Module 1 Medicinal Products No Assessment

Module 1 - Medicinal Products
1. GMP01
1.1 Module 1 Introduction to GMP 1 - Medicinal Products
Notes:
1.2 About this module
Notes:
Published by Articulate® Storyline www.articulate.com

1.3 Objectives
Notes:
1.4 Definitions
Notes:

1.5 Quick quiz 1
(Matching Drag-and-Drop, 10 points, unlimited attempts permitted)
Correct Choice
Good Laboratory Practice GLP
Good Automated Manufacturing Practice GAMP
Current Good manufacturing Practice cGMP
A casual term used as an abstract from a GxP

specific quality guideline
Feedback when correct:
That's right! Remember, the Quick Quiz is not part of your final score. Use these questions to
check your knowledge before attempting the Final Assessment.
Feedback when incorrect:
You did not select the correct response. Remember, the Quick Quiz is not part of your final score.
Use these questions to check your knowledge before attempting the Final Assessment.
Notes:

Correct (Slide Layer)
Incorrect (Slide Layer)

Try Again (Slide Layer)
1.6 Who regulates GMP rules?
Notes:

1.7 Risk based approach
Notes:
1.8 What is GMP?
Notes:

1.9 What is GMP cont...
Notes:
1.10 Overview of quality assurance
Notes:

1.11 Manufacturing
Production and control operations should be clearly specified
cGMP compliant procedures should be made for the manufacture, supply,

and use of the correct starting and packaging materials
All necessary controls on intermediate products, and any other in-process

controls and validations must be carried out

1.12 Finished product
The finished product should be correctly processed and checked, according

to the defined procedures
Products should not be sold or supplied before an authorized person has

certified that each production batch has appropriate quality
Products should be stored, distributed and subsequently handled so that

quality is maintained throughout their shelf life

1.13 Self-inspection
There should be a procedure for self-inspection which regularly appraises

the effectiveness and applicability of the quality assurance system
1.14 Responsibilities
Managerial responsibilities should be clearly specified and documented

1.15 What does the QC department do?
Notes:
1.16 Foundations of quality control
Notes:

Foundations (Slide Layer)
Procedures (Slide Layer)
Testing (Slide Layer)

Starting materials (Slide Layer)
Records (Slide Layer)
Finished products (Slide Layer)

Release (Slide Layer)
Sampling (Slide Layer)

1.17 GMP and the law
Notes:
1.18 GMP code

1.19 Quality management
(click on each tab to see relevant information)
Intro (Slide Layer)

International standards (Slide Layer)
Governance (Slide Layer)

1.20 Product quality review
Notes:
1.21 Quality risk management
Notes:
1.22 Quick quiz 2
(Multiple Choice, 10 points, 1 attempt permitted)

Correct Choice
A) There were a large number of QC samples awaiting analysis, some dated from
previous weeks.
B) The QA manager had a large pile of documents needing to be approved and

signed.
C) The receiving area in the warehouse was crowded with goods, waiting to be
booked in.
X D) All of the above.
E) None of the above.
That's right! All of these situations may indicate inadequate staffing levels. They may also
indicate a need to review procedures for efficiency!
The correct answer was 'D) all of the above'. All of these situations may indicate inadequate
staffing levels. They may also indicate a need to review procedures for efficiency!
Notes:


1.23 Personnel
QA systems and adherence to GMP guidelines relies exclusively on people
Notes:

1.24 Having the right number of personnel
The GMP guidelines recognize how critical people are to ensuring product
quality.
To meet GMP requirements, it's essential to have:
the right number of people, and
that they have the right qualifications and experience to do the job
To meet these requirements it's essential that what 'right' means has
been identified for every function and process.

1.25 Personnel training
The GMP guidelines recognize that training is very important.
During an audit, an auditor might ask to see:
competency matrices – identifying the skills and training required for each
role in the organization
training records to show when someone was trained and what they were
trained on
These records must be kept for everyone who works in a GMP area,
including:
contractors
cleaners
supplier’s representatives who visit frequently, such as equipment service

engineers

1.26 Contractors
Contractors, such as salespeople and cleaners, are a common source of

non-compliance
It is critical that contracting companies supply only GMP trained

personnel to work in production areas
Untrained staff, filling in for someone who is away, will not understand
how much they can impact product quality
Example:
A piping contractor, installing a filter housing, unknowingly left waste

materials in the water system. The system supplied sterile water for the
manufacture of injectable drugs. However, the water system would
contain an on-line TOC or a conductivity meter to detect and dump un-
sterile water before it gets into the distribution loop. Also, QC tests on the
water would detect such a problem before any drugs were released.

