Production%20management.ppt

Pharmaceutical Production Management

PRODUCTION MANAGEMENT Production

management,

management,

planning

also

and

called

control

of

operations industrial

processes to ensure that they move smoothly at the required level. In manufacturing operations, production management includes responsibility for product and process design, planning and control issues involving capacity and quality, organization and supervision of the workforce. The ultimate goal of production management is to produce ‘Quality Drug’

Quality of Drugs Generally we take drug to prevent and to treat a disease. If the drug is therapeutically active and has the capability to show its credit for the desired reason then we can call the drug as a quality drug. We should remember that the elegance as well as appearance can increase the drugs acceptability. Aspects of the quality of a drug: Drug is one of the prime tools for saving lives. A medicinal product must satisfy certain standards to claim it to be a quality drug. The main criteria for quality of any drug, in dosage form, are its -Safety -Potency -Efficacy -Stability -Acceptability -Regulatory compliance

Quality of Drugs (cont.)

1. Safety: Safety of medicine implies that the drug substance must meet certain safety requirements relating to its intended use. The drug related risks (side effects) are needed to be compared with the benefits given by that to the patient that is evaluation of the risk-benefit ratio. 2. Potency: The product must contain adequate drug substance in its active form. Harmful degradation products must be absent or below defined limits.

Quality of Drugs (cont.)

3. Efficacy: A product must be biologically effective. From its dosage form the drug itself is required to be biologically available to the recipients. In case of an established drug substance, the pharmacopoeial monographs provide basic information on dosage forms and the dosage, but for a new drug substance animal test, human volunteer and clinical trials are necessary to establish the efficacy claim. 4. Stability: The drug substance itself and its dosage form must be sufficiently stable to retain its minimum potency recommended by the national or international Pharmacopoeial monograph. The finished product must be marketed in suitable packs to ensure its stability for use up to the expiry date when stored under specified conditions.

Quality of Drugs (cont.)

5. Acceptability: Acceptability refers to the consumer or market acceptability. A product with unpleasant taste is not normally acceptable; similarly a discoloration though harmless may not be acceptable to the user. A medicine should have pharmaceutical elegance for market acceptability. 6. Regulatory compliance: Each unit pack of the product must be clearly and correctly labeled. Moreover, the product must fulfill the regulatory requirements. Information contained in support of the product such as potency claim, indications, side effects, precautions, storage conditions, shelf-life, instructions for use etc must comply with the drug legislation.

Figure: The Aim for Quality

Quality Assurance Quality Assurance is a wide ranging concept which covers all matters which individually or collectively influence the quality of a product. “Quality assurance is the sum total of the organized arrangements made with the object of ensuring that the products will be of the quality required for their intended use.” The Quality assurance (QA) activity stretches from product development stage to the use of the product. QA = Product design + GMP + QC + Quality goal activities

Objectives of Quality Assurance Quality Assurance works for the manufacture, packaging and distribution of products having following objectives: • Medicinal products are designed and developed in a way that takes account of the requirements of Good Manufacturing Practice and Good Laboratory Practice. • Production and control operations are clearly specified and Good Manufacturing Practice adopted • Arrangements are made for the manufacture, supply and use of the correct starting and packaging materials. • All necessary controls on intermediate products, and any other in-process controls and validations are carried out.

Objectives of Quality Assurance (cont.)

• The product contains the correct ingredients in the correct proportions and has the purity required. • Enclosed in its proper container, which bears the correct label. • The finished product is correctly processed and checked, according to the defined procedures, stored and distributed.

Thus the aim or objective of quality assurance is to ensure the following intrinsic and extrinsic qualities of a product: Intrinsic quality Drug substance activity Drug efficacy

Extrinsic quality

Drug safety

Appearance of product

Appearance of pack

No harmful contamination

Pharmaceutical elegance

Printing quality

Drug bioavailability

Product stability

Tamper Perceived quality evidence

Moisture protection of the pack

Compatibility of the packing materials

Original pack dispensing

Easy to administer

Quality Control Quality control is a part of quality assurance. Quality control refers to the process of striving to produce a perfect product by a series of measures requiring an organized effort by the entire company to prevent or eliminate errors at every stage in production. It concerns quality control of raw materials, finished products and packaging materials.

QC = Test + Assessment IN-PROCESS QUALITY CONTROL:

The in-process control is the checks made during the course of manufacture which aims to ensure that the product will comply with specifications. The control of the environment or equipment may also be regarded as a part of in-process control.

