Introduction to Quality Control
PHARMACEUTICAL ANALYSIS 2
(Instrumental Methods of Analysis)
TOPIC 1: INTRODUCTION TO
QUALITY CONTROL
2nd Semester, SY 2023 - 2024 PRELIM - Pharmaceutical Analysis 2 (PHAN212)
Learning Outcomes:
At the end of this unit, the students are expected to:
✔ Define and discuss pharmaceutical analysis and its importance
in the pharmaceutical industry.
✔ Recognize the ICH Quality guidelines.
✔ Differentiate the different types of errors in analysis.
✔ Differentiate accuracy from precision.
✔ Discuss the validation of analytical procedure.
✔ Define quality control, quality assurance and other related
terms.
✔ Describe the quality control organizational chart and the QC
system.
✔ Differentiate the QC divisions by their functions.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
Unit Outline:
• Pharmaceutical Analysis
• Errors in analysis
• Accuracy and Precision
• Validation of analytical procedure
• Introduction to quality control
• Quality Control System
• Total Quality Management
• Accreditation (ISO)
• Organization of Quality Control
• Common divisions in a manufacturing firm
• Control functions
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
Checklist
Attend Onsite Lecture
Duration: 3 hours
✔ Read course and unit outcomes.
✔ Read study guide prior to onsite
attendance.
✔ Read required learning resources.
✔ Proactively participate in onsite
discussions.
✔ Answer and submit course unit
tasks.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
The development of the
pharmaceuticals brought a revolution
in human health.
These pharmaceuticals
would serve their intent only
if they are free from
impurities and are
administered in an
appropriate amount.
SOURCE: Masoom Raza Siddiqui, Zeid A. AlOthman, Nafisur Rahman, Analytical techniques in pharmaceutical analysis: A review , Arabian Journal of Chemistry, Volume 10, Supplement 1, 2017, Pages S1409 - S1421,
ISSN 1878 - 5352,
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
To make drugs serve their purpose, various chemical and
instrumental methods were developed at regular intervals
which are involved in the estimation of drugs.
SOURCE: Masoom Raza Siddiqui, Zeid A. AlOthman, Nafisur Rahman, Analytical techniques in pharmaceutical analysis: A review , Arabian Journal of Chemistry, Volume 10, Supplement 1, 2017, Pages S1409 - S1421,
ISSN 1878 - 5352,
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
These pharmaceuticals may develop impurities at various stages of
their development, transportation and storage which makes the
pharmaceutical risky to be administered thus they must be
detected and quantitated.
SOURCE: Masoom Raza Siddiqui, Zeid A. AlOthman, Nafisur Rahman, Analytical techniques in pharmaceutical analysis: A review , Arabian Journal of Chemistry, Volume 10, Supplement 1, 2017, Pages S1409 - S1421,
ISSN 1878 - 5352,
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
For this, analytical instrumentation
and methods play an important
role.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
What is
Pharmaceutical
Analysis ?
• It is a branch of practical chemistry that
involves a series of process for
identification, determination,
quantification and purification of a
substance, separation of the
components of a solution or mixture, or
determination of structure of chemical
compounds .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
SOURCE: Watson, David G., Pharmaceutical Analysis: A Textbook for Pharmacy Students & Pharmaceutical Chemist, 4th ed. 2017. Elsevier. ISBN: 978 - 0 - 7020 - 7029 - 7
Pg. 2
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
International
Conference on
Harmonisation (ICH)
• International Conference on Harmonisation of Technical
Requirements For Registration of Pharmaceuticals for
Human Use
• Addressed the requirements for control of the quality of
methods of analysis ( validation ) .
• Initiated in Brussels in 1990
• Representatives of regulatory agencies and industry
associations of Europe, Japan and the USA .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
International
Conference on
Harmonisation (ICH)
PURPOSE : to standardise the requirements for medicines
regulation throughout the world .
Most important analytical procedures that require validation are:
• Identification tests
• Quantitative tests for impurities
• Limit tests for the control of impurities
• Quantitative tests of the active moiety in samples of drug
substance or drug product or other selected component(s) in the
drug product.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
With such large amounts of money being spent on
analytical quality control, great importance must be
placed on providing accurate and precise analyses.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
2 TYPES OF CHEMICAL ANALYSIS
Quantitative
Qualitative analysis analysis
• is performed to establish • techniques are mainly used to
composition of natural/synthetic quantify any compound or
substances . substance in the sample .
Examples : Examples :
• Distillation, extraction, color • Titration, gravimetric analysis,
change, chromatography, etc . etc .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
TYPES OF ERRORS
ERROR
- may be defined as a deviation from the absolute value or
from the true average of a large number of results .
