cGMP

IN
BUILDINGS AND FACILITIES

BY
SACHIN KANKATE

What is GMP ?
GMP is that part of Quality assurance
which ensures that the products are
consistently manufactured and controlled
to the
desired Quality standards
appropriate for intended use
"GMP" - A set of principles and procedures
which, followed by manufacturers for
therapeutic goods, helps ensure that the
products manufactured the required quality.

cGMP Requirements
for Facility Design
21 CFR 211 subpart C--Buildings and
Design and construction feature
211.44 Lighting
211.46 Ventilation, air filtration, air heating
cooling
211.48 Plumbing
211.50 Sewage and refuse
211.52 Washing and toilet facilities
211.56 Sanitation
211.58 Maintenance

Facilities

211.42

and

LOCATION AND SURROUNDINGS

A pharmaceutical manufacturing facility should be located in such an
environment, which protect the manufacturing process, presents minimum
risk of causing any contamination to the material or products.

For this purpose it should have a good surrounding environment, with

sufficient protection from drains, sewage or other nearby factories producing
undesirable fumes, odours or other gaseous or liquid effluents which have
direct or potential danger of contamination of the materials and products
being processed in the factory premises.
M.H.R.A. (U.k.) and U.S. F. D. A. are now asking the organizations to
provide the profile or industry surrounding the pharmaceutical facility. They
even ask the general profile of industries in the areas of about 15 km radius
to assess the potential danger of contamination of the product being produce
with a sufficient length of time in future.

Other

factors which should be considered are direction of natural air flow,

annual rainfall, temperature and relative humidity of the area during the
various seasons of the years. The knowledge of the history of the naturals
calamities like, floods, earthquakes, storms etc. may also be useful in
deciding the location of the pharmaceutical plant.

 Following are some of the major guidelines provided by the

various regulatory authorities.
1) The buildings used for the factory shall be so situated and
shall have such measures as to avoid risk of contamination
from eternal environment including open sewage, drains,
public lavatories or which produces disagreeable or obnoxious
odours, fumes, excessive soot, dust smoke or chemical or
biological emissions.
2) Premises should be situated in an environment that, when
considered together with measures to protect the
manufacturing process, present minimum risk of causing any
contamination of materials or products

Design and Construction Features:

CFR-211.42 gives the guidelines:
Any

building or buildings used in the manufacture, processing,

packing or holding of drug product shall be of suitable size,
construction and location to facilitate cleaning, maintenance, and
proper operations.
Regarding buildings and facilities, there are two major areas of
concern: the external environment and the internal environment. The
external environment must be amenable to the location of welldesigned and constructed buildings.

The addition of any new drug to a production environment must be

carefully evaluated as to its impact on other products already under
production and changes that will be necessary to the building and
facility. Construction of new walls, installation of new equipment, and
other significant changes must be evaluated for their impact on the
overall compliance with GMP requirements.

 For example: new products, such as

cephalosporins, would require that the firm
demonstrate through appropriate separation and
controls that cross-contamination can not occur
with regard to other products being made in the
same facility. Also, facilities that may already be
operating at full capacity may not have adequate
space for additional products.

PLANT LAYOUT

Proper

layout :
productivity
Helps in proper utilization of
man

material

money

machines
Increase

Types of layouts

circular flow

parallel flow

crossover traffic

LIGHTING
CFR-211.44 gives following guidelines:

Adequate

lighting shall be provided in all areas.

order to meet lighting requirement, it is necessary for the manufacturer to define the term "adequate".

This may be done by defining 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 types for work. Normally, a range of 30-50 foot-candles ensures worker comfort and 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.

Once the light levels have been defined, it is necessary that they may be measured periodically and the results recorded. The
specifications should call either for replacement of light sources when some level above the established minimum has been reached or
alternatively, routine replacements of light sources on some schedule that has been shown adequate to ensure that light levels do not
drop below the established minimum.

