Basic Principles of GMP

Introduction, History of
GMP, Sanitation &
Hygiene

Module 1

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Introduction
Objective of the Programme
To

impart training on cGMP

Modules

and Trainers

Breakout

sessions

Evaluation

Module 1

and Certification of Trainees

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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.
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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

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Basic Principles of GMP

Sanitation and
Hygiene

Module 1

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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Sanitation and Hygiene

Practices to Avoid Cross-Contamination

Segregated areas and separate facilities for

harmonal products
penicillin products
campaign processing

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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

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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

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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

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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

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No analyst is having
worksheets / STPs / Records

Module 1

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Module 1

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Cleaning while
processing

Module 1

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Module 1

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