Basic Principles of GMP
Introduction, History of
GMP, Sanitation &
Hygiene
Module 1
Slide 1 of 21
Introduction
Objective of the Programme
To
impart training on cGMP
Modules
and Trainers
Breakout
sessions
Evaluation
Module 1
and Certification of Trainees
Slide 2 of 21
Brief History of GMP
Year
Event
Act
Impact
1902
Tragedy of contaminated Diphtheria
vaccine.
Biologics
Control Act
Inspection
of
Biologics
Manufacturing Facilities.
1906
Revelations about contaminated meat
processing units at Chicago in the
book The Jungle written by Upton
Sinclair.
Pure Food
and Drug
Act
It made it illegal to sell
adulterated or misbranded food
or drugs.
1938
Tragedy due to usage of Sulfanimalide
formulated with Poisonous chemical
(diethylene glycol).
Federal
Food, Drug
and
Cosmetic
(FD&C) Act
Requires manufacturers to prove
the Safety of Products before
Marketing.
1941
Tragedy due to usage of Sulfathiazole
tablets contaminated with Sedative
drug Phenobarbital.
Public
Health
Services
(PHS) Act
FDA revised manufacturing and
Quality Control requirements
drastically (leading to what
would later be called as GMPs).
1962
Tragedy in Europe due to usage of
Thalidomide by pregnant women
resulted in birth defects of babies.
KefauverHarris Drug
Amendment
s
Manufacturers must prove
efficacy of Products before
marketing and ensure strict
control over testing.
Slide 3 of 21
Module 1
Brief History of GMP
Year
Event
Act
Impact
1976
Tragedy due to usage of defective
medical device (contraceptive
intrauterine device)
Medical
Device
Amendments
This
laws
strengthens
FDA
authority to oversee medical
revises.
1978
None
Code of
Federal
Regulations
21 CFR Part 210 and
211established current GMPs.
1982
Deaths due to Poisoned
Acetaminophen Capsules.
Federal 90
Tampering
Act in 1983
Introduction of Tamper Resistant
packaging in market.
Module 1
Slide 4 of 21
Basic Principles of GMP
Sanitation and
Hygiene
Module 1
Slide 5 of 21
Sanitation and Hygiene
Applicable to all aspects of manufacturing
1)
Personnel
2)
Premises
3)
Production Operations :
Equipment / Instrument sanitation / hygiene
Production materials and container handling
Products for cleaning and disinfection procedure
effectiveness
4)
Cross Contamination :
Avoid all potential sources of cross-contamination
Module 1
Slide 6 of 21
Sanitation and Hygiene
Personnel Hygiene
Smoking, eating and drinking should not be allowed in any
manufacturing area, including laboratories and storage rooms .
Chewing of gum should be banned.
Health examinations
On recruitment for direct operators , repeated on regular basis
Training - check
induction training for new operators includes basic personal
hygiene training
written procedures - to wash / disinfect hands before entering
a manufacturing area
signs in changing rooms to reinforce hand washing / disinfection
Illness
staff with illness or open lesions should not handle starting
materials, intermediates or finished products
Module 1
Slide 7 of 21
Sanitation and Hygiene
Personnel Hygiene
Adverse conditions
operators trained to recognize risks
willingness to report illness to the area supervisor
Contact between product and operator
avoid direct contact
if direct handling unavoidable, gloves should be worn
check glove disinfection (for sterile production) and disposal
dont touch equipment product contact surfaces with bare hands
Clothing and changing facilities
check changing rooms (handwashing, disinfectant dispensers hot air hand dryers)
check if used clothing stored in separate closed containers while awaiting cleaning
Module 1
Slide 8 of 21
Sanitation and Hygiene
Personnel Hygiene
laundering of clean area clothing must be to SOP and
in appropriate facility
check for procedure for sterilizing and storing
clothing for use in sterile area
Module 1
Slide 9 of 21
Sanitation and Hygiene
Premises
Design to meet Sanitary needs
Walls, floors, ceilings, ledges, drains, air supply, dust
extraction
Prevention of build-up of dirt and dust to avoid
unnecessary risks of contamination
Cleaning programme, appropriate cleaning, cleaning
records
Effective cleaning and disinfection
choice of materials and chemicals, validation
Protection from insects, vermin and weather
from receipt of raw materials to despatch of released
product
Module 1
Slide 10 of 21
Sanitation and Hygiene
Premises
There should be no living plants kept inside any
manufacturing areas.
