STOCK

1 Is there a procedure available for controlling the transfer of finished products from the packaging unit through a detainment in a quarantine area to the finished product warehouse?

2 Does the procedure specify all the requirements that should be met, including a complete packaging record for the Quality Control unit to evaluate before releasing the product?

3 Is the quarantine area for finished product restricted to people access other than to authorized persons?

4 Are the finished products requiring special storage conditions appropriately labeled and stored under the specified condition in the quarantine area?

5 Does the quality control evaluation for final release of a batch of finished product include satisfactory completion of the following requirements: the batch meets all processing and packaging specifications

a. retention of sufficient quantity of finished product samples

b. packaging and labeling have been correctly performed

c. the reconciliation of packaging materials is acceptable

d. the quantity transferred to the warehouse for marketing complies with the quantity shown on the transfer documents?



Page 32 of 73


Sr.

No



7 Is the finished product checked properly for identity and its condition before transfer to the warehouse?

8 If the identity and condition of finished product indicate non- compliance or raise suspicion, will it be retained in the quarantine area pending quality control inspection and disposition?

9 Is the approved batch of finished product immediately removed from the quarantine area and transferred to the warehouse?

10 Is the batch of released finished product entered in the corresponding inventory card upon receipt by the warehouse unit?

J. FINISHED PRODUCT WAREHOUSE

1 Is there an area of adequate size for the storage of the finished products?

2 Are lighting and ventilation adequate?

3 Are there special areas with temperature and/or humidity control, if required?

4 Is there any program for general housekeeping?

5 Is there any program for protection from insects, rodents and birds?

6 Is there proper supervision?

7 Have the personnel received GMP training?

8 Do the personnel receive up-date training?

9 Are finished released batches of drug products physically separated or otherwise controlled?

10 Are there distribution records which include

a. date and quantity transferred? b batch numbers? c name and address of distributors?



Page 33 of 73


Sr.

No



12 Is there a segregated area for returned goods?

13 Are there records to show dates, quantity and reasons for returned goods?

14 Is there a system designed for controlling shipment of drug products to ensure that the first incoming batch of product is distributed first (FIFO)?

15 Does the system allow to generate records of distribution of each batch of product that will facilitate tracing of the batches for investigation purposes or in the event of a product recall?

16 Is there a procedure available to describe the proper distribution of a drug product?

17 Is deviation from the FIFO concepts of distribution discouraged or only allowed for short periods only by special authorization of a responsible management?



Page 34 of 73


Sr.

No


VI. QUALITY CONTROL Y N NA

A. GENERAL PROVISION

Does the quality control unit do the following principle duties ?

1 Establish and revise control procedures and specifications?

2 Periodic revision of the specifications to comply with the latest edition of the pharmacopoeia

3 Prepare detailed written instructions for carrying out each inspections, test and analysis?

4 Establish written sampling plan and sampling procedures?

5 Maintain retained sample for future reference?

6 Release or reject each batch of starting material, intermediate, bulk or finished product?

7 Review all documentation relating to the batch processing, packaging and testing of each batch of finished product before authorizing release for distribution?

8 Evaluate the stability of all finished products on an on-going basis and raw materials where necessary, and to establish instructions for the storage of materials and products within the manufacturing plant on the basis of their stability data?

9 Establish expiry dates and shelf-life of raw materials and finished products based on their stability data and storage condition?

10 Is the quality control unit assigned a responsibility for evaluating and/or approving

a. Master Processing Procedure b Packaging Procedure

b. Changes made to the Master Processing Procedure which could affect product quality.

c. Production equipment cleaning and sanitation procedure.



Page 35 of 73


Sr.

No



11 Evaluate and approve any reprocessing procedure for products?

12 Approve those suppliers of raw materials and packaging materials known and believed to be capable of and reliable for supplying starting materials that meet the company's established quality specifications?

13 Take part or assist in validation program?

14 Evaluate all complaints received or deficiencies noted about any batch, if necessary in cooperation with other departments of the company, and to take appropriate corrective action?

15 Prepare secondary reference standards as specified in the current procedure for testing and to store these standards under proper condition?

16 Maintain analytical records of the tests of all samples taken?

17 Evaluate return drug products and determine whether such drugs could be released or reprocessed or should be destroyed?

18 Participate in the self-inspection program with other departments of the company?

B. PERSONNEL

1 Does each individual engaged in the supervision or conduct of a laboratory operation have proper education, training and experience or combination thereof to enable him to perform the assigned function?

2 Are detailed, written job descriptions available for all employees?

3 Are the duties and responsibilities of each individual clearly defined in his job description or by other suitable means?

