**To achieve the objectives listed below, each licensee shall evolve appropriate methodology, systems and procedures which shall be documented and maintained for inspection and reference; and the manufacturing premises shall be used exclusively for production of drugs and no other manufacturing activity shall be undertaken therein.
Documentation is an essential part of the Quality assurance system and, as such, shall be related to all aspects Good Manufacturing Practices (GMP). Its aim is to define the specifications for all materials, method of manufacture and control, to ensure that all personnel concerned with manufacture know the information necessary to decide whether or not to release a batch of drug for sale and to provide an audit trail that shall permit investigation of the history of any suspected defective batch.
(1). Location and surroundings:- The factory building(s) for manufacture of drugs shall be so situated and shall have such measures as to avoid risk of contamination from external environmental including open sewage, drain, public lavatory or any factory which product disagreeable or obnoxious odor, fumes, excessive soot, dust, smoke, chemical or biological emissions.
(2). Building and premises: – The building(s) used for the factory shall be designed, constructed, adapted and maintained to suit the manufacturing operations so as to permit production of drugs under hygienic conditions. They shall conform to the conditions laid down in the Factories Act, 1948 (63 of 1948).
(3). Water System:-There shall be validated system for treatment of water drawn from own or any other source to render it potable in accordance with standards specified by the Bureau of Indian Standards or Local Municipality, as the case may be, so as to produce Purified Water conforming to Pharmacopoeial specification. Purified Water so produced shall only be used for all operations except washing and cleaning operations where potable water may be used. Water shall be stored in tanks, which do not adversely affect quality of water and ensure freedom from microbiological growth. The tank shall be cleaned periodically and records maintained by the licensee in this behalf.
(4). Disposal of waste: –
 The disposal of sewage and effluents (solid, liquid and gas) from the manufactory shall be in conformity with the requirements of Environmental Pollution Control Board.
 All bio-medical waste shall be destroyed as per the provisions of the Bio-Medical Waste (Management and Handling) Rules, 1996.
 Additional precautions shall be taken for the storage and disposal of rejected drugs. Records shall be maintained for all disposal of waste.
 Provisions shall be made for the proper and safe storage of waste materials awaiting disposal. Hazardous, toxic substances and flammable materials shall be stored in suitably designed and segregated, enclosed areas in conformity with Central and State Legislations.
B. Warehousing Area:
(1). Adequate areas shall be designed to allow sufficient and orderly warehousing of various categories of materials and products like starting and packaging materials, intermediates, bulk and finished products, products in quarantine, released, rejected, returned or recalled, machine and equipment spare parts and change items.
(2). Warehousing areas shall be designed and adapted to ensure good storage conditions. They shall be clean, dry and maintained with acceptable temperature limits, where special storage conditions are required (e.g. temperature, humidity), these shall be provided, monitored and recorded. Storage areas shall have appropriate house-keeping and rodent, pests and vermin control procedures and records maintained. Proper racks, bins and platforms shall be provided for the storage of materials.
(3). Receiving and dispatch bays shall protect materials and products from adverse weather conditions.
(4). Where quarantine status is ensured by warehousing in separate earmarked areas in the same warehouse or store, these areas shall be clearly demarcated. Any system replacing the physical quarantine, shall give equivalent assurance of segregation. Access to these areas shall be restricted to authorized persons.
(5). There shall be a separate sampling area in the warehousing area for active raw materials and excipients. If sampling is performed in any other area, it shall be conducted in such a way as to prevent contamination, cross-contamination and mix-up.
(6). Segregation shall be provided for the storage of rejected, recalled or returned materials or products. Such areas, materials or products shall be suitably marked and secured. Access to these areas and materials shall be restricted.
(7). Highly hazardous, poisonous and explosive materials such as narcotics, psychotropic drugs and substances presenting potential risks of abuse, fire or explosion shall be stored in safe and secure areas. Adequate fire protection measures shall be provided in conformity with the rules of the concerned civic authority.
(8). Printed packaging materials shall be stored in safe, separate and secure areas.
(9). Separate dispensing areas for β (Beta) lactum, Sex Hormones and Cytotoxic substances or any such special categories of product shall be provided with proper supply of filtered air and suitable measures for dust control to avoid contamination. Such areas shall be under differential pressure.