Quality Control (cont.)

All IPC checks carried out during the manufacturing process are not part of the final product specifications although production records need to be checked as a part of control evidence that the correct operational conditions are applied during manufacture. For instance: Maintenance of a certain temperature Mixing time Sterilization record Disintegration / dissolution time Uniformity of weight Color and appearance Moisture content of the in-process material Hardness

Quality Control (cont.)

 Thickness  Friability  Autoclave pressure  Aseptic area microbiological quality etc.

All these requirements are not contained in the final product specifications. Some checks like disintegration time, average weight etc. appear in the final product specifications. Some Commonly Performed IPC Checks: The IPC checks are designed to ensure that the process is under control throughout the manufacturing.

Some commonly performed IPC checks are given below: PROCESS

IN-PROCESS CHECKS

1. Dispensing

Weighing and Recording.

2. Mixing

Time and Speed, Temperature.

3. Granulation Time and Speed, Homogeneity of the content. 4. Drying

Temperature (inlet and outlet air), Time, Pressure / vacuum, Moisture content.

5. Tableting

Machine speed, Compression pressure, Thickness, Hardness, Appearance, Friability, Dissolution / DT.

6. Coating

Temperature, Speed, Uniformity and weight.

7. Oral liquids Temperature curve of heating jacket.

8. Ointments

Stirrer speed, Process time, Viscosity.

9.Parenteral preparations

Bubble point testing of membrane filter, Aseptic area pressure, Aseptic area microbiological quality.

Can IPC eliminate end-point testing? Having successfully established an excellent control over the entire process, the question whether the end product testing can be waived may still be debatable. But clearly the trend is towards more extensive inprocess testing with diminishing emphasis on the end product testing. Such an objective is no doubt ideal for quality assurance, the view of the regulatory authorities has to be considered and also the attitude of a jury in the event of a claim for damages for injury caused by a product. Most regulatory authorities still consider the system of QC laboratory tests for batch release mandatory as independent checks.

In manufacturing plants where most processes are manually controlled the `bulk product release’ test to specifications should be considered essential as an independent double check. In the absence of on-line packing, where the bulk has to be stored, the identity check of the final pack is also a must to make sure that the product is in the right pack. On the whole it can be said that, IPC can diminish the risk of error in the end point testing but it will not be a wise decision to eliminate the end-point testing in the manufacturing process.

GMP or cGMP The word GMP stands for ‘Good Manufacturing Practice’ and cGMP stands for ‘current Good Manufacturing Practice’. The Drug Authority in the USA formulated the first official regulations for current Good Manufacturing practice for finished pharmaceuticals in 1963 which is reviewed and regularly updated. WHO defines GMP as “that part of quality assurance” which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use and as required by the marketing authorization.” Brief concept: Pharmaceutical industries + FDA → GMP regulation of 1971 FDA increased surveillance by introducing International Drug Inspection Program (IDIP) & Drug Enforcement Administration (DEA).

Purposes of GMP: To deliver the public of life saving drugs of the highest quality and purity. “Quality must be built into a product and cannot be inspected in” - A serious & particular application in pharmaceutical production. QC department can monitor/indicate/help in quality production but the production department bears the ultimate responsibility for quality. Production further supported by engineering dept such as: -Equipments selection (contact surfaces are not reactive) -Equipments location (to prevent cross contamination) -Air quality in sterile operations -Design and construction of building (for adequate storage, cleaning, sewage disposal, adequate portable water).

GMP GUIDELINES (A) Personnel: ‘Personnel’ covers the wide range of people from various departments, whose combined effort is to build quality product, like- Quality control department, Production department, Engineering department etc.

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. There should be sufficient number of competent personnel having adequate education, training and experience to perform assigned functions.

GMP GUIDELINES (Cont.)

3. The personnel in responsible positions should not have any interests outside the manufacturer’s organizations that may prevent or restrict their devotion to assigned responsibilities. 4. All personnel in production area or QC Laboratories shall receive training appropriate to the duties and responsibility assigned to them. They shall be provided with regular inservice training. The quality of production in one department has an important effect on the operations of another, and employees should be trained to understand such relationships. Example: If the tablet department is producing a product of low hardness range, in turn causing excessive tablet breakage during packaging, then one department is transferring problems to another department, thereby making the problem more difficult and expensive to correct.

