Friday, April 3, 2009

cgmp requirement of Building and Facilities (Plant Building)

1. Area for Building:
According to GMP (Pakistan published) an area of building should not less than 2000 sq. yards. However the GMP (WHO) says the building should be of suitable size with the adequate space for future expansions.
2. Location:
The building should be located preferably in industrial area not in congested and residential area or commercial area.
3. Surroundings
The building should be in an environment when considered with measures to protect manufacturing process, presents, minimum risk of contamination of materials or products, it should be away from filthy surroundings should not connected with open sewerage, drains, public lavatory or any factory which produces a disagreeable or obnoxious odor or fumes or large quantity of dust or smoke which may not contaminate the drug being manufactured.
The building should be constructed according to the approved plan and the layout should be laid in such a way as to allow the production to take place in areas connected a logical order corresponding to the sequence of the operations. The inter relationship of different operations should minimize the potential for cross contamination and component mix up during storage and interdepartmental shipping.
The passages constructed for the movements of the workers should be constructed in such a way that dust and other contaminate may not come inside the building.
The passages around the building should be carpeted roads or any other material which does not allow accumulation of dust, accumulation of water and facilitate easy cleaning.
Walls of the Building:
Walls in manufacturing areas, corridors, and packaging areas should be of plaster finish on high-quality concrete blocks or gypsum board. The finish should be smooth, usually with enamel or epoxy paint and projections in walls should be avoided.

a. The floors should be of made of chips for heavy movement, ceramic and vinyl tiles should be avoided, however if vinyl tiles or ceramic tiles are used they should be sealed in such a way that they should not shed particles.
b. Epoxy flooring provides a durable and readily cleanable surfaces.
Doors of the Building:
The doors of the building should be of non flammable material. While we have doors of wooden made which are flammable.
4. Emergency Exit:
The building must have emergency exit door which is not available in present premises.
Design of Building:
The building should be designed in such a way that it provides maximum protection against contamination (by creating buffer sections), easy transportation of materials, storage of materials, suitable facilities like temperature control, humidity, light, filtered air etc, which facilitate easy work.
Construction of Building:
The building should be constructed according to international standard which requires building security system, absorbance of vibrations, to bear earth quack, sound proof or if noise is produce it should be acceptable for working conditions. Material used for building must have the quality according to the building quality standards of materials. The building must be access able for easy maintenance cleaning and other services.
Wash Areas:
In the wash areas the hot and cold washing facilities should be provided with cleaning antiseptic soap, single use towels, or laser dryers. The taps used for washing should be foot operative.
A comprehensive procedure for washing use of towels, use of water taps, use of laser dryers should be present. Signs indicating hazards by misuse must also be present.
Toilets should not be present inside the building it should be around the building. The toilets should be designed in such a way that the person can enter only from one door and leave the toilet area after washing hands through another door. The construction of the doors should be in such a way that the person can only be enter from one door he cannot leave the toilet area from the same door, for leaving the toilet area another door should be used. The leaving door does not allow to worker to come inside the toilet. A small washing area for washing their hands should be present in the toilet area.
A procedure should be present for the use of toilets and their sanitation.

A Suitably Designed Area Must Be Like:

Workers Entry
Separate passage should be present for the entry and for the outgoing workers after work. However the GMP rules permit entitled entry.
Workers after use of toilets and washing their hands will enter the change area where he will only change his uniforms keep them in lockers then he will change his shoes wash their hands enters into the corridors by decreasing their Bio burdens (air curtains) and in the respective production section where his entry will be entitled, then wear the glove and mask and will enter into the respective working section or room. Before entering he will make sure the minimum hygienic conditions have been adopted for respected production process.
To restrict workers movement from inside building to outside the building canteen can be made on the top floor of the building with separate passage or near the building.
Change Rooms:
In present change area no special rooms are present for the change of uniforms.

