INTRODUCTION
A
sterility test may be defined as — ‘a test that critically assesses whether a sterilized
pharmaceutical product is free from contaminating microorganisms’.
According to
Indian Pharmacopoea (1996) the sterility testings are intended for detecting the
presence of viable forms of microorganisms in or on the pharmacopoeal preparations.
In actual practice, one invariably comes across certain absolutely important guidelines and vital
precautionary measures that must be adhered to strictly so as to accomplish the utmost accuracy and
precision of the entire concept of sterility testing for life-saving secondary pharmaceutical products
(drugs). A few such
cardinal factors, guidelines, and necessary details are as enumerated under :
(
a) Sterility testing, due to its inherent nature, is intimately associated with a statistical process
wherein the portion of a batch is sampled almost randomly* ; and, therefore, the chance of the particular
batch (lot) duly passed for actual usage (consumption) solely depends upon the
‘sample’ having passed
the stringent sterility test.
(
b) Sterility tests should be performed under conditions designed to avoid accidental contamination
of the product (under investigation) during the test. Nevertheless, such particular precautions precisely
taken for this purpose must not, in any case, adversely affect any microbes that should be revealed in the
test ultimately.
(
c) Working environment wherein the sterility tests are meticulously carried out must be adequately
monitored at regular intervals by sampling the air and the surface of the working area by performing
necessary control tests.
(
d) Sterility tests are exclusively based upon the principle that in case the bacteria are strategically
placed in a specific medium that caters for the requisite nutritive material and water, and maintained
duly at a favourable temperature (37
± 2°C), the microbes have a tendency to grow, and their legitimate
presence may be clearly indicated by the appearance of a
turbidity in the originally clear medium.
(
e) Extent of probability in the detection of viable microorganisms for the tests for sterility usually
increases with the actual number supposedly present in a given quantity of the preparation under examination,
and is found to vary according to the species of microorganisms present. However, extremely
low levels of
contamination
cannot be detected conveniently on the basis of random sampling of a batch.*
(
f) In case, observed contamination is not quite uniform throughout the batch, random sampling
cannot detect contamination with absolute certainty. Therefore,
compliance with the tests for sterility
individually cannot certify absolute assurane of freedom from microbial contamination.
Nevertheless,
greater assurance of sterility should invariably originate from reliable stringent manufacturing procedures
vis-a-vis
strict compliance with Good Manufacturing Practices (GMPs).
(
g) Tests for sterility are adequately designed to reveal the presence of microorganisms in the
‘samples’
used in the tests. However, the interpretation of results is solely based upon the assumption that
the contents of each and every container in the batch, had they been tested actually, would have
complied
with the tests.
As it is not practically possible to test every container, a sufficient number of containers
must be examined to give a
suitable degree of confidence in the ultimate results obtained of the tests.
(
h) It has been duly observed that there exists no definite sampling plan for applying the tests to
a specified proportion of discrete units selected carefully from a batch
is capable of demonstrating that
almost all of the untested
units are in fact sterile absolutely. Therefore, it is indeed quite pertinent that
while determining the number of units to be tested, the manufacturer must have adequate regar to the
environment parameters of manufacture, the volume of preparation per container together with other special
considerations specific to the preparation under investigation. For this Table 8.1 records the guidance on
the exact number of items recommended to be tested with regard to the number of items in the batch on the
assumption that the preparation has been duly manufactured under specified stringent parameters designed
meticulously to exclude any untoward contamination.