GOOD MANUFACTURING

PRACTICE
Prepared by : Dr. Mohamed Fekry
Module 1

Introduction
Good Manufacturing practice

• GMP is the part of quality management which

ensure that each medicine products are produced
and controlled according to the quality standards
to be fit for its intended purpose as required by
the product specification.
 Quality Management
The aspect of management function that determines and
implements the “quality policy”

The overall intention and direction regarding quality, as formally

expressed and authorized by top management
• The basic elements are:
An appropriate infrastructure or “quality system” involving the
organization structure, procedures, processes and resources
The systematic actions necessary to ensure adequate confidence
that a product (or service) will satisfy given requirements for
“Quality”
The totality of these actions is termed “Quality Assurance”
Quality
Management

• Quality assurance Is
a management tool

• QA , GMP and
Quality Control are
interrelated aspect
of Quality
Management
 Premises

Equipment

Personnel

Elements of GMP materials

Documentation

Production
 Quality control

Complaints

Product recall
Elements of GMP
Sanitation and Hygiene

Self inspection
 Why GMP?
1. To ensure safety
2. To ensure purity
3. To ensure effectiveness

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Basis of GMP

1. To prevent an error is much more better &

cheaper than correcting it
2. Constructing quality inside a pharmaceutical
product during different production processes is
better & correct than checking & inspecting the
products at the end of production steps
Glossary
• Active pharmaceutical ingredient (API). Any substance or mixture of
substances intended to be used in the manufacture of a pharmaceutical
dosage form and that, when so used, becomes an active ingredient of that
pharmaceutical dosage form

• Airlock. An enclosed space with two or more doors, which is interposed

between two or more rooms, e.g. of differing classes of cleanliness, for the
purpose of controlling the airflow between those rooms when they need to
be entered. An airlock is designed for use either by people or for goods
and/or equipment.

• Batch (or lot). A defined quantity of starting material, packaging material, or

product processed in a single process or series of processes so that it is
expected to be homogeneous
Glossary
• batch number (or lot number). A distinctive combination of numbers and/or
letters which uniquely identifies a batch on the labels, its batch records and
corresponding certificates of analysis, etc.
• batch records. All documents associated with the manufacture of a batch of
bulk product or finished product. They provide a history of each batch of
product and of all circumstances pertinent to the quality of the final product.
• bulk product. Any product that has completed all processing stages up to,
but not including, final packaging
• intermediate product. Partly processed product that must undergo further
manufacturing steps before it becomes a bulk product
• finished product. A finished dosage form that has undergone all stages of
manufacture, including packaging in its final container and labelling.
Glossary
• contamination. The undesired introduction of impurities of a chemical or
microbiological nature, or of foreign matter, into or on to a starting material or
intermediate during production, sampling, packaging or repackaging, storage or
transport.
• cross-contamination. Contamination of a starting material, intermediate product
or finished product with another starting material or product during production
• calibration. The set of operations that establish, under specified conditions, the
relationship between values indicated by an instrument or system for measuring
(especially weighing), recording, and controlling, or the values represented by a
material measure, and the corresponding known values of a reference standard.
• validation. Action of proving, in accordance with the principles of GMP, that any
procedure, process, equipment, material, activity or system actually leads to the
expected results
Glossary
• in-process control. Checks performed during production in order to monitor and, if
necessary, to adjust the process to ensure that the product conforms to its specifications.
• qualification. Action of proving that any premises, systems and items of equipment work
correctly and actually lead to the expected results
• quarantine. The status of starting or packaging materials, intermediates, or bulk or finished
products isolated physically or by other effective means while a decision is awaited on their
release, rejection or reprocessing.
• reconciliation. A comparison between the theoretical quantity and the actual quantity
• standard operating procedure (SOP). An authorized written procedure giving instructions
for performing operations not necessarily specific to a given product or material (e.g.
equipment operation, maintenance and cleaning; validation; cleaning of premises and
environmental control; sampling and inspection).
Module 2

GMP PREMISES
 Module 2
GMP PREMISES
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INTRODUCTION
 INTRODUCTION

The location, layout and design of buildings should be

suitable for the intended operations and should
minimise the risk of cross contamination and errors
during all aspects of manufacture, filling and
packaging.
They should allow effective cleaning and maintenance
in order to avoid build up of dust or dirt, and any
adverse effect on the product or the surrounding
environment.
 SCOPE

Applies to all premises related to the

production of pharmaceutical
products.

