“QUALITY-CONTROL”WITH “QUALITY

PREMISES” IN PHARMACEUTICAL
INDUSTRY
11 February 2013 / 0 Comments

About Authors:
Sharma Monish*, Kumar Bhupender
Seth G.L Bihani S. D. College of Technical Education,
Institute of Pharmaceutical Sciences & Drug Research. Sri Ganganagar,
Rajasthan (INDIA)
*[email protected]
INTRODUCTION1:  GMP emphasis on the Quality Control on environment and
facilities, testing of the materials, components and Product in accordance with the
standard.

As Per INDIAN GMP2  :  Following Five elements in the schedule M are  inter-related

and these are:
i)        Factory Premises(location& surrounding, building& premises)
ii)      Warehousing area;
iii)    Production area;
iv)    Ancillary area;
v)      Quality control area.

WHO Provides Guidelines for Quality Premises who fulfill the following Objectives :-
i)      Suitability of premises to carryout intended operations.
ii)     Minimizing risk of errors.
iii)    Permitting effective cleaning & maintenance.
iv)    Minimizing contamination.

REFERENCE ID: PHARMATUTOR-ART-1646

To achieve these objective, consideration has considered :

i) Location
ii) Design
iii) Construction
iv) Adoption &
v) Maintenance

Quality Premises Principle3&4 :- (As Per European Guidance on Good Manufacturing

Practice & WHO Guidelines :-
Premises and equipment must be located, designed, constructed, adapted and
maintained to suit the operations to be carried out. Their layout and design must
aim to minimize the risk of errors and permit effective cleaning and maintenance in
order to avoid cross contamination, buildup of dust or dirt and, in general, any
adverse effect on the quality of products. (building& premises shall confirm to the
conditions laid down in the Factories Act ,  1948 (63 of 1948).

Elements Of Quality Premises :-

1.    Factory Premises3 :- As per European Guidance on GMP

 Premises should be situated in an environment which, when considered

together with measures to protect the manufacture, presents minimal risk of
causing contamination of materials or products.

 Premises should be carefully maintained, ensuring that repair and

maintenance operations do not present any hazard to the quality of products.
They should be cleaned and, where applicable, disinfected according to
detailed written procedures.

 Lighting, temperature, humidity and ventilation should be appropriate and

such that they do not adversely affect, directly or indirectly, either the
medicinal products during their manufacture and storage, or the accurate
functioning of equipment.

 Premises should be designed and equipped so as to afford maximum

protection against the entry of insects or other animals.

 Steps should be taken in order to prevent the entry of unauthorised people.

Production storage and quality control areas should not be used as a right of
way by personnel who do not work in them.
Schedule M (II)1 to the Drugs and Cosmetic Rules stated as under5:
“The building used for factory shall be constructed so as to permit production under
hygienic conditions and not to permit entry of insects, rodents and flies etc.  The
walls of the room in which manufacturing operations are carried out , shall be upto
a height of six feet from the floor, water proof and capable of being kept clean. The
flooring shall be smooth, even and washable and shall be such as not to permit
retention or accumulation of dust.”

Walls Floors Ceilings

Warehouse Painted Hardened

concrete, sealed

Dispensary Epoxy Epoxy or in situ Epoxy coved

coved terrazzo coved

Solids manufacturing Epoxy Epoxy or in situ Epoxy coved

coved terrazzo coved

Liquids  manufacturing Epoxy Epoxy or in situ Epoxy coved

coved terrazzo coved

Solids packaging Painted Sealed concrete, Suspended

terrazzo tile, or ceiling
vinyl

Liquids packaging Epoxy Epoxy or in situ Epoxy coved

(nonsterile) coved terrazzo coved

Laboratory Epoxy Terrazzo tile or Suspended

epoxy sheet ceiling

Table 1: Typical Finishes As per USFDA Guidelines

i)                 Construction materials   :- (As per USFDA Guidelines)

i.                    Walls6 :-

 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.

 Prefabricated partitions may be used in packaging areas where flexibility of

layout is important. Prefabricated units have also been used in other areas,
including sterile suites where panel joints must be given particular attention.
Where possible, walls should be flush and projections should be avoided.

ii.                  Floors6 :-    Floor covering should be selected for durability as well as

cleanability and resistance to the chemicals with which it is likely to come into
contact.

 Terrazzo provides a hard-wearing finish.

 Epoxy flooring provides a durable and readily cleanable surface.

iii.                Ceilings6  :-  Suspended ceilings may be provided in office areas,

laboratories, toilets, and cafeterias. They usually consist of layin acoustical panels of
non brittle, non friable, non asbestos, and non-combustible material. Manufacturing
areas require a smooth finish, often of seamless plaster or gypsum board.

iv.                Lighting6  :-        

 Adequate lighting shall be provided in all areas.

 Range 30–50 foot-candles .

 The minimum recommended intensity of light is 500 lux.

v.                  Plumbing6  :-  Potable water shall meet the standards  prescribed in the
Environmental Protection Agency’s Primary Drinking Water Regulations.

The text of the  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. The Public Health Service Drinking Water Standards are now administered
by the Environmental Protection Agency (EPA).

