Section A: Table of Content
Parts Content Page No.
Part II Section A Table of content 1-2
Section B Quality Overall Summary 3-5
S. Drug Substance 6
S.1. General Information 6
1.1 Nomenclature 6
1.2 Structure 6
1.3 General Properties 6
S.2. Manufacture 7
2.1 Manufacturer 7
S.3. Characterization 7
3.1 Elucidation of Structure and other 7
Characteristics
3.2 Impurities 7
S.4 Control of Drug substance 7
4.1 Specification 7
4.2 Analytical Procedure 7
4..3 Validation of Analytical Procedures 7
S.5 Reference Standards of materials 7
S.6 Stability 7
P Drug Product 8
P.1 Description and Composition 8
P.2 Pharmaceutical Development 8
2.1 Components of the Drug Product 8
2.2 Finished Product 8-9
2.3 Container closure system 10
2.4 Microbiological Attributes 11
2.5 Compatibility 11
P.3 Manufacture 11
3.1 Batch formula 11
3.2 Manufacturing process and process 12
control
1
3.3 Control of critical steps and 12
intermediates
3.4 Process validation and /or 12
Evaluation
P.4 Control of excipients 12
4.1 Specification 13
4.2 Analytical Procedure 13
4.3 Excipient of Human or Animal 13
Origin
P.5 Control of Finished product 13
5.1 Specification 13
5.2 Analytical procedure 13
5.3 Validation of Analytical procedure 13
5.4 Batch Analysis 13
5.5 Characterization of impurities 13
5.6 Justification of Specification(s) 13
P.6 Reference standards or materials 13
P.7 Container Closure System 14
P.8 Stability 14
P.9 Product Interchangeability, Equivalence 14
evidence
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Section B: Quality Overall Summary (QOS)
Sr. PARAMETERS COMPONENTS
No.
S. DRUG SUBSTANCE
S.1. General Information
1.1 Nomenclature - Drug substance (Montelukast Sodium)
1.2 Structure - C35H35ClNNaO3S
1.3 General Properties - ATC Code : R03DC03
S.2. Manufacture
2.1 Manufacturer - Lee Pharma Limited, India
S.3. Characterization
3.1 Elucidation of Structure and - According to supplier information.
other Characteristics
3.2 Impurities Not Applicable
S.4 Control of Drug substance
4.1 Specification
Specification is set in house according to different
quality guidelines which is attached in section C
4.2 Analytical Procedure
Analytical procedures are developed and validated in
house
4..3 Validation of Analytical
Procedures Methods (where applicable) are validated according to
recognized guidelines
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4.4 Batch Analysis Certificates of analysis is attached
S.5 Reference Standards of materials Working standard is used supplied by the supplier
S.6 Stability Stability reports attached
P DRUG PRODUCT
P.1 Description and Composition Asmatab tablet is a white to off-white colored, round
shaped film coated tablet having a break line on one
side and other side embossed with V
Microcrystalline Cellulose (Avicel PH-102), Sodium
Starch Glycollate, Colloidal Sillicon Dioxide (Aerosil
200), Magnesium Stearate, Opadry II 85G58921 White
P.2 Pharmaceutical Development
2.1 Components of the Drug Active ingredient
Product Literature data
Excipients
2.2 Finished Product Formulation Development
The Active with excipient was blended and then pass
through suitable mesh. After QC release tablet was
compressed and then coated with coated suspension.
2.3. Container Closure -Alu-Alu Blister of 10s (Pack of 3 x 10s)
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2.4 Microbiological Attributes Not Applicable
2.5 Compatibility Product is stable
Manufacture
3.1 Batch formula Master Formula attached
3.2 Manufacturing process and Attached
P.3 process control
3.3 Control of critical steps and For controlling critical steps like in-process parameters
intermediates in various stages, environmental factors related to
manufacturing of the product strictly kept in control.
3.4 Process validation and /or
Evaluation Description, documentation, and results of the
validation and/or evaluation studies for critical steps or
critical assays used in the manufacturing process
P-4 4.1 Specification Control of Specifications of testing parameters for all excipients
excipients attached
P.4 4.2 Analytical Procedure Standard testing procedure for testing of the all the
excipient attached
4.3 Excipient of Human or Animal Not used in any step of the formulation of the product
Origin
Control of Finished product
5
5.1 Specification Specifications of testing parameters for Finished
product attached
P.5 5.2 Analytical procedure
Standard testing procedure for testing of Finished
product attached which was developed in house.
5.3 Validation of Analytical
procedure Analytical Method was validated according to different
recognized guidelines.
5.4 Batch Analysis
Certificate of analysis of Batch No. 402003 is attached
5.5 Characterization of impurities
N/A
P.6 Reference standards or materials
No Reference Standard is required
P.7 Container Closure System
Specifications are attached.
P.8 Stability
Stability data demonstrating that
product is stable through its proposed shelf
life is attached.