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GENERAL PRINCIPLE
OF PREMISES

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DESIGN
1. Facilities should be designed for:
➢ logical flow of materials and people
➢ adequacy of working space and logical positioning of
equipment
➢ smooth/crack-free/easy to clean interior surfaces

1. Sterile Production areas should be separated from others

➢ non-hazardous products can share premises provided that
care be applied to prevent cross contamination and risk of
mix-up.
DEFINED AREA (1)
There should be defined areas or other control systems for the following
activities

❖ Receiving of starting & packaging materials

❖ Sampling

❖ Weighing/dispensing

❖ Gowning/ change room

❖ Storage areas for approved raw material, packaging materials, and

finished goods

❖ Quarantine & reject areas

❖ Processing
DEFINED AREA (2)

❖ QC laboratory

❖ Equipment washing

❖ Storage of cleaned equipment

❖ Staging of bulk products

❖ Packaging/ labeling operations

❖ Storage of cleaning tools and supplies

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DESCRIPTION
OF DESIGN, LAYOUT
& CONSTRUCTION
FLOORS , WALLS & CEILINGS

•walls, floors and ceilings should be smooth

and free from cracks and open joints, should
not shed particulate matter, and should
permit easy and effective cleaning
 FLOORS

 Solid concrete for warehouse

 Solid concrete with epoxy is suitable

for processing areas as it has a non-

porous non skid surface and retards

bacterial growth.
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WALLS & CEILINGS

Ceiling without joint

Floor

Ceiling with joint

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JOINTS & FRAMES

The design of joints and frames should be such that cleaning and
sanitation can be done easier

the joints of all the designs of windows and the way

surfaces they fit into the frames
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VENTILATION
Air should be appropriately filtered specifically in
the processing and filling areas.
❑ One pass filtration air or circulation for wet, non-powdered and dry
preparations.
❑ Powdered product should have a dust collection system installed.
HVAC (Heat ,Ventilation and Air
conditioning )
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DEFINED AREA
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STORAGE AREA (1)

Storage areas should be of sufficient capacity to allow orderly storage of various

categories of materials and products with proper segregation.
Status labeling of materials should be observed.
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STORAGE AREA (2)

Storage of Returned / recalled Printed packaging

toxic substance products materials
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LOADING & UNLOADING

1-Goods received and dispatched at the docks, bays or platforms should

be protected from dust, dirt and rain
2 –use of air curtains for loading and unloading
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FLAMMABLE WAREHOUSE 9

Applicable to national laws

alcohol and flammable warehouse can be located in a separate location, with good
ventilation, fenced, locked, This warehouse should be indicated by inflammable and
sufficient safety signs.`
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QUARANTINE & REJECTED AREAS

Any system replacing physical
quarantine should have an equivalent
security.

Reject area should be kept under lock

and key.
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SAMPLING

Sampling should be conducted in such a

way to prevent cross contamination.
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WEIGHING & DISPENSING

The weighing of starting materials should be carried out in a separate weighing

area designed for that use with provisions for dust control.
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PROCESSING AREA

Adequate working space should :

• permit the orderly & logical positioning of
equipment and materials to minimize the
risk of confusion
• avoid cross contamination and reduce the
risk of wrong application of any of the
manufacturing or control steps.
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PROCESSING AREA INTERIOR (1)

 Smooth, cleanable, easy to
maintain

 Covings where floor meets walls

may be observed.

 Recessed light fittings where

appropriate.
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PROCESSING AREA INTERIOR (2)

MINIMUM REQUIREMENTS

No coving with proper Light with cover

cleaning procedure
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PACKAGING AREA

Premises for filling/ packaging should be designed and laid out to

avoid mix-ups or cross contamination.
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WASHING & CLEANING TOOLS

Washing area Cleaning tools area

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STORAGE OF CLEAN EQUIPMENT

A separate room may be
needed for storing clean,
idle equipment which
should be kept dry at all
times.

Proper storing of
hoses allowing them
to dry should also be Cupboard for clean
observed to prevent equipments
retention of liquid.
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UTILITY STORAGE

A storage area for clean

equipment used for
production should be
provided.
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CHANGING ROOM

 Store working shoes separately.

 Keep gowns in cabinet to avoid dirt and dust.
 Soap for hand cleaning must be installed near the
sink. Paper towels or hand drier should be
provided whichever is suitable.
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QC LABORATORY

Reference standard Laboratory apparatus

QC lab should be designed to

fit intended operations. There
should be adequate storage
space for samples, reference
standards, solvents, reagents &
Record cupboard
records. Reagent & solvent
Module 3

GMP EQUIPMENT
 INTRODUCTION
Each manufacturer should assure that production
equipment and quality control measurement equipment
are:
➢ suitable for the intended use.
➢ capable of producing valid results.
➢ operated by trained employees; and
➢ properly calibrated versus a suitable standard.

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GENERAL REQUIREMENTS

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 DESIGN & CONSTRUCTION (1)

1. Surfaces must not

be:
➢ Reactive
➢ Additive
➢ Adsorptive

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DESIGN & CONSTRUCTION (2)

2. Easily cleanable

Before cleaning

After cleaning 52
 DESIGN & CONSTRUCTION (3)

3. Must not affect the

product through
leaking valves,
inappropriate
maintenance, etc.

