3.2.S.

5 REFERENCE STANDARDS OR MATERIALS

Standard Operating Procedure for the preparation, characterization / evaluation of in-house
reference/ working standards is provided in this section.

The certificate of analysis for Tramadol Hydrochloride working standard (Batch No.:
TMD/WS/001/17), which is evaluated against EP CRS along with IR spectra is provided in
this section.

JUBILANT GENERICS LIMITED

-------------------------------------------------------------------------------------------------------------------------------------------------------------
This information is intended only for the person or entity to which it is addressed and contains confidential / privileged material. Any review, dissemination by persons
or entities other than the intended recipients is prohibited. Photocopying or copying by any other mechanical means is not allowed.
 3.2.S.6 CONTAINER CLOSURE SYSTEM

The packing and labeling methodology adopted for Tramadol Hydrochloride produced by
Jubilant is described hereunder.
Packaging and labeling Methodology
Empty and clean HDPE drum containing double polyethylene bags is weighed for tare
weight. The required material is filled in the inner polythene bag and tied with PVC strip
inter locking. A label is inserted in between the inner and outer polythene bags and then, the
outer polythene bag is tied with PVC strip inter locking. Then, a label is pasted on it. Then,
the HDPE drum is closed and sealed with a seal bearing company monogram with a specified
number. HDPE Drum is also affixed with label. These labels containing details like Product
name, Batch no., Manufacturing date, Expiry/Retest Date, Gross weight, Tare weight, Net
weight, Container no., Manufacturing license no., Storage conditions and address of the
manufacturer.
Storage conditions
Store in airtight containers at below 25 Deg. Celsius.
Packaging material specifications
Information on packaging material and packaging size of Tramadol Hydrochloride are
provided below in the table.

S. No. Name of the packing material Packing size

1.0 Polythene bag 25 Kg , 50 Kg

2.0 HDPE drum 25L , 100L

The specifications, test methods for the packing materials in the above table and their typical
certificates of analyses, food grade certificate and IR spectra for polythene bag and Specimen
label are provided on following pages in this section.

Note: The typical packing sizes are mentioned in the above table. However, the pack
sizes will vary based on customer order.

JUBILANT GENERICS LIMITED

-----------------------------------------------------------------------------------------------------------------------------
This information is intended only for the person or entity to which it is addressed and contains confidential / privileged material. Any review, dissemination by persons or entities
other than the intended recipients is prohibited. Photocopying or copying by any other mechanical means is not allowed
 'Wi QUALITY CONTROL DEPARTMENT
fUBIIANf ANALYTICAL SPECIFICATION
GENERICS

Product Name : Poly bag (White-25 Kg} Effective date :29.11 .14
(antistatic)
Specification# :QCD/SP/PMMi25/001-Rs Supersedes : QCD/SP/PM/W25/001-Rs
Dated: 24.06.14
Reference :In-house Page : 1 of 1

Tests Specification

1 .0 Description Transparent bags sealed at one end, without

any black spots I strips.

2.0 IR Absorption The IR absorption spectrum of sample should

be concordant with that of USP LOPE
reference standard.
3.0 Dimension

-Width 27 to 29"
-Length 39to41"

4.0 Weight 80 to 90 g.

5.0 Sealing Satisfactory sealing.

6.0* Heavy metals Not more than 1 ppm

7.0* Non-volatile residue Does not exceed 12.0 mg when water is used
as extracting medium.
Does not exceed 75.0 mg when alcohol is
used as extracting medium.
Does not exceed 350.0 mg when hexanes are
used as extracting medium.
8.0 Microbial quality
Total Aerobic microbial count (TAMC) Not more than 103 cfu
Total combined Yeasts and Molds Not more than 102 cfu
count (TYMC)

Note: Microbial quality will be carried out once 1n year for the first shipment of each vendor.
*Anal sis shall be carried out for ever 10 1h batch of each vendor.
Previous Current
Rs

by~ Q .
~
Prepared by Reviewed Approved by :

Date ,~L \~~ Date : ll \ V) Date :~~~\\\1\f

\

JUBILANT GENERICS LIMITED, NANJANGUD

 '~
JUBUANT QUALITY CONTROL DEPARTMENT
GENERiCS
METHOD OF ANALYSIS
Product Name : Poly bag - White 25 Kg Effective date :29.11.14
(antistatic)
Method# :QC DIM HIP M!W25/00 1-Rs Supersedes :QCD/MH/PM!W25/001-R 5
Dated: 24.06.14

Reference :In-house Page : 1 of 4

1.0 Description:

Determine as per current version of general method QCD/GTP/011.