P.9 Product Interchangeability,
Equivalence evidence Bioequivalence study not applicable
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Section C: Body of Data
S DRUG SUBSTANCE
S1 General Information
S1.1 Nomenclature
Recommended International Nonproprietary Name:
Montelukast Sodium
Chemical Name:
sodium;2-[1-[[(1R)-1-[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2-hydroxypropan-
2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetate
S1.2 Structural Formula
Molecular Structure
Molecular Formula: C35H35ClNNaO3S
Molecular Mass: 608.16
S1.3 General Properties:
Appearance:
White to off white free flowing powder
Physiochemical Properties:
Montelukast sodium is a hygroscopic, optically active, white to off-white, free-flowing powder. It is
freely soluble in ethanol, methanol, and water and practically insoluble in acetonitrile.
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S.2 Manufacturer
S2.1 Name and full address of manufacturer:
Lee Pharma Ltd.
Factory: Sy. No. 10/G-1, Gaddapotharam Village, Jinnaram Mandal, Medak Dist. Pin Code: 502319
Andhra Pradesh, India
Factory: +91-08458-277311/251 Office: +91-40-66170335/336
S.3 Characterization
S3.1 Elucidation of structure and characteristic:
E) Characterisation
The drug substances have been adequately characterized by the drug substance manufacturer.
Therefore structures of APIs are not characterized separately.
S3.2 Impurities
Not Applicable
S4 Control of Drug Substance
S4.1 Specification
Attached in Annexure I
S4.2 Analytical Procedure
Attached in Annexure I
S4.3 Validation of Analytical Procedure
Attached in Annexure II
S 4.4 Certificate of analysis of drug substance
Attached in Annexure III
S5 Reference Standard
No Impurity Standard is required
S6 Stability
Will be given if DMF is available from manufacturer
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P DRUG PRODUCT
P1 Description & Composition
Trade name of the product: Asmatab Tablet
Active substance name : Montelukast Sodium
Pharmaceutical form : Oral Solid
Concentration : Each tablet contains:
Montelukast Sodium 11.37 mg (equivalent to Montelukast 10 mg)
Excipients..q.s.
Route of administration : Oral
Unit Formula:
Name of the Substance Specification Quantity /Tablet Overage Function
(mg)
Active Ingredient
Montelukast Sodium 10.370* Active Ingredient
INN (Equivalent to
Montelukast 10.0 mg)
Excipients
Microcrystalline Cellulose 78.695 Diluent
(Avicel PH 102) BP
Sodium Starch Glycolate 4.750 Disintegrant
BP
Colloidal Silicon Dioxide 0.712 Lubricant
(Aerosil 200) BP
Magnesium Stearate 0.473 Lubricant
BP
Coating Materials
Opadry II 85G58921 Ph. Gr. 2.790 Coating Polymer
White
Purified water BP 27.900 Coating Solvent
* Based on 100% potency.
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P2 Pharmaceutical development
P2.1 Component of Drug Product
P2.1.1 Active Ingredients
Each Tablet contains Montelukast 10 mg as Montelukast Sodium INN.
Montelukast sodium is a hygroscopic, optically active, white to off-white, free-flowing powder. It is
freely soluble in ethanol, methanol, and water and practically insoluble in acetonitrile.
Drug Substance and Excepients are compatible with each other.
P2.1.2 Excipients:
Excipients Formulation Expectation
Microcrystalline Cellulose Used as tablet diluent in conc. 82.83%
(Avicel PH 102)
Sodium Starch Glycolate Used as disitegrant in conc. 5.00%
Colloidal Silicon Dioxide (Aerosil 200) Used as Lubricating agent & Glidant in conc.
0.75%
Magnesium Stearate Used as lubricant in conc. 0.50%
P2.2 Finished Product
P2.2.1 Formulation development
Asmatab was developed as immediate release tablet for oral delivery. During formulation
development of Asmatab, different Excipients in varing concentration were used and comparative
studies were done. The formulation mentioned in P.1 was found the best.
P2.2.2 Overages
Not Applicable.
P2.2.3 Physiochemical and Biological Properties
Physicochemical Properties
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Results
Tests
Description A white to Off white colored, round shaped film coated
:
tablet with V engraved on one side and other side break
line
Identification Must be positive for Montelukast Sodium
:
Average weight/Tablet (mg) 92.0 mg 102.0 mg (97.0 mg 5 %)
:
Out of 20 Tablets maximum 2 tablets shall deviate 7.5%
:
Uniformity of weight of average weight and none shall deviate 15% of average
weight
LOD (%)/Water (%) Not more than 3.5%
:
Average Hardness (Kp) Not less than 4
:
Not more than 30 minutes
:
Disintegration time
Dissolution NLT 70% within 45 minutes
:
Assay (mg/tablet) 9.0 mg 11.0 mg (90.0 % 110.0 % of the label claim)
:
Biological Properties
Montelukast is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of
asthma and to relieve symptoms of seasonal allergies. It is usually administered orally. Montelukast
blocks the action of leukotriene D4 on the cysteinyl leukotriene receptor CysLT1 in the lungs and
bronchial tubes by binding to it. This reduces the bronchoconstriction otherwise caused by the
leukotriene, and results in less inflammation. Because of its method of operation, it is not useful for
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the treatment of acute asthma attacks. Again because of its very specific locus of operation, it does
not interact with other allergy medications such as theophylline.
