A sterile filter
is generally intended for the elimination of harmful particles and microbes
from process fluid. The fibre-shedding characteristics of filters should be
minimal and the filter system must be inert; the filter system should not add
or remove anything from the fluid, even though it may not be regarded as a
contaminant at first glance. Extractable
leachable study, Filter compatibility, bacterial challenge tests and physical
integrity tests are the major tests to be performed during filter validation.
What are the factors which
affects filter performance?
Factors
that can affect filter performance generally include (1) viscosity and
surface tension of the product to be filtered, (2) pH, (3) compatibility of
the material or formulation components with the filter itself, (4) pressures,
(5) flow rates, (6) maximum use time, (7) temperature, (8) osmolality, (9)
and the effects of hydraulic shock.
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Why a challenge concentration
of 107 organisms per cm2 of effective filtration area is generally
used in filter validation for bacterial retention study.
It’s a guidance requirement. According to “Sterile
Drug Products Produced by Aseptic Processing —Current Good Manufacturing
Practice” - “A challenge concentration of at least 107 organisms per cm2 of
effective filtration area should generally be used, resulting in no passage
of the challenge microorganism. The challenge concentration used for
validation is intended to provide a margin of safety well beyond what would
be expected in production”.
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What is the maximum accepted
bioburden level?
With reference to the EMA Human and Veterinary
Notes for Guidance on Manufacture of the Finished Dosage Form
(CPMP/QWP/486/95 and EMEA/CVMP/126/95) a bioburden limit of no more than 10
CFU/100 ml is specified. When a prefilter is installed, this value should
also be achieved prior to the prefilter. Higher bioburden limits should not
be justified by the higher capacity of two consecutive bacteria retaining
filters.
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Why is filter validation
important to drug development?
Filter validation plays an
essential role in the drug development process. It’s required by the
regulatory bodies in support of product submissions that require a sterilizing
filter. Anything that is aseptically manufactured and goes through a
sterilizing filter needs to be validated through my department.
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Why Brevundamonas dimuta is used for filter validation
(Bacterial retention study)?
Brevundamonas dimuta is well-characterized,
well-known and well-standardized. Use of this microorganism provides several
advantages
v It is Generally regarded as nonpathogenic to
humans, ordinary microbiology laboratories can use it without major biohazard
concerns;
v
It can be
consistently cultured under controlled conditions to yield very small, mono dispersed
cells with a narrow size distribution. These can penetrate 0.45 m filters
reproducibly in small numbers at high challenge levels, thus representing a
potential worst-case challenge.
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What are the main parameters
for sterile filter validation
1.Integrity Testing (Bubble
point)
2.Filter Compatibility
3.Bacterial retention
4.Extractables & Leachable
5.Preservative binding
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