Sample SQOS Chemical Drug

7/29/2019 Sample SQOS Chemical Drug

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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE JANUARY 2009 SINGAPORE QUALITY OVERALL SUMMARY FOR CHEMICAL DRUGS

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP Appendi x 8 - Page 1 of 25

APPENDIX 8 SINGAPORE QUALITY OVERALL SUMMARYNew Drug Applications and Generic Drug Applications (Chemicals)

The Quality Overall Summary (QOS) should be completed to summarize the Quality (i.e.,Chemistry, Manufacturing and Controls) portion of a New Drug Application (NDA) or a Generic Drug

Application (GDA) for a chemical drug product. Both hard copy and electronic copy of the Singapore QOSshall be submitted for review.

The applicant is responsible for completing all sections and fields as much as possible. Sections and fieldsthat are not applicable should be indicated with NA. An explanatory note must immediately follow all NAentries.

INTRODUCTION

Proprietary Name of Drug Product HSA Paracetamol

INN Common Name of DrugSubstance

Acetaminophen

Product Owner Name Somewhere Pte Ltd

Licence Holder Name HSA

Dosage Form Tablets

Strength(s) 100mg

Route of Administration Oral

Proposed Indication(s) Common analgesic and antipyretic drug that is used for therelief of fever and headaches and minor aches and painsand for the treatment of cancer.

Other int roductory information:

Approved in Singapore, Australia and USA.

HSA Paracetamol Tablets 100mg are round, white flat, plain tablets packaged in Alu Alu blisters. The

presentation is 10 tablets per blister strip and 2 strips per carton container box. The indication is forpain and cancer therapy and all appropriate and relevant information has been submitted inaccordance with the current HSA guidelines. A shelf life of 2 years when stored at or below 300C isproposed.

The Singapore Reference Product is Initial Paracetamol, Singapore (SIN01234) which is approved in1999.


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S DRUG SUBSTANCE

S 1 GENERAL INFORMATION

Check appropriate box.

DMF (open) part is attached.

DMF (open and restricted) and Letter of Access to be submi tted by 01/01/2009 (within onemonth of PRISM submission),

OR

Letter of Access to the DMF filed with HSA (015:________) is provided.

* CEP (Certificate of Suitability from EDQM) for Drug Substance is attached.

CEP Number:

CEP (Certificate of Suitability from EDQM) for Raw materials and Excipients i s attached.

Drug Substance meets the current USP/PhEur/BP/JP (delete as appropriate)requirements.

Drug Substance meets other pharmacopoeia standards.

Drug Substance meets in-house specifications .

Drug Substance meets other pharmacopoeia standards. Analytical methods andappropriate analytical method validation data are included in the dossier.

Drug Substance meets in-house specifications. Analytical methods and appropr iateanalytical method validation data are included in the dossier.

* If CEP is provided and Ph.Eur standard is claimed for drug substance, please fill in S1, S2.1, S4.4 and #S7If CEP is provided and other standards are claimed for drug substance, please fill in S1, S2.1, S4.1 to S4.5 and #S7(#To be provided if re-test period/shelf life is not stated on CEP)

S 1.1 Nomenclature

Hard Copy Location/Pages: Module 3 Pg 1-5

E-Copy Location/File Name: CD 03 / S1.pdf

Chemical Name: para-acetylaminophenol

Other names: (e.g. INN, BAN, USAN, common name) Paracetamol

Company or laboratory code: APAP - 1234

Chemical Abstracts Service (CAS) registry number: 103-90-2

S 1.2 Structure




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Structural formula (including stereochemistry):

Molecular formula: C8H9NO2

Molecular Mass: 151.169 g/mol

S 1.3 General Properties

Hard Copy Location/Pages: Module 3 Pg11-15


Physical description (e.g., appearance, colour, physical state): White to off-white powder

Physical form (e.g., polymorphic form, solvate, hydrate):

Two other known crystallineanhydrous polymorphs denoted as

Form A and Form B. The XRPDpatterns for all crystalline forms aredifferent and XRPD has been usedto routinely differentiate the multiplecrystalline forms.