1 ) Determinate or constant 2 ) Indeterminate errors
- are those that, although - caused by uncontrollable
sometimes unsuspected, may be fluctuations in variables that
avoided or determined and affect experimental results
corrected once they are
uncovered .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ERRORS IN ANALYSIS
1 . Gross Error
- takes into account human oversight and other mistakes
while reading, recording, and readings .
- easily recognized since they involve a major breakdown in
the analytical process such as :
• samples being spilt,
• wrong dilutions being prepared or
• instruments breaking down or being used in the wrong way .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ERRORS IN ANALYSIS
2 . Random Error
- the random errors are those errors, which occur irregularly
and hence are random .
- these can arise due to random and unpredictable
fluctuations in experimental conditions
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ERRORS IN ANALYSIS
3 . Systematic Error
- ENVIRONMENTAL 🡪 arises in the measurement due to the effect of
the external conditions on the measurement .
• Examples : temperature, pressure, humidity
- OBSERVATIONAL 🡪 arise due to an individual’s bias, lack of proper
setting of the apparatus, or an individual’s carelessness in taking
observations .
- INSTRUMENTAL 🡪 arise due to faulty construction and calibration of
the measuring instruments .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ACCURACY and PRECISION
In an experiment, PRECISION is
defined as the reproducibility of
results and measurements,
while ACCURACY refers to how
close the value is to the actual or
true value .
It may be that the results are both
accurate and precise, neither or
accurate but not precise or not
accurate but precise .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ACCURACY and PRECISION
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
SOURCE: Watson, David G., Pharmaceutical Analysis: A Textbook for Pharmacy Students & Pharmaceutical Chemist, 4th ed. 2017. Elsevier. ISBN: 978 - 0 - 7020 - 7029 - 7
Pg. 5
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
VALIDATION OF ANALYTICAL
PROCEDURE
The Analytical Procedure
- provides an exact description of how the analysis is carried out.
- It should describe in detail the steps necessary to perform each analytical test.
The full method should describe:
i. the quality and source of the reference standard for the
compound being analyzed
ii. the procedures used for preparing solutions of the reference
standard
iii. the quality of any reagents or solvents used in the assay and their
method of preparation
iv. the procedures and settings used for the operation of any
equipment required in the assay
v. the methodology used for calibration of the assay and
methodology used for the processing of the sample prior to
analysis.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
“ QUALITY ”
• is the combination of attributes or
characteristics of a product which, when
compared to a standard, serves as a basis
for measuring the uniformity of the product
and determines its degree of acceptability .
“ CONTROL
”
• Refers to the measure or step that is used to
prevent or eliminate drugs risks /hazards to
make it safe & effective .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
QUALITY CONTROL
• Is a tool, which gives the assurance
that a product conforms to standards
and specifications through the system
of inspection, analysis and action .
• The operational techniques and
activities used to fulfill requirements
for quality,
• To assure safe, pure and effective
drug product .
• Quality is everybody’s business .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
QUALITY ASSURANCE
• The sum total of the organized
activities performed with the
intent to ensure that all active
pharmaceutical ingredients are of
the quality required for their
intended use .
• All the planned and systematic
activities implemented in a quality
system so that quality
requirements for a product or
service will be fulfilled (American
Society for Quality, ASQ) .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
QA QC
Set of preventive Detection activities
activities
Ensures that standards are Defines the standards to be
followed at every step followed
Process - oriented Product - oriented
Focus on defect Focus on defect
prevention identification
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
QUALITY
CONTROL
SYSTEM
- established at the conception of a
new product, during production of
the batch, and during distribution of
the commercial package .
- This system is a combination of
those administrative and technical
procedures, which must be used to
produce and deliver a safe, pure,
and effective product to the end
user .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
QUALITY
CONTROL
SYSTEM
Guarantees that the drug product is :
✔ Free from impurities
✔ Physically and chemically stable .
✔ Having the amount of active ingredient as stated on the
label .
✔ Providing an optimal release of active ingredients when
the drug product is administered .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
QUALITY
CONTROL
SYSTEM
BENEFITS :
1 . The system minimizes or eliminates the risk of
marketing unsafe products
2 . It guarantees conformance to regulatory
requirements
3 . It guarantees product efficacy
4 . It reduces operating costs
5 . It reduces operating losses
6 . It produces higher employee morale
7 . It motivates the pharmaceutical/medical professions
to sell or prescribe the product
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
• a process inside an organization with the aim to improve
its performance by learning about good practices for
primary and/or support processes through looking at
those processes in other, better - performing
organizations, building on evaluation of relevant
performances in own and other organizations .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
TOTAL QUALITY
MANAGEMENT (TQM)
• A management approach for an
organization, centered on quality,
based on the participation of all
its members and aiming at long -
term success through customer
satisfaction, and benefits to all
members of the organization and
to society .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
Primary
Elements of
Total Quality
Management
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ACCREDITATION
• Quality assessment with an
attached judgment that the
evaluated unit (program or
organization) is good enough to
have the right to exist in a
particular system .