(10). Sampling and dispensing of sterile materials shall be conducted under aseptic conditions conforming to Grade A, which can also be performed in a dedicated area within the manufacturing facility.
(11). Regular checks shall be made to ensure adequate steps are taken against spillage, breakage and leakage of containers.
(12). Rodent treatments (Pest control) should be done regularly and at least once in a year and record maintained.
C. Production area:-
(1). The production area shall be designed to allow the production preferably in uni-flow and with logical sequence of operations.
(2). In order to avoid the risk of corss-contamination, separate dedicated and self-contained facilities shall be made available for the production of sensitive pharmaceutical products like: penicillin or biological preparations with live microorganisms. Separate dedicated facilities shall be provided for the manufacture of contamination causing and potent products such as Beta-Lactum, sex hormones and Cytotoxic substances.
(3). Working and in-process space shall be adequate to permit orderly and logical positioning of equipment and materials and movement of personnel to avoid cross-contamination and to minimize risk of omission or wrong application of any manufacturing and control measures.
(4). Pipe-work, electrical fittings, ventilation openings and similar services lines shall be designed, fixed and constructed to avoid creation of recesses. Services lines shall preferably be identified by colours and the nature of the supply and direction of the flow shall be marked/ indicated.
D. Ancillary Areas:-
(1). Rest and refreshment rooms shall be separate from other areas. These areas shall not lead directly to the manufacturing and storage areas.
(2). Facilities for changing, storing clothes and for washing and toilet purposes shall be easily accessible and adequate for the number of users. Toilets SHOULD separate for males and females and shall not be directly connected with production or storage areas. There shall be written instructions for cleaning and disinfection of such areas.
(3). Maintenance workshops shall be separate and away from production areas. Whenever spares, changed parts and tools are stored in the production area, these shall be kept in dedicated rooms or lockers. Tools and spare parts for use in sterile areas shall be disinfected before these are carried inside the production areas.
(4). Areas housing animals shall be isolated from other areas. The other requirements regarding animal houses shall be those as prescribed in Rule 150-C (3) of the Drugs and Cosmetics Rules, 1945 which shall be adopted for production purposes.
E. Quality Control Area:-
(1). Quality Control Laboratories shall be independent of the production areas. Separate areas shall be provided each for physico-chemical, biological, microbiological or radio-isotope analysis. Separate instrument room with adequate area shall be provided for sensitive and sophisticated instruments employed for analysis.
(2). Quality Control Laboratories shall be designed appropriately for the operations to be carried out in them. Adequate space shall be provided to avoid mix-ups and cross-contamination. Sufficient and suitable storage space shall be provided for test samples, retained samples, reference standards, reagents and records.
(3). The design of the laboratory shall take into account the suitability of construction materials and ventilation. Separate air handling units and other requirements shall be provided for biological, microbiological and radioisotopes testing areas. The laboratory shall be provided with regular supply of water of appropriate quality for cleaning and testing purpose.
(4). Quality Control Laboratory shall be divided into separate sections i.e. for chemical, microbiological and wherever required, biological testing. These shall have adequate area for basis installation and for ancillary purposes. The microbiology section shall have arrangements such as airlocks and laminar air flow work station, wherever considered necessary.
F. Personnel:
(1). The manufacture shall be conducted under the direct supervision of competent technical staff with prescribed qualifications and practical experience in the relevant dosage and / or active pharmaceutical products.
(2). The head of the Quality Control Laboratory shall be independent of the manufacturing unit. The testing shall be conducted under the direct supervision of competent technical staff who shall be whole time employees of the licensee.
(3). Personnel for Quality Assurance and Quality Control operations shall be suitably qualified and experienced.
(4). Written duties of technical and Quality Control personnel shall be laid and following strictly.
(5). Number of personnel employed shall be adequate and in direct proportion to the workload.
(6). The licensee shall ensure in accordance with a written instruction that all personnel in production area or into Quality Control Laboratories shall receive training appropriate to the duties and responsibility assigned to them. They shall be provided with regular in-service training.
