Basic Principles of GMP
Premises
John Startup
Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and
.assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda
Premises
Objectives
1. To review general requirements
2. To list key requirements for site choice
3. To consider specific requirements for main areas
4. To list major facilities required in a multifunction site
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Principle
Important aspects to be kept in mind to ensure the suitability of
the operations to be carried out for different dosage forms and
product range:
Location
Design
Construction
Adaptation
Maintenance
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
12.1
Premises
Location
Geography, climate, noise and economic factors
Neighbours
What do they do?
What impact can they have on the
business?
Pollution/effluent control
Minimum risk for contamination of products and materials
12.1, 12.4
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Principle
Premises must be
located to minimize
risks of crosscontamination, e.g.
not located next to a
malting factory with
high airborne levels of
yeast
12.4
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
General
The layout and design should aim to:
Minimize risks of errors
Permit effective cleaning
Permit effective maintenance
Avoid cross-contamination, build-up of dirt and dust
Avoid any adverse effect on the quality of products
12.2
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Design Principles
Keep in mind:
Material flow
People flow
Process flow
Ensure logical flow
12.10
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Example of Materials and People Flow
Arrival of goods
Entrance for visitors
QC
Entrance for Workers Shipment of goods
Offices
Canteen
Gowning
Incoming
goods
Material Flow
Corridor
Shipping
Corridor
Corridor
Raw
Materials
&
Packaging Weighing
Storage
Zone: Clean
Zone: Packaging
Processing
Washing
Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Filling
Packaging Finished Zone: Controlled
Products
Storage
Machine
Shop
Utilities and Services
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People Flow
Corridor
Waste Treatment
Premises
Design
Suitable design and construction to facilitate good sanitation
Cleaning and disinfecting according to detailed written
procedures records maintained
Maximum protection against entry of insects, birds and animals
Procedure for rodent and pest control
12.5, 12.7, 12.9
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Construction
Suitable materials
Electrical supply
Suitable lighting (especially for visual on-line checks)
Temperature and relative humidity control
Appropriate and effective ventilation
These may affect products during manufacture or storage as well
as functioning of equipment
12.8, 12.32
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
The temperature and relative
humidity should be
controlled, monitored in
accordance with an SOP, and
the results recorded. The
limits should be appropriate
according to the materials
stored and product
processed
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Construction
Dust generating operations
e.g. during sampling, weighing, mixing, packing of powders,
etc.)
Measures should be taken to prevent cross-contamination
Measures to facilitate cleaning
12.3
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
Design of areas for weighing of
materials
Proper air supply
Dust control measures
(including extraction of dust
and air)
Easily cleanable surfaces
No areas for dust
accumulation
Protection of material,
product and operator
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Maintenance
Careful maintenance done
Repairs and maintenance should not present any hazard to the
quality of the products
12.6
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Specific areas
Review some recommendations for specific areas in the following
slides (Part 2):
Ancillary areas
Storage areas
Weighing areas
Production areas
Quality control areas
12.11 12.36
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Ancillary Areas
Rest and refreshment rooms separate from manufacturing and
quality control areas
Changing, washing and toilet areas accessible and appropriate
numbers
Maintenance workshops separated from production - if not
possible tools in reserved areas
Animal houses well isolated separate air handling and
entrance
12.11 12.14
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
FACTO RY
CHANGE
ROOM
A IR
LOCK
T O IL E T S
CANTEEN
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
Separate receiving and
dispatch bays
Materials and
products protected
from weather
Area to clean incoming
materials provided
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
Cleaning of incoming
containers
Cleaning with a cloth, or
duster
Cleaning by using a vacuum
cleaner
Use of air curtains and air
tunnels
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Storage areas - 1
Storage areas of sufficient capacity
Orderly storage of categories of materials and products
Separate and segregated areas: starting materials, packaging
materials, intermediates, bulk, finished products, quarantined,
released, rejected, returned and recalled products and
materials
12.15, 12.16
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Storage areas - 2
Appropriate temperature and relative humidity conditions within
defined limits
Provided, controlled, monitored and recorded
Good storage conditions: clean, dry and appropriate lights
12.16, 12.17
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Storage areas - 3
Quarantine area: clearly marked and access restricted
A separate sampling area is the norm: no risk for contamination
or cross-contamination
Segregated areas for rejected, recalled and returned materials
and products
Safe and secure areas for highly active, radioactive materials,
narcotics and other materials (risk of abuse, fire, explosion)
12.18 12.20, 12.22
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Storage areas 4
Printed packaging materials
Critical to ensure compliance with correct labelling of products
Special attention to sampling
Special attention to safe and secure storage
Ensure compliance with specifications, prevent mix-ups
12.21
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Weighing areas
Weighing operations in separated areas
Appropriate design (see also training material on HVAC)
Provision for dust control
Smooth, impervious, durable, easy-to-clean finishes
Cleaning procedures and records
Documentation, e.g. SOPs, logs and records
12.23
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Production areas - 1
Minimize risk of cross-contamination:
Dedicated and self-contained facilities for some products such
as highly sensitizing materials (e.g. penicillins) or biological
preparations (e.g. live microorganisms)
Separate facilities for other products such as some antibiotics,
hormones, cytotoxic substances
Non-pharmaceuticals normally not in the same facility, e.g.
pesticides, herbicides
12.24
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Production areas -2
Layout in accordance with sequence of production
Appropriate cleanliness level
Adequate work and in-process storage space
Orderly and logical positioning of equipment
minimizes risk of contamination, mix-ups and missing
production steps
Specially designed areas for packaging
Layout to avoid mix-ups and cross-contamination
12.32, 12.26, 12.31
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Production areas - 3
Starting and packaging materials, intermediates and bulk
exposed to environment:
Interior surfaces (walls, floors, ceilings) smooth, free from
cracks and open joints
No shedding of particles
Easy and effective cleaning permitted
Disinfection if needed
12.27
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Production areas - 4
Design of pipework, light fittings, and ventilation points no
recesses that are difficult to clean
Access for maintenance from outside production areas
Drains of adequate size, and equipped to prevent back-flow
Open channels avoided
12.28, 12.29
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Production areas - 5
Effective ventilation with air control facilities
Including filtration of air to a sufficient level to prevent
contamination and cross-contamination also external
environment
Control of temperature and relative humidity where necessary
Regular monitoring of conditions during production and nonproduction periods
12.30
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Quality Control areas - 1
QC laboratories should be separate from production areas
Separate areas for biological, microbiological and radioisotope
methods
Suitable design with sufficient space to avoid mix-ups and
cross-contamination
Suitable space for storage samples, reference standards,
solvents, reagents and records
12.33, 12.34
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Basic Principles of GMP
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
Premises
Quality Control areas - 2
Suitable construction materials
Prevention of fumes
Ventilation
Separate air supply (production and QC)
Separate rooms for some instruments to protect them from
interference (e.g. electrical, vibration, moisture, etc.)
12.35, 12.36
See supplementary training on QC laboratories
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Artemisinin based combined medicines
February 23-27, 2009, Kampala, Uganda