• Often, accreditation is given for a
limited period of time (usually
between 4 and 10 years) and is
repeated in a cyclical process at
the end of the period of validity .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
• Popular name for International Organization For
Standardization .
• A voluntary, non - treaty federation of standards setting bodies
of some 130 countries . Founded in 1946 - 47 in Geneva as a UN
agency, it promotes development of standardization and
related activities to facilitate international trade in goods and
services, and cooperation on economic, intellectual, scientific,
and technological aspects
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ORGANIZATION OF QUALITY
CONTROL
Part of a manufacturing firm is a defined
organization .
⮚ functions and responsibilities
⮚ effective coordination
⮚ all activities are performed towards the production
of a product of the highest standard and at the
lowest cost .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
COMMON DIVISIONS IN A
MANUFACTURING FIRM:
1. Finance
2. Production
3. Quality Assurance (Quality Control)
4. Marketing (optional in a third - party contract
manufacturer)
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
CONTROL FUNCTIONS:
Control functions may appear varied and never quite
identical in any two companies by basically, these
functions can be classified into four categories :
1. Analysis Function
2. Monitor Function
3. Record Review and Release Function
4. Audit Function.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
1. Analysis Function
⮚ To assure the acceptability of a product .
⮚ Conducts testing on the raw materials and packaging
components and bulk products :
during processing
after packaging
after distribution
⮚ Product against which a complaint is registered may also be
analyzed to determine its validity and the cause of the reported
deficiency .
⮚ Appropriate steps may then be taken to prevent recurrence of
similar problem .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
2. Monitor Function
⮚ To sample and examine materials
⮚ To assure that even though production personnel have the
primary responsibility for control over their processes, these
processes are maintained and that any deviation from specified
requirements is reported .
⮚ To conduct environmental monitoring .
⮚ To control the microbial and particulate matter content of
environmental air in areas where pharmaceuticals such as
parenterals are processed .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
3. Record Review and
Release Function
⮚ To determine accuracy and
completeness of all records
generated during the course of
production prior to the release
of each lot of finished product
to the market .
⮚ A detailed checklist is
frequently employed by the
reviewer .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
4. Audit Function
⮚ To train employees to comply with
the SOP’s and to understand why
and how these SOPs are to be
followed .
⮚ The quality audit is designed to
detect areas where the established
SOPs are not being followed and to
report these findings to the
supervisor for appropriate action .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
QUALITY CONTROL
DIVISIONS
A. Materials Inspection Section
B. Analytical Laboratory
C. Biological Testing Laboratory
D. Quality Coordination Office
E. Specification and Analytical
Development
Figure 1: shows a typical organization within the quality control department.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
A. Materials Inspection Section
Inspectors are alert individuals
who had experience and who are
familiar with the physical
characteristics of the materials they
sample and are well versed in
sampling techniques .
Inspection stations are placed in the area of operation,
warehouse, manufacturing and packaging areas .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
A. Materials Inspection Section
The functions of this section are:
1. To sample and examine all raw materials received.
2. To sample and conduct physical tests on:
• All shipments of packaging materials
• All manufacturing, filling and packaging operations
3. To maintain periodic examination on the quality of
inventories throughout all phases of storage, shipping
and distribution .
4. To perform an audit which is independent of the
work done byproduction personnel
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
B. Analytical Laboratory
• The analytical laboratory should be in an
accessible area and protected from noise and
vibration common to manufacturing
operations .
• This division performs all qualitative and
quantitative analysis on raw materials,
intermediate and finished products .
⮚ The analysts should know the usual gravimetric and
volumetric analysis .
⮚ They should be skillful in handling instruments
(Spectrometry, Aqueous and Non - aqueous titrimetry,
Chromatography)
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
C. Biological Testing
Laboratory
⮚ The staff in a biological testing laboratory should be well
trained and experienced in both simple and complex
microbiological procedures and biological interactions .
⮚ A veterinarian is recommended to supervise the care and
maintenance of the various species of animals used in the
tests .
⮚ The area :
✔ should be provided with particular rooms where
biological tests are conducted .
✔ should be protected against noise specifically the
areas where animals are used .
✔ should be provided with an animal house so maintained
and is a separate unit from the main laboratory, if
necessary .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
C. Biological Testing
Laboratory
⮚ The staff in a biological testing laboratory should be well
trained and experienced in both simple and complex
microbiological procedures and biological interactions .
⮚ A veterinarian is recommended to supervise the care and
maintenance of the various species of animals used in the
tests .