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PIPES & PIPELINES (1)

Fixed pipelines for the transfer of
products and materials should :
🖙 be clearly labelled
🖙 indicate contents
🖙 show direction of flow

✓ ✓
 PIPES & PIPELINES (2)
Water, steam, pressure
and vacuum lines where
applicable should be:
➢ easily accessible
➢ clearly identified
➢ instrument
monitoring control

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 PIPES & PIPELINES (3)
➢ The material quality and quantity that
uses piping system should be
monitored and checked periodically.

➢ Pipelines for hazardous gas and liquid

installation…
should be clearly labeled
and pipe connections should use the
right materials

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 SAFETY DEVICES
All safety and regulator devices should be checked
and calibrated regularly

Pressure gauge & Control panel

Air pressure regulator
release valve

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LOCATION & INSTALLATION (1)
1. Avoid crowding.
2. Properly identified.
3. Easily accessible during all
phases of operation.

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LOCATION & INSTALLATION (2)
Equipment layout and design must aim:
to minimize risks of error
to permit effective cleaning
to permit effective maintenance
And to avoid:
cross-contamination
dust and dirt build-up
any adverse effect on the quality of products
Equipment must be installed to:
minimize risks of error
minimize risks of contamination

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FLEXIBLE HOSES
➢ The transfer system
of liquid product may
be through flexible
hoses made of
suitable material and
compatible with the
product used,
cleaning &,
disinfecting agents
and steam.
➢ It should be clearly
identified.
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 TYPE OF MATERIALS USED
Most of the pipelines should
be used with Stainless Steel
316L as it is stable 1- when in
contact with the materials, 2-
during hot sanitation & disinfection.

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CLEANING EQUIPMENT (1)

Clean In Place
 MAINTENANCE SCHEDULE
A manufacturer should establish schedules to maintain, clean,
and adjust equipment used in the manufacture of
pharmaceutical products.
To maintain, clean, or adjust equipment, the manufacturer
should:

➢ have a written schedule;

➢ have special instruction, where adjustment is necessary to

maintain proper operation;
➢ document the maintenance activities;
➢ check periodically;
➢ audit the activities and document the inspection results.

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 CALIBRATION
➢ The GMP calibration requirements is to assure
adequate and continuous performance of
measurement equipment with respect to
accuracy and precision.
➢ The equipment should be calibrated according
to written procedures that include specific limits
for accuracy and precision. All results should be
documented.
➢ Proper and periodic calibration will assure that
the selected equipment continues to have the
desired accuracy

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Equipment Qualifications

• appropriate qualification of critical equipment and ancillary systems should be

completed. Qualification is usually carried out by conducting the following activities,
individually or combined:
• − Design Qualification (DQ): documented verification that the proposed design of the
facilities, equipment, or systems is suitable for the intended purpose.
• − Installation Qualification (IQ): documented verification that the equipment or systems,
as installed or modified, comply with the approved design, the manufacturer’s
recommendations and/or user requirements.
• − Operational Qualification (OQ): documented verification that the equipment or
systems, as installed or modified, perform as intended throughout the anticipated
operating ranges.
• − Performance Qualification (PQ): documented verification that the equipment and
ancillary systems, as connected together, can perform effectively based on the approved
process method and specifications.
Module 4

GMP PRODUCTION
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INTRODUCTION
SCOPE

➢ receiving & recording of starting materials

➢ sampling of starting materials
➢ preparation of production documents, including master formula
➢ weighing activities
➢ cleaning & sanitization of equipment
➢ preparation of bulk
➢ filling & packing activities
➢ reconciliation of production output
➢ proper recording of each activity to ensure traceability of finished
products
➢ quarantine and delivery to warehouse
➢ reprocessing, if necessary
 BASIC DESCRIPTIONS

 PRODUCTION is defined as all activities starting from processing to

• packaging to obtain finished products

 PROCESSING is part of production cycle starting from weighing of raw

• materials to obtain a bulk product

 PACKAGING is part of production cycle starting from bulk product to

obtain the finished product

 STARTING MATERIALS consist of raw materials and packaging

materials used in the production of pharmaceutical products
 PRODUCTION MAPPING
Raw material
preparation Weighing

Production operations must follow

clearly defined procedures in
accordance with approved
specifications, with the objective of
obtaining products of desired quality. Bulk storage

Processing
Production activities start from :
❖ - preparation of raw materials
❖ - weighing of raw materials
❖ - mixing & bulk preparation
❖ - filling and packaging Delivery to
Filling & packing
to obtain finished products that can be warehouse

released to the market.