2.0 IR absorption:

Record theIR absorption spectrum of the sample by folding it into two folds in the range
of 3800 - 650 cm· 1 using Attenuated total reflectance (ATR) accessory, compare with
that of USP LOPE reference standard recorded in the same way by overlapping. The IR
absorption spectrum of sample should be concordant with that of USP LOPE reference
standard.

3.0 Dimension:

Determine the width and length of the bag using meter scale.

4.0 Weight:

Place 18 x 12 em poly pouch on a balance pan and tare the weight. Fold and insert the
sample poly bag into 18 x 12 em poly pouch and keep on the balance pan. Record the
displayed weight.

5.0 Sealing:

By physical observation.

6.0* Heavy metals:

Preparation of sample: Cut 150 cm 2 (5 x 30 em) poly bag and subdivide into strips
approximately 3 mm in width and as near to 5 em in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250 mL conical flask and add about 150 mL of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.

Prepared by : y Reviewed by : Approved by :

Date · I \I
. \.S"\\\
Date Date ~1\l~
JUBILANT GENERICS LIMITED, NANJANGUD
 \ /

:;<~
--~--
QUALITY CONTROL DEPARTMENT
JUBILANT METHOD OF ANALYSIS
GENERICS

Product Name : Poly bag - White 25 Kg Effective date :29.11 .14

(antistatic)
Method# :QC D/M H/P MM/25/00 1-Rs Supersedes :QCD/MH/PMM/25/001-Rs
Dated: 24.06.14

Reference :In-house Pa_g_e :2 of 4

Transfer the sample to a round bottom flask and add 20.0ml of purified water. Heat on a
water bath I steam bath at 70°C for 24 hours. Cool but not below 20°C. Immediately
decant the extract into a suitably cleansed container and close.

Procedure: Filter the sample if necessary and transfer into 50 mL color comparison
tubes. Adjust with 1N acetic acid or 6N ammonium hydroxide to a pH between 3.0 to 4.0
using short-range pH paper as external indicator, dilute with water to about 35 ml and
mix.

Into the second color-comparison tube pipette out 2.0ml of standard lead solution and
add 20 ml of the water. Adjust with 1N acetic acid or 6N ammonium hydroxide to a pH
between 3.0 to 4.0 using short-range pH paper as external indicator, dilute with water to
about 35 ml and mix. To each tube add 1.2 ml of thioacetamide-glycerin base TS and 2
ml of pH 3.5 acetate buffer, dilute with water to 50 ml and mix. Any brown color
produced within 10 minutes in the tube containing the extract of the prepared sample
does not exceed that in the tube containing the standard lead solution, both tubes being
viewed downward over a white surface (1 ppm in extract).

7.0* Non-volatile residue:

In water medium:

Preparation of sample: Cut 150 cm 2 (5 x 30 em) poly bag and subdivide into strips
approximately 3 mm in width and as near to 5 em in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250 ml conical flask and add about 150 ml of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.
Transfer the sample to a round bottom flask and add 50.0 ml of water. Heat on a water
bath I steam bath at ?Ooc for 24 hours. Cool but not below 20°C. Immediately decant the
extract into a suitably cleansed container and close.