1.27 The GMP essentials
Because personnel are such a critical part of GMP, the GMP guidelines
specify that:
all staff must have the education, experience, and training to perform
their duties
documentary evidence of this must be maintained, including resumes,

professional qualifications, and training records
an organizational chart is mandatory (and can be subject to auditing)
the responsibilities of each position must be defined and documented
the head of production and quality control must be independent from

each other
good personal hygiene is critical – staff must be trained and equipped to

ensure good personal hygiene

1.28 Good hygiene
It is critical that staff reduce the risk of introducing infections and bacteria
into the area where products are being made. This includes:
reporting open sores or any illness to their supervisor
appropriate washing of their hands
no eating, drinking, chewing or smoking, and no storage of food, drink,

smoking materials or personal medication in production and storage
areas
all personnel entering the manufacturing areas should wear clothing

appropriate for the area and the operations to be carried out
unhygienic practices within the manufacturing areas or other areas where

product may be adversely affected should be forbidden
Notes:

1.29 Manufacturing equipment
Ensure manufacturing equipment:
is designed, located, and maintained to suit its intended use
is designed so that it can be easily and thoroughly cleaned
has procedures for how and when to clean each piece of equipment that
can impact product quality
has procedures that clearly state who is responsible for the cleaning and
have cleaning records
Notes:

1.30 Design
The GMP guidelines ensure that manufacturing facilities are designed to

minimize product contamination and mix-ups.
For example:
Using coved ceilings, floors and corners within manufacturing areas

minimizes debris and thus bacterial accumulation
Machines should be located to allow easy access for regular maintenance
Dedicated lines or facilities i.e. physical separation, should be used when

manufacturing products that have high cross-contamination potential

1.31 Equipment placement
Example:
In one company, the maintenance schedule for a piece of production

equipment required the oil to be changed and 55 sensor points to be
checked every 3 months.
During an audit, the auditor discovered that this was only being done
during the annual shutdown period.
Why?
The machine had been installed very close to the wall. The maintenance
engineer could only access the back of the machine when it was moved
away from the wall. This could only be done during the annual shutdown,
when a mobile crane was available to lift the machine.

1.32 Premises design
Modern warehouses at commercial manufacturing sites are totally

automated and their status and location are controlled by an enterprise
management system. A modern warehouse is divided into a receiving
area and a storage area in which there are specific areas to store rejected,
recalled or returned materials or products. Optimally, rejected product
would be kept in a caged area.
Again, the aim is to prevent contamination and mix-ups. It would be very

easy for a batch of recalled products to be accidentally shipped out to
customers if the recalled products were not kept physically separate from
the final products in the warehouse.
QC labs are separate from production areas.

1.33 Facilities
The facilities should be designed and equipped to prevent entry of pests or

animals
Steps should be taken to prevent entry of unauthorized personnel
Where special storage conditions are required (e.g., temperature,

humidity) these conditions should be provided, checked and monitored
and also validated
(e.g., temperature mapping) on a periodic basis

1.34 Premises and equipment

1.35 Data collecting equipment
The GMP guidelines require equipment to be fit for purpose. If the

weighing step is critical to product quality, then equipment should be used
that will ensure an appropriate level of accuracy.
A good practice is to display the usable range on all scales. As a rule of

thumb, the minimum weight that the scale interval can introduce should
be less than a 0.5% error.
This means if a scale can weigh up to 1000g and the scale interval is to
0.1g, then the minimum of 20g may be weighed on that scale.
If the scale rounded to say 0.5g intervals, then the minimum permissible
weight should be 100g.
The above is only a 'rule of thumb' - all scales should be validated for their
intended purpose.

1.36 Scenario
Notes:
1.37 Quick quiz 3
Correct Choice
A) She should have repeated the measurements three times and calculated the
average to ensure the result was accurate.

X B) She should have requested scales that had a range from 0-1kg and displayed
x.xg.
C) She should have held 10 products to make the weight more appropriate for the
scale, dividing the weight difference by 10 to calculate the final weight of each
product.
That's right! You selected the correct response.
The correct answer is B. She should have requested scales that had a range from 0-1 kg and
displayed x.x g.

1.38 Documentation

Documentation (Slide Layer)
Documentation types (Slide Layer)
Equipment logbooks (Slide Layer)

Document control (Slide Layer)
Things that go wrong with documents (Slide Layer)
Document essentials (Slide Layer)

1.39 Quick quiz 4
Correct Choice
A) Development and production
B) Production and batch release
C) Distribution and development
X D) All of the above
That's right! You selected the correct response
The correct answer is D. Pharmaceutical manufacturers must have documented quality

procedures covering all of these processes.