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THE STARTING MATERIALS

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MATERIAL BASIC REQUIREMENTS (1)

➢ All incoming materials should be

quarantined immediately after receipt until
they are released for use in production
➢ Raw materials should be stored under
appropriate condition.
➢ Storage condition should be controlled,
monitored and recorded
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MATERIAL BASIC REQUIREMENTS (2)

➢ Storage of materials should be orderly to
avoid mix up and cross contamination
➢ Ensure that there is an effective system in
controlling stocks
➢ Ensure that consumption of starting materials
follows :
✓ FIFO ~ First-In-First-Out, or
✓ EEFO ~ Earliest Expiry, First Out.
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MATERIAL BASIC REQUIREMENTS (3)

➢ Personnel in charge of raw material purchase should have
sufficient knowledge of the materials, products and suppliers of
the materials

➢ Raw materials should be purchased from qualified suppliers.

➢ Raw materials should have approved specification accompanying

with a certificate of analysis.

➢ it is suggested to purchase raw materials directly from

manufacturers or appointed distributors .
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LABELS OF INCOMING MATERIALS

Name of Material
Internal Code
Batch No.

Status QUARANTINE
Expiry Date Date Received
Date Signature

Name of Material Name of Material

Internal Code

Internal Code Batch No.

Status RELEASED
Batch No / Expiry Date Retest Date

Receiving No. Date Signature

Quarantine / Release / Name of Material

Status Internal Code

Rejected / Hold ( Use Color) Batch No.

Status REJECTED
Expiry Date Retest Date
Expiry Date

Date Signature
Receiving Date Signature
Name of Material

Internal Code

Batch No.

Status HOLD
Expiry Date Retest Date

Date Signature
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SAMPLING LABEL
🞖 Sampled containers identification
A procedure has to be followed for sampling
the material.
The containers from which samples were
taken, should be identified (e.g. a label).

Name of Material Alcohol 1 of 12

Sample has
Internal Code AL 001 been taken
by QC
Batch No /
11/OF/2005
Receiving No.
Status QUARANTINE
Expiry Date Retest Date

Receiving Date 14- 06-2005 Signature Tia

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REJECTED MATERIALS
🞖 Clearly marked
➢ Rejected materials should be clearly marked .
🞖 Stored separately in off-limits area
➢ Access to the area should be controlled.
🞖 Actions:
➢ rejected materials should be returned to the suppliers,
destroyed or reprocessed;
➢ the action should be described and defined in a procedure;
➢ the action to be taken should be approved by authorized
personnel;
➢ the action and approval must be recorded.
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PRODUCTION
PROCEDURES
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PROCESSING GUIDANCE (1)

There are several guidelines that should be followed prior, during
and after each production activities. These are:
➢ Area clearance or lines clearance should be done, to avoid mix
up of starting materials or finished products
➢ In-process and environmental controls should be carried out
and recorded.
➢ Failure of equipment or services should be monitored and only
equipments in good condition should be available in the
production area.
➢ Cleaning procedures should be written and approved
➢ Containers should be cleaned prior to use
➢ Any deviation from requirements and expected result should be
recorded and investigated prior to start of production and prior
to release of the finished product
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PROCESSING GUIDANCE (2)

➢ Any significant deviation from the expected yield should be
recorded and investigated.
➢ Checks should be carried out to ensure that pipelines and
other pieces of equipment used for the transportation of
products from one area to another are connected in a
correct manner.
➢ Measuring, weighing, recording, and control equipment
should be serviced and calibrated at pre-specified intervals
and records are maintained.
➢ Repair and maintenance operations should not present any
hazard to the quality of the products.
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WEIGHING & MEASUREMENT

🖙 Weighing should be carried out :
- in defined areas
- using calibrated equipment.

🖙 All weighing and measurement carried out should be:

- recorded
- counter checked
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IN-PROCESS CONTROL
◼ Done within the production area and by production people and/or
Quality Unit
◼ Should be recorded and done as per approved/written SOP
◼ Sampling done to verify:
➢ physical aspects (weight, volume, amount, etc)
➢ text on labels
➢ other performance requirements
◼ Sampling maybe conducted based on need :
➢ during processing activity
➢ during packaging (filling & packing) activities :

random, sequential, or statistical

◼ Samples taken away from the packaging line should not be returned
if containers were opened

◼ Record of in-process control should be part of the BMR.

