INTRODUCTION TO PHARMACEUTICAL
ANALYSIS 2 AND QUALITY ASSURANCE
a. raw materials – or unprocessed
materials
b. defects – undesirable characteristics
of a product
c. sampling – the act of getting a
representative from the entire population
d. risk - a situation involving exposure to danger
What is quality?
Quality means differently to different people.
a. MARKETING
 quality means better performance, nicer
features, other improvements (sometimes
costly)
b. MANUFACTURING
 conforming to standards and “making it right
the first time”
c. The American Society for Quality
 “The totality of features and characteristics
of a product or service that bears on its ability
to satisfy implied or stated needs.”
Three Pillars of Drug Products:
1. Safety
2. Efficacy
3. Quality
Governing Bodies:
1. FDA – Food and Drug Administration
2. cGMP – current Good Manufacturing
Practices
The aspects of quality assurance.
QUALITY ASSURANCE vs. QUALITY CONTROL
QUALITY ASSURANCE
It is the sum total of organized arrangements
made with the object of ensuring that product
will be of quality required by their intended use.
 It includes all those planned or systematic
actions necessary to provide adequate
confidence that a product will satisfy the
requirements for faculty.
 Its approach is company-based.
It is responsible for ensuring that the
quality policies adopted by the company
are followed.
 Its functions includes monitoring of
environmental conditions.
Quality Control
 It is the part of GMP which is concerned
with sampling, specifications, testing and
within organization, documentation, and
release procedures which ensure that the
necessary and relevant tests are carried
out.
It includes operational laboratory
techniques and activities used to fulfill the
requirement of quality.
Its approach is laboratory-based.
It is responsible for the day-to-day control
of quality within a company.
Its functions includes quality monitoring
and audit function.

QA Departmental Functions
1. Assures policies are followed inept to
economic issues associated with manufacturing
and distribution of product
2. Cooperate with regulatory agencies and final
authority for product acceptance or rejection
3. Helps to identify and prepare necessary SOP’s
relative to control of quality
4. Audit and quality monitoring
QC Functions
1. Testing and acceptance of only highly quality
raw material, representative samples
2. IP tests against criteria
3. Monitors environmental conditions
4. Control packaging components
3 Main Areas of QC:
1. Raw Material Quality Control (RMQC)
2. In Process Quality Control (IPQC)
3. Finished Product Quality Control (FPQC)
Terms to be defined:
1. Monograph - Document that specifies all the
tests to be conducted on a product and/or
appropriate references containing details of
procedure and expected result
2. Certificate of Analysis (COA) - Document with
the results of all tests conducted on material to
show compliance or non-compliance with the
standard specifications
3. Formula - This is concise and precise
statement of the ingredients that comprise the
product, together with the percentage and/or
weight of each.
4. Standard Operating Procedures (SOP) - This is
a step by step method on how to go about a
job.
5. Sample – a representative obtained from a
certain population
QUALITY CONTROL
 sampling, specifications and testing as well as
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.
Things to consider:
1. It must be staffed with persons who are
trained academically and is capable of
evaluating the acceptability of material tested.
2. Equipment and instrumentation must be
suitable in an accurate and efficient manner.
3. Detailed specifications must be available, as
well as validated test methods.
4. Procedures must be validated and strictly
followed.
Quality Management System
 This quality objective is the responsibility of
senior management and requires the
participation and commitment by staff in many
different departments and at all levels within
the company, by the company’s suppliers and
by the distributors.
1. All parts of the Quality Assurance systems
should be adequately resourced with
competent personnel, and suitable and
sufficient premises, equipment and facilities.
2. It assures that the holder of a manufacturing
authorization must manufacture medicinal
products so as to ensure that they are fit for
their intended use, comply with the
requirements of the Marketing Authorization
and do not place patients at risk due to
inadequate safety, quality or efficacy.
3. Fully documented and its effectiveness
monitored.
cGMP
 current Good Manufacturing Practice
 concerned with both production and quality
control
 the part of QA which ensures products are
consistently produced and controlled to the
quality standards appropriate for their intended
use
March 1979
- the FDA issued revised GMP regulations
which presents the minimum requirements to
be met by industry when manufacturing,
packaging, and holding human and veterinary
products
Why follow GMP regulations?
Some of the main risks are:
1. unexpected contamination of products,
causing damage to health or even death.
2. incorrect labels on containers, which could
mean that patients receive the wrong medicine.
3. insufficient or too much active ingredient,
resulting in ineffective treatment or adverse
effects.
Quality Risk Management
 a systematic process for the assessment,
control, communication and review of risks to
the quality of the medicinal product. It can be
applied both proactively and retrospectively.
in all aspects of products and services that are
important to the customer
 combined team effort to develop, produce,
market, distribute, and control products that
are safe and effective
1. Quality must be designed into products.
a. product quality criteria are established
b. detailed specifications are written
c. written procedures must be prepared
d. processes must be validated
e. raw materials must provide products of
uniformly high quality
f. facilities must provide the proper stable
environment
g. equipment must prevent cross-
contamination
h. personnel must be trained properly
2. Distribution department  responsible for
controlling the shipping and handling of
products (inventory system and FIFO/FEFO)
3. Marketing Department  must be sensitive
to the customer’s needs and be responsive to
complaints
4. QA/QC Department  gives approval if all of
the aspects of GMP have been satisfied