Workers Hygiene:
1- A minimum requirement of workers health, hygienic protocols and clothing for personal (uniform) should be present in written according to process requirement must be present, ensuring clean and sanitation production of drugs.
2- No person who affected with or is a career of a disease in communicable form or has an open lesion on any exposed area of the body shall be employed for area’s where a drug during any stage its production is exposed.
The minimum requirement of health should be in written and provide the following information.
i) Pre employed medical examination
ii) Assessment of an employee’s health prior to return to his place of employment following illness involving in a communicable disease.
iii) Action to be taken in the event of positive diagnosis of disease.
iv) Routine supervisory check of employees.
v) The hygienic program shall clearly define clothing requirements and hygienic procedures for company personal and visitors.
vi) Where a potential for the contamination of raw material in process material or drug exists, individuals shall wear clean clothing and protective covering.
vii) Eating, smoking, or any unhygienic practice shall not be permitted in production areas.
viii) Requirements concerning personal hygiene, with emphasis on hand hygiene.
ix) Requirements concerning cosmetics and jewelry worn by employees.
Flow Charts
Flow charts of following procedures must be present;
Raw Material Incoming & Packing Material, Weight to Batch Process
Batch Manufacturing processes Syrups, Capsules, Tablet, Dry Suspension etc.
Process Flow Chart of Incoming Finished Good.
Flow Chart of Workers entry to Their Work Place.
Some of the flow charts are already present but require streamlining.
According to GMP in validation flow chart must be present and verified.(Flow charts are present but not verified & needs streamlining)
Entry of the Raw Materials:
Separate passage should be present for the entry of the raw material under sanitation and hygienic conditions and for the leaving of rejected materials.(In the present building there is no proper way for the entry of raw materials)
Rejected Material:
Adequate area should be present for the separation of rejected materials, the rejected material should be disposed off as early as possible through define procedures.
The building must have following systems or facilities.
1. lighting
2. Ventilation, air filtration, air heating and cooling.
3. Plumbing (water system).
4. Sewage.
5. Washing facilities.
6. Sanitation.
7. Maintenance.
The boundary wall must be present and should be constructed in such a way that it does not allow animals inside, should have proper route for the drainage of water and drainage passage also does not allow the animals to come inside.
Around the building if possible carpeted road should be present, doors of the building must be sealed that does not allow the crawling animals to go inside the building, the doors of the production areas should be constructed in such a way that they should prevent cross contamination.
The walls must be smooth free of notches, scratches and painted with slow fire catching paints (epoxy paints can also be used) and the floors should be smooth may be of chips or any other material which the may does not allow to collect the dust and the corner should be round inside the building, windows should be minimum and should be constructed in such a way so that it should be seem to be a part of wall, the windows present must not permit the sunlight in the production areas.
1 Non productive areas
2 Productive areas
2.1 Non sterile areas (Oral liquids, capsules, tablets etc)
2.2 Sterile Area’s (Injectabels, Injections, eye drops etc.)
A written program and procedure should be available for sanitation productive and non productive area’s excluding sterile area’s.
ii) For the sanitation of productive area’s and non productive area’s sanitation procedure evaluations of sanitation procedures their effectiveness use of chemicals and their concentrations, detergents and any other materials their effectiveness for individual production area’s should be present.
iii) List of critical points to be checked after cleaning must be present and cleaning must be verified by an authorized person, the authorized person may be qualified person or may be any other person trained for this purposes.
iv) Procedure for the collected wastage during cleaning and their dispose of must be present.

Sterile Area
The sanitation of sterile area is very important they shall be cleaned prevently and thoroughly in accordance with a written program and procedure approved by the quality control department.
Use of Disinfectants and Detergents
Disinfectants and detergents are used for microbial count, the record of disinfectant and detergent used their concentration, procedure for use and control of microbial count must be present and verified.
Use of Ultraviolet Light
Ultraviolet lights are also used for microbial count but these are not alternative of chemical use.
Fumigation is used to control the microbial count, the record should be kept containing area to be fumigate, quantity of chemicals used for fumigation, control of microbial counts and procedures must be present.
Disinfectant areas shall be monitored at planed intervals during operation by mean of microbial count of air and surface, the area where an aseptic operations are performed monitoring shall be frequent that the enviournment is within specification. The results of monitoring are also considered when batches are accessed for approval, air particulate matter; quality may also be accessed evaluated on regular basis.
Drains of adequate size shall be present where necessary should not permit backflow and should be fully covered, plain to the floor which does not allow to collect water, dust and any other material. The drain should be connected to main drainage system if available or if not present the drain water should be collected in a pound and re circled and sent to water channels and if after treatment the quality permits may be used.
i) Layout plan should be present which should be independent of power supplies to production instruments. The layout plan must show lighting points lines protection equipment and earthling.
ii) The lighting wires should be according to the electric power requirement.
iii) The lighting wires must be inside the walls and the distribution boards must be smooth and equalized with the walls so that dust may not collect on them.
iv) The lights should be concealed so that dust may not collect on them.
v) The maintenance department must have the record of total number of lights, record of starters, chokes, manufacturer, current rating, warrantee and the warrantee of the tube rods from the manufacturer that they does not emit toxic rays and the evaluation for no of tube light for particular section. The paint color, their light absorbency and reflection of light from paint must be also considered during the planning of lights in particular section.
vi) The maintenance department must have the schedule to clean the tube lights, fans, air conditioners, their procedure for cleaning, work instructions, and safety equipments and their use.
vii) The maintenance department must have the record of replacement of parts and their reasons and deviation records to use the parts other than the approved parts.
viii) Design should include of map supply of supply lines, protective instruments requirements of electrical supply for particular area and supplied voltage.
ix) The maintenance department, the lightning instrument should be numbered according to the requirement of particular area’s. The lightning instrument should be numbered and should be according to the light requirement of particular area and should be counseled So that dust may not be collected on them, fans and air conditions should be numbered and their cleaning procedures and trainings record should be present. The light emitted from lightning instruments should be non toxic and non hazards to health (warnings for the area’s where UV lights are used and the written procedures should be present to save from them.
x) The power supply cables should be under ground and protected from any other damage.
xi) The lightning supply lines should be according to design