Prepared by Reviewed by : Approved by:

Date Date Date

JUBILANT GENERICS LIMITED, NANJANGUD

 ~'
QUALITY CONTROL DEPARTMENT
JUBILANT
GENERICS METHOD OF ANALYSIS

Product Name : Poly bag - White 25 Kg Effective date :29.11 .i4

(antistatic)
Method# :QCDIMHIPM/W251001-R 6 Supersedes :QCDIMHIPM/W251001-Rs
Dated: 24.06.14
Reference : In-house Page :3 of 4

Procedure: Transfer 50.0 mL to a suitable tarred crucible and evaporate the volatile
matter on a steam bath. Similarly evaporate 50.0 mL of the water (blank) in a second
crucible. Dry at 105°C for 1 hour. Calculate the difference between the amounts obtained
from the sample and the blank. The difference should not exceed 12.0 mg.

In alcohol medium:

Preparation of sample: Cut 150 cm 2 (5 x 30 em) poly bag and subdivide into strips
approximately 3 mm in width and as near to 5 em in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250mL conical flask and add about 150mL of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.

Transfer the sample to a round bottom flask and add SO.OmL of alcohol. Heat on a water
bath I steam bath at 70oC for 24 hours. Cool but not below 20°C. Immediately decant the
extract into a suitably cleansed container and close.

Procedure: Transfer SO.OmL to a suitable tarred crucible and evaporate the volatile
matter on a steam bath. Similarly evaporate 50.0mL of the alcohol (blank) in a second
crucible. Dry at 105oC for 1 hour. Calculate the difference between the amounts obtained
from the sample and the blank. The difference should not exceed 75.0 mg.

In Hexanes medium:

Preparation of sample: Cut 150 cm2 (5 x 30 em) poly bag and subdivide into strips
approximately 3mm in width and as near to Scm in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250 mL conical flask and add about 150 mL of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.

Transfer the sample to a round bottom flask and add SO.OmL of Hexanes. Heat on a
water bath I steam bath at 50°C for 24 hours. Cool but not below 20°C. Immediately
decant the extract into a suitably cleansed container and close.

Reviewed by :

Date

JUBILANT GENERICS LIMITED, NANJANGUD

 \~
I:J:rJ~ QUALITY CONTROL DEPARTMENT
METHOD OF ANALYSIS
Product Name : Poly bag - White 25 Kg Effective date :29.11 .14
(antistatic)
Method# :QCD/MH/PMW25/001-Rs Supersedes :QCD/MH/PM/W25/001-R 5
Dated: 24.06.14
Reference : In-house Page :4 of 4

Procedure: Transfer 50.0 ml to a suitable tarred crucible and evaporate the volatile
matter on a steam bath. Similarly evaporate 50.0ml of the Hexanes (blank) in a second
crucible. Dry at 105°C for 1 hour. Calculate the difference between the amounts
obtained from the sample and the blank. The difference should not exceed 350.0 mg.

8.0 Microbial quality: For method of analysis please refer to SOP# QCD/SOP/518.

Previous Current Details of Revision

Rs Rs Change in Company name and logo.

Reviewed by : Approved by :

Date Date

JUBILANT GENERICS LIMITED, NANJANGUD

 'W, QUALITY CONTROL DEPARTMENT
JUBilANT ANALYTICAL SPECIFICATION
GENERICS

Product Name : Poly bag -White 50 Kg Effective date :29.11.14

(antistatic)
Specification# :QCD/SP/PMM/50/001-Rs Supersedes : QCD/SP/PMM/50/001-Rs
Dated: 24.06.14
Reference :In-house Page : 1 of 1

Tests Specification

1.0 Description Transparent bags sealed at one end, without

any black spots I strips.

2.0 IR Absorption The IR absorption spectrum of sample should

be concordant with that of USP LOPE
reference standard.
3.0 Dimension

- Width 31 to33"
- Length 47 to 49"

4.0 Weight 140 to 150 g.

5.0 Sealing Satisfactory sealing.

6.0* Heavy metals Not more than 1 ppm

7.0* Non-volatile residue Does not exceed 12.0 mg when water is used
as extracting medium.
Does not exceed 75.0 mg when alcohol is
used as extracting medium.
Does not exceed 350.0 mg when hexanes are
used as extracting medium.
8.0 Microbial quality
3
- Toatal Aerobic microbial count (TAMC) Not more than 10 cfu
2
- Total combined Yeast and Molds count Not more than 10 cfu
(TYMC)
Note: Mrcrobral quality wrll be earned out once tn year for the frrst shrpment of each vendor.
*Anal sis shall be carried out for eve 10 1h batch of each vendor.
Current
Rs 0.

