PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

GUIDE TO MANUFACTURING FACILITIES:

The document is intended to provide the guidance regarding GMP for the
manufacturing of active pharmaceutical ingredients under an appropriate
system for managing quality.
In this guide manufacturing is defined to include all operations of
receipt of materials, production, packaging, repackaging, labeling,
reliability, quality control, release, storage and distribution of active
pharmaceutical ingredients and the related controls.
The guide as a whole does not cover safety aspects for the personnel
engaged in the manufacturer, nor aspects of protection of the
environment. These controls are inherent responsibilities of the
manufacturers and are governed by national laws.
FACILITIES:
1) DESIGN &CONSTRUCTION:
Buildings &facilities used in the manufacture of intermediates
&active pharmaceutical ingredients (APIS) should be located, designed &
constructed to facilitate cleaning maintenance & operations as appropriate
to the type & stage manufactures.
a) Facilities should also be designed to minimize potential contamination.
b) It should have an adequate space for the orderly placement of
equipments & materials to prevent mix ups & contamination.
c) The equipment itself provides protection of the material,such equipment
should be located outdoors.

NAGARAJA Y S ,Dept. of Pharmaceutics.

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PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

d) Laboratory areas/operations should normally be separated from

production areas.
UTILITIES
1) All utilities that could impact on product quality (ex: steam, gases,
compressed air, heating, ventilation & air conditioning) must be qualified
& appropriately monitored & must be taken when limits are exceeded.
Drawings for these systems must be available.
2)

Adequate ventilation, air filtration & exhaust systems must be

provided.
If air is recirculated to production areas, measures must be taken to control
the risk of contamination.
3)

Permanently installed pipe work must be appropriately identified &

must be located to avoid risk of contamination.

4)

Drains must be of adequate size & must be provided with an air break

or a suitable device to prevent back siphon age.

CONTAINMENT
Dedicated production areas which can include facilities air

handling

equipment &/or process equipment must be employed maintained,

repaired & kept in clean condition.
1) Production of highly sensitizing materials like penicillins &
cephalosporins.
2) Any

production

activities

(including

weighing,

milling&

packaging) of highly toxic non pharmaceutical materials like

herbicides & pesticides must not be conducted using the buildings &
or equipment being used for the production of APIS handling &

NAGARAJA Y S ,Dept. of Pharmaceutics.

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PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

storage of these highly toxic non pharmaceutical materials must be

separate from API.
LIGHTING
Adequate lighting must be provided in all areas to facilitate cleaning
maintenances & proper operations.
SEWAGE & REFUSE
Sewage, refuse & other waste ( ex: solids, liquids, or gaseous by
products from manufacturing) in & from buildings & the immediate
surrounding area should be disposed of in a safe, timely & sanitary
manner. Containers and/or pipes for waste material must be clearly
identified.

SANITATION & MAINTENANCE

a. Buildings used in the manufacture of intermediates and API must be
prewritten procedures must be established assigning responsibility for
sanitation & describing the schedules, methods, equipment, & materials
to be used in cleaning buildings &v facilities.
b. When necessary written procedures must also be established for the
use of suitable rodenticides, insecticides &fungicides, fumigating agents
& cleaning & sanitizing agents to prevent the contamination of
equipment, raw materials packaging labeling materials, intermediates &
API.
DISPOSAL

NAGARAJA Y S ,Dept. of Pharmaceutics.

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PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

Disposal options vary considerably between situations & the ideal

solution may not be feasible.
The aim of these guidelines is to propose the simplest, safest & most
practical alternatives.
DISPOSAL METHODS
1) RETURN TO DONAR OR MANUFACTURE
Wherever practical the possibility of returning unusable drugs for safe
disposal by the manufacturer should be explored; particularly drugs
which present disposal problems, such as antineoplastics. For unwanted
unrequested donations especially those that arrive past or unreasonable
near their expiry date it may be possible to return them to the donor for
disposal.
2) LANDFIL
To landfill means to place waste directly into a land disposal site without
prior treatment or preparation. Landfill is the oldest & the most widely
practiced method of disposing of solid waste.
Three types are recognized:
a) highly engineered sanitary landfill
b) waste immobilization: encapsulation
c) Waste immobilization: inertization.
3) EXPIRED OR UNWANTED PHARMACEUTICALS
Pharmaceuticals that should never be used & should always be
considered as pharmaceutical waste are:
a) All expired pharmaceuticals.