Power Supplies to Production Instruments:

àThe electrical department must have the layout plan of power supply to different machines in different sections and must have the record of, the power supply requirements, the supplied power, the power supply wires sizes, their capacity (in terms of amperes & voltage) and must have the warrantee from the manufacturer that the power cables and lines must bear the load according to the designed.
àThe power supply panels LT or HT must be in the separated room with damage protective instruments and must have the complete record of LT and HT distribution connections, and the colours of different supply lines and identification tags. The colour of different lines should be marked, in maps or layouts with international standards.
The maintenance department should have the full instructions and written procedures for working electrical staff on LT and HT panels with full safety measures and safety instruments.
3.1 Security System for Premises
3.2 Entry Procedure, which includes
3.3 Identity of person (photograph, telephone no, e-mail or fax address and other information), Searching (by hands and by instrument), time record of entering and leaving premises, Keeping hazard materials at gate, Keeping of cameras, Keeping of any type of weapon like knife etc, keeping of materials like matches, cigarettes (which help in burning, CD’s and Floppies which helps leakage of information should be kept at gate).
3.4 Security personnel
3.5 Uniforms
3.6 Uniforms with Batches & Name Strips
3.7 Weapons (Kind of weapons, their license, cleaning procedures, validation of cleaning procedures, bullets, their manufacturer expiry dates(validity date)
3.8 Training of Security personnel ( use of weapon, training of conditions under which it should be used, alarming use of weapons, responsibility of a person who will order for use of weapon in conditions in which there is no order present, extensive training to catch the persons without the use of weapon and check of these trainings.
4 Time office building
4.1 Separate rout of incoming workers
4.2 Separate rout of outgoing workers
4.3 Record of timings, equipments and their validation & calibration
4.4 Building should be builted according to building rules and should have temperature control faculties.
4.5 Separate toilet faculties, retiring room
4.6 Room for chief security officer (for watching workers behavior)
4.7 Separate room for keeping weapons
4.8 Room or space for keeping things caught during body searching
4.9 Searching program for surroundings of manufacturing building.
Water (Drinking Water or Potable Water):
The potable water used for drinking should be supplied under continuous pressure through non corrosive pipes sealed joints and approved for drinking purposes according to the FDA regulations. The design and layout of supply lines should be present in the maintenance department. The record of checking the potable water after every 6 moths or year must be present.
Purified Water:
Water purified by suitable means having the quality according to the standards of BP / USP released by quality control department should be used in pharmaceutical operations in oral dosage. The purifying water equipment should be in separate room. The interior surfaces of the room where the deionizer is installed (walls, floors and ceilings) should be smooth, free from cracks and open joints, and should not shed particulate matter and should permit easy and effective cleaning. The appearance and outlook of the equipment should appeal the person. The following documents should be present in maintenance department.
1- Design and layout of equipment used for purifying water
2- SOP for preparation of purified water
3- Signs indicating flow of water in the purifying water equipment
4- Design and layout of piping
5- Numbering of valve used (complete list)
6- Direction of operating the valves (by signs and arrows)
7- Presence of certificates of non toxicity of piping and materials used in manufacture of purifying equipment including insulation which directly comes into contact with water.
8- Presence of document validation of the above procedure
9- Approval of procedure and deviation.
10- The record of no of regenerations, the steps done by and the quantity of the chemical used must be present, in case of change of reason, reason of change approved by quantity change, date and time must also be present.

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