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Golden Rules of Good Manufacturing Practice (GMP)

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DOI: 10.5281/zenodo.2575336

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 Journal of Pharma and Drug Regulatory Affairs
Volume 1 Issue 1

Golden Rules of Good Manufacturing Practice (GMP)

Vijay Kumar1*, Meenu Bist2, Arti Banyal3, Kirti Patial4
1
Regulatory Affairs Officer, Ind Swift Pvt. Ltd., Punjab, India
2
Assistant Professor, Department of Pharmacognosy, School of Pharmaceutical Science, Lovely
Professional University, Punjab, India
3
Assistant Professor, Department of Pharmacy, KC Institute of Pharmaceutical Science, Una,
Himachal Pradesh, India
4
Assistant Professor, Department of Pharmaceutics, Shivalik College of Pharmacy, Nangal, Punjab,
India
*Email: vijayrajput071@gmail.com
DOI: http://doi.org/10.5281/zenodo.2575336

Abstract
The basic rules in any good manufacturing practice (GMP) regulations postulate that the
pharmaceutical manufacturer must maintain appropriate documentation and records.
Documentation helps to build up a detailed interpretation of what a manufacturing function
has done in the past and what it is doing now and, thus, it provides a base for planning what
it is going to do in the future. Regulatory evaluators, during their inspections of
manufacturing sites, often devote much time on examining a company’s documents and
records. Effective documentation boosts the visibility of the quality assurance system.

Keywords: Documentation, GMP, Quality assurance

INTRODUCTION contamination are human beings,

GOOD MANUFACTURING
PRACTICES
Good Manufacturing Practices (GMP) is
that part of Quality Assurance, which
guarantees that products are regularly
produced and controlled to the quality
standards suitable to their intended use.
GMP is intended mainly at diminishing the
risk characteristic in any pharmaceutical
production. Such risks are essentially of
two types:
1. Cross-contamination (in particular,
with unexpected contaminants)
2. Mix-ups (for example, false labelling).
Cross Contamination
Cross contamination is defined as the
contamination of a starting material,
intermediate product or finished product
with another starting material, intermediate
product or finished product is called cross-
contamination. The main sources of cross
equipment, air, raw materials and water.
Human beings serve as carriers for
microbial contamination like
staphylococcus species during
manufacturing process. This may also
serve for introducing microbial species
into medicines which may be life
threatening and may cause allergic
reactions. Sometimes the microbes may be
resistant to antimicrobials. Use of such
cross contaminated drugs may cause sepsis
in the patients taking them handling of
penicillin products need special caution as
some personnel may be sensitive to them.
These may also be cross contaminated
during campaign process and may cause
severe anaphylactic reactions in cases
where in same production line more than
one drug is manufactured which causes
cross contamination air carries many
organic & inorganic particles which may
contaminate the product and degrades its

