2118-2517-Methylphenidate 27 MG Atras (2de2)

:
:
:
:
The signature page is the first page of the

document
THIS IS A PRINTED COPY OF AN ELECTRONIC DOCUMENT. PLEASE CHECK ITS VALIDITY BEFORE USE.
Document No. GP000189

5.0; Effective
: 04-Jan-2018
Version No. 02-Jan-2021
DISPERSION
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE
Full Name Title Department Date Justification

Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM 02-Jan- Created By
LABS 2018
Bhaskar Reddy
Manager, Quality Assurance QUALITY CONTROL-TR-OHM LABS 02-Jan-2018 Reviewed and Approved By
Bhupendra
Patel Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM 03-Jan-2018 Reviewed and Approved By
LABS
This document was approved and signed electronically and this is the manifestation of the
electronic signature.
Printed By : Arti Printed Time (IST) : 13-Mar-2019 3:13 AM 1

Pandya
The signature page is the first page of this document
GENERAL PROCEDURE
Document No. : GP000189
Version No. : 5.0; Effective
Effective Date : 04-Jan-2018
Review Due : 02-Jan-2021
Title : DISPERSION
Title : DISPERSION
Pharmacopeial Status : In-House
Objective : Dispersion is provided to determine compliance with the

requirements specified in the individual specification.
PROCEDURE (FOR DRY POWDER):
Method A: For Opadry Powder (Dry Dispersion coating systems (Dry Dispersions –
Film Coating Systems))
1. Place about 100 g of powder sample onto a 600 micrometer testing sieve
(U.S. #30 Standard).
2. Manually shake sieve, allowing powder to fall through.
3. Examine retain material. Guidelines for approval are as follows:
Foreign material: No foreign matter should be observed.
Undispersed Pigments: Specks observed should be equal to or less than 5.
Retained Material:
 Particles should be small, soft, and uniform in size and break up easily with
pressure applied with fingertip.
 Hard pieces that do not break up easily, but do disperse in water.

document
THIS IS A PRINTED COPY OF AN ELECTRONIC DOCUMENT. PLEASE CHECK ITS VALIDITY
GENERAL PROCEDURE
Title : DISPERSION
Printed By : Page No: 2/5
Arti Pandya Printed Time (IST) : 13-Mar-2019 3:13 AM
This document is signed electronically in Documentum-version 6.5

document
Method B: For Lakes and Pigment blends (Dry Pigment blends)
1. Place about 50 g of powder sample onto a 600 µm testing sieve (U.S. Sieve No. 30).
Manually shake the sieve, allowing powder to fall through. Examine the retained material.
2. Pour approximately 10 g of the blend onto a piece of white paper (or paper towel). Using
a spatula spread it over the paper towel or white piece of paper, examining for pigment
specks or streaks.
3. A passing result is seeing a completely dispersed product with no pigment specks or

streaks. Some blends cannot appear completely uniform due to its compatibility with
other ingredients, so where doubt exists, use a previously acceptable batch for
comparison.
4. An unacceptable result is seeing multiple undispersed pigment specks or lumps in which

case the batch will require additional processing.
Method C: For Opalux (Liquid Dispersions)
1. Pour approximately 10 grams of Product onto a piece of white paper.
2. Examine for foreign matter. None Present – PASS
3. Using a spatula, spread it over the paper, examining for pigment specks or streaks
 No specks: PASS
 Specks observed: FAIL
 Batch requires additional processing
4. Where doubt exists for any of these tests, review product history and/or evaluate
previously acceptable batches.
Page No: 3/5

Printed By : Arti Pandya Printed Time (IST) : 13-Mar-2019 3:13 AM
Method D For Product line 21s, 24k, 21A540005 (Colorcon D10 procedure):
1. Place about 100 g of powder sample onto a 600 micrometer testing sieve
(U.S. #30 Standard).
2. Manually shake sieve, allowing powder to fall through.
3. Examine retain material. Guidelines for approval are as follows:
4. Undispersed Pigments: Specks observed should be equal to or less than 5.
Retained Material:
5. Particles should be small, soft, and uniform in size and break up easily with pressure
applied with fingertip.
6. Hard pieces does not breakup easily, should dissolve in Methylene chloride or
Anhydrous Ethanol.
Page No: 4/5

This document is signed electronically in Documentum-version
6.5 The signature page is the first page of the document
Page No: 5/5
HISTORY OF CHANGES
CCR Supersedes Change(s) Made

Number (Number and
last
version)
Not Not Applicable  New General Test Procedure as per Colorcon
Applicable Standard Test
Method GLO-QC-TM-0729 Revision No. 4 for
Dispersion Test.
CC032281 GP000189 Ver.1.0  Procedure clarified as Method A and B so that

it can be used appropriately.
CC055802 GP000189 Ver.2.0  Method C Dispersion procedure for

OPALUX materials added.
CC058321 GP000189 Ver. 3.0 Method D added for For Product line 21s,
24k, 21A540005.
CC098598 GP000189 Ver. 4.0 Logo / template revised from “Ranbaxy” to

“Sun Pharma” due to the merger.
************* End of the document *************


4.0; Effective
: 16-Jun-2016
Version No. 15-Jun-2019
RESIDUE ON IGNITION/SULFATED ASH
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Daniel Savad
QA Senior Documentation Associate QUALITY ASSURANCE-TR-OHM LABS 09-Jun- Created By
2016
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 13-Jun-2016 Reviewed and Approved By
Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM LABS 14-Jun-2016 Reviewed and Approved By

Pandya
GENERAL PROCEDURE
Effective Date : 16-Jun-2016
Review Due : 15-Jun-2019
Title : RESIDUE ON IGNITION/SULFATED ASH
Title : RESIDUE ON IGNITION / SULFATED ASH
Pharmacopeial Status : USP
Objective : The test for RESIDUE ON IGNITION / SULFATED ASH

is provided to determine compliance with the requirements
given in the individual monograph/specifications.
Principle : The Residue on Ignition / Sulfated Ash test uses a

procedure to measure the amount of residual substance
not volatilized from a sample when the sample is ignited in
the presence of Sulfuric acid according to the procedure
described below. This test is usually used for determining
the content of inorganic impurities in an organic
substance.
Sulfated ash is the residue of metallic oxides if present in

the drug substance. Any metallic impurity present in the
drug substance is converted into sulfates by the addition
of Sulfuric acid. This is then ignited at a specific
temperature and for a specific time period as mentioned in
the individual monograph/specifications. The residue thus
obtained is the oxide of the metallic impurity.
Procedure:
Ignite the clean suitable crucible (silica, platinum, quartz or porcelain) at 600 ± 50° C for
30 min, allow to cool in a desiccator (silica gel or other suitable desiccant), then weigh.
Record the weight (W1).
Weigh accurately 1-2 g of the substance (W), or the amount specified in the individual
monograph in the crucible. Record the weight.

document
GENERAL PROCEDURE
Title : RESIDUE ON IGNITION/SULFATED ASH

document
Moisten the sample with small amount (usually 1 mL) of Sulfuric acid. Heat, gently at first, at a
temperature as low as practicable, until the substance is thoroughly charred, cool, then, unless
otherwise directed in the individual monograph moisten the residue with small amount (usually
1 mL) of Sulfuric acid, heat gently until white fumes no longer are evolved, and ignite at
600 ± 50°C unless another temperature is specified in the individual monograph, until the
residue is completely incinerated. Ensure that flames are not produced at any time during the
procedure.
Cool the crucible in a desiccator (over silica gel or other suitable desiccant), weigh, record the
weight (W2) and calculate the percentage of residue.
Unless otherwise specified, if the amount of the residue so obtained exceeds the limit
specified in the individual monograph, repeat moistening with Sulfuric acid, heating and
ignition as before, using a 30 minute ignition period until two successive weighing do not differ
by more than 0.5 mg or until the percentage of residue complied with the limit prescribed in the
individual monograph. Note the final weight. (W2).
Sulfated ash /
(W2 – W1)
Residue on ignition = × 100
(% w/w) W
Where:
W = Weight of substance taken, in g.

W1 = Weight of the empty crucible, in g.
W2 = Weight of crucible + ash in g.
Calibration of the muffle furnace may be carried out using an appropriate digital temperature
meter and a working thermocouple probe calibrated against a standard thermocouple
traceable to the National Institute of Standards and Technology.
Verify the accuracy of the measuring and controlling circuitry of the muffle furnace by checking
the positions in the furnace at the control set point temperature of intended use. Select
positions that reflect the eventual method of use with respect to location of the specimen
under test. The tolerance is ± 25°C at each position measured.
P rinted By : Arti Pandya

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9- Mar-2019 1:22 AM
Precautions:
1. Ensure that the muffle furnace is clean.
2. If more than one crucible is used it should be marked before weighing.
3. The tongs used to handle the crucible must be clean.
4. Cooling must be done in a desiccator.
5. Sulfuric acid used should be AR grade and free from any contamination.
6. Ignition must be conducted in a well-ventilated hood, protected from air currents.
7. Conduct the ignition at a temperature to affect the complete combustion of the carbon
without sample spill out.
8. Muffle furnace should be calibrated by an appropriate digital temperature meter.
9. Use heat resistant gloves while placing and removing the crucible from the muffle
furnace.
Page No: 4/5

Page No: 5/5
HISTORY OF CHANGES

Number (Number and last
version)
CC000481 GP000141 Version  Harmonizing General Procedure in the new
1.0 (Refer old electronic Documentum Compliance Manager
document STP-014 (DCM) system.
Rev.04).  Revised to bring in-line with Ranbaxy General
procedure GP000056 (Old number GP009).
CC035061 GP000141 Version  Corrected typographical / formatting errors (as

2.0 applicable).
 Fixed formatting of equation for calculation of
result (with numerator denominator lining up
with the division bar.
 No changes have been made to the content
of the document at this time.
CC080331 GP000141 Version  Revised Document Logo/Template from

3.0 “Ranbaxy” to “SUN Pharma”.
 Revised “If the amount of the residue so
obtained exceeds the limit…” to “Unless
otherwise specified, if the amount of the
residue so obtained exceeds the limit…”


4.0; Effective
: 02-Dec-2017
Version No. 30-Nov-2020
IODINE VALUE
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Nija Nobin
Executive-Quality Control QC OSD - DEWAS 07-Nov- Created By
2017
Hemendra Makwana
Manager - Quality Control - OSD - Dewas QC OSD - DEWAS 08-Nov-2017 Reviewed and Approved By
Kamal Sharma (QC)

Manager -2 - Quality Control QC PHARMA - PAONTA 08-Nov- Reviewed and Approved By
2017
Raju Naik
Senior Executive-Quality Assurance-Goa QUALITY CONTROL PHARMA – GOA 08-Nov- Reviewed and Approved By
2017
Dalip Kumar (QA)

Sr. Executive- Quality Assurance QA 09-Nov- Reviewed and Approved By
2017
Dinesh Singh (Solrex)

Sr.Executive-Quality Control Quality Control 11-Nov- Reviewed and Approved By
2017
Kirtan Lal Kewat

Manager - Quality Assurance - OSD - Dew QA OSD - DEWAS 13-Nov- Reviewed and Approved By
2017
Printed By : Arti Printed Time (IST) : 9- Mar-2019 1:35 AM 1

Pandya
GENERAL PROCEDURE
Effective Date : 02-Dec-2017
Review Due : 30-Nov-2020
Title : IODINE VALUE

Pharmacopeial Status : USP / BP / Ph. Eur / IP
Objective (if applicable) : This General Procedure provides guidelines for

carrying out the test for Iodine value.
Principle (if applicable) : The Iodine value is the number which expresses in
grams the quantity of halogen, calculated as Iodine
which is absorbed by 100 g of the substance under
the described conditions. Iodine value is a measure
of unsaturation in a compound.
Procedure:
USP METHODS
METHOD –I (HANUS METHOD)
Unless otherwise specified in the individual monograph, use the following quantity of the
substance being examined.
Iodine Weight in g,
value ± 0.1
expecte
<5 3.0
5-20 1.0
21-50 0.4
51-100 0.2
101-150 0.13
151-200 0.1
Page No: 2/13

GENERAL PROCEDURE
Page No: 3/13

Procedure
1. Unless otherwise specified, weigh accurately the quantity of the substance being
examined, stated as above table. Place it in a dry 250-mL Iodine flask. Add 10 mL of
Chloroform and dissolve.
2. Add slowly 25 mL of Iodobromide TS insert the stopper and allow to stand in the dark
for 30 min, unless otherwise specified in the monograph, shaking frequently.
3. Add 30 mL of Potassium iodide TS and 100 mL of water and titrate with 0.1 M Sodium
thiosulphate using starch TS, added towards the end of titration as indicator. Note the
number of mL required (a).
4. Carry out the operation in exactly the same manner, but without the substance being
examined. Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
W x 0.1
Where
b = Volume in mL of Sodium thiosulphate consumed in blank titration.

a = Volume in mL of Sodium thiosulphate consumed in sample titration.
M = Actual molarity of 0.1 M Sodium thiosulphate.
Note
If more than half of the Iodobromide TS is absorbed by the portion of the sample taken,
repeat the determination using a smaller portion of sample under examination.
METHOD II
Iodine Weight in g,
value ± 0.1
expecte
<5 3.0
5-20 1.0
21-50 0.4
51-100 0.2
101-150 0.13
151-200 0.1
Procedure
1. Melt the sample, if it is not already liquid. (Note: - The temperature during melting
should not exceed the melting point of the sample solution by more than 10°C).
2. Pass through two pieces of filter paper to remove any solid impurities and the last
traces of moisture. The filtration may be performed in an air oven at 100 °C but should
be completed within 5 min ± 30 sec. The sample must be absolutely dry. All
glassware must be absolutely clean and completely dry.
3. After filtration, allow the filtered sample to achieve a temperature of 68 °C to 71 ± 1 °C
before weighing the sample. Once the sample has achieved a temperature of 68 °C to
71 ± 1°C, immediately weigh the sample into a 500-mL Iodine flask, using the weights
and weighing accuracy noted in the accompanying table.
4. Add 15 mL of a mixture of fresh cyclohexane and Acetic acid (1:1), and swirl to
dissolve the sample.
5. Add 25.0 mL of Iodochloride TS, insert the stopper securely in the flask, and swirl to
mix. Allow it to stand at 25 ± 5 °C, protected from light, with occasional shaking, for
1.0 h. or 2.0 h. (If the Iodine value is less than 150, then shake for 1.0 h, if Iodine value
is equal or more than 150 then shake for 2.0 h). Then, within 3 min after the indicated
reaction time, add, in the order named, 20 mL of Potassium iodide solution(10 % w/v)
and 150 mL of recently boiled and cooled water, and mix.
6. Within 30 min, titrate the liberated Iodine with 0.1 M Sodium thiosulfate, while stirring
by Mechanical means after each addition of thiosulfate. When the yellow Iodine color
has almost disappeared, add 1 - 2 mL of Starch indicator solution, and continue the
titration with 0.1 M Sodium thiosulfate until the blue color is discharged.
7. Perform a blank test at the same time with the same quantities of the same reagents
and in the same manner.
Calculations
V x 1.269 x M
Iodine value = ------------------
w x 0.1
Where
V = Difference of test and blank titration reading, in mL.

w = Weight of substance taken, in g.
M = Actual molarity of 0.1 N Sodium thiosulphate.
Note: The weight of the substance must be such that there will be an excess of
Iodochloride TS of 50 - 60 % of the amount added, that is, 100 % to 150 % of the amount
absorbed).

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Arti Pandya Printed Time (IST) : 9- Mar-2019 1:35 AM

document
BP/ PH. EUR. METHODS
METHOD A
Presumed Iodine value Quantity required (g)
< 20 1.0
20 – 60 0.5 - 0.25
60 – 100 0.25 - 0.15
> 100 0.15 - 0.10
Procedure
examined, stated as above table. Place it in a dry 250-mL Iodine flask which is dry or
has been rinsed with glacial Acetic acid and add 15 mL of Chloroform and dissolve
unless otherwise specified in the monograph.
2. Add slowly 25 mL of Iodine bromide solution (2 % w/v in glacial acetic acid). Insert the
stopper and allow to stand in the dark for 30 min, unless otherwise specified in the
monograph, shaking frequently.
3. Add 10 mL of Potassium iodide 100 g / 1000 mL solution and 100 mL of water and
titrate with 0.1 M Sodium thiosulphate. Shaking vigorously until the yellow colour is
almost discharged. Add 5 mL of starch solution and continue the titration adding the
0.1 N sodium thiosulphate dropwise until the colour is discharged. Note the number of
mL required (a).
Page No: 6/13

Page No: 7/13
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
W x 0.1
Where

Method B
Procedure
examined, stated in the below Table. Place it in a dry 250-mL Iodine flask fitted with a
ground stopper and which is dry or has been rinsed with glacial Acetic acid. Add 15 mL
of mixture of equal volume of Cyclohexane & glacial acetic acid and dissolve unless
otherwise specified in the monograph. If necessary, melt the substance before
dissolution (melting point greater than 50 °C).
Presum Mass (g) Mass (g) Iodine

ed (correspondi (correspondi chloride
value ng to an ng to an solution
II excess of excess (ml)
<3 150 10
% ICI) of 10010% ICI) 25
3 8.4613 10.5760 25
5 5.0770 6.3460 25
10 2.5384 3.1730 20
20 0.8461 1.5865 20
40 0.6346 0.7935 20
60 0.4321 0.5288 20
80 0.3173 0.3966 20
100 0.2538 0.3173 20
120 0.2115 0.2644 20
140 0.1813 0.2266 20
160 0.1587 0.1983 20
180 0.1410 0.1762 20
200 0.1269 0.1586 20
2. Add very slowly the volume of Iodine Chloride solution (1.4 % w/v solution in glacial
acetic acid) stated in the above table. Close the flask and keep it in the dark for 30 min,
unless otherwise prescribed. Shaking frequently.
3. Add 10 mL of Potassium iodide 100 g / 1000 mL solution and 100 mL of water and
Titrate with 0.1 M sodium thiosulphate , shaking vigorously until the yellow colour is
almost discharged. Add 5 ml of starch solution and continue the titration adding the
0.1 M sodium thiosulphate dropwise until the colour is discharged. Note the number of
mL required (a).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where


document

Arti Pandya Printed Time (IST) : 9- Mar-2019 1:35 AM

document
IODINE MONOCHLORIDE METHOD (AS PER BP)
1. Dissolve the specified quantity of the substance being examined, accurately weighed, in
10 mL of dichloromethane in a dry 250 mL Iodine flask.
2. Add 20.0 mL of Iodine monochloride solution, insert the stopper, previously moistened
with dilute Potassium iodide solution(10 % w/v), and allow to stand in the dark at 15 °C
to 25 °C for 30 min.
3. Place 15 mL of dilute Potassium iodide solution(10 % w/v) in the cup top, carefully
remove the stopper, rinse the stopper and the sides of the flask with 100 mL of water,
shake and titrate with 0.1 M Sodium thiosulphate using starch mucilage, added towards
the end of the titration, as indicator. Note the number of mL required (a).
4. At the same time carry out the operation in exactly the same manner, but without the
substance being examined. (Blank titration). Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where

NOTES
1. The approximate weight, in g, of the substance to be taken may be calculated by

dividing 20 by the highest expected Iodine value.
2. If more than half of the available Halogen is absorbed, the test must be repeated, using
a smaller quantity of the substance.
Page No: 9/13

Printed By : Arti Pandya Printed Time (IST) : 9- Mar-2019 1:35 AM
IP METHODS
METHOD A (WIJS METHOD OR IODINE MONOCHLORIDE METHOD)
Procedure
1. Dissolve the specified quantity of the substance being examined, accurately weighed, in
10 mL Carbon tetrachloride in a dry 500 mL Iodine flask.
2. Add 20.0 mL of Iodine monochloride solution, insert the stopper and allow to stand in the
dark at 15 °C to 25 °C for 30 min.
3. Place 15 mL of Potassium iodide solution(16.6% w/v) in the cup top, carefully remove
the stopper, rinse the stopper and the sides of the flask with 100 mL of water, shake and
titrate with 0.1 M Sodium thiosulphate using starch solution, added towards the end of
the titration, as indicator. Note the number of mL required (a).
substance being examined. (Blank titration). Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where

NOTES

dividing 20 by the highest expected Iodine value.
Page No: 10/13

METHOD B (IODINE MONOBROMIDE METHOD OR HANUS METHOD)
Presumed Iodine value Quantity required

(g)
Less than 20 1.0
20 – 60 0.25 - 0.5
61 – 100 0.15 - 0.25
More than 100 0.10 - 0.15
Procedure
examined, stated as above.Place it in a dry 300 mL Iodine flask which is dry or has
been rinsed with glacial Acetic acid unless otherwise specified in the monograph. Add
15 mL of Chloroform and dissolve.
2. Add slowly from a burette 25 mL of Iodine bromide solution. Insert the stopper and
allow to stand in the dark for 30 min, unless otherwise specified in the monograph,
shaking frequently.
3. Add 10 mL of Potassium iodide solution (16.6 % w/v) and 100 mL of water and titrate
with 0.1 M Sodium thiosulphate using starch solution, added towards the end of
titration as indicator. Note the number of mL required (a).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
W x 0.1
Page No: 11/13

Where

METHOD C (PYRIDINE BROMIDE METHOD)
Procedure
1. Dissolve the specified quantity of the substance being examined in 10 mL of Carbon

tetrachloride in a dry Iodine flask.
2. Add 25 mL of Pyridine bromide solution, allow to stand for 10 min, in the dark place.
Add 15 mL of Potassium iodide solution (16.6 % w/v) in the cup top, carefully remove
the stopper, rinse the stopper and the sides of the flask with 100 mL of water, shake
and titrate with 0.1 M Sodium thiosulphate using starch solution, added towards the
end of the titration, as indicator. Note the number of mL required (a).
substance being examined. Note the number of mL required (b).
Calculations
(b-a) x 1.269 x M
Iodine value = -----------------------
w x 0.1
Where

Page No:
Page No:
Note

dividing 12.5 by the highest expected Iodine value.
Note: The reference of Legacy General Procedure number is GP058.
HISTORY OF CHANGES
CCR Number Supersedes Change(s) Made

(Number and
last
version)
CC014811 1. Routine GP review.
GP000083/1.0 2. Specified weight for expected iodine
value amended under the table for USP
grade material in line with current USP.
3. GP amended in line with
current Pharmacopeia.
4. GP template revised.
CC056392 GP000083/2.0 1. Routine GP review.

2. Separate method made as per
Pharmacopeia(BP/Ph. Eur./IP/USP).
3. Concentration of Iodine Bromide, Iodine
Chloride and potassium iodide solution
defined.
4. Editorial changes done.
CC096575 GP000083 Ver. 3.0 1. Routine GP revision.
2. Template logo changed from Ranbaxy to
Sun Pharma.