4 Are there training programs for the staff on concerned areas?

5 Are the training records of the staff up-to date?



Page 36 of 73


Sr.

No

Requirements Compliance Auditors Comments


6 Have the employees undergone training in the following areas during the last year?

a. GMPs /GLPs b SOPs c Analytical Techniques.

b. Microbiological Techniques.

7 Are the employees knowledgeable about their job functions?

8 Have the employees undergone qualification according to the relevant SOP?

9 Is an up-to date organizational chart of the Quality Control Department available?

10 Do personnel wear protective clothing and safety equipments such as respirators, face mask, safety glasses and acid or alkali resistance gloves appropriate to the duties being performed?

C. PREMISES

1 Is the quality control laboratory designed, equipped and of sufficient space to suit the relevant operations?

2 Does the design of the laboratory consider the suitability of construction materials, fume prevention and ventilation?

3 Is the laboratory physically separated from the production room?

4 Are the biological, microbiological and chemical laboratories segregated from each other?

5 Is processed and adequate air supply assured in instrumental, biological and microbiological laboratories ?

6 Are separate air handling units installed for biological, microbiological and instrumental laboratories?



Page 37 of 73


Sr.

No



7 Are service pipings and devices adequately marked?

8 Are non-interchangeable connections or adapters provided for dangerous gases and liquids?

9 Is the laboratory maintained in a good state of repair?

10 Is the laboratory neat and orderly with sufficient space for equipment and operations?

11 Is there evidence of good housekeeping?

12 Is there a special room for microbiological and sterility testing?

13 Is the environment in the microbiological room controlled?

14 Is there a separate room for instruments to protect them against electrical interference, vibration, contact with excessive moisture and other external factors or where there is need to isolate the instrument?

15 In the room for sensitive instruments

a. Are temperature and humidity controlled?

b. Is there any vibration-proof bench for balances?

16 Are provisions made for the proper and safe storage of waste materials a waiting disposal?

17 Are toxic substances and inflammable materials stored in suitably designed and separated enclosed cupboard?

18 Is access into each room limited?



Page 38 of 73


Sr.

No



D. EQUIPMENT / INSTRUMENT

1 Are equipment and instruments available suitable to the testing procedures undertaken?

2 Are instruments properly maintained?

3 Are equipment and instruments serviced and calibrated at pre-specified intervals?

4 Are records of validation maintained?

5 Are there limits for accuracy and precision?

6 Are there provisions for corrections when limits are not met?

7 Is there a valid calibration sticker in each instrument?

8 Are the date of calibration and servicing and re-calibration due date clearly indicated on the equipment or by other approximate means?

9 Are provisions made to indicate failure of an equipment?

11 Are defective equipment withdrawn from use until the defect has been rectified?

12 Are safety shower and eye-bath provided in close proximity to the laboratory working area?

E. REFERENCE STANDARDS

1 Are reference standards under responsibility of a designated person?

2 Are official reference standards used only for the purpose described in the appropriate monographs?

3 Are secondary or working standards established by the applications of appropriate tests?



Page 39 of 73


Sr.

No



4 Are checks for secondary reference made at regular intervals to correct deviations and to assure the accuracy of the result?

5 Are all reference standards stored and used in a manner which will not adversely affect their quality?

6 Does the label of the secondary reference standards indicate the assay, date of manufacture, date of standardization, expiry date, and storage conditions where appropriate?

7 Is there any system to record when the closure of primary or secondary reference standard was first opened ?

F. REAGENTS AND CULTURE MEDIA

1 Are all chemicals, reagents and culture media recorded upon receipt or preparations?

2 Are written guidelines available for the preparation of reagents ?

3 Are reagents in the laboratory prepared following written procedures?

4 Are the reagents adequately labeled with respect to date of preparation, concentration, standardization, shelf-life, re-standardization date, storage condition and signature of the person preparing the reagent ?

5 Is there guidelines available for the grade and quality of chemicals and reagents to be used ?

G. SPECIFICATIONS AND TESTING PROCEDURES

1 Are there approved test procedure available for all tests performed in the laboratory?

2 Are the instructions given in the relevant test procedure for each material or product followed properly ?



Page 40 of 73


Sr.

No



3 Is the result, especially where calculations are involved, checked by the supervisor before the material or product is released or rejected?

4 Examine the work currently being performed by one analyst.

a. Is the test procedure at hand? b Is it up-to-date? c Is it being accurately followed?

b. Has the test method been validated for accuracy, precision and reliability?

5 Are accuracy and reproducibility of the test methods established?

6 Are specifications and testing procedures established for each raw material, intermediate, bulk and finished product and packaging materials approved and maintained by the quality control department?