1.40 Production
Intro (Slide Layer)

GMP (Slide Layer)
Containment (Slide Layer)

Personnel (Slide Layer)
Labeling (Slide Layer)
Process (Slide Layer)

1.41 Quality control
intro (Slide Layer)

QC is not confined to a lab (Slide Layer)
QC is at the core of every process (Slide Layer)
QC from start to finish (Slide Layer)

1.42 Contract manufacture
Notes:
1.43 Responsibilities – contract giver

1.44 Responsibilities – contract acceptor
The contract acceptor must have adequate premises and equipment,

knowledge and experience, and competent personnel to carry out
satisfactorily the work ordered by the contract giver.
The contract acceptor must ensure that all products or materials delivered
are suitable for their intended purpose.
The contract acceptor must not pass to a third party any of the work
entrusted under the contract without the contract giver’s prior evaluation
and approval of the arrangements.

1.45 Responsibilities
There must be a designated person responsible for handling the

complaints and deciding the measures to be taken.
Notes:
1.46 Defined procedures

1.47 Investigation
If a product defect is discovered or suspected in a batch, other batches

must be checked in order to determine whether they were also affected.
In particular, other batches which may contain reworks of a defective

batch must be investigated.
1.48 Record keeping

1.49 Traceability
Distribution records must:
be readily available
contain sufficient information on wholesalers and directly supplied

customers, including those for exported products and medical samples
1.50 Product reconciliation after a recall
1.51 Quick quiz 5

Correct Choice
X A) Recorded
B) Ignored unless there is a trend
C) Passed onto the appropriate department
D) Recalled immediately
That's right! All product complaints must be recorded and investigated thoroughly.
The correct answer is A. All product complaints must be recorded and investigated thoroughly.


1.52 Self-inspection
Notes:
1.53 The 10 Golden Rules

Facility design (Slide Layer)
Validations (Slide Layer)

Training and development (Slide Layer)
Good record keeping (Slide Layer)
Responsibilties (Slide Layer)

Hygiene (Slide Layer)
Maintenance (Slide Layer)
Quality (Slide Layer)

Audits (Slide Layer)
The 10 golden rules of GMP (Slide Layer)

1.54 Case study - hygiene & cleaning
1.55 Things that go wrong! - example one
Notes:
Despite the emphasis, strict procedures and training, things

sometime go wrong. These can be predictable, such as things that
go wrong as a result of failing to follow written procedures, or
unpredictable, as a result of contamination from an unexpected
source.
However, no matter what the root cause, such incidents are

avoidable. In the examples below the actions needed to avoid things
going wrong should be self-evident:

Example 1:
Frequent problems of contamination in a clean room by an organism

normally found in water and soil (dirt or earth). On investigation there
were three contributing factors to the root cause:
a.Operators walking out of the clean room wearing their
dedicated shoes and then walking back into the clean room
without cleaning the shoes or putting on clean overshoes
b.Inadequate clean up following frequent spillages
c.Inadequate and infrequent clean up of condensate from a
heat exchanger dripping onto the clean room floor
Lessons learned:
• Dedicated shoes are dedicated to a specific clean room suite

and to a specific operator. Operators need to understand
why they are wearing them and how contamination can be
spread on the feet!
• Spillage and leakage must be dealt with immediately, not just
at the end of the shift, or the day, or the week! This is not
routine cleaning.

1.56 Things that go wrong! - example two
Notes:
Example 2:
Following a fire alarm in the factory, the clean room operators assembled at the
fire assembly point in the parking lot still wearing their clean room gowns, since
the fire regulations require that everyone evacuates the building immediately and
does not stop for any reason! The gowns were not changed when the operators
returned to work because the gowning procedure only required a daily gown
change and did not cover fire evacuation. This resulted in high levels of
microbial contamination, which took a lot of cleaning and monitoring before it was
cleared. This demonstrated a lack of awareness of the purpose of the gowning.
Lesson learned:
Awareness of the concepts of hygiene and gowning and the problems that bad
practices can cause, is as important as completing the “how to” training.