Drains should also be regularly disinfected. Drains should be of adequate size, and
have trapped gullies. Open channels should be Avoided where possible, but if
necessary, they should be shallow to facilitate cleaning and disinfection.

vi.                Sewage and Refuse6 :-Sewage, trash, and other refuse in and from the
building and immediate premises shall be disposed of in a safe and sanitary manner.

vii.          Washing and toilet facilities6:- Adequate washing facilities shall be provided,

including hot and cold water,  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.

viii.            Sanitation6&7 :- Walls, floors, ceilings, and equipment in an aseptic area are

cleaned and disinfected in accordance with a written program.

Disinfectants and detergents are monitored for microbial contamination; should be

sterile when used in grade A and B areas, dilutions are kept in previously cleaned  
containers and are not stored for long periods unless sterilized. Partly emptied
containers are not topped up.

[Note: While this agrees in part with item # 38 of the Annex 1 of the European Union
GMPs, microbial monitoring of sterile disinfectants and detergents is not current
industry practice.]

ix.                Maintenance6 :- Any building used in the manufacture, processing,    

packing, or holding of a drug product shall be maintained in a good state of repair.

2.        Warehousing Area  :- (As Per WHO GMP)

 Warehousing areas shall be designed and adapted to ensure good storage

conditions.

 Adequate areas shall be designed to allow sufficient and orderly warehousing

of various categories of materials and products like starting and packaging
materials, intermediates, bulk and finished products, products in quarantine,
 released, rejected, returned or recalled, machine and equipment spare parts
and change items.

 They shall be clean, dry and maintained with acceptable temperature limits.

Figure : 1 – Warehouse Facilities 9

3.    Production area :-

 The production area shall be designed to allow the production preferably in

uni-flow and with logical sequence of operations.

 In order to avoid the risk of cross-contamination, separate dedicated and

self-contained facilities shall be made

 Production areas should be effectively ventilated, with air control facilities

(including temperature and, where necessary, humidity      and filtration)
appropriate both to the products handled, to the operations undertaken
within them and to the external environment.

4.    Ancillary Areas3 :- ( As per EUROPEAN guidance on GMP)

 Rest and refreshment rooms shall be separate from other areas. These areas
shall not lead directly to the manufacturing and storage areas.

 Facilities for changing, storing clothes and for washing and toilet purposes
shall be easily accessible and adequate for the number of users.

 Areas housing animals shall be isolated from other areas. The other
requirements regarding animal houses shall be those as prescribed in Rule
150-C(3) of the Drugs and Cosmetics Rules, 1945 which shall be adopted for
production purposes.

5.    Quality- control area :-

  Quality Control Laboratories shall be independent of the production areas.
Separate areas shall be provided each for physico-chemical, biological,
microbiological or radio- isotope Analysis. Separate instrument room with
adequate area shall be provided for sensitive and sophisticated instruments
employed for analysis.

 Quality Control Laboratories shall be designed appropriately for the

operations to be carried out in them. Adequate space shall be provided to
avoid mix-up sand cross-contamination. Sufficient and suitable storage space
shall be provided for test samples, retained samples, reference standards,
reagents and records.

REFERENCES
1.    Mc Cormick Kate, “Quality- pharmaceutical Engineering Series”, First edition
2002.Published by British Library. P.NO.- 24-72
2.    Sharma P.P., “ How to Practice GMPs A Guide for c GMP Compliance with PAT &
HACCP”, fifth edition. Vandana Publications Pvt. Ltd. Delhi P.NO.- 128-153
3.    MHRA Rules and Guidance for Pharmaceutical Manufacture and Distributors
2007, Pharmaceutical Press. P.NO.-53-56, 74-79
4.    Schedule M, “ Good manufacturing practices and Requirements of Premises,
Plant and Equipment For Pharmaceutical Products” (rule 71,74,76 and 78)
5.    Sharma P.P., “Cosmetics-Formulation, Manufacturing and Quality control,”
fourth edition. Vandana Publications Pvt. Ltd. Delhi P.NO.- 36-41
6.    Willig H. Sidney & Stroker R. James, “Good Manufacturing Practices for
Pharmaceuticals A plan for Total Quality Control” fourth edition revised & expanded
P.NO.- 33-51
7.    PDA suggested revision to Section C.02.029 (Sterile Products) of the Good
Manufacturing Practices Guideline, Therapeutic Products Programme (Canada) on
October25, 2000. P.NO.- 1-12
8.    PDA suggested revision to Section C.02.029 (Sterile Products) of the Good
Manufacturing Practices Guideline, Therapeutic Products Programme (Canada) on
October25, 2000. P.NO.- 1-12
9.    Facilities& Operation for warehouse, Available from URL fgb.com.au/facilities
( Accessed on 28-Dec.-2010)
10.    Quality assurance of pharmaceuticals, “A compendium of guidelines and
related materials”, Volume 2, Good manufacturing practices and inspection. P.NO.-
28-33
11.    ICH Harmonised Tripatite Guideline of Good Manufacturing Practice Guide for
Active Pharmaceutical Ingredients Q7A by The ICH steering committee. P.NO.7-9
12.    GAD COX SHAYNE , “Pharmaceutical Manufacturing Handbook-Regulation and
Quality”, Wiley-Interscience, A John Wiley & Sons, INC., Publication P.NO.-5
13.    Orange Guide, “Concept & philosophy Of TQM, GLP, GMP”.