Pharma guidelines new updates

TOC Analyzer
Ø Ensurethat the instrument is in calibrated
condition before use.
Ø Ensureall the connections of the
instrument are proper before use.
Ø Opencarrier gas used for TOC (Zero air
cylinder) with cylinder pressure and gas
line pressure maintained at 4-6 Kg/cm2.
Ø Thepressure of the carrier gas i.e. Zero
air should be 2 Kg/cm2 (200kpa) and flow
should be 150 ml/min.Adjust if necessary by
opening the front doorand adjusting gas
pressure controller and mass flow controller.
Ø Ensurelevel of the water in the humidifier
should be kept between two marks shown
on the bottle i.e. between(High and Low
mark).
Ø Getthe raw data (printout) of the analysis
checked.
·        Disintegration test Apparatus
Ø Ensurethat the instrument s in calibrated
condition before use.
Ø Ensureall the connections of the
instrument are proper before use.
Ø Ensure,the bath is filled with water up to
the level marked (without beakers)
Ø Setthe temperature to 37oC unless
otherwise specified.
Ø Cleanthe basket rack assembly, beakers,
and discs after use.
·        Friabilator
Ø Ensurethat the instrument s in calibrated
condition before use.
Ø Ensureall the connections of the
instrument are proper before use.
Ø Fortablets with a unit weight equal to or
less than 650 mg, take a sample of whole
tablets corresponding as nearas possible to
6.5 g. For tabletswith a unit weight of
more than 650 mg, take a sample of 10
whole tablets.
Ø Thetablets should be carefully dedusted
prior to testing.
Ø Accuratelyweigh the tablet sample, and
place the tablets in the drum. After
testing remove the tablets. Remove any
loose dustfrom the tablets as before,
andaccurately weigh.
Ø Afterconducting friability test, weighing of
the tablets shall be done within 15minutes.
·        Statistical tools for evaluation of data
Ø Meanand Standard deviation:
Mean(arithmetic mean) is given by the
formula
x
=
X1 + x2 + x3 + ……. xn-1 + xn
n
Standard deviation (S), isgiven by the
formula
S
=
∑ (x - x)2
n-1
Relativestandard deviation (RSD), is given by
formula
RSD
=
S
x
Ø Comparisonof results
Thecomparison of the values obtained from
a set of results with either the truevalue or
with other sets of data makes it possible to
determine whether theanalytical procedure
has been accurate and / or precise, or if it is
superiorto another method. There are two
common method for comparing results,
Student’st-test and the variance ratio test
(F-test).
Student’st-test
This is the test used forsmall samples; its
purpose is to compare the mean from a
sample with somestandard value and to
express some level of confidence in the
significance ofthe comparison. It is also
used to test the difference between the
means of twosets of data x1 and x2.
The value of t is obtainedfrom the equation
t
=
( x - µ)
n
s
Whereµ is the true value.
F-test
Thisis used to compare the precisions of two
sets of data, e.g. the results of twodifferent
analytical methods or the results from two
different laboratories. Itis calculated from
the equation
F
=
S2A
S2B
Thelarger value of S is always used as the
numerator, so the value of F is
alwaysgreater than unity.
Ø Comparingthe means of two samples
Whena new analytical method is being
developed it is usual practice to compare
thevalues of the mean and precision of the
new (test) method with those of
anestablished (reference) procedure.
The value of t whencomparing two sample
means x1 and x2 is given by theexpression
t
=
x1- x2
Sp 1/n1 + 1/n2
WhereSp, the pooled standard deviation, is
calculated from the two samplestandard
deviations S1 and S2, as follows:
Sp
=
(n1-1)s21 + (n2-1)s22
n1 + n2 - 2
Notethat there must not be a significant
difference between the precisions of
themethods. Hence the F-test is applied
before using the t-test in equation.
Whenusing instrumental methods it is often
necessary to carry out a
calibrationprocedure by using a series of
samples (standards) each having a
knownconcentration of the analyte to be
determined. A calibration curve
isconstructed by measuring the instrumental
signal for each standard and plottingthis
response against concentration. Provided the
same experimental conditionsare used for
the measurement of the standards and for
the test (unknown)sample, the
concentration of the testsample may be
determined from the calibration curve by
graphical interpolation.
Correlationcoefficient
Toestablish whether there is a linear
relationship between two variables x1and
y1, use Pearson’s correlation coefficient r:
r
=
n∑ x1y1 - ∑x1∑y1
{[n∑x21 – (∑x1)2][n∑y21 –(∑y1)2]}1/2
Wheren is the number of data points.
Thevalue of r must lie between +1 and -1;
the nearer it is to ± 1, the greater
theprobability that a definite linear
relationship exists between the variables
xand y; values close to +1 indicate positive
correlation and values close to -1indicate
negative correlation. Values of r that tend
towards zero indicate thatx and y are not
linearly related (they may be related in a
non-linear fashion).
· Microbiologytesting
Ø Usecorrect incubation period and
temperature specified in the method of
analysis.
Ø Ensurethat the growth promotion test is
performed for the media to be used
foranalysis.
Ø Takeall required precautions while
handling the Microbiological cultures.
Ø Ensurethat the Microscope is calibrated
and working properly.
Ø Ensurethat all the glassware's used for
microanalysis are decontaminated properly.
Ø Culture/ suspending / sub culturing
should be traceable.
· Generalprecaution
Precautions:
Ø Crosscheckthe exactness of instrument
method / program & sequence with respect
to themethod of analysis.
Ø Crosscheckthe exactness of sequence
with respect to the samples loaded in auto
sampler.
Ø Alwayscompare response obtained with
previous data as a tool of crosscheck.
Ø Usecorrect excel sheet for calculation.
Ø Avoidglassware breakage. Upon breakage
of any glassware intimate to your
respectivesupervisor so that the requirement
for the same can be raised to avoid
shortageof glassware.
Ø Keepthe allocated samples in the
respective designated area during and
afteranalysis duly labeled.
Ø Recordthe temperature and humidity of
the areas daily once and intimate to
immediatesupervisor if any excursion is
observed for more than half an hour.
· Interpretation
Ø Interpretationshould be aligned with the
requirements in the method of analysis.
Ø Interpretationshould be done by
considering the category of the method e.g.
Relatedsubstances, assay etc.
Ø Donot use manual integration events for
quantification method unless
otherwisespecified in the method.
Ø Comparethe chromatographic data with
specimen chromatogram.
Ø Ifthe results are not as per trend then
inform immediately to immediatesupervisor.
· Records& Reports
Ø Recordthe values & results online.
Ø Checkthe entered values & figures for
correctness online.
Ø Calculatethe results using correct
formulae (as per method of analysis) &
recheckonce online.
Ø Donot overwrite the wrong entry. Cross it
out with a line permitting the readingof
original entry. Clearly write the correct entry
near the cross out &sign the data along with
the date on which correction is made.
Ø Donot leave the blank spaces. Draw a line
across the page from left to right.
Ø Allthe document entries shall be made
with indelible black ink in clear &legible
hand writing.
Ø Columnsor rows not required shall be
marked as ‘N.A.’ or ‘—’.
Ø Validateexcel sheet whenever required for
calculation of results of CU/BU &dissolution
(Profile/ Single point).
Ø Usecorrect path of validated excel sheet
for calculation of results.
Ø Ensurethat the usage and consumption
entry is made in the respective instrument
andcolumn log book and working standard
log book respectively.
Ø Ensurethat the respective index is updated
when any SOP/ Document is created /
revised.