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EQUIPMENTS FOR LARGE SCALE MANUFACTURE FOR PARENTRAL PRODUCTS

PRESENTED BY : KUMAR SATYAM

• 2271010017

GUIDED BY • Dr. S. SANGEETHA

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EQUIPMENTS

The following equipments as per schedule- M has been recommended

a. Manufacturing area: Storage equipment for ampoules , vials &

closures Washing and drying equipments Dustproof storage cabinet Water still Mixing and preparation tanks or other containers Mixing equipments Filtering equipments hot air sterilizer

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b) Aseptic filling and sealing rooms: Benches for filling and sealing Bacteriological filters Filling and sealing unit under laminar flow

work station c) General Room : Inspection table Leak testing table Labeling and packing benches Storage of equipment including cold

storage and refrigerators (if necessary)

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STERILE GARMENT CABINET

Stainless steel Sterility is maintained by

use of UV disinfectant May be designed

horizontal air flow system and clean air through HEPA filter

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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 fibers.

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.

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TYPES OF CONTAINER FOR PARENTERAL

AMPOULES• Intended for single use• Product must be filtered before use

VIALS• Glass or plastic containers are closed

with a rubber stopper and sealed with an aluminum crimp

PREFILLED SYRINGE • Intended for quickest administration

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AMPOULE WASHING MACHINE

Thoroughly cleaned with detergents. Washed with tap water &

distilled water

finally rinsed with water

for injection

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VIAL WASHING MACHINEIt 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 andarranged in the washing machine. •After washing completes the vial run through depyogenation zones. •Here the ampoules /vials are made to free from pyrogens (sterilization is done here)

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FILLING MACHINE

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

VIALS FILLING• The comprises of an intake section which

loads the vials• Transferred through an intermittent transport

section.• Liquid filling section which fills the vials with

predetermined quantity.• Finally the filled and rubber Stopperd vials

are released and discharged.

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QUALITY CONTROL

The three general area of quality control are incoming stock, manufacturing and the finished product.

Types of Quality Control:• LEAKERS TEST• CLARITY TEST• PYROGEN TEST• STERILITY TEST

LEAKERS TEST

Filled and sealed ampoules

Dipped in 1% methylene blue solution under negative pressure in vacuum chamber

Vacuum released coloured solution enter into the ampoule

Defective sealing

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

Vials and bottles are not suitable in this test because the sealing material is not rigid.

CLARITY TEST A clear having a high polish conveys product is of

exceptional quality and purity. Practically impossible to prepare sterile product perfectly

free from visible particulate matter(size 30-40 µm). Quality control departments responsibility – to detect and

discard unclean products. 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 size distribution.

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PYROGEN TEST

Pyrogen test

LAL testRabbit test

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RABBIT TEST

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 selected.

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METHODNormal

Temperature is recorded prior to

the test

Dilute the test substance in pyrogen free

saline solution

Warm the solution to

38.5oC

Volume of injection is maintained

between 0.5 -10ml/kg

Test solution is injected through

an ear vein

Body temperature is recorded by a clinical rectal thermometer

Record temperature at an interval of 30min for 3hr

The difference between initial

and final temperature is

recorded

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LAL TESTLIMULUS AMEBOCYTE LYSATE TEST

• To detect endotoxins of gram negative bacterial origin.

• Reagent: Amebocytes of Limulus polyphemus.

Technique: 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.

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METHOD

Equal Volume of LAL reagent and test solution (usually 0.1 ml of each) are mixed in a depyrogenated test-tube

  Incubation at 37°C, 1 hour  Remove the tube   Invert at (180°) observe the result  Pass-fail test(GEL FORMATION)

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STERILITY TESTIt 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 medium.

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 sterile

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INDUSTRIAL PHARMACY• Leon Lachman• Herbert A. LiebermanWWW.PHARMAMACHINE.COM• PHARMALES.CO.IN

REFERENCE:

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