Solubilities (e.g., in common solvents, aqueous/non-aqueoussolubility profile):

Freely soluble in water at pH7.0.

pH and pKa values: pKa = 9.5

Other (e.g., partition coefficients, melting or boiling points,optical rotation, refractive index (for a liquid), hygroscopicity,UV absorption maxima and molar absorptivity):

Melting Point = 169C

Non-hygroscopic

S 2 MANUFACTURE

S 2.1 Manufacturer(s)

Name, address, and activity of each manufacturer, including contractors, and each proposedproduction site or facility involved in manufacture and testing:

Activi ty Name and Address *GMP Compliance (Please

indicate Approving Agency)

Site of ManufactureGo Get Chemicals22 Pine ValleyCaliforniaUSA

Yes, US FDA

Site of Release testingGood Testers23 Grove RoadUSA

No

Site of Batch ReleaseGo Get Chemicals22 Pine ValleyCaliforniaUSA

Yes, US FDA

* For information only.


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S 2.2 Descrip tion of Manufacturing Process and Process Controls

Hard Copy Location/Pages: Module 3 15-20 and DMF (Restricted)

E-Copy Location/File Name: CD 03 / S2.pdf and CD_DMF (Restricted)

Typical production batch size: 100kg

Flow diagram of the synthetic process (es):


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S 2.3 Control of Materials



S 2.4 Controls of Crit ical Steps and Intermediates



S 2.5 Process Validation and/or Evaluation



S 2.6 Manufacturing Process Development



S 3 CHARACTERISATION

S 3.1 Elucidation of Structure and other Characteristics


E-Copy Location/File Name: CD 03/S3.pdf

S 3.2 Impurities

Summary of potential and actual impurities arising from the synthesis, manufacture and/or degradation:

ChemicalName/Laboratory Code

Origin/Type of Impurity Structure

4 aminophenol Degradation Product Structure of impurity should be insertedhere, if available.

2 aminophenol Degradation ProductStructure of impurity should be inserted

here

1 aminophenol Synthetic impurityStructure of impurity should be inserted

here


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Process-related impurities (e.g., residual solvents):

Compound Name Step in Process

Methanol Crystallisation

Benzene Extraction

S 4 CONTROL OF THE DRUG SUBSTANCE

S 4.1 Specification

Standard Claimed for the Drug Substance (e.g., USP, BP,etc.):

USP

Test Method(e.g., HPLC)

Source (e.g.,USP, in-house)

Acceptance Criteria

Appearance Visual In-house White to off white powder againstmatt white background

Identity test by IR IR USP IR spectrum of the standard conformsto the IR spectrum of the sample

Identity test by HPLC HPLC USP The HPLC chromatogram of thestandard peak corresponds to thepeak obtained in the chromatogramfor the sample solution

pH pH meter USP 3.5-5.5

Loss on drying USP USP Dry at 1050C, weight loss NMT 0.5%of its weight

Residue on ignition USP USP NMT 0.1%

Impurities (%w/w)

4 Aminophenol3 Aminophenol2 AminophenolAny other unidentifiedTotal

HPLC In-house

NMT 0.2NMT 0.1NMT 0.2NMT 0.1NMT 0.5

Assay (%w/w) on a dried basis HPLC In-house 98.5-101.0


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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE SINGAPORE QUA LITY OVERALL SUMMARY FOR CHEMICAL DRUGS

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

S 4.2 Analytical Procedures

S 4.3 Validation of Analytical Procedures

For each test, please indicate yes or no as appropriate

Test Name MethodDescription

Selectivity

Linearity

Range

Accuracy

Precision

-

Repeatability

-

Intermediate

Precision

-

Reproducibility

LimitofDetection

LimitofQuantitation

Assay of Paracetamol Yes Yes Yes Yes Yes Yes Yes YeImpurities by HPLC Yes Yes Yes Yes Yes Yes Yes Ye


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S 4.4 Batch Analyses

Batch Number Batch SizeBatch Type

(production/pilot)Date of

ProductionSite of Production

CA001 100kg Production 1 Jan 2001Go Get Chemicals22 Pine ValleyCaliforniaUSA

CA002 100kg Production 15 Sept 2002

CA003 100kg Production 30 April 2003

S 4.5 Just ification of Specification


E-Copy Location/File Name: CD 03/ S4.pdf

Test Just ification of Specifications

Appearance Visual inspection allows for identification & detection of possibledefects

ImpuritiesThe acceptance criteria applied is based on: 1) the maximum contentof impurities found in the batches used during the development for

toxicology studies and in the intentionally degraded and spiked batchNo. FE 349 used to qualify the impurities (Information located in3.2.S.3.2.) 2) the qualification level of each impurity.