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LINE CLEARANCE
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◼ 1- line clearance should be done prior to processing and filling

operations
◼ 2- prepare a clearance checklist for each operation
◼ 3- material from previous batch should be removed from the
line
◼ 4- filling machine should be connected to the right outlet of the
bulk storage tank
◼ 5- number of personnel should be enough to operate the line
◼ each personnel has clear understanding of their roles and
responsibilities in the processing or filling operation
◼ 6- processing line should be clearly identified and labeled with
the name of the product and batch number
◼ 7- filling lines should be physically identified with the product
name, size, batch no, and if needed the destination of products
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RECONCILIATION
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🖛 Any deviation from the procedures should be avoided

as much as possible. If deviations occur, they should
be approved in writing by a designated person, with
the involvement of the quality control department.
🖛 Checks on yields and reconciliation quantities should
be carried out as necessary to ensure that there are
no discrepancies outside acceptable limits.
🖛 These are some points to be considered in the
reconciliation of the batch:
- quantity of starting materials
- output of finished products
- machine efficiency
🖛 All activities of reconciliation should be conducted
based on written standard operating procedures.
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BATCH NUMBERING SYSTEM (1)

🖙 A product identification number/batch number should be
assigned to:
🟎 every finished product
🟎 every bulk and semi finished product
which enables the history of the product to be traced.
🖙 A batch numbering system should be unique
🟎 specific for the product
🟎 non repetitive for the same product

🖙 Creation of batch number should be based on written

guideline (SOP)
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BATCH NUMBERING SYSTEM (2)

🖙 The batch number should be printed on:
🟎 primary packaging
🟎 secondary packaging (as necessary)
🖙 A batch number may give information on :
🟎 date and year of production
🟎 country, manufacturer or subcontractor
🟎 sequence of production
🖙 Records of batch number should be kept and maintained
🟎 for every finished product
🟎 until at least 1 year after the expiry date
🟎 for traceability factor
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HANDLING OF REJECTED OUTPUT

➢ - Rejected product should be properly labeled and physically
separated

➢ - Investigation of the root cause of rejection should be done

by production and assisted by quality Unit

➢ - SOP in handling rejected product should be established,

written and approved
➢ - If rework can be done, written procedure should be prepared
by production and approved by quality control

➢ - Stability of reworked products should be verified and if

necessary additional testing should be performed
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REPROCESSING
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➢ There should be a written policy which clearly states that

such action is allowed to be done.
➢ Reprocessing of rejected product should only be done in
exceptional cases.
✓ It should only be allowed if the quality of the product is
not negatively affected and the product quality still
complies with the specifications.
✓ It should consider additional testing of reprocessed
product, e.g. stability testing of the batch.
➢ Complete records should be maintained for reprocessed
product
➢ A reprocessed product should be given a new batch
number.
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RETAINED SAMPLES

Sample retention program should be carried out for

reference and retesting for stability and in case of
product complaint.
PRODUCTION DOCUMENTS
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PRODUCTION DOCUMENTS

Production documents of each

pharmaceutical product should consist
of:-
➢ Batch manufacturing record ( BMR )
➢ Record of Quality Control
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BATCH MANUFACTURING RECORD

a. Batch Manufacturing Record should be prepared for each batch of
product.
b. Each BMR should include the following :
➢ Name of product
➢ Batch formula
➢ Brief manufacturing process
➢ Batch number
➢ Date of the start and finish of processing and packaging
➢ Identity of individual major equipment and lines or location used
➢ Records of cleaning and sanitation of equipment used for
processing as appropriate
➢ In-process control and laboratory results, such as pH and
temperature test records
➢ Packaging line clearance inspection records
➢ Any sampling performed during various steps of processing
➢ Results of examinations on packed and labelled products
Module 5

GMP Quality control

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QUALITY CONTROL PRINCIPLES

 GENERAL PRINCIPLES

➢ Each holder of a manufacturing authorization should have a QC Department

➢ Independence from production and other departments is considered to be

fundamental

➢ Under the authority of an appropriately qualified and experienced person

with one or several control laboratories at his or her disposal.

➢ If do not have any facility, it can be managed by appointed respective

external laboratory institution(s).

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BASIC REQUIREMENTS OF
QUALITY CONTROL
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BASIC REQUIREMENTS
Quality Control department should have :
 resources:
➢ adequate facilities
➢ qualified personnel
➢ approved written procedures
 tasks :
➢ sampling, inspecting, testing,
➢ releasing or rejecting
➢ monitoring
 objects :
➢ Starting materials, intermediates, bulk, and finished products
➢ Returned products
➢ Environmental conditions
 QUALITY CONTROL UNIT
• Large firms : Quality Control Unit(s).
• Small firms :
✓ specific tasks unit with limited laboratory instrument,
or
✓ contract analysis with respective external laboratory
institute(s)
• Responsibilities defined in written procedures
• Independence from production and other
departments is fundamental
• Under the authority of an appropriately qualified
and experienced person

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RESPONSIBILITIES

• Examines, approves or rejects incoming materials, intermediates,

• bulk, the finished products, and returned products.

• Does the inspection during production (in-process control)

• Establishes, standardizes, and implements all QC procedures, and also

establish the specification of each incoming materials.