1.57 Things that go wrong! - example three
Notes:
Example 3:
A clean room operator, involved in the manufacture of biological drug substances,

was also the owner of a small farm and a small dairy herd. He would come to
work each day after milking the cows. During the environmental monitoring of
the manufacturing areas, a resistant and unusual microorganism was found in
high numbers.
On investigation it was found that this organism is normally found on the udders
of cows!
There have also been examples of organisms that are typically found on dogs,
cats and horses!
Lessons learned:
• Personal hygiene for pharmaceutical personnel, both manufacturing

personnel and others who enter manufacturing areas, is important at all
times, not just at work!
• Removing street clothing and regular handwashing in production areas
are necessary

1.58 Case study - operator error
Notes:
Case Study - Operator Error
1.59 Description of problem
Notes:
This case study involves a semi-automated process for protein capture, which
involved taking the harvest from a cell culture process that involved protein
expression. The harvest was a typical process involving centrifugation to remove
the culture medium, lysis of the cells and capture of the protein that had been
expressed, using a capture chromatography column. Following capture, the

protein was eluted into an eluate tank and once the protein had been eluted from
the column, the column was cleaned with Sodium Hydroxide solution.
The Sodium Hydroxide was accidentally eluted into the eluate tank with the
protein solution and the entire batch was lost because the Sodium Hydroxide
solution caused hydrolysis and destroyed the protein.
It didn’t just happen once, but it happened twice before the company took
effective action!
1.60 How was this resolved?
Notes:
The automated system should have prevented this error, BUT, the automated
process was overridden by the operator. The root cause was determined to be
the operator, who was counselled and re-trained. However the retraining of the
operator was not sufficient because the same problem occurred again, this time
involving a different operator.
After the second incident the company introduced a fix in the software to prevent
such an operator intervention without a second operator checking. Was this fix
sufficient? The risk still remains because two operators, both with a vested

interest in taking a short cut, could still, together override the system and there is
a risk, albeit a much smaller risk, that both operators could make the same
mistake.
1.61 Lessons learned
Notes:
The main lesson learned was that while the primary root cause may have been
operator error, there was also a secondary root cause, which might also be
considered as the primary root cause and that is that the automation software
was not secure.
Operators may try to take short cuts to save time, but may not understand the
impact of their shortcuts. The automation was designed to prevent such an error
from occurring, but the flaw in the software design was that it could be overridden
by the operator. Even an override by two operators, is not completely secure.
Operators should not be allowed to override an automated process. Any

override should only be performed by someone with supervisor or administrator
rights and should only be performed under change control or as a planned
deviation (or as a temporary approved change to the process).

1.62 Final assessment

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Module 1 - Medicinal Products

1.1 Module 1 Introduction to GMP 1 - Medicinal Products

1.2 About this module

Published by Articulate® Storyline www.articulate.com

Published by Articulate® Storyline www.articulate.com

(Matching Drag-and-Drop, 10 points, unlimited attempts permitted)

Good Laboratory Practice GLP

Good Automated Manufacturing Practice GAMP

Current Good manufacturing Practice cGMP

A casual term used as an abstract from a GxP

Feedback when correct:

Feedback when incorrect:

Published by Articulate® Storyline www.articulate.com

Incorrect (Slide Layer)

Published by Articulate® Storyline www.articulate.com

1.6 Who regulates GMP rules?

Published by Articulate® Storyline www.articulate.com

1.8 What is GMP?

Published by Articulate® Storyline www.articulate.com

1.10 Overview of quality assurance

Published by Articulate® Storyline www.articulate.com

Production and control operations should be clearly specified

cGMP compliant procedures should be made for the manufacture, supply,

All necessary controls on intermediate products, and any other in-process

Published by Articulate® Storyline www.articulate.com

The finished product should be correctly processed and checked, according

Products should not be sold or supplied before an authorized person has

Products should be stored, distributed and subsequently handled so that

Published by Articulate® Storyline www.articulate.com

There should be a procedure for self-inspection which regularly appraises

Managerial responsibilities should be clearly specified and documented

Published by Articulate® Storyline www.articulate.com

1.16 Foundations of quality control

Published by Articulate® Storyline www.articulate.com

Procedures (Slide Layer)

Testing (Slide Layer)

Published by Articulate® Storyline www.articulate.com

Records (Slide Layer)

Finished products (Slide Layer)

Published by Articulate® Storyline www.articulate.com

Sampling (Slide Layer)

Published by Articulate® Storyline www.articulate.com

1.18 GMP code

Published by Articulate® Storyline www.articulate.com

(click on each tab to see relevant information)

Intro (Slide Layer)

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Governance (Slide Layer)

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1.21 Quality risk management

1.22 Quick quiz 2

(Multiple Choice, 10 points, 1 attempt permitted)

Published by Articulate® Storyline www.articulate.com

B) The QA manager had a large pile of documents needing to be approved and

X D) All of the above.

E) None of the above.

Feedback when correct:

Feedback when incorrect:

Published by Articulate® Storyline www.articulate.com

Incorrect (Slide Layer)

Published by Articulate® Storyline www.articulate.com

QA systems and adherence to GMP guidelines relies exclusively on people

Published by Articulate® Storyline www.articulate.com