Prepared by : k Reviewed by : Approved by :

Date : l t ('I t I ~ Date Date

JUBILANT GENERICS LIMITED, NANJANGUD

 ··~··
fUBfLANT
GENERICS
QUALITY CONTROL DEPARTMENT
METHOD OF ANALYSIS

Product Name : Poly bag - White 50 Kg Effective date :29.11 .14

(antistatic)
Method# :QCD/MH/PM/W50/001-Rs Supersedes :QCD/MH/PM/W50/001-Rs
Dated: 24.06.14

Reference : In-house Page : 1 of 3

1.0 Description:.

Determine as per current version of general method QCD/GTP/011.

2.0 IR absorption:

Record the IR absorption spectrum of the sample by folding it into two folds in the range
of 3800- 650 cm· 1 using Attenuated total reflectance (ATR) accessory, compare with
that of USP LOPE reference standard recorded in the same way by overlapping. TheIR
absorption spectrum of sample should be concordant with that of USP LOPE reference
standard.

3.0 Dimension:

Determine the width and length of the bag using meter scale.

4.0 Weight:

Place 18 x 12 em poly pouch on a balance pan and tare the weight. Fold and insert the
sample poly bag into 18 x 12 em poly pouch and keep on the balance pan. Record the
displayed weight.

5.0 Sealing:

By physical observation.

6.0* Heavy metals:

Preparation of sample: Cut 60 cm 2 (5 x 12 em) poly bag and subdivide into strips
approximately 3 mm in width and as near to 5 em in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250 mL conical flask and add about 150 mL of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.
Transfer the sample to a round bottom flask and add 20.0mL of purified water. Heat on
a water bath I steam bath at 70°C for 24 hours. Cool but not below 20°C. Immediately
·decant the extract into a suitably cleansed container and close.

Prepared by : # Reviewed by : Approved by :

Date ~rt \ j1 ~
1 Date Date

JUBILANT GENERICS LIMITED, NANJANGUD

 \;W
'~~~-·-
QUALITY CONTROL DEPARTMENT
fUBIIANr METHOD OF ANALYSIS
GENERICS

Product Name : Poly bag - White 50 Kg Effective date :29.11 .14

(antistatic)
Method# :QCD/MH/PMM/50/001-Rs Supersedes :QCD/MH/PMM/50/001-Rs
Dated: 24.06.14

Reference : In-house Page :2 of 3

Procedure: Filter the sample if necessary and transfer into 50 mL color comparison tubes.
Adjust with 1N acetic acid or 6N ammonium hydroxide to a pH between 3.0 to 4.0 using
short-range pH paper as external indicator, dilute with water to about 35 mL and mix.

In Into the second color-comparison tube pipette out 2.0 mL of standard lead solution and
add 20 mL of the water. Adjust with 1N acetic acid or 6N ammonium hydroxide to a pH
between 3.0 to 4.0 using short-range pH paper as external indicator, dilute with water to
about 35 mL and mix. To each tube add 1.2 mL of thioacetamide-glycerin base TS and 2
mL of pH 3.5 acetate buffer, dilute with water to 50 mL and mix. Any brown color produced
within 10 minutes in the tube containing the extract of the prepared sample does not
exceed that in the tube containing the standard lead solution, both tubes being viewed
downward over a white surface (1 ppm in extract).

7.0* Non-volatile residue:

In water medium:

Preparation of sample: Cut 150 cm 2 (5 x 30 em) poly bag and subdivide into strips
approximately 3 mm in width and as near to 5 em in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250 mL conical flask and add about 150 mL of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.

Transfer the sample to a round bottom flask and add 50.0 mL of water. Heat on a water
bath I steam bath at 70cC for 24 hours. Cool but not below 20°C. Immediately decant the
extract into a suitably cleansed container and close.