Assay The HPLC weight percent assay specification of 98.5-101.0% wasestablished from a review of the release data generated to date andfrom consideration of the assay variability. The weight percentrelease results ranged from 98.5% to 100.7% in the batch data. Thespecification of 98.5-101.0% by weight describes the consistentlyhigh quality of the drug substance and allows for typical analyticalvariability.

Other tests Comply with USP requirements.

S 5 REFERENCE STANDARDS OR MATERIALS



Batch Number Source (e.g., USP, in-house)

Primary Reference Standard USP 1111 USPWorking Standard CA 0000 In-house


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S 6 CONTAINER CLOSURE SYSTEM

Description of the container closure system(s) for the storage of the drug substance:

Drug substance in polyethylene bags, double layered with a twist tie.

S 7 STABILITY

S 7.1 Stability Summary and Conclus ions

Stability study details:

Storage

Conditions(C, % RH, light)

Batch

Number

Batch Size Site of

Manufacture

Completed Test Intervals

(months)

30C/75%RH CA011 100kgGo Get Chemicals22 Pine ValleyCaliforniaUSA

0, 3, 6, 9, 12, 18, 24, 36 and 48

CA012 100kg 0, 3, 6, 9, 12, 18, 24, 36 and 48

CA013 100kg 0, 3, 6, 9, 12, 18, 24

40C/75%RH CA011 100kg

Go Get Chemicals

22 Pine ValleyCaliforniaUSA

0, 3 and 6

CA012 100kg 0, 3 and 6

CA013 100kg 0, 3 and 6

Summary and discussion of all stability study results:

Hard Copy Location/Pages: Module 3 Pg 80-85E-Copy Location/File Name: CD 03/ S7.pdf

Proposed storage conditions and re-test period (or shelf life, as appropriate):

Container ClosureSystem

Storage Condit ions Re-test Period (or Shelf Life, asappropriate)

Polyethylene bags Store at or below 30C Retest period of 24 months

S 7.2 Post-approval Stability Protocol and Stability Commitment


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Stability protocol for commitment batches (if applicable):

Protocol Parameter Descrip tion

Number of batches and batch sizes None

Tests and acceptance criteria None

Container closure system(s) None

Testing frequency None

Storage conditions (and tolerances) of samples None

Other None

S 7.3 Stability Data



P DRUG PRODUCT

P 1 DESCRIPTION AND COMPOSITION OF THE DRUG PRODUCT

(1) Description of the dosage form:

The tablets are round, white, flat plain and contain 100mg of acetaminophen. The tablets are packaged intoAlu Alu blister strips. There are 2 blister strips per carton box.

(2) Composition, i.e., list of all components of the dosage form, and their amounts on a per unit basis(including overages, if any):

Strength (Label claim): 100mg

Components Qual ity Standard Quanti ty per uni t % Function

Acetaminophen USP 100mg 50 Active

Microcrystalline cellulose BP 20mg 10 Diluent

Starch PhEur 20mg 10 Diluent

Polyvinvyl pyroolidone JP 20mg 10 Binder

Magnesium stearate USP 20mg 10 Lubricant

Sodium starch glycolate BP 18mg 9 Disintegrant


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(2) Composition, i.e., list of all components of the dosage form, and their amounts on a per unit basis(including overages, if any):


Components Qual ity Standard Quanti ty per uni t % Function

Brilliant Colour Coating In-house 2mg 1 Coating

Total 200mg 100

(3) Composition, i.e., qualitative list of all components of proprietary materials (e.g., capsule shells,colouring blends, imprinting inks, etc.): Brilliant Colour Coating

Proprietary Material Qualitative Composition Quantitative Composition

Iron Oxide Red NF NF 40%w/w

Hydroxy propyl methyl cellulose USP 50%w/w

Glycol JP 10%w/w

(4) Description of accompanying reconstitution diluent(s), if applicable:

Not applicable.