8.0; Effective
: 16-Nov-2018
Version No. 14-Nov-2021
DESCRIPTION
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM 13-Nov- Created By
LABS 2018
Jignesh Soni
Associate Director QC 14-Nov- Reviewed and Approved By
2018
Bhupendra
Patel Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM Reviewed and Approved By
LABS 15-Nov-2018
Printed By : Arti Printed Time (IST) : 11-Mar-2019 9:25 PM 1

Pandya
GENERAL PROCEDURE
Effective Date : 16-Nov-2018
Title : DESCRIPTION
Title : DESCRIPTION
Objective : The test for Description is provided to determine compliance

with the requirements given in individual monograph /
specifications.
Principle : Description is a general requirement given for information in

most of the monographs. The property is not standard for
purity even though it may directly assist in the preliminary
evaluation. Where, however, description is included under the
heading ‘standards’ the drug shall comply with the
requirement.
Procedure:
ODOR
1. Examine a sample of not more than 25 g immediately after opening the package.
2. If any odor is perceptible, transfer the sample rapidly to an open container and
re-examine after 15 min.
3. If the odor is still there, the sample does not comply with the description odorless.
NOTE: The terms ‘odorless’ or ‘practically odorless’ or ‘faint’ characteristics odor are
descriptive only and are not to be regarded as standards of purity for a particular lot of
an article, except in those cases where a particular odor is specifically prohibited in the
monograph under ‘standards’.
The flavors may be checked by comparing it with the latest approved batch kept in a
well closed container.
Page No: 2/8

Printed By : Arti Pandya Printed Time (IST) : 11-Mar-2019 9:25 PM
GENERAL PROCEDURE
Effective Date : 16-Nov-2018
Title : DESCRIPTION
Page No: 3/8

TASTE
Statements on taste are provided only in cases where this property is a guide to the
acceptability of the material. Such statements are not part of the official standards.
COLOR
1. The test for color may be checked by spreading the material/powder/beads under test on
a clean butter paper in a well illuminated area and may be compared with the color of
the last / previously approved batch / lot or checked with the unaided eyes.
2. Any variation may be noted down and reported.
3. The color of the solvents may also be checked by taking the sample in a clean
stoppered test tube.
4. White color may be checked against a black background and black and other colors may
be checked against white background.
Quantity of the dosage units shall be taken for description as per below table.
Table
Sr. No. Types of dosage unit Required quantity
1 Tablets Minimum five Tablets

2 Capsules Minimum five Capsules
3 Dry syrup Minimum one bottle
4 Liquid orals Minimum one bottle
5 Injection Minimum two vial/ Ampoules
6 Ointment/Cream Minimum one tube
7 Eye drops Minimum one bottle/vial/other pack
Note: Description can be checked during execution of other tests also e.g. Average
weight, Viscosity etc. and less quantity also can be used for description test based on
availability of dosage units.
TABLETS
A. UNCOATED/CORE TABLETS
1. Observe the shape, nature of the edges, scoring, color and imprints of a representative
sample.
2. In case of uncoated tablets, also observe the presence of foreign matter, sticking,
chipping, capping, mottling and color uniformity.
3. The color of the tablets should match the current color shade requirements. The color of
a previously approved batch may be taken as a reference.
B. FILM COATED TABLETS
1. Observe and record the nature of tablets, shape, shine, color, color uniformity and
intactness (batch to batch and within the batch).
C. SUGAR COATED TABLETS
1. Observe and record the nature of tablets, shape, shine, color, color uniformity and
intactness (batch to batch and within the batch).
CAPSULE
A. HARD GELATIN CAPSULES
1. Observe the color combination of cap and body, color of imprints on cap and body, self-
locking, size and any abnormality.
2. Open capsules and collect the powder on a clean white paper and record the color and
nature of the powder.
B. SOFT GELATIN CAPSULES
Observe, record and report the color, imprints, shape and any abnormality. Open capsules
and record the color and nature of the collected semi-solid mass.
Page No: 4/8
document

document
DRY SYRUP (POWDER FOR ORAL SUSPENSION)
1. Take out the contents from the dry syrup bottles and report the color, flavor and nature
of the powder.
2. Reconstitute as directed on the label and report its nature, color, suspendibility, taste
and flavor.
LIQUID ORALS
1. Observe and note the description of the oral liquid preparation (clear liquid; syrupy
liquid; suspension), color of the liquid, taste and flavor of the liquid.
2. For description and color of the liquid observation is done by pouring out adequate
quantity from a bottle to a clean and dry transparent glass container (test tube, or
beaker).
INJECTIONS
A. AMPOULES
Take out the contents from the ampoule and transfer into a clean dry test tube. Observe
and record the nature, color and foreign particles, if any.
B. VIALS
1. Take out the contents from the vial on a white paper and observe the nature and color
of the powder.
2. Reconstitute the injection in a vial by injecting a quantity of water for injection as
specified for the product in the pharmacopeia or in the directions for use.
3. Observe and record the solubility, color and nature of solution or suspension.
Page No: 5/8

INTRAMAMMARY INJECTION
Take out the contents of a disposable syringes on a butter paper and record the apparent
consistency, transparency or translucency, color and grittiness.
OINTMENT
Take out the contents of a collapsible tubes, bottles / jars or cartridges, on a butter paper
and record the apparent consistency, transparency or translucency, color and grittiness.
EYE DROPS
Shake and transfer the contents to a clean dry container and record the color, nature (clear
liquid / suspension) and presence of any suspended ingredients.
NOTE: The description for color, taste and odor may vary from person to person, however,
until there is significant difference, all the statements should be treated as same.
OPADRY’S
Perform the Film Formation test for both standard and sample. For the Description test,
compare the films of standard and sample.
REFERENCES
BP / Ph. Eur / IP / USP
Page No: 6/8

Page No: 7/8
HISTORY OF CHANGES

(Number and last
version)
CC003544 GP000054 Version  Revised to the current Documentum format.
1.0 (Refer to old
document GP001 –
05)
CC039645 GP000054 Ver. 2.0 Revised to provide new effective date.
No change in the content of the document.

CC057781 GP000054 Ver. 3.0 1. Quantity of Dosage units specified for the
requirement of testing and corresponding
note included.
2. Powder/beads specified under the
procedure of “Color”.
3. Editorial changes done.
CC060057 GP000054 Ver. 4.0  Revised COLOR section step 1 to “The

test for color may be checked by
spreading the material/powder/beads under
test on a clean butter paper in a well
illuminated area and may be compared
with the color of the last/previously
approved batch / lot or checked with the
unaided eyes.”
 Revised FILM COATED TABLETS section,
step 1 to “Observe and record the nature
of tablets, shape, shine, color, color
uniformity and intactness (batch to batch
and within the batch).”
 Removed step 2 from FILM COATED
TABLETS section
 Removed step 2 from SUGAR COATED
TABLETS section
GP072002 GP000054 Ver. 5.0 Company name/Logo changed from Ranbaxy
to Sun pharma
HISTORY OF CHANGES
CCR Number Supersedes (Number Change(s) Made
and last version)
CC106916 GP000054 Ver. 6.0 Routine GP Review.
CC108262 GP000054 Ver. 7.0 New section for Opadry’s added.


7.0; Effective
: 01-Feb-2018
MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
:
Effective Date : MICROORGANISMS
Review Due
:
Title
:
SIGNATURE PAGE

Daniel Savad
Coordinator, Quality Assurance QUALITY ASSURANCE-TR-OHM LABS 30-Jan- Created By
2018
Bhaskar Reddy
Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM LABS 30-Jan-2018 Reviewed and Approved By
Pandya
GENERAL PROCEDURE
Effective Date : 01-Feb-2018
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED
MICROORGANISMS
Title : MICROBIAL ENUMERATION TESTS AND TESTS FOR

SPECIFIED MICROORGANISMS
1.0 MICROBIAL ENUMERATION TESTS AND TESTS FOR SPECIFIED

MICROORGANISMS
2.0 OBJECTIVE
This document describes the general procedure to be employed in microbial

enumeration tests and tests for specified microorganisms at OHM laboratories, Inc,
New Jersey Facilities
3.0 SCOPE
This procedure is used for testing raw materials, finished products, intermediates and
drug substance or excipients for Total Aerobic microbial count (TAMC), Total
combined Molds and Yeasts count (TYMC) and for the presence of Staphylococcus
aureus, Pseudomonas aeruginosa, Salmonella species, Escherichia coli, Candida
albicans and Bile tolerant Gram negative bacteria. In accordance with the
harmonized USP Microbiological Examination of Non sterile Products: ‘Microbial
Enumeration Tests’ referenced in USP <61>, Tests for ‘Specified Microorganisms’
referenced in USP <62>, and the ‘Acceptance Criteria of Pharmaceutical
Preparations and Substances for Pharmaceutical Use, referenced in USP <1111>.
4.0 RESPONSIBILITY
4.1. All microbiologists shall be responsible for testing all test samples per
this procedure
4.2. QC Group leaders or designee shall be responsible for implementing this

procedure
Page No: 2/36

GENERAL PROCEDURE
MICROORGANISMS
Page No: 3/36

5.1 PROCEDURE
5.1. TEST REQUIREMENTS:
Approximately 45 g or 45 mL of Test sample.
5.2. SAFETY:
Always observe safe laboratory practices. Consult the appropriate safety

Data Sheet (MSDS) before handling any chemical if you are unfamiliar with
the proper safety precautions.
5.3. EQUIPMENT:
1 Top loading or Analytical 9 Sterile Culture tubes 12 x75 mm, with

balance capable of weighing screw caps or suitable sterile covers,
10.0-100.0g and French square bottles
2 Incubator –capable of 10 Water bath- capable of maintaining
maintaining a temperature of a temperature of 37 -45°C.
30-35°C.
3 Incubator –capable of 11 Colony counter with magnification to
maintaining a temperature of aid in counting colonies.
20-25°C.
4 Incubator –capable of 12 Biological Safety Cabinet
maintaining a temperature of
42-44°C.
5 Sterile Petri dishes- 100 x 13 Vortexer.
20
6 mm, 100
Sterile x 15 mm Loops –
Inoculating 14 pH Meter
10
7 µL
Inoculating wire 15 Pipettes
8 Ultra violet light source.
5.4. CULTURE MEDIA AND REAGENTS
5.4.1.CULTURE MEDIA
1 Soybean Casein Digest Broth 9 Mannitol Salt Agar (MSA)

(SCB) or Trypticase Soy Broth
(TSB)
2 Soybean Casein Digest Broth 10 Sabouraud Dextrose Agar (SDA)
or Trypticase Soy Broth) with
4 % Polysorbate 20 and
0.5% Lecithin (*SCB) or
3 (*TSB)
Soybean Casein Digest Agar 11 Enterobacteria Enrichment Broth Mossel
(SCDA) or Trypticase Soy
Agar (TSA) with 4%
Polysorbate 20
(Tween 20) and 0.5% Lecithin
4 (*SCDA) orCasein
Soybean (*TSA)Digest Agar 12 Violet Red Bile Glucose Agar (VRBGA)
(SCDA) or (Trypticase Soy
Agar) (TSA)
5 Sabouraud Dextrose Agar 13 Sabouraud Dextrose Broth (SDB)
containing 50.0 mg or 0.05 g
of Chloramphenicol (SDA+)
6 MacConkey Agar (MCA) 14 Rapport Vassiliadis
Salmonella Enrichment
7 MacConkey Broth (MCB) 15 broth (RVSEB)
Xylose Lysine Deoxycholate Agar
8 Cetrimide Agar (CET) 16 Potato Dextrose Agar (PDA)
Note: “*” used to denote media with added 4 % Polysorbate 20 and 0.5 % lecithin “+”
used to denote SDA with added Chloramphenicol
5.4.2. REAGENTS
1 Buffered Sodium Chloride-Peptone Solution pH 7.0

2 Sodium Hydroxide (1N)
3 Hydrochloric acid (1N)
4 Glycerol
5 Mammalian Plasma- standardized, desiccated rabbit plasma or equivalent
(For coagulase Test)
6 Oxidase test Disks or strips impregnated with N, N-dimethyl-p –
phenylenediamine dihydrochloride
5.5. MEDIA PREPARATION:
5.5.1. The media required in this procedure are made from the
ingredients listed herein.
5.5.2. Minor modifications to the individual ingredients can be made or

reconstituted dehydrated media may be substituted, provided the
resulting media possesses equal or better growth promoting
properties.
5.5.3. Adjust the solution with either 1N Sodium hydroxide or 1N

Hydrochloric acid as required so that after steam sterilization the
pH is as specified at 25 ± 2°C.
5.5.4. Sterilize the media in an autoclave, using a validated process.
NOTE: When reconstituting dehydrated media follow the

manufacturer’s direction, otherwise refer to current USP
method.
5.6. MEDIA AND SOLUTIONS USED DURING TESTING:
A
Buffered Sodium Chloride-Peptone Solution pH 7.0
Potassium Dihydrogen Phosphate 3.6 g
Disodium Hydrogen Phosphate Dihydrate 7.2 g t 0.06 M
(equivalent o 7
Sodium Chloride phosphate)
4.3 g
Peptone (meat or casein) 1.0 g
Purified Water 1000 mL
Adjust the pH so that after sterilization it is 7.0 at 25 °C. Sterilize in an autoclave using a
validated cycle
B
Stock Buffer Solution
Transfer 34.0g of potassium dihydrogen phosphate to a 1000-mL volumetric
flask, dissolve in 500 mL of purified water, adjust with sodium hydroxide to a
pH of 7.2 ±0.2, add purified water to volume, and mix. Dispense in containers,
and sterilize in an autoclave, using a validated cycle. Store at a temperature of
2°C to 8°C
C
Phosphate Buffer Solution pH 7.2
Prepare a mixture of Purified Water and Stock Buffer Solution (800:1 v/v), and
sterilize
D
Soybean-Casein Digest Agar (SCDA or TSA)
Pancreatic digest of Casein 15.0 g
Papaic Digest of Soya bean meal 5.0 g
Sodium chloride 5.0 g
Agar 15.0 g
Sterilize in an autoclave using a validated cycle. Adjust pH so that after sterilization it is
7.3 ± 0.2 at 25 °C or according to Manufacturer’s label
E
Soybean Casein Digest Agar with 4 % Polysorbate 20 (Tween 20)
and 0.5 % Lecithin (*SCDA or *TSA)”
Papaic Digest of Soya bean meal 5.0 g
Agar 15.0 g
4 % Tween 20 40 mL
0.5% % Lecithin 5.0 g
Adjust pH so that after sterilization, it is 7.3 ± 0.2 at 25°C or according to Manufacturer’s
label. Autoclave using a validated cycle.
F
Soybean-Casein digest Broth (SCD or TSB)
Papaic Digest of Soybean 3.0 g
Dibasic Potassium Phosphate 2.5 g
Dextrose 2.5 g
Purified Water 1000mL
Adjust the pH so that after sterilization it is 7.3 ± 0.2 at 25°C or according to
manufacturer’s label. Sterilize in an autoclave using a validated cycle.
G
Soybean Casein Digest Broth with 4 % Polysorbate 20 and 0.5 %
Lecithin (*SCB or *TSB)
Papaic Digest of Soybean 3.0 g
Dibasic Potassium Phosphate 2.5 g
Dextrose 2.5 g
4% Polysorbate 20 (tween 20) 40 mL
0.5 % Lecithin 5.0 g
Adjust the pH so that after sterilization it is 7.3 ± 0.2 at 25°C or according to the
manufacturer’s label. Sterilize in an autoclave using a validated cycle
H
Sabouraud Dextrose Broth (SDB)
Mixture of Peptic Digest of Animal Tissue 10.0 g
and Pancreatic Digest of Casein (1:1)
Dextrose 20.0 g
Adjust the pH so that after sterilization it is 5.6 ± 0.2 or according to manufacturer’s label.
Sterilize in an autoclave using a validated cycle.
I
Sabouraud Dextrose Agar (SDA)
Mixture of Peptic Digest of Animal Tissue 10.0 g
and Pancreatic Digest of Casein (1:1)
Dextrose 40.0 g
Agar 15.0 g
Adjust the pH so that after sterilization it is 5.6 ± 0.2 at 25°C or according to the
J
Sabouraud Dextrose Agar with 0.05g (50.0 mg)
Chloramphenicol (SDA+)
Dextrose 40 g
Mixture of equal parts of peptic
Digest of animal tissue and 10 g
pancreatic digest of Casein
Agar 15 g
Lecithin 5g
Chloramphenicol 0.05 g
Add 0.05 g of Chloramphenicol to each 1000 mL of re-hydrated medium. Heat to boiling.
Adjust the pH so that after sterilization it is 5.6 ± 0.2. at 25°C or according to the
K
Enterobacteria Enrichment Broth Mossel
Pancreatic Digest of Gelatin 10.0 g
Glucose Monohydrate 5.0 g
Dehydrated Ox Bile 20.0 g
Disodium Hydrogen Phosphate Dihydrate 8.0 g
Brilliant Green 15 mg
Purified water 1000 mL
Adjust the pH so that after heating it is 7.2 ±0.2 at 25 °C. Heat at 100°C for 30 minutes
and cool immediately.
L
Violet Red Bile Glucose Agar (VRBGA)
Pancreatic Digest of Gelatin 7.0 g
Yeast Extract 3.0 g
Bile Salts 1.5 g
Sodium Chloride 5.0 g
Glucose Monohydrate 10.0 g
Agar 15 0 g
Neutral Red 30 mg
Crystal Violet 2 mg
Adjust pH so that after heating it is 7.4 ± 0.2 at 25 °C or according to the manufacturer’s
label. Heat to boiling; do not heat in an autoclave.
M
MacConkey Agar (MCA)
Pancreatic digest of Gelatin 17.0 g
Peptone (meat and Casein) 3.0 g
Lactose (Lactose Monohydrate) 10.0 g
Sodium chloride 5.0
Bile salts 1.5 g
Agar 13.5 g
Neutral red 3.0 mg
Crystal violet 1 mg
Adjust pH so that after sterilization it is 7.1± 0.2 at 25°C or according to the
N
MacConkey Broth (MCB)
Pancreatic digest of Gelatin 20.0 g
Lactose 10.0 g
Dehydrated Ox Bile (Oxgall) 5.0 g
Bromocresol Purple 10 mg
Adjust the pH so that after sterilization, it is 7.3 at 25°C. Sterilize in an autoclave
using a validated cycle.
O
Rappaport Vassiliadis Salmonella Enrichment Broth (RVSEB)
Soya Peptone 4.5 g
Magnesium Chloride Hexahydrate 29.0 g
Dipotassium Phosphate 0.4 g
Malachite Green 0.036 g
Dissolve by warming slightly. Sterilize in autoclave using validated cycle. Adjust the pH
so that after heating and sterilization, it is 5.2±0.2 at 25°C or according to the
manufacturer’s label.
P
Xylose Lysine Deoxycholate (XLD) Agar
Xylose 3.5 g
L-Lysine 5.0 g
Lactose (Lactose Monohydrate) 7.5 g
Sucrose 7.5 g
Yeast extract 3.0 g
Phenol red 80 mg
Agar 13.5 g
Sodium Deoxycholate 2.5 g
Sodium Thiosulfate 6.8 g
Ferric Ammonium Citrate 0.8 g
Adjust pH so that after heating it is 7.4 ± 0.2 at 25°C or according to the manufacturer’s
label. Heat just to boil, cool to 50°C in a water bath and pour into Petri dishes. Do not
heat in an autoclave.
Q
Cetrimide (CET) Agar
Pancreatic digest of gelatin 20.0 g
Magnesium Chloride 1.4 g
Potassium sulfate 10.0 g
Agar 13.6 g
Cetrimide 0.3 g
Glycerol 10.0 mL
Add 10 mL of Glycerol in a liter of the solution. Heat to boiling for 1 minute with shaking.
Adjust the pH so that after sterilization it is 7.2±0.2 at 25°C or according to
R
Mannitol Salt Agar
Peptic digest of Animal Tissue 5.0 g
Beef extract 1.0 g
D- Mannitol 10.0 g
Phenol red 0.025 g
Agar 15.0 g
Heat to boiling for 1 minute with shaking. Adjust the pH so that after sterilization it is
7.4 ± 0.2. at 25 °C or according to the manufacturer’s label. Sterilize in an autoclave
using a validated cycle.
S
Potato Dextrose Agar
Infusion from potatoes 200 g
Dextrose 20.0 g
Agar 15.0 g
Adjust the pH so that after sterilization it is 5.6±02 at 25 °C or according to
manufacturer’s label. Sterilize in an autoclave using a validated cycle
5.7. TEST PROCEDURE:

 All steps should be performed using aseptic techniques and sterile
equipment, whenever possible.
 Expose pre-solidified plates of TSA and SDA+ Plates during the
procedure for air monitoring. After the testing has been completed
incubate as indicated for each culture medium.
5.7.1. USP <61>): TOTAL AEROBIC MICROBIAL COUNT (TAMC) AND
TOTAL COMBINED MOLDS AND YEASTS COUNT (TMYC)
(MICROBIAL ENUMERATION TEST, POUR PLATE METHOD:
5.7.1.1. SAMPLE PREPARATION
5.7.1.1.1. Prepare the product to be examined by using the

quantity corresponding to not less than 10 g or 10 mL
and transferring into a suitable amount of Soybean
casein Digest Broth (TSB) with or without 4%
Polysorbate 20 and 0.5% Lecithin (e.g. 10 g or 10 mL
to 90 mL TSB or other diluent) to have a 1:10 dilution.
Further dilutions, where necessary, are prepared with
the same diluent.
5.7.1.1.2. For Petri dishes 9 cm in diameter, transfer 1 mL of the

sample into each of duplicate Petri dishes.
5.7.1.1.3. For total aerobic microbial count (TAMC), add 15 to

20 mL of Soy Bean Casein Digest Agar (TSA) with or
without 4% Polysorbate 20 (Tween 20) and 0.5%
Lecithin, which had been cooled to 44 – 46°C into
each of the duplicate Petri dishes and allow to
solidify. For total combined molds and yeasts count
(TYMC), transfer 1 mL of the sample into each of
duplicate Petri dishes and add 15 to 20 mL of
Sabouraud Dextrose Agar with antibiotics (SDA+) that
has been cooled to 44 to 46°C and allow to solidify.
NOTE: Unless otherwise specified, the agar

culture medium must be added within 15
minutes of the TSB sample preparation.

document


document
GENERAL PROCEDURE
MICROORGANISMS
5.7.1.1.4. Prepare negative diluent controls by pipetting 1 mL of

the same lot of TSB or other diluents used in the
sample preparation into each of duplicate Petri dishes.
Add 15-20 mL of TSA with or without 4% Polysorbate
20 (Tween 20) and 0.5% Lecithin, which has been
cooled to 44-46 °C. Pipette another 1 mL of TSB or
other diluents of the same lot of TSB/other diluents
used in the test into each of duplicate Petri dishes and
add 15-20 mL of Sabouraud Dextrose Agar with
antibiotics (SDA+) which has been cooled to
44 – 46°C. Allow the agar plates to solidify.
5.7.1.1.5. Prepare negative media controls by adding 15-20 mL

of the same lot of each of the agar medium used in
the test into a Petri dish and allow to solidify.
5.7.1.2. SAMPLE INCUBATION, PLATE READING AND

INTERPRETATION OF RESULTS
5.7.1.2.1. Incubate the TSA agar plates at 32.5 ± 2.5°C for

3- 5 days and the SDA+ plates at 22.5 ± 2.5°C for
5 – 7 days.
5.7.1.2.2. Count colony forming units (CFU) in each Petri dish

using a colony counter. (Where it is not possible to
use a colony counter, count manually and provide an
explanation).
5.7.1.2.3. Select the plates corresponding to a given dilution and

showing the highest number of colonies less than
250 for TAMC and 50 for TYMC. Take the arithmetic
mean per culture medium of the counts, and calculate
the number of CFU per g or per mL of product.
GENERAL PROCEDURE
MICROORGANISMS
5.7.2. USP <62>: TESTS FOR SPECIFIED MICROORGANISMS, TESTS

FOR STAPHYLOCOCCUS AUREUS, PSEUDOMONAS
AERUGINOSA, ESCHERICHIA COLI,SALMONELLA SPECIES,
CANDIDA ALBICANS, AND BILE-TOLERANT GRAM-NEGATIVE
BACTERIA
5.7.2.1. TEST FOR STAPHYLOCOCCUS AUREUS (S. aureus):
5.7.2.1.1. Prepare a sample using a 1 in 10 dilution of not less

than 1g or 1 mL of the product to be examined as
described in Section 5.7.1.1 (Sample Preparation),
and use 10 mL or the quantity corresponding to 1 g or
1 mL to inoculate a suitable amount of Soybean-
Casein Digest broth (TSB) with or without 4%
Polysorbate 20 and 0.5% Lecithin e.g. 10 g or 10 mL
to 90 mL TSB with or without 4% Polysorbate 20 and
0.5% Lecithin to have a 1:10 dilution.
5.7.2.1.2. Incubate the sample solution at 32.5 ± 2.5°C for

18 - 24 hours .
5.7.2.1.3. Using a sterile inoculating loop, streak a portion of the

sample on the surface of Mannitol Salt Agar plate
and incubate the plate at 32.5 ± 2.5°C for
18 - 72 hours
5.7.2.1.4. After incubation, examine the Mannitol Salt Agar

plates. If no growth is evident, the sample meets the
requirements for absence of Staphylococcus aureus.
5.7.2.1.5. If growth is present, the possible presence of

S. aureus is indicated by the presence of yellow or
white colonies surrounded by a yellow zone.

MICROORGANISMS
5.7.2.1.6. Perform Gram stain on the discreet typical colonies.