GMP GUIDELINES (cont.)

(B) Premises: GMP has the far reaching effects on space allocation for the buildings and equipment to maintain the concerning issues of quality manufacturing. It is obvious that the production department (~45%) and the warehouse (30%) occupy most of the space of prescription product manufacturers. General requirements: Drugs should be stored, labeled and tested in premises that are suitable for those purposes. Some general conditions are given below:

1) The compatibility of different manufacturing operations that may be carried out in the same or adjacent premises.

GMP GUIDELINES (cont.)

2) The adequacy of the working space which should allow orderly and logical placement of equipment and materials to a. ensure efficient flow of work and effective communication and supervision. b. minimize the risk of confusion between drugs or their components. c. control the possibility of cross contaminations. 3) Those physical aspects to be maintained of premises that could affect the quality and safety of products, such as a. building should be well designed. b. interior surfaces (walls, floors and ceilings) should be smooth. c. drains should be curved. 4) Penicillin & non-penicillin rooms should be separated. 5) Lighting, heating, ventilation and if necessary, air conditioning are required to maintain with appropriate level.

Components of GMP (cont.)

Materials, Lighting, & Air-Conditioning Specifications:

GMP refer to adequate cleaning construction, lighting, ventilating and other important factors in a production operation. A choice of materials can be made from an enormous array of available materials based on: -Personal preference -The experiences of other companies • These decisions are important when a new building is being designed, but become extremely difficult in the redesigning of an old facility where some other extra precaution must be taken into consideration as like wooden floors, ceiling height, other outmoded features. • In the selection of construction materials, initial costs are only a partial consideration, since maintenance enters into total cost.

Components of GMP (cont.)

The selection of materials for walls, floors, and ceilings should be done which have proven years of durability. For example, for the floors in weighing, granulation, tableting, coating, liquid manufacturing, packaging & warehousing areas ‘high-density concrete’ and ‘concrete metal chips’ have proven durable.

The selection of decorating colors in the manufacturing and office areas is important, especially in plants with few or no windows. The sectional use of different colored paints in long corridors avoids a tunnel-like impression. The hanging of washable wallpaper in such as the packaging room provides both pleasant surroundings and low maintenance costs.

GMP GUIDELINES (cont.)

Specific requirements: Storage area: There should have1) Adequate space and lay out to permit effective and orderly segregation of the various categories of materials. 2) Quarantine area for incoming goods as a safeguard that goods can not be used before release by the QC department. 3) Special segregated area for: a. substance or products to be stored at low temperature. b. highly toxic and narcotic drugs. c. substances with explosive power.

GMP GUIDELINES (cont.)

Production areas: 1) Close to the working area, changing room should be installed with facilities related to the type of work to be done. 2) Adjacent to every production, section room should be available for washing equipment and for disinfection if necessary. 3) In the solution department adequate draining system should be available. 4) In tablet section, segregated room should be available for all successive unit operations. 5) In the area of capsule production the R.H. of air should be constant (40% or less). 6) Adequate dust extraction system where necessary. 7) Aseptic room environment for aseptically filled sterile products and almost similar environment except sterile air supply for terminally sterilized products.

GMP GUIDELINES (cont.)

(C) Equipments: a.Design and construction: 1.The design and construction of the equipment should be suitable for its intended use and easy to clean. 2. The equipment material should be minimally reactive, additive or adsorptive with respect to the materials/drugs to be processed.

b. Location and installation: 1. The equipment should be located and installed to – -minimize cross contamination of materials. -minimize confusion or omission of any processing step.

-avoid congestion. 2.Every equipment should be marked with an identifying mark. Each equipment shall be provided with a logbook, wherever necessary.

GMP GUIDELINES (cont.)

c. Weighing and measuring equipments: 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. Equipments used for weighing / measuring should be calibrated and standardized at regular time intervals by standardized / calibrated recordings. d. Cleaning and maintenance: Equipment should be thoroughly cleaned and when necessary, sterilized, and should be maintained in accordance with specific written directions.

Defective equipment shall be removed production and Quality Control areas.

from

GMP GUIDELINES (cont.)

(D) Sanitation / Hygiene: 1) Good personnel hygiene is a primary condition requires adequate washing facilities before entrance into a production area. 2) Manufacturing premises, facilities equipments and materials should be regularly cleaned and maintained in accordance with sanitary standards. 3) Manufacturing personnel should be in good health and maintain required hygienic standards. They should be medically examined periodically, at least once a year. 4) All personnel shall wear clean body coverings appropriate to their duties.