In

VENTILATION, AIR FILTRATION, AIR HEATING

AND COOLING:
CFR-211.46 gives following guidelines:
Adequate

ventilation shall be provided.

Equipment for adequate control over air pressure, microorganisms, dust,

humidity, and temperature shall be provided when appropriate for the
manufacture, processing, packing, or holding of a drug product.
Air-handling systems for the manufacture, processing and packing of
penicillin shall be completely separate from those for other drug products
for human use.

Placement of air inlet and outlet ports. These should be sited to minimize
the entry of airborne particulates or odors from the surrounding areas.
Outlets should not be sited near inlets.

Where recirculation of air is acceptable, adequate precautions must be

taken to ensure that particulates from a processing areas are removed.
This will usually require an alarm system or an automatic cutoff in the
event that a filter develops a hole.

The degree of filtration and the air volumes should be

matched to the operations involved.
Temperature and humidity conditions should provide
personnel comfort-which will enhance employee performance.
Where differential pressures are required between adjacent
areas, suitable monitoring equipment must be provided.
For example, solids manufacturing areas are usually maintained
at a negative pressure in relation to adjacent rooms and corridors
in order to minimize the possibility of dust migration to these
other areas.
The final air filters close to each room being services
eliminates concerns regarding the possibility of small leaks in
the air duct system. Air usually enters rooms near the ceiling and
leaves from the opposite side near the floor.

PLUMBING
CFR-211.48 gives following guidelines

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 Primary Drinking Water
Regulations set forth in 40 CFR Part 141. Water not meeting
such standards shall not be permitted in the potable water
system.

Drains shall be of adequate size and, where connected

directly to a sewer, shall be provided with an air break or
other mechanical deice to prevent back-siphonage.
:

SEWAGE AND REFUSE:

CFR-211.50 gives following guidelines:

Sewage, trash, and other refuse in and from the building and immediate premises
shall be disposed of in a safe and sanitary manner.
Product disposal: Any product requiring disposal should initially be separated
from its packaging if approved landfill site should not be left in impermeable
glass, plastic, or other containers which would significantly delay destruction.

Disposal procedures should involve agents with a proven record of dealing with
such sensitive materials or the use of company personnel to accompany the
material from plant to disposal. Ideally, incineration procedures have preference
over landfill. Where incineration is used, product in plastic of other flammable
packaging may not need to be returned to bulk.

Printed packaging disposal. The disposal of printed packaging components

including labels, inserts, and cartons posses 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 preferable be
incinerated.

WASHING AND TOILET FACILITIES

CFR-211.52 gives following guidelines:
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.
The legal requirements of Good Manufacturing Practices
specify minimum facilities for personnel. Management concern
with employee morale, and extra measures to ensure minimum
probability of contamination, suggest additional emphasis and
activities.

SANITATION

CFR-211.56 gives following guidelines:

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). Trash
and organic waste matter shall be held and disposed of in a timely and sanitary manner.
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.

There shall be written procedures for use of suitable rodenticides, insecticides, fungicides,
fumigating agents and cleaning and sanitizing agents. Such written procedures shall be
designed to prevent the contamination of equipment, components, drug product containers,
closures, packaging, labeling materials, or drug products and shall be followed.
Rodenticides, insecticides and fungicide shall not be used unless registered and used in
accordance with the Federal Insecticide Fungicide, and Rodenticide Act

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.

MAINTENANCE

CFE-211.58 gives following guidelines:

Facility

maintenance includes the following things

Spoilage of plaster.
Peeling off of paints.
Leakages from ceiling or other surfaces.
Leakage from pipelines of water, steam, gases.
Plumbing problem.
Loose or broken tiles.
Improper closing of doors.
Improper ekectrical wiring.
Improper electrical fittings
Missing tubelights.
A detailed check list may be prepared for the points to be looked into,
during routine inspection o the facilities and indentified deficiencies
rectified immediately and the facility must always be maintain in a
state of good repair.

THANK YOU