Procedure: Transfer 50.0 mL to a suitable tarred crucible and evaporate the volatile
matter on a steam bath. Similarly evaporate 50.0 mL of the water (blank) in a second
crucible. Dry at 105°C for 1 hour. Calculate the difference between the amounts obtained
from the sample and the blank. The difference should not exceed 12.0 mg.

Prepared by : Approved by :

Date :~~\,"\\t.r Date

JUBILANT GENERICS LIMITED, NANJANGUD

 -·
~
!J:!::i:/g QUALITY CONTROL DEPARTMENT
METHOD OF ANALYSIS
Product Name : Poly bag - White 50 Kg Effective date :29.11 .14
(antistatic)
Method# :QCDIMHIPM/W501001-R6 Supersedes :QCDIMHIPM/W501001-R 5
Dated: 24.06.14
Reference : In-house Page :3 of 3

In alcohol medium:

Preparation of sample: Cut 150 cm 2 (5 x 30 em) poly bag and subdivide into strips
approximately 3 mm in width and as near to 5 em in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250 mL conical flask and add about 150 ml of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.

Transfer the sample to a round bottom flask and add 50.0 ml of alcohol. Heat on a water bath
I steam bath at 70oc for 24 hours. Cool but not below 2o·c. Immediately decant the extract
into a suitably cleansed container and close.

Procedure: Transfer 50.0 ml to a suitable tarred crucible and evaporate the volatile matter on
a steam bath. Similarly evaporate 50.0ml of the alcohol (blank) in a second crucible. Dry at
105°C for 1 hour. Calculate the difference between the amounts obtained from the sample
and the blank. The difference should not exceed 75.0 mg.

In Hexanes medium:

Preparation of sample: Cut 150 cm 2 (5 x 30 em) poly bag and subdivide into strips
approximately 3 mm in width and as near to 5 em in length as in practical. Transfer the
subdivided sample to a glass-stoppered 250 ml conical flask and add about 150 ml of
purified water. Agitate for about 30 seconds, discard the liquid and repeat with a second
washing.

Transfer the sample to a round bottom flask and add 50.0 ml of Hexanes. Heat on a water
bath I steam bath at 5o•c for 24 hours. Cool but not below 20°C. Immediately decant the
extract into a suitably cleansed container and close.

Procedure: Transfer 50.0 ml to a suitable tarred crucible and evaporate the volatile matter
on a steam bath. Similarly evaporate 50.0 ml of the Hexanes (blank) in a second crucible.
Dry at 1o5•c for 1 hour. Calculate the difference between the amounts obtained from the
sample and the blank. The difference should not exceed 350.0 mg.

8.0 Microbial quality: For method of analysis please refer to SOP# QCDISOPI518.
10 1h batch of each vendor.
Details of Revision
Rs Change in Company name and logo.

Prepared by Reviewed by : Approved by :

Date Date Date

JUBILANT GENERICS LIMITED, NANJANGUD

 w QUALITY CONTROL DEPARTMENT
JUBilANT ANALYTICAL SPECIFICATION
GENERICS

Product Name : HOPE Drum ( 25 Lts ) Effective date :29.11.14

Specification # : QCD/SP/PM/H25/001-R 4 Supersedes : QCD/SP/PM/H25/001-R 3

Dated: 02.01.12

Reference :In-house Page : 1 of 1

Tests Specification

1.0 Description A blue coloured HOPE drum with black

coloured lid and a metallic ring without time
logo or block.
2.0 Dimension

- Outer Diameter 9" to 12"

- Height 15" to 20"

- Weight 1.3 to 1.8 Kg ( with lid and ring )

3.0 Condition of lock Should be galvanized.

Previous Current Details of Revision

R3 R4 Change in Company name and logo.

Prepared by Reviewed by : Approved by :

Date Date Date

1
)u kf

JUBILANT GENERICS LIMITED, NANJANGUD

 ·.·~
QUALITY CONTROL DEPARTMENT
JUBilANT METHOD OF ANALYSIS
GENERICS

Product Name : HOPE Drum ( 25 Lts ) Effective date :29.11.14

Method# : QCD/MH/PM/H25/001-R4 Supersedes : QCD/MH/PM/H25/001-R 3

Dated: 02.01.12

Reference :In-house Page : 1 of 1

1.0 Description:

By physical observation.