G. Health, clothing and sanitation of workers:-
(1). The personnel handling Beta-lactum antibiotics shall be tested for Penicillin sensitivity before employment and those handling sex hormones, cytotoxic substances and other potent drugs shall be periodically examined for adverse effects. These personnel should be moved out of these sections (except in dedicated facilities), by rotation, as a health safeguard.
(2). Prior to employment, all personnel, shall undergo medical examination including eye examination, and shall be free from Tuberculosis, skin and other communicable or contagious diseases. Thereafter, they should be medically examined periodically, at least once a year. Records shall be maintained thereof. The licensee shall provide the services of a qualified physician for assessing the health status of personnel involved in different activities.
( 3). All persons prior to and during employment shall be trained in practices which ensure personnel hygiene. A high level of personal hygiene shall be observed by all those engaged in the manufacturing processes. Instructions to this effect shall be displayed in change rooms and other strategic locations.
(4). No person showing, at any time, apparent illness or open lesions which may adversely affect the quality of products, shall be allowed to handle starting materials, packing materials, in-process materials, and drug products until his condition is no longer judged to be a risk.
(5). All employees shall be instructed to report about their illness or abnormal health condition to their immediate supervisor so that appropriate action can be taken.
(6). Direct contact shall be avoided between the unprotected hands of personnel and raw materials, intermediate or finished, unpacked products.
(7). All personnel shall wear clean body coverings appropriate to their duties. Before entry into the manufacturing area, there shall be change rooms separate for each sex with adequate facilities for personal cleanliness such as wash basin with running water, clean towels, hand dryers, soaps, disinfectants, etc. The change room shall be provided with cabinets for the storage of personal belongings of the personnel.
(8). Smoking, eating, drinking, chewing or keeping plants, food, drink and personal medicines shall not be permitted in production, laboratory, storage and other areas where they might adversely influence the product quality.
H. Manufacturing Operations and Controls.-
(1). All manufacturing operations shall be carried out under the supervision of technical staff approved by the Licensing Authority. Each critical step in the process relating to the selection, weighing and measuring of raw material addition during various stages shall be performed by trained personnel under the direct personal supervision of approved technical staff. The contents of all vessels and containers used in manufacture and storage during the various manufacturing stages shall be conspicuously labeled with the name of the product, batch number, batch size and stage of manufacture. Each label should be initialled and dated by the authorized technical staff. Products not prepared under aseptic conditions are required to be free from pathogens like Salmonella, Escherichia coli, Pyocyanea, etc.
(2). Precautions against mix-up and cross-contamination.
I. Sanitation in the Manufacturing Premises:-
(1). The manufacturing premises shall be cleaned and maintained in an orderly manner, so that it is free from accumulated waste, dust, debris and other similar material. A validated cleaning procedure shall be maintained.
(2). The manufacturing areas shall not be used for storage of materials, except for the material being processed. It shall not be used as a general through fare.
(3). A routine sanitation program shall be drawn up and observed, which shall be properly recorded.
(4). The adequacy of the working and in-process storage space shall permit the orderly and logical positioning of equipment and materials so as to minimize the risk of mix-up between different pharmaceutical products or their components to avoid cross contamination, and to minimise the risk of omission or wrong application of any of the manufacturing or control steps.
(5). Production areas shall be well lit, particularly where visual on-line controls are carried out.
J. Raw Materials:-
(1). The licensee shall keep an inventory of all raw materials to be used at any stage of manufacture of drugs and maintain records as per Schedule U.
(2). All incoming materials shall be quarantined immediately after receipt or processing. All materials shall be stored under appropriate conditions and in an orderly fashion. All incoming materials shall be checked to ensure that the consignment corresponds to the order placed.
(3). All incoming materials shall be purchased from approved sources under valid purchase vouchers. Wherever possible, raw materials should be purchased directly from the producers.
(4). Authorized staff appointed by the licensee in this behalf, which may include personnel from the Quality Control Department, shall examine each consignment on receipt and shall check each container for integrity of package and seal. Damaged containers shall be identified, recorded and segregated.
(5). If a single delivery of material is made up of different batches, each batch shall be considered as a separate batch for sampling, testing and release.
(6). Raw materials in the storage area shall be appropriately labeled.
(7). There shall be adequate separate areas for materials and equipment to allow dry, clean and orderly placement of stored materials and products, wherever necessary, under controlled temperature and humidity.
