Good Manufacturing Practices

Definition
• Good Manufacturing practices or GMP is a term that is recognized
worldwide for the control and management of manufacturing and quality
control testing of foods, pharmaceutical products and medical devices.

• The first GMP regulations were introduced in 1963 and since then they
have periodically revised and updated

• The only difference between GMP and cGMP is that GMP is the predefined
standards regarding control and management and cGMP are those
standards which are being currently employed during the process. That is
why they are called cGMP.

• cGMP regulations are established by FDA to ensure that minimum

standards are met for drug product quality. Current guidelines proposed by
FDA in QC and production department.
 Quality and Quality Assurance
• In the drug industry at large, quality management is usually defined as the
aspect of management function that determines and implements the
“quality policy”, i.e. the overall intention and direction of an organization
regarding quality, as formally expressed and authorized by top
management. The basic elements of quality management are: — an
appropriate infrastructure or “quality system”, encompassing the
organizational structure, procedures, processes and resources; —
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 assurance” is a wide-ranging concept covering all matters that
individually or collectively influence the quality of a product. It is the
totality of the arrangements made with the object of ensuring that
pharmaceutical products are of the quality required for their intended use.
Quality assurance therefore incorporates GMP and other factors, including
those outside the scope of this guide such as product design and
development.
 INTRODUCTION
• GMP is that part of QA which ensures that products are consistently
produced and controlled to the quality standards appropriate to their
intended use and as required by the marketing authorization. GMP are
aimed primarily at diminishing the risks inherent in any pharmaceutical
production. Such risks are essentially of two types: cross contamination (in
particular of unexpected contaminants) and mix-ups (confusion) caused by,
for example, false labels being put on containers.
• Good documentation is an essential part of the QA system and, as such,
should exist for all aspects of GMP . Its aim is to define the specifications
and procedures for all materials and methods of manufacture and control;
to ensure that all personnel concerned with manufacture know what to do
and when to do it; to ensure that authorized persons have all the
information necessary to decide whether or not to release a batch of a drug
for sale, to ensure the existence of documented evidence, traceability, and
to provide records and an audit trail that will permit investigation. It
ensures the availability of the data needed for validation, review and
statistical analysis. The design and use of documents depend upon the
manufacturer.
 UNDER GMP
(a) All manufacturing processes are clearly defined, systematically
reviewed in the light of experience, and shown to be capable of
consistently manufacturing pharmaceutical products of the required quality
that comply with their specifications;
(b) qualification and validation are performed
(c) all necessary resources are provided, including:
i. appropriately qualified and trained personnel;
ii. adequate premises and space;
iii. suitable equipment and services;
iv. appropriate materials, containers and labels;
v. approved procedures and instructions;
vi. suitable storage and transport;
vii. adequate personnel, laboratories and equipment for in-process
controls;
(d) instructions and procedures are written in
clear and unambiguous language, specifically SAFETY

applicable to the facilities provided;

(e) operators are trained to carry out procedures QUALITY IDENTITY

correctly; GMP
(f) records are made during manufacture to show
that all the steps required by the defined
procedures and instructions have in fact been Strength PURITY

taken and that the quantity and quality of the

product are as expected; any significant
deviations are fully recorded and investigated;