The quality risk management system should

ensure that:
- the evaluation of the risk to quality is
based on scientific knowledge, experience with
the process and ultimately links to the
protection of the patient
- the level of effort, formality and
documentation of the quality risk management
process is commensurate with the level of risk
Total Quality Management
 or Total Product Management
The eight elements of TQM.
 improves productivity and customer
satisfaction
 refers to a quality emphasis that
encompasses the entire organization from top
management to rank and file
 stresses a commitment by management to
have a company wide drive towards excellence
QUALITY CONTROL
he key features of any laboratory QC system are
that the system is documented, understood,
stable, reliable and supports continuous
quality improvement. The laboratory must be
able to demonstrate that there is a ‘system’ in
place and not just a series of unco-ordinated
activities. These activities must be subject to
audit (external and internal) and review
(Badrick, 2008).
The foundation for a successful Quality
Assurance program is the quality control
maintained by the Producer to assure that all
materials submitted for acceptance conform to
the contract requirements. To accomplish this,
the Producer is required to have a functional
plan to keep the process in control, quickly
determine when the process goes out of
control, and respond adequately to bring the
process back into control.
a. cGMP – means current Good
Manufacturing Practices
b. specifications - a detailed description
of the design and materials used to make
something
c. sterile – free from any contamination
Manufacturing firm
 recognized as a major industry which
requires a clearly defined organization and
effective coordination; towards the production
of a drug or cosmetic of the highest standard
and at the lowest cost
 must be done in compliance with cGMP (AO
No. 220, s 1974)
Common Divisions in a Manufacturing Firm
(under a general manager):
1. Finance
2. Production
3. Quality Assurance (Quality Control)
4. Marketing (optional)
QUALITY CONTROL
 enforces cGMP
 organized to be the core of the company’s
quality audit program
 a tool which gives the assurance that a
product conforms to standards and
specifications through a system of inspection,
analysis and action
Quality control system
Potential 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
professionals to sell or prescribe the product.
The umbrella of quality.
Standards and specifications
 developed to serve as a basis for accepting or
rejecting a product to avoid producing a
defective product
1. Formula – concise and precise statement of
the raw materials with percentage and/or
weight of each
2. Raw Material Specification – characteristics
and permissible range of purity
3. Standard Operating Procedure – all
information and instructions to assure that
variations will be held within acceptable
established ranges
4. Finished Product Specification – all
characteristics
5. Packaging Material Standard – set for
everything that goes around the product
a. The units may have to run on a high-
speed line.
b. The may involve a complicated
assembly.
c. The package may be functional.
d. The package must be completely
compatible with the product.
e. The package must protect the
product and assure its stability.
f. The package must ship well.
6. Testing Methods – must be standardized and
validated to ensure precision and accuracy on
application
DEFECTS
 an undesirable characteristic of a product
 a failure to conform to specifications
1. According to MEASURABILITY:
a. Variable defect – can be measured directly
by instruments
b. Attribute defect – cannot be measured
directly by instruments
2. According to SERIOUSNESS or GRAVITY:
a. Critical defect – may endanger the life or
property and may render the product non-
functional
b. Major defect – may affect the function of
the object and may render the product useless
c. Minor defect – does not endanger life or
property nor will affect the function
3. According to NATURE:
a. Ocular defect – visible defect
b. Internal defect – not seen although
present
c. Performance defect – a defect in function
Sources and control of quality variation
1. Materials
a. Variation between suppliers of same
substance.
b. Variation between batches from
same supplier.
c. Variation within a batch.
2. Machines
a. Variation of equipment for the same
process.
b. Difference in adjustment of
equipment.
c. Aging and improper care.
3. Methods
a. Inexact procedures.
b. Inadequate procedures.
c. Negligence by chance.
4. Men
a. Improper working conditions.
b. Inadequate training, and
understanding.
c. Dishonesty, fatigue and carelessness.
ORGANIZATION OF QUALITY CONTROL
Quality Control Manager
 Material Inspection Section
 Analytical Laboratory
 Biological Testing Laboratory
 Specifications and Analytical
Development
 Quality Coordinating Office
Materials Inspection Section
1. To sample and examine all raw materials
received.
2. To sample and conduct physical tests on:
a. All shipments of packaging materials
b. 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 by production personnel.
Analytical Laboratory
 should be in an accessible area and
protected from noise and vibration
 performs physical and chemical
analysis
Biological Testing Laboratory
 provides sterile conditions,
precludes noise
1. To performs and evaluate microbiological and
pharmacological assays, sterility, pyrogen and
bacteriological tests, irritation, safety or acute
toxicity tests.
2. To conduct environmental monitoring.
Specifications and Analytical Development
1. To coordinate with research, product
development, production, sales and
management towards improvement of a
product.
2. To establish specifications for raw and
packaging materials.
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.
Quality Coordination Office
 main responsibility is
documentation
1. To maintain and store records that represent
the history of the batch from start to finish
(batch and master formula records, raw
material analytical records, printed and
packaging material inspection reports and
retention files).
2. To be able to furnish data that will aid in
analyzing product performance in the market
(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 regarding any aspect that
provides a basis for improvement of a product
for consideration and action.
5. To provide data that give scientific and legal
status (function of the distribution section or
warehouse).
6. To maintain and develop SOP’s.
CONTROL FUNCTIONS
1. ANALYSIS FUNCTION
 made on:
a. raw materials and packaging
components
b. bulk products during processing and
after packaging prior to its release to the market
c. finished products after distribution
to the end user subjected to shelf life studies
d. product against a complaint
2. MONITOR FUNCTION
a. to sample and examine materials while
they are being processed
b. to do environmental monitoring on a
time basis
3. RECORD REVIEW AND RELEASE FUNCTION
 responsible for carefully reviewing the batch
record for a specific lot and assuring that all
necessary records are present, complete and
accurate (if feasible to determine)
4. AUDIT FUNCTION
 designed to detect areas where the
established SOP’s are not being followed and to
report these findings to the supervisor for
appropriate action

