2. PREMISES
CONTENT Design and construction
Principle features
Facilities Aseptic processing
Ancillary area Lighting
Storage area Plumbing
Weighing area Product Disposal
Production area Sanitation
Quality Control Area Maintenance
Services References
3. Principle
Premises must be located, designed, constructed,
adapted and maintained for the operations:
Minimize risks of errors and cross-contamination
Permit effective cleaning
Permit effective maintenance
Minimize build-up of dirt and dust
Eliminate any adverse effects on quality
4. PREMISES
Principle
Premises must be
located to minimize
risks of cross-
contamination; e.g. not
located next to a
malting factory with
high airborne levels of
yeast
5. PREMISES
Arrival of goods Visitors entrance Workers entrance Shipment of goods
Material Flow C
Q Offices Canteen
Gowning
Incoming
goods Shipping
People Flow Corridor
Corridor
Corridor
Raw
Materials
Packaging Finished
& Filling Products
Packaging Weighing Processing
Storage
Storage
Washing Machine
Shop
Corridor
Utilities and Services Waste Treatment
6. PREMISES
FACILITIES
Adequate space for future expansion.
Zoning laws – to allow anticipated development , restricting
undesirable developments in the vicinity.
Availability of water (quality and quantity) , power , fuel , sewage and
waste – removal .
Accessibility for employees, materials, and visitors
Environmental issues such as site history ; soil , water , and air
quality.
Proximity of undesirable activities likely to pollute.
Availability of a suitable labor force (people , skill , wage expectations
,, access to further education sources).
Ability to provide adequate security arrangements.
Political situation - government stability, trade policies and taxation
(for foreign - based operations), financial incentives.
7. PREMISES
The site development plan will include
Compliance with appropriate laws and regulations and any
additional company standards.
Site resources and infrastructure.
Site security and access – fences , cameras .
Buildings - sitting, layout, usage, function interrelationships for
efficiency, possible expansion, surface finishes.
Utilities – design, layout, backup (especially for critical utilities as
electricity and nitrogen for some chemical operations).
Equipment – design, layout , spares, capacity.
Traffic flow – pedestrian and vehicular.
Safety – for personnel and equipment, containment for hazardous
materials, emergency egress.
Ease of maintenance
8. PREMISES
ANCILLARY AREAS
Rest and refreshment rooms should be separate from
manufacturing and control areas.
Facilities for changing and storing clothes and for washing
and toilet purposes should be easily accessible and
appropriate for the number of users. Toilets should not
communicate directly with production or storage areas.
Maintenance workshops should if possible be separated
from production areas. Whenever parts and tools are stored
in the production area,they should be kept in rooms or
lockers reserved for that use.
Animal houses should be well isolated from other areas, with
separate entrance (animal access) and air-handling
facilities.
9. PREMISES
AIR
CHANGE
FACTORY LOCK
ROOM
TOILETS
CANTEEN
10. PREMISES
Storage areas
Storage areas should be of sufficient capacity to allow orderly
storage of the various categories of materials and products with
proper separation and segregation.
Storage areas should be designed or adapted to ensure good
storage conditions. In particular, they should be clean, dry,
sufficiently lit and maintained within acceptable temperature
limits.Special storage conditions - provided, controlled, monitored
and recorded where appropriate.
Receiving and dispatch batches should be separated and protect
materials and products from the weather. Receiving areas should
be designed and equipped to allow containers of incoming
materials to be cleaned if necessary before storage.
11. PREMISES
Where quarantine status is ensured by storage in separate areas,
these areas must be clearly marked and their access restricted to
authorized personnel.
Segregation should be provided for the storage of rejected,
recalled, or returned materials or products.
Highly active and radioactive materials, narcotics, other dangerous
drugs, and substances presenting special risks of abuse, fire or
explosion should be stored in safe and secure areas.
Printed packaging materials and labels – require safe and secure
storage
There should normally be a separate sampling area for starting
materials. (If sampling is performed in the storage area, it should
be conducted in such a way as to prevent contamination or cross-
contamination.)
12. PREMISES
Weighing areas
The weighing of starting materials and the
estimation of yield by weighing should be carried
out in separate weighing areas designed for that
use.
Such areas may be part of either storage or
production areas.
13. PREMISES
Production areas
In order to minimize the risk of a serious medical hazard
due to cross-contamination, dedicated and self-contained
facilities must be available for the production of particular
pharmaceutical products, such as highly sensitizing
materials (e.g. penicillin) or biological preparations (e.g.
live microorganisms).