GMP GUIDELINES (cont.)

5) Sufficient clean, well-ventilated toilet facilities should be available. 6) Smoking, eating and drinking should be strictly prohibited in working areas. 7) Cyclone collector, wet scrubbers, replaceable filters, cloth bags, HEPA filters or combination of some of these should be used to prevent dust or cross contamination. Cross Contamination constitutes an ever present danger in pharmaceutical manufacturing. Identification and removal of its causes have had a profound effect on plant layout as well as on the design and construction of production areas.

Components of GMP (cont.)

Wet Collector: - A ‘wet scrubber’ operates by mixing the dust-laden air stream with water in an enclosed chamber, which discharges the effluent into the sewer or treatment plant. - A ‘Rotoclone’ operates by spraying the air in the collector and mixing it by means of high-speed paddles. This type of scrubber is efficient and uses a minimal amount of water. Both systems are particularly effective when a dye is used as the component of dosage form, and it is therefore necessary to prevent trace quantities from contaminating nearby operations. These can also be used when water-soluble, volatile solvents are used in pharmaceutical manufacturing, since the entrained vapors are diluted with water to a safe level of concentration.

Components of GMP (cont.)

Filters, Bags and High-efficiency Particulate Air Filter: The most commonly used dust collectors are the replaceable filter, cloth bag and HEPA types. In large operations, the collectors are placed on the roof. HEPA filters are effective at 100% in particle ranges of a few microns. At one time HEPA filters were used exclusively in sterile operations to reduce particulate matter. The current emphasis on reducing cross-contamination, has resulted in their use in many dry product operations, such as: Granulating, Tableting, Capsule filling etc. The handling of products containing attenuated viruses requires the use of HEPA filters with no return air circulation as a minimum precaution, when viable pathogenic viruses or other dangerous organisms are being processed, it is best to incinerate all exhaust air at a temperature above 8000F.

GMP GUIDELINES (cont.)

E) Starting material:

1) An inventory should necessary materials.

be

made

for

all

2) The supplier should be chosen with care since his information is important for the judgment of quality. 3) A starting material should be used only after assessing by QC that it conforms to specified standards.

GMP GUIDELINES (cont.)

(F) Manufacturing operation: 1)There should be well established written procedures for manufacturing operations. 2)Before any operation is started it should be checked by the supervisor that the apparatus have been cleaned and no materials or other than those required for the operation concerned, are present.

3) All vessels, containers and equipments used in the manufacturing process should be labeled for identification. 4) No simultaneous manufacture of different products in one room should be allowed. 5) All operations should be recorded by the worker. 6) In-process controls should be carried out.

GMP GUIDELINES (cont.)

(G) Packaging and labeling: 1) Packaging materials and in particular printed material should be issued in quantities related to the bulk to be filled. 2) A surplus of printed packaging materials may never be returned to the stock.

3) Every filling, packaging or labeling action should begin with an inspection. 4) Products of similar appearance should not be handled at the same time in one room.

GMP GUIDELINES (cont.)

(H) Quality control system: 1.The QC department should have adequately staffed and fully equipped laboratory for performing all quality control tests on starting materials, intermediate bulk, finished products and the environment of manufacturing, packaging or storage areas. 2. The department should establish authorized specifications regarding raw and packaging materials, finished products and environment.

3. The department should carry out a stability test program and establish specifications on expiry date and storage condition of the materials and products. 4. The department should authorize instructions for sampling, analysis, storage and in-process control.

GMP GUIDELINES (cont.)

5. All instruments shall be calibrated and testing procedures validated before these are adopted for routine testing. 6. Sufficient samples of starting materials & products must be retained to permit future examination of the product if necessary.

7. The IPC checks are designed to ensure that the process is under control throughout the manufacturing. The control of the environment or equipment may also be regarded as a part of IPC.

8. The department is responsible for release or rejection of materials and products.

9. The department should maintain adequate analytical records concerning the examinations of all samples taken.

GMP GUIDELINES (cont.)