COMPENDIAL REQUIREMENTS FOR SOLID AND

SEMI-SOLID DOSAGE FORMS - aka TOLUENE or XYLENE METHOD
- also used in ALCOHOL CONTENT
a. titrimetry - refers to a group of DETERMINATION
methods of quantitative analysis in which an c. Method III (Gravimetry)
analyte is determined basing on its - preferred for articles from botanical origin
stoichiometric reaction with a reagent of - Apparatus: Ohaus Moisture-Balance Analyzer
established concentration introduced to a
sample gradually until the analyte is consumed
quantitatively
b. gravimetry - used where weights of reactants
and products of chemical reactions are
reproducible, stable and reflect the presence of
constituents which are important in the
establishment of identity

IN-PROCESS QUALITY CONTROL

 IPQC is concerned with providing
accurate, specific, & definite
descriptions of the procedures to be
employed, from, the receipt of raw
materials to the release of the finished
dosage forms.
 In process Quality Control, IPQC tests
are mostly performed within the
production area.
 They should not carry any risk for the
quality of product.
 In process testing enables easier
identification of problems. It sometime
identifies a defective product batch
that can be corrected by rework,
whereas once that batch has been
completed, this may not be possible.
 Failure to meet in process control
specification indicates either that
procedure were not followed or some
factor (S) out of control.
Apparatus used to determine the moisture
content of powders or granules.
2. Adequacy of Wetness
- Final Moisture Content: 0.5 - 1.0%
3. Particle Size Determination
a. Optical microscopy - most reliable
b. Sieve analysis - fastest
- LIMITATIONS:
large sample size needed (NLT 25g)
not for oily/cohesive materials
- APPARATUS: set of sieves with varying mesh
number
increase in sieve no. = decrease in particle size
SIEVING METHOD: Mechanical Agitation/Dry
Sieving – >75μm particles
Air jet sieving – single sieve
Sonic sifter sieving – nest of sieves