The production of certain other highly active
products, such as some antibiotics, hormones, cytotoxic
substances and certain non-pharmaceutical
products, should not be conducted in the same facilities.
The manufacture of technical poisons, such as pesticides
and herbicides, should not be allowed in premises used for
the manufacture of pharmaceutical products.
14. PREMISES
Premises should preferably be laid out in such a way as to allow the
production to take place in areas connected in a logical order
corresponding to the sequence of the operations and to the requisite
cleanliness levels.
The adequacy of the working and in-process storage space should
permit the orderly and logical positioning of equipment and materials
so as to minimize the risk of confusion between different
pharmaceutical products or their components, to avoid cross-
contamination, and to minimize the risk of omission or wrong
application of any of the manufacturing or control steps.
Where starting and primary packaging materials and intermediate or
bulk products are exposed to the environment, interior surfaces
(walls, floors and ceilings) should be smooth and free from cracks
and open joints, should not shed particulate matter.
15. PREMISES
Pipe work, light fittings, ventilation points
Drains
Effectively ventilated, with air-control
facilities
well lit
16. PREMISES
Quality control areas
Quality control laboratories should be separated from production areas.
Areas where biological, microbiological or radioisotope test methods
are employed should be separated from each other.
Quality control laboratories should be designed to suit the operations to
be carried out in them. Sufficient space should be given to avoid mix-
ups and cross-contamination.
The design of the laboratories should take into account the suitability of
construction materials, prevention of fumes and ventilation. There
should be separate air supply to laboratories and production areas.
Separate air-handling units and other provisions are needed for
biological, microbiological and radio-isotope laboratories.
A separate room may be needed for instruments to protect them
against electrical interference, vibration, contact with excessive
moisture and other external factors.
18. TABLE 1 PROVIDES SOME GUIDANCE ON TYPICAL
FINISHES FOR VARIOUS OPERATIONS.
TYPICAL FINISHES
WALLS FLOORS CEILINGS
Warehouse Painted HardenAed
concrete, sealed
Dispensary Epoxy coved Epoxy or in situ Epoxy coved
terrazzo coved
Solids Epoxy coved Epoxy or in situ Epoxy coved
manufacturing terrazzo coved
Liquids Epoxy coved Epoxy or in situ Epoxy coved
manufacturing terrazzo coved
Solids packaging Painted Sealed concrete, Suspended ceiling
terrazzo tile, or
vinyl
Liquids packaging Epoxy coved Epoxy or in situ Epoxy coved
(nonsterile) terrazzo coved
Laboratory Epoxy Terrazzo tile or Suspended ceiling
epoxy sheet
19. PREMISES
Services
In the building design, provisions must be made
for drains, water, steam, electricity, and other
services to allow for ease of maintenance.
Access should be possible without disruption of
activity within the actual rooms provided with
the services.
20. PREMISES
Design and construction features
Any such building shall have adequate space for the
Orderly placement of equipment and materials
To prevent mix-ups between different components,
drug product containers, closures, labeling, in-
process materials, or drug products.
To prevent contamination.
The flow of components, drug product containers,
closures, labeling, in-process materials, and drug
products through the building or buildings shall be
designed to prevent contamination.
21. PREMISES
Aseptic processing
Floors, walls, and ceilings of smooth, hard surfaces that are
easily cleanable;
Temperature and humidity controls;
An air supply filtered through high-efficiency particulate air
filters under positive pressure, regardless of whether flow is
laminar or nonlaminar;
A system for monitoring environmental conditions;
A system for cleaning and disinfecting the room and equipment
to produce aseptic conditions;
A system for maintaining any equipment used to control the
aseptic conditions.
22. PREMISES
Lighting
Adequate lighting shall be provided in all area
“ adequate “. Define the amount of light (lux or foot- candles)
reaching the working surface for each area involved in the
production of pharmaceuticals.
Public standards exist for some type of work. Normally, a range
of 30 – 50 foot – candles ensures worker comfort and have
ability to perform efficiently and effectively, however, 100 foot-
candles may be needed in some areas, as well as special
lighting for some operations, such as inspection of filled vials.
23. PREMISES
Ventilation, air filtration, air heating and cooling
(a)Adequate ventilation shall be provided.
(b)Equipment for adequate control over air pressure, micro-organisms, dust,
humidity, and temperature shall be provided when appropriate for the
manufacture, processing, packing, or holding of a drug product.