30 Page 30-37 © MAT Journals 2019. All Rights Reserved

 Journal of Pharma and Drug Regulatory Affairs
quality. Water may also contamination
when the pipe that carries water is not
sanitized. Contamination can cause any
number of problems, including study
failure, premature animal death and illness
of staff. These problems can be prevented
by using and implementing an effective
Risk Management policy [1].
Preventive Measures
To prevent cross contamination the
personnel should be taught of gowning
practices and maintaining of personal
hygiene. The personnel should wash their
hands regularly. Penicillin like sensitive
products should be handled carefully as
they may cross contaminate and cause
fatal effects. Hence there production
should be carried in dedicated facilities
separation in time along suitable cleaning
procedures ensures that cross
contamination doesn’t occur when more
than one product is produced in same line
of production proper air filtration systems
should be installed to prevent
contamination by air with appropriately
designed air supply extraction system.
Filters should be cleaned regularly pipes
should be sanitized as per the written
procedures.
Mix Up
Mix up is the contamination of one
product with another product by human
errors or inadequate process or plant
design. Mix ups occur during labelling,
packing, line clearance problems or
receipting.
Preventive Measures
Physical segregation of the products with
proper labelling and identification details
proper design for the flow of materials
packing should be done in compliance
with the written procedures.
31 Page 30-37 © MAT Journals 2019. All Rights Reserved
Volume 1 Issue 1
Good Manufacturing Practices To Avoid
Contamination and Mix Up
Procedures should be clear and should be
followed to achieve the objective of
quality for the product. All the procedures
regarding materials and products regarding
their receipts, sampling, storage, cleaning,
labelling, quarantine and dispensing
should be in accordance with written
procedures [2].
Guidelines by Different Authorities
Worldwide, there are different official
regulatory statements and guidelines, both
national and international, for GMP for
pharmaceutical (or ‘drug’ or ‘medicinal’)
products. They may be regulations (as in
the USA and Japan,), directives (as in the
EU), guides (as in the UK), codes (as in
Australia), or a WHO code (as in many
Southeast Asia Countries) [3]. Among
them, the following stand out as the most
influential and most frequently referenced:
 In United States they follow Current
Good Manufacturing Practices for
Finished Pharmaceuticals regulations.
 In European Union there is European
Commission Guide to Good
Manufacturing Practice for Medicinal
Products.
 The ICH Q7 guidelines are there for
Good Manufacturing Practice Guide
for Active Pharmaceutical Ingredients.
 In India, Good Manufacturing
Practices guidelines come under
Schedule M, The Drugs and Cosmetics
Act and Rules, 1945 [4].
DOCUMENTATION
Documentation is the key to GMP
compliance and ensures traceability of all
development, manufacturing, and testing
activities. Documentation provides the
route for auditors to assess the overall
quality of operations within a company
and the final product. Different rules of
GMP discussed in this article Figure 1.
 Journal of Pharma and Drug Regulatory Affairs
Volume 1 Issue 1

Figure 1: Golden Rules of GMP.

GOLDEN RULES OF GMP A reasonable and well-organized layout

Get the Facility Design Right from the
Start
Active Pharmaceutical Ingredient and
Finished Product Manufacturer objectives
to operate their business in accordance
with the principles of Good Manufacturing
Practice (GMP). It is the responsibility of
the manufacturer to design the layout for
facilities and equipment right from the
start.
Facility Layout
Lay out the production area to uniform the
sequence of operations. The main focus is
to reduce the chances of cross
contamination and to avoid the mix-ups
and errors during manufacturing process.
will improve output. Sometimes you need
to remove unnecessary movement in the
production area which could result in a
lethal environment. It is necessary to
segregate materials, products, and their
components to minimise confusion and
potential for mix-ups and errors.
Environment
It is important to control the lighting,
ventilation, air, water, temperature, and
humidity within a plant so that it does not
impact product quality. It is necessary to
design the facilities to reduce the risk of
contamination from the environment.
Lighting, temperature, humidity and
ventilation must be appropriate. Interior
surfaces (walls, floors and ceilings) are