(h) the proper storage and distribution of the products minimizes any risk to their
quality;
(i) a system is available to recall any batch of product from sale or supply;
(j) complaints about marketed products are examined, the causes of quality defects
investigated, and appropriate measures taken in respect of the defective products
to prevent recurrence.
 Key elements of GMP
1. Organization and Personnel Requirements
Responsibilities of QC Department:
A. The regulations that a QC unit have the authority and responsibility for all the
functions that may affect product quality
B. This includes accepting or rejecting product components, product specifications,
finished products, packaging and labeling.
C. Adequate laboratory facilities shall be provided, written procedures followed and
records are maintained.
D. Quality control is the part of GMP concerned with sampling, specifications and
testing, and with the organization, documentation and release procedures which
ensure that the necessary and relevant tests are actually carried out and that
materials are not released for use, nor products released for sale or supply, until
their quality has been judged to be satisfactory.
Personnel Qualification and Responsibilities:
The establishment and maintenance of a satisfactory system of QA and the correct
manufacture and control of pharmaceutical products and active ingredients rely
upon people. For this reason there must be sufficient qualified personnel to carry
out all the tasks for which the manufacturer is responsible
All personnel engaged in the manufacturing processing, packing or holding of a
drug product, including those in supervisory positions are required to have the
education, training or experience needed to fulfill the assigned responsibility.
A. Appropriate programs of skill development and continuing education are
essential for maintain the quality assurance
B. Key personnel include the head of production, the head of quality control and
the authorized person. Normally, key posts should be occupied by full-time
personnel. The heads of production and quality control should be independent
Consultants
A. Any consultants advising on scientific ad technical matters should possess
require qualification for the tasks
2. Buildings and Facilities
A. The regulations of this section include the design, structural features and
and functional aspects of buildings and facilities
B. Each building’s structure space, design and placement of equipment's
must be such to enable thorough cleaning, inspection and safe and
effective use for the designed operations.
C. Proper consideration must be given to such factors as water quality
standards, security, materials used for floor , walls , ceilings, lightening ,
segregated quarantine areas for raw materials and product components
subject to QC approval; holding areas for rejected components; storage
area for release components, weighing and measuring rooms, flammable
materials and storage areas and finished product storage, control of heat,
humidity, temperature and ventilation, and waste handing employee
facilities and safety procedures in compliance with occupational safety
and health administration regulations and procedures and practice of
personal sanitation.
3. Maintenance
A. A log of building maintenances must be kept to document this component
of the regulations.
• Equipment
Equipment's Design , size and Location
Equipment must be located, designed, constructed, adapted, and
maintained to suit the operations to be carried out. The layout and design
of equipment must 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.
The equipment surface and parts must not interact with the processes or
product’s components so as to alter the purity, strength or quality.
Equipment's cleaning and Maintenance
Standard operating procedures must be written and followed for the proper
use , maintenance and cleaning of each piece of equipment and appropriate
logs and records must be kept.
Automatic and Electrical Equipment's
Automated equipment's and components used in the processes must be
routinely calibrated, maintained and validated for accuracy.
• Control of components, containers and closures
Central Requirements:
Written procedure describing the receipt , identification, storage, handling
and sampling testing and approval or rejection of all drug product
components , product containers and closures must be maintained and
followed bulk pharmaceutical chemicals, containers and closures must meet
the exact physical and chemical specifications established the with the
supplier at the time of ordering
Raw Material Inspection
An incoming raw material inspection program is a GMP requirement. There
should be written procedures describing all actions of raw material inspection
program covering a minimum of the parameters
Each raw material should have corresponding written specification that was
developed to ensure the appropriate quality of material used in the
manufacturing process. In order to be released the material must meet the
specifications . Once raw material are approved for use, the material
management department is responsible for using the oldest material first .
This is known as FIFO = First In, First Out. There should be a procedure in
place that describes how a quality assurance unit will handle raw material
rejection.
• When raw materials are received, they should go directly in
quarantine unit until they have been tested and approved for
manufacturing use . Raw materials are brought in by receiving
department . This group should check the obvious damage to the
shipping containers and match up the type and quantity of the
material to the purchase order .If the information is correct the
material is moved to designated quarantine area. When it has been
determined that material is suitable for identification testing and any
other testing requirements, the lot is appropriately identified with a
quarantine sticker. At this time, quality assurance or the incoming
raw material inspectors are notified of receipt its quarantine status .
The material will remain in quarantine until it has been approved for
manufacturing.
Items needed to identify Materials
The inspector used raw material inspection sheet/document which
consists of following information. After the entire acceptance criteria
have been met for a raw material it is marked as approved for
manufacturing use. The entire lot is physically moved from the
quarantine area to approved area . And if any acceptance criteria have
not been met for the raw materials then it is marked as rejected and
returned to the suppliers.
 Raw Material Inspection Program
1. Describe how materials are received
2. Describe how they are identified
Each lot of each shipment must be uniquely identified with traceability to the
supplier manufacturing lot number
Each lot is to be identified with its status : quarantine, approved or rejected
3. Describe how they are stored and what are the various storage conditions
Quarantine until tested or examined and disposition as approved for
manufacturing use by quality unit
Storage should prevent contamination
4. Describe how raw materials are handled, sampled, and tested
Representative samples are to be taken, the no. of containers sampled and
sample amount is to be statistically appropriate.
Sampling techniques should prevent contamination
Samples are to be appropriately identified
A minimum of at least one identify test should be conducted
5. Describe what the approved and rejection process is for raw material.
 Items Needed To Identify Materials
1. Name of the manufacturer
2. Identify and quantity of each shipment of each batch of raw
materials, intermediated or labeling and packaging materials for
API’s
3. Name of supplier
4. Suppliers control numbers, if known or other identification
number
5. The number allocated on receipt
6. Date of receipt
7. The results of any tests or examination performed and conclusion
derived from this
8. Records tracing the use of materials
9. Documentation of the examination and review of API labeling and
packaging materials, for conformity with established specifications
10. The final decision regarding rejected raw materials, intermediated
or API labeling and packaging materials.
• Production and Process Control
Written Procedure Deviation:
Production operations must follow clearly defined procedures in accordance
with manufacturing and marketing authorizations, with the objective of
obtaining products of the requisite quality. identity , strength and purity
These procedures which include the charge-in of all components use of in
process controls, sample testing and process and equipment validation must be
followed for quality assurance. Any deviation from the written procedures
must be recorded and justified. In most instances the operator records time and
date of each key operation and the and the supervisor signs off on it. When
operations are controlled by automated equipment, such equipment's must be
validated regularly for precision.

