GOOD MANUFACTURING PRACTICES

Presented ByPOOJA S. KESARI

GMP regulations were introduced in the form of

amended Schedule M in 1988 has again been amended

in a major way by the Drug and Cosmetic Rules,2001.

That embraces Rules71,74,76 and 78 under the Drug

and Cosmetic Rules,1945.

This rules were not to apply to the manufacturers who

are licensed to manufacture drugs for period up to 31st

December,2004.

GMP UNDER SCHEDULE M

The GMP guidelines are a means to assure the

QUALITY of the drug.

Provides a high level assurance that medicines are

manufactured in a way that ensures their SAFETY,

EFFICACY and QUALITY.

Medicines are manufactured such that they comply with

their marketing authorization.

QUALITY is built in..

WHY GMP??

Design and construct the facilities and equipments

properly. Follow written procedures instructions. Document work involves SOP,BMR,MFRetc. Validate work Monitor facilities and equipment Write step by step operating procedures and work on

instructions Design, an demonstrate job competence Protect against contamination. Control components and product related process Conduct planned and periodic audits

10 BASIC PRINCIPLES OF GMP

Testing is a part of GMP but alone does not provide good level of Quality Assurance-Apart from it GMP is also applicable to FPI’S and API’S.

QUALITY MANAGEMENT

QUALITY ASSURANCE

GOOD MANUFACTURING PRACTICES

PRODUCTION AND QUALITY CONTROL

GMP actually a Good Common Sense

General Requirements -Location and Surroundings -Buildings and Premises -Water System -Disposal of Waste Ware Housing Area Production Area Ancillary Area Quality Control Area Personnel Health, Clothing and Sanitation of Workers

REQUIREMENTS OF GMP

Manufacturing Operations and Controls Sanitation in the Manufacturing Premises

Raw Materials Equipments

Documentation and Records Labels and other Printed Materials

Quality Assurance Self Inspection and Quality Audit

Quality Control System

Master Formula Record

Packaging Record

Batch Packing Record

Batch Processing Record

Standard Operating Procedure

Location and surroundings: Avoid risk of contamination from external environment including open sewage, drain or another factory producing fumes, smoke etc.

Building and premises: production of drugs under hygienic conditions, conforming to the conditions laid down in the Factories Act, 1948

Water System: Purified Water conforming to Pharmacopoeia specification

Disposal of waste: The disposal of sewage and effluents shall conform with the requirements of Environment Pollution Control

Board / Bio-medical waste shall be destroyed as per the provisions of the Bio-Medical Waste (Management and Handling) Rules, 1996

GENERAL REQUIREMENTS

Adequate area Good storage conditions Ensure quarantine status area Separate area for sampling of active/excipients Safe/secure area for poisonous/hazardous

substances. Separate area for printing/packaging Separate area for dispensing hormones/cytotoxic. Separate aseptic area for sterile materials Pest control at least once in 1 year

WARE HOUSING AREA

WARE HOUSING AREAS

Logical sequence of operations Logical positioning of equipments Adequate space in-working area Construction and proper fixation of facilities in

order to avoid creation of recesses Marked direction of flow

PRODUCTION AREA

Separate rest/refreshment rooms from manufacturing area.

Written instruction for cleaning of washrooms which should be easily assecible.

Separate maintenance workshops Separate animal house: Rule 150-C(3) of the

Drugs and Cosmetics Rules, 1945

ANCILLARY AREAS

Independent of production area Design approximately with adequate space Separate area for biological, microbiological and

radioisotopes Separate chemical, microbiological and

wherever required, biological testing is carried out.

QUALITY CONTROL AREA

Competent technical staff with prescribed qualifications and practical experience

Separate Head for QC lab not from manufacturing unit.

Suitably qualified person for QA and QC. Written duties of Technical & QC personnel Sufficient number of persons employed as per

work load. Regular in-service training

PERSONNEL

High level of personal hygiene.

Drug sensitivity tests e.g. penicillin

Medical examination before employment

Personnel hygiene training to all

Sick persons not allowed in working area

Clean body covering as per the duties

Tobacco / Drinks not allowed

HEALTH, CLOTHING AND SANITATION OF WORKERS

Operations carried out under Supervision of

technical staff approved by Licensing authority.

Proper labelling with the name of the product, batch

number, batch size and stage of manufacture.

Products not prepared under aseptic conditions

are required to be free from pathogens like

Salmonella, Escherichia coli, Pyocyanea etc.

MANUFACTURING OPERATIONS AND CONTROL

A validated cleaning procedure Maintenance to avoid accumulation of waste. A routine written down sanitation program Adequate storage space for logical positioning

of equipments / materials Well lit, particularly where visual on-line controls

SANITATION IN THE MANUFACTURING PREMISES

Inventory of all raw materials Quarantined immediately after receipt Purchased from approved sources under valid

purchase vouchers Authorized staff to examine each consignment Each batch shall be considered as a separate batch

for sampling, testing. Appropriately labeled. Separate areas for materials under test, approved

and rejected. Shelf life certification by QC. Containers of raw materials should not be kept

directly on floors.

RAW MATERIALS

Adequate location, layout and design of

equipment

Accuracy / percision/ caliberation of measuring

equipments as per SOPs

Wherever possible, non-toxic/edible grade

lubricants should be used.

EQUIPMENT

Documents essential part of QA system as well as to all aspects of GMP.

Documents shall be approved, signed and dated by authorized persons.

Records retained for at least one year after the expiry date of the finished product

Data may be recorded by electronic data processing systems or other reliable means, but Master Formulae and detailed operating procedures relating to the system in use shall also be available in a hard copy to facilitate checking of the accuracy of the records

DOCUMENTATION AND RECORDS

Appropriate labels Separate storage Labels to be checked by QC Record keeping of all the receipts Labels shall also shall indicate name of the

formulation,concentration, manufacturing date, expiry date etc.

LABELS AND OTHER PRINTED MATERIALS

GMP/GLP/GCP Compliant Arrangements for correct starting and packaging

materials. Adequate controls on starting materials,

intermediate products, and bulk products In-process controls, calibrations, and

validations Finished product released only after QC

assurance.

QUALITY ASSURANCE

Master Formula Record should be their relating to all manufacturing procedures for each product and batch size to be manufactured.

It should contain:- Name of the product with reference code. The patent along with generic name. Description of dosage form, strength, composition of product and

batch size. Detail regarding starting materials. Statement of expected final yield with acceptable limit Methods for cleaning, assembling, caliberating of equipments. Packing details and specimen labels.

MASTER FORMULA RECORD

Textbook of Forsenic Pharmacy by N.K.Jain, Seventh Edition, Vallabh Prakashan, Pg.nos.83

http://www.health.ed.ac.uk/CIDHP/ourreseach/DF/DESRetraps.htm

http://www.picscheme.org http://www.albemarle.com http://www.who.int/prequal

REFERENCES