1. Presented by
G.Krishnam Raju
M.Pharmacy
Pharmaceutical Analysis &
Quality Assurance 1st year
1st semester
HT.NO:-13TK6S0401
SVS Group Of Institutions
SVS school of pharmacy
1

2. • Definition
• Introduction
• Various IPQC Tests
• Conclusion
• Reference
CONTENT:-
2

3.  Definition:-Injections are sterile, pyrogen-
free solutions or dispersions (emulsions or
suspensions) of one or more active
ingredients in a suitable vehicle.
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4. 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.
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5.  In general, the majority of a manufacturer's time
and resources are spent tightening tolerances,
ensuring compliance, and/or increasing post-
process destructive and non-destructive testing.
 While such efforts are important to a quality-
assured and quality-controlled process, there are
diminishing returns for higher standards through
increased destructive and non-destructive testing.
 In most manufacturing environments, the process
itself is treated as a black box, where the inputs
are tightly controlled and the resulting product is
thoroughly tested but the in-process behavior is
largely overlooked.
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6. 1. Environmental control
2.PH
3.Viscosity
4.Osmolality (Occasionally)
5.Condectivity measurements
6.Temperature for heat sterilization
7.Volume filled
8.Lekage test
9.Clarity test
10.Pyrogen test
11.Sterility test
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7. Traffic control:-
 A carefully designed arrangement to control traffic.
 Personnel should be permitted into aseptic areas
only after following rigidly prescribed procedures.
Surface disinfection personnel:-
 Must be inherently neat ,orderly ,reliable and alert.
 Should be in good health.
Air control:-(HEPA filters)
 It is composed of glass fibers and filters.
 It is 99.97% efficient removes particles of 0.3um
size and larger.
 Velocity is 100+/- 20 ft/min.
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8. 2.PH MEASUREMENT
Two different types of methods used in the measurement of PH.
1.Dip a piece of PH paper into the sample.
2.PH meter.

9. These devices also are known as glass
capillary viscometers or Ostwald viscometers,
named after Wilhelm Ostwald.
which consists of a U-shaped glass tube held
vertically in a controlled temperature bath.
In one arm of the U is a vertical section of
precise narrow bore (the capillary).
 Above this is a bulb, with it is another bulb
lower down on the other arm.
In use, liquid is drawn into the upper bulb by
suction, then allowed to flow down through the
capillary into the lower bulb.
Two marks (one above and one below the
upper bulb) indicate a known volume.
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10.  The time taken for the level of the liquid
to pass between these marks is
proportional to the kinematic viscosity.
 Most commercial units are provided
with a conversion factor, or can be
calibrated by a fluid of known
properties.
 The time required for the test liquid to
flow through a capillary of a known
diameter of a certain factor between two
marked points is measured.
 By multiplying the time taken by the
factor of the viscometer, the kinematic
viscosity is obtained.
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11. Osmolality is a count of the number of particles in a fluid sample.
The osmolality of a solution can be measured by osmometer.
Freezing point depression osmometer is widely used.
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12. Conductivity is measured by conductometer
It is measured the conductivity of vehicle used in sterile
preparation.
The conductivity of the pure water is 0.55 micro-
siemens/cm.
5.Condectivity measurements
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13. It is important to maintain the constant temperature
during heat sterilization of product.
The temperature changes may causes some
undesirable changes like change in potency, change in
isotonicity etc.
The temperature can be determined by normal
thermometer, digital thermometer.
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14. Volume in container
An injection container is filled with a volume in slight excess
of the labeled size
Determination of filled volume:
10 mL or more 1 container
3-10 mL 3 containers
Less than 3 mL 5 containers
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15.  Lekage test is employed to test the package
integrity.
 Package inegrity reflects its ability to keep the
product in and to keep potential contamination
out.
 Which is the flow of matter through the barrier
itself.
 Lekage tests are 4 types
a) visual inspection
b) bubble test
c) dye tests
d) vacuum ionization test
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16. A) VISUAL INSPECTION
Visual inspection is the easiest leak test method to
perform.
The method is used for the evalution of large volume
parentrals.
To increase the sensitivity of the method the visual
inspection of the sample container may be coupled with the
application of vacuum to make leckage more readily
obeservable.
This method is simple and inexpensive.
Dis-advantage: less sensitive is increased by
pressure/vacuum.
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17.  The test package is submerged in liquids.
 A differential pressure is applied on the container.
 The container is observed for bubbles.
 Sometimes, surfactant added liquid is used for immersion of test
package.
 Any leakage is evident after the application of differential pressure
as the generation of foaming in immersion liquid.
 The method is simple and inexpensive.
 The location of the leaks can be observed in this method.
 However, it is relatively insensitive and the findings are operator
dependent and are qualitative.
 The optimized conditions can be achieved using a surfactant
immersion fluid along with the dark background and High intensity
lighting.
• Generation of a differential
positive pressure of 3 psi inside
the vial and observation of any
leakage using magnifying glass
within a maximum test time of
15 minutes. 17

18.  The test container is immersed in a dye bath.
 Vacuum and pressure is applied for sometime.
 The container is removed from the dye bath and
washed.
 The container is then inspected for the presence of
dye either visually or by means of UV spectroscopy.
 The dye used may be of blue, green, yellowish-green
color.
 The dye test can be optimized by use of a surfactant
and or a low viscosity fluid in the dye solution to
increase the capillary migration through the pores.
 The dye test is widely accepted in industry and is
approved in drug use.
 The test is inexpensive and is requires no special
equipment required for visual dye detection.
 However, the test is qualitative, destructive and slow.
 The test is used for ampoules and vials. 18