(c)Air filtration systems, including prefilters and particulate matter air filters,
shall be used when appropriate on air supplies to production areas
measures shall be taken to control recirculation of dust
adequate exhaust systems ,dust extraction system.
(d) Air-handling systems for the manufacture, processing, and packing of
penicillin shall be completely separate from those for other drug
products for human use.
24. PREMISES
Air –handling systems should consider the following
factors:
Placement of air inlet and outlet ports.
Adequate precautions
Temperature and humidity conditions should provide personnel
comfort
Where differential pressures are required between adjacent
areas suitable monitoring equipment must be provided
Siting of final air filters : Air usually enters rooms near the
ceiling and leaves from the opposite side near the floor.
25. PREMISES
Plumbing
Potable water shall be supplied under continuous positive pressure
in a plumbing system free of defects that could contribute
contamination to any drug product.
Potable water shall meet the standards prescribed in the
Environmental Protection Agency's
Drains shall be of adequate size and, where connected directly to a
sewer, shall be provided with an air break or other mechanical device
to prevent back-siphonage.
26. PREMISES
Sewage and refuse
Sewage, trash, and other refuse in and from the building
and immediate premises shall be disposed of in a safe and
sanitary manner.
A pharmaceutical plant may consider disposal in several
different ways :
Product disposal
Printed packaging disposal
General trash and sewage
27. PREMISES
Product disposal
Any product requiring disposal should initially be separated from
its packaging if appropriate. For example, any product to be
disposed of in an approved landfill site should not be left in
impermeable glass, plastic, or other containers which would
significantly delay destruction.
There are risks associated with the destruction of products –
potential for the product to get diverted and contamination of
groundwater. Ideally, incineration procedures have preference over
landfill. Where incineration is used, product in plastic or other
flammable packaging may not need to be returned to bulk.
28. PREMISES
Printed packaging disposal
The disposal of printed packaging components including
labels, inserts, and cartons poses no health risk. However, ineffective
disposal , such as into public landfill, can give rise to public concern that
product may be associated with the packaging. Such materials should
preferably be incinerated.
General trash and sewage
Normal local services will usually be adequate for trash and sewage.
However , internal procedures should be sufficiently monitored to ensure
that product and packaging waste does not get intermixed. Containers
used within the plant to accumulate waste materials should be clearly
marked to denote their designated use.
29. PREMISES
Washing and toilet facilities
Adequate washing facilities shall be provided, including hot and
cold water, soap or detergent, air driers or single-service towels,
and clean toilet facilities easily accessible to working areas.
In addition to GMP regulations, occupational safety & health
administration (OSHA ) regulations impact on washing and toilet
facilities. These require toilet rooms to be separate for each sex
except where individual locked toilet rooms are available and
also define the minimum number of water closets based on the
number of users.
30. PREMISES
Sanitation
(a)Any building used in the manufacture, processing, packing, or
holding of a drug product shall be maintained in a clean and
sanitary condition, Any such building shall be free of infestation
by rodents, birds, insects, and other vermin (other than
laboratory animals).
(b)There shall be written procedures assigning responsibility for
sanitation and describing in sufficient detail the cleaning
schedules, methods, equipment, and materials to be used in
cleaning the buildings and facilities; such written procedures
shall be followed.
31. PREMISES
(c) There shall be written procedures for use of suitable
rodenticides, insecticides, fungicides, fumigating agents, and
cleaning and sanitizing agents .
written procedures shall be designed and followed.
Rodenticides, insecticides, and fungicides shall not be used
unless registered and used in accordance with the Federal
Insecticide, Fungicide, and Rodenticide Act .
(d) Sanitation procedures shall apply to work performed by
contractors or temporary employees as well as work performed
by full-time employees during the ordinary course of operations.
32. PREMISES
Maintenance
Any building used in the
manufacture, processing, packing, or holding of a drug
product shall be maintained in a good state of repair
Monitor cracks and holes in walls,floors and ceilings ;
damage to insulation or pipes ; dust accumulation on light
fittings etc.
Building inspection and maintenance programs should be
defined in writing and a record kept.
Essential services will include
water, steam, vacuum,compressed air and other
gases, electricity, dust extraction, product/material pipe
line, drainage.
33. REFERENCES
Sidney H. willig, James R. stoker
Good manufacturing practices for
pharmaceuticals,volume 72,4th addition, page no:
31
http://whqlibdoc.who.int/trs/WHO_TRS_937_
eng.pdf
http://www.ich.org/cache/compo/276-254-1.html
P.P.Sharma,How to practice GMPs,Vandana
publication,Page no-163-187
