equipment for large scale paretral and quality control
EQUIPMENTS FOR LARGE
SCALE MANUFACTURE FOR
• Dr. S. SANGEETHA
The following equipments as per schedule- M has been
a. Manufacturing area:
Storage equipment for ampoules , vials & closures
Washing and drying equipments
Dustproof storage cabinet
Mixing and preparation tanks or other containers
Filtering equipments hot air sterilizer
b) Aseptic filling and sealing rooms:
Benches for filling and sealing
Filling and sealing unit under laminar flow work
c) General Room :
Leak testing table
Labeling and packing benches
Storage of equipment including cold storage and
refrigerators (if necessary)
STERILE GARMENT CABINET
Sterility is maintained by use of
May be designed horizontal air
flow system and clean air
through HEPA filter
HEPA filters can remove at least 99.97% of airborne
particles 0.3 µm in diameter.
HEPA filters are composed of a mat of randomly arranged
Key factors affecting function are fiber density and
diameter, and filter thickness.
The air space between HEPA filter is much greater than
0.3µm. The common assumption that a HEPA filter acts
like a sieve where particles smaller than the largest
opening can pass through is incorrect.
TYPES OF CONTAINER FOR PARENTERAL
• Intended for single use
• Product must be filtered before use
• Glass or plastic containers are closed with a rubber
stopper and sealed with an aluminum crimp
• Intended for quickest administration
AMPOULE WASHING MACHINE
Washed with tap
finally rinsed with
water for injection
VIAL WASHING MACHINE
It has several channels for
washing of the vial.
The vials travel through these
channels and simultaneously
purified water , air ,water for
injection, are introduced
through various nozzles and
arranged in the washing
•After washing completes the
vial run through depyogenation
•Here the ampoules /vials are
made to free from pyrogens
(sterilization is done here)
AMPOULE FILLING MACHINE
• Filling range is between 1 ml - 20 ml.
• At the mean time Sealing is done either by laser sealing
system or conventional gas flame
• The comprises of an intake section which loads the vials
• Transferred through an intermittent transport section.
• Liquid filling section which fills the vials with
• Finally the filled and rubber Stopperd vials are released
The three general area of quality control are incoming
stock, manufacturing and the finished product.
Types of Quality Control:
This test is to detect incompletely sealed ampoules. The sealed
ampoules are subjected to small cracks which occurs to rapid
temperature changes or due to mechanical shock
Filled and sealed ampoules
Dipped in 1% methylene blue solution under
negative pressure in vacuum chamber
Vacuum released coloured solution enter into
Vials and bottles are not suitable in this test because the sealing
material is not rigid.
A clear having a high polish conveys product is of exceptional quality and
Practically impossible to prepare sterile product perfectly free from
visible particulate matter(size 30-40 µm).
Quality control departments responsibility – to detect and discard
USP states that good pharmaceutical practice requires that all containers
be visually inspected and that any with visible particles may be discarded.
For large volume infusions,the USP has established a limit of 50 particles
of 10 µm and larger and five particles of 25 µm and larger per ml.
Visual inspection of products containers usually done by individual human
inspection of each externally clean container under a good light and
viewed against a black and white background.
Contents set in motion with a swirling action.
Instrumental method of evaluation of particles utilizes principles of light
scattering, light absorbtion and electrical resistance for particle count and
Rabbits are used as the test animal because
they show a physiological response to
pyrogens similar to that of human beings.
3 healthy adult rabbits of either male or
female, each weighing not less than 1.5 kg are
recorded prior to
Dilute the test
pyrogen free saline
Test solution is
injected through an
Volume of injection
between 0.5 10ml/kg
Warm the solution
is recorded by a
temperature at an
interval of 30min for
between initial and
final temperature is
LIMULUS AMEBOCYTE LYSATE TEST
To detect endotoxins of gram negative bacterial origin.
Reagent: Amebocytes of Limulus polyphemus.
Gel Clot technique:
In the presence of pyrogenic endotoxins from gram –ve
bacteria , a firm gel is formed within 60 min when
incubated at 37º C.
Equal Volume of LAL reagent and test solution
(usually 0.1 ml of each) are mixed in a
Incubation at 37°C, 1 hour
Remove the tube
Invert at (180°) observe the result
Pass-fail test(GEL FORMATION)
It is a procedure carried out to detect confirm absence of any
viable form of microbes in product.
Principle: sterlity testing only shows that organisms capable of
growing in selected conditions are absent from the fraction of
batch that has been tested. If the microorganism are present
in the product can be indicated by a turbidity in the clear
Objective of Sterility Testing:
For validation of sterilization process
To prevent issue of contaminated product in market
To check presence of microorganism in preparation which are
• Leon Lachman
• Herbert A. Lieberman