19.  Vacuum ionization test is useful for testing leakage in the
vials or bottled sealed under vacuum.
 This test is used for online testing of the lyophilized products.
 High voltage, high frequency field is applied to vials which to
cause residual gas, if present to glow.
 Glow intensity is the function of headspace vacuum level.
 The blue glow is the indicative of vacuum while the purple
glow indicative of no vacuum.
 The sensitivity of the method is not documented.
 This test is on-line, rapid and is non destructive test.
 However, the proteins present in the test sample may be
decomposed.
 This method is used for the lyophilized vials
of biopharmaceuticals.
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20.  Clarity test is carried out to check the particulate
matter in the sample.
 It is practically impossible that every unit of lost is
perfectly free from visible particulate matter , that
is ,from particles that are 30 to 40 micrometer and
large in size.
USP limits for large volume infusions
Particle size Particle limit
10 mm (or) larger/ml 50
25 mm (or) larger/ml 5
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21. 1.VISUAL INFECTION BY NAKED EYE:-
 Each injectable is inspected visually against
White and Black backgrounds.
 The white background aids in detection of
dark coloured particles.
 The light or reflective particles will appear
against the black background.
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22. 2. INSTRUMENTAL METHODS:-
 This is also called as the particle count method
particle counting may be based on any one of
the following principles; change in
 Electrical resistance
 Light absorption
 Light scattering
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23. 10.PYROGEN TEST
•Pyrogens are products of metabolism in
microorganisms Gm-ve bacteria produces most
potent pyrogens.
•These are lipopolysacchrides chemically and
heat stable and are capable of passing through
bacteria retentive filter.
•When these pyrogens are introduced into a
body they produce a mark response of fever with
body ache and vasoconstriction within an onset
of 1 hour.
• Basically there are test performed to detect the
presence of pyrogens in sterile parenteral
products they are
1) Rabbit Test
2) LAL Test. 23

24. •This test basically involves the injection Sample solution
which is to be tested into a Rabbits Which are use as test
animals through ear vein.
•The Temperature sensing probe (Clinical Thermometer,
Thermosestor or similar probe) into a rectum cavity of
Rabbit at the depth of 7.5 cm, the test solution must be
warmed at 37 degrees prior to injection.
• Then Rectal temperature is recorded at 1,2,3 hr
subsequent to injection.
• This test is performed in separate area designed solely for
this purpose under environmental conditions similar to
animal house should be free from disturbances that likely to
excite them.
RABBIT TEST
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25. No. of Rabbits Individual
Temp/Rise
(degree Celsius )
Temp rise in
group(degree
Celsius )
Test
3 rabbits 0.6 1.4 pass
If above not
pass
3+5=8 rabbits
0.6 3.7 pass
If above test not passes perform the test again
If above test not passes, the sample is said to be
PYROGENIC
• Initially this test is performed on 3 Rabbits but if required results are
not obtained this test is repeated on 5 additional Rabbits with same
sample solution administer to initial 3 rabbits.
• Prior to 1hr of injecting sample solutions the control temperatures of
rabbits are determined.
•Use only those rabbits whose control temperature is no vary by more
than 1 degree Celsius.
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26. LAL TEST
 It is an recently developed in-vitro test method for
pyrogen utilizing gelling property of lysates of amebocytes
of limulus polyphemus which is found only at specific
locations along the east coast of North America and along
southeast Asia.
 It is derived from horse shoe crab; the basic procedure is
the combination of 0.1 ml of test sample with LAL Reagent
after incubation for 1 hr at 37 degree Celsius the mixture
is analyzed for the presence of Gel clot.
 The LAL Test is positive indicating that the presence of
endotoxin.
 Its applications are mainly to Pharmaceutics, Biological,
devices, disease states, food, and validation of heat cycles.
 This method has several advantages of Rabbit test they are
Greater sensitivity andreliability specificity, less variation,
wider application, less expensive and simplicity.
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27.  Sterility is the most important and absolutely Essential
characteristics of Parenteral products.
 Sterility means complete absence of all viable Micro-
organism. It is an absolute term.
 The methods which are used to perform sterility test are
a) Direct transfer method.
b) membrane filtration method.
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28. A) Direct Transfer method:-
 it is an traditional sterility test method
which involves a direct inoculation of
required volume of a sample in two tests
tube containing a culture medium that is
FTM, SCDM.
 This method is simple in theory but
difficult in practice when the demand for
repetition in opening container, sampling
Transferring, and mixing increases causes
potential error in operator technique.
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29. B) Membrane Filtration method:-
 It is official in U.S.P. 1970.
 This method basically involves filtration of
Sample through membrane filters of porosity
0.22 micron and Diameter 47mm.
 The filtration is assisted under Vacuum, after
filtration completion the membrane is cut into 2
halves and one halve is placed in two test tubes
containing FTM, SCDM medium.
*Interpretation:–If no visible evidence of microbial
growth in culture medium in test tube then it is
interpreted that the sample representing lot is
without intrinsic contamination.
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30. •Quality control should be a fundamental segment of
parenteral products manufacturing.
• All of the 4 basic tests which are performed are essential
and have its own importance in parenteral production.
• All of these tests ensure that product meet its quality
which has been judged to satisfactory also.
• Each test is unique and provides detailed assessment of
quality control for parenteral products.
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31. 1)Mehta R.M, Sterilization, pharmaceutics- I.Delhi
Vallabh prakashan, 2002. P. 227-228.
2) Lachman.L, Liberman HA, Kaniz JL, Editions, T
he Theory and practice of industrial pharmacy
Bombay, Varghese publication House;1986.P.673-
675.
3) Akers.MJ, Larrimor DS, Guazzao morton D,
Parenteral Quality control, New York, Marcel
Deckker; 2006. P. 1-183.
http://www.nscbip.org/?p=708
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