P 2 PHARMACEUTICAL DEVELOPMENT

P 2.1 Components of the Drug Product


E-Copy Location/File Name: CD 03/ P2.pdf

P 2.2 Drug Product

P 2.2.1 Formulation Development



P 2.2.2 Overages



P 2.2.3 Physicochemical and Biological Properties


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P 2.3 Manufacturing Process Development

Discussion of the development of the manufacturing process of the drug product (e.g., optimization ofthe process, selection of the method of sterilization, etc.):



P 2.4 Container Closure System

Discussion of the suitability of the container closure system (described in P 7) used for the storage,

transportation (shipping), and use of the drug product (e.g., physicochemical tests, biological reactivitytests, leaching, etc.):



P 2.5 Microbiological Attr ibutes

Discussion of microbiological attributes of the dosage form (e.g., preservative effectiveness studies):



P 2.6 Compatibility

Discussion of the compatibility of the drug product with reconstitution diluent(s) or dosage devices (e.g.,precipitation of drug substance in solution, sorption on injection vessels, etc.):



P 3 MANUFACTURE

P 3.1 Manufacturer(s)

Name, address, and activity of each manufacturer, including contractors, and each proposedproduction site or facility involved in manufacture and testing of product intended for Singapore:

Activi ty Name and Address

Site of Fabrication, Manufacturing HSA11 Biopolis WaySingapore


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Name, address, and activity of each manufacturer, including contractors, and each proposedproduction site or facility involved in manufacture and testing of product intended for Singapore:

Activi ty Name and Address

Site of Primary Packaging Good PackagersJohore BahruMalaysia

Site of Secondary PackagingExcellent PackingBintanIndonesia

Site of Release TestingTrust TestersBangkokThailand

Site of Batch ReleaseHSA11 Biopolis WaySingapore

P 3.2 Batch Formula

List of all components of the dosage form to be used in the manufacturing process, and their amountson a per batch basis (including overages, if any):


Batch Size (Number of dosage units): 200kg (1000 000 tablets)

Component and Quality Standard (and Grade, if applicable) Quantity per batch

Acetaminophen 100kg

Microcrystalline cellulose 20kg

Starch 20kg

Polyvinvyl pyroolidone 20kg

Magnesium stearate 20kg

Sodium starch glycolate 18kg

Brilliant Colour Coating 2kg

Total 200kg

P 3.3 Descrip tion of Manufacturing Process and Process Controls



Flow diagram of the manufacturing process(es):


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P 3.4 Controls of Critical Steps and Intermediates



P 3.5 Process Validation and/or Evaluation


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Please check appropriate boxes.

Development Pharmaceutics Report Starting page #:Ending page#:

91130

Validation Scheme Starting page #:Ending page#:

151155

3 (e.g. 2) Pilot batches were used in the validationstudy

Starting page #:Ending page#:

151155

_____ (e.g. 3) full production batches were used inthe validation study

Starting page #:Ending page#:

Type of Validation

Retrospective

Prospective

Concurrent*

Others; please specify:

* Prior consultation with HSA is required.

Manufacturing site at which the validation is carried out: HSA, Singapore

Batch Number (Batches must be consecutive) Batch SizeBatch Type

(production/pilot/experimental)

SQ1100 150kg Pilot

SQ2200 150kg Pilot

SQ3300 150kg Pilot

Post-Approval Commitment

(1) Validation protocol for commitment batches:


Number of batches per strength 3 batches

Batch Size 200kg

P 4 CONTROL OF EXCIPIENTS

P 4.1 Specifications

Specifications for non-compendial excipients and for compendial excipients which includesupplementary tests not required by the monograph(s) may be found in:


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P 4.2 Analytical Procedures



P 4.3 Validation of Analytical Procedures



P 4.4 Just ification of Specifications

Justification of the specifications (e.g., evolution of tests, analytical procedures, and acceptance criteria,exclusion of certain tests, differences from compendial standard, etc.):



P 4.5 Excipients of Human or Animal Origin

Hard Copy Location/Pages: Module 3 Pg 176


P 4.6 Novel Excipients

Hard Copy Location/Pages: Module 3 Pg 176



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P 5 CONTROL OF DRUG PRODUCT

P 5.1 Specification(s)

Standard Claimed for the Drug Product(e.g., USP, Ph.Eur, BP, JP etc.):

In-house

Test Method (e.g.,HPLC)

Source (e.g.,USP, In-house)

ReleaseSpecification

Shelf LifeSpecification

Appearance Visual In-house Round, white, flat plain tablets

Identification by IR IR In-house The IR spectrum of the sampleconforms to the reference IR

Identification by HPLC HPLC In-house The HPLC peak in the referencestandard conforms to the peak in theHPLC chromatogram of the sample

Weight Variation BP Method BP Complies to BP -

Dissolution Time (Q at 30min)

USP Method USP 80 70

Assay (% of label claim) HPLC In-house 95.0-105.0 90.0-110.0

Impurities (%w/w)