A. SOLID DOSAGE FORMS IPQC PROCEDURES

I. Granules and Powders
1. Initial Moisture Content
- Wet Granulation
- Acceptance Limit: 31-35%
- Methods:
a. Method I (Karl-Fischer
Titrimetry)
Karl-Fischer Reagent – 1mL
KFR = 15mg water
Components: SO2, iodine,
pyridine, anhydrous methanol
Types:
Method Ia (direct) Set-up for sieving analysis.
Method Ib (residual) - ENDPOINT DETERMINATION: If ≥5% of sample
Method Ic (coulometric) weight is present on a sieve, % weight change is
NMT 5%.
b. Method II (Azeotropic Distilation)
If <5% of sample weight is present on a sieve, %
weight change is NMT 20%
-FORMULA:

4. Density
a. Bulk Density – ratio of mass of an
untapped sample and its volume, including its
interparticulate void volume
METHODS:
Graduated Cylinder (I)
Volumeter (II) – Scott Volumeter
Vessel (III) – 100 mL stainless steel cylindrical
vessel
Method 1 of determining the powder’s bulk
density. b. Hausner Ratio and Carr’s (Compressibility)
Index- measures of a powder’s ability to settle
b. Tapped Density – an increased bulk density
attained after tapping a powder/granule sample
METHODS:
Method I and II
i. Tap 10 times (V10)
ii. Tap 500 times (V500)
iii. Tap 1,250 times (V1250)
iv. Determine the tapped volume
 If V500 – V1250 ≤ 2mL, V1250 = tapped volume
 If V500 – V1250 > 2mL, repeat in increments of
1,250 taps until difference is < 2mL.
Method III
i. 50-60 taps/min
ii. 200 taps
iii. 400 taps

5. Powder Flow
a. Angle of Repose - constant 3D angle
(relative to horizontal base) assumed by a cone-
like pile of material
APPARATUS: Fixed Funnel,
Tilting Box, Revolving Cylinder
c. Flow Through Orifice- measured as mass per
time flowing from any container
d. Shear Cell
6. Loss on Drying  amount of volatile matter
driven off; 110-120°C

7. Content Uniformity
- acceptance criteria: + 2% of active component
98% - 102%

II. Tablets
1. Tablet Hardness  measure of a tablet’s
resistance to mechanical shocks
 affects friability, disintegration and
dissolution
 “rule of thumb”
- UNIT: Kg
- HARDNESS TESTERS:
a. Stokes-Monsanto – uses a barrel with
compressible spring applied diametrically to a thickness x 0.05)
tablet Lower Limit = specified thickness - (specified
thickness x 0.05)
3. Tablet Weight  unofficial test based on USP
XX
- STEPS:
A Stokes Monsanto tablet hardness tester. i. Get 20 tablets.
b. Strong-Cobb – force produced by a manually ii. Weight individually.
operated air pump iii. Compute for average tablet weight.
iv. Determine acceptable % variation.

v. Compute for acceptable

tablet weight range.
- ACCEPTANCE CRITERIA:
a. NMT ≥ 2 tablets are outside acceptable tablet
weight range.
b. No unit is outside twice acceptable %
variation.
Strong cobb tablet hardness tester.
c. Pfizer – makes use of hand pliers as aid
Pfizer-type tablet hardness tester.
d. Erweka – use of suspended weight

Erweka tablet hardness tester.

f. Schleuniger – most common; motorized anvil;
horizontally position
- CRITERIA:
Compressed Uncoated Tablets – 4-10 kg
Buccal Tablets – 7-10 kg
Chewable/Sublingual Tablets – 2-3 kg

. Tablet Thickness  for consumer acceptance

 facilitates packaging
- APPARATUS: Vernier Caliper

Parts of Vernier caliper, apparatus used to

measure tablet thickness.
CRITERIA: +/- 5% of specifications
Upper Limit = specified thickness + (specified