คู่มือการยื่นขึ้นทะเบียนยาใหม่

/ (New Drugs) ASEAN HARMONIZATION

1

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1 . 1 / . 2 3 1. 3 2. 3 3. 1 (Part 1): 3 (ADMINISTRATIVE DATA AND PRODUCT INFORMATION) 4. 2 (Part 2) : (Quality Document) 5 5. 3 (Part 3) : ... 6 (Nonclinical Document ) 6. 4 (Part 4) : 6 (Clinical Document) 7. .. 7 U 1 :U . 9 / ( .. 8 .. 8) 10 ( .. 1 .1) 12 U 2 :U (Model Certificate of a Pharmaceutical Product ) 19 (Certificate of Free Sale) U 3 :U 27 ASEAN HARMONIZATION U 4 :U . 35 .. 36 (New Drugs).. 37

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.. 39 .. 41 U 5 :U (Checklist) 42 .ND1 43 .ND2 47 .ND3 54 .ND4 59

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/ (New Drugs) ASEAN HARMONIZATION

U (New Drugs) 1. (New Chemical Entities) 2. (New Indication) 3. (New Combination) / 2 4. (New Delivery System) Bioavailability 5. (New Route of Administration) 6. (New Dosage Form) 7. (New strength)

U 2 1. .. 8 ..8 (One Stop Service Center) 2. .. 1 .1 (One Stop Service Center)

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U / U

1. / 2. 2.1 .. 8 / .. 8 3 (One Stop Service Center) 2.2 .. 8 / .. 8 1 / ..8/..8 3.

3.1 .. 8 .. 8 2 ( 1) 3.2 3.3 3.4

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U

U 1. U / U 2. U [ASEAN COMMON TECHNICAL DOSSIER (ACTD) FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE] (New Drugs) 4 (Parts) U 1U (Part 1) (ADMINISTRATIVE DATA AND PRODUCT INFORMATION)

U 2 (Part 2)U (QUALITY DOCUMENT) U 3 (Part 3)U (NONCLINICAL DOCUMENT) U4 (Part 4) U (CLINICAL DOCUMENT) U3. 1 (Part 1): (ADMINISTRATIVE DATA AND PRODUCT INFORMATION) 3 (Section) A, B C U A U (Introduction) ASEAN Harmonization . U BU (Table of Contents) 1 U CU (Documents required for registration) 1. ( 1)

1.1 ( ..1) 1.2 ASEAN HARMONIZATION ( .1)

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/ 2. (Certificates) 2.1 - - GMP 2.2 - -(Certificate of Pharmaceutical Product) (Certificate of Free Sale) ( 2) - GMP () 3. (Labeling) ( 3) 4. (Product Information) ( 3) 4.1 Summary of Product Characteristics (SPC) Product Data Sheet 4.2 (Package Insert, PI) 4.3 (Patient Information Leaflet, PIL) U

(1.) NCE SPC SPC PI PI

(2.) NCE SPC PI SPC

(3.) PIL SPC/PI PIL PIL PIL

(4.)

5. .8 .8

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6. (Applicant declaration) ( 4)

6.1 6.2 6.3 6.4 6.5 () -

- ( / )

- - Invoice Proforma Invoice Letter of

Credit () - () - 7. 8. - 9. U 4. 2 (Part 2) : (Quality Document) 4 (Section) A,B,C D U AU (Table of Contents) 2 U BU (Quality Overall Summary) U CU (Body of Data) U DU (Key Literature References) 2 (New Drugs) ASEAN HARMONIZATION

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U 5. 3 (Part 3) : (Nonclinical Document )U 5 (Section) A, B, C, D, E U AU (Table of Contents) 3 U BU (Nonclinical Overview) U CU (Nonclinical Summary : Written and Tabulated) U DU () (Nonclinical Study Report) (as requested) U EU (List of Key Literature References) 3 (New Drugs) ASEAN HARMONIZATION U 6. 4 (Part 4) : (Clinical Document) 6 (Section) A, B, C, D, E F U AU (Table of Contents) 4 U BU (Clinical Overview) U CU (Clinical Summary) U DU (Tabular Listing of All Clinical Studies) U EU () (Clinical Study Reports) ( If applicable) U FU (List of Key Literature References) 4 (New Drugs) ASEAN HARMONIZATION U 7.