Gram Stain Characteristics: Gram positive cocci in
irregular grape like clusters.
5.7.2.1.7. Confirm presence of S. aureus by identification test

such as Coagulase test.
5.7.2.1.8. CONFIRMATORY TEST FOR STAPHYLOCOCCUS

AUREUS: COAGULASE TEST (TUBE METHOD):
5.7.2.1.8.1. Using an inoculating loop, transfer representative

suspect colonies from the agar surface of the
Mannitol Salt Agar medium into a sterile
12 mm x 75 mm tubes containing 0.5 mL of re-
hydrated mammalian plasma and mix gently.
5.7.2.1.8.2. Transfer a large loopful of pure 24 hour colonies

of Staphylococcus aureus ATCC# 6538 from
TSA plate into a sterile 12 mm x 75 mm tube
containing 0.5 mL reconstituted coagulase
reagent as positive control, and colonies of
Staphylococcus epidermidis ATCC# 12228 into
another sterile tube as a negative control
5.7.2.1.8.3. Mix thoroughly to emulsify the test isolates
5.7.2.1.8.4. Incubate in a water bath or incubator at 35-37C

or follow the manufacturer’s instructions.
5.7.2.1.8.5. Examine the tubes every 60 minutes for clotting

by gently slanting the tubes. Do not shake the
tubes.
5.7.2.1.8.6. If no clot is visible after 4 hours, leave the tubes

in the water bath or the incubator at 35-37C.
over night (24 hours). An optional method is to
leave the tubes over night up to 24 hours at
25°C.
Page No: 17/36

GENERAL PROCEDURE
MICROORGANISMS
Note: If no clot is observed in the tube

containing the test sample at the end of
the incubation period, the sample meets
the requirements for absence of
Staphylococcus aureus. If clotting is
observed, staphylococcus aureus is
confirmed to be present.
5.7.2.2. TEST FOR PSEUDOMONAS AERUGINOSA:

than 1g or 1 mL of the product to be examined as
described in Section 5.7.1.1 (Sample Preparation),
and use 10 mL or the quantity corresponding to 1 g or
1 mL to inoculate a suitable amount of Soybean-
Casein Digest broth (TSB) with or without 4%
Polysorbate 20 and 0.5% Lecithin e.g. 10 g or 10 mL
to 90 mL TSB with or without 4% Polysorbate 20 and
0.5% Lecithin to have a 1:10 dilution.

18 - 24 hours
5.7.2.2.3. Using a sterile inoculating loop, streak a portion of the

sample on the surface of Cetrimide Agar plate and
incubate the plate at 32.5 ± 2.5°C for 18 - 72 hours
5.7.2.2.4. After incubation, examine the Cetrimide agar plate. If

no growth is evident, the sample meets the
requirements for absence of Pseudomonas
aeruginosa.
Page No:
GENERAL PROCEDURE
MICROORGANISMS
Page No:
5.7.2.2.5. If growth is present, the possible presence of

Pseudomonas aeruginosa is indicated by the
presence of greenish bluish colonies.
5.7.2.2.6. Perform Gram stain on discreet typical colonies
Gram stain characteristics: Gram negative rods.
5.7.2.2.7. Confirm the presence of Pseudomonas aeruginosa by

identification tests such as Oxidase and Pigment tests.
5.7.2.2.8. PIGMENT TEST FOR PSEUDOMONAS

AERUGINOSA:
5.7.2.2.8.1. Using an inoculating loop, streak representative

discreet colonies from the Cetrimide agar plate
on the surface of Pseudomonas Agar plate for
detection of fluorescein (Psa-F) and on
Pseudomonas Agar plate for detection of
Pyocyanin (Psa-P) and incubate the plates at
32.5 ± 2.5°C for not less than three days.
5.7.2.2.8.2. Examine the colonies under ultra violet light.
5.7.2.2.8.3. Determine whether colonies having the following

characteristics are present:
Psa-F Psa-P
Colony Morphology: Generally Greenish Generally greenish
to Yellow
Fluorescence in UV Yellow Blue
Light:
Note: If the colonies which have the characteristics listed in Section 5.7.2.2.8.3
(refer to Table)are present confirm the presence of Pseudomonas aeruginosa
with Oxidase test
5.7.2.2.9. OXIDASE TEST FOR CONFIRMATION OF
PRESENCE OF PSEUDOMONAS AERUGINOSA
5.7.2.2.9.1. Transfer suspect discreet colonies to oxidase

strips or disks.
Note: The development of a pink color that
changes to purple indicates a positive Oxidase
test.
Colonies that have characteristics listed in
Section 5.7.2.2.8.3 and are Oxidase positive
confirm the presence of Pseudomonas
aeruginosa in the sample, otherwise the absence
of Pseudomonas aeruginosa is confirmed.
5.7.2.3. TEST FOR ESCHERICHIA COLI:

than 1g of the product to be examined as described in
Section 5.7.1.1 (Sample Preparation), and use 10 mL
or the quantity corresponding to 1 g or 1 mL to
inoculate a suitable amount of Soybean-Casein Digest
broth (TSB) with or without 4% Polysorbate 20 and
0.5% Lecithin e.g. 10 g or 10 mL to 90 mL TSB with or
without 4% Polysorbate 20 and 0.5% Lecithin to have
a 1:10 dilution.

18 - 24 hours
5.7.2.3.3. After incubation, pipette 1 mL of the sample into

100 mL of MacConkey broth and incubate at
42 to 44°C for 24 to 48 hours.

document


document
GENERAL PROCEDURE
MICROORGANISMS
5.7.2.3.4. After incubation , subculture sample on MacConkey

agar plate and incubate for 18 to 72 hours at
32.5±2.5°C
Note: If no growth is evident the sample meets the

requirements for absence of Escherichia coli.
If growth is present, the possible presence of
E. coli is indicated by black red colonies that
may have surrounding zone of precipitated bile.
5.7.2.3.5. Perform Gram stain of representative colonies
Gram stain characteristics: Gram negative rods

(cocco bacilli)
5.7.2.3.6. Confirm the presence of E coli by Identification tests
5.7.2.3.7. IDENTIFICATION TEST USING OXIDASE TEST

(ELIMINATION TEST )
5.7.2.3.7.1. Transfer suspect discreet colonies to oxidase

strips or disks
NOTE: If a pink colony, which changes to purple,

develops indicating a positive Oxidase
test, then the colony is not E. coli. If there
is no color development, proceed to
confirmatory test for E. coli
5.7.2.3.8. Confirmatory Test for E coli Using Levine’s Eosin

Methylene Blue (L-EMB) Agar
5.7.2.3.8.1. Using a sterile inoculating loop, transfer

representative colonies from MacConkey agar
plate to the surface of L-EMB agar plate.
GENERAL PROCEDURE
MICROORGANISMS
5.7.2.3.8.2. Incubate the L-EMB plates at 32.5 ± 2.5°C for

24 to 48 hours
5.7.2.3.8.3. Examine the colonies on the L-EMB plates. If

none of the colonies exhibits both a characteristic
metallic sheen under reflected light, and a blue –
black appearance under the transmitted light, the
sample meets the requirements for the absence
of Escherichia coli.
NOTE: The sample complies with the test if no

colonies are present or if the
identification tests are negative.
5.7.2.4. TEST FOR SALMONELLA SPECIES:

than 1g of the product to be examined as described in
Section 5.7.1.1 (Sample Preparation), and use 10 mL
or the quantity corresponding to 1 g or 1 mL to
inoculate a suitable amount of Soybean-Casein Digest
broth (TSB) with or without 4% Polysorbate 20 and
0.5% Lecithin e.g. 10 g or 10 mL to 90 mL TSB with or
without 4% Polysorbate 20 and 0.5% Lecithin to have
a 1:10 dilution.

18 - 24 hours
5.7.2.4.3. After incubation pipette 0.1 mL of the sample into

10 mL of Rappaport Vassiliadis Salmonella
Enrichment Broth (RVSEB) and incubate at
32.5±2.5°C for 18 to 24 hours.

MICROORGANISMS
5.7.2.4.4. After incubation of sample, subculture on a Xylose

Lysine Deoxycholate (XLD) agar plate, and incubate
at 32.5± 2.5°C for 18 to 48 hours.
5.7.2.4.5. After incubation, examine the agar plates. If no

growth is evident, the sample meets the requirements
of absence of Salmonella species.
Note: If growth is present, the possible presence of

Salmonella is indicated by the growth of well-
developed red colonies with or without black
centers.
5.7.2.4.6. Perform Gram Stain of representative colonies.
Gram stain characteristics: Gram negative rods.
5.7.2.4.7. Confirm the presence of Salmonella species by

identification tests
5.7.2.4.8. CONFIRMATORY TEST FOR SALMONELLA

SPECIES USING TRIPLE SUGAR IRON (TSI) AGAR
SLANTS
5.7.2.4.8.1. Using a sterile inoculating loop, streak the

surface of the Triple Sugar Iron agar slant tube,
and stab the butt of the tube with the inoculating
loop.
5.7.2.4.8.2. Incubate the TSI slants for 24 - 48 hours at

32.5 ± 2.5°C.

MICROORGANISMS
Note: If on the examination of the TSI slant

there is no evidence of tube having
alkaline (red) slant, and an acid (yellow)
butt (with or without concomitant
blackening of the butt from hydrogen
sulfide production), the sample meets the
requirements for the absence of
Salmonella species, otherwise, the
presence of Salmonella species is
confirmed.
Additional confirmatory evidence may be

obtained by further suitable cultural,
serological, and biochemical tests.
5.7.2.5. TEST FOR CANDIDA ALBICANS:
5.7.2.5.1. Using a sterile pipette , pipette 1 ml of the sample

prepared in 5.7.1.1 (Sample Preparation) into 100 mL
of Sabouraud dextrose broth (SDB) and incubate at
32.5 ± 2.5°C for 3 to 5 days
5.7.2.5.2. Subculture on a Sabouraud Dextrose Agar plate and

incubate at 32.5 ± 2.5°C for 24 to 48 hours.
NOTE: Growth of white colonies may indicate the

presence of Candida albicans. This is
confirmed by identification such as Gram
Stain. Sample complies with the test if such
colonies are not present or if confirmation and
identification test are negative.

MICROORGANISMS
5.7.2.6. TEST FOR BILE TOLERANT GRAM NEGATIVE

BACTERIA
5.7.2.6.1. SAMPLE PREPARATION AND PRE-INCUBATION:
5.7.2.6.1.1. Prepare a sample using a 1 in 10 dilution of not

less than 1g of the product to be examined as
described in Section 5.7.1.1 (Sample
Preparation), and use 10 mL or the quantity
corresponding to 1 g or 1 mL to inoculate a
suitable amount of Soybean-Casein Digest broth
(TSB) with or without 4% Polysorbate 20 and
0.5% Lecithin e.g. 10 g or 10 mL to 90 mL TSB

with or without 4% Polysorbate 20 and 0.5%
Lecithin to have a 1:10 dilution.
5.7.2.6.1.2. Incubate sample at 20 to 25°C for a time

sufficient to resuscitate the bacteria but not
sufficient to encourage multiplication of the
organisms (usually 2 hours but not more than
5 hours)
5.7.2.6.2. TEST FOR ABSENCE
5.7.2.6.2.1. Use the volume corresponding to 1 g or 1 mL of

the product as prepared in section 5.7.2.6.1
(Sample Preparation and Pre-Incubation) to
inoculate Enterobacteria Enrichment Broth
Mossel.
5.7.2.6.2.2. Incubate at 32.5 ± 2.5°C for 24 to 48 hours.
5.7.2.6.2.3. Subculture on plates of Violet Red Bile Glucose

Agar and incubate at 32.5 ± 2.5°C for
18 to 24 hours.

MICROORGANISMS
NOTE: The product complies with the test if

there is no growth of colonies
5.8. Report:
Use the report format as per Attachment IV to report the test results.
6.0 ATTACHMENTS:
ATTACHMENT I: MEDIA/REAGENTS LOT NUMBER AND TRACKING

INFORMATION
ATTACHMENT II: MICROBIAL COUNTS ON SOLID/LIQUID/SEMI LIQUID
SAMPLES
ATTACHMENT III: TESTS FOR SPECIFIED MICROORGANISMS (USP) <62>
ATTACHMENT IV: HARMONIZED USP MICROBIAL LIMIT REPORT
ATTACHMENT V: COAGULASE TEST
Page No: 26/36

MICROORGANISMS
ATTACHMENT I
Page No: 27/36

MICROORGANISMS
ATTACHMENT II

T ime (IST) : Page No: 28/36

Printed 13-Mar-2019 3:27 AM
MICROORGANISMS
ATTACHMENT II (Continued)
Page No: 29/36

MICROORGANISMS
ATTACHMENT III
Page No: 30/36

MICROORGANISMS
ATTACHMENT III (Continued)

Page No: 31/36

MICROORGANISMS
ATTACHMENT III (Continued)

Page No: 32/36

MICROORGANISMS
ATTACHMENT IV
Page No: 33/36

GENERAL PROCEDURE
MICROORGANISMS
ATTACHMENT V
Page No:
GENERAL PROCEDURE
MICROORGANISMS
Page No:
HISTORY OF CHANGES

(Number and last
version)
CC007809 GP000046  Reformatted the General Procedure as per
Version the Documentum Compliance Manager
1.0 (Refer to old format.
document STP - 037  Included the test procedure for Candida
Rev. 02) albicans and updated the attachments
accordingly.
CC029753 GP000046  Added procedure for Oxidase Test for E.

coli (Elimination) as section 6.6,
Version 2.0 renumbering subsequent steps accordingly.
 In Attachment I, added more rows to test
tables under “Sample Description”, “Total
Aerobic Microbial Count’ and Total
Combined Molds and Yeasts Count.”
 In Attachment II, added incubator, incubator
calibration due date, incubated at, to the
test box for E. coli.
 In Attachment III, added columns for
sample lot number and sample tracking
information.
 Added new attachment for Coagulase
Testing as Attachment V.
 All attachments have been made controlled
forms and assigned appropriate control
numbers.
 In section 4 “Culture Media” clarified a
notation for additives.
 Revised titles of subsections G, I, and R
of section 4.1 “Other Chemicals” to properly
use notation of additives.
HISTORY OF CHANGES – CONTINUED

(Number and last
version)
CC032282 GP000046  Version 3.0 of this document was approved
and made effective (ref CC029753), but
Version 3.0 signed off incorrectly by a signatory.
Therefore a new document version is
required to fix the signing error.
No changes have been made to content

of document.
CC033598 GP000046 Ver. 4.0  Interpretation of results section added as

per USP36.
CC058000 GP000046 Ver. 5.0  This procedure has been revised in

its entirety.
CC099426 GP000046 Ver. 6.0  Revised Document Logo/Template

from “Ranbaxy” to “SUN
Pharma”.


8.0; Effective
: 11-Dec-2018
Version No. 09-Dec-2021
MICROBIOLOGICAL WATER TESTING
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Daniel Savad
Coordinator, Quality Assurance QUALITY ASSURANCE-TR-OHM LABS 06-Dec- Created By
2018
Aarohi Shah
QC Senior Chemist QUALITY CONTROL-TR-OHM LABS 06-Dec-2018 Reviewed and Approved By
Frank Piechota
Manager QA QA 06-Dec-2018 Reviewed and Approved By
Jignesh Soni
Associate Director QC 07-Dec- Reviewed and Approved By
2018
Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM 07-Dec- Reviewed and Approved By
LABS 2018

Pandya
GENERAL PROCEDURE
Review Due : 09-Dec-2021
Title : MICROBIOLOGICAL WATER TESTING
1. INSTRUMENTS AND EQUIPMENT
Petri dishes 15 mm x 100 mm, Sterile

o
Incubator capable of maintaining a temperature of 32.5 ± 2.5 C
o
Incubator capable of maintaining a temperature of 22.5 ± 2.5 C
Colony Counter with a suitable magnification to aid in counting colonies.
2. SAFETY
Always observe safe laboratory practices. Consult the appropriate material safety
Data sheet (MSDS) before handling any chemical if you are unfamiliar with the
proper safety precautions.
3. PROCEDURE
3.1. Organisms, Media, Other Chemicals and Reagents:
Escherichia coli (ATCC #8739), Pseudomonas aeruginosa (ATT #9027),

Salmonella choleraessuis spp enteritidis (ATCC #13076 or 13311)
Plate count agar (PCA), Soybean casein digest agar (SCD) / Trypticase
Soy Agar (TSA)
R2A Agar Medium, MacConkey Agar (MCA), Cetrimide Agar (CET), Violet
Red Bile (VRBA) Agar
Phosphate Buffer pH 7.2,
Hydrochloric acid (1N)
Sodium Hydroxide (1 and 0.1 N)
10% Sodium thiosulfate or commercially available Coliform sample
containers (e.g. Corning Brand)

document
GENERAL PROCEDURE
Review Due : 09-Dec-2021
Arti Pandya Printed Time (IST) : 11-Mar-2019 9:27 PM

document
3.2. Media Preparation:
The culture media required in this procedure are made from the ingredients
listed herein.
Enter the media, reagents and solutions information used for the testing in
the ATTACHMENT VI - MEDIA, REAGENTS, SOLUTIONS AND POSITIVE
CONTROL ORGANISMS TRACKING INFORMATION.
Minor modifications of the individual ingredients may be made or

reconstituted dehydrated media may be substituted, provided the resulting
media possess equal or better growth promoting properties.
When reconstituting dehydrated media follow the manufacturer’s direction
otherwise refer to current USP.
Adjust the solution with either 1 N sodium hydroxide or 1 N hydrochloric
acid as required so that after steam sterilization the pH is as specified.
Sterilize by autoclaving; the exposure time depending on the volume to be
sterilized.
3.3. Plate Count Agar:
Approximate formula * per Liter

Pancreatic Digest of Casein 5.0 g
Yeast Extract 2.5 g
Dextrose 1.0 g
Agar 15.0 g
Final pH 7.0 ± 0.2

Page No: 3/23

3.4. R2A Agar:

Yeast Extract 0.5 g
Proteose peptone 0.5 g
No.3 Casamino 0.5 g
Acids
Dextrose 0.5 g
Soluble 0.5 g
starch 0.3 g
Sodium Pyruvate 0.3 g
Dipotassium 0.05 g
Phosphate 15.0 g
Magnesium sulfate
Agar
3.5. Violet Red Bile Agar:
Yeast 3.0 g
Extract 7.0 g
Peptone 1.5 g
Bile salt 10.0 g
No.3 5.0 g
Lactose 15.0 g
Sodium 0.03 g
Chloride Agar 0.002 g
Neutral
Final pH 7.4 ± 0.2

P rinted Time (IST) : Page No: 4/23

11-Mar-2019 9:27 PM
3.6. McConkey Agar

Pancreatic digest of casein 17.0 g
Peptone meat and Casein 3.0 g
Lactose 10.0 g
Bile salt 1.5 g
Agar 13.5 g
Neutral red 30 mg
Crystal violet 1 mg
pH after sterilization it is 7.1 ± 0.2
3.7. Cetrimide Agar:
Pancreatic digest of gelatin 20.0 g

Magnesium Chloride 1.4 g
Potassium sulfate 10.0 g
Agar 13.6 g
Cetyl Trimethyl ammonium Bromide (Cetrimide) 0.3 g
Glycerin 10.0 mL
Water 1000 mL
pH after sterilization : 7.2 ± 0.2

Page No: 5/23

3.8. Soybean-Casein Digest or Trypticase Soy Agar:

Enzymatic Digest of Soya bean meal 5.0 g
Agar 15.0 g
Water 1000 mL
pH after sterilization : 7.3 ± 0.2
3.9. Preservation and Storage:
Note for Potable water samples: Within one hour of receipt, treat
chlorinated samples (and other samples containing residual halogens) with
10% Sodium thiosulfate or sample directly into commercially available
Coliform containers. 0.1 mL of 10% Sodium thiosulfate per 120 mL of
sample is required. Mix well.
Start microbiological examination of water sample promptly after collection

to avoid unpredictable changes. Use an ice cooler for storage during
transportation to the laboratory If water samples cannot be processed
within 1 hour after collection, refrigerate the samples at 2°C - 8°C upon
receipt. The time elapsing between collection and testing should not
exceed 24 hours.
3.10. Total Aerobic Plate Count:
3.10.1. By Pour Plate method:
3.10.1.1. Perform all operations of the test using rigid

aseptic techniques and under controlled
conditions (i.e. biological safety cabinet or
laminar flow hood)
Page No: 6/23

3.10.1.2. Positive and negative controls must be
performed on all media used in the testing
procedures. As a positive control, prepare plates
of PCA/R2A and allow to solidify. Streak a loop
full of saline suspension of a suitable
Pseudomonas species (for example ATCC
#9027) onto the surface of the plate. As a
negative control, plate one dish of PCA/R2A
alone and incubate inverted at 32.5 ± 2.5°C for
48 to 72 hours.
3.10.1.3. For air monitoring during the procedure, expose

two pre-solidified plates of SCD agar. Incubate
SCD air controls along with the sample plates at
the same temperature.
3.10.1.4. For each sample to be tested, label two

15 mm x 100 mm Petri dishes with the sample
number and dilution, if applicable. All water
samples should be plated in duplicate at the
dilution of 10°.
3.10.1.5. Mix the sample thoroughly. Flame the neck of the

sample bottle and pipette out 2.0 mL of water
sample.
3.10.1.6. Transfer 1.0 mL aliquots of sample into each

appropriate labeled Petri dishes.
3.10.1.7. Pour 15-20 mL of PCA/R2A agar into each Petri

dish, swirl to mix, then allow agar to solidify.
3.10.1.8. Invert plates and incubate at 32.5°C ± 2.5°C or

(30-35°C) for 48 to 72 hours
3.10.1.9. At the completion of the incubation period,

examine the plates for microbial growth.