(I) Documentation: Documentation is necessary – a) for easy availability of all data required for manufacturing, packaging and QC. b) to record the history of a batch to permit investigation and tracing of defective products. c) to reduce the risk of mistakes inherent in verbal communication. Documentation comprises at least: 1) Specifications of all starting materials, packaging materials and products. 2) Prescriptions and instructions for all manufacturing, packaging and testing procedures, cleaning and disinfection, maintenance of equipment, monitoring of working conditions and use of specific dressings etc. 3) Records including batch manufacturing records, batch packaging records, test records and records of non-product related operations, like cleaning, disinfection, maintenance etc.

GMP Guidance to Pharmaceutical Manufacturing Facilities Weighing area The first important step in the manufacturing process has been receiving an increasing attention because of possibilities for cross-contamination and misbranded products due to incorrect ingredients or quantities. Many companies have adopted a central weighing department to service all of the processing areas. Advantages of Central Weighing Department: -Centralization of responsibility -Avoidance of duplicating weighting facilities -Lower labor costs A chemical weighing department should be designed to provide: Proper weighing equipment, Lighting, Dust collection, Supervision, Checkers and Adequate sanitation.

-High potency drugs such as steroids and alkaloids should be weighed in a separate room equipped with absolute filters to avoid even minimal cross contamination.

-Sinks and drain boards should be conveniently located to facilitate frequent cleaning of measuring equipment. -Cabinets should be provided for the storage of utensils. -Vacuum hoses should be available in the weighing area immediately adjacent to the weighing booths so that the tops of drums and other containers can be cleaned free of dust before they are opened for removal of contents.

-Balances and scales having the proper capacity and sensitivity needed for weighing operations should be specified, and arrangements made for frequent calibration. -Printing scales that record weights on formula sheets and container labels should also be provided.

-Meters should be used when liquid materials are transferred from storage tanks directly to manufacturing tanks. Each quantity should be recorded on batch sheets, either manually or by means of a printing system. The meters should be calibrated and checked periodically.

Tablet Granulating Area In general, several different products are in production at any given time, the numerous steps in the granulating procedure increase the possibilities of cross-contamination, incorrect product identification and/or mix-ups. To eliminate these possibilities, a separate room or booth is recommended for each step. Compartmentalizing the granulating process needs more fragments in the operation space increases space, capital and labor costs. Granulating should be considered a unit operation composed of closely integrated manufacturing steps and process development work should be directed to this area for cost reduction and process improvement.

A washing facility should be available for cleaning portable equipment. To facilitate cleaning of nonportable equipment, each room should be provided with -Floor drains -Pitched floor -Hot water -Cold water -Steam Particular attention should be devoted to the cleaning of drying racks and trays, which should be designed for easy cleaning and made of stainless steel or other non rusting material. If the department is not air-conditioned, all windows should be screened against the entrance of insects.

Tablet Compression Area Booths or Rooms: Separate rooms for tablet machines necessary to avoid cross contamination. When special low humidity conditions are necessary to ensure product stability, the room is kept satisfactory for relative humidity levels below 20%. Such rooms should have special low vapor transmission treatment of walls and equipped with air locks. The compression rooms can all be the same size or vary in size to accommodate the smallest and largest presses. The booth walls should extend from floor to ceiling. Space should be provided for in-process equipment such as balances and tablet hardness testers.

Tablet Presses: A room should be made available nearby for the cleaning of presses and replacement of punches and dies for the next product. Each press should be mounted on metal frames so that it can be moved by lift trucks into a cleaning area and replaced by one that has been cleaned and prepared for the next product. The exact number of tablets produced is compared to the expected yield by a process called ‘reconciliation’. A major discrepancy between theoretic and actual yields signifies that an error may have been introduced at some stage of the procedure. To discover the discrepancy, rotary presses should be equipped with automatic counters.

Tablet Coating Area Traditionally, tablet coating has been considered an art and has required a rather lengthy apprenticeship. The process is noisy and dusty, and it is a labor consuming and somewhat inefficient procedure. In recent years, a number of technologic developments have introduced some automated techniques. The developments are increased pan sizes, improved drying cycles and automated spray coating. These technologic changes have necessitated a new approach to the design and layout of a coating department. For example, enclosing pans offer some advantages like low noise. Polishing should be isolated from the general coating operation.

Solvent laden exhaust should be sufficiently diluted with air to meet fire and environmental standards of safety.