• Approves reprocessing instruction and rework instruction

• Involves in all decisions concerned with the product quality

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 OTHER RESPONSIBILITIES
 Evaluating, maintaining, storing, and monitoring all
reference standards and retained samples
 Maintaining correct specification of materials and
finished products
 Stability testing of each finished product
 Participating in :
➢ complaint investigations
➢ environmental monitoring

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 IN-PROCESS CONTROL

• Inspection and testing based on process monitoring

• Shall be documented in Batch Manufacturing Record
• The result shall conform to Batch Manufacturing /
Packaging Record requirements
• Control chart/other statistical tools for process capability
may be used for trend analysis

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 LABORATORY DOCUMENTATION
Laboratory documentation includes
➢ Sampling procedures
➢ Calibration and Maintenance Equipment
➢ Stability Procedures, where applicable
➢ Environment Monitoring, where applicable
➢ Testing procedures and records (including worksheets
and/or laboratory notebooks)
➢ Analytical reports and/or certificates

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TASKS OF
QUALITY CONTROL
RECEIPT
• There should be written procedure on the receiving, internal labeling,
quarantine and storage of starting materials, packaging materials and
other materials as appropriate
• Upon receiving of the supplied goods, its identity, legibility of batch
number, integrity of its primary packaging and seal shall be verified prior to
acceptance.
• Certificate of Analysis shall be provided by the supplier with the
receiving of starting materials
• Quarantined goods shall be segregated from “Released”goods
• Rejected goods shall be stored in a define area with
consideration of control access (e.g. Locked area)

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SAMPLING
• The sample taking shall be done in accordance with
written procedure that describe:
• The method of sampling
• The sampling tools used
• The amount of samples to be taken
• The type and condition of the sample container to be
used
• (i.e. amber glass bottle)
• The identification of the container sampled
• Special precaution for hazardous materials
• The storage condition (if any)
• Instruction for cleaning and storage of
sampling equipment
• Instruction for re-sealing the opened container.
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 All tests shall be
performed in accordance
with the test methods as
TESTING stated in the specification
&
ANALYSIS Test can be performed by
in-house laboratory or
external laboratory

106
 RETAINED SAMPLES (1)
• Retained sample should be representative of the batch of
materials or products from which they are taken.
• Retained sample shall be of a size sufficient to permit at
least 2 full re-examinations
• Retain samples for each batch of finished products shall be
retained for a defined period
• Finished product should be kept in their final packaging and
stored under the recommended condition (e.g.. Consumer
used condition , at room temperature)

107
 RETAINED SAMPLES (2)

• A retained sample log shall be maintained with

the sample identification, batch number and its
storage location for ease of retrieval
• Prior to disposal of retain sample, visual
inspection should be carried out

108
OUT OF SPECIFICATION INVESTIGATION (OOS)

• Written procedure should be made available.

• Typically, an investigation includes:
• A review of the calculations to ensure they are correct.
• A review of test procedures utilized.
• A review of equipment, columns, charts and previous analyses of
samples of the same product/material
• A review of reagent/ standardization carried out for the test
(e.g.,pipettes).
• A complete investigation and evaluation of initial results prior to a
retest.
• A review of product/material history
• Assigned person responsible for investigation
• Documented rational for retest and re-samplin.

109
 ENVIRONMENT MONITORING
• Environment Monitoring to be implemented where
appropriate.
• The objective is to demonstrate that manufacturing
environment is functioning at an adequate level of
microbial control for the specific product/product
group.

110
 Module 6

GMP Sanitation and hygiene

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OBJECTIVES

The aim of sanitation and

hygiene measures is to
eliminate all potential
sources of contamination
and cross-contamination
from all areas where the
product quality is at risk.
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SCOPE
◼ Sanitation and hygiene should be practiced to
avoid contamination of personnel and avoid
contamination during manufacturing of
products.
◼ It should cover all aspects of manufacturing:
➢ Personnel
➢ Premises
➢ Equipment and apparatus
➢ Production materials and containers
➢ Products for cleaning and sanitation
➢ All potential sources of contamination
 2
4
1

CLEANING PRINCIPLES
🖛 Cleaning operations shall be performed in a manner to prevent
contamination of materials and products.

🖛 All cleaning compounds and sanitizers shall be properly labelled

and stored in a locked compartment, away from production and
storage areas.