(8). Containers from which samples have been drawn shall be identified.
(9). Only raw materials which have been released by the Quality Control Department and which are within their shelf-life shall be used. It shall be ensured that shelf life of formulation product shall not exceed with that of active raw materials used.
(10). It shall be ensured that all the containers of raw materials are placed on the raised platforms/racks and not placed directly on the floor.
K. Equipment:-
(1). Equipment shall be located, designed, constructed, adapted and maintained to suit the operations to be carried out. The layout and design of the equipment shall aim to minimise the risk of errors and permit effective cleaning and maintenance in order to avoid cross-contamination, build-up of dust or dirt and, in general any adverse effect on the quality of products. All equipments shall be provided with a logbook, wherever necessary.
(2). Balances and other measuring equipment of an appropriate range, accuracy and precision shall be available in the raw material stores, production and in process control operations and these shall be calibrated and checked on a scheduled basis in accordance with Standard Operating Procedures and records maintained.
(3). The parts of the production equipment that come into contact with the product shall not be reactive, additive or adsorptive to an extent that would affect the quality of the product.
(4). To avoid accidental contamination, wherever possible, non-toxic/edible grade lubricants shall be used and the equipment shall be maintained in a way that lubricants do not contaminate the products being produced.
(5). Defective equipment shall be removed from production and Quality Control areas or appropriately labeled.
L. Documentation and Records: –
(1). Documents shall be approved, signed and dated by appropriate and authorized persons.
(2). Documents shall specify the title, nature and purpose. They shall be laid out in an orderly fashion and be easy to check. Reproduced documents shall be clear and legible. Documents shall be regularly reviewed and kept up to date. Any alteration made in the entry of a document shall be signed and dated.
(3). The records shall be made or completed at the time of each operation in such a way that all significant activities concerning the manufacture of pharmaceutical products are traceable. Records and associated Standard Operating Procedures (SOP) shall be retained for at least one year after the expiry date of the finished product.
(4). Data may be recorded by electronic data processing systems or other reliable means, but Master Formulae and detailed operating procedures relating to the system in use shall also be available in a hard copy to facilitate checking of the accuracy of the records. Wherever documentation is handled by electronic data processing methods, authorized persons shall enter modify data in the computer. There shall be record of changed and deletions. Access shall be restricted by ë-passwords or other means and the result of entry of critical data shall be independently checked. Batch records electronically stored shall be protected by a suitable back-up. During the period of retention, all relevant data shall be readily available.
M. Labels and other Printed Materials: – Labels are absolutely necessary for identification of the drugs and their use. The Printing shall be done in bright colours and in a legible manner. The label shall carry all the prescribed details about the product.
(1). All containers and equipment shall bear appropriate labels. Different colour coded tablets shall be used to indicate the status of a product (for example under test, approved, passed, rejected).
(2). To avoid chance mix-up of printed packaging materials, product leaflets, relating to different products, shall be stored separately.
(3). Prior to release, all labels for containers, cartons and boxes and all circulars, inserts and leaflets shall be examined by the Quality Control Department of the licensee.
(4). Prior to packaging and labeling of a given batch of a drug, it shall be ensured by the licensee that samples are drawn from the bulk and duly tested, approved and released y the quality control personnel.
(5). Records of receipt of all labeling and packaging materials shall be maintained for each shipment received indicating receipt, control reference numbers and whether accepted or rejected. Unused coded and damaged labels and packaging materials shall be destroyed and recorded.
(6). The label or accompanying document of reference standards and reference culture shall indicate concentration, lot number, potency, date on which containers was first opened and storage conditions, where appropriate.
N. Quality Assurance:- The system of quality assurance appropriate to the manufacture of pharmaceutical products shall ensure that;
(1). The pharmaceutical products are designed and developed in a way that takes account of the requirement of Good Manufacturing Practices (GMP) and other associated codes such as those of Good Laboratory Practices (GLP) and Good Clinical Practices (GCP).
(2). Adequate arrangements are made for manufacture, supply and use of the correct starting and packaging materials.
(3). Adequate controls on starting materials, intermediate products, and bulk products and other in-process controls, calibrations, and validations are carried out.
(4). The finished product is correctly processed and checked in accordance with established procedures.
