REVIEW - QUALITY CONTROL OF PARENTERAL PRODUCTS
In a pharmaceutical organization a quality control is a fundamental segment that
refers to a process of striving to produce a product by a series of measures
requiring an organized effort by entire company to eliminate or prevent error at any stage of production.
Quality control deals with testing, sampling, specification, documentation, release procedure which ensure
that all tests are actually carried out prior to release of material for sale or use. Until its quality judged
to satisfactory. This article deals with quality control of parenteral preparation which have 4 basic area that
are Sterility, Freedom form Pyrogens, Freedom from particulate matter and leakers. It gives details on each of these
4 Basic areas. The achievement of sterile, non-pyrogenic and particulate free parenteral product provides a significant
challenge to ingenuity and creativity of parenteral scientist and technologist.
Quality control shall be concerned with sampling, Specifications, Testing, documentation, Release procedure which ensure that necessary and relevant tests are actually carried out and materials are not release for its use or for sale, until its quality has been judged to satisfactory. The 3 General areas of parenteral quality control are incoming stocks, manufacturing and Finished products. The Basic quality control tests which are performed on sterile parenteral products include: -
1) Sterility Tests
2) Pyrogen Tests
3) Leaker Tests
4) Particulate matter testing.
1) Sterility tests: -
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 tests are:
A) Direct transfer method. B) membrane filtration method.
A) Direct Transfer method: -
it is a 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 fatigue to the operator and detoriation in operator technique. So, chances of Accidental contamination are there.
B) Membrane Filtration method: -
It is official in U.S.P. 1970. It is more popular and widely used method over direct transfer method. Successful Employment Requires a more skill and knowledge than Direct transfer method. This method basically involves filtration of Sample through membrane filters of porosity 0.22 micron and Diameter 47mm with hydrophobic characteristics. 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. If visible microbial growth is seen or if the test is judged to be invalid because of inadequate environmental conditions the sterility test is repeated such interpretation must be made by those personnel who have adequate knowledge of aseptic processing, industrial sterilization methods, and environmental control procedures used in test facility.
2) Pyrogen Test: -
Pyrogens are products of metabolism in microorganisms Gm-ve bacteria produces most potent pyrogens. These are lipopolysaccharides 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 C) Rabbit Test D) LAL Test.
C) Rabbit test: -
This test basically involves the injection Sample solution which is to be tested into a Rabbits Which are used as test animals through ear vein. The Temperature sensing probe (Clinical Thermometer, Thermosistor 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. 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.
*Interpretation: -The solution is judged to be non-pyrogenic if no single rabbit show rise in temperature of 0.5 degree Celsius but if this condition is not met then the test if repeated on 5 additional rabbits with same preparation administer to initial first 3 rabbits the solution is judged to be non-pyrogenic if NMT 3 of 8 rabbits show individual temperature rise of 0.5 degree Celsius.
D) LAL test: -
It is a recently developed in vitro test method for pyrogen utilizing gelling property of lysates of amoebocytes 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 and reliability specificity, less variation, wider application, less expensive and simplicity.