NAGARAJA Y S ,Dept. of Pharmaceutics.

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PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

b) All unsealed syrups or eye drops (expired or unexpired).

a) All cold chain damaged unexpired pharmaceuticals that should have been
stored in a cold chain but were not (for ex: insulin, polypeptide hormones,
gamma globulins & vaccines.)
b) All unsealed tubes of creams, ointments, etc. (expired or unexpired).
PROCESS EQUIPMENT
a) Equipment used in the manufacture of intermediates and API should be of
appropriate design & adequate size & suitably located for its intended
use, cleaning, sanitization & maintenance.
b) Equipment should be constructed so that surfaces that contact raw
materials intermediates or APIS do not alter the quality of the
intermediates.
c) If the equipment is opened appropriate precautions should be taken to
minimize contamination.
EQUIPMENT MAINTENANCE & CLEANING
a) Schedules & procedures should be established for the preventative
maintenance of equipment.
b) Written procedures should be established for cleaning of equipment &
its consequent release for use in the manufacture of intermediates &
APIS.
WASHING FACILITIES:
The importance of washing facilities would add to their comfort,
health & efficiency. We recommend that for workers engaged in dirty
process, the provision for washing place & water should be made
obligatory.

NAGARAJA Y S ,Dept. of Pharmaceutics.

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PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

a) adequate & suitable facilities for washing shall be provided &

maintained for the use of workers.
b) Separate & adequate screened facilities shall be provided for the use
of male & female workers.
c) Such facilities shall be conveniently accessible & shall be kept clean.

FACILITIES FOR STORING AND DRYING CLOTHING:

The provisions there in of suitable places for keeping clothing not worn
during working hours and for the drying of wet clothing.
FACILITIES FOR SITTING:
In every factory suitable arrangements for sitting shall be provided &
maintained for all workers obliged to work in a standing position, in order
that they may take advantage of any opportunities for rest which may
occur in the course of their work.
FIRST AID APPLIANCES:
It should be provided & maintained so as to readily accessible during all
working hours first aid boxes or cupboards equipped with the prescribed
contents & the number of such boxes or cupboards to be provided and
maintained shall not be less than 150 workers ordinarily employed at any
one time.
Each first aid box or cupboards shall be kept in the charge of a separate
responsible person who holds a certificate in first aid treatment
recognized by the state government & who shall always be readily
available during the working hours.

NAGARAJA Y S ,Dept. of Pharmaceutics.

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PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

In every factory where in more than 500 workers are ordinarily employed
there shall be provided & maintained an ambulance room of the
prescribed size, containing the prescribed equipment & in the charge of
such medical & nursing staff as may be prescribed & those facilities shall
always be made readily available during the working hours.

CANTEENS:
The state government may, according to section 46(1), make rules
requiring that in any specified factory wherein more than 250 workers are
ordinarily employed, a canteen or canteens shall be provided &
maintained by the occupiers for the use of the workers.
Thus subsection (1) confers general rule for making power upon the state
government & subsection (2) of section 46 authorizes the state
government to make rules providing for:c. The date by which canteen shall be provided.
d. The standards in respect of construction, accommodation, furniture &
other equipment of the canteen.
e. The foodstuffs to be served therein & the charges which may be made
thereof
f. The delegation to the chief inspector, subject to such condition as may
be prescribed, of the power to make rules under clause(c).
SHELTERS, RESTROOMS & LUNCH ROOMS:
In every factory wherein more than 150 workers ordinarily employed,
adequate & suitable shelters or rooms & a suitable lunchrooms, with
provision for drinking water, where workers can eat meals brought by
them, shall be provided & maintained for the use of the workers.
NAGARAJA Y S ,Dept. of Pharmaceutics.

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PREFORMULATION AND PRODUCTION MANAGEMENT

GUIDE TO
MANUFACTURING FACILITIES.

Shelters or restrooms or lunch rooms shall be sufficiently lighted &

ventilated & shall be maintained in a cool & clean condition.

NAGARAJA Y S ,Dept. of Pharmaceutics.

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