3.10.1.10. Count the colonies with the aid of a colony
counter.
3.10.1.11. Count the total CFU from the plate and report
CFU/mL.
3.10.1.12. Record all results in the microbiological

monitoring record, as applicable. (Refer to
Attachment I - IV).
3.10.1.13. Report all results using the Microbiological Water

Testing Report Form (Refer to Attachment V).
3.10.2. By Membrane filtration method:
3.10.2.1. Perform all operations of the test using rigid

aseptic techniques and under controlled
conditions (i.e. biological safety cabinet or
laminar flow hood)
3.10.2.2. Positive and negative controls must be

performed on the media used in the testing
procedures. As a positive control, prepare plates
of R2A and allow to solidify. Filter 100mL of
sterile water spiked with 0.1ml Quanti-cult plus
suspension of a suitable Pseudomonas species
cell population <100 cfu(for example ATCC
#9027) and place filter onto solidified R2A plate.
As a negative filter control, filter 100mL of sterile
phosphate buffer pH 7.2. and place filter
aseptically onto solidified R2A plate. As a
negative media control, plate one dish of R2A
alone and incubate all plates inverted at 30-35°C
or (32.5°C ± 2.5°C) for not less than 5 days

3.10.2.3. For air monitoring during the procedure, expose
two pre-solidified plates of SCD agar. Incubate
SCD air controls along with the sample plates at
the same temperature.
3.10.2.4. Shake the water sample vigorously. Sanitize the

outside of sample container with 70% Isopropyl
alcohol and pour 100 mL of the water sample into
the filter funnel. Use the graduations on the filter
funnel to measure the water volume tested.
3.10.2.5. For each sample to be tested, label 15 mm x

100 mm Petri dish of pre-poured R2A plate with
the sample number and dilution if applicable.
3.10.2.6. Perform determination of TAMC from purified

water, using current EP on “Membrane Filtration
Procedure for Total Aerobic Microbial Count” for
purified water. Filter 100 mL of purified water
through 0.45 μ cellulose nitrate membrane filter.
Rinse the filter funnel with 3 x 100 mL of sterile
phosphate buffer pH 7.2 and place the filter
paper on R2A medium plate. (In case where high
count is expected, filter smaller volume, e.g.
50 mL or 10 mL or 1 mL )
3.10.2.7. Incubate R2A plates at 32.5 ± 2.5ºC for a

minimum of 5 days.
3.10.2.8. For negative media control, incubate one R2A

plate at 32.5 ± 2.5°C for a minimum of 5 days.
3.10.2.9. Count the total colony forming units (CFU) on the

plate and report as CFU/100mL and CFU/mL
3.10.2.10. Record all results in the microbiological

monitoring record, as applicable (Refer to
Attachments I - IV).
Page No: 9/23

3.10.2.11. Report all results using the Microbiological Water
Testing Report Form (Refer to Attachment V).
3.11. Total Coliform/Indicator Organisms Test: By membrane filtration

method. (E. coli, Salmonella species, and Pseudomonas species)
3.11.1. Expose one pre-solidified plate of SCD medium during the

sample manipulations for air monitoring.
3.11.2. Shake the water sample vigorously. Flame the neck of the
bottle or sanitize the outside of sample container with 70%
Isopropyl alcohol and pour 100 mL of the water sample into the
filter funnel. Use the graduations on the filter funnel to measure
the water volume tested.
3.11.3. Vacuum filter each water sample through 0.45 µm membrane

filter funnel. Rinse the filter funnel with 3 x 100 mL of sterile
phosphate buffer pH 7.2.
3.11.4. Aseptically transfer the filters onto a prepared MacConkey,

Violet Red Bile and Cetrimide agar plates. Carefully place the
filter membrane top side up on the agar in a rolling motion to
avoid entrapping air bubbles. Invert the plates and incubate for
48-72 hours at 32.5 ± 2.5°C.
3.11.5. Prepare a positive control of each indicator organism, negative

diluent/ filter controls and negative control of each media used.
media type. For positive control add 0.1 mL of saline
suspension of each organism to 100 mL sterile phosphate
buffer pH 7.2 filter and transfer to appropriate pre-solidified
media.
3.11.6. As a negative diluent/filter control, filter 100 mL of sterile

phosphate buffer pH 7.2 and transfer to appropriate pre-
solidified media. As a negative medium control, plate one dish
of each medium alone.

3.11.7. Invert all control plates and incubate for 48-72 hours at 32.5 ±
°
2.5 C.
3.11.8. After incubation, examine all plates for suspect colonies. If

growth is present subculture growth on TSA plate, perform
gram stain, oxidase, coagulase and other cultural and
biochemical tests for identification of coliform and indicator
organisms. (Refer to current version of GP000046 as
applicable)
3.11.9. For total Coliforms from the filter report result as Present or
Absent In 100mL water sample.
3.11.10. Record all results in the microbiological monitoring record, as

applicable (Refer to Attachment I - IV.)
Specifications:
Total microbial count:

Alert Limit: Total plate count : NMT 70 cfu/mL
Maximum Permissible Limit : NMT 100 cfu/mL
Total Coliforms : Absent
4. ATTACHMENTS:
ATTACHMENT I: WATER MONITORING RECORD (LA SITE)

ATTACHMENT II: WATER MONITORING RECORD (TR SITE-PHASE 3)
ATTACHMENT III: WATER MONITORING RECORD (TR SITE-PHASE 4)
ATTACHMENT IV: WATER MONITORING RECORD (TR SITE- PHASES 5 & 6)
ATTACHMENT V: MICROBIOLOGICAL WATER TESTING REPORT
ATTACHMENT VI: MEDIA, REAGENTS, SOLUTIONS AND POSITIVE CONTROL
ORGANISMS TRACKING INFORMATION
Page No: 11/23

Attachment I
WATER MONITORING RECORD (LA SITE)


Printed 11-Mar-2019 9:27 PM
Attachment I (Continued)
Page No: 13/23

Attachment II:
WATER MONITORING RECORD (TR SITE- PHASE 3) (PW-05)

Page No: 14/23

Attachment II (Continued)


Attachment III
WATER MONITORING RECORD (TR SITE- PHASE 4) (PW-06)
Page No: 16/23

Attachment III (Continued)


Attachment IV
WATER MONITORING RECORD (TR SITE- PHASES 5 & 6) (PW-07)


Attachment IV (Continued)


Attachment V
MICROBIOLOGICAL WATER TESTING REPORT
Page No: 20/23

Attachment VI
MEDIA, REAGENTS, SOLUTIONS AND POSITIVE CONTROL ORGANISMS TRACKING
INFORMATION
Page No:
Page No:
HISTORY OF CHANGES

version)
CC028761 GP000041 Version  New format as per electronic
1.0 (reference to old documentum compliance Manager (DCM)
document series system.
STP- 032 Rev. 01)  Replaced all forms in attachments I through
IV with 6 controlled forms.
Added sections 3.11.1.12 and 3.11.2.10.
 Removed TOC/Conductivity testing
throughout document
CC032282 GP000041 Version  Version 2.0 of this document was approved
2.0 and made effective (ref CC029753), but
signed off incorrectly by a signatory.
Therefore a new document version is
required to fix the signing error.
No changes have been made to content

of document.
CC050182 GP000041 Version  Corrected typographical error in section

3.0 3.6 (corrected from 7.4±0.2 to 7.1±0.2).
 Section 3.10 updated for water
sample preservation and storage method
 Revised Attachments I, II, III, IV and V.
CC091901 GP000041 Ver. 3.0  Logo / template revised from “Ranbaxy” to

“Sun Pharma” due to the merger.
 Attachments I, II, III, IV and VI revised.
CC092631 GP000041 Ver. 4.0 Attachments I, II, III, IV and VI revised.
CC106674 GP000041 Ver. 5.0 No changes made

HISTORY OF CHANGES – CONTINUED
CCR NumberSupersedes(Number Change(s) Made

and last version)
CC106674 GP000041 Ver. 6.0  Revised section 3.11.2.6.

 Revised Attachments 1, 2, 3, and 4.
 Added entry in history ofchanges for
GP000041 Ver. 5.0 (correction of a workflow
error).
CC108360 GP000041 Ver. 7.0  Added reference to Attachment VI to section 3.2

 Added note to section 3.10 regarding Potable
water samples.
 Removed section 3.9 (Sampling procedure) and
section 3.13 (Exceeding Alert / Action Limits).


4.0; Effective
: 14-Jun-2016
SOLUBILITY
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Daniel Savad
QA Senior Documentation Associate QUALITY ASSURANCE-TR-OHM LABS 06-Jun- Created By
2016
Dalvinder Singh
Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM LABS 07-Jun-2016 Reviewed and Approved By

Pandya
GENERAL PROCEDURE
Title : SOLUBILITY
Title : SOLUBILITY
Objective : The test for Solubility is provided to determine guidelines

with the requirements specified in individual
monograph/specifications.
Principle : The extent to which a substance dissolves in a given system

depends largely on the nature and intensity of the forces
present in the solute and the resultant solution.
Procedure:
Take the sample quantity (1 g) or proportionately less quantity as specified, in a dry

stoppered test tube and pour the solvent quantity from the minimum volume mentioned in the
table given below with vigorous shaking. Check for the solubility. If the solution is not clear,
increase the addition of solvent gradually up to the maximum volume mentioned thereby
checking after each addition. A material is considered to be passing in solubility if it dissolves
completely in given range producing a clear solution without any material left undissolved at
the bottom of the test tube. The term “miscible” pertains to a substance that yields a
homogeneous mixture when mixed in any proportion with the designated solvent.
Descriptive Term Parts of Solvent Required for

1 Part of Solute
Very soluble Less than 1
Freely soluble From 1 to 10
Soluble From 10 to 30
Sparingly soluble From 30 to 100
Slightly soluble From 100 to 1000
Very slightly From 1000 to 10,000
soluble
Practically Greater than or equal to 10,000.
insoluble, or
Insoluble
Page No: 2/4

GENERAL PROCEDURE
Title : SOLUBILITY
Page No: 3/4

NOTES:
1) Soluble Pharmacopeial and National Formulary articles, when brought into solution,
may show traces of physical impurities, such as minute fragments of filter paper,
fibers, and other particulate matter, unless limited or excluded by definite tests or
other specifications in the individual monographs.
2) This test is for information purposes only and is only applicable if it is part individual
Monograph.
HISTORY OF CHANGES

Number
(Number and last
CC000481 GP000040 Version  Revised to bring in-line with Ranbaxy
1.0 (Refer old General procedure GP000055 (Old number
document STP-031 GP002).
Rev.02).  Harmonizing General Procedure in the new
electronic Documentum Compliance Manager
(DCM) system.
CC035061 GP000040 Version 2.0  Corrected typographical / formatting errors
(as applicable).
 Added the definition for “miscible” as
per current USP/NF.
CC080073 GP000040 Version 3.0  Revised Document Logo/Template

from “Ranbaxy” to “SUN Pharma”.
 Added notes to end of procedure section.


4.0; Effective
: 22-Aug-2017
Version No. 20-Aug-2020
PARTICLE SIZE (BY SIEVE ANALYSIS)
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM 16-Aug-2017 Created By
LABS
Dalvinder Singh
Associate Director, Quality Control QUALITY CONTROL-LA-OHM LABS 16-Aug-2017 Reviewed and Approved By
Bhupendra Patel
Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM 17-Aug-2017 Reviewed and Approved By
LABS

Pandya
GENERAL PROCEDURE
Effective Date : 22-Aug-2017
Review Due : 20-Aug-2020
Title : PARTICLE SIZE (BY SIEVE ANALYSIS)
Pharmacopeial Status : In-house
Procedure
Sieve Analysis:
In the Sieving process a weighed quantity of the powder is passed over a perforated screen,
sufficiently small particles will pass through, while those that are oversized will be retained
on the sieve. The test is performed by using a particular sieve or a set of sieves as
specified, and calculating in percentage the amount passing through or retained on the
sieve. The test is performed by using a set of USP standard sieves, mounted on a
mechanical sieve shaker which gives both gyratory and vertical tapping motions. The sieves
are arranged vertically in the order of increasing fineness with the receiver placed below the
finest mesh. Sieve analysis is performed by one of the following methods.
A. Alpine Vacuum Siever
Procedure:
1. Weigh accurately and mount the specified Sieve on the machine.

2. Weigh accurately about 10 g of sample and transfer to the sieve. (For R&D
material use 5 g of sample)
3. Set the timer for four minutes.
4. At the end of four minutes, carefully weigh the sample retained on the sieve.
Calculation:
Weight of sample retained x 100

% retained = -----------------------------------------------
Weight of sample taken

document
GENERAL PROCEDURE
Review Due : 20-Aug-2020
Page No: 2/5

document
B. By Gilsonic Auto Siever
Procedure:
1. Weigh accurately all the specified sieves individually.

2. Weigh accurately about 1 g of sample and transfer on the top most sieve of
specified mesh size.
3. Pull the two metals apart from the unit.
4. Select the number of minutes for sieving, it must be a total of 5 min.
5. At the end, weigh accurately the material retained on each specified sieve.
Calculation:

% retained = -----------------------------------------------
For Cumulative: Add all the results
C. By Rotap Sifter Siever:
Procedure:
1. Weigh accurately the specified sieve individually.

2. Weigh accurately about 10 g of sample and transfer on the top most sieve of
specified mesh size. (For R&D material use about 5 g of sample) (For blend
sample use 25 g of sample).
3. Set the timer for four minutes
4. Press the start button to start the Rotap sifter.
5. At the end of four minutes, carefully weigh the sample retained on each specified
sieve.
Page No: 3/5

Calculation:

% retained = -----------------------------------------------
For Cumulative: Add all the results
NOTE:
1) The test sieves should be thoroughly cleaned after each use, using only air jet or
a liquid stream followed by drying of the sieves.
2) Sieve should be checked for gross distortions and fractures, especially at their
screen frame joints, before use.
3) For more than one sample, clean and dry the specified sieve and reuse the same
sieve.
Page No: 4/5

HISTORY OF CHANGES

and last version)
CC014237 GP000039 Ver. 1.0 Format revised as per the new electronic
(reference to old docDocumentum Compliance Manager (DCM) system.
series STP-030 Rev. 03)
CC054660 GP000039 ver. 2.0 Triennial review of document with no change in

content.
CC094763 GP000039 Ver. 3.0 Logo / template revised from “Ranbaxy” to “Sun
Pharma” due to the merger.

Page No: 5/5


4.0; Effective
: 04-Jun-2016
SPECIFIC GRAVITY
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM 02-Jun- Created By
LABS 2016
Dalvinder Singh
Bhupendra
Patel Site Head of Quality QUALITY ASSURANCE-TR-OHM LABS 02-Jun-2016 Reviewed and Approved By

Pandya
GENERAL PROCEDURE
Title : SPECIFIC GRAVITY
Objective : This General Procedure provides a guideline for carrying out

the test for Specific Gravity.
Principle : The Specific Gravity of a substance is the ratio of the weight /

mass of a given volume of the substance to the weight / mass
of an equal volume of water both weighed at 25 C or at a
specified temperature (unless otherwise specified, the
Specific Gravity is only applicable to liquids). If the substance
is solid at 25 C, determine the Specific Gravity at the
temperature specified, and refer to water at 25 C. Specific
Gravity gives information about the nature and purity of a
compound.
Method
 Select a thoroughly clean and dry pycnometer.
 Note down the tare weight (Wt).
 If required, calibrate the pycnometer by filling it with recently boiled and cooled water at
25 C or specified temperature and weigh (Wc). (Assuming that the weight of 1 ml of
water at 25 C when weighed in air of density 0.0012 g/mL is 0.99602 calculate the
capacity of pycnometer).
 Adjust the temperature of the substance to be examined, to about 20 C and fill the
pyconometer with it.
 Adjust the temperature of the filled pyconometer to 25 C or specified temperature,

remove any excess of substance and weigh (Ws).

document
GENERAL PROCEDURE

document
 Determine the Specific Gravity by the given formula:
(Ws – Wt)
Specific Gravity = -----------------
(at specified temp.) (Wc – Wt)
Where:
Ws = Weight of sample + pycnometer.

Wt = Weight of pycnometer.
Wc = Weight of water + pycnometer.
Calibration:
The constants A and B are determined by operating the instrument with the U-tube
filled with two different samples of known density (e.g., degassed water and air).
Perform the control measurements daily, using degassed water. The results displayed
for the control measurement using degassed water do not deviate from the reference
3
value (r25 = 0.997043 g/cm ) by more than its specified error. Precision is a function of
the repeatability and stability of the oscillator frequency. Density meters are able to
–3 –5 3
achieve measurements with an error on the order of 1 × 10 g/cm3 to 1 × 10 g/cm
–4 3 –6 3
and a repeatability of 1 × 10 g/cm to 1 × 10 g/cm . For example, an instrument
–4 3 3
specified to ±1 × 10 g/cm must display 0.9970 ± 0.0001 g/cm in order to be suitable
for further measurement, otherwise a readjustment is necessary. Calibration with
certified reference materials should be carried out regularly.
Procedure:
Using the manufacturer's instructions, perform the measurements using the same
procedure as for Calibration. If necessary, equilibrate the liquid to be examined at
25°C before introduction into the tube to avoid the formation of bubbles and to reduce
the time required for measurement. Factors affecting accuracy include the following:
• temperature uniformity throughout the tube,
• nonlinearity over a range of density,
• parasitic resonant effects, and
• viscosity, if the oscillating transducer density meters used do not provide
automatic compensation of sample viscosity influence.
Page No: 3/4

HISTORY OF CHANGES
CCR Number Supersedes (NumberChange(s) Made

and last version)
CC000407 GP000028 Version Revised to bring in-line with Ranbaxy General

1.0(Refertoold procedure GP000071 (old number GP038-05).
document STP-017 Reformatted as per the Documentum format.
Rev. 03)
CC034443 GP000028 VersionTriennial review with no change in the content.

2.0
CC079937 GP000028 Ver. 3.0  Logo / template revised from "Ranbaxy" to

"Sun Pharma" due to the merger.
 Calibration and Procedure sections added to
the procedure.

Page No: 4/4


8.0; Effective
: 01-Aug-2016
Version No. 31-Jul-2019
pH MEASUREMENT
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM 28-Jul- Created By
LABS 2016
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 29-Jul- Reviewed and Approved By
2016
Rama Chitirala
QA Sr. Manager, Operations Oversight QUALITY ASSURANCE-TR-OHM LABS Reviewed and Approved By
29-Jul-2016

Pandya
GENERAL PROCEDURE
Review Due : 31-Jul-2019
Title : pH MEASUREMENT
Objective : The following procedure determines the acidity or basicity of

the substance.
Principle : The quantity pH is the logarithm (to the base 10) of the
reciprocal of the hydrogen ion concentration or is equal to the
logarithm of the hydrogen ion concentration with negative
sign. The method has the advantage that all states of acidity
and alkalinity between those of solutions containing 1 mol/L of
hydrogen ions and 1 mol/L of hydroxide ions can be
expressed by a series of positive number 0 and 14.
Apparatus
Suitable pH meter with a glass electrode and a reference electrode.
Note: The measuring system has traditionally been referred to as the “pH meter”. While the
pH meter is still in common use, the measuring system can also be embedded inside
the pH sensor, and the pH signal can be transmitted digitally to an external device
such as a computer, Programmable Logic Controller (PLC), Distributed Control
System (DCS), data acquisition system, terminal, or other microprocessor-controlled
device.
Temperature
Lab based pH measurements are typically performed at 25°C ± 2°C unless otherwise
specified in individual monograph or herein. However temperatures outside this range are
acceptable if samples are more conveniently prepared at alternative temperatures.
For most applications, a temperature measurement will be necessary for compensation of

the Nernst temperature influence described above. A temperature device may be embedded
into the pH sensor, or an external temperature device may be used.

document
GENERAL PROCEDURE

document
Requirements
Reference buffer solutions for calibration
The instrument is calibrated against the reference buffer solutions for the purpose of
establishing a practical and operational system. The buffer solutions must be stored in
bottles of alkali free glass or plastic containers and should be protected from atmospheric
Carbon dioxide.
PREPARATION OF REFERENCE BUFFER SOLUTIONS
Prepare the solutions as mentioned below, pH of the solutions at various temperatures

should be as given in Table I. Preparation of alternative volumes at the same concentrations
to those indicated below is acceptable.
Preparation of Buffer Potassium tetraoxalate, 0.05 m:

Dissolve 12.61 g of KH3(C2O4 )2·2H2O, and dilute with water to make 1000.0 mL.
Preparation of Buffer Potassium hydrogen tartrate, saturated at 25°C:

Add C4H5KO6 to water until saturation is exceeded at 25°C. Then filter or decant.
Preparation of Buffer Potassium dihydrogen citrate, 0.05 M:

Dissolve 11.41 g C6H7KO4, and dilute with water to make 1000.0 mL.
Preparation of Buffer Potassium biphthalate, 0.05 m:

Dissolve 10.12 g of KHC8H4O4, previously dried at 110°C for 1 h, and dilute with water to
make 1000.0 mL.
Preparation of Buffer Equimolal phosphate, 0.05 m:

Dissolve 3.53 g of Na2HPO4 and 3.39 g of KH2PO4 , each previously dried at 120°C for 2 h,
and dilute with water to make 1000.0 mL.
Preparation of Buffer Potassium dihydrogen phosphate, 0.0087 M, and disodium

hydrogen phosphate, 0.0303 M:
Dissolve 1.18 g of KH2PO4 and 4.30 g Na2HPO4, both dried for 2 h at 120 ± 2°C, and dilute
with water to make 1000.0 mL.
Page No: 3/10

Page No: 4/10
Preparation of Buffer Sodium tetraborate, 0.01 m:

Dissolve 3.80 g of Na2B4O7·10H2O, and dilute with water to make 1000.0 mL. Protect from
absorption of carbon dioxide.
Preparation of Buffer Sodium carbonate, 0.025 M, and sodium bicarbonate, 0.025 M:

Dissolve 2.64 g of Na2CO3 and 2.09 g NaHCO3, and dilute with water to make 1000.0 mL.
Preparation of Buffer Calcium hydroxide, saturated at 25°C:

