CHE

SAFETY IN PROCESS INDUSTRY

CG OOD
195
urrent

M anufacturing
Practices
 Current
Good
Manufacturin
g Practice

key factor for industries

to produce good quality,
safe and affordable
products.
 GOOD system of quality assurance aimed at ensuring that
MANUFACTURING products are consistently manufactured and
controlled to the Quality standards appropriate to their
PRACTICES intended use

Some of the risks . . .

unexpected contamination GMP covers

of products, causing minimize the risks all aspects
damage to health or even of
death. production
incorrect labels on pharmaceutical from the
containers, which
could mean that starting
patients receive the food manufacturing materials,
wrong medicine. premises and
insufficient or too much
active ingredient, cannot be eliminated through testing equipment to
resulting in ineffective the training
the final product and
treatment or adverse
effects. personnel
 Why GMP is important?

A poor quality A medicine that

medicine may
contains little
contain toxic
substances that or none of the
have been claimed
unintentionally ingredient will
added. not have the
intended
therapeutic
 QC, GMP, QA
part of GMP concerned with
INTER-RELATIONSHI P sampling, specification & testing,
documentation & release procedures
QC which ensure that the necessary &
relevant tests are performed & the
product is released for use only
after ascertaining it’s quality
part of Quality Assurance aimed at
GMP ensuring that products are
consistently manufactured to a
quality appropriate to their
intended use
sum total of the organized
QA arrangements with the objective of
ensuring that products will be of
QA GMP QC the quality required for their
intended use
 Difference between QC and QA

QC
QC Operational and
used to fulfill the
requirement of Quality Lab-based
company-based
All those or
necessary to provide adequate confidence that a

QA
product will satisfy the requirements for
quality
QA
 GOOD
GMP covers. . .
MANUFACTURING
PRACTICES

Detailed,
written There must be
all aspects
systems to
of production procedures provide
from the are documented proof
starting essential that correct
materials, for each procedures are
premises and process consistently
equipment to that could followed at each
step in the
the training affect the manufacturing
and personnel quality of process - every
hygiene of the time a product
 10 PRINCIPLES
GOOD MANUFACTURING P R A C T I C E S

Design and construct the Write step by step operating

facilities and equipment properly procedures and work on instructions

Follow written procedures and Design ,develop and demonstrate job

Instructions competence

Protect against contamination

Document work
Control components and product
Validate work related processes

Monitor facilities and equipment Conduct planned and periodic audits

 ATTRIBUTES OF A
GOOD DOCUMENT

List of important documents 1. Accurate

2. Clear
3. Complete
Policies 4. Consistent
SOP (Standard Operating Procedures) 5. Indelible
Specifications 6. Legible
MFR (Master Formula Record)
BMR 7. Timely
Manuals 8. Direct
Master plans/ files 9. Authentic
Validation protocols 10. Authorized
Forms and Formats
Records
 GOOD
CURRENT
refers to the Current Good Manufacturing Practice
MANUFACTURING regulations enforced by the Food and Drug
PRACTICES Administration (FDA)).

cGMP provide for systems that

assure proper design, monitoring
cGMP regulations assures and control of manufacturing
IDENTITY processes and facilities.
strong quality management systems
STRENGTH
obtaining appropriate quality raw materials
QUALITY establishing robust operating procedures

PURITY detecting and investigating product quality deviations

maintaining reliable testing laboratories

 GOOD
CURRENT

MANUFACTURING
PRACTICES
requiring companies to use technologies and
systems that are up-to-date in order to company
with the regulations

curren Systems and equipment that may have been “top-

of-the-line” to prevent contamination, mix-ups,
t and errors 10 or 20 years ago may be less than
adequate by today’s standards.
BASIC cGMP GUIDELINES
Personnel/Organization
Premises
Equipment
Sanitation and Hygiene
Storage of Raw Materials & Final Products
Production
Packaging
Finished Product Quarantine & Delivery
Quality Control
Documentations
Self-Inspection
Product Complaint, Product Recall & return
Sterile Products (for drug manufacturing)

The manufacturing company shall be
conducted under the direct supervision
of competent technical staff with
prescribed qualifications and practical
experience in the relevant dosage and/or
active pharmaceutical products.
There shall be an adequate number of
personnel at all levels having
knowledge, skills and capabilities
relevant to their assigned
functions, in good mental and
physical health to be able to
ORGANIZATION
and PERSONNEL
The organizational
structure of the company
shall be such that the
production and the
quality assurance are
headed by different
managers.
All employees who are directly and
indirectly engaged in the
manufacturing activities shall be
trained in the particular operations
that the employees perform in
accordance with the principles of
Buildings
and facilities

Suitable size
operation
design
cleaning
construction
maintenance
location

The individual working areas shall be adequate so that any

risk of confusion, cross-contamination and other mistakes
that will adversely affect the quality of drugs and devices
will be avoided.
 located EQUIPMENTS
designed
Defective equipment shall be removed from production and
constructed Quality Control areas or appropriately labeled.

adapted

maintained

The layout and design of the equipment shall aim to

minimize the risk of errors and permit effective cleaning
and maintenance in order to avoid cross-contamination,
build-up of dust or dirt and, in general any adverse effect
on the quality of products. Each equipment shall be
provided with a logbook, wherever necessary.
High level of sanitation shall be practiced in every SANITATION
aspect of manufacturing drug products. and HYGIENE
The scope of the sanitation and hygiene program covers:
1) Personnel
The sanitation 2) Premises
and the 3) Equipment & Apparatus
hygiene 4) Production Materials & Containers
5) Any probable Source of Contamination
procedures
should be
validated and Potential sources of contamination shall
periodically be eliminated through an integrated
assessed to comprehensive program of sanitation
ensure that and hygiene.
the
effectiveness
of the
Production process of making sure that production is constantly
and Process maintained to produce the products of given specifications.
control
Production control process can be made by

Setting standards

Production controls are to Measuring the job performance

ensure that orders are not
misunderstood, standards are not Getting feedback of results
violated and objectives are not Taking corrective action
shifted unknowingly.

