GOOD MANUFACTURING

PRACTICE
DEFINITION:

Good Manufacturing Practice or GMP (also referred to as 'cGMP' or

'current Good Manufacturing Practice') 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.

Difference between GMP and cGMP

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

INTRODUCTION:

GMP takes the holistic approach of regulating the manufacturing and

laboratory testing environment itself. An extremely important part of GMP is
documentation of every aspect of the process, activities, and operations
involved with drug and medical device manufacture. If the documentation
showing how the product was made and tested (which enables traceability
and, in the event of future problems, recall from the market) is not correct
and in order, then the product does not meet the required specification and is
considered contaminated (adulterated in the US).

Additionally, GMP requires that all manufacturing and testing equipment has
been qualified as suitable for use, and that all operational methodologies and
procedures (such as manufacturing, cleaning, and analytical testing) utilized
in the drug manufacturing process have been validated (according to
predetermined specifications), to demonstrate that they can perform their
purported function(s).

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Current good manufacturing practice regulations are established by food and
drug administration to ensure that minimum standards are met for drug
product quality. The first GMP regulations were introduced in 1963 and
since then they have periodically revised and updated.

The cGMP regulations establish requirements for all aspects of

pharmaceutical manufacture. They apply to domestic and to foreign
suppliers and manufacturers whose bulk components and finished
pharmaceutical products are imported, distributed or sold in this country.

The code of federal regulation contains requirements for the Current Good
Manufacturing Practice for Finished Pharmaceuticals
An additional cGMP requirement for biologic products
Medicated articles
Medical devices
Currency and compliance with cGMP regulations is supported
through notices in the federal register and through the FDAs
compliance policy guide and various other guides issued by FDA.

Topical Outline of Current Good Manufacturing Practice:

A topical outline of current good manufacturing practice regulations is
provided in the following table

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 1) Organization and Personnel Requirements:

Responsibilities of quality control department:

A. The organization and personnel section of the regulation deals with
the responsibilities of the quality control unit, employees, and
consultants.
B. The regulations require that a quality control unit have the authority
and responsibility for all the functions that may affect product quality.
C. This includes accepting or rejecting product components, product
specifications, finished products, packaging and labeling.
D. Adequate laboratory facilities shall be provided, written procedures
followed and all records are maintained.
Personal qualification and responsibilities:
A. 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.
B. Appropriate programs of skill development, continuing educations are
essential for maintaining quality assurance.
Consultants:
A. Any consultants advising on scientific and technical matters should
possess requisite qualifications for the tasks.

2) Buildings and Facilities:

Design and construction features:

A. The regulations of this section include the design, structural features,
and functional aspects of buildings and facilities.
B. Each buildings structure, space, design, and placement of equipment
must be such to enable thorough cleaning, inspection, and safe and
effective use for the designated operations.
C. Proper consideration must be given to such factors as water quality
standards, security, materials used for floors, walls and ceilings,
lighting, segregated quarantine areas for raw materials and product
components subject to quality control approval; holding areas for
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 rejected components, storage area for released components, weighing
and measuring rooms, flammable materials storage areas, finished
product storage, control of heat, humidity, temperature and
ventilation, waste handling, employee facilities and safety procedures
in compliance with occupational safety and health administration
regulations and procedures and practice of personal sanitation.
Maintenance:
A. A log of building maintenances must be kept to document this
component of the regulations.
3) Equipment:

Equipment design, size and location:

A. Each piece of equipment must be of appropriate design and size and
suitably located to facilitate operations for its indented use, cleaning
and maintenance.
B. The equipments surfaces and parts must not interact with the
processes or products components so as to alter the purity, strength or
quality.
Equipment 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 equipments:
Automated equipment and computers used in the processes must be
routinely calibrated, maintained and validated for accuracy.