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7.1 (Checklist) 7.1.1 . ND1 : (New Drugs) ASEAN Harmonization 1 (Part 1) (Administratve data and Product information) 7.1.2 . ND2 : (Checklist of ASEAN Common Technical Document : Part Quality) 2 (Part 2) (Quality Document) 7.1.3 . ND3 : (Checklist of ASEAN Common Technical Document : Part Nonclinical) 3 (Part 3) (Safety : Nonclinical Document) 7.1.4 . ND4 : (Checklist of ASEAN Common Tecnical Document : Part Clinical) 4 (Part 4) (Efficacy : Clinical Document) ( .ND1, .ND2, .ND3 .ND4 5) 7.2 . . .

(1.) 1. . ND1 1 (Part1) 2. . ND2 2 (Part2) 3. . ND3 3 (Part3) 4. . ND4 4 (Part4) (2.) 1. .1 2. .1 3. 4. (Labeling) 5. (Product Information) 6. 7. . ND2 2 (Part2) (3.) 1. .1

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2 .1 3. 4. (Labeling) 5. (Product Information) 6. 7. - 8. . ND3 3 (Part3) 9. . ND4 4 (Part4) 7.3

NCE* NI* NCO* ND* NR* NDOS* NS*

1 1 1 1 1 1 1

2 - 2 2 2 2 2

4 4** 4** 4** 4** 2 4**

* NCE = New Chemical Entity, NI = New Indication, NCO = New Combination, ND = New Delivery system, NR = New Route of administration, NDOS = New Dosage form of Approved New Drug, NS = New Strength of Approved New Drug ** Part 3 Nonclinical 2 7.4 . (One Stop Service Center)

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7.5 . ()

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1

/ .. 8 ..8 .1 .1

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.. 8

.............................................. ................................................... ...................................

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( ) 6. ( ) ( ) ( ) 7. ............................................................................................................. ................................ / ............................... ................................. ..................................... / ............................. / ...................... ................................... ................................... 8. .......................................................................................................... ................................. / .............................. ................................. ...................................... / ............................ / ...................... .................................. ....................................

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9. ................................................................... ................................ / ............................... ................................. ..................................... / ............................. / ...................... .................................. .................................... 10. ........................................ ........................................

( ) ........................................ _______________________________________________________________________________ :- 9

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( )

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15

.1

. ..

(APPLICATION FORM OF ASEAN PHARMACEUTICAL REGISTRATION)

(Modern Drug) (Traditional Drug) (Type) (Manufacture) (Repack) (Import) (License number)

1. (DETAILS OF APPLICANT AND MANUFACTURER) 1.1

(Name of Authorisation Holder and Address)

................................ / ............................... ................................. ..................................... / ............................. / ......................

................................. ......................... 1.2 ( Manufacturers Name and Address)

................................ / ............................... .................................

..................................... / ............................. / ...................... ................................. ......................... 1.3 (Manufacturer responsible for final batch release s Name and Address)

................................ / ............................... .................................

..................................... / ............................. / ...................... ................................. .........................

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(Other manufacturers) (Name and Address) *(Role)

: * granulation bulk, finished dosage form, contract research organization

2. (DETAILS OF PRODUCT) 2.1 (Product Name, Dosage Form and Strength)

(Product Name).... (Dosage Form) (Strength) .

2.2 () Product Description ()

2.3 (Generic Name and Quantity of active ingredients and excipients)

(Generic Name)

(Reference)

(..) Quantity/unit dose

(Active ingredients)

..

(Excipients)

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3. (TECHNICAL DOCUMENTS) 3.1 (Quality Documents ) 3.2 (Safety Documents ) 3.3 (Efficacy Documents )

4. (PATENT/TRADEMARK EVIDENCE) () 5. (REFERENCE PRODUCT) () 6. (APPLICANT DECLARATION)

( ) ........................................