7 Do testing procedure include

a. Amount of sample necessary for testing and retention for future analysis

b. Amount of each reagent, buffer solution, etc necessary for the tests

c. Equipment and instruments required for the tests

d. Guidelines for calculation of result

e. Target value and tolerance allowable for each test ?



Page 41 of 73


Sr.

No



H. RECORD OF ANALYSIS

1 Are standard formats available to record the procedure and result of analysis ?

2 Does the record of analysis include the following ?

a) Name and batch number of the sample

b) Name of the person receiving the sample

c) Method of analysis

d) All data, such as weight, burette reading, volumes and dilutions made with calculation

e) Statement of permitted tolerances

f) Statement of compliance or non-compliance with specifications

g) Statement of approval or rejection and recommendation for its disposal, signed and dated by the authorized person

h) Name of supplier, total quantity and number of containers received , in case of raw materials and packaging materials and similar relevant information in case of intermediate, bulk and finished product.

i) Signature of the persons responsible of analysis and checking

I. RETAINED SAMPLES

1 Are the finished product samples stored under condition which simulate marketing conditions as indicated on the labeling?

2 Do retained samples consist of at least the twice the quantity necessary to perform all the required tests except those for sterility?



Page 42 of 73


Sr.

No



3 Are appropriately labeled samples collected from each batch of raw material and finished products retained?

4 Do these include :

a. A representative sample of each batch of an active ingredient?

b. A quantity at two times the amount required for all tests necessary to determine whether the active ingredient meets all specifications?

5 Are the retained samples stored?

a. under labeled condition?

b. In the same container closure system in which the drug is marketed, or one of essentially the same characteristics?

J. VALIDATION

1 Is there an approved annual validation program for all equipment in the laboratory?

2 Examine the most recent validation file for any one equipment

a. Was the validation performed on schedule?

b. Do the results meet the relevant acceptance criteria?

3 Does the quality control department conduct validation of assay procedures?

4 Is the calibration of the instruments specified in the testing procedure conducted on the regular basis to ensure that they are always performing satisfactory?

5 Does the quality control department provide assistance or take part in the periodic validation tests carried out by other department, especially the production department to ensure that each manufactured products consistently meets the established specifications?



Page 43 of 73


Sr.

No



6 Are testing procedures validated in the context of available facilities and equipment before they are adopted for routine testing?

K. PRODUCTION CONTROL : Sampling

1 Is sampling equipment cleaned, if necessary sterilized, before and after each use and stored separately from another laboratory equipment?

2 Are all sampling equipment, which come in contact with the material clean?

3 Are samples collected by Quality Control personnel or by other person authorized by Quality control department ?

4 Is care taken during sampling to guard against contamination or mix-up of, or by, the material being sampled?

5 Are special precautions made to sampling of some particularly hazardous or potent materials?

6 Have the personnel received training in the disciplines related to correct sampling , which at least, include the following areas:

a) sampling plan; written sampling procedures; the techniques and equipment for sampling;

b) the risk of cross-contamination

c) the precautions to be taken with regard to unstable and / or sterile substances;

d) the importance of considering the visual appearance of materials, containers and labels;

e) the importance of recording any unexpected or unusual circumstances.

7 Is there provision of regular on-going program of training for sampling ?



Page 44 of 73


Sr.

No



8 Does each sample container bear a label indicating -

a. Name of sampled material; The batch or lot number reference;

b. The number of the container from which the sample has been taken;

c. The signature of the person who takes the sample; The date of sampling.

9 Are the samples properly stored before and after testing ?

10 Is there approved procedure for sampling so that the sample be representative of the batch?

11 Does the plan include the statistical method to determine the number of containers for mixing samples to make representative sample ?

12 Are samples collected from all containers so that at least identification test is done on these samples ?

13 Is there a time limit on how long a sample may remain in the laboratory prior to testing?

14 Are samples of products taken at random from a batch?

15 Are samples of sterile products taken from the potentially coolest part of heat-sterilized load and from the beginning and end of an aseptically filled batch ?

16 Are the following consideration included for the sampling of packaging materials ?

a) sampling plan; b) quantity received; c) description of the material;

d) quality assurance by the manufacturer.



Page 45 of 73


Sr.

No



17 Are the containers, after sampling, resealed and labeled appropriately ?

Raw materials

18 Are all raw materials tested for conformity with specification with respect to identity, strength, purity and other quality parameters ?

19 If tests are carried out partially, is the performance of the other laboratory who has done the testing , is evaluated or the laboratory audited ?

Re-testing of Approved Materials

20 Are storage time limits assigned to starting materials and processed products?

21 Is re-testing done on full quality parameters and according to their established specifications before re- approving or rejecting the material, if they have been stored beyond the assigned time limit ?

22 Is re-testing done for materials which have been subjected to unusual storage condition before use in productions?

Intermediate and bulk products

23 To ensure batch uniformity and integrity, is in- process control conducted by testing representative samples for intermediate and bulk product of each batch for identity, strength, purity and quality as appropriate?

24 Is quality control approval of the product made mandatory after completion of critical steps of production or after the product has been stored for a long period?

25 Are the rejected intermediate and bulk products controlled under a quarantine system designed to prevent their use in further processing unless such product is judged suitable for reprocessing later on?



Page 46 of 73


Sr.

No



26 Is there an approved SOP for in-process control of various products?

27 Does the in- process control procedure describe

a. the type of examination to be conducted at specified interval of time?

b. the established controls and test specifications?

28 Are the in-process control specifications consistent with the finished product specifications and derived from previous acceptable process average and process variability estimates?

Packaging Material Packaging Control

29 Does the Quality control department test the packaging materials according to specifications and approve their use ?

30 Is the line clearance of a packaging line performed by the packaging unit and verified by the quality control before proceeding with the packaging operations?

31 Are packed samples collected from the packaging line by the in-process control inspector at the beginning, middle and end of packing operations?

32 Are packed batches of finished products quarantined while awaiting release by the quality control unit?

Finished Product

33 Is each finished batch checked for compliance with established specifications before being released or distributed?



Page 47 of 73


Sr.

No



34 Does the checking include

a. Identity of raw materials and packaging components?

b. Identity and strength of all active ingredients?

c. Acceptance and rejection levels?

35 Are drug products failing to meet the established specifications and any other relevant quality criteria rejected?

36 If reprocessing be performed, if feasible, is the reprocessed product tested according to specification and other quality criteria prior to its acceptance and release?

Rejected Batches

37 When a batch fails the test, is the cause of the failure investigated?

38 Is a suitable remedial action taken?

Reprocessing

39 Is there a SOP for reprocessing products?

40 Has formal assessment been made on potential risk, and been rated as negligible, before deciding for reprocessing?

41 Is the method for reprocessing reviewed and approved by the quality control department and specifically authorized before implementation?

42 Are additional tests performed on the reprocessed batch, as required?

43 Is there a follow-up stability study done on a reprocessed batch?



Page 48 of 73


Sr.

No



Production Record Review

44 Does quality control review and approve all production and control records to assure compliance with established, written procedures before a batch is released or distributed?

45 Is an investigation conducted in any case where deviations from established standard occurs?

46 Is such investigation extended to other batches of the same product and/or other products that may have been associated with the specific failure or discrepancy?

47 Is the record of such investigation available and does it contain conclusion and follow-up action ?

L. ENVIRONMENT CONTROL

1 Is the process water system regularly monitored for chemical and microbiological quality?

2 Is the process water monitoring also performed at the point of use?

3 Is the microbiology test specific and using sample size that will enable to detect presence of low level indicator microorganism, e.g. Pseudomonas?

4 Is the production area monitored for microbiological and other product contaminants, on periodic basis?

5 Is there a procedure for controlling airborne contaminants in the production area?

6 Are disinfectants used for disinfections of the clean room in the microbiological laboratory ?

Microbiological Laboratory

1 Is the medium labeled with an expiration date?

2 Are cultures maintained at regular intervals?



Page 49 of 73


Sr.

No



3 Do results of environmental monitoring in the clean room conform with the limits stated in the SOP?

N. ASSESSMENT OF THE SUPPLIERS

1 Is the quality control department assigned with the responsibility to approve a supplier who is considered capable and reliable to supply starting materials that meet established specifications? (

) alone. ( √ ) jointly with other departments

2 Are prospective suppliers evaluated before orders are placed to them?

3 Is the guidelines available for such evaluation ?

4 Are the established suppliers re-evaluated even after establishing record of excellence in reputation?

5 Is there a list of approved suppliers and list of materials they are approved for supply?

O. STABILITY STUDIES

1 Is a written program available for stability studies?

2 Does this program specify or include :

a. Sample size and test intervals;

b. Sample storage conditions;

c. Reliable, meaningful and specific test method?

d. Testing in the same container/closure systems in which the product is marketed?

e. Testing requirement for product intended for reconstitution before use?



Page 50 of 73


Sr.

No



3 Is stability study performed for the following situation

a. new products

b. new packages

c. change in formulation, processing method or source of raw materials

d. batches released by exception e.g. reprossed products or properties differing from standards?

e. Products currently being marketed?

P. CONTRACT WITH OUTSIDE LABORATORY

1 Is there any contract with outside laboratory for testing ?

2 Is the contract agreement made with an outside laboratory clearly defining the nature and extend of any contract analysis undertaken?

3 Has the manufacturer evaluated the outside laboratory to determine its capability to perform tests and analysis as specified by the manufacturer?

4 Does the quality control department of the manufacturer still bears responsibility for quality of the product tested outside ?

5 Are relevant and updated testing procedures supplied by the manufacturer to the outside laboratory?

6 Does the contract agreement provide schedule for arrangement of retained samples? .



Page 51 of 73


Sr.

No



7 Does the format for recording test the results include the following information

a. name of outside laboratory?

b. Product name, strength, dosage form and batch number?

c. Testing parameters and test results?

d. Signature of analyst?

e. Date of analyst?

f. Signature of the analyst



Page 52 of 73


Sr.

No

Requirements Compliance Comment

VIII. DISTRIBUTION, HANDLING OF PRODUCT COMPLAINT, PRODUCT RECALL AND

RETURNED DRUG PRODUCT

Y N NA

A. Distribution

1 Is warehouse secure?

2 Is it environmentally controlled?

3 Is there refrigerated storage?

4 Is material stored in pallet racking etc.?

5 Is there written distribution method to customers?

6 Is there FIFO system?

B. PRODUCT COMPLAINT

1 Are written procedures for handling all written and oral complaints available?

2 Are there designated persons for receiving, channeling, reviewing and evaluating of product complaints?

3 Are complaints reviewed by quality control?

4 Does the investigation conducted, where appropriate, include discussion with manufacturing and marketing personnel and examination of retained samples?

5 Are written record for each complaint maintained in a specific file for a specific period?



Page 53 of 73


Sr.

No




Y N NA

6 Do these records include, wherever known

a. name and strength of drug product?

b. batch number? C dosage form?

c. name of complainant?

d. nature of complaint?

e. response to complainant?

If an investigation is conducted, is a written report maintained for a specified period?

If yes, how long?

8

Does the investigation results cover the following items

a. the condition of the product under complaint at the market place, how it is used, etc.?

b. analytical test results from cross investigation to the retained sample?

c. the quality control laboratory

d. evaluation of the investigation results and conclusion derived there of

9 Are any complaints involving adverse reaction evaluated by qualified person?

10 Where significant, are unexplained adverse reactions reported, and are the appropriate Health Authorities notified?



Page 54 of 73


Sr.

No




Y N NA

B. RETURNED DRUG PRODUCT

1 Are written procedures available for receipt and control of returned drug products?

2 Are records of returned goods maintained which include

a. name and strength of drug product? b dosage form? C batch number?

d reason for return? E quantity returned? E date of return?

b. ultimate disposition and date?

3 If reasons for returning the product implicates other batches, is an investigation made?

4 Are returned products specifically identified and stored in a separate area?

5

Are returned drug products destroyed unless Quality Control determines reprocessing is possible?

6 Are there written procedures for reprocessing?

7 Do these include

a. specifications and characteristic for approval?

b. identification of batch to reflect reprocessing?

c. repeat stability studies, if necessary?



Page 55 of 73


Sr.

No




Y N NA

8 Are the following returned products destroyed because they have been subjected to improper storage conditions such as

a. extreme temperature, humidity and pressure?

b. damaged due to fire, fumes and flood?

9 Are special precautions taken in handling returned products to avoid possibility of the products getting into the hands of unauthorized persons?

10 Is the quality control unit assigned the responsibility to evaluate any returned products from the market due to complaint, expiration and other reasons which may prejudice the quality of products?

11 Are returned products evaluated for necessary follow-up actions which include physical inspection and analytical testing as warranted by their conditions?

C. PRODUCT RECALL

1 Is there any written procedure for handling a product recall?

2 Who decides to recall a product? And who notify authority?

3 Is there a written procedure indicating the urgency of the execution in recalling a product recall including the embargo action?

4 Is there any records and report of a product recall including the result of product recall and embargo action?

5 Is the competent authority involved in complains and decision to recall?

6 Can recall be affected below wholesale level?



Page 56 of 73


Sr.

No


IX. DOCUMENTATION Y N NA

A. GENERAL PROVISION

1 Is there a description of the documentation system?

(Responsibility for preparation, revision, distribution, storage of master documents, SOP)

2 Are document prepared and designed carefully for easy and effective use?

3 Are the document periodically reviewed, updated or amended and formally authorized?

4 How is document controlled?

5 Is there a system for preventing the use of a superseded document?

6 Is documentation readily available to all concerned?

7 Are the document and record of a batch as well as reference sample of finished product and starting material retained for a specified period?

8 Are there document production/process specification, raw material specification, packaging component specification, standard process instructions including packaging, batch record, analytical methods, QA release procedure?

9 Are the following documents available and in use: equipment specifications, specification for cleaning materials, SOPs, QC procedures, training procedures; documentation control of process deviation; calibration and test documents; validation documents; reconciliation of batches of RM and major packing components?

10 How long document retained after release of the batch?



Page 57 of 73


Sr.

No



B. SPECIFICATION

Raw Material Specification

1 Does the specification of raw materials include

a. product name and code designated by the company?

b. product name and code designated by the supplier?

c. product description, physical and chemical characteristics of the material and its microbiological standards, if any?

d. reference monograph or pharmacopoeia or the method employed for testing the material?

e. retest interval of the material in store, if required?

f. storage requirement and other safety precautions?

g. shelf life of the material?

h. name of approved supplier?

i. date of issue?

j. authorization by signature of the quality control manager?

2 Where the raw material specification kept?



Page 58 of 73


Sr.

No



Packaging Material Specification

3 Does the specification for packaging materials include

a. product name and code designated by own company?

b. product name and code designated by the supplier

c. product description?

d. technical drawing where applicable?

e. reference monograph?

f. retest interval of the material in store, if required?

g. storage requirements and other safety precautions?

h. shelf life of material?

i. name of approved supplier?

j. date of issue?

k. authorization by signature of the quality control manager?



Page 59 of 73


Sr.

No



Specifications for intermediate product, bulk product and finished product

4 Does the specification for intermediate product, bulk product and finished product, according to its dosage form and stage of manufacturing include

a. product code and name? B dosage form and strength of product? c product description?

b. reference monograph?

c. physical properties such as viscosity, density, hardness, friability etc.?

d. the finished product specification?

e. shelf-life of the product?

f. storage requirements and other safety precautions?

g. date of issue?

h. authorization by signature of the quality control manager?

5 Where the specifications for intermediate product, bulk product and finished product kept?

C. PRODUCTION DOCUMENT

Master Production Document

1 Does the master production document include

a. the production name dosage form strength and description?

b. the name of the author and department?

c. name of verifier and list of document distribution?



Page 60 of 73


Sr.

No



2 Does the master production document contain the following data.

a. general information describing the type of packaging material, statement of the product stability safety precautions during storage and other precautions to be taken during processing and packaging of the product?

b. product composition?

c. a complete list of raw material whether they remain unchanged or become altered during processing?

d. specification of raw materials?

e. a complete list of packaging materials?

f. specification of packaging materials?

g. processing and packaging procedures?

h. list of equipments which may be used for processing and packaging?

i. in-process control during processing and packaging?

j. product shelf-life?

k. date of issue?

l. authorization by signatures of the verifiers on each page?

Master Processing Procedure

3 Does the master processing procedure outline a complete and detail procedure and instruction for processing a product including the required in-process control which should be performed by production and quality control staff?

4 Are safety precautions and specific conditions to be applied throughout the process and during storage of intermediate and bulk product included in the Master Processing Procedure?



Page 61 of 73


Sr.

No



5 Is the Master Processing Procedure dated and signed by the production manager and independently checked, dated and countersigned by the quality control manager on each page?

6 Does the master Processing Procedure include the following

a. product name, dosage form and strength?

b. a complete list of raw materials, designating the names and codes which specify their quality?

c. quantity of each active and inactive material expressed in a metric system unit of measurement for one dosage unit or batch size?

d. statement of calculate overage of a raw material used in the process?

e. permissible quantity of a product residue which may be added to the batch in process?

f. numbers of different batches or lot of an active or inactive raw material which may be used in a batch of product?

g. statement of the theoretical weight?

h. statement of the theoretical yield and percentage limits of the actual yield?

i. process location and equipment to be used?

Master Packaging Procedure

7 Does the Master Packaging Procedure outline a complete and detail procedure and instruction for packaging a product including the required in-process control which should be performed by production and quality control staff?

8 Are safety precautions and specific conditions to be applied throughout the packaging operation included in the Master Packaging Procedure?



Page 62 of 73


Sr.

No



9 Is the Master Packaging Procedure prepared, dated and signed on each page by the production manager and independently checked, dated and countersigned by the quality control manager?

10 Does the master packaging procedure include the following

a. product name, dosage form and strength and description of bulk product?

b. a description of containers, closure and other packaging materials?

c. procedure for reconciliation of the issued quantities of bulk product and packaging materials with the number of unit packs produced?

d. statement of the theoretical yield and percentage limits of the actual yield?

e. packaging line and equipment to be used?

Batch Processing Record

11 Is the Batch Processing Record prepared for each batch of product?

12 Is the Batch Processing Record derived form the reproduction of the corresponding Master Processing Procedure?



Page 63 of 73


Sr.

No



13 Does the Batch Processing Record show steps of processing which have been accomplished and include the following data

a. batch number?

b. dates of starting and finishing the process?

c. identity of major equipment and lines or location used?

d. actual weight or volume and the lot or batch number of each raw material used in the process and the signatures of the persons checking and counter-checking the dispensing of the materials as well as processing the batch?

e. batch number and the quantity of any product residue or recovered material used in the process?

f. in-process control and laboratory test results?

g. actual yield and its percentage against the theoretical yield?

h. any sampling performed during various steps of processing including the quantity taken?

i. initials of the operator and supervisor who performed and checked each step of the process?

j. detail of any deviation from the Master Processing Procedure and approval for such deviation?

k. signature and date of approval from authorized persons to signify that all steps of processing have been performed in accordance with the Master Processing Procedure?



Page 64 of 73


Sr.

No



Batch Packaging Record

14 Is a Batch Packaging Record prepared for each batch of product?

15 Does the record contain a complete information of the packaging and control of the batch?

16 Is the Batch Packaging Record derived from the reproduction of the corresponding Master Processing Procedure?

17 Does the batch packaging record shows steps of packaging which have been accomplished and contain the following data

a. batch number?

b. dates of starting and finished the packaging?

c. identity of major equipment and lines or location used?

d. quantity and batch number of each packaging material and bulk product used, and signature of the persons weighing or counting the quantity and performing the counter check?

e. in-process control results?

f. record of cleaning of the equipment used for packaging?

g. line clearance check by an authorized person before and after use of the line?

h. actual yield and its percentage against the theoretical yield at the completion of packaging?

i. samples of packaging materials used

j. any sampling performed during and after packaging including the quality taken?

k. initials of the operator and supervisor who perform and check each step of the packaging?



Page 65 of 73


Sr.

No



D. QUALITY CONTROL DOCUMENT

Procedure for Sampling

1 Is there a procedure for sampling?

2 Does the procedure include the following

a. method of sampling including the sampling plan and standard used in the sampling plan?

b. equipment and sample container to be used?

c. precautionary measures taken during sampling including use of special clothing by the person taking the sample?

d. name of person or unit authorized to take the sample? location of sampling?

e. quantity of sample taken?

f. method sub-dividing the sample taken, if required?

Test Method

3 a. Is there a test method for sampling and testing of a starting materials? b bulk and finished products? C against their specifications?

4 Does the test method include the name of reagent for analysis? ,identification test?

a. assay of the material under test as well as the computation formula to obtain the analytical result?



Page 66 of 73


Sr.

No



5 Are there a record of analysis and test report?

6 Does the record of analysis contain the following dats

a. date of test? product name including the code number if existing?

b. supplier's name? date of receipt of the material or product?

c. original batch number? batch number assigned by quality control?

d. quantity received? date of sampling and the quantity taken?

e. reference method of testing? test report with date and signature of the analyst and supervisor?

f. statement of release or rejection from quality control with signature of the responsible person and the date?

7 Does the certificate of analysis contain the following data

a. name and address of the manufacture or organization issuing the certificate?

b. number of the certificate of analysis?

c. name, dosage form and strength of the product?

d. batch number?

e. test result including its tolerance limits?

f. statement of release or rejection with explanations where necessary?

g. date and signature of the analyst and quality control manager?



Page 67 of 73


Sr.

No



8 Does the record of stability test include the following

a. date of test?

b. product name including the code number if existing?

c. supplier's name?

d. date of receipt of the material or product?

e. original batch number?

f. batch number assigned by quality control?

g. quantity received?

h. date of sampling and the quantity taken?

i. reference method of testing?

j. test report with date and signature of the analyst and supervisor?

k. statement of release or rejection from quality control with signature of the responsible person and the date?

l. number assigned to the certificate to release or rejected product?

m. reference number of previously issued certificate if required?



Page 68 of 73


Sr.

No



E. WAREHOUSE AND DISTRUBUTION DOCUMENT

Inventory Card

1 Does the inventory card contain the following data

a. material or production name and code number? date of receipt and issuing or delivery?

b. quantity received or issued and the balance stock? batch number or material or product?

c. storage location? status of material or product, whether under quarantine, released or rejected?

2 Is there any deviation to the first in first out or first expiry first out principle?

3 Is the deviation only for a short term and approved by an authorized manager?

Record of Distribution of Finished Product

4 Is there a distribution record of finished products?

5 Does the record contain complete up-to date and progressive data of distribution which are easily followed and retrievable to enable the manufacturer to impose a drug recall quickly and effectively, whenever it becomes necessary?

6 Does the record of distribution contain the following data

a. name and address of consignee? B delivery order date and number?

b. name, dosage form and strength of the product B.no ,MFG & EXP of the product?

c. quantity delivered?



Page 69 of 73


Sr.

No



F. DOCUMENT FOR MAINTENANCE, CLEANING AND MONITORING OF MANUFACTURING

AREA AND EQUIPMENT

1 Is there a procedure and record for maintenance and cleaning of equipment?

2 Does the procedure include the job description and the maintenance schedule?

3 Does the record of the maintenance of an equipment include the repair job and replacement of spare parts?

4 Is there a procedure for cleaning a production equipment which specify cleaning of the equipment prior to change of batch as well as change of product?

5 Does the procedure include the method of cleaning and the tools and cleaning materials to be used?

6 Is the cleaning operation be documented and become part of the batch record?

Procedure and Record for Pest Control

7 Is there a standard operating procedure for pest control?

8 Does the procedure include

a. the scope and schedule of pest control?

b. the method of control?

c. the tools and pesticide to be used?

d. precautionary measures and the persons of units involved in the pest control?

9 Is the pest control operation documented?



Page 70 of 73


Sr.

No



Procedure and Record for Monitoring Airborne Particles and Microorganisms

10 Is there a procedure for monitoring airborne particles and micro-organisms?


a. the method of monitoring?

b. areas to be monitored?

c. specifications including alert and action levels?

12 Is the result of monitoring documented?

G. DOCUMENT FOR HANDLING OF PRODUCT COMPLAINT, PRODUCT RECALL, RETURNED

DRUG PRODUCTS AND DESTRUCTION OF DRUGS PRODUCT

Handling Procedure and Record of Product Complaints

1 Is there procedure available for handling product complaints and report of adverse reaction of a drug product?


a. the definition of product complaint and adverse reaction?

b. the type of complaint and report?

c. method of handling and evaluation of the complaint and report?



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Sr.

No

Requirements Compliance Comment


3 Does the record of product complaints and adverse reaction report contain the following data

a. product name and batch number?

b. type of complaint or report?

c. source of complaint or report?

d. sample of complaint or reported product?

e. summary of complaint or report?

f. result of investigation?

g. evaluation of complaint or report?

h. response and follow-up action to the complaint or report?

Handling Procedure and Record of Returned Drug Product

4 Is there a procedure available for handling returned drug products?

5 Does the procedure include the guidelines for making decision either to salvage, reprocess or destroy the returned drug product?

6 Is the handling and disposition of returned drug products documented?

Procedure and Record of Product Recall

7 Is there a procedure available for recalling a batch or lot or all of a finished product from market distribution?



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Sr.

No



8 Does the product recall record contain the following data

a. product name, batch number and batch size?

b. date of starting and completion the product recall?

c. reason of recall?

d. warehouse stock and distributed stock of the product being recalled at the start of recall?

e. quantity of recall product returned from the market?

f. evaluation of product recall?

g. follow-up action taken?

h. report on the handling of product recall to the management and to the government authority if required?

Procedure and Record of Destruction of Rejected Material or Product

9 Is there a procedure available for destruction of rejected materials or products?

10 Does the procedure include precautionary measures to prevent pollution of the environment?

11 Does the record of rejected material or product destruction contain the following data

a. product name, batch number and quantity of rejects?

b. source of rejected material or product?

c. method of destruction?

d. persons performing and witnessing the destruction?



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Sr.

No



H. DOCUMENTS FOR SPECIFIC EQUIPMENT

1 Is there a procedure for operating a specific equipment to prevent mishandling of equipment that may influence the quality of a product?

2 Is there a procedure for calibrating a specific equipment to ensure that the equipment always weighs or measures accurately?


A. the calibration schedule? reference standard? reagents and tools to be used?

4 Is the calibration preformed documented?

Guideline and Record of Personnel Training on Good Manufacturing Practices

8 Is there a training guideline on Good Manufacturing Practices relevant to the duties and responsibilities of personnel?

9 Is there the record of training organized?

10 Does the record of training contain the following data

a. date of training? name of persons attending the training?

b. name of instructor, department or institute conducting the training?

c. training materials and training aids?

d. demonstration provided, if any?

e. evaluation of trainee?

Documents

Pharmaceutical Guidelines Page 1 73 SELF INSPECTION CHECK …