4) Control of Components, Containers, and Closures:

General requirements:
Written procedures describing the receipt, identification, storage,
handling, 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 with the supplier
at the time of ordering.
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Raw Material Inspection
An incoming raw materials inspection program is a GMP
requirement. There should be written procedures describing all actions of the
raw material inspection program covering a minimum the parameters listed
in the following table

Each raw material should have a corresponding written specification that

was developed to ensure the appropriate quality of material is used in the
manufacturing process. In orded to be released the materials must meet those
specfications. Once raw materials are approved for use, the materials
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 the quality assurance unit will handle taw material
rejection.
When raw materials are received, they should go directly in quarantine until
they have been tested and approved for manufacturing use. Raw materials
are brought in by the receiving department. This group should check the

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obvious damage to the shipping containers and match up the type and
quantity of the material to the purchase order. If this information is correct,
the material is moved to designated quarantine area. When it has been
determined that the 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 and its quarantine status. The material will remain in
quarantine until it has been approved for use in manufacturing.

Items needed to identify materials

The inspector uses raw material inspection sheet document which consists of
following information

After all the 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.

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 5) Production and Process Control:

Written procedure deviation:

Written procedures are required for production and process
controls to ensure that the drug products have the correct identity, strength,
quality 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
supervisor signs off on it. When operations are controlled by automated
equipment, such equipment must be validated regularly for precision.
Equipment identification:
All product ingredients, equipment, and drums or other containers of
bulk finished product must be distinctively identified by labeling as to
content and or status.
Sampling and testing of in process material:
In-process samples are taken from the production batches periodically for
product control.

In-process controls are of two general types:

Those performed by production personnel at the time of operation to
ensure that the machinery is producing output within pre-established
control limits. (tablet size, hardness)
Those performed by quality control laboratory personnel to ensure
compliance with all product specifications and batch to batch
consistency.( tablet content, dissolution)

6) Packaging and Labeling Control:

A. Written procedures are required for the receipt, identification, storage ,

handling, sampling, and testing of drug product and issuance of
labeling and packaging materials.

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B. Labeling for each variation in drug product- strength, dosage form, or
quantity of contents- must be stored separately with 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 and labeling
of product until approved and released by the quality control unit.
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 facilites must be
inspected to ensure that all drug products and labels have been
removed from the pervious operations.
H. During operation the products are visually or electronically inspected
for correct labeling and packaging.
I. All records of inspections and controls must be documented in the
batch production records.

7) Holding 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 until
released by the quality control department.
C. Products must be stored and shipped under conditions that dont affect
product quality.
D. Ordinarily the product oldest approved stock is distributed first.

8) Laboratory Controls:

A. Laboratory controls are requirements for the establishment of and

conformance to written specifications, standards, sampling plans, test
procedures and other such mechanisms.

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 B. The specifications, which apply to each batch of dreug product,
include provisions for sample size, test intervals, sample storage,
stability and special testing requirement 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 the drug product.

9) 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 maintainance logs; specifications; and lot numbers
of product componenets, including raw materials andproduct containers and
closures; and label 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
Special notations
Equipment used
In-process controls
Sampling and laboratory methods and assays results
Calibration of instruments
Distribution records
Dated and employee identified records

These master records must document that each step in the production,
control, packaging, labeling, and distribution of the product was
accomplished and approved be the quality control unit. Depending on the

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operation, the operators and or superivisors full signatures, initials, or
written or electronic identification codes are required.
Records of written and oral complaints regarding a drug product must also
be maintained, along with the information regarding the internal disposition
of each complaint. All records must be made available at the time of
inspection by FDA officals.

10) Returned and Salvaged Drug Products:

A. Returned drug products (e.g from wholesalers) must be identified by

lot number and product quality determined through appropriate
testing.
B. Drug products that meet specifications may be salvaged or
reprocessed.
C. Those that donot, along wih those that have been subjected to
improper storage (e.g extremes in temperature), shall not be returned
to marketplace.
D. Records for all returned products must be maintained and must
include the date and reasons for the return; quantity and lot number of
product returned; procedures employed for holding, testing, and
reprocessing the product; and the products disposition.

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