Add Ca(OH)2 to water until saturation is exceeded at 25°C. Use water that has been recently
boiled and protected from atmosphere to limit carbon dioxide absorption. Then filter or decant.
Table I
pH of reference buffer solution at various temperature will be as follows:
Potassiu
Potassiu
m Potassium Potassiu Equimol
Temperatu m Tetra-
Hydrogen Dihydrogen m al
re oxalate,
Tartrate Citrate, 0.05 Biphthala Phospha
(°C) 0.05 m
Saturated M te, te,
10 1.67 at 25°C
— — 4.00 6.92
15 1.67 — 3.80 4.00 6.90
20 1.68 — 3.79 4.00 6.88
25 1.68 3.56 3.78 4.01 6.86
30 1.68 3.55 3.77 4.02 6.85
35 1.69 3.55 3.76 4.02 6.84
40 1.69 — — 4.04 6.84
45 1.70 — — 4.05 6.83
50 1.71 — — 4.06 6.83
55 1.72 — — 4.08 6.83
60 1.72 — — 4.09 6.84
∆pH/∆C 0.0010 0.0014 0.0022 0.0018 0.0016
(Continued)
(Continued)
Potassium
Dihydrogen Calcium
Sodiu Sodium Carbonate,
Temperatu Phosphate, 0.0087 Hydroxid
m 0.025 M, and
re M, and Disodium e,
Tetrabora Sodium
(°C) Hydrogen Saturated
te, Bicarbonate,
Phosphate, 0.0303 at 25°C
0.01 m 0.025 M
10 M
— 9.33 — 13.00
15 7.45 9.28 10.12 12.81
20 7.43 9.23 10.06 12.63
25 7.41 9.18 10.01 12.45
30 7.40 9.14 9.97 12.29
35 7.39 9.10 9.93 12.13
40 — 9.07 — 11.98
45 — 9.04 — 11.84
50 — 9.01 — 11.71
55 — 8.99 — 11.57
60 — 8.96 — 11.45
∆pH/∆C 0.0028 0.0074 0.0096 0.0310
Commercially available buffer solutions for pH measurement system, standardized by

methods traceable to the National Institute of Standards and Technology (NIST) or
other national authorities, labeled with a pH value accurate to 0.02 pH unit may be
used. Solutions prepared from ACS reagent grade materials or other suitable
materials, may be used provided the pH of the resultant solution is the same as that of
the solution prepared from the NIST (or other national authorities) certified material.
Buffer solutions that are greater than 12 should be used immediately, or should be
prepared using freshly boiled water, and stored under conditions to minimize carbon
dioxide absorption and ingress.
PROCEDURE
1. Calibrate the pH meter as per the calibration procedure using buffer solutions as prepared
above. Instrument should read the pH according to the pH of buffer solution.
2. Examine the electrodes, especially the reference electrode and electrolyte level, if a liquid
electrolyte is used. If necessary, replenish electrolyte supply, and observe other
precautions indicated by the instrument and electrode manufacturers. The calibration or
verification of the pH measurement system should be periodically executed. The historical
performance of the measurement system, the criticality of the pH measurement, the
maintenance of the pH sensor, and the frequency of measurement operation is used to
determine the frequency of the calibration/verification. If the pH of the buffer is sensitive
to ambient carbon dioxide, then use Purified Water that has been recently boiled, and
subsequently stored in a container designed to minimize ingress of carbon dioxide.
2.1 To standardize the pH measurement system, select three buffer solutions for
standardization, preferably either 1.68, 4.00 & 7.00 or 4.00, 7.00 &10.01, such that
the expected pH of the material under test falls within their range. Two of the
buffers are used for the calibration process, and the third buffer is used for
verification. The value of the verification buffer should be between the calibration
buffers. If the operational range of the pH sensor is beyond the pH range of the
buffer solutions in Table 1, then either 1) select two nearby pH buffers from Table 1
or 2) select one from Table 1 and another documented prepared buffer that is
outside the range. Note: Commercially available buffer solutions of 4.01 and 10.00
may also be used.
2.2 Rinse the pH sensor several times with water, then with the first buffer solution.
2.3 Immerse the pH sensor in the first buffer solution.
2.4 Continue the 2-point calibration sequence with the second buffer according to
manufacturer's instructions.
2.5 If automatic temperature measurement and compensation is not included in the

measuring system, manually enter the temperature of the buffer and pH value of
the buffer solution at that temperature into the instrument.
P rinted By :
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Printed Time (IST) : Page No: 6/10
Arti Pandya 11-Mar-2019 8:57 PM

document
document

document
2.6 Remove the pH sensor from the first buffer and rinse the electrode(s) with water,
and then the second buffer solution.
2.7 Immerse the pH sensor in the second buffer.
2.8 Continue the 2-point calibration sequence with the second buffer according to
manufacturer's instructions.
2.9 After completion of the 2-point calibration process, verify that the pH slope and
offset are within acceptable parameters. Typical acceptable parameters are slopes
ranging from 90%–105% and an offset of 0 ± 30 mV (0.5 pH units at 25°C).
Depending on the pH instrumentation, the pH slope and offset may be determined
in software or by manual methods. If using manual methods, follow supplier
instructions to calculate the pH sensor slope/offset. If these parameters are not
within acceptable parameters, the sensor should be properly cleaned, replenished,
serviced, or replaced, and the 2-point calibration process shall be repeated.
2.10 Remove the pH sensor from the second buffer, and rinse thoroughly with water,
and then the verification buffer.
2.11 Immerse the pH sensor in the verification buffer.
2.12 If automatic temperature measurement and compensation is not included in the

measuring system, manually enter the temperature of the buffer and pH value of
the buffer solution at that temperature into the instrument.
2.13 The pH reading shall be within ±0.05 pH of the buffer solution.
2.14 Use buffer values at respective temperatures (refer to Attachment I of SOP

OP006391).
3. Wash the electrode with distilled / deionized water and blot dry. Immerse the electrode in
the solution under test and measure the pH at the same temperature as for the buffer
solutions.
4. Note the value and report the results.

Page No: 7/10

NOTES
1. All solutions and suspensions of substances being examined and the reference buffer
solutions must be prepared in Carbon dioxide-free water.
2. Activate the new electrode by dipping it in 0.1 N Hydrochloric acid overnight and make it
free from acid by washing it with purified water thoroughly.
3. When the apparatus is used frequently, checking of the pH scale must be carried out
regularly. If the apparatus is not in frequent use, checking should be carried out before
each measurement.
PRECAUTIONS
1. Temperature of the sample should be within the acceptable range.
2. Do not take pH for non-polar and organic solvents.
3. Always keep the electrode properly immersed in water / buffer solution as recommended
by the electrode manufacturer.
4. If the electrode response is slow and drifting, change the electrolyte in the electrode.
Page No: 8/10

Page No: 9/10
HISTORY OF CHANGES

version)
CC000407 GP000026 Version  Revised to bring in-line with Ranbaxy
1.0 (Refer to old General procedure GP000062 (old number
document STP – 010 GP021-07).
Rev. 07)  Reformatted as per the Documentum format.
CC034526 GP000026 Version  Expanded names of Buffer solutions.
2.0  Revised preparation method of Buffer
Solution B and Buffer Solution C
 Corrected typographical errors in
following sections:
o PROCEDURE section, item 2
o NOTE section, item 3
o Title of NOTE section changed to NOTES
CC041772 GP000026 Ver. 3.0  Typographical errors corrected
under Preparation of Buffer Solution B.
CC044467 GP000026 Ver. 4.0  Degree symbol corrected under Preparation
of Buffer solution C.
CC055562 GP000026 Ver. 5.0  Added text to Apparatus section expanding
the definition of “pH meter” to include
various computerized systems for pH data
aquisition.
 Added text to Temperature section
specifying that temperature may be
compensated manually, or by a temperature
device embedded into the pH sensor.
 Replaced Preparation of Reference Buffer
Solutions section in its entirety (including
Table I).
HISTORY OF CHANGES (Contd.)

and last version)
CC071606 GP000026 Ver. 6.0 Procedure and Calibration sections revised.

Notes section revised to remove # 3 and 4.
Documentlogo/templaterevisedfrom "Ranbaxy" to
CC082206 GP000026 Ver. 7.0 Step 2.9 under procedure section revised for manual
methods statement and offset.
Page No: 10/10

Page No: 10/10

4.0; Effective
: 23-Apr-2016
Version No. 22-Apr-2019
DETERMINATION OF WATER
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM 21-Apr-2016 Created By
LABS
Daniel Savad
QA Senior Documentation Associate QUALITY ASSURANCE-TR-OHM LABS 21-Apr-2016 Reviewed and Approved By
Hemendra Makwana
Senior Executive-Quality Control QC OSD - DEWAS 22-Apr-2016 Reviewed and Approved By
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 22-Apr-2016 Reviewed and Approved By
Bhupendra
Patel Site Head of Quality QUALITY ASSURANCE-TR-OHM LABS 22-Apr-2016 Reviewed and Approved By

Pandya
GENERAL PROCEDURE
Effective Date : 23-Apr-2016
Review Due : 22-Apr-2019
Title : DETERMINATION OF WATER
Objective : The test for water content is provided to determine compliance

with the requirements specified in the individual monograph /
specification. When the article contains water of hydration, the
Method I (Titrimetric), the Method II (Azeotropic), or the
Method III (Gravimetric) is employed, as directed in the
individual monograph, and the requirement is given under the
heading Water.
Principle : The titrimetric determination of water is based upon the

quantitative reaction of water with an anhydrous solution of
Sulfur dioxide and Iodine in the presence of a buffer that reacts
with hydrogen ions. The reaction for the oxidation of the alkyl
sulfite anion to alkyl sulphate by Iodine is given below.
Procedure:
Method (KF / Titrimetric / Coulometric Titration)
There are three methods available to determine the water content when the articles contain
water of hydration.
Method Ia : Direct titration
Method Ib : Residual titration
Method Ic : Coulometric titration
- i Coulometric titration by using oven

- ii Coulometric titration without using oven

document
GENERAL PROCEDURE
Effective Date : 23-Apr-2016
Review Due : 22-Apr-2019

document
Method I (Titrimetric)
Determine the water by Method Ia, unless otherwise specified in the individual monograph.
NOTE :
In case of Coulometric titration unless otherwise specified in the specification carry out the
determination of water by Method Ic – i for coulometric titration without using oven.
1.1 Method Ia (Direct Titration):
Principle:
In the original titrimetric solution, known as Karl Fischer Reagent, the Sulfur dioxide and
Iodine are dissolved in Pyridine and Methanol. The sample may be titrated with the
Reagent directly, or the analysis may be carried out by a residual titration procedure. The
stoichiometry of the reaction is not exact, and the reproducibility of a determination
depends upon such factors as the relative concentrations of the Reagent ingredients, the
nature of the inert solvent used to dissolve the sample and the technique used in the
particular determination. Therefore, an empirically standardized technique is used in
order to achieve the desired accuracy. Precision in the method is governed largely by the
extent to which atmospheric moisture is excluded from the system. The titration of water
is usually carried out with the use of anhydrous Methanol as the solvent for the test
specimen. In some cases, other suitable solvents may be used for special or unusual test
specimens. In these cases, the addition of at least 20% of methanol or other primary
alcohol is recommended.
Precautions for Sampling:
 Crush the lumps, if present, to a fine powder.

 Weigh the sample carefully especially in case of hygroscopic materials to avoid
exposure to atmospheric moisture.
 Use squeeze bottle for liquid samples and take special care to transfer the volatile
samples.
 Transfer the sample carefully to avoid sticking to the walls of the vessel.
Page No: 3/12

11.1 Apparatus:
A suitable manual or auto KARL FISCHER titrator.
Commercially available stabilised solution of Karl Fischer type reagent may be

used. Standardise the reagent before use. Protect it from light and moisture while
in use.
11.2 Standardization of the Reagent:
Standardization of the reagent can be done by any one of the two methods.
11.3 Method A (Preferred method if technology allows determination of water

accurately below 1%)
Medium: Dehydrated Methanol (Unless otherwise specified in the monograph).
For precise determination of significant amount of water use purified water for
standardisation.
1. Place about 30 mL of Methanol or other suitable solvent in the titration vessel

and titrate with Karl Fischer reagent to the end point potentiometrically.
2. Quickly add, between 10 and 250 mg of water, accurately weighed by

difference, from a weighing pipet or from a precalibrated syringe or micropipet
and titrate with Karl Fischer reagent to the end point.
3. Calculate the water equivalence factor F, in mg of water per mL of reagent by

the formula.
F= W / V
Where:
W = Weight of water taken, in mg.

V = Volume of the reagent required, in mL.
Page No: 4/12

11.4 Method B (Alternate to Method A if technology does not allow determination
of water accurately below 1%):
For determination of trace amount of water (less than 1%) it is preferable to use
reagent with a water equivalency factor of NMT 2.0 Sodium tartarate dihydrate
may be used as a convenient water reference substance.
1. Place about 30 mL of Methanol or other suitable solvent in the titration vessel

and titrate with Karl Fischer reagent to the end point potentiometrically.
2. Add quickly 75-125 mg of Sodium tartarate dihydrate (C4H4Na2O6·2H2O)

accurately weighed, by difference into the titration vessel and dissolve.
3. Titrate with Karl Fischer reagent to the end point potentiometrically. Calculate
the water equivalence factor F, in mg of water per mL of reagent by the
formula.
F = 0.1566 W / V
Where:
W = Weight of the Sodium tartrate dihydrate, in mg.

V = Volume of the reagent consumed in titration, in mL.
11.5 Preparation of Sample Solution:
Use the following quantities unless otherwise specified in the individual

monograph.
1.5.1 For Raw materials:
Use an accurately weighed or measured amount of sample under test

estimated to contain 2 - 250 mg of water. The amount of water depends
on the water equivalency factor of the reagent and on the method of
endpoint determination.

In most cases the minimum amount of specimen in mg can be estimated
using the formula:
FCV/KF
Where :
F = Water equivalency factor of the reagent in mg/mL.

C = Volume used in percent of capacity of burette.
V = Burette volume in mL.
KF = Limit or reasonable expected water content of the sample
in percent.
Note: C is between 30% and 100% for manual titration, and between 10%
and 100% for the instrumental method endpoint determination.
1.5.2 For Dosage Forms:
1.5.2.1 Capsules:
Use a portion of the mixed content of not less than 4 capsules.

Take an amount of powder accurately weighed or measured
under test estimated to contain 10 - 250 mg of water.
1.5.2.2 Tablets:
Use powder from not less than 4 tablets ground to a fine

powder in an atmosphere of temperature and relative humidity
known not to influence the results. Take an amount of powder
accurately weighed or measured under test estimated to
contain 10 - 250 mg of water.
Page No: 6/12

1.5.2.3 Powder for oral suspension / non-hygroscopic powder /
intermediate blend:
Use an accurately weighed or measured amount of sample

under test estimated to contain 10 - 250 mg of water.
1.6 Procedure for Water Determination of Sample for Direct Titration:
1.6.1 Transfer 35-40 mL of Methanol or other suitable solvent to the titration

vessel and neutralize it with the reagent potentiometrically or visual end
point to consume any moisture that may be present. (Disregard the volume
consumed, since it does not enter into the calculations).
1.6.2 Quickly add the samples solution, mix and again titrate with the Karl Fischer
reagent to the end-point potentiometrically.
1.7 Calculations:
V x F x 100
Water = -----------------
(%w/w) W
Where:
V = Volume in mL of Karl Fischer reagent

F = consumed.
Water equivalence factor of the reagent
W = (mg/mL).
Weight of sample taken in mg.
2.0 METHOD Ib (Residual titration):
Principle:
In the Residual titration, excess Reagent is added to the test specimen, sufficient time is
allowed for the reaction to reach completion, and the unconsumed Reagent is titrated
with a standard solution of water in a solvent such as Methanol. The Residual titration
procedure is applicable generally and avoids the difficulties that may be encountered in
the direct titration of substances from which the bound water is released slowly.
Page No: 7/12

Precautions for Residual Titration:
1. Electrode should be properly cleaned before analysis.

2. Self-indicating Silica gel should be replaced when its colour changes from blue to
white.
3. Ensure constant stirring during titration, avoiding splashing of the solvent on the
walls of the vessel.
For apparatus, reagents, and preparation of sample solution proceed as given

under Method Ia.
2.1 Standardization of Water Solution for Residual Titration:
Prepare a water solution by diluting 2 mL of water with Methanol or other suitable

solvent to 1000 mL. Standardize this solution by titrating 25.0 mL with the
Reagent, previously standardized as directed under Standardization of the
Reagent.
Calculate the water content, in mg per mL, of the water solution taken by the
formula:
VF / 25
Where:
V =
Volume of the Reagent consumed.
F =
Water equivalence factor of the
Reagent.
Determine the water content of the water solution weekly, and standardize the
Reagent against it periodically as needed.
2.2 Procedure for Water Determination of Sample for Residual Titration:
Where the individual monograph specifies that the water content is to be

determined by Method Ib, transfer 35 - 40 mL of Methanol or other suitable solvent
to the titration vessel, and titrate with the Reagent to the electrometric or visual
endpoint. Quickly add the sample solution, mix, and add an accurately measured
excess of the Reagent.
Printed :
Time (IST)
Printed By : Arti Pandya
11-Mar- 2019 8:58 PM

Page No: 8/12
Allow sufficient time for the reaction to reach completion, and titrate the
unconsumed Reagent with standardized Water solution to the electrometric or
visual endpoint. Calculate the water content of the sample, in mg, taken by the
formula :
F(XI - XR)
Where:
F = Water equivalence factor of the Reagent.

XI = Volume of the reagent added after introduction of the sample, in mL.
X = Volume of standardized water solution required to neutralize the
unconsumed Reagent, in mL.
R = Ratio, V/25 (mL Reagent / mL Water solution), determined from the
standardization of Water solution for Residual titration.
Notes:
1) If the sample reacts with medium then this method is not valid.
2) Use Pyridine as medium for Keto compounds.
3) This method is applicable where method mentions determination of water Ia
and Ib, otherwise refer the pharmacopoeia as per the status of the material.
3.0 Method Ic (Coulometric Titration):
Principle:
The Karl Fischer reaction is used in the coulometric determination of water. Iodine,
however, is not added in the form of a volumetric solution but is produced in an Iodide-
containing solution by anodic oxidation. The reaction cell usually consists of a large
anode compartment and a small cathode compartment that are separated by a
diaphragm. Other suitable types of reaction cells (e.g., without diaphragms) may also be
used. Each compartment has a platinum electrode that conducts current through the cell.
Iodine, which is produced at the anode electrode, immediately reacts with water present
in the compartment. When all the water has been consumed, an excess of iodine occurs,
which usually is detected electrometrically, thus indicating the endpoint. Moisture is
eliminated from the system by pre-electrolysis.
Page No: 9/12

Changing the Karl Fischer solution after each determination is not necessary since
individual determinations can be carried out in succession in the same reagent solution.
A requirement for this method is that each component of the sample is compatible with
the other components, and no side reactions take place. Samples are usually transferred
into the vessel as solutions by means of injection through a septum. Gases can be
introduced into the cell by means of a suitable gas inlet tube. Precision in the method is
predominantly governed by the extent to which atmospheric moisture is excluded from the
system; thus, the introduction of solids into the cell is not recommended, unless elaborate
precautions are taken, such as working in a glove-box in an atmosphere of dry inert gas.
Control of the system may be monitored by measuring the amount of baseline drift, which
does not preclude the need of any blank correction when used as a vehicle for sample
introduction. This method is particularly suited to chemically inert substances like
hydrocarbons, Alcohols, and Ethers. In comparison with the volumetric Karl Fischer
titration, coulometry is a micro-method. When appropriate, the water may be desorbed or
released from the sample by heat in an external oven connected with the vessel, to where
it is transferred with the aid of an inert and dried gas such as pure nitrogen. Any drift due
to the transport gas should be considered and corrected. Care should be taken in the
selection of the heating conditions to avoid the formation of water coming from
dehydration due to decomposition of the sample constituents, which may invalidate this
approach.
3.1 Apparatus:
Any commercially available apparatus consisting of an absolutely tight system fitted

with the necessary electrodes and a magnetic stirrer is appropriate. The
instrument's microprocessor controls the analytical procedure and displays the
results. Calibration of the instrument is not necessary, as the current consumed can
be measured absolutely.
3.2 Reagents:
See Reagent under Method Ia.


3.3 Preparation of Sample Solution:
3.3.1 For Soluble Solids:
Where the sample is a soluble solid, dissolve an appropriate quantity,

accurately weighed, in anhydrous Methanol or other suitable solvents.
3.3.2 For Liquids:
Liquids may be used as such or as accurately prepared solutions in

appropriate anhydrous solvents.
3.3.3 For Insoluble Solids:
Where the sample is an insoluble solid, the water may be extracted using a
suitable anhydrous solvent from which an appropriate quantity, accurately
weighed, may be injected into the analyte solution. Alternatively an
evaporation technique may be used in which water is released and
evaporated by heating the sample in a tube in a stream of dry inert gas, this
gas being then passed into the cell.
3.4 Procedure:
Using a dry syringe, quickly inject the sample solution, accurately measured and
estimated to contain 0.5 to 5 mg of water, or as recommended by the instrument
manufacturer into the analyte, mix, and perform the Coulometric titration to the
electrometric endpoint. Read the water content of the sample solution directly from
the instrument's display, and calculate the percentage that is present in the sample.
Perform a blank determination, and make any necessary corrections.
Page No: 11/12

HISTORY OF CHANGES

and last version)
CC000111 GP000025 Ver. 1.0 Revised to bring in-line with Ranbaxy General
procedure GP000059 (old number GP015-09),
electronic system Documentum format and current
USP.
CC032458 GP000025 Ver. 2.0 Sections for principle under 1.0 (Method Ia) and
3.0 (Method Ic) revised.
CC078567 GP000025 Ver. 3.0 Logo / template revised from Ranbaxy to Sun
Pharma due to the merger.
No change to the content of the document
except version number.

Page No: 12/12


5.0; Effective
: 01-Aug-2018
MELTING RANGE OR TEMPERATURE
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Daniel Savad
Coordinator, Quality Assurance QUALITY ASSURANCE-TR-OHM LABS 31-Jul- Created By
2018
Jalpa Pandya
Chemist - II QC 31-Jul- Reviewed and Approved By
2018
Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM LABS Reviewed and Approved By
31-Jul-2018

Pandya
GENERAL PROCEDURE
Title : MELTING RANGE OR TEMPERATURE
Pharmacopeial Status : USP<741>
Objective : The test for MELTING RANGE is provided to determine

compliance with the requirements specified in the
individual specifications or monograph.
Principle : Melting range or temperature of a solid is defined as

those points of temperature within which or the point at
which the substance begins to coalesce and is
completely melted except as defined otherwise for
certain substances. This is physical property of a
compound, however, it indicates the purity of the
compound to some extent.
1. For Class Ia and Class II:
The terms melting range, melting point, or melting temperature are all used in
pharmacopeial contexts. Most substances exhibit a melting transition, spanning the
temperatures at which the first detectable change of phase or liquid phase is detected
to the temperature at which no solid phase is apparent. The transition may appear
instantaneous for a highly pure material, but usually a range is observed from the
beginning to the end of the process. Factors influencing this transition include the
sample size, the particle size, the efficiency of heat diffusion within the sample, and
the heating rate, among other variables, that are controlled by procedure instructions.
For pharmacopeial purposes, the temperatures of the beginning (onset temperature)
and end of transition (clear temperature) represent the melting range, except as
defined otherwise for Procedure for Class II and Procedure for Class III below. The
terms melting point and melting temperature are considered to be equivalent.
Substances which melt with no decomposition or chemical change are known to melt
congruently. In these cases, the melting point is taken to be the end of the melting
range, i.e., the temperature at which no solid phase is apparent. In some articles, the
melting process is accompanied by simultaneous decomposition, which is visually
evidenced as a side event like darkening of the material, charring, bubbling, or other
incident. These transitions are known to be non-congruent. The visual impact of this
Page No: 2/7
document
GENERAL PROCEDURE

document
side reaction frequently obscures the end of the melting process, which may be
impossible to accurately determine. In those circumstances, only the beginning of the
melting can be accurately established, and it is to be reported as the melting point.
Since there may be a thermal lag between the heating medium and the sample within
the capillary tube, in order to achieve consistency and repeatability, it is important to
perform the melting determination at a heating rate, also referred to as ramp rate, of
1°/min.
In some articles, the melting process is accompanied by simultaneous decomposition,

which is visually evidenced as a side event like darkening of the material, charring,
bubbling, or other incident. The visual impact of this side reaction frequently obscures
the end of the melting process, which it may be impossible to accurately determine. In
those circumstances, only the beginning of the melting can be accurately established;
and it is to be reported as the melting temperature.
When no class is designated in the monograph, use the procedure for Class Ia for
crystalline or amorphous substances and the procedure for Class II for waxy
substances.
The procedure known as mixed-melting point determination, whereby the melting

range or temperature of a solid under test is compared with that of a an intimate
mixture of equal parts of the solid and an authentic specimen of it, e.g. the
corresponding USP reference standard, if available, may be used as a confirmatory
identification test. Agreement of the observations on the original and the mixture
constitutes reliable evidence of chemical identity.
Apparatus with cameras or other computerized equipment to improve accuracy,

sensitivity, or precision may be used provided that the apparatus is properly qualified.
1.1 Apparatus I:
An example of a suitable melting range Apparatus I consists of a glass

container for a bath of transparent fluid, a suitable stirring device, an accurate
thermometer, and a controlled source of heat. The bath fluid is selected with a
view to the temperature required, but light paraffin is used generally and certain
liquid silicones are well adapted to the higher temperature ranges. The fluid is
deep enough to permit immersion of the thermometer to its specified immersion
depth so that the bulb is still about 2 cm above the bottom of the bath. The heat
Page No: 3/7


may be supplied by an open flame or electrically. The capillary tube is about
10 cm long and 0.8 to 1.2 mm in internal diameter with walls 0.2 to 0.3 mm in
thickness.
1.2 Apparatus II:
An instrument may be used in the procedures for Classes I, Ia and Ib. An

example of a suitable melting range Apparatus II consists of a block of metal
that may be heated at a controlled rate, its temperature being monitored by a
sensor. The block accommodates the capillary tube containing the test
substance and permits monitoring of the melting process. The detector signal
may be processed by a microcomputer to determine and display the melting
point or range, or the detector signal may be plotted to allow visual estimation
of the melting point or range. Some approaches broadly used by automated
systems employ optical methods such as light absorption or bulk reflection.
2. Procedure (for Class Ia, Apparatus II):
Reduce the substance under test to a very fine powder, and, unless otherwise
directed, render it anhydrous when it contains water of hydration by drying it at the
temperature specified in the monograph, or, when the substance contains no water of
hydration, dry it over a suitable desiccant for not less than 16 hours (or at the
conditions stated in Loss on Drying <731>, if appropriate).
Charge a capillary glass tube, one end of which is sealed, with a sufficient amount of
the dry powder to form a column in the bottom of the tube to a nominal height of 3 mm
high when packed down as closely as possible by moderate tapping on a solid
surface. Due to the instrument design, alternative sample sizes may be used as
instructed by the instrument manufacturer.
Operate the apparatus according to the manufacturer's instructions. Heat the block
until the temperature is about 5 degrees below the expected melting point and is rising
at a rate of about 1°/min. Insert the capillary as directed in Procedure for Class I,
Apparatus I, and continue heating until melting is complete.
The temperature at which the column of the substance under test is observed to
collapse definitely against the side of the tube at any point indicates the beginning of
melting, and the temperature at which the test substance becomes liquid throughout
Page No: 4/7


corresponds to the end of melting or the melting point. The two temperatures fall
within the limits of the melting range. If melting occurs with decomposition, the melting
temperature corresponding to the beginning of the melting (melting point) is within the
range specified.
3. Procedure (for Class II, Apparatus I):
Carefully melt the material to be tested at as low a temperature as possible, and draw
it into a capillary tube, which is left open at both ends, to a depth of about 10 mm.
Cool the charged tube at 10°, or lower, for 24 hours, or in contact with ice for at least
2 hours. Then attach the tube to the thermometer by suitable means, adjust it in a
water bath so that the upper edge of the material is 10 mm below the water level.
Heat the bath until the temperature is about 5° below the expected melting point.
Continue the heating, with constant stirring, sufficiently to cause the temperature to
achieve the ramp rate of about 1.0 degrees per minute.
The temperature at which the material is observed to rise in the capillary tube is the
melting temperature.
Precautions:
Temperature should be increased slowly at the rate specified.
Calibrate the thermometer against reference standard, that melt nearest to the melting
range of the substances to be tested.
In case of any ambiguity working/reference standard should be tested simultaneously.
For substances which decompose on heating note the temperature at which frothing
begins or note the temperature at which decomposition starts till the complete
decomposition occurs. Report melting with decomposition.
Page No: 5/7

