Skip to main content

QUALITY CONTROL WITH QUALITY PREMISES IN PHARMACEUTICAL INDUSTRY

 

Clinical courses

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)
*monish28sharma@gmail.com

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 coved

Epoxy or in situ terrazzo coved

Epoxy coved

Solids manufacturing

Epoxy coved

Epoxy or in situ terrazzo coved

Epoxy coved

Liquids  manufacturing

Epoxy coved

Epoxy or in situ terrazzo coved

Epoxy coved

Solids packaging

Painted

Sealed concrete, terrazzo tile, or vinyl

Suspended ceiling

Liquids packaging (nonsterile)

Epoxy coved

Epoxy or in situ terrazzo coved

Epoxy coved

Laboratory

Epoxy

Terrazzo tile or epoxy sheet

Suspended 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.

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”.

NOW YOU CAN ALSO PUBLISH YOUR ARTICLE ONLINE.

SUBMIT YOUR ARTICLE/PROJECT AT articles@pharmatutor.org

Subscribe to Pharmatutor Alerts by Email

FIND OUT MORE ARTICLES AT OUR DATABASE