32 Page 30-37 © MAT Journals 2019. All Rights Reserved

 Journal of Pharma and Drug Regulatory Affairs
smooth, free from cracks and do not shed
Particulate matter. Interior surfaces are
easy to clean. Pipe work, light fittings, and
ventilation points are easy to clean and
drains are sized adequately and have
trapped gullies.
Equipment
Design and install equipment in an area
where it can be easily cleaned and Suitable
for its intended use. Equipment’s must be
calibrated at defined intervals and clearly
labelled [5].
Validate Processes
Consistent performance is the key to
maintaining safety and effectiveness of
every product and enhances a company’s
status for quality and trustworthiness.
Validation provides a high degree of
assurance that we are making products
with good quality. In each step they have
specific written procedures for every step.
Validation is required if any changes are
there in manufacturing process, batch size
or new methods. All validation activities
should be well planned and clearly
defined. This is usually by means of a
Validation Master Plan (VMP). Before
you get to this stage consider all the
critical parameters that may be affected
and impact product quality.
Validation usually involves:
 Installation Qualification, which is
testing to verify that the equipment is
installed correctly
 Operational Qualification, which is
testing to verify that the equipment
operates correctly
 Performance Qualification, which is
testing to verify that product can be
consistently be produced to
specification.
A protocol describing each test and the
acceptance criteria should be prepared, and
once the testing is complete, a report
written that is called process validation
report (PVR).
33 Page 30-37 © MAT Journals 2019. All Rights Reserved
Volume 1 Issue 1
Change Control
Change control means if there is any
change in process, method or
specifications change (Finished product
and shelf life). If any correction in
procedure or wrongly something written
then with change control we can correct
that. After change control approve we can
continue with new methods, procedures
and specifications.
A change control system should be in
place to document all changes to facilities,
equipment, or processes that may have an
impact on product quality [6].
Write Good Procedure and Follow
Them
Think about what happens in a workplace
if written procedures are not available.
People depend on longer-term employees
to tell them how to do things and then do
their job from memory. This is fine for a
companies who making garden pots, but
not so respectable when the products you
are making can cause decease. In the food,
drug and medical device industry it’s
serious that good procedures are in place
to ensure a precise and constant
performance; it’s an essential part of GMP.
Procedures must be clear, summarizing,
and reasonable. Some companies hiring
consultants for technical writing. Unlike
permanent employees they know how to
write good procedures. Having an
autonomous party reviewing your
procedures also leads to process
developments.
Documentation Requirements
The following documents mentioned
further are typical in the food, drug, and
medical device industry:-
1. Specifications: These detail the
requirements with which products and
materials have to conform, i.e. they
serve as a basis of quality evaluation
2. Operating Instructions: These detail
material and equipment requirements
and describe the steps to complete a
task
 Journal of Pharma and Drug Regulatory Affairs
3. Operating Procedures: These give
direction for performing certain tasks
and provide higher-level instruction
than operating instructions.
4. Records: These provide a history of
each batch and provide a mechanism to
check that you are following operating
procedures and instructions.
Writing Good Procedures
Plan the task before you begin writing the
procedure. Generate a brief breakdown of
the important steps and key points related
to the task; a flow chart is a useful tool.
Remember that people don’t usually read
processes from start to end; they have a
habit of to scan the document for key
words. It’s better to break the procedure
into portions and use like; Headings,
tables, bullet points and diagrams. This
will help to understand and follow the
procedure easily. When writing procedures
try to visualise the person who going to
use these. Write in language they will
understand and don’t include too much or
too little information. You can increase the
readability of your procedures by using
simple sentences and by writing in a
conversational style. It is a GMP
requirement to frequently review
documentation to ensure that it’s up to
date. Most companies have a three-year
review cycle for their documents however
this can be set according to the possibility
of change in the procedure that the
document relates to.
Following Procedures
It’s all very well to have great written
processes in place but to certify a
controlled and consistent performance they
need to be followed; it’s a GMP requisite.
Frequently, the steps described in a written
procedure may not appear to be the most
efficient way of working. Taking shortcuts
may save time or make the task easier, but
you should never diverge from a written
procedure without the approval of a
manager or the Quality Division [7].