4 Aminophenol3 Aminophenol2 AminophenolAny other unspecifiedTotal

HPLC In-house



Microbial Limit Test USP USP - Complies


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GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE SINGAPORE QUA LITY OVERALL SUMMARY FOR CHEMICAL DRUGS

HEALTH SCIENCES AUTHORITY HEALTH PRODUCTS REGULATION GROUP

P 5.2 Analytical Procedures

P 5.3 Validation of Analytical Procedures

For each test, please indicate yes or no as appropriate

Test Name MethodDescription

Selectivity

Linearity

Range

Accuracy

Precision

-

Repeatability

-

Intermediate

Precision

-

Reproducibility

LimitofDetection

Assay of Paracetamol Yes Yes Yes Yes Yes Yes Yes

Impurities Method Yes Yes Yes Yes Yes Yes Yes


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P 5.4 Batch Analyses

Batch Number Batch SizeBatch Type

(production/pilot)Date of

ProductionSite of

ProductionSite of Batch

Release

SQ55 200kg Production 1 Mar 2000 HSA 11Biopolis WaySingapore

HSA 11 BiopolisWay Singapore

SQ66 200kg Production 2 Apr 2001

SQ77 200kg Production 5 July 2004

P 5.5 Characterisation of Impurities

Information on the characterization of impurities, not previously provided in S 3.2 (e.g., summary ofactual and potential degradation products, basis for setting the acceptance criteria, etc):

Chemical Name/LaboratoryCode

Origin/Type of Impurity

4 Aminophenol Degradation product

P 5.6 Just ification of Specification(s)




Appearance Visual inspection allows for identification & detection of possibledefects

IdentificationTwo identification tests carried out routinely: HPLC and infraredspectrum. Although the retention times obtained from HPLC may notbe regarded as being specific, the combination of infrared spectrumwith it is sufficient and acceptable to identify the drug substancewithout ambiguity.

ImpuritiesThe acceptance criteria applied is based on: 1) the maximum contentof impurities found in the batches used during the development fortoxicology studies and in the intentionally degraded and spiked batchNo. FE 250 used to qualify the impurities 2) the qualification level ofeach impurity.

Assay The HPLC weight percent assay specification was established froma review of the release and stability data generated to date and fromconsideration of the assay variability. The specification describes

the consistently high quality of the drug product and allows fortypical analytical variability.


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Other tests Comply with Pharmacopeia requirements.

P 6 REFERENCE STANDARDS OR MATERIALS

If the reference standard is a secondary standard (in house /working standard), evidence that thesecondary standard has been standardised against an official standard should be provided Data ofstudies performed on working standard against primary standard should be included, together withappropriate Certificate of Analysis.



Batch Number Source (e.g., USP, in-house)Primary Reference Standard USP 1111 USP

Working Standard SQ 0000 In-house

P 7 CONTAINER CLOSURE SYSTEM

Description of the container closure systems:

Descrip tion of Container Closure Quantity Per Container Pack Size

Alu Alu Blisters 10 tablets per blister strip 2 strips per carton

P 8 STABILITY

P 8.1 Stability Summary and Conclusions



Proposed Commercial Batch Size (kg): 200kg

BatchNumber

Batch Size Date of Manufacture

Site ofManufacture

Source of ActiveIngredient andBatch Number

ContainerClosureSystem

BA001 100kg 1 June 2003HSA11 Biopolis WaySingapore

Go Get Chemicals22 Pine ValleyCaliforniaUSA

Alu Alu blisters

BA002 100kg 2 June 2003 Alu Alu bisters

BA003 100kg 3 June 2003 Alu Alu bisters


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Storage Condi tions (C, % RH,light)

Completed Test Intervals

30C/75%RH 0, 3, 6, 9, 12, 18 and 24 months

40C/75%RH 0, 3 and 6

Light cabinet 1, 2 weeks

In-use stability testing (where applicable): Not applicable as no in-use shelf life is claimed

In-use Storage Conditions(C, % RH, light)

Length of Storage prior to Startof In-use Stability Testing

Completed In-use Test Intervals(e.g. minutes/ hours/ days)

Proposed storage conditions and shelf life:

Container ClosureSystem

Storage Condit ions (and In-useStorage Conditions, if

applicable)

Shelf Life (and In-use Period, ifapplicable)