⮚ The area :
✔ should be provided with particular rooms where
biological tests are conducted .
✔ should be protected against noise specifically the
areas where animals are used .
✔ should be provided with an animal house so maintained
and is a separate unit from the main laboratory, if
necessary .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
C. Biological Testing
Laboratory
The functions of this division are :
1. To perform and evaluate
microbiological and pharmacological
assays, sterility, pyrogen and
bacteriological tests, irritation, safety
or acute toxicity tests .
2 . To conduct environmental monitoring .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
D. Specification and Analytical
Development
This section should have firm background not only in the
principles of quality control and analytical procedures but also in
manufacturing, research, product development and in statistics in
order to perform the following functions :
1. To coordinate with research, product development,
production, sales and management towards improvement
of a product.
1. To establish specifications for raw and packaging materials.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
D. Specification and Analytical
Development
Other functions of this division are :
3 . To validate existing and tentative
procedures of testing .
4 . To establish specifications based on
validated procedures .
5 . To develop new assay methods for in -
house use .
6 . To develop and improve
specifications for quality characteristics
of the final product being manufactured .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
E. Quality Coordination Office
⮚ This section should be accessible to all
manufacturing and packaging operations
since documentation is its main
responsibility .
⮚ The functions of this section are :
1. To maintain and store records that represent
the history of the batch from start to finish .
These records include the batch and master
formula records, raw material analytical
records, printed and packaging material
inspection reports and retention files .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
E. Quality Coordination Office
Other functions of this division are:
2 . To be able to furnish data that will aid in analyzing product performance
in the market . These documents are the stability studies and returned
goods reports .
3 . To investigate customer complaints or inquiries on product quality and
to forward the results of the investigations in the form of technical
reports to the sales organization .
4 . To call the attention of the appropriate development group any aspect
that provides a basis for improvement of a product for consideration and
action .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
E. Quality Coordination Office
Other functions of this division are:
5 . To provide data that give scientific and legal status, i . e . , data
generated from the use of recognized standard compendia . This
is essentially a function of the distribution section or warehouse .
6 . To maintain and develop SOP’s .
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
OTHER AREAS IN MANUFACTURING
FIRM THAT A PHARMACIST CAN WORK:
✔ Marketing
✔ Medical Affairs
✔ Medical Liaisons
✔ Research and Development
✔ Production
✔ Legal or Regulatory Affairs
✔ Administration
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
1. Define cGMP
2. Define and explain quality control in pharmacy.
3. Differentiate QA from QC
4. What is the importance of quality in pharmaceutical
products?
5. Define TQM.
6. What are the control functions in quality control?
7. Enumerate the benefits of QCS.
8. What is the importance of accreditation in an institution?
9. What is an SOP? Give its importance in manufacturing
procedures.
10. TRUE OR FALSE. Inspection stations are placed in the
area of operation, warehouse, manufacturing and
packaging areas.
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
Watch this video:
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OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
References:
Jenkins, Glenn L, Jenkins Quantitative Pharmaceutical
Chemistry, N . Y, N . Y . : Mc Graw, Latest Edition
Watson, David G . , Pharmaceutical Analysis : A
Textbook for Pharmacy Students & Pharmaceutical
Chemist, 4 th ed . 2017 . Elsevier . ISBN : 978 - 0 - 7020 -
7029 - 7
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
Activities for next meeting:
1 . Quiz No . 1 : Introduction to Quality Control
2 . Assignment No . 1 : Quality Control
3 . Lecture Topic : Quality Control
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
THANK YOU!
Any questions?
You can find me at:
2nd Semester, SY 2023 - 2024 PRELIM - Pharmaceutical Analysis 2 (PHAN212)
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ERRORS IN ANALYSIS
2. Random Error
- the random errors are those errors, which occur irregularly
and hence are random.
- these can arise due to random and unpredictable
fluctuations in experimental conditions
OLFU - College of Pharmacy PRELIM - Pharmaceutical Analysis 2 (PHAN212)
ERRORS IN ANALYSIS
3. Systematic Error
- ENVIRONMENTAL 🡪 arises in the measurement due to the effect of
the external conditions on the measurement.
• Examples: temperature, pressure, humidity
- OBSERVATIONAL 🡪 arise due to an individual’s bias, lack of proper
setting of the apparatus, or an individual’s carelessness in taking
observations.
- INSTRUMENTAL 🡪 arise due to faulty construction and calibration of
the measuring instruments.
ACCURACY and PRECISION
In an experiment, PRECISION is
defined as the reproducibility of
results and measurements,
while ACCURACY refers to how
close the value is to the actual or
true value.
It may be that the results are both
accurate and precise, neither or
accurate but not precise or not
accurate but precise.