34 Page 30-37 © MAT Journals 2019. All Rights Reserved
Volume 1 Issue 1
There are two main reasons for this:
1. Many shortcuts may create pitfalls that
can be costly in the end.
2. Each step in a procedure has been
included for a purpose.
Even though the sense of a particular step
may not be directly apparent, it may be
there as a check for another stage of the
process. Ideas for improvement should
always be encouraged but don’t change
procedures without assessing the impact
on the entire process.
Identify Who Does What
All employees should clearly understand
what they have to do each day. It avoids
misunderstandings and minimises the risk
to product quality. [8]
There must be a job description for each
role to define:
1. job title
2. job objective
3. duties and responsibilities
4. Skill requirements.
There should be no gaps or overlaps in
responsibilities. Create an organisational
chart and display it on the intranet or a
local notice board. This way everyone in
the organisation can see who does what.
Some areas that are vulnerable to overlap
include: cleaning, validation and
calibration. When preparing procedures for
these areas carefully consider and define
the responsibilities. It’s also vital that
employees are trained to undertake a task
that they are assigned responsibility too.
Keep Good Records
Good records empower you to track all
activities those are performed during the
manufacturing of batch from the receiving
of raw materials, to the final product
release; they provide a history of the batch
and its supply. [9] It is a vital part of GMP
to keep truthful records because this will
help during an audit; it also helps to
convey that you are following the written
 Journal of Pharma and Drug Regulatory Affairs
procedures. It also reveals that procedures
are known and under control.
GOOD RECORD KEEPING
Follow the below mentioned guidelines
to ensure that good record keeping is
part of your everyday culture:
Record all needed information instantly
upon accomplishment of a task. Never
trust your memory or write results on loose
pieces of paper. Write your name with
legibly ink. Remember that by signing
records you are verifying that the record is
accurate and that you have done the task as
per the well-defined procedure. Its
necessary to draw a single line through any
mistakes, and initial and date the
correction. Include a reason for the
correction at the bottom of the page.
Retention Requirements
You must keep records for every phase of
the manufacturing process. Some required
records include:
a. Product master records
b. Batch manufacturing records
c. Batch Packing records
d. Material / component control records
e. Employees records
f. Training records
g. Equipment log books
h. Cleaning log books
If you follow these guidelines, you will
easily be able to examine each step of
the manufacturing process should you
need to [9].
Train and Develop Staff
To meet GMP necessities it’s essential to
have the right people to do the precise job.
It is very important that employees have
the abilities and awareness to complete
their job [10].
Training
It is our responsibility to provide training
for all employees, whose duties take them
into production areas or laboratories, and
whose activities can affect the quality of
the product. This includes basic training on
35 Page 30-37 © MAT Journals 2019. All Rights Reserved
Volume 1 Issue 1
the theory and practice of GMP as well as
specific training related to their job profile.
Sometimes it’s unavoidable to take an
unexperienced visitor into a production
area. If this happens, then it is our
responsibility to provide them with some
information in advance, mainly relating to
personal hygiene, and closely supervise
them at all times. It is also essential to
confirm that training requirements are
highlighted as part of the change control
system. Employees must know how to use
newly installed piece of equipment. It is
important to check that training is
complete during validation or add it as a
separate change control task. The same
process will also apply for any update to
procedures or instructions.
Demonstrating Job Competence
Employees must demonstrate their job
ability every day by manufacturing quality
products in a safe and well-organized
manner. Good manufacturing Companies
need people who know how to do the job
right the first time, every time. Annual
performance reviews (APR) are also a
prodigious technique to formally discuss
an employee’s development and
performance. It is a good way to review,
what the employee has accomplished and
to identify any gaps or areas for further
progress.
Practice Good Hygiene
Personnel hygiene plays a vital role in any
manufacturing company. It is not just
putting sanitization program, so with that
you can reduce contamination. Develop a
program to meet the standards of
cleanliness necessary for the product. The
fight against contamination is a constant
battle and is one that requires the attention
of every single employee, every day [11].
Keep these practices in mind:
a. Always practice good personal hygiene
by washing your hands and wearing
the required protective garments.
 Journal of Pharma and Drug Regulatory Affairs
b. Inform your supervisor if you are ill;
you may not be allowed to enter the