:- 9

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2

(Model Certificate of a Pharmaceutical Product) (Certificate of Free Sale)

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Model Certificate of a Pharmaceutical Product Certificate of a Pharmaceutical ProductP1P This certificate conforms to the format recommended by the World Health Organization (general instructions and explanatory notes attached). Certificate No : ______________________________ Exporting (certifying) country : ____________________________________________ Importing (requesting) country : ___________________________________________ 1. Name and dosage form of product :

___________________________________________ 1.1 Active ingredient(s)P2P and amount(s)P3P per unit dose :

___________________________________________ ___________________________________________ ___________________________________________ For complete composition including excipients, see attached.P4

1.2 Is this product licensed to be placed on the market for use in the exporting country?P5 P Yes No

1.3 Is this product actually on the market in the exporting country? Yes No unknown

If the answer to 1.2 is yes, continue with section 2A and omit section 2B. If the answer to 1.2 is no, omit section 2A and continue with section 2B.P6

2A.1 Number of product licenseP7 Pand date of issue :

___________________________________________

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2A.2 Product-license holder (name and address) : Name : ___________________________________________ Address : ___________________________________________

2A.3 Status of product-license holder :P8P a b c 2A.3.1 For categories b and c the name and address of the manufacturer producing the dosage form are :P9

Name : ___________________________________________ Address : ___________________________________________

2A.4 Is Summary Basis of Approval appended?P10P Yes No 2A.5 Is the attached, officially approved product information complete and consonant with the license?P11P (yes/no/not provided) Yes No Not provided 2A.6 Applicant for certificate, if different from license holder (name and address) :P12

Name : ___________________________________________ Address : ___________________________________________

2B.1 Applicant for certificate (name and address) :

Name : ___________________________________________ Address : ___________________________________________

2B.2 Status of applicant :P8

a b c 2B.2.1 For categories b and c the name and address of the manufacturer producing the dosage form are :P9

Name : ___________________________________________ Address : ___________________________________________

2B.3 Why is marketing authorization lacking? not required under consideration not requested refused

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2B.4 Remarks :P13

________________________________________________ 3. Does the certifying authority arrange for periodic inspection of the manufacturing plant in which the dosage form is produced?P14P Yes No N/A P

PIf no or not applicable proceed to question 4.

3.1 Periodicity of routine inspections (years) : _____________________ 3.2 Has the manufacture of this type of dosage form been inspected? Yes No

3.3 Do the facilities and operations conform to GMP as recommended by the

World Health Organization?P15 P Yes No N/A

4. Does the information submitted by the applicant satisfy the certifying authority on all aspects of

the manufacture of the product?P16

If no explain : ____________________________________

Address of certifying authority : ___________________________________________ Telephone number : _________________ Fax number : ________________________

Name of authorized person : _________________________________________________

Signature of authorized person : _________________________________________________ Stamp and date : _________________________________________________

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Explanatory notes 1 This certificate, which is in the format recommended by WHO, establishes the status of the pharmaceutical

product and of the applicant for the certificate in the exporting country. It is for a single product only since manufacturing arrangements and approved information for different dosage forms and different strengths can vary.

2 Use, whenever possible, International Nonproprietary Names (INNs) or national nonproprietary names. 3 The formula (complete composition) of the dosage form should be given on the certificate or be appended. 4 Details of quantitative composition are preferred, but their provision is subject to the agreement of the product-

license holder. 5 When applicable, append details of any restriction applied to the sale, distribution or administration of the

product that is specified in the product license. 6 Sections 2A and 2B are mutually exclusive. 7 Indicate, when applicable, if the license is provisional, or the product has not yet been approved. 8 Specify whether the person responsible for placing the product on the market : (a) manufactures the dosage form; (b) packages and/or labels a dosage form manufactured by an independent company; or (c) is involved in none of the above. 9 This information can be provided only with the consent of the product-license holder or, in the case of non-

registered products, the applicant. Non-completion of this section indicates that the party concerned has not agreed to inclusion of this information.

It should be noted that information concerning the site of production is part of the product license. If the production site is changed, the license must be updated or it will cease to be valid.