2.0 Dimension:

Outer Diameter: Measure the circumference at the centre of the drum using the
measuring tape and calculate the diameter using the formula given below.

Note: There should not be any air gap between the measuring tape and the drum while
measuring the circumference.

Diameter= Circumference X 7/22

Height : Measure using measuring tape.

Weight :Determine using weighing balance.

3.0 Condition of lock:

By physical observation.

Previous Current Details of Revision

R3 R4 Change in Company name and logo.

Prepared by : Reviewed by: Approved by : Q~ . \f

Date :. !~ t\J\ Date Date /(f1dt \l 1
))'

JUBILANT GENERICS LIMITED, NANJANGUD

 W' QUALITY CONTROL DEPARTMENT
JUBILA.NT ANALYTICAL SPECIFICATION
GENERICS

I Product Name : HOPE drum ( 100 Lts ) Effective date :29.11.14

Specification# : QCD/SP/PM/H100/001-R 5 Supersedes : QCD/SP/PM/H100/001-R4

Dated: 02.01.12

Reference : In-house Page : 1 of 1

Tests Specification

1.0 Description A blue coloured HOPE drum with black

coloured lid and a metallic ring without any
time logo or block.
2.0 Dimension

- Outer Diameter 16to20"

- Height 25 to 31"

- Weight 4.6 to 5.3 Kg ( with lid and ring)

3.0 Condition of lock Should be galvanized.

Previous Current Details of Revision

R4 Rs Change in Company name and logo.

I
Prepared by :~ Reviewed by : Approved by : "

Date . : ti[ ll lt~ Date Date ~j,,jl~

JUBILANT GENERICS LIMITED, NANJANGUD
 W'· QUALITY CONTROL DEPARTMENT
II
JUBilANT METHOD OF ANALYSIS
GENERICS

Product Name : HOPE drum ( 100 Lts) Effective date : 29.11.14

I
Method# : QCD/MH/PM/H100/001-R 5 Supersedes : QCD/MH/PM/H100/001-R4
Dated: 02.01.12

Reference : In-house Page : 1 of 1

1.0 Description:

By physical observation.

2.0 Dimension:

Outer Diameter: Measure the circumference at the centre of the drum using the
measuring tape and calculate the diameter using the formula given below.

Note: There should not be any air gap between the measuring tape and the drum while
measuring the circumference.

Diameter= Circumference X 7/22

Height : Measure with lid using measuring tape.

Weight : Determine using weighing balance.

3.0 Condition of lock:

By physical observation.

Previous Current Details of Revision

R4 Rs Change in Company name and logo.

Prepared by : ~ Reviewed by : Approved by : jt

Date Jt \,\
t\
l1
Date Date /(f~l1 1 \\~
\

JUBILANT GENERICS LIMITED, NANJANGUD

 ~--- ~-

\~ QUALITY CONTROL DEPARTMENT

JUB//.ANT GENERALTESTPROCEDURE
GENERICS

Title : Description I Appearance test Effective date :04.03.15

Method# : QCDIGTPI011-R 2 Supersedes : QCDIGTPI011-R1

I
Dated: 01.06.11
Reference : In-house Page : 1 of 1

Asses the Description I Appearance as described below:

Solids:

Transfer about 5 grams of sample into watch glass, visually examine the sample against
white I Black background and report the colour.

Move sample around using spatula and report the presence and appearance of any foreign
particles.

Liquids:

Transfer about 5 mL of sample into transparent test tube, visually examine the sample
against white I Black background and report the colour.

Shake the test tube and report the presence and appearance of any foreign particles

Previous Current Details of Revision

R1 R2 Change in Company name and logo.

Prepared by :/I Reviewed by:~ Approved by : ,,

\ /

Date
:«bl l;~J \( Date : ?~ o?·hr- Date
~
i
oW"
\ .\l,. \ ')

JUBILANT GENERICS LIMITED, NANJANGUD