Production control is a means of building quality

A company should only use validated manufacturing processes
 The function of the packaging operation is to subdivide and control
Packaging bulk product. These operations shall be performed under strict control
designed to protect the identity, integrity and quality of the final
and labelling package.`
control
Materials examination and usage criteria Integrity of individual
packaging strips and
Labeling issuance
blisters shall be subjected
to vacuum test
Packaging and labeling operations
periodically to ensure
leak proofness of each
Tamper-evident packaging requirement for over-the-
pocket strip and blister
counter (OTC) human drug products
and records maintained.

Drug product inspection

Expiration dating
Finished Product Distribution procedure
Quarantine and Distribution
The record of distribution covers distribution of finished
product. The record shall be complete, up to date and the
last point of control before the progressive data of distribution can be easily followed and
product enters the warehouse and retrievable to enable the manufacturer to impose a drug recall
becomes available for distribution quickly and effectively whenever it becomes necessary.
to the market

Warehousing procedure
name and address of consignee

Prior to distribution or dispatch of Delivery order date and number

given batch of a drug, it shall be
ensure that the batch has been duly Name, dosage form and strength of the product
tested, approved and released by the
quality control personnel Quantity delivered

The most important documents in this Product batch number

area are inventory card and
distribution record. Expiration date

Special storage requirements

Quality control Analytical functions performed in the laboratory

sampling Stability test

inspecting Environmental monitoring

Testing of starting materials, intermediate, Validation tests
bulk and finished product
Review of batch documentation

Establishing and maintaining current specification of materials, products and their test
methods
A quality control system shall be
developed and designed so as to ensure identity purity
that finished products contain the
correct materials of specified quality strength quality safety
and quantity and are manufactured
under proper conditions following
standard procedures
“If it’s not written down, then it didn’t happen!”
Documentations
part of management information system.
Good documentation
Documentation is the key to GMP compliance and
constitutes an ensures traceability of all development,
essential part of the manufacturing, and testing activities.
quality assurance
Documentation provides the route for auditors to
Clear documentation assess the overall quality of operations within a
“If it’s not written down, then it didn’t happen!”
company and the final product.
is fundamental for
ensuring that each
personnel receives
clear and detailed
description of the The records should be made or completed at the time each action is
relevant job assignment taken and in such a way that all significant activities concerning the
to minimize the risk of manufacture of pharmaceutical products are traceable. They should
be retained for at least one year after the expiry date of the finished
misinterpretation and
product.
error, which are
normally associated
should have unambiguous contents Documentations
title, nature and purpose should be clearly stated
They should be laid out in an orderly fashion and be easy to check
designed
Reproduced documents should be clear and legible
prepared
should be regularly reviewed and kept up-to-date
reviewed
When a document has been revised, systems should be
operated to prevent inadvertent use of superseded
documents
distributed

should not be hand-written approved

although, where documents require the entry data; these Appropriate and
entries may be made clear, legible, indelible handwriting. authorized persons signed
Sufficient space should be provided for such entries.
dated
 SELF-INSPECTION
evaluate the manufacturer’s compliance with Good Manufacturing
Practices on all aspects of production and quality control

A checklist for self-inspection shall be established

to provide a minimum and uniform standards of
The self-inspection requirements.
 Personnel; premises including personnel facility
program shall be
 Storage of starting materials and finished produ
designed to detect any
shortcoming towards the
 Equipment
implementation of Good  Production
Manufacturing Practices  Quality control
and to recommend the  Documentation
necessary corrective  Maintenance of building and equipment
actions.
 PRODUCT COMPLAIN, PRODUCT RECALL AND RETURNED PRODUCTS

All complaints and other information concerning potentially defective products must be
carefully reviewed according to written procedures. In order to provide for all
contingencies, a system should be designed to recall, if necessary, promptly and effectively
products known or suspected to be defective from the market.

PRODUCT RECALL RETURNED PHARMACEUTICAL PRODUCT

process of withdrawing
one or more batches or
all of a certain
product from market
distribution. A product
recall is instituted
following discovery of
a quality defect or if
there is a report of
serious adverse
reaction of a
pharmaceutical product
which may cause health
Total withdrawal of a
pharmaceutical product from
market distribution may
result in a suspension or
discontinuation of
manufacturing of the product
finished product which is already in
distribution and returned to the
manufacturer due to complaint of
damage, expiration or other reasons
such as the condition of the container
or package which may cast doubt on
the product identity, quality, quantity
and safety
 PRODUCT COMPLAIN, PRODUCT
RECALL AND RETURNED PRODUCTS Documentations
Returned products which cannot be reprocessed
should be destroyed. A procedure for destruction
of rejected materials or product should be
available. The procedure should include
precautionary measures to prevent pollution of the
environment and misuse of the material or
product by unauthorized persons.
The handling or returned product and the follow-up
actions should be documented and reported. If the
product is to be destroyed, the documentation should
include a certificate of destruction which is dated and
signed by the persons performing and witnessing the
destruction.