Page No: 6/7
HISTORY OF CHANGES
(Number and last

CC014036 GP000024 version 1.0 New format as per electronic
(Refer old document documentum compliance Manager (DCM)
series STP-008 Rev. system.
01)
CC054813 GP000024 Version 2.0  Added sample preparation instructions
and test parameters to section “For Class
Ia and Class II.”
 To Apparatus section added text
regarding use of instruments with
integrated cameras/computerized
equipment.
 To section for Apparatus II, added text
regarding processing of data by
microcomputer or determining melt range
visually.
 In section for Procedure (for Class Ia,
Apparatus II):
o Added to drying instructions “(or at
the conditions stated in Loss on
Drying
<731>, if appropriate).”
o Revised instructions for charging the
capillary tube.
o Revised instrument parameters and
heating rate.
 In section for Procedure (for Class II,
Apparatus I):
o Replaced “Continue the heating, with
constant stirring, sufficiently to cause
the temperature to rise at a rate of
about 0.5 to 1.0 degrees per
minute.” with “Continue the heating,
with constant stirring, sufficiently to
(Number and last

CC054813 GP000024 Version (Continued)
(Continued) 2.0 (Continued) about 1.0 degrees per minute.”
o Removed “Continue heating
until melting is
complete.”
CC096188 GP000024 Version 3.0  Revised Document Logo/Template
from “Ranbaxy” to “SUN Pharma”.
CC106263 GP000024 Version 4.0  Revised first three paragraphs of “For

Class Ia and Class II” section in their
entirety.
 At end of section 1.2 (Apparatus II)
added, “Some approaches broadly used
by automated systems employ optical
methods such as light absorption or
bulk reflection.”
 In “Procedure (for Class Ia, Apparatus
II)” section, revised heating instructions
 Made various grammatical changes
throughout document for clarification of
procedures.


4.0; Effective
: 04-Jun-2016
LOSS ON DRYING
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM 02-Jun- Created By
LABS 2016
Dalvinder Singh
Bhupendra
Patel Site Head of Quality QUALITY ASSURANCE-TR-OHM LABS 02-Jun-2016 Reviewed and Approved By

Pandya
GENERAL PROCEDURE
Title : LOSS ON DRYING
Objective : This test is provided to determine compliance with the “Loss

on drying” requirements where specified in the individual
specifications for a raw material, Active Pharmaceutical
Ingredient (API) and Finished Product.
Principle : Loss on drying is the loss in weight or mass at the specified

condition and expressed as % w/w or % m/m. It determines
the absorbed water or water of hydration under specified
conditions. This loss in weight represents residual volatile
constituents including organic solvents as well as water.
Safety : Always observe safe laboratory practices. Consult the

appropriate Material Safety Data Sheet (MSDS) before
handling any chemical if unfamiliar with the proper safety
precautions.
Method I
Apparatus
1. Weighing bottle
2. Thermostatic oven/vacuum oven (Drying chamber)
3. Desiccator/vacuum desiccators
Sample Quantity
a. For Raw Material/Drug Substance
Use 1 - 2 g of substance unless otherwise directed in the individual specifications.

document
GENERAL PROCEDURE

document
b. For Tablets
Use powder as specified in the specification or monograph from not less than 4 tablets
ground to a fine powder.
c. For Capsules
Use powder as specified in the specification or monograph from a portion of the mixed
contents of not less than 4 capsules.
d. Powder for oral suspension / intermediate blend
Use 1 - 2 g of substance unless otherwise directed in the individual specifications.
NOTE :
If the sample is in the form of large particle size, reduce the particle size to about 2 mm
by quickly crushing.
PROCEDURE
1. Place the weighing bottle with stopper with an identity mark under the same conditions to
be used in the determination of Loss on drying for 30 min.
2. Cool it to room temperature in a desiccator and weigh (W1). Record the weight.
3. Put the specified quantity of sample into the bottle. Replace the stopper and accurately
weigh the bottle and the contents (W2). Record the weight.
4. Distribute the sample evenly as practicable to a depth of 5 mm generally and not more
than 10 mm in case of bulky materials by gentle sidewise shaking.
5. Place the bottle in the drying chamber, remove the stopper and leave it in the drying
chamber.
Page No: 3/7

6. Dry the sample at the temperature and for the time as specified in the individual
monograph or to a constant weight under one of the following conditions.
NOTE: The temperature specified in the monograph is to be regarded as being within the
range of + 2°C of the stated figure.
Desiccator
 In a desiccator over Phosphorous pentoxide or any other desiccant as specified in the

individual monograph, at atmospheric pressure and normal room temperature, unless
otherwise specified.
 Where drying in a desiccator is specified, exercise particular care to ensure that the
desiccant is kept fully effective by frequent replacement.
In Vacuum (Over desiccant)
The term in vacuum denotes exposure to a pressure of less than 20 mm (2.67 kPa) of
mercury unless otherwise indicated.
Calculations
W2 – W3
Loss on drying = ----------------- x 100
(%w/w) W2 – W1
Where:
W = Weight of weighing bottle with stopper.

1
W = Weight of the weighing bottle with stopper + sample before drying.
W
2 = Weight of the weighing bottle with stopper + sample after drying.
3
Page No: 4/7

NOTE
a. The term constant weight means that two consecutive weights do not differ by more
than 0.5 mg/g of material, the second weighing being made after an additional hour of
drying under the specified conditions.
b. If individual monograph directs that loss on drying be determined by thermo gravimetric

analysis, a sensitive electrobalance is to be used.
c. Record the time of beginning and time of ending of the test.
METHOD II – (Applicable for analysis of product intermediate stage sample)
1. Set the drying temperature knob of IR moisture balance at 105°C or as specified in the
individual specifications or individual manufacturing instruction.
2. Set the instrument in mode of auto calculation of moisture content.
3. Set the swith off time limit of instrument.
4. Place sample (1 – 2 g or quantity as specified in the individual specifications or

individual manufacturing instruction) on tared aluminum sample pan kept on weighing
pan holder of IR moisture balance.
5. Evenly distribute the sample on sample pan of balance.
6. Start the instrument.
7. Note down the moisture content of sample displayed on display board of IR moisture
balance once the loss on drying over.
Page No: 5/7

PRECAUTIONS
1. Maintain the temperature of drying chamber as specified in the individual monograph

within the range of + 2°C of the stated figure.
2. Where drying in a desiccator is specified, exercise particular care to ensure that the
desiccant is kept fully effective by frequent replacement.
3. Number the bottle/bottle stopper before weighing.
4. Use rust free clean tongs for handling the weighing bottle.
5. Ensure that the oven is clean from inside before placing the bottle inside the oven.
6. If the substance melts at a lower temperature than that specified for the determination
of Loss on drying, maintain the bottle with its contents for 1 – 2 hours at a temperature
5 - 10°C below the melting temperature, then dry at the specified temperature.
7. If the substance is moisture sensitive, weigh in de-humidified conditions.
8. Where drying in vacuum over a dessicant is directed in the individual monograph, a

vacuum dessicator or a vacuum drying pistol, or other suitable vacuum drying
apparatus, is to be used.
9. Where drying in a capillary-stoppered bottle in vacuum is directed in the individual

monograph, use a bottle or tube fitted with a stopper having a 225 ± 25 μm diameter
capillary, and maintain the heating chamber at a pressure of 5 mm or less of mercury.
At the end of the heating period, admit dry air to the heating chamber, remove the
bottle, and with the capillary stopper still in place allow it to cool it to cool to room
temperature in a desicator before weighing.
Page No: 6/7

HISTORY OF CHANGES

and last version)
CC000407 GP000022 Version 1.0Revised to bring in-line with Ranbaxy General

(Refer to old documentprocedure GP000058 (old number GP012-09).
STP - 006 Rev. 03) Reformatted as per the Documentum format.
CC034442 GP000022 Version 2.0 Triennial review with no change in the content of
document.
CC079936 GP000022 Ver. 3.0 Logo / template revised from "Ranbaxy" to "Sun
Pharma" due to the merger.
Two new Precautions added.

Page No: 7/7


5.0; Effective
: 04-Jan-2018
HEAVY METALS
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
Manager, Quality Assurance QUALITY ASSURANCE-TR-OHM 03-Jan- Created By
LABS 2018
Bhaskar Reddy
Bhupendra
Patel Senior Director, Quality Assurance QUALITY ASSURANCE-TR-OHM 03-Jan-2018 Reviewed and Approved By
LABS

Pandya
GENERAL PROCEDURE
Title : HEAVY METALS
Pharmacopeial Status : In-house
Objective : Test for Heavy metals is provided to determine compliance

with the requirements specified in the individual
specification.
Principle : This test is provided to demonstrate that the content of

metallic impurities that are colored by sulfide ion. The
percentage of Lead in the test substance is determined by
concomitant visual comparison with a control prepared
from a standard Lead Solution. Note – Substances that
typically will respond to this test are lead, mercury,
bismuth, arsenic, antimony, tin, cadmium, silver, copper,
and molybdenum.
Methods:
Method-I: Determine the amount of heavy metals by Method-I, unless otherwise specified.
Method-I is used for substances that yield clear, colorless preparations under the specified
test conditions.
Method-II: Method-II is used for substances that do not yield clear, colorless preparations
under the test conditions specified for Method-I, or for substances that, by virtue of their
complex nature, interfere with the precipitation of metals by sulfide ion, or for fixed and volatile
oils.
Method-III: A wet-digestion method, is used only in those cases where neither Method-I nor
Method-II can be used.

document
GENERAL PROCEDURE

document
Procedure:
Lead Nitrate Stock Solution:
Dissolve 159.8 mg of Lead nitrate in 100 mL of water to which has been added 1 mL of Nitric
acid, then dilute with water to 1000 mL. Prepare and store this solution in glass containers
free from soluble lead salts.
Standard Lead Solution:
Prepare on the day of use. Dilute 10.0 mL of Lead Nitrate Stock Solution with water to
100.0 mL. Each mL of Standard Lead Solution contains the equivalent of 10 µg of lead. A
comparison solution prepared on the basis of 100 µL of Standard Lead Solution per g of
substance being tested contains the equivalent of 1 part of lead per million parts of substance
being tested.
Glycerin Base TS:
To 200 g of glycerin add water to bring the total weight to 235 g. Add 140 mL of 1 N sodium
hydroxide and 50 mL of water.
Thioacetamide TS:
Dissolve 4 g of thioacetamide in 100 mL of water.
Thioacetamide - Glycerin Base TS:
Mix 0.2 mL of thioacetamide TS and 1 mL of glycerin base TS, and heat in a boiling water bath
for 20 seconds. Use the mixture immediately.
1. METHOD-I:
pH 3.5 Acetate Buffer:
Dissolve 25.0 g of Ammonium acetate in 25 mL of water, and add 38.0 mL of 6 N

Hydrochloric acid. Adjust, if necessary, with 6 N Ammonium hydroxide or 6 N
Hydrochloric acid to a pH of 3.5, dilute with water to 100 mL, and mix.
Page No: 3/9

Standard Preparation:
Into a 50 mL color-comparison tube pipet 2 mL of Standard Lead Solution (20 µg of

Pb), and dilute with water to 25 mL. Using a pH meter or short-range pH indicator
paper as external indicator, adjust with 1 N Acetic acid or 6 N Ammonium hydroxide to
a pH between 3.0 and 4.0, dilute with water to 40 mL, and mix.
Test Preparation:
Into a 50-mL color-comparison tube place 25 mL of the solution prepared for the test as
directed in the individual specification; or, using the designated volume of acid where
specified in the individual specification, dissolve in and dilute with water to 25 mL the
quantity, in g, of the substance to be tested, as calculated by the formula:
2.0/(1000L)
in which L is the Heavy metals limit, as a percentage. Using a pH meter or short-range

pH indicator paper as external indicator, adjust with 1 N Acetic acid or 6 N Ammonium
hydroxide to a pH between 3.0 and 4.0, dilute with water to 40 mL, and mix.
Monitor Preparation:
Into a third 50-mL color-comparison tube place 25 mL of a solution prepared as

directed for Test Preparation, and add 2.0 mL of Standard Lead Solution. Using a pH
meter or short-range pH indicator paper as external indicator, adjust with 1 N Acetic
acid or 6 N Ammonium hydroxide to a pH between 3.0 and 4.0, dilute with water to
40 mL, and mix.
Procedure:
To each of the three tubes containing the Standard Preparation, the Test Preparation,
and the Monitor Preparation, add 2 mL of pH 3.5 Acetate Buffer, then add 1.2 mL of
Thioacetamide glycerin base TS, dilute with water to 50 mL, mix, allow to stand for
£
2 minutes, and view downward over a white surface the color of the solution from the
Test Preparation is not darker than that of the solution from the Standard Preparation,
and the color of the solution from the Monitor Preparation is equal to or darker than that
of the solution from the Standard Preparation.
Page No: 4/9

Note: If the color of the Monitor Preparation is lighter than that of the Standard
Preparation, use Method II instead of Method-I for the substance being tested.
2. METHOD-II:
pH 3.5 Acetate Buffer: (Prepare as directed under Method I)
Standard Preparation: (Prepare as directed under Method I)
Test Preparation:
Use a quantity, in g, of the substance to be tested as calculated by the formula:
2.0 / (1000L)
in which L is the Heavy metals limit, in percentage. Transfer the weighed quantity of
the substance to a suitable crucible, add sufficient Sulfuric acid to wet the substance,
and carefully ignite at a low temperature until thoroughly charred. (The crucible may be
loosely covered with a suitable lid during the charring.) Add to the carbonized mass
2 mL of Nitric acid and 5 drops of sulfuric acid, and heat cautiously until white fumes no
longer are evolved. Ignite, preferably in a muffle furnace, at 500°C to 600°C, until the
carbon is completely burned off. Cool, add 4 mL of 6 N Hydrochloric acid, cover, digest
on a steam bath for 15 minutes, uncover, and slowly evaporate on a steam bath to
dryness. Moisten the residue with 1 drop of Hydrochloric acid, add 10 mL of hot water,
and digest for 2 minutes. Add 6 N Ammonium hydroxide drop wise until the solution is
just alkaline to litmus paper, dilute with water to 25 mL, and adjust with 1 N Acetic acid
to a pH between 3.0 and 4.0, using short-range pH indicator paper as an external
indicator. Filter if necessary, rinse the crucible and the filter with 10 mL of water,
combine the filtrate and rinsing in a 50-mL color-comparison tube, dilute with water to
40 mL, and mix.
Procedure:
To each of the tubes containing the Standard preparation and the Test preparation, add
2 mL of pH 3.5 Acetate Buffer, then add 1.2 mL of Thioacetamide-glycerin base TS,
dilute with water to 50 mL, mix, allow to stand for 2 minutes, and view downward over a
£
white surface : the color of the solution from the Test Preparation is not darker than that
of the solution from the Standard Preparation.
Page No: 5/9

3. METHOD-III:
pH 3.5 Acetate Buffer: (Prepare as directed under Method I)
Standard Preparation:
Transfer a mixture of 8 mL of Sulfuric acid and 10 mL of Nitric acid to a clean, dry,

100 mL Kjeldahl flask, and add a further volume of Nitric acid equal to the incremental
volume of Nitric acid added to the Test Preparation. Heat the solution to the production
of dense, white fumes; cool; cautiously add 10 mL of water; and, if Hydrogen peroxide
was used in treating the Test Preparation, add a volume of 30 percent Hydrogen
peroxide equal to that used for the substance being tested. Boil gently to the
production of dense, white fumes. Again cool, cautiously add 5 mL of water, mix, and
boil gently to the production of dense, white fumes and to a volume of 2 to 3 mL. Cool,
dilute cautiously with a few mL of water, add 2.0 mL of standard Lead Solution (20 µg
of Pb), and mix. Transfer to a 50-mL color-comparison tube, rinse the flask with water,
adding the rinsing to the tube until the volume is 25 mL, and mix.
Test Preparation:
Unless otherwise indicated in the individual specification, use a quantity, in g, of the

substance to be tested as calculated by the formula:
2.0/(1000L)
in which L is the Heavy metals limit, as a percentage.
For Solids:
Transfer the weighed quantity of the test substance to a clean, dry, 100 mL Kjeldahl
flask.
Note: A 300 mL flask may be used if the reaction foams excessively.

Page No: 6/9

Clamp the flask at an angle of 45°, and add a sufficient quantity of a mixture of 8 mL of
Sulfuric acid and 10 mL of Nitric acid to moisten the substance thoroughly. Warm
gently until the reaction commences, allow the reaction to subside, and add portions of
the same acid mixture, heating after each addition, until a total of 18 mL of the acid
mixture has been added. Increase the amount of heat, and boil gently until the solution
darkens. Cool, add 2 mL of Nitric acid, and heat again until the solution darkens.
Continue the heating, followed by addition of Nitric acid until no further darkening
occurs, then heat strongly to the production of dense, white fumes. Cool, cautiously
add 5 mL of water, boil gently to the production of dense, white fumes, and continue
heating until the volume is reduced to a few mL. Cool, cautiously add 5 mL of water,
and examine the color of the solution. If the color is yellow, cautiously add 1 mL of
30 percent hydrogen peroxide, and again evaporate to the production of dense, white
fumes and a volume of 2 to 3 mL. If the solution is still yellow, repeat the addition of
5 mL of water and the Peroxide treatment.
Cool, dilute cautiously with a few mL of water, and rinse into a 50 mL color-comparison
tube, taking care that the combined volume does not exceed 25 mL.
For Liquids:
Transfer the weighed quantity of the test substance to a clean, dry, 100-mL Kjeldahl
flask.
Note: A 300-mL flask may be used if the reaction foams excessively.
Clamp the flask at an angle of 45°, and cautiously add a few mL of a mixture of 8 mL of
Sulfuric acid and 10 mL of Nitric acid. Warm gently until the reaction commences, allow
the reaction to subside, and add portions of the same acid mixture, heating after each
addition, until a total of 18 mL of the acid mixture has been added. Increase the
amount of heat, and boil gently until the solution darkens. Cool, add 2 mL of Nitric acid,
and heat again until the solution darkens. Continue the heating, followed by addition of
Nitric acid until no further darkening occurs, then heat strongly to the production of
dense, white fumes. Cool, cautiously add 5 mL of water, boil gently to the production of
dense, white fumes, and continue heating until the volume is reduced to a few mL.
Cool, cautiously add 5 mL of water, and examine the color of the solution. If the color is
yellow, cautiously add 1 mL of 30 percent hydrogen peroxide, and again evaporate to
the production of dense, white fumes and a volume of 2 to 3 mL. If the solution is still
yellow, repeat the addition of 5 mL of water and the Peroxide treatment.
Page No: 7/9

Cool, dilute cautiously with a few mL of water, and rinse into a 50-mL color-comparison
tube, taking care that the combined volume does not exceed 25 mL.
Monitor Preparation:
Proceed with the digestion, using the same amount of sample and the same procedure
as directed in the subsection If the substance is a solid in the section Test Preparation,
until the step “Cool, dilute cautiously with a few mL of water.” Add 2.0 mL of Lead
Standard Solution (20 µg of lead), and mix. Transfer to a 50 mL color comparison tube,
rinse the flask with water, adding the rinsing to the tube until the volume is 25 mL, and
mix.
Procedure:
Treat the Test preparation, the Standard preparation, and the Monitor preparation as
follows. Using a pH meter or short-range pH indicator paper as external indicator,
adjust the solution to a pH between 3.0 and 4.0 with Ammonium hydroxide (a dilute
Ammonia solution may be used, if desired, as the specified range is approached), dilute
with water to 40 mL, and mix. To each tube add 2 mL of pH 3.5 Acetate Buffer, then
add 1.2 mL of Thioacetamide–glycerin base TS, dilute with water to 50 mL, mix, allow
£
to stand for 2 minutes, and view downward over a white surface : the color of the Test
Preparation is not darker than that of the Standard Preparation, and the color of the
Monitor Preparation is equal to or darker than that of the Standard Preparation.
£ In those countries or jurisdictions where Thioacetamide cannot be used, add 10 mL of

freshly prepared hydrogen sulfide TS to each of the tubes, mix, allow to stand for
5 minutes and view downward over a white surface
Page No: 8/9

Page No: 9/9
HISTORY OF CHANGES

version)
CC000481 GP000020 Version 1) Harmonizing General Procedure in the new
1.0 (Refer old electronic Documentum
document STP-004 Compliance Manager(DCM)system.
Rev.06).
2) Revised to bring in-line with Ranbaxy
General procedure GP000066 (Old number
GP027)
CC035014 GP000020 Version No changes have been made to the content of
2.0 the document at this time.
CC080403 GP000020 Ver. 3.0  Footnote added after view downward over a
white surface for countries where
Thioacetamide cannot be used.
 Preparation for Glycerin-base TS,
Thioacetamide TS and Thioacetamide-
Glycerin TS removed.
 Logo / template revised from "Ranbaxy" to
CC097958 GP000020 Ver. 4.0  Document revised to incorporate

some preparations from USP.
 Revised pharmacopeial status
 Revised principal attribute.
 Removed references to USP
monograph wherever applicable.