Equipment Identification
All product ingredients, equipment and drums or other containers of bulk
finished products must be distinctively identified by labeling as to content and
or status.
• Sampling and Testing of In process Material
In process sample are taken from the prodution batches periodically for product control. In
process control are of two general types.
i. Those performed by product personnel at the time of operation to ensure that the machinery
is producing output within pre established control limits. (Tablet size and hardness)
ii. Those performed by Quality control personnel to ensure compliance with all produt
specifications and batch to batch consistency (tablet content, dissolution)

• Packaging and Labeling Control

A. Written procedure are required for receipt, identification, storage, handling, sampling and
testing for drug product and issuance of labeling and packaging materials.
B. Labeling for each variation in drug product, strength dosage form or quantity of contents
must be stored separately for suitable identification.
C. Obsolete and outdated labels and other packaging materials must be destroyed
D. Access to storage area must be limited to authorized personnel
E. All materials must be withheld for use in the packaging materials and labeling
F. Control procedures must be followed and record procedures must be maintained for the
issuance and use of product labeling.
G. Before labeling operation commence, the labeling facilities must be inspected to ensure that
all drug products and labels have been removed from the previous operations.
H. During operations the products are visually or electronically control labeling and packaging
I. All records of inspections and controls must be documented in the batch production records
• Handling and Distribution
A. Written procedures must be established and followed for the
holding and distribution of product
B. Finished pharmaceuticals must be quarantined in storage unit
released by quality control department
C. Product must be stored and shipped under conditions that does
not affect product quality
D. Ordinarily the product oldest approved stock is distributes first

• Laboratory Controls
A. Laboratory controls are requirement for the establishment of and
conformance to written specifications, standards sampling plans ,
test procedures and other such mechanisms
B. The specifications which apply to each batch of drug product
include, provisions for sample size, test intervals, sample storage
stability and special testing requirements for certain dosage
forms.
C. Reserve samples must be retained for distributed products for
specified periods depending on their category.
D. Reserve samples must be maintained 1 to 3 years after the
expiration date of the last lot of drug product
3. Sanitation and hygiene
A high level of sanitation and hygiene should be practiced in every
aspect of the manufacture of drug products. The scope of sanitation and
hygiene covers personnel, premises, equipment and apparatus,
production materials and containers, products for cleaning and
disinfection, and anything that could become a source of contamination
to the product. Potential sources of contamination should be eliminated
through an integrated comprehensive programme of sanitation and
hygiene.
4. Qualification and validation
In accordance with GMP, each pharmaceutical company should identify
what qualification and validation work is required to prove that the
critical aspects of their particular operation are controlled. The key
elements of a qualification and validation programme of a company
should be clearly defined and documented in a validation master plan.
• Records and Reports:
Production, control and distribution records must be
maintained for at least a year following the expiration date of
a product batch. This includes equipment cleaning and
maintenance logs; specifications; lot numbers of product
components, including raw materials and product containers
and closures; and lbel records. Complete master production
and control records for each batch must be kept and must
include the following.
 Name and strength of the product
 Dosage form
 Quantitative amounts of components and dosage units
 Complete manufacturing and control procedures
 Specifications
 10 Attributes of Good Document
• Accurate
• Clear
• Complete
• Consistent
• Indelible
• Legible
• Timely
• Direct
• Authentic
• Authorized
 Some Benefits of GMP
• Quality and Safety
• High efficacy
• High Purity
• High Work speed
• Cost Control
• High Profit
• Less deviation
• Reduced Wastages
• Less complaints
• Less recall
• Less returns
• Continual Improvement