(5). The pharmaceutical products are not released for sale or supplied before authorized persons have certified that each production batch as been produced and controlled in accordance with the requirements of the label claim and any other provisions relevant to production, control and release of pharmaceutical products.
O. Self Inspection and Quality audit:- It may be useful to constitute a self- inspection team supplemented with a quality audit procedure for assessment of all or part of a system with the specific purpose of improving it.
(1). To evaluate the manufacturer’s compliance with GMP in all aspects of production and quality control, concept of self-inspection shall be followed. The manufacturer shall constitute a team of independent, experienced, qualified persons from within or outside the company, who can audit objectively the implementation of methodology and procedures evolved. The procedure for self-inspection shall be documented indicating self-inspection results; evaluation, conclusions and recommended corrective actions with effective follow up program. The recommendations for corrective action shall be adopted.
(2). The program shall be designed to detect shortcomings in the implementation of Good Manufacturing Practice and to recommend the necessary corrective actions. Self-inspections shall be performed routinely and on specific occasions like; when product recalls or repeated rejections occur or when an inspection by the licensing authorities is announced. The team responsible for self-inspection shall consist of personnel who can evaluate the implementation of Good Manufacturing Practice objectively; all recommendations for corrective action shall be implemented.
(3). Written instructions for self-inspection shall be drawn up which shall include the following: –
 Personnel.
 Premises including personnel facilities
 Maintenance of buildings and equipment
 Storage of starting materials and finished products
 Equipment
 Production and in-process controls
 Quality control
 Documentation
 Sanitation and hygiene
 Validation and revalidation programmes
 Calibration of instruments or measurement systems
 Recall procedures
 Complaints management
 Labels control
 Results of previous self-inspections and any corrective steps taken.
P. Quality Control System. – Quality control shall be concerned with sampling, specifications, testing, documentation, release procedures which ensure that the necessary and relevant tests are actually carried and that the materials are not released for use, nor products released for sale or supply until their quality has been judged to be satisfactory. It is not confined to laboratory operations but shall be involved and all decisions concerning the quality of the product. It shall be ensured that all quality control arrangements are effectively and reliably carried out the department as a whole shall have other duties such as to establish evaluate, validate and implement all Quality Control Procedures and methods.
Q. Specification:-
(1). For Raw materials and packaging materials includes- the designated name and internal code reference; qualitative and quantitative requirements with acceptance limits; name and address of manufacturer or supplier and original manufacturer of the material; specimen of printed material; directions for sampling and testing or reference to procedures; storage conditions; and maximum period of storage before re-testing.
(2). All containers and closures intended for use shall comply with the Pharmacopoeial requirements.
(3). For in-process and bulk products; the specifications should be authenticated.
(4). For finished products: Appropriate specifications for finished products shall include- the designated name of the product and the code reference; the formula or a reference to the formula and the Pharmacopoeial reference; directions for sampling and testing or a reference to procedures; a description of the dosage form and package details; the qualitative and quantitative requirements, with the acceptance limits for release; the storage conditions and precautions, where applicable and the shelf-life.
R. Master Formula Records: –
The master Formula shall include:
(1). The name of the product together with product reference code.
(2). The patent or proprietary name of the product along with the generic name, a description of the dosage form, strength, composition of the product and batch size.
(3). Name, quantity, and reference number of all the starting materials to be used.
(4). Processing location and the principal equipments to be used.
(5). The methods, or reference to the methods, to be used for preparing the critical equipments including cleaning, assembling, calibrating, sterilizing.
(6). Detailed stepwise processing instructions and the time taken for each step
(7). The requirements for storage conditions of the products, including the container, labeling and special storage conditions where applicable
(8). Packing details and specimen labels.
S. Packing Records: – There shall be authorized packaging instructions for each product, pack size and type which includes:
(1). Name of the product.
(2). Description of the dosage form, strength and composition.
(3). The pack size expressed in terms of the number of doses, weight or volume of the product in the final container.
(4). Complete list of all the packaging materials required for a standard batch size, including quantities, sizes and types with the code of reference number relating to the specifications of each packaging material.
(5). Special precautions to be observed, including a careful examination of the area and equipment in order to ascertain the line clearance before the operations begin.