4.0; Effective
: 14-Jul-2016
ARSENIC
:
Effective Date :
Review Due
:
Title
:
SIGNATURE PAGE

Gira Shah
QA Group Leader, Documentation QUALITY ASSURANCE-TR-OHM 12-Jul- Created By
LABS 2016
Dalvinder Singh
QC Senior Manager, Raw Materials QUALITY CONTROL-LA-OHM LABS 12-Jul- Reviewed and Approved By
2016
Rama Chitirala
QA Sr. Manager, Operations Oversight QUALITY ASSURANCE-TR-OHM LABS Reviewed and Approved By
13-Jul-2016

Pandya
ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ ANTES D
PROCEDIMIENTO GENERAL
Version No. : 4.0; EffectivO
Fecha : 14-Jul-2016
efectiva : 13-Jul-2019
Review Due :
ARSENICO
Title
Título : ARSENICO
Estado de la farmacopea: Capítulo General de la USP <211>
Objetivo: Este Procedimiento General proporciona directrices para llevar a cabo

la prueba límite para el arsénico
Principio: Este procedimiento está diseñado para determinar la presencia de rastros

cantidades de arsénico convirtiendo el arsénico de una sustancia bajo prueba en arsina, que luego
se pasa a través de una solución de dietilditiocarbamato de plata para formar un complejo rojo. El
color rojo así producido se compara, ya sea visualmente o espectrofotométricamente, con el color
producido de forma similar en un control que contiene una cantidad de arsénico equivalente al
límite dado en la especificación individual. Los límites se establecen en términos de Arsénico
(ppm). El contenido de arsénico no debe exceder el límite dado en la especificación individual.
Métodos (USP)
Se proporcionan dos métodos. Los métodos difieren únicamente en el tratamiento preliminar de la

sustancia de ensayo y la norma. En general, el método I se utiliza para los materiales inorgánicos,
mientras que el método II se utiliza para los materiales orgánicos.
Page No: 2/8

Impreo por Arti Pandya Tiempo de 09-Mar-2019 4:08 AM
: impression (IST) :
Este documento está firmado electrónicamente en versión Documentum 6.5
La página de la firma es la primera página del

documento
Aparato
El aparato consiste en un generador de arsina (a) provisto de un depurador (c) y un tubo
absorbedor (e) con rótulas estándar o de tierra (b y d) entre las unidades. Sin embargo, puede
utilizarse cualquier otro aparato adecuado que incorpore el principio del montaje descrito e
ilustrado.
Page No: 3/8

Imprero por Arti Pandya Tiempo de 9- Mar-2019 4:08 AM

Solución madre de trióxido de arsénico
Disolver 132,0 mg de trióxido de arsénico, previamente secado a 105 C durante 1 hora y pesado con
precisión, en 5 mL de solución de hidróxido de sodio (1 de cada 5) en un matraz volumétrico de 1 L.
Neutralizar la solución con ácido sulfúrico 2 N, añadir 10 mL más de ácido sulfúrico 2N, luego añadir
agua recién hervida y enfriada a volumen, y mezclar.
Solución estándar de arsénico
Transfiera 10,0 mL de solución madre de trióxido de arsénico a un matraz aforado de 1000 mL, añada
10 mL de ácido sulfúrico 2 N, luego añada agua recién hervida y enfriada para completar el volumen,
y mezcle. Cada mL de Solución de Arsénico Estándar contiene el equivalente a 1 µg de Arsénico (As).
Mantenga esta solución en un recipiente de vidrio y utilícela dentro de los 3 días.
1. MÉTODO I
1.1. Preparación estándar
Pipetee 3,0 mL de Solución de Arsénico Estándar en un matraz generador, y dilúyalo con agua hasta
35 mL.
1.2. Preparación de la prueba
A menos que se indique lo contrario en la monografía individual, transfiera al matraz generador la

cantidad, en gramos, de la sustancia de ensayo calculada por la fórmula:
3.0 / L
en el que L es el límite de arsénico en ppm, se disuelve en agua y se diluye con agua hasta 35 mL.
1.3. Reactivos
Ácido sulfúrico (7 N)
Solución de yoduro de potasio TS (16,5 % p/v) Ácido más fuerte Solución de cloruro estanoso
Dietilditiocarbamato de plata TS
Page No: 4/8

Impreso por Arti Pandya Tiempo de 09-Mar-2019 4:08 AM
: impresion IST) :
1.1. Procedure
Traten la preparación estándar y la preparación de la prueba de la siguiente manera:
1. Añada 20 mL de ácido sulfúrico 7 N, 2 mL de yoduro de potasio TS, 0,5 mL de ácido más

fuerte de cloruro de estaño TS, 1 mL de alcohol isopropílico y mezcle.
2. 2. Dejar reposar a temperatura ambiente durante 30 min. 3. Llenar el tubo depurador (c)
con dos trozos de algodón que han sido empapados en una solución saturada de
acetato de plomo, liberados del exceso de solución por expresión, y secados al vacío a
temperatura ambiente, dejando un espacio de 2 mm entre los dos trozos. Lubrique las
juntas (b y d) con una grasa adecuada para la llave de paso diseñada para su uso con
disolventes orgánicos, y conecte la unidad de depuración al tubo absorbedor (e).
3. 3. Transfiera 3.0 mL de dietilditiocarbamato de plata TS al tubo absorbedor.
4. 4. Añada 3,0 g de zinc granulado (malla 20) a la mezcla del matraz, conecte
inmediatamente la unidad depuradora montada y permita que la evolución del
Hidrógeno y el desarrollo del color prosigan a temperatura ambiente durante 45 min,
agitando el matraz suavemente a intervalos de 10 min.
5. 5. Desconecte el tubo absorbedor de las unidades generadora y depuradora y transfiera

la solución absorbente a una célula de absorción de 1 cm.
6. Cualquier color rojo producido por la Preparación de la Prueba no excede el producido

por la Preparación Estándar.
NOTA: Si es necesario o deseable, determinar la absorbencia a la longitud de onda de máxima

absorbencia entre 535 nm y 540 nm, con un espectrofotómetro o colorímetro adecuado,
utilizando el dietilditiocarbamato de plata TS como blanco .
Page No: 5/8

2. MÉTODO II
NOTAS:
1. Precaución - Algunas sustancias pueden reaccionar con violencia explosiva cuando se

digieren con peróxido de hidrógeno. Tome las precauciones de seguridad en todo momento.
2. Si hay presentes compuestos que contienen halógenos, utilice una temperatura más baja
mientras calienta la muestra de prueba con ácido sulfúrico, evite hervir la mezcla y añada el
peróxido de hidrógeno con precaución, antes de que comience la carbonización, para evitar la
pérdida del arsénico trivalente.
3. Si la sustancia de ensayo reacciona con demasiada rapidez y comienza a carbonizarse

con 5 mL de ácido sulfúrico antes de calentarla, utilice en su lugar 10 mL de ácido sulfúrico
diluido enfriado (1 de cada 2) y añada unas pocas gotas de peróxido de hidrógeno antes de
calentarla.
2.1. Preparación estándar
Pipetee 3,0 mL de Solución de Arsénico Estándar en un matraz generador, añada 2 mL de

ácido sulfúrico, mezcle y añada la cantidad total de 30 por ciento de peróxido de hidrógeno
utilizado en la preparación de la prueba. Caliente la mezcla hasta que emita vapores fuertes,
enfríela, añada con cuidado 10 mL de agua y vuelva a calentarla hasta que emita vapores
fuertes. Repita este procedimiento con otros 10 mL de agua para eliminar cualquier rastro de
peróxido de hidrógeno. Enfríe, y diluya con agua hasta 35 mL.
2.2. Preparación de la prueba
A menos que se indique lo contrario en la monografía individual, transfiera a un matraz

generador la cantidad, en gramos, de la sustancia de ensayo calculada por la fórmula:
3.0/ L
en el que L es el límite de arsénico en ppm. Añada 5 mL de ácido sulfúrico y unas pocas

cuentas de vidrio, y digiera en una campana extractora, preferiblemente en una placa caliente y
a una temperatura que no exceda los 120 C, hasta que comience la carbonización. (Puede ser
necesario ácido sulfúrico adicional para humedecer completamente algunos especímenes, pero
el volumen total añadido no debe exceder de 10 mL).
Impreso por impression

: Arti Pandya Tiempo de (IST) : 09-Mar-2019 4:08 AM
Page No: 6/8

Añade con precaución, gota a gota, un 30 por ciento de peróxido de hidrógeno, permitiendo que la reacción
se calme y que se caliente de nuevo entre gotas. Añada las primeras gotas muy lentamente con suficiente
mezcla, para evitar una reacción rápida. Interrumpa el calentamiento si la espuma se vuelve excesiva.
Cuando la reacción haya disminuido, calentar con precaución, girando el matraz de vez en cuando para evitar
que el espécimen se apelmace en el vidrio expuesto a la unidad de calentamiento. Mantener las condiciones
de oxidación en todo momento durante la digestión añadiendo pequeñas cantidades de la solución de
peróxido de hidrógeno siempre que la mezcla se vuelva marrón u oscura. Continúe la digestión hasta que la
materia orgánica sea destruida, elevando gradualmente la temperatura de la placa calefactora hasta que los
vapores del trióxido de azufre evolucionen copiosamente y la solución se vuelva incolora o conserve sólo un
ligero color pajizo. Enfríe, añada cautelosamente 10 ml de agua, mezcle y vuelva a evaporar hasta obtener
una fuerte humareda, repitiendo este procedimiento para eliminar cualquier rastro de peróxido de hidrógeno.
Enfríe, añada con precaución 10 mL de agua, lave los lados del matraz con unos pocos mL de agua y diluya
con agua hasta 35 mL.
2.3. Procedimiento
Siga el procedimiento descrito en el Método I.
NOTA: Los productos químicos que interfieren
Los metales o las sales de metales como el cromo, el cobalto, el cobre, el mercurio, el molibdeno, el níquel, el
paladio y la plata pueden interferir en la evolución de la arsina. El Antimonio, que forma la Estibina, produce
una interferencia positiva en el desarrollo del color con el Dietilditiocarbamato de Plata TS; cuando se
sospecha la presencia de Antimonio, los colores rojos producidos en las dos soluciones de
Dietilditiocarbamato de Plata pueden ser comparados en la longitud de onda de máxima absorbencia entre
535 nm y 540 nm, con un colorímetro adecuado, ya que a esta longitud de onda la interferencia debida a la
Estibina es insignificante
Page No: 7/8

: impresion
Este documento está firmado (IST) :
electrónicamente en Documentum-versión 6.5
La página de la firma es la primera página del documento
HISTORIAL DE CAMBIOS
CCR Sustituye (Número y Cambio(s) realizado(s)
Número última versión)
CC001397 GP000018 Versión  - Revisado para que se ajuste al procedimiento

1.0 (Referirse al general de Ranbaxy GP000068 (antiguo
antiguo documento número GP032-06).
STP - 002 Rev. 04)  - Formateado según el formato Documentum.
CC037166 GP000018 Version  - Corregidos los errores de formato.
2.0  - Eliminado todas las instrucciones de
preparación de la Solución de Prueba que no
se dan explícitamente en el Capítulo General
de la USP <211>.
 - En la preparación de la Solución madre de
trióxido de arsénico, se sustituyó "132 mg" por
CC081696 GP000018 Ver. 3.0  - Logotipo/plantilla revisado de "Ranbaxy" a
"Sun Pharma" debido a la fusión.
 - No hay cambios en el contenido del
documento.
************* Fin del documento *************

ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ ANTES DE USARLA.
Document No. FS000418

5.0; Effective
: 12-Jul-2016
AGUA PURIFICADA, USP
:
Effective Date :
Review Due
:
Title
:
PÁGINA DE
FIRMAS
Nombre completo Título Departamento Fecha Justificación

Daniel Savad
Asociado superior de GARANTÍA DE CALIDAD-TR-OHM 29-Jun- Creado por
documentación de control de LABS 2016
calidad
Bhaskar Reddy CONTROL DE CALIDAD - LABORATORIOS 29-Jun-2016

Líder del Grupo QC, Materias TR-OHM Revisado y aprobado por
Primas
Dalvinder Singh Gerente Principal de QC, Materias Primas 30-Jun-2016

Revisado y aprobado por y
CONTROL DE CALIDAD-
LABORATORIOS LA-OHM
Ronak Patel
oTTROSS Asuntos 11-Jul-2016 Revisado y aprobado por
Regulatorios
Gira Shah
Líder del Grupo QA, GARANTÍA DE CALIDAD-TR-OHM 11-Jul- Revisado y aprobado por
Documentación LABS 2016
Este documento fue aprobado y firmado electrónicamente y esta es la manifestación de la firma
electrónica.

Pandya
ESPECIFICACIÓN DE LA MATERIA PRIMA

Document No. : FS000418
Fecha : 12-Jul-2016
efectiva : 11-Jul-2022
Revisión :
debida
Título : AGUA PURIFICADA, USP
Tipo de documento : Liberación / Regulación

Mercado : EE.UU.
Código SAP : 8001907
Estado de la farmacopea: USP
Almacenamiento : No aplicable
Embalaje : No se aplica
Nombre del fabricante: No Aplicable
Page No: 2/4


document
PRUEBA REQUISITO
REFERENCI
A DEL
MÉTODO
DESCRIPCIÓN Líquido claro, incoloro e inodoro GP000054
CARBONO ORGÁNICO TOTAL (ppb) Límite de alerta: 200 USP General

Límite de acción: 400 Chapter <643> /
Cumple con el requisito de la FT005305
USP.
CONDUCTIVIDAD DEL AGUA (µs/cm) Alert Limit: 1.1 USP General

Action Limit: 1.2 Chapter <645> /
Meets the USP requirement. FT005305
- LÍMITES USP General

MICROBIANOSTotal NMT 70 Chapter <1231> /
Microbial Count GP000041
Alert Limit: Total Plate Count
(cfu/mL) NMT 100
Límite máximo permitido
(cfu/mL)
Ausente
- Total Coliforms
PageNo: 3/4
: impression
Este documento está firmado (IST) : en
electrónicamente
Documentum-versión 6.5
PageNo: 4/4
: impression
Este documento está firmado (IST) : en
electrónicamente
Documentum-versión 6.5
CCR Sustituye (Número y Cambio(s) realizado(s)
Número última versión)
CC002199 FS000418 Ver. 1.0  - Formato de especificación actualizado según el

(referencia antigua nuevo sistema electrónico del Gerente de
serie de documentos Cumplimiento Documentum (DCM).
8001907 Rev.  - El requisito de especificación de TOC cambió
05) de "NMT 500 ppb" a "Cumple con los requisitos
de la USP".
CC021668 FS000418 Ver. 2.0  - Reformuló el requisito de la prueba de
conductividad del agua de "NMT 2.1*" a "Cumple
los requisitos de la USP".
 - Revisó la especificación de los Límites
Microbianos, Coliformes Totales de "Negativo" a
"Ausente".
CC065778 FS000418 Ver. 3.0  - El documento se revisa para dar una nueva
fecha de entrada en vigor.
 - El logo/plantilla del documento ha sido
revisado de "Ranbaxy" a "Sun Pharma".
CC078134 FS000418 Ver. 4.0  - Para la prueba de Carbono Orgánico Total:

 o Indicar las unidades como "ppb".
 o Requisito revisado.
 - Requisito revisado para la prueba de
conductividad del agua.
 - Se eliminó la prueba de sustancias oxidables y
la nota de pie de página "**" asociada.

ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ ANTES DE USARLA.
Document No. FT005305

4.0; Effective
: 12-Jul-2016
:
Effective Date :
Review Due
:
Title
:
PÁGINA DE
FIRMAS
Nombre completo Título Departamentot Fecha Justificación

Daniel Savad
Asociado superior de GARANTÍA DE CALIDAD-TR-OHM 29-Jun- Created By
documentación de control de LABS 2016
calidad
Bhaskar Reddy CONTROL DE CALIDAD - LABORATORIOS 29-Jun-2016

Líder del Grupo QC, Materias TR-OHM Reviewed and Approved By
Primas
Dalvinder Singh 29-Jun-2016

Reviewed and Approved By
CONTROL DE CALIDAD-
Gerente Principal de QC, Materias Primas LABORATORIOS LA-OHM
Venkata Adduri Gerente de QC, Raw Marterials

CONTROL DE CALIDAD - 29-Jun-2016 Reviewed and Approved By
LABORATORIOS TR-OHM
Ronak Patel
OTROS Asuntos 11-Jul-2016 Reviewed and Approved By
Regulatorios
Gira Shah Approved By

Líder del Grupo QA, GARANTÍA DE CALIDAD-TR-OHM Review
Documentación LABS11-Jul-2016 ed and
electrónica.

Pandya
PROCEDIMIENTO DE PRUEBA ESTÁNDAR

Documento No. : FT005305
No. de la :
versión. 4.0; Effectivo
Fecha de
: 12-Jul-2016
entrada en vigor : 11-Jul-2022
Revisión debida :
Título
Título : AGUA PURIFICADA, USP
Tipo de documento : Liberación / Regulación

Mercado : EE.UU.
Fabricante de API : No Aplica
Page No: 2/12

: impression
Este documento está firmado (IST) : en Documentum-versión 6.5
electrónicamente
1.0 Abreviaturas y definiciones:
TOC Carbono orgánico total

USP Farmacopea de los Estados Unidos
SOP Procedimiento operativo estándar
L Literatura
mL Mililitro
P Pureza de la norma
CB Concentración de 1,4 - Estándar de benzoquinona
CS Concentración del estándar de sacarosa
RE Eficiencia de respuesta
TOCB Lectura de TOC de 1,4 - Benzoquinona
TOCS Lectura de TOC de la sacarosa
TOCBL Lectura del TOC de la zona en blanco...
Rw Respuesta del blanco = TOCBL
RS Respuesta del Estándar de Sacarosa = TOCS
RSS Responsabilidades de la norma de idoneidad del sistema =
NMT No más que
µS/cm microSiemens por centímetro
pH potencia del Hidrógeno
°C grado Centígrado
2.1 Carbono orgánico total:
El carbono orgánico total (COT) del agua puede ser medido en línea o en el
modo de muestra de agarre (modo fuera de línea).
2.2 Idoneidad del sistema :
2.2.1 Agua en blanco / reactiva:

(Concentración NMT 100 ppb)
Agua con reactivo USP / Agua MilliQ como agua con reactivo USP
2.2.2 Estándar de idoneidad del sistema:
Estándar de 1,4-Benzoquinona (Concentración alrededor de 500 ppb)
Pesar con precisión 0,075 g de 1,4- Benzoquinona y transferirla a un

matraz volumétrico de 1 L, disolverla y diluirla a volumen con el Agua
Reactiva USP. Pipetear 10 mL de estándar madre de benzoquinona en
un matraz volumétrico de 1 L, completar hasta el volumen con el agua
del reactivo USP.
Calcule la Concentración Estándar de Benzoquinona (CB) de la
siguiente manera: CB = Peso estándar × P × 0.6666 × 10
100
2.2.3 Solución estándar de sacarosa:
Estándar de sacarosa (Concentración aproximada de 500 ppb)
Pesar 0,059 g de sacarosa y transferirla en un matraz volumétrico de 1

L. Disolver y diluir hasta el volumen con el agua del reactivo USP.
Pipetear 10 mL de la solución madre de sacarosa estándar en un
matraz volumétrico de 500 mL y completar hasta el volumen con el
agua del reactivo USP. Calcule la Concentración del Estándar de
Sucrosa (CS) de la siguiente manera:
6
Std wt. × P × 0.421 × 10
CS = 50
Page No: 4/12


Nota:
1. Utilice números redondeados de CS y CB en el cálculo de RE para obtener el

valor en línea con los números de reporte del instrumento.
2. Usar y almacenar los estándares de la USP como se indica en la etiqueta.
3. La estabilidad de la norma de la sacarosa y la norma de idoneidad del sistema
debe ser de 7 días a partir de la fecha de preparación. (Según el informe analítico de GE)
4. Almacenar el conjunto de normas de idoneidad del sistema (es decir, en blanco,
norma de idoneidad del sistema y norma de la sacarosa) a 2 - 8 0C para mantener la vida
propia. (Según el informe analítico de GE)
5. C/Mol.wt=72.06g carbono/108.1 g 1,4- Benzofenona = 0.6666
6. C/Mol.wt=144.1 g de carbono/342.3 g de sacarosa = 0.4210
2.2.4 Procedimiento:
Ejecutar el blanco/, la solución estándar de idoneidad del sistema, y la solución estándar

de sacarosa según el protocolo de idoneidad del sistema de GE..
Calcular la Eficiencia de Respuesta (RE) usando la fórmula: RE % = CS × (TOCB-
TOCBL) × 100
CB (TOCS - TOCBL)
Especificación de idoneidad del sistema: Eficiencia de respuesta: 85% - 115%

2.2.5 Calendario para la adecuación del sistema del analizador TOC en línea / fuera de
línea:
2.2.5.1 Realizar la adecuación del sistema del instrumento TOC fuera de línea una vez por
semana y/o antes de probar las muestras de agarre.
2.2.5.2 Realizar la adecuación del sistema del instrumento COT en línea una vez por
semana.
2.1.1.1 2.2.5.3 El Analizador COT en línea debe ser monitoreado por el Supervisor de
Producción diariamente.
Page No: 5/12

Este documento está firmado electrónicamente en Documentum-versión 6 .5
2.3 Pruebas de agua purificada: Especificación: NMT (TOCS - TOCBL)

2.3.1 Para el análisis del COT fuera de línea del agua purificada para todos los
puertos de usuario se debe
realizado una vez a la semana según la versión actual de OP000058.
2.3.2 Para el análisis COT en línea, las mediciones del agua purificada del tanque
de agua se harán automáticamente por un analizador de COT.
2.3.3 Para el análisis COT en línea, en caso de cualquier
emergencia/mantenimiento de cualquier instrumento COT, los datos
generados dentro de las 24 horas del intervalo de tiempo serán aceptados
para el uso de producción de agua purificada.
3.1 Conductividad del agua:
3.2 La conductividad del agua purificada para todos los puertos de usuario debe
realizarse semanalmente una vez según la versión actual de OP000058.
3.3 Se debe utilizar un medidor de conductividad calibrado para medir la

conductividad del agua.
3.4 Si se cumplen las condiciones de prueba y los límites de conductividad en

cualquiera de las dos etapas preliminares incluidas en el método de
prueba, el agua cumple los requisitos de esta prueba. No es necesario
pasar a la tercera etapa de la prueba. Sólo en caso de fallo en la etapa
final se considera que la muestra no cumple los requisitos de la prueba.
3.5 Etapa 1:
3.5.1 Determinar la temperatura del agua y la conductividad del agua utilizando

una lectura de conductividad no compensada por temperatura. La medición
puede realizarse en un recipiente adecuado o como una medición en línea.
Nota: Utilice un recipiente de HDPE calificado para recoger el agua para la prueba
de conductividad
Pag No: 6/12

