QC/QA
Product Quality Review (PQR)
OUTLINE
I. Basic Principles
II. Raw Material Quality Control
(RMQC)
III. Packaging Material Quality Control
(PMQC).
I. BASIC PRINCIPLES
A. DEFINITION OF TERMS
1. Quality
 totality features or conformance to
specifications of a product
 Ensures that products:
 Are fit for their intended use
 Safe
 Compliant with the
requirements of the
marketing authorization
2. Total Quality Management (TQM)
 A combined team effort to develop,
produce, market, distribute, and
control products that are safe and
will be effective for the time they
remain in the marketplace
3. Quality Assurance (QA)
 totality of the organized
arrangements made with the
objective of ensuring that products
are of the quality required for their
intended use
4. Current Good Manufacturing Practice
(cGMP)
 part of QA which ensures that
products are consistently produced
and controlled to the quality
standards appropriate to their
intended use
5. Quality Control (QC)
 part of cGMP concerned with
sampling, specifications, testing,
organization, documentation, and
release procedures
6.
 regular periodic quality reviews of
all registered drug products to verify
consistency of the existing process
and to identify product and process
improvements.
7. Quality Risk Management (QRM)
 a systematic process for the
assessment, control,
communication, and review of risks
to the qualitv of the product
B. QUALITY UNIT
 An organizational unit independent
of Production which fulfills both
Quality Assurance and Quality
Control responsibilities.
CA UNIT
 ensures that quality policies
 are followed
 audit and monitoring
 primary contact with
regulatory agencies
 prepares SOPs
QC UNIT
 conducts sampling and
testing of RM & FP
 inspects PM components
 performs environmental
 monitoring
C. DOCUMENTS
1. Monograph
 specifies all the tests to be
conducted on a material and the
expected results
2. SOP
 step-by-step instruction for doing a
particular task or activity
3. COA
 shows the actual results of all tests
conducted on a material to show
compliance with standards
4. MSDS
  contains information on the
potential health effects of exposure
to chemicals and on safe working
procedures when handling chemical
products
D. SAMPLING
 the process of removal of an
appropriate number of items (n)
from a population (N)
 Sampling Plans:
1. MIL-STD-105E - most common
(old)
2. ANSI/ASQZ1.4-2008 - most
common (new)
3. Square Root System - easier (use
in exam)
E. CONTROL CHARTS
 graphs on which the quality of the
product is plotted as manufacturing
is actually proceeding
 Types:
1. p-Chart - proportion of defectives
2. np-Chart-non-proportion
(number) of defectives
3. X Bar Chart - used for measurable
characteristics
 Warning Limit – alerts the
operator to closely monitor the
process
 Action Limit – alerts the operator
to stop the process and do
corrective action
F. VALIDATION & QUALIFICATION
1. Validation - the action of proving
and documenting that any process,
procedure or method actually leads
to the expected results.
2. Qualification - the action of
proving that premises, systems or
equipment work correctly and
actually lead to expected results.
G. PRODUCT DEFECTS
 non-conformance to a standard
or requirement
 Classification:
1. According to Magnitude
a. Critical Defect - may endanger
life of patient
b. Major Defect - does not
endanger life of patient but
affects the function of the
product
C. Minor Defect - does not
endanger life of patient & does
not affect the function of the
product
2. According to Measurability
a. Variable Defect - measured by
an instrument
b. Attributive Defect – measured
by inspection
3. According to Nature
a. Ocular Defect - can be seen by
the naked eye
b. Internal Defect - cannot be
seen by the nakedeye
H. PRODUCT RECALL
 removal of product from the market
because it is either defective or
potentially harmful
 Classification of Product Recall:
1. Class I Recall - may cause death
or serious adverse health
consequences
2. Class I Recall - may cause
temporary/medically reversible
adverse health consequences
3. Class III Recall - not likely to
cause adverse health
consequences
I. STABILITY STUDIES
1. Stability
 capacity of a drug to remain within
specification
 Minimum Acceptable
 Potency: 90%
 Drug products are mainly
decomposed by:
 a. Hydrolysis
o Prevented by reduction or
elimination of water from
the preparation
b. Oxidation
o Prevented by antioxidants
(ex: Vit C & E)
c. Photolysis
o Prevented by using light-
resistant containers
2. Shelf-life (tgo)
 period of time during which a
product is expected to remain within
specification
 estimated using the Arrhenius
equation
3. Expiration Date
 time or date prior to which a
product is expected to remain stable
and after which it must not be used
 calculated using this formula:
o Expiration Date =
Manufacturing Date + Shelf-
life
4. Stability Studies
 used to estimate the shelf-life of a
drug product
 evaluated over time in the same
container closure
 system in which the drug product is
marketed
 based on ASEAN Guidelines on
Stability Studies
 Climatic Zones
 Types of Stability Studies
b. Accelerated Studies
o designed to increase the rate
of chemical degradation by
using exaggerated storage
conditions
o Testing Period: 0, 3, 6
c. Stress Testing
 elucidates the intrinsic
stability of the drug
substance and identify the
likely degradation products
 carried out under more
severe conditions
II.Raw Material Quality Control (RMQC)
A. HANDLING OF RM
o Quarantine - status of materials
which are isolated physically while a
decision is awaited on their release,
rejection, or reprocessing
o All quarantined materials are
labeled with
o YELLOW color
o Materials that conform to
tests are labeled with GREEN
color
o Materials that failed or are
rejected are labeled with
RED color
o Warehouse Distribution Practices:
1. First in-First out (FIFO)
o In this technique, the rule is
to move first the stocked
products or the products
that are brought in first
2. First expiry-First out (FEFO)
o In this technique, the
products whose expiration
dates are approaching are
moved out of the warehouse
first
B. IDENTIFICATION TEST
o to confirm the identity of a chemical
substance
o Methods:
1. Chemical Methods
o Color reactions
 o Precipitation
o Evolution of gas
2. Instrumental Methods
o Spectroscopy
o Chromatography
C. ASSAY
o to determine the amount of API or
biologic activity
o Methods:
1. Chemical Assay
o Titrimetry
o Instrumental methods D. LIMIT TEST
2. Biologic Assay o to measure small amounts of
o Animal assay impurities in a RM
o Microbial assay o Types of Impurities:
a. Animal Assay 1. Gross Impurities - dirt or insoluble
matter
2. Biological Impurities -
microorganism
3. Chemical Impurities - by-products,
degradation products, reagents,
catalysts, ligands, heavy metals, or
b. Microbial Assay residual solvents
o Methods: o Examples:
1. Cylinder Plate Method
o uses a cylinder or paper
disc impregnated with
the sample, placed on a
solidified nutrient
medium in a Petri dish
o based on the diameter of E. PHYSICAL TESTS
o can be used for identification and
the zone of inhibition
2. Turbidimetric Method determination of concentration of a
o uses a test tube filled with component
o may also be used to determine the
fluid nutrient medium,
where the test organism is presence of impurities
inoculated 1. Specific Gravity
o based on measurement of o the ratio of the density of a
transmittance substance to that of a
reference substance at 25 °C
o measured using a
pycnometer or Mohr
Westphal balance
 o Alcohol: measured using a  Method IB: Residual
hydrometer at 15.56 °C  Method IC:
2. Refractive Index (n) Coulometric
o ratio of the velocity of light in air to
the velocity of light in the substance
at 25°C
o represented by the formula:

o where i= angle of incident ray

o measured using an Abbe

refractometer

3. Optical Rotation (a)

o measure of its ability to rotate an
incident plane of polarized light
o may be dextrorotatory or o Method I: Azeotropic Distillation
levorotatory  based on distillation of
o measured using a polarimeter water with toluene/
xylene
4. Solubility
 uses a toluene-moisture
apparatus
o Method Ill: Gravimetry
 based on loss on drying
at 110-120 °C for
inorganic materials and
105 °C for organic
materials
5. BP-MP III.Packaging Material Quality Control
o indicates presence of impurities (PMQC).
6. Loss on Drying A. TESTS FOR GLASS
o determines the amount of volatile 1. Hydrolytic Resistance (Leaching)
matter driven off after drying o Old SP Tests
7. Water Determination
o Method I: Karl-Fischer Titrimetry
o based on the rxn of water
and KFR
o KFR Components:
 Sulfur dioxide a. Powdered Glass Test
 lodine o Sample: crushed Type I and
 Pyridine Type III glass
 Anhydrous Methanol o Method: Acid-base titration
o Types: with 0.02 N H,SO VS using
 Method IA: Direct
 methyl red as indicator

b. Water Attack Test

o Sample: inner surface of
Type Il glass
o Method: Acid-base
titration with 0.02 N
H,SO, VS using methyl
red as indicator
c.Surface Glass Test
o Sample: inner surface of
Type I and Ill glass
o Method: Acid-base
titration with 0.1 N HCI
VS using methyl red as
indicator
 New USP Tests

2. Light Transmission
 for colored glass containers
 Limit: NMT 10% at any wavelength
in the range of 290 to 450 nm
3. Arsenic
 for Type I or Type Il glass container
 Method: same w/ limit test for As
 Limit: NMT 0.1 ug per g

B. TESTS FOR PLASTIC

1. Biological Reactivity Tests In Vivo

2. Biological Reactivity Tests In Vitro