🖛 Cleaning equipment and tools shall be supplied and be readily

available for use. All cleaning equipments shall be maintained and
stored in such a way as not to contaminate product or equipment.
 2
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2

BENEFITS
For personnel :
◼ To prevent contamination risk that effect personnel health

For product :
◼ To prevent contamination of the products
◼ To maintain the high standard of product quality

For company :
◼ To save on cost, avoid reworks and rejects
◼ To avoid consumer complaints
◼ To avoid potential product recall

For consumers :
◼ To get safe and good quality product
PERSONNEL
HYGIENE

243
 2
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4

BASIC HYGIENE
Personal hygiene will usually be the main element in
the term “hygiene”
Bacteria causing diseases may be carried and
transmitted to surfaces and products by workers
handling materials and products.
 2
4
5

HEALTHY & GOOD HABITs

Employees shall be encouraged to practice good

personal hygiene habits at all times.
Personnel should be healthy and capable to perform


their assigned duties.
Regular medical examination must be conducted for
all production personnel involved in manufacturing
processes.
X
➢ during recruitment process
➢ every regular period
 2
4
6

GOOD PERSONNEL HYGIENE

Personnel must practice good
personal hygiene.
 regular bathing every day
 brushing of teeth
 washing hands
✓ before entering
the production
area
✓ after visiting the toilet
✓ after eating
✓ after smoking
 2
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HAND WASHING GUIDELINES

1. Wet your hand with 4. Rinse your hand
flowing water with flowing water

2. Use soap around 5. Dry your hand with

your hand and tissue or hand dryer at
fingers. 320 – 600C.

3. If needed use brush 6. Don’t touch anything.

to clean your nails If can not be avoided,
repeat step 1-5
 2
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8

VISIBLE ILLNESS & OPEN LESIONS

Personnel who have an illness or open wound
that are likely to present a risk to the product,
should not be allowed to carry out operations
that involve handling of starting materials,
intermediates or finished products until the
condition has cleared up.
 2
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9

PERSONNEL WITH ILLNESS

Personnel should be instructed
and encouraged to report to their
immediate supervisor when they
are ill or when they see any
conditions that may adversely
affect the product quality.
 2
5
1

NO EATING, DRINKING & SMOKING

“No Eating”, “No Drinking”, “No Smoking”, and “No Chewing
Gum” policy shall be strictly implemented
Food shall not be kept in production, warehouse or laboratory area.

No Eating,

No Drinking

No Smoking
 2
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2

SANITATION FACILITIES
Each plant shall be equipped with adequate sanitary facilities
including, but not limited to:
a. Water supply
b. Plumbing
c. Toilet facilities
d. Hand washing facilities
e. Rubbish disposal
f. Changing facility or locker
which should be sufficient, adequate in size and design,
and properly installed for easy cleaning and sanitation
processes.
 2
5

Sanitation Facilities
3

WATER SUPPLY & PLUMBING

🖝 Water is the main source of product
contamination.
🖝 The water supply shall be sufficient for the
operations intended and shall be derived from
an adequate source.
🖝 Plumbing shall be of adequate size and design
and adequately installed and maintained to:
➢ carry sufficient quantities of water to
required locations
➢ properly convey sewage and liquid
disposable waste
➢ provide adequate floor drainage in all areas
➢ ensure that there is no back-flow from, or
cross-connection between piping systems
 2
5

Sanitation Facilities
4

HAND WASHING & TOILET

Adequate employee’s washing and well

ventilated toilet facilities should be provided and
separated from the production area.
◼ Must be kept clean at all times
◼ Well maintained
◼ With adequate supply of water
◼ Provided with soap, hand dryer or paper towel
◼ Used properly by all employees
 2
5

Sanitation Facilities
5

RUBBISH DISPOSAL
Waste material should be placed in suitable container and
regularly collected for disposal outside the production areas.
Regular & timely collection of garbage
Garbage bins must be properly covered at all times
No food wrapper to be thrown in garbage cans inside
the production area
Do not use product shipping cases as garbage bins
 Sanitation Facilities
CHANGING ROOM(S)

Suitable changing facilities or locker

should be provided at appropriate
location for the storage of employees’
clothing and personal belongings

Personal belonging
shall be kept in lockers
or drawers.

128
 Module 7

GMP Product Complaint

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COMPLAINT HANDLING
PRINCIPLES
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COMPLAINT HANDLING PRINCIPLES

1. Complaints should be handled in accordance with a
written procedure
2. Carefully reviewed and handled positively
3. Managed by an appointed responsible person
4. Must be given importance
5. complete investigation of the cause is essential
6. A major source of information and learning
7. Enable possible production defects to be remedied before
they lead to a recall.
8. Necessary actions taken - even a recall decision
9. All complaints should be well documented
 2
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1

RESPONSIBLE PERSON

Within each company a person with

adequate knowledge shall be
assigned the task of dealing with
complaints.
This person must also have the
authority to decide the measures
and actions to be taken.
 INVESTIGATION
➢ The person in charge of complaints is responsible for initiating
the investigation immediately. The person responsible for
Quality Control should normally be involved in the
investigation.
➢ The investigation shall be documented in writing.
➢ If a product defect is discovered or suspected in a batch,
consideration should be given to determine whether other
batches are also affected.
➢ The investigation should also cover:
 distribution condition
 condition under which the product is used

133
 REMEDIAL ACTIONS
➢ The person in charge of complaints is responsible for
the remedial action decided upon completion of
investigation.