Alu Alu Blisters Store at or below 300C 24 months

P 8.2 Post-Approval Stabilit y Protocol and Stability Commitment

(1) Stability protocol for commitment batches:


Number of batches per strength and batchsizes

Three production batches, 200kg

Tests and acceptance criteria Same as registered in P5.1

Container closure system(s) Alu Alu Blisters

Testing frequency 0, 3, 6, 9, 12, 18 and 24 months

Storage conditions (and tolerances) of samples 30C/75%RH and 40C/75%RH

Other None


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(2) Stability protocol for continuing (i.e., ongoing) batches:


Number of batches per strength per year andbatch sizes

One batch per year, 200kg

Tests and acceptance criteria Same as registered in P5.1

Container closure system(s) Alu Alu Blisters

Testing frequency 1, 12 and 24 months

Storage conditions (and tolerances) of samples 30C/75%RH

Other None

P 8.3 Stabili ty Data




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P 9 PRODUCT INTERCHANGEABILITY

P 9.1 Bioavailability / Bioequivalence Study

Details of the batches usedfor BA/BE study

Generic Product Submitted toHSA for Registration

Current RegisteredSingapore Reference

Product

Product Name HSA Paracetamol Initial Paracetamol, Singapore

Strength of Dosage Form 100mg 100mg

Site of Manufacture HSA11 Biopolis Way

Singapore

First OneGrange Road

Singapore

Site of Batch Release N/A

Batch No. BE1001 RF1001

Batch size 200kg N/A

Product formula Same as section P.3.2

Yes

No, please provide justification

N/A

Study Report Number 12111

BA/BE Study Site (Name & Address) BE Site

Wheelock Road

Singapore

Date of Inspection of Study 1 Jan 2004

Name of Inspecting Agency/Author ity XX Authority of YYY

Availabi li ty of Inspection Report (Yes/No) Yes

Generic Product Usedin BA/BE Study

Reference Product Usedin BA/BE Study

Product Name HSA Paracetamol Initial Paracetamol, Hong Kong


Site of Manufacture HSA11 Biopolis Way

Singapore

First OneGrange RoadHong Kong

Site of Batch Release HSA11 Biopolis Way

Singapore

First OneGrange RoadHong Kong

Country where the supply issourced for this study:

Singapore Hong Kong


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P 9.2 Comparative Dissolution Profil e

Product 1: = Initial Paracetamol, Hong Kong

Product 2: = Initial Paracetamol, Singapore

Study Report Number: 12111

Profile of Product 1 Profile of Product 2

Product Name Initial Paracetamol, Hong Kong Initial Paracetamol, Singapore


Site of Manufacture First OneGrange RoadHong Kong

First OneGrange RoadSingapore

Site of Batch Release First One

Grange RoadHong Kong

First One

Grange RoadSingapore

Dissolution Method Used USP Paddle USP Paddle

Country where the supply issourced for this study:

Hong Kong Singapore

Dissolution Test Results Profile of Product 1 Profile of Product 2

Medium 1 pH 1

Range 99.0-102.2 98.0-105.3

Mean of 12 tablets 100.1 101,1

RSD 1.0 1.2

F2 Calculation 70

Medium 2 pH 4.6

Range 98.0-101.2 98.0-110.3

Mean of 12 tablets 100.4 101.7

RSD 1.0 1.2

F2 Calculation 68

Medium 3 pH 8.2

Range 99.0-102.2 98.0-102.3

Mean of 12 tablets 100. 101.1

RSD 1.0 1.2

F2 Calculation 71

Graphical Presentation Presented in Pages 12-24


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Statistical Analysis



Other Relevant Information:

Bioequivalence study and dissolution comparison test results showed that the generic paracetamol isequivalent to Singapore Innovator Product.

A APPENDICES

A 1 FACILITIES AND EQUIPMENT (NAME, MANUFACTURER)

Hard Copy Location/Pages: NA- not a requirement for Generic SubmissionE-Copy Location/File Name:

A 2 ADVENTITIOUS AGENTS SAFETY EVALUATION (NAME, DOSAGE FORM, MANUFACTURER)

Hard Copy Location/Pages: NA- not a requirement for Generic Submission

E-Copy Location/File Name:

A 3 NOVEL EXCIPIENTS

Hard Copy Location/Pages: NA- No novel excipients are used

E-Copy Location/File Name:

Tan Ah Meng 01 Jan 2009

Applicants Name: Date:

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Sample SQOS Chemical Drug