Rest and refreshment areas should be separate
from manufacturing areas.
Toilets should not open directly into production or
storage areas.
Module 1
Slide 11 of 21
Sanitation and Hygiene
Production Operations
Work-flow
designed to avoid potential contamination.
Access
to production areas restricted to authorized personnel
direct operators, QC / QA staff, warehouse staff,
maintenance personnel, cleaners
the more critical the area - fewer number of persons
there
Simultaneous operations
not permissible to process different products in different areas
with a common ventilation/ air handling system
Module 1
Slide 12 of 21
Sanitation and Hygiene
Production Operations
Area clearance checks
Process of checking
all materials and documentation from the previous batch removed
all plant and equipment thoroughly cleaned and appropriate status
labelling
checklist useful
The area clearance check should be carried out by two people
between batches of same product
for product changeover, second check carried out by QA staff
all checks carried out in accordance with written SOP and results
recorded on the batch documentation.
Module 1
Slide 13 of 21
Sanitation and Hygiene
Production Operations
Cleaning and cleaning validation
degree of cleaning depends on whether consecutive
batches are of same or different product
Check cleaning agent is fully removed
all cleaning and disinfecting solutions carefully
prepared and expiry dated
Final rinse with purified water, or water for injection
(for sterile products)
Full records kept
Module 1
Slide 14 of 21
Sanitation and Hygiene
Production Operations
Water systems
Water - major constituent of most products
SOP for cleaning and sanitisation of the water
purification system should include distribution
pipework
Maintenance and repair
activities inevitable in manufacturing area.
Should present no risk to product
Module 1
Slide 15 of 21
Sanitation and Hygiene
Production Operations
Whenever possible, all planned maintenance
outside normal operating hours
Emergency work in working area followed by
thorough clean down and disinfection before
manufacturing recommences
Module 1
Slide 16 of 21
Sanitation and Hygiene
Practices to Avoid Cross-Contamination
Segregated areas and separate facilities for
harmonal products
penicillin products
campaign processing
Module 1
Slide 17 of 21
Sanitation and Hygiene
Practices to Avoid Cross-Contamination
Ventilation systems and airlocks
design of ventilation system
incoming air should be filtered
pressure differentials and air extraction
airlocks change over practices, movement
airflow patterns and equipment design
recirculation versus 100% fresh air supply
Module 1
Slide 18 of 21
Sanitation and Hygiene
Practices to Avoid Cross-Contamination
Clothing
protection of operator and product
highly potent products or those of particular risk need for special protective clothing
personnel should not move between areas
producing different products
garments need to be cleaned
Module 1
Slide 19 of 21
Sanitation and Hygiene
Practices to Avoid Cross-Contamination
Closed processing systems
For example: totally enclosed water purification systems
tanks fitted with appropriate filtration - without
removable lids
in case of cleaning difficulties, sometimes use clean-in-place
(CIP)
Cleaning and decontamination
procedure for removing soil and dirt
remove all cleaning chemical residues or disinfectant
residues
must remove or reduce micro-organisms
Module 1
Slide 20 of 21
Sanitation and Hygiene
Breakout Session
Look at the photographs in the handout and record as many
sanitation
and hygiene issues as you can
Module 1
Slide 21 of 21
No analyst is having
worksheets / STPs / Records
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Slide 22 of 21
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Slide 23 of 21
Cleaning while
processing
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