➢ If it has been decided to make a recall , Product

Recall Procedure shall be applied.

134
 COMPLAINT DECISION

• Complaint justified
➢ Actions to prevent reoccurrence
➢ Ongoing observation of process
➢ Recall product may be required

• Complaint not justified

➢ Advise customer of findings
➢ Appropriate marketing response

135
 2
6
5

COMPLAINT & DEFECTS CLASSIFICATION

• If complaint is justified, then there has been a failure of the
quality system
• Once defect has been identified, company should be dealing
with it in an appropriate way, even recall.
• The definition of defects is useful :-
➢ Critical defects
➢ Major defects
➢ minor defects
 2
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6

CRITICAL DEFECTS
Those defects which can be life threatening
and require company to take immediate action
by all reasonable means, whether in or out of
business hours
Examples :
➢ Product labeled with incorrect name or incorrect formula
➢ Counterfeit or tampered product
 MAJOR DEFECT
A defect, which is a non conforming product,
in view of the consumer, it may not be
hazardous.

Example:
➢ Microbiological contamination of products with
some risk for users
➢ sub standard products

138
 MINOR DEFECT
A defect ,which has no important effect upon
the use of the product and does not produce a
hazard.

Example :
Lacking in labeling , packaging.

139
 DOCUMENTATION
Documentation of complaint investigation :
✓ Each individual complaint and relevant
attached documents shall be filed.
✓ A final report shall be prepared and
documented.
✓ In the event of product recall (product
safety) the authority should be notified

140
 Module 8

GMP Product Recall process

 2
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1

INTRODUCTION
 2
7
2

OBJECTIVES

⚫ To identify the key issues of product

known or suspected to be defective.

⚫ To put in place a system, procedures and

resources to make the product recall.
 SCOPE

This system is applicable to the

pharmaceutical manufacturer during
product recall .

273
 2
7
4

GENERAL DESCRIPTION
 DEFINITION (1)
• Product recall :
is a process taken by the responsible person who
placed the product on the market, to remove or
withdraw a particular product from all links of
distribution.

• The removal or withdrawal may be due to critical

quality defects discovered or serious adverse
reactions reported causing health risks to users
during and after distribution of the product

275
 2
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6

DEFINITION (2)
⚫ Safety Alert :
Advice regarding a specific situation of a product,
which is not conforming with the safety specification.
When there is a risk of significant hazard to
consumers of a product which has been distributed
on the market ,the manufacturer should disseminate
the safety alert through mass communication media
available including newspaper, radio and television
 DEFINITION (3)
⚫ Withdrawal:
Removal of product from sale or use for reasons
not connected with quality and safety such as
change of packaging etc. as a marketing
strategy

⚫ Recall for Product Correction:

the removal of product for rework.

277
 2
7

REASONS FOR RECALL

8

Voluntary recall :
⚫ Customer complaint
⚫ Detection of quality and safety failure
after release
⚫ Result from the ongoing stability testing
⚫ Result of an inspection
⚫ Tampering
⚫ Reportable adverse event

Mandatory recall :
⚫ Directed by the national regulatory
authorities
 2
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9

RECALL PRINCIPLE

There should be a system to recall

products known or suspected to be
defective from the market
effectively.
 2
8

BASIC REQUIREMENTS
0

⚫ the responsible person is independent from seller or marketing

⚫ Must have an effective recall SOP in place.
⚫ Distribution records should be readily available to responsible
person.
⚫ Secured storage for goods awaiting disposition.
⚫ If required, public warning/notices will be issued in order to alert
the
customers.
⚫ Progress recorded and final report issued
⚫ Reconciliation between delivered and recovered quantities.
 2
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1

RECALL CLASSIFICATION

NO CLASSIFICATION SITUATION DURATION

A Class I Recall Products with major health It should be
risks within 7 days

B Class IIRecall Products with minor / It should be

unlikely health risks or sub within one
standard month

The class of product recall is classified according to the seriousness of

quality defects and adverse events of the products.
 2
8
2

LEVEL OF RECALL

NO LEVEL OF RECALL The level of the product

recall depends on :
A Up to all consumers (end users) • the nature of the
problem,
B Up to all points of sales (e.g. pharmacies) • the extent of the
product's distribution
and,
• the degree of hazard
C Up to all sub distributors (wholesalers) involved.

D Up to all importers and main distributors.

 THE FINAL RECALL REPORT
• Final Recall Report, a written evaluation
summarizing the circumstances leading to the recall,
corrective actions taken and the disposition of the
recalled product, will be prepared by the Recall Team
once the recall is considered closed.

• Report consists of:

➢ Fate of the products
➢ Reconciliation result
➢ Disposal report/certificate if any

154
Thank you