10 This refers to the document, prepared by some national regulatory authorities, that summarizes the technical

basis on which the product has been licensed. 11 This refers to product information approved by the competent national regulatory authority, such as a Summary

of Product Characteristics (SPC). 12 In this circumstance, permission for issuing the certificate is required from the product-license holder. This

permission must be provided to the authority by the applicant. 13 Please indicate the reason that the applicant has provided for not requesting registration :

(a) the product has been developed exclusively for the treatment of conditions - particularly tropical diseases - not endemic in the country of export;

(b) the product has been reformulated with a view to improving its stability under tropical conditions; (c) the product has been reformulated to exclude excipients not approved for use in pharmaceutical

products in the country of import; (d) the product has been reformulated to meet a different maximum dosage limit for an active ingredient;

(e) any other reason, please specify.

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14 Not applicable means that the manufacture is taking place in a country other than that issuing the product

certificate and inspection is conducted under the aegis of the country of manufacture. 15 The requirements for good practices in the manufacture and quality control of drugs referred to in the

certificate are those included in the thirty-second report of the Expert Committee on Specifications for Pharmaceutical Preparations (WHO Technical Report Series, No. 823, 1992, Annex 1). Recommendations specifically applicable to biological products have been formulated by the WHO Expert Committee on Biological Standardization (WHO Technical Report Series, No. 822, 1992, Annex 1).

16 This section is to be completed when the product-license holder or applicant conforms to status (b) or (c) as

described in note 7 above. It is of particular importance when foreign contractors are involved in the manufacture of the product. In these circumstances the applicant should supply the certifying authority with information to identify the contracting parties responsible for each stage of manufacture of the finished dosage form, and the extent and nature of any controls exercised over each of these parties.

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(Certificate of Free Sale) 1. CFS CFS

1.1 1.2

1.3

2. CFS 2.1 2.2

2.2.1

2.2.2 CFS

3. CFS 1 2.1 2.2.1 4. CFS

4.1 4.2 4.3 4.4

- - (model) individual products

5. CFS

6. CFS

26

7. CFS CFS

8. CFS CFS CFS 2 CFS 398/2544 4 2544 122/2548 25 2548 477/2549 29 2549

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3

ASEAN HARMONIZATION

28

ASEAN HARMONIZATION

(LABELLING)

ACTD 3 Unit Carton, Inner Label Blister/Strips

U (UNIT CARTON) 1. (Product name ) 2. (Dosage form) 3. ( Name of Active Ingredient(s) ) 4. ( Strength of Active ingredient(s) ) 5. ( Batch number ) 6. ( Manufacturing date) 7. ( Expiration date ) 8. (Route of Administration ) 9. ( Storage condition) 10. ( Countrys Registration Number) 11. ( Name and address of Marketing Authorization Holder) 12. ( ( Name and address of manufacturer) 13. ( special labeling ) , 14. (Recommended Daily Allowance) 15. (Warning) 16. (Pack sizes)

29

UU 1. Unit Carton 2. . Dosage Form Route of Administration 2.1 Dosage form Tablet Suppository XYZ Capsule 2.2 Route of administration IM IV 1 3 3. Recommended Daily Allowance % RDA vitamins minerals % RDA RDA Thai RDA RDA 4. Marketing Authorization Holder 11

U INNER LABEL 1. (Product name ) 2. * (Dosage form) 3. ( Name of Active Ingredient(s) ) 4. ( Strength of Active ingredient(s) ) 5. ( Batch number ) 6. * ( Manufacturing date) 7. ( Expiration date ) 8. (Route of Administration ) 9. * ( Storage condition) 10. * ( Countrys Registration Number) 11. * ( Name and address of Marketing Authorization Holder) 12. (* ( Name and address of manufacturer) 13. * (special labeling ) ,

30

14. * (Recommended Daily Allowance) 15. * (Warning) 16. (Pack sizes)

* exempted for small ampoule and vial

1. Inner Label 2. small ampoule and vial 3

(BLISTER/STRIPS) 1. (Product name ) 2. # ( Name of Active Ingredient(s) ) 3. # ( Strength of Active ingredient(s) ) 4. ( Batch number ) 5. ( Expiration date) 6. / //

(country specific) 7. ( Countrys Registration Number) (country specific) # 3 multivitamins and multiminerals 1. 6

2. 7

1. 2. 3 (Blister/Strips) Expiry date Exp 3.

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(PRODUCT INