GMP Guideleines

Good Manufacturing Practices

According to GMP Guidelines and Drug and Cosmetics Act 1940

GENERAL

• Name of the Company
• Date of Incorporation
• Is the Company acting as an Organization
• Regulated Sectors : Drug License Number and validity, Laboratory Registration & Categories of Drugs permitted
• Do the Company have a policy of customer satisfaction (quality policy)? If yes, obtain a copy of the same and attach.

Show Its Various Functions, Their Interrelation and Responsibility Control

S. No.	Function	Functional Head(Mr./Ms./Mdm)	Age, Education, Training & Experience	Record of Qualification /certification by Drug Controllers
1	Management (Function of Planning that Includes Control of All Resources e.g., Investment, Banking & Finance, Human Resources and Legal Compliance)
2	Product Development & Technology (Including Standardization of Quality Plan, Specification and Processes)
3	Marketing, Sales and Distribution (Includes Warehousing)
4	Production
5	Purchasing & Stores of Incoming
6	Inspection and Quality Control (Including Setting up Assurance Standards)

PERSONNEL

• Number of Production Supervisors Asst. mfg. Chemist.
• Number of Analysts
• Are production and quality functions independent of each other.
• Are all sections adequately staffed (supervisor/Asst. Mfg. Chemist) taking into consideration the works load.
• Is recruitment of an employee proceeded by medical examinations.
• What is the periodicity of subsequent medical examinations.
• Is an employee whose state is doubtful immediately removed from work side until he is fully recovered.
• Do all personnel receive GMPs training check course content of training.
• Is training documented.
• What is the periodicity of training.
• Are protective steps against likely damage to health due to occupational hazards satisfactory.

PREMISES

• Are there any sources of pollution in the neighborhoods of the building.
• Is plant layout of suitable size, design and construction sufficient for production and quality control of drugs being produced.
• Any person drain blocked sewer of public lavatory nearby.
• Is their adequate space for equipment, material and movement of personnel and materials.
• Is there any programmed to check entry of birds, rodents and insects.
• Are any products other than drugs manufactured in the same building.
• Are buildings & facilities properly constructed to facilitate adequate cleaning and sanitation.
• Are lighting and ventilation adequate.
• Are facilities for changing street clothes footwear, washing & toilets adequate and satisfactorily maintained.
• Are sewage, trash and other effluent disposal adequate whether production of penicillin’s/ B-Lactum Antibiotics have been segregated.
• Whether production of other specified products like hormones, cylotoxic drugs segregated or whether production is carried out on campaign basis.
• State of maintenance of building (check whether the firm/company have preventive maintenance program)
• Are floors, walls and ceilings properly constructed and easy to clean, maintain and disinfect.

STORAGE OF STARTING MATERIALS

• Are there physically segregated areas for Raw Materials & Packing Materials.
• Is their quarantine area for incoming raw Material
• Is their segregated area for rejected material
• Are there separate areas for materials requiring Special storage conditions e.g. Controlled temperature & Flame Proof
• Are the areas adequate for storage of the materials in relation to their a amount and facilities provided
• Do all containers of active RM excepients and intermediates bear appropriate label at all stage of manufacture?( In no give details)
• Are empty containers freed of old labels and checked immediately prior to use.
• Is lighting and ventilation adequate in Warehouse
• Have the areas requiring special storage conditions provided with monitoring devices and data maintained.
• Is there any program for general housekeeping.
• Is there any evidence of entry of insects Rodents & birds.
• Are their warehousing operating instructions.
• Are these instructions being followed.
• Are there labels for materials of different status i.e. quarantine tested and released for use and rejected
• Are there labels of different colors.
• Are labels on containers of RMS to be used in manufacture checked with regards to identity, quantity & CA approval? If no, give details.
• Are there the following informations on labels.
  -Name of Material
  -Batch Number
  -Analysis number
  -Date of release/rejection
  -Date of expiry
  -Date of testing
• Do Quality Control personnel perform the sampling.
• Are their sampling procedures.
• Are there the following informations of each sample taken.
  -Name of person who performed sampling?
  -Number of samples taken?
  -Number of containers sampled?
  -Dated of sampling?
• Are the containers provided for storage of raw materials suitable to preserve the quality.
• Is there stock rotation program (i.e. FIFO).
• Are the printed packing materials stored in orderly manner and well separated to prevent mixing.
• Are they recorded on stock cards register.
• Are enclosed and locked areas provided for storage of narcotic or highly toxic drugs.
• Is exterior storage available
  -Solvent storage area.
  -Inflammable material storage area
  -Whether safety measures provided have
  -Been assessed by regulatory agency if any?
  -Are SOP’s available for handling of these :
  -Materials

WEIGHING AREA

• Is the weighing area segregated.
• Are lighting and ventilation adequate.
• Is the area clean.
• Do the personnel wear appropriate clothing.
• Is their danger of cross contamination during weighing.
• Are the scales & balances calibrated regularly and records maintained.
• After the containers of the raw materials to be weighed, cleaned before opening.
• Are the raw materials for each batch, after weighing properly identified.
• Are adequately clean and dried equipment used for dispensing materials from the containers.

EQUIPMENT

• Is the equipment adequate for intended use?(State size, capacity and check batch size)
• Is it constructed in such a way that lubricant coolant, etc. cannot contaminate the drug product.
• Does the equipment permit cleaning and maintenance
• Does the equipment show its status i.e. clean dirty, bath contents.
• Do all apparatus equipment bear appropriate labels to identity the product for which the equipment is used, its batch no., date etc.
• Are SOPs available for cleaning maintenance and sanitation.
• Are logbooks maintained for cleaning maintenance and sanitation of major equipment
• Are SOPs readily available to operators.
• If automatic electronic or mechanical equipment is used, are there?
  -Written Programmes for calibration inspection?
  -Records of such programmes?
  -Checks to ensure that any changes are
  -Made only by authorized person?

FACILITIES AND UTILITIES

• Are airs handling units adequate and properly located and functional.
• Is air conditioning system adequate and functional.
• Are steam generation facilities adequate and functional.
• Are vacuum systems adequate and functional.
• Is compressed air system adequate and properly functioning.
• Is water supply system adequate? Check whether
• MCD or Tube well supplies. If tube well supply Whether potable.
• Is distilled water quality and supply system adequate.
• Is demineralised water quality and supply system adequate.
• Sanctioned Power___________HP
• Generator _________________KVA provided

SANITATION AND HYGIENE

• Are cleaning schedule available for
  -Floors?
  -Walls?
  -Ceiling?
  -Doors and windows?
  -Electrical fittings?
• Are SOPs available for cleaning and sanitization.
• Are disinfectants used rotated.
• Are logbooks maintained for cleaning and sanitation.
• Is microbial load monitored in different section.
• Are adequate facilities available for personal hygiene before entering into production area.
• Are personnel instructed to observe personal hygiene.
• Are clean sterile protective clothing’s changed every time a person enters sterile area.

PRODUCTION AND IN-PROCESS CONTROL

• Are cleaning schedule available for
• Are alterations to processes recorded and authenticated by competent authorized persons
• Is an appropriate in process control being performed.
• Are non-sterile products tested for microbial load & whether microbial load is less than limits recommended by WHO.
• Are adequate measures taken to prevent cross contamination during production of different products in the same facility.
• If drying ovens are used Whether one product is dried at one time
• Are instruments used for temperature, pressure or other recording calibrated periodically and records maintained.
• Are semi finished products stored properly and are identified.
• Is stage of manufactured clearly indicated on containers.
• Is quality of water monitored, The following points may be checked.
  -Source of Water?
  -Is it potable?
  -In case deiorized water, source of feed water?
  -Frequency of charging columns, sampling
  frequency?
  -In case of water for Injection information like
  -Is it prepared by distillation or reverse osmosis?
  -Whether storage temperature is maintained at not less than 800 C and circulated.
• Do the containers and closures meet required secifications.
• Are containers checked for cleanliness and suitability for packaging before use.
• Are containers of intermediates and FPs intended for use in the plant closed properly.
• Is homogeneity maintained during filling of ointment, creams and lotions.
• Are the following controls carried out during filling operations
  -Check of volume, weight or counts.
  -Visual inspection of empty and filled containers
  -Visual inspection of closures
• Is their adequate separation of packaging lines to prevent mix-ups.
• Is each line identified with name of the product batch no. and packaging size.
• Is there only one batch of product on packaging line at any given time.
• Is an inspection carried out of each packaging line before labeling and packing operation.
• Is the inspection verified by quality control.
• Is significant discrepancy in actual yield investigated.
• Is inspection carried out of each packaging line after operation to ensure that all excess/rejected labeling material area removed.
• Are all excess or rejected coded labels and cartons destroyed.
• Is batch production record prepared for each batch of product and maintained.
• Do the batch production records indicate that each significant step in manufacturing was performed and checked by second individual wherever appropriate.
• Are master instructions or procedures readily available in production area.
• Are these instructions and procedures being followed.
• Are only materials, containers and appliances necessary for the job in hand stored in the vicinity of the manufacturing areas and are these properly labeled with name of the product, batch no. date, etc.
• In inert gas used in any operation including packing.
• If yes, identify the gas and the products for which Used.

PRINTED LABELING AND PACKING MATERIAL CONTROL

• Is specimen copy of each label and printed packaging material approved before sending it to the printer
• Are labels and other printed packing materials checked and approved by Quality Control before release to productions.
• Is access labels and other printed packaging material store limited to authorized persons.
• Is there any designated individual to control and issue labels and other printed packaging materials.
• Are individual labels stored separately.
• Are printer’s counting accepted or counted by factory workers for inventory purposes.
• Do batch production records indicate
  -Number of labels or other printed
  -Batch or control code?
  -Reconciliation of number/amount of label and printed packing material issued, used and destroyed?.

QUALITY CONTROL

• Are master control procedures Signed and dated by responsible person.
• Do these control procedures included specifications, test procedures or other control procedures for:
  -Raw materials?
  -In-Process materials?
  -Packaging and labeling materials?
  -Finished products?
• Are the procedure in written form and readily
  Available to QC personnel.
• Are there procedures and specifications for acceptance of reprocessed materials.
• Are there written sampling procedures for
  -Raw materials?
  -In process material
  -Packaging and labeling materials?
  -Finished Products?
• Are samples collected by Q.C. personnel
• Is there special room for microbiological and sterility testing.
• Is the environment of room controlled.
• Cultures, Sub Cultures
  -Are microbial stains obtained from authorized/reputed source?.
  -Frequency of sub-culturing
  -Frequency of identification of organism by microscopically or biochemical test.
  -Are records of subculturing and identification of strains maintained?
• Are animal test performed.
• Are animals properly housed.
• Are the temperature and humidity of animal house controlled.
• Are records of animals used maintained.
• Are the animal quarantined on receipts and examined for infection/disease.
• In access to animal house restricted to authorized persons.
• Is fresh water and animal feed available in animal house
• Are all raw materials, containers, closures, labels and printed packaging materials approved and released by Q.C. for use in manufacture of drug products.
• Are semi finished products tested for appropriate tests when necessary.
• Is bulk finished products tested for established specifications before packaging.
• Is every finished products tested for established specifications before release for sale.
• Are there any deviations from established procedures or specifications and are these justified.
• Does the QC maintain records of all the test carried out.
• Does the QC reviews all production and control records to ensure compliance with established written procedures before a batch of the products is released for sale.
• Reference standards
  (a)Are reference standards(R.S.) available?
  (b)Are these primary or working R.S ?
  (c)Are working RC calibrated against primary R.S. or CRS ?
  (d)Is R.s. stored properly (at low temperature under dehumidified conditions)?.
  (e)Are records of R.S. their calibration maintained?
• Are samples in sufficient quantity for testing twice retained of starting materials and finished products for future examination, in case of need.
• Is written program available for stability studies including the following
  -Sample storage condition?
  -Room temperature?
  -Accelerated again test?
  -Sample size and test intervals?
  -Reliable and specific test methods?
  -Testing in the same containers closure system in which it is marketed?

STORAGE OF FINISHED PRODUCTS

• Is the area adequate with reference to materials stored.
• Are lighting and ventilation adequate.
• Whether special areas with temperature and humidity control required? Have these been provided.
• Is their stock rotation program (FIFO).
• Are the inventory records to show
  -Amounts?
  -Batch Number ?
  -Date of receipt ?
• Have distribution records been maintained.
• Do distribution records provide sufficient information for drug recall purpose.
• Is there segregated are for retrieved goods.

DOCUMENTATION

• Are SOPs available for the following
  -Receipt of raw materials and other components?
  -Quarantine and storage?
  -Quality Control System and approval/ rejection?
  -Release to production?
  -Weighing and dispensing ?
  -Processing and production operations?
  -Packaging and labeling ?
  -Quality Control?
  -In Process
  -Finished Products?
  -Storage of Finished Products?
  -Distribution?
  -Returned goods?
  -Recall and complaints?
  -Cleaning and maintenance ?
  -Quality control of Water
  -For reworking of nonconforming batches in existence? If yes, check records
• Have these SOPs been prepared, signed and dated by responsible person.
• Are there additional documents like logbooks notebooks or other similar records available to show execution of various functions.
• In case of review and changes, does responsible person singe SOPs and do these show their date of effectiveness.
• Are there records of receipt of raw material sand
  Do these have following information?(Goods Receipt Note-GRN)
  -Receiving GRN documents number?
  -Date of receipt?
  -Manufacturer?
  -Manufacturers batch number?
  -Type and size of containers?
  -Number of containers and conditions?
• Are there records of stock and issue of raw materials and do these have following information:
  -Opening balance
  -Date of receipt
  -Quantity received?
  -Name and batch number assigned by the manufacturer?
  -Invoice number, date, name and address of supplier?.
  -Analysis report number and date
  -Date of expiry
  -Date of issue?
  -Name and batch number of product for manufacture of which issued?
  -Balance?
  -Signature of issuing person?
• Is there a master formulation record for each drug product being produced.
• Is there as separate master production documents for each dosage form/batch size
• Are these master production records signed and dated by competent person? Do they show the following particulars.
  -The name, strength and description of the dosage form?.
  -Name and quantity of each active ingredient per dosage unit or per unit of weight or measure of the drug product?
  -The total weights or measures of any dosage unit?.
  -A complete list of components identified by name the /codes?.
  -An accurate statement of the quantity of Each component?
  -Calculated axcess of component, if any?
  -Theoretical weight or measure at appropriate processing stage?
  -Description of containers, losures and packaging materials?
  -Complete manufacturing instruction?
  -Sampling & testing procedures including in-process controls?
  -Specification & precautions to be taken?
• Is a batch production records prepared for every batch produced.
• Is it reproduction of the appropriate master production documents or it has all critical information about the batch.
• Has it been checked for accuracy signed and dated by a responsible person.
• Are the records maintained by QC for all the test carried out.
• (xiii)Do these records include:
  -Graphs charts, spectra etc.?
  -Calculations?
  -Signatures of individuals who performed the test?
  -Signature of the designated person
  responsible for the review of the records for accuracy and compliance with established standards?
• Are other associated records available.
• Is documentation available readily for examination.
• Where errors have been made in entering or transcribing data
  -Have errors been crossed out with one line?
  -Have corrections been made above those crossed out?
  -Are corrections dated and initialed?
• Are batch production records capable of giving complete history of the batch right from the RM stage to the distribution of FP.

CALIBRATION OF INSTRUCTIONS AND MEASUREMENT SYSTEM

• Are the balances calibrated routinely.
• Have measuring equipments been calibrated.
• Have thermometers / thermocouples been calibrated? (Temperature at which calibrated)
  -Minimum
  -Maximum
• Have the pressure gauges been calibrated.
• Are instruments routinely calibrated.
• What is the periodicity of calibration.
• Are records maintained for all calibration.

Note : Draw a list of all major instruments available and Check calibration records.

VALIDATION AND REVALIDATION

• Are validation studies carried out for the following
  -Cleaning and sanitation procedures?
  -Process?
  -Testing?
• Have qualification studies been carried out for equipment before validation studies.
• Are validation protocols available for validation studies.
• Do the validation reports show recorded resultsand conclusions.
• Are validation studies carried out periodically.
• Is revalidation carried out in event of significant change in materials(s) or equipment.

Note : Check a few qualification and validation studies in details.

COMPLAINTS

• Are their written procedures for handling complaints.
• Is an investigation carried out wherever necessary including discussion with manufacturing personnel.
• Does QC review complaints.
• Is there a designated person for overall evaluation
• Are records maintained for complaints and do these include the following
  -Name of the product with strength?
  -Batch Number
  -Name of complainant
  -Nature of complaint?
• Is a report of investigation made.
• Do qualified personnel evaluate complaints involving adverse reactions.
• In case of significant adverse reactions, are appropriate Health Authorities notified.

PRODUCT RECALLS

• Is their written procedure for product recall in case of products know of suspected to be defective.
• Is there a designated person responsible for execution and coordination of product recalls.
• Have the degrees of recalls been specified (i.e Degree 1, Degree II and Degree III)
• Is the following information available
  -Fax, Telex, telephone numbers and addresses or national, regional and local regulatory authorities?
  -Fax, Telex, telephones numbers and addresses of radio, television and press agencies?
  -Fax, telex and telephone numbers and addresses of distributors, wholesalers, hospitals, etc.?
  -Fax, Telex and telephone numbers and addresses of competent authorities of the countries to which the drug products are exported?
• Is there as system so that distribution records are readily available to the designated person responsible for product records.
• Is the progress of product recalls recorded and final report issued including reconciliation bettween the delivered and recovered quantities of the product.
• Is the effectiveness of product recalls evaluated from time to time.
• Is there a segregated are for recalled products.

RETURNED AND SALVAGED DRUG PRODUCTS

• Are written procedures available for receipt and control of returned products.
• If reasons for returning the product implicated other batches are an investigation made and report prepared.
• Are returned or salvaged drug products destroyed unless QC determines their reprocessing.
• Are records of returned products maintained including their disposition.
• Are there written procedures for reprocessing and do these include
  -Specifications and characteristics for approval?
  -Identification of batch to reflect reprocessing?
  -Revised stability data, if necessary

SAFETY

• Is a safety manual available.
• Are safety equipment, shoes, goggles, glove, showers, aprons, masks, breathing apparatus, etc., available in the factory.
• Is adequate first aid equipment available at convenient place in the factory.
• Is adequate first aid equipment available at convenient place in the Factory.
• Is periodic first aid training given to staff
• Is flame - proof equipment used where flamable solvents or materials are stored or handled during manufacture.
• Is adequate fire fighting equipment like fire extinguishers, ladders, fire buckets filled with water/sand, etc., available.
• Are staffs trained in fire fighting operations.
• Is the building safe and provided with emergency exit, escape routes ladders, etc.
• Does the firm maintain accident history/records? if yes, comment on its adequacy.

POLLUTION CONTROL

• Are arrangements for the following adequate.
• Disposal of solid/semi-solid waste.
• Disposal of sewerage.
• Disposal of liquid laboratory waste.
• Management of gaseous pollutants.<.li>
• Is effluent treatment plant is existence? If yes, comment on it.
• Are fume hoods of adequate design in existence and used wherever necessary.

RESULTS OF PREVIOUS SELF INSPECTION AND CORRECTIVE MEASURES TAKEN

• Is the report of previous self-inspection available.
• Recommendations of previous self-inspection.
• Whether corrective measures have been taken as recommended by previous self-inspection team.

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