Sufficient floor drains should be provided for adequate cleaning of floors and equipment because of generating of dust and use of dye. Pumps should be used for the transfer of wash water from coating pans to either floor drains or nearby sink. If coated tablets are imprinted with a monogram or a product identification number, each printing machine should be in a separate booth to avoid cross contamination. For inspection of coated tablets, the inspection equipment should be placed in separate booths.

Area for Manufacturing of Liquids Separate facilities are used for oral, external and cosmetic preparations. If not possible a separating wall should be constructed to isolate one group from another to avoid cross contamination and the transference of odors. Special attention should be given to the design and installation of equipment and washing facilities for those drug that are susceptible for microbiological contamination. Sanitary pumps and fittings should be used together with stainless steel tubing with snap on connections to facilitate easy removal and cleaning.

Potable water is necessary in all operations. So deionizers and other water treatment equipment are used and routine microbiologic and chemical testing should be done. If the same tanks are used to manufacture more than one product, liquid meters and tank calibrations are important to product reconciliation. Manufacturing tanks should be located far away from each other to avoid cross contamination. The elevated platforms should be sufficiently large to permit the positioning of pallets or raw materials around the tanks and still provide sufficient room for the separation of adjoining tanks.

Packaging Area Packaging lines should be far enough apart to prevent cross contamination, product mixup.

U shaped lines are preferable due to eliminates noise, heavy traffic, and paper dust and reduce air conditioning loads in the packaging department. Roll labels have many advantages over cut levels in avoiding mislabeling or label mixups in either the label printing operations or the storage and handling of labels in packaging. Labels should be stored in an air conditioned room and in winter, relative humidity should be controlled of about 50% to avoid overdrying of labels. Room should have sufficient space for storage of approved and unapproved labels and inserts.

Department should be equipped with an adequate number of sinks to permit washing of measuring utensils and packaging line equipment parts. Cleaning of dry products filling equipment by vacuum or compressed air should be conducted during shutdown hours for avoid cross contamination. Space should be available for use by departmental or quality control line inspectors and in process testing equipment and also cabinets should be provided for clean utensils and parts. Staging area should be available for the storage of packaging equipment not in use and machine change parts.

Warehousing Special attention should be focused on maintaining cleanliness, freedom from infestation and orderliness. The entire warehousing area should be cleaned as often as necessary to maintain sanitary conditions.

A quarantine area for incoming raw materials and packaging components is necessary and an enclosed quarantine area must be provided for rejected raw materials, packaging components, bulk products and finished goods.

Shipping and Receiving Constant movement of materials in & out of the building subjects this area to the greatest possibility of insect & rodent infestation. Air curtains have been used to prevent flying insects from coming into the building. Inside dock should be large enough to permit both the trailer and the tractor to park inside the building. Overhead doors can be used to close off the dock area. Only approved finished goods should be kept in the shipping area. Items awaiting quality control approval should be kept in the quarantine area.

Alcohol and other combustible solvents should be stored in explosion proof rooms equipped with special fire protection facilities. Approved vaults must be used for storage of finished goods, raw materials of narcotics and other dangerous drug. Sampling booth should be provided adjacent to the receiving dock for statistical inspection and the sampling of raw materials and finishing suppliers. Dust collection hoses should be provided to clean the tops of containers prior to placement in the general warehouse. An inspection center immediately adjacent to the receiving dock should be provided where facilities for the examination of incoming materials are made available.

Cost Control in Manufacturing GMP is a set of guidelines that ensure product safety, quality & efficacy are constantly being met through a well designed plant, skilled personnel and required environmental conditions. GMP reduces manufacturing cost by the following ways1. Creating the best facilities and selecting the best equipment according to GMP requirements reduces the long term high maintenance cost. For example, it is best to invest in the right type of flooring for a particular area rather than incur high annual maintenance cost in cleaning or patching floors not properly specified for that area.

2. GMP necessitates personnel of various departments who in collaboration can -make a good quality manufacturing facility like the proper and effective installation of the buildings and equipments which prevents extra cost and wastage -operate a quality manufacturing cycle 3. GMP outlines the plant layout as well as the design and construction of production areas to avoid cross contamination and mix-ups which are the ever dangers in pharmaceutical manufacturing, so unwanted and accidental costs are reduced.

4. GMP imposes training need for the employee which makes them skilled on their works thus increasing efficiency and reducing cost. 5. GMP outlines cleanliness, adequate lighting and air conditioning in every section of manufacturing as necessary, so the process becomes smooth and proper which in turn reduce the cost of extra maintenances and hazards.