manufacturing area until you are well
again.
c. Minimise contact with product or
product contact surfaces and
equipment.
d. Never eat, drink, smoke or chew in
manufacturing areas.
e. Always follow cleaning and sanitation
procedures.
f. Report any condition that may cause
product contamination.
Following these points nothing more than
common sense and is your best defence to
reduce the risk of product contamination.
To be necessary to aware the staff against
the importance of washing their hands
after toileting, ask the microbiology
department to take fingerprint samples
from each operator after they have washed
their hands.
Maintain Facilities and Equipment
It is necessary to have a maintenance
schedule for facilities and equipment.
Consistent equipment maintenance averts
equipment breakdowns, which can be
costly. It also helps to reduce the risk of
contamination and maintains the ‘validated
state’ of the facility or equipment.
Sometimes an unexpected event may
affect the facility or equipment and under
such circumstances, you need to carry out
repairs immediately. [12] You should have
written processes for all planned and
emergency maintenance. These should
detail who does the work, the tasks
involved, and define any lubricants,
coolants, cleaning agents etc. required. It’s
also a GMP requirement to have a
maintenance schedule in place with the
frequency determined by the criticality of
the equipment.
Maintenance Records
GMP requires you to keep accurate
records relating to maintenance activities.
Use equipment logs to record information
such as:
1. when the equipment was last used
2. what is was used for
36 Page 30-37 © MAT Journals 2019. All Rights Reserved
Volume 1 Issue 1
3. when it was cleaned
4. when it was last inspected or repaired
5. When it was last calibrated.
Regularly walk around the plant and check
all the calibration stickers you can see. If
they are out of date then your maintenance
process is not being controlled properly.
Design Quality into the Whole Product
Lifecycle
By working in the, drug, and medical
device industry you know that the health
and safety of the customer depends on the
quality of the product. The Quality control
department can only inspect for quality so
it’s critical that you build quality into the
product lifecycle. Every step in the product
lifecycle requires effective controls to
assure product quality. Here are four
critical areas:
Controlling Components
It is very important step to check all
materials and components when they enter
the plant to ensure they meet the well-
defined specifications. Identify
components and store them in a quarantine
area for sampling and testing. All materials
and components must be approved prior to
release for manufacturing, or if rejected,
they must be identified and stored in a
secure area to prevent accidental use [13].
Controlling the Manufacturing Process
Establish records and procedures to ensure
that employees perform the same job every
time. Each product must have:
1. A master record that outlines the
specifications and manufacturing
procedures.
2. Individual batch or history records to
document conformance to the master
record.
3. Written schedules and procedures for
cleaning and maintaining the
equipment and areas.
Packaging and Labelling Controls
Packaging and labelling are the areas
where the higher chances of mix-ups and
errors occur. To reduce this, assign a batch
 Journal of Pharma and Drug Regulatory Affairs
or lot number to each product. Before a
new batch or lot is processed, inspect
packaging and labelling areas to ensure
that it contains no material from a old
batch. Follow all the procedures and
carefully document your work.
Holding and Distribution Controls
The company must have controls against
contamination, mix-up, and errors. There
must be separate areas for quarantine and
finished product testing. It is necessary to
prepare procedures for handling and
storage of products and distribution
records to keep traceability of the
shipments.
Perform Regular Audits
Audits must be conducted to evaluate
whether you are following the GMP
guidelines. External bodies such as the
Food and Drug Administration (USFDA)
or the Therapeutic Goods Association
(TGA), Australia will conduct these audits
[14]. It is important to carry out in-house
audits, or self-inspections, to ensure GMP
compliance. It’s a good practice to
undertake a self-audit a few times a year
and to target different manufacturing areas
and departments each time.
CONCLUSION
From this review, we conclude that GMP
has the purpose to primarily eliminate any
risks which may affect the process of
pharmaceutical production. It is necessary
to follow GMP guidelines in every single
step of drug discovery and development,
postulates production, control operations
and includes the use of systems, starting
materials, active substances, equipment,
sanitation of premises, facilities and
production plants. However, in order to
ensure high rate of effectiveness, it is
necessary to carry out internal audits also.
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Cite this article as:
Vijay Kumar, Meenu Bist, Arti Banyal,
& Kirti Patial. (2019). Golden Rules of
Good Manufacturing Practice (GMP).
Journal of Pharma and Drug
Regulatory Affairs, 1(1), 30–37.
http://doi.org/10.5281/zenodo.2575336