P.2.3 Container Closure System
Primary Packaging material Alu-Alu blister (Printed Aluminium Foil & Unprinted Aluminium
film)
Secondary Packaging material Inner carton made of Sweedish board & Paper based outer carton
Alu-Alu blister is suitable and compatible with Asmatab Tablet which was proved by stability
studies because no significant change of product occurred during long term & accelerated condition
P2.4 Microbiological attributes
No preservatives are added to the formulation and hence preservative efficiency test are not
carried out.
The product is not a sterile product so the need of additional test to consider microbiological
aspect is not necessary.
P2.5 Compatibility
The product is studied by keeping it in stability chambers maintaining different temperature
and humidity conditions over a span of shelf life (predicted for the product). No significant
change in physical properties as well as qualitative aspect observed. In specificity test during
analytical method validation no interference of excipients are observed. So all the
components are compatible.
P3 Manufacture
P3.1 Batch formula:
Product Name Asmatab Tablet Product Code BD 001
Generic Name Montelukast Sodium INN Master Formula No. FMN-7711
Dosage Form Film coated Tablet Department Quality Assurance
Strength/tablet 10 mg Version No. 00
Specification In House Date Originated June 2013
Pack size 3 x 10s Revision Date New
Batch Size By Number 2, 39,000 Tablets Batch Size By Weight 22.705 kg
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Code No. Material Name Specificat Unit Standard QC Actual Dispensed Checked Check
ion for Quan Ref. Qu by (WH) by ed by
mu tity No. ant (Prod.) (QA)
la (Kg) ity
(m
g) (Kg)
1113010 Montelukast 10.370** 2.478*
Sodium INN
1113004 Microcrystalline 78.695 18.808*
Cellulose BP
(Avicel PH 102)
1119001 Sodium Starch 4.750 1.135
Glycolate BP
1103001 Colloidal Silicon 0.712 0.170
Dioxide (Aerosil BP
200)
1113002 Magnesium 0.473 0.113
Stearate BP
1115005 Opadry II Ph. Gr. 2.790 0.667
85G58921 White
* Based on calculation Factor- Montelukast Sodium: Montelukast = 1.037:1
P3.2 Manufacturing Process and process control.
(Flow chart of manufacturing and packaging process)
Attached in Annexure IV
P3.3. Control critical steps and intermediates
All equipments are cleaned as per written procedures and is being checked by Quality
Assurance department for cleanliness before use to avoid contamination with residue of
previous products.
All production and in-process Quality control personnel handling the formulation should
wear caps, face masks and latex gloves.
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Material of previous batch /product is removed from the premises prior to manufacturing
process to avoid any type of mix up.
Manufacturing operations are to be carried out only in specified areas.
Following environmental conditions are maintained strictly during manufacturing process.
Temperature: NMT 25 C
Relative Humidity: NMT 50%
Mixing Time, Drying time and temperature, compression force is strictly controlled.
Homogeneity is checked through assay testing by QC.
Friability and Disintegration time is checked frequently during operation.
Any deviations from the technical directions should have concurrence from Quality
Assurance Manager and General Manager Operations.
P3.4 Process validation
Process validation is attached in Annexure V
P4 Control of excipients
P4.1 Specifications
Attached in Annexure VI
P 4.2 Analytical Procedures (standard testing procedure)
Attached in Annexure VI
P 4.3 Excipients of human or animal origin
Not Applicable.
P5 Control of finished product
14
P5.1 Specification
Specification for the finished product attached in Annexure-VII.
P5.2 Analytical Procedure (standard testing procedure)
Analytical Procedure for the finished product attached in Annexure-VII
P5.3 Validation of the Analytical Procedure
Finished product analytical procedure was validated according to recognized guideline and
attached in Annexure- VIII.
P 5.4 Batch Analysis
Certificate of analysis of Batch No. 402003 is attached in Annexure- IX.
P5.5 Characterization of Impurities
As per Raw material supplier certificates
P6 Reference Standards or material
No Impurity Reference standard is required
P7 Container closure system
Asmatab Tablets packed in a form of blister and such blisters are placed in carton.
Primary container:
ALU / ALU Blister
Specification of Primary container are attach in Annexure -X.
Secondary container:
Carton made-up of chromo board free from dirt, crack, edges and none gluing and glue squeeze.
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Note: For more information specifications of packing materials, used are attached in Annexure-X
Analytical Procedure of Packaging materials
Annexure -X
P8 Stability Report
Stability reports for three batches attached in Annexure XI.
P9 Product interchangeability equivalence evidence
Dissolution of Asmatab Tablet is equivalent to MONAS 10 Tablet of The ACME specialized
Pharmaceuticals Ltd., Bangladesh
Comparative Dissolution attached in Annexure- XII
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