Impreso por Arti Pandya Tiempo impreso 13-Mar-2019 3:40 AM
: (IST) :
3.5.2 Utilizando la tabla de requisitos de temperatura y conductividad de la Etapa 1, encuentre la

temperatura, es decir, la siguiente temperatura más baja. El valor de conductividad correspondiente en
esta tabla es el límite. [Nota- No interpolar.]
3.5.3 Si la conductividad medida no es mayor que el valor de la tabla, el agua cumple los requisitos de
la prueba de conductividad. Si la conductividad es mayor que el valor de la tabla, proceda con la Etapa
2.
Pag No: 7/12

: impresion (IST) :
Etapa 1 - Requisitos de temperatura y conductividad:
(sólo para mediciones de conductividad no compensadas por temperatura)
Requisitos de conductividad de temperatura

(µS/cm)+
0 0.6
5 0.8
10 0.9
15 1.0
20 1.1
25 1.3
30 1.4
35 1.5
40 1.7
45 1.8
50 1.9
55 2.1
60 2.2
65 2.4
70 2.5
75 2.7
80 2.7
85 2.7
90 2.7
95 2.9
100 3.1
+
µS/cm (microSiemen per centimeter) = µmho/cm = reciprocal of Megohm-cm.
I mpreso por : Arti Pandya

ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDE
i mpresion (IST) : Pag No: 8/12

Tiempo de 13-Mar-2019 3:40 AM
3.6 Etapa 2:
3.6.1 Transferir una cantidad suficiente de agua (100 mL o más) a un recipiente

adecuado y agitar la muestra de ensayo. Ajustar la temperatura si es necesario, y
mientras se mantiene a 25°C ± 1°C comenzar a agitar enérgicamente la muestra de
ensayo mientras se observa periódicamente la conductividad. Cuando el cambio de
conductividad (debido a la absorción de dióxido de carbono atmosférico) sea inferior
a un neto de 0,1 µS/cm por 5 minutos, observe la conductividad.
3.6.2 Si la conductividad no es superior a 2,1 µS/cm, el agua cumple los requisitos

de la prueba de conductividad. Si la conductividad es superior a
2,1 µS/cm, proceda con la Etapa 3.
3.7 Etapa 3:
3.7.1 Efectúe esta prueba en un plazo aproximado de 5 minutos a partir de la

determinación de la conductividad en la sección 3.2.1, manteniendo la temperatura
de la muestra a 25°C ± 1°C. Añada una solución saturada de cloruro de potasio a la
misma muestra de agua (0,3 mL por 100 mL de la muestra de ensayo) y determine
el pH con una precisión de 0,1 unidad de pH, como se indica en el capítulo general
de la USP <791>.
3.7.2 Con referencia a la tabla de requisitos de la etapa 3-pH y de conductividad,

determinar el límite de conductividad en el valor de pH medido. Si la conductividad
medida en la sección 3.2.1 no es mayor que los requisitos de conductividad para el
pH determinado en la sección 3.3.1, el agua cumple los requisitos de la prueba de
conductividad. Si la conductividad medida es superior a este valor o el pH está
fuera del rango de
5.0 a 7.0, el agua no cumple los requisitos de la prueba de conductividad..
Pag No: 9/12

: Impresion (IST) :
Etapa 3-pH y requisitos de conductividad

(sólo para muestras equilibradas de atmósfera y temperatura)
pH Requisito de conductividad
(µS/cm)
5.0 4.7
5.1 4.1
5.2 3.6
5.3 3.3
5.4 3.0
5.5 2.8
5.6 2.6
5.7 2.5
5.8 2.4
5.9 2.4
6.0 2.4
6.1 2.4
6.2 2.5
6.3 2.4
6.4 2.3
6.5 2.2
6.6 2.1
6.7 2.6
6.8 3.1
6.9 3.8
7.0 4.6
Pag No: 10/12

Impreso por Arti Pandya Tiempo de Impresion 13-Mar-2019 3:40 AM
: (IST) : electrónicamente en Documentum-versión 6.5
Este documento está firmado
Pag No: 11/12
Impreso por Arti Pandya Tiempo de Impresion 13-Mar-2019 3:40 AM
: (IST) : electrónicamente en Documentum-versión 6.5
Este documento está firmado
HISTORY OF CHANGES
Número de Sustituye (Número y Cambio(s) realizado(s)

CCR última versión)
CC002199 FS000418 Ver. 1.0  - Procedimiento de Prueba Estándar creado por

(referencia antigua separado según el nuevo sistema electrónico del
serie de documentos Gerente de Conformidad Documentum (DCM).
8001907 Rev.  - Sección 1.0, Carbono Orgánico Total, revisado
05) para actualizar el procedimiento de muestreo,
sustituir "Agua Milli Q" por "Agua Reactiva USP",
revisar los límites de COT para el agua de "NMT
250 ppb" a "NMT
 100 ppb", corregir el error tipográfico en la solución
estándar de sacarosa de "Benzoquinona" a
"Sacarosa", revisar la frecuencia de las pruebas,
eliminar "Calcular el promedio de COT de cuatro
lecturas de Blanco, Benzoquinona y Sacarosa", y
añadir el criterio de aceptación "NMT (COT -
TOCBL)".
 - Sección 2.0, Sustancias oxidables, revisada para
eliminar "Sievers 800" de la nota.
CC021890 FT005305 Version 1.0  - En la sección 3.3.1:

 o Se sustituyó la referencia al "Paso 3.2.1" por la
"Sección 3.2.1".
 o Después de "como se indica bajo el pH" agregar, "en el
Capítulo General de la USP <791>".
 - En la sección 3.3.2:
 o Se sustituye la referencia al "Paso 4" por la "Sección
3.2.1".
 o Se ha sustituido la referencia al "Paso 6" por "Sección
3.3.1".
 - Se eliminó la declaración redundante al final de la
sección 3.0 (declaración introductoria repetida).
ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ AN
HISTORIA DE LOS CAMBIOS - CONTINUACIÓN

Número de Sustituye (Número y Cambio(s) realizado(s)
CCR última versión)
CC065777 FT005305 Ver. 2.0  - El logo/plantilla del documento fue revisado

de "Ranbaxy" a "Sun Pharma" debido a la
fusión.
 - Documento revisado para proporcionar una
nueva fecha de entrada en vigor.
CC078991 FT005305 Version 3.0  - Se añadió la sección de abreviaturas y definiciones.
 - En la sección en blanco 1.1 , MilliQ Agua añadió
 - En la sección 1.2 del Estándar de Aptitud del Sistema y
en la sección 1.3 del Estándar de Sacarosa, se añadió la
corrección de pureza/potencia y se corrigió el nombre del
estándar para que estuviera en línea con el velquest.
 - Después de la Sección 1.3, se añadió la nota
 - Después de la especificación de idoneidad del sistema,
se añadió la sección de programación de idoneidad del
sistema en línea y fuera de línea.
 - Renombrada Solución de Prueba como Prueba de Agua
Purificada y se agregó una subsección.
 - Eliminada la prueba de sustancias oxidables.
 - En la Sección de Conductividad del Agua, se agregó la
subsección y la nota.

ESTA ES UNA COPIA IMPRESA DE UN DOCUMENTO ELECTRÓNICO. POR FAVOR, COMPRUEBE SU VALIDEZ ANTES DE USARLA
Documento No. FT009560

2.0;Effectivo
: 05-Jan-2019
DIÓXIDO DE SILICIO COLOIDAL, NF
:
Fecha efectiva :
Revisión debida
:
Titulo
:
PÁGINA DE
FIRMAS
Nombre completo Titulo Departmento Fecha Justificacion

Suryakant Patel
Especialista en AR & D 04-Ene- Creado por
documentación 2019
Mukul Sanghvi
Gerente Senior AR&D 04-Ene- Revisado y aprobado por
2019
Babasaheb Kale Director, AR & D

AR & D
04-Ene- Revisado y aprobado por
2019
Bhupendra
Patel Director Superior de Garantía de GARANTÍA DE CALIDAD-TR-OHM 04-Ene- Revisado y aprobado por
Calidad LABS 2019
electrónica.
Impreso por Arti Tiempo de impresion (IST) : 13-Mar-2019 3:43 AM 1

: Pandya
La página de la firma es la primera página de este documento
PROCEDIMIENTO DE PRUEBA ESTÁNDAR

Documento No. : FT009560
No. de la versión. : 2.0; Effectiva
Fecha efectiva : 05-Ene-2019
Revisión debida : 04-Ene-2025
Título : DIÓXIDO DE SILICIO COLOIDAL, NF
Título : Dióxido de Silicio Coloidal, NF
Tipo de documento : Liberación/Regulación
Mercado : Estados Unidos de América
Fabricante : CABOT
Pag No: 2/10

Impreso Arti Pandya Tiempo impreso 13-Mar-2019 3:43 AM
por : (IST) :
1.1 IDENTIFICACIÓN (Referencia del método: USP)
1.2 Equipo de identificación A:
Balanza analítica
Detenga el reloj.
Reactivos:
Reactivos de grado reactivo ACS de carbonato de potasio anhidro o
agua purificada equivalente
Remítase a Soluciones de Prueba USP (TS) para la preparación de

la siguiente solución: Molibdato de amonio TS
Procedimiento:
Transfiera 5 mg de la muestra a un crisol de platino y mézclelo con
200 mg de carbonato de potasio anhidro. Caliente el crisol hasta que
adquiera un color rojo con la ayuda de un mechero Bunsen o
cualquier otra fuente de calor adecuada durante 10 minutos, y
enfríelo. Disuelva el fundido en 2 mL de agua recién destilada,
calentándolo si es necesario, y añada lentamente 2 mL de molibdato
de amonio TS a la solución. Se produce un color amarillo intenso.
Obsérvese:
No descarte la solución resultante. Guárdela para la prueba de
identificación B.
1.3 Equipo de identificación B:

Balanza analítica
Reactivos:
O-tolidina. Reactivos de grado reactivo ACS o
equivalente
Ácido acético glacial. Reactivos de grado reactivo de ACS o
equivalente
Hidróxido de amonio. Reactivos de grado reactivo ACS o
equivalente
p r:
Impreso o Arti Pandya Tiempo de impresion
(IST) : 13-Mar-2019 3:43 AM Pag No: 3/10

Este documento está firmado electrónicamente en Documentum-versión 6.5
Procedimiento:
Precaución:
Evite el contacto con o-tolidina al realizar esta prueba, y realice la prueba en una campana bien
ventilada.
Procedimiento:
Coloque una gota de la solución amarilla de silicomolibdato obtenida en la prueba de identificación
A en un papel de filtro, y evapore el disolvente. Añada 1 gota de una solución saturada de o-
tolidina en ácido acético glacial para reducir el silicomolibdato a azul de molibdeno, y coloque el
papel sobre hidróxido de amonio. Se produce una mancha azul verdosa.
2.0 pH (Referencia del método: USP <791>)
Equipo: Balanza analítica Medidor de pH adecuado Termómetro
Reactivos:
Agua (Milli Q o equivalente)
Procedimiento:
Pesar con precisión alrededor de 1 g de la muestra y añadir 25 mL de agua. Agitar continuamente
para formar una dispersión uniforme. Determine el pH a 25 ± 2 °C.
3.0 Pérdida al secar (Referencia del método: USP <731>)
Equipo: Horno de secado Balanza analítica Cronómetro
Procedimiento:
Secar la muestra en un crisol de platino tarado a 105 °C durante 2 horas.
Pag No: 4/10

Impreso por Arti Pandya Tiemp de impreson 13-Mar-2019 3:43 AM
: (IST) :
Pesar un crisol de platino que ha sido secado durante 30 minutos a 105 °C y enfriado a
temperatura ambiente en un desecador (W1).
Transfiera alrededor de 1 a 2 g de muestra en el crisol y pese con precisión el crisol con la muestra
(W2).
Mediante una suave sacudida lateral, distribuya la muestra de prueba lo más uniformemente
posible. Colocar el crisol cargado en el horno de secado. Secar la muestra a 105 ° C durante 2
horas. Al abrir la estufa, retire el crisol rápidamente y déjelo alcanzar la temperatura ambiente en un
desecador antes de pesarla. (W3)
Nota: Retenga la muestra seca en el crisol para que se pierda en la prueba de ignición. Cálculo:
Determine la pérdida por secado utilizando la siguiente fórmula.
W2 - W3
% Pérdida del secado =
W2 - W1 x 100
Dónde,
W1 = Peso del crisol de platino vacío
W2 = Peso del crisol de platino y de la muestra antes del secado.
W3 = Peso del crisol de platino y de la muestra después del
secado
4.0 Pérdida de ignición (Referencia del método: USP <733>)
Equipo: Horno de mufla con temporizador de equilibrio analítico

Procedimiento:
Pesar el mismo crisol retenido de la prueba para la pérdida en el secado. Encender el
crisol cargado a una temperatura de 1000 °C (± 25 °C) por períodos sucesivos de 1 hora.
Al final de cada ignición, déjelo enfriar en un desecador a temperatura ambiente antes de
pesarlo. Continúe las igniciones hasta un peso constante.
Pag No: 5/10
: impresion (IST) :
Este documento está firmado electrónicamente en Documentum-versión 6. 5
Calculos:
Calcule el % de pérdida en la ignición a peso constante usando la siguiente fórmula:
% Pérdida de la W2 Wn
ignición = W2
100
W1
Dónde,
W1 = Wt. del crisol vacío de la prueba de pérdida en el secado.
W2 = Wt. de la muestra con el crisol antes de la ignición por la prueba de pérdida por secado
Wn = Wt. de la muestra y el crisol después de los encendidos a peso constante (n = 3, 4, 5,...)
5.0 ARSÉNICO (Referencia del método: USP <211>) (Método I)
Contratado a un laboratorio externo para hacer pruebas o realizarlas internamente como sigue:
Solución madre de trióxido de arsénico:

Disolver unos 132 mg de trióxido de arsénico, previamente secado a 105oC durante 1 hora y pesado con precisión,
en 5 mL de solución de hidróxido de sodio (1 de cada 5) en 1000 mL
un matraz volumétrico. Neutralice la solución con ácido sulfúrico 2 N, añada 10 mL más de ácido sulfúrico 2 N, luego
añada agua recién hervida y enfriada al volumen, y mezcle.
Solución estándar de arsénico:

Transferir 10 mL de Solución madre de trióxido de arsénico a un matraz aforado de 1000 mL, añadir 10 mL más de
ácido sulfúrico 2 N, luego agregar agua recientemente hervida y enfriada a volumen, y mezclar. Cada mL de Solución
de Arsénico Estándar contiene el equivalente a 1 µg de arsénico (As). Guarde esta solución en un recipiente de cristal
y utilícela en un plazo de 3 días.
Preparación estándar:
Pipetear 3 mL de Solución de Arsénico Estándar en un matraz generador, y diluir con agua hasta 35 mL.
Preparación de la prueba:
Transferir 2,5 g a un matraz, añadir 50 mL de ácido clorhídrico 3 N y refluir durante 30 minutos utilizando un
condensador de agua. Enfríe, filtre con la ayuda de la succión, y transfiera el filtrado a un
Pag No: 6/10

: impresion (IST) :
Un matraz volumétrico de 100 ml. Lave el filtro y el matraz con varias porciones de agua
caliente, y añadir los lavados al frasco. Enfríe, diluya con agua hasta el volumen y mezcle:
una porción de 15.0- mL de esta solución, a la que se han añadido 3 mL de ácido
clorhídrico, cumple con los requisitos de la prueba. Se omite la adición de ácido sulfúrico
7N..
Procedimiento:
Trate la preparación estándar y la preparación para la prueba de manera similar como se indica a
continuación. Añada 2 mL de yoduro de potasio TS, 0.5 mL de cloruro de estaño de ácido más
fuerte TS, y 1 mL de alcohol isopropílico, y mezcle. Deje reposar a temperatura ambiente durante
30 minutos. Empaquetar el tubo depurador con dos trozos de algodón empapados en una solución
saturada de acetato de plomo, liberados del exceso de solución por expresión, y secados al vacío a
temperatura ambiente, dejando un espacio de 2 mm entre los dos trozos. Lubrique las uniones con
una grasa adecuada para la llave de paso diseñada para su uso con disolventes orgánicos, y
conecte la unidad del depurador al tubo absorbedor. Transfiera 3.0 mL de dietilditiocarbamato de
plata TS al tubo absorbedor. Añada 3,0 g de zinc granulado (malla 20) a la mezcla del matraz,
conecte inmediatamente la unidad depuradora ensamblada y permita que la evolución del
hidrógeno y el desarrollo del color prosiga a temperatura ambiente durante 45 minutos, agitando el
matraz suavemente a intervalos de 10 minutos. Desconecte el tubo absorbedor de las unidades
generadora y depuradora, y transfiera la solución absorbente a una celda de absorción de 1 cm.
Cualquier color rojo producido por la Preparación de la Prueba no excede el producido por la
Preparación Estándar. Si es necesario o deseable, determine la absorbencia a la longitud de onda
de máxima absorbencia entre 535 y 540 nm, con un espectrofotómetro o colorímetro adecuado,
utilizando el dietilditiocarbamato de plata TS como blanco..
6.0 6.0 ENSAYO (Referencia del método: USP)
Equipo:
Horno de mufla
Balance analítico
Temporizador
Reactivos:
Ácido sulfúrico. Reactivos de grado reactivo ACS o equivalente
Ácido fluorhídrico. Reactivos de grado reactivo ACS o equivalente
El alcohol. Reactivos de grado reactivo de ACS o
equivalente
Pag No: 7/10
Impreso por Arti Pandya Tiempo de impression 13-Mar-2019 3:43 AM
(IST) :
Procedimiento:
Pesar un crisol de platino, previamente encendido a 1000 ± 25 °C durante 30 minutos y enfriado a
temperatura ambiente en un desecador (W1). Transfiera con precisión unos 500 mg de la muestra a un
crisol de platino y registre el peso combinado de la muestra y el crisol (W2). Enciéndalo a 1000 ± 25 °C
durante 2 horas, enfríelo en un desecador y péselo (W3). Añadir 3 gotas de ácido sulfúrico, y añadir
suficiente alcohol para humedecer completamente la muestra. Añadir 15 mL de ácido fluorhídrico, y en una
campana bien ventilada evaporar en una placa caliente hasta la sequedad, usando calor medio (95 °C a
105 °C) y teniendo cuidado de que la muestra no se salpique al acercarse a la sequedad. Caliente el crisol
hasta que adquiera un color rojo con la ayuda de un quemador Bunsen. Encienda el residuo a 1000 ± 25
°C durante 30 minutos, enfríe en un desecador y pese (W4). Si queda un residuo, repita el procedimiento,
comenzando por "añadir 15 ml de ácido fluorhídrico". El peso perdido por la muestra, previamente
encendido a 1000 ± 25 °C, representa el peso de SiO2 en la porción tomada.
Calculo:
% VALORACION = (W3 - W1) - (W4 - W1)
(W3 - W1)
100
Dónde,
W1 = Peso del crisol vacío

W2 = Peso del crisol con la muestra
W3 = Peso del crisol después de la ignición
W4 = Peso del crisol con el residuo
Pag No: 8/10

: Impresion (IST) :
Número de CCR Sustituye (Número y última versión) Cambio(s) realizado(s)

Ninguno Nuevo método según Sun Pharm,
NA
Cranbury, NJ documento #
RMARE10088ND_CAB/05 para la
prueba Identificación (según
PR#136725, se incluye la identificación
(refiérase a los breves recortes adjuntos
de PR #136725). Nota: La descripción se
realizará utilizando el GP000054.
CC108821 FT009560 V 1.0 Added method for the tests pH,
Loss on Drying, Loss on Ignition,
Arsenic and Assay as per
USPNF and Sun Pharm,
Cranbury, NJ document #
RMARE10088ND_CAB/05.
Fin del documento
Pag No: 9/10

: Impresion(IST) :
Número de CCR Sustituye (Número y última Cambio(s) realizado(s)

versión)
NA Ninguno Nuevo método según Sun Pharm,
Cranbury, NJ documento #
RMARE10088ND_CAB/05 para la
prueba Identificación (según
PR#136725, se incluye la
identificación (refiérase a los
breves recortes adjuntos de PR
#136725). Nota: La descripción se
realizará utilizando el GP000054.
Fin del documento
Pag No: 10/10

Impreso por Arti Pandya Tiempo 13-Mar-2019 3:43 AM
: deImpresion (IST) :
T su documento está firmado electrónicamente en Documentum-versión 6.5

2118-2517-Methylphenidate 27 MG Atras (2de2)

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The signature page is the first page of the

Document No. GP000189

Full Name Title Department Date Justification

Printed By : Arti Printed Time (IST) : 13-Mar-2019 3:13 AM 1

Pharmacopeial Status : In-House

Objective : Dispersion is provided to determine compliance with the

PROCEDURE (FOR DRY POWDER):

2. Manually shake sieve, allowing powder to fall through.

3. Examine retain material. Guidelines for approval are as follows:

Foreign material: No foreign matter should be observed.

Undispersed Pigments: Specks observed should be equal to or less than 5.

 Hard pieces that do not break up easily, but do disperse in water.

The signature page is the first page of the

The signature page is the first page of the

Foreign material: No foreign matter should be observed.

3. A passing result is seeing a completely dispersed product with no pigment specks or

4. An unacceptable result is seeing multiple undispersed pigment specks or lumps in which

Method C: For Opalux (Liquid Dispersions)

1. Pour approximately 10 grams of Product onto a piece of white paper.

2. Examine for foreign matter. None Present – PASS

Page No: 3/5

2. Manually shake sieve, allowing powder to fall through.

3. Examine retain material. Guidelines for approval are as follows:

Foreign material: No foreign matter should be observed.

4. Undispersed Pigments: Specks observed should be equal to or less than 5.

Page No: 4/5

CCR Supersedes Change(s) Made

CC032281 GP000189 Ver.1.0  Procedure clarified as Method A and B so that

CC055802 GP000189 Ver.2.0  Method C Dispersion procedure for

CC098598 GP000189 Ver. 4.0 Logo / template revised from “Ranbaxy” to

************* End of the document *************

Document No. GP000141

Full Name Title Department Date Justification

Printed By : Arti Printed Time (IST) : 09-Mar-2019 1:22 AM 1

Title : RESIDUE ON IGNITION / SULFATED ASH

Pharmacopeial Status : USP

Objective : The test for RESIDUE ON IGNITION / SULFATED ASH

Principle : The Residue on Ignition / Sulfated Ash test uses a

Sulfated ash is the residue of metallic oxides if present in

The signature page is the first page of the

The signature page is the first page of the

W = Weight of substance taken, in g.

P rinted By : Arti Pandya

P rinted Time (IST) : Page No: 3/5

1. Ensure that the muffle furnace is clean.

2. If more than one crucible is used it should be marked before weighing.

3. The tongs used to handle the crucible must be clean.

4. Cooling must be done in a desiccator.

6. Ignition must be conducted in a well-ventilated hood, protected from air currents.

8. Muffle furnace should be calibrated by an appropriate digital temperature meter.

Page No: 4/5

CCR Supersedes Change(s) Made

CC035061 GP000141 Version  Corrected typographical / formatting errors (as

CC080331 GP000141 Version  Revised Document Logo/Template from

************* End of the document *************

Document No. GP000083

Full Name Title Department Date Justification

Kamal Sharma (QC)

Dalip Kumar (QA)

Dinesh Singh (Solrex)

Kirtan Lal Kewat

Printed By : Arti Printed Time (IST) : 9- Mar-2019 1:35 AM 1

* End of the document *

* End of the document *

* End of the document *

* End of the document *