(6). Description of the packaging operation, including any significant subsidiary operations and equipment to be used.
(7). Details of in-process controls with instructions for sampling and acceptance.
(8). Upon completion of the packing and labeling operation, reconciliation shall be made between number of labeling and packaging units issued, number of units labeled, packed and excess returned or destroyed. Any significant or unusual discrepancy in the numbers shall be carefully investigated before releasing the final batch.
T. Batch Packaging Records: –
1. Before any packaging operation begins, check shall be made and recorded that the equipment and the work stations are clear of the previous products, documents or materials not required for the planned packaging operations, and that the equipment is clean and suitable for use.
U. Batch Processing Records:-
During processing, the following information shall be recorded at the time each action is taken and the record shall be dated and signed by the person responsible for the processing operations- the name of the product; the number of the batch being manufactured; dates and time of commencement of significant intermediate stages and of completion of production; initials of the operator of different significant steps of production; the batch number and/or analytical control number as well as the quantities of each starting material actually weighed; a record of the in-process controls and the initials of the person(s) carrying them out and the results obtained; the amount of product obtained after different and critical stages of manufacture (yield); comments or explanations for significant deviations from the expected yield limits shall be given.
V. Standard Operating Procedures (SOPs) and Records:-
(1). Receipt of materials; there shall be written Standard Operating Procedures and records for the receipt of each delivery of raw, primary and printed packaging material.
(2). Sampling; there shall be written Standard Operating Procedures for sampling which include the person(s) authorized to take the samples; method of sampling and the sampling plan etc.
(3). Batch Numbering.
(4). Testing
(5). Records of Analysis.
W. Reference Samples:-
(1). Each lot of every active ingredient, must go through with all the tests, except sterility and pyrogens / Bacterial Endotoxin Test, shall be retained for a period of 3 months after the date of expiry of the last batch produced from that active ingredient.
(2). Samples of finished formulations shall be stored in the same or simulated containers in which the drug has been actually marketed.
X. Reprocessing and Recoveries:-
(1). Where reprocessing is necessary, written procedures shall be established and approved by the Quality Assurance Department that shall specify the conditions and limitations of repeating chemical reactions. Such reprocessing shall be validated.
(2). If the product batch has to be reprocessed, the procedure shall be authorized and recorded. An investigation shall be carried out into the causes necessitating re-processing and appropriate corrective measures shall be taken for prevention of recurrence. Re-processed batch shall be subjected to stability evaluation.
(3). Recovery of the product residue may be carried out, if permitted, in the master production and control records by incorporating it in subsequent batches of the product.
Y. Distribution records: Prior to distribution or dispatch of given batch of a drug, it shall be ensure that the batch has been duly tested, approved and released by the quality control personnel. Pre-dispatch inspection shall be performed on each consignment on a random basis to ensure that only the correct goods are dispatched. Detailed instructions for warehousing and stocking of Large Volume Parenterals, if stocked, shall be in existence and shall be complied with after the batch is released for distribution. Periodic audits of warehousing practices followed at distribution centers shall be carried out and records thereof shall be maintained. Standard Operating Procedures shall be developed for warehousing of products.
Z. Validation and process validation: –
(1). Validation studies shall be an essential part of Good Manufacturing Practices and shall be conducted as per the pre-defined protocols. These shall include validation of processing, testing and cleaning procedures.
(2). A written report summarizing recorded results and conclusions shall be prepared, documented and maintained.
(3). Processes and procedures shall be established on the basis of validation study and undergo periodic revalidation to ensure that they remain capable of achieving the intended results. Critical processes shall be validated, prospectively for retrospectively.
(4). When any new Master Formula or method of preparation is adopted, steps shall be taken to demonstrate its suitability for routine processing.
(5). Significant changes to the manufacturing process, including any changes in equipment or materials that may affect product quality and/or the reproducibility of the process, shall be validated.
Other Important procedures which are need to be taken care of:
(A) Product Recalls:
(1). A prompt and effective product recall system of defective products shall be devised for timely information of all concerned stockists, wholesalers, suppliers, upto the retail level within the shortest period. The licensee may make use of both print and electronic media in this regard.
(2). There shall be an established written procedure in the form of Standard Operating Procedure for effective recall of products distributed by the licensee. Recall operations shall be capable of being initiated promptly so as to effectively reach at the level of each distribution channel.
(3). The distribution records shall be readily made available to the persons designated for recalls.
(4). The designated person shall record a final report issued, including reconciliation between the delivered and the recovered quantities of the products.
(5). The effectiveness of the arrangements for recalls shall be evaluated from time to time.
(6). The recalled products shall be stored separately in a secured segregated area pending final decision on them.
(B). Complaints and Adverse Reactions:-
(1). All complaints thereof concerning product quality shall be carefully reviewed and recorded according to written procedures. Each complaint shall be investigated /evaluated by the designated personnel of the company and records of investigation and remedial action taken thereof shall be
(2). Reports of serious adverse drug reactions resulting from the use of a drug along with comments and documents shall be forthwith reported to the concerned licensing authority.
(3). There shall be written procedure describing the action to be taken, recall to
be made of the defective product.
(C). Site Master File:-
The licensee shall prepare a succinct document in the form of Site Master File containing specific and factual Good Manufacturing Practices about the production and/or control of pharmaceutical manufacturing preparations carried out at the licensed premises. It shall contain the following: –
(1). General information:
 Brief information of the firm.
 Pharmaceutical manufacturing activities as permitted by the licensing authority.
 Other manufacturing activities, if any, carried out on the premises.
 Type of product licensed for manufacture with flow charts mentioning procedure and process flow.
 Number of employees engaged in the production, quality control, storage and distribution.
 Use of outside scientific, analytical or other technical assistance in relation to manufacture and analysis.
 Short description of the Quality Management System of the firm.
 Products details registered with foreign countries.
(2). Personnel:
 Organizational chart showing the arrangement for quality assurance including production and quality control.
 Qualification, experience and responsibilities of key personnel.
 Outline for arrangements for basic and in-service training and how the records are maintained.
 Health requirements for personnel engaged in production.
 Personal hygiene requirements, including clothing.
(3). Premises:
 Simple plan or description of manufacturing areas drawn to scale;
 Nature of construction and fixtures/fittings;
 Brief description of ventilation systems. More details should be given for critical areas with potential risk of airborne contamination (schematic drawing of systems). Classification of the rooms used for the manufacture of sterile products should be mentioned.
 Special areas for the handling of the highly toxic, hazardous and sensitizing materials.
 Brief description of water system (schematic drawings of systems), including sanitation.
 Description of planned preventive maintenance programs for premises and of the recording system.
(4). Equipment:
 Brief description of major equipment used in production and Quality Control Laboratories (a list of equipment required);
 Description of planned preventive maintenance programs for equipment and of the recording system; and
 Qualification and calibration including the recording systems and arrangements for computerized systems validation.
(5). Sanitation:
 Availability of written specification and procedures for cleaning manufacturing areas and equipment.
(6). Documentation:
 Arrangements for the preparation, revision and distribution of
 Necessary documentation for the manufacture
 Any other documentation related to product quality that is not mentioned elsewhere (e.g. microbiological controls about air and water)
(7). Production:
 Brief description of production operations using, wherever possible, flow sheets and charts specifying important parameters;
 Arrangements for the handling of starting materials, packaging materials, bulk and finished products, including sampling, quarantine, release and storage;
 Arrangements for the handling of rejected materials and products; and
 Brief description of general policy for process validation.
(8). Quality Control:
 Description of the quality control system and of the activities of the Quality Control Department. Procedures for the release of the finished products.
(9). Loan license manufacture and licensee:
 Description of the way in which compliance of Good Manufacturing Practices by the loan licensee shall be assessed.
(10).Distribution, complaints and product recall:
 Arrangements and recording system for distribution.
 Arrangements for handling of complaints and product recalls.
(11).Self inspection:
 Short description of the self inspection system indicating whether an outside, independent and experienced external export was involved in evaluating the manufacturer’s compliance with Good manufacturing Practices in all aspects of production.
(12).Export of drugs:
 Products exported to different countries; and
 Complaints and product recall, if any.
Please find all articles related to SCHEDULE M below-
SCHEDULE M-I-Requirements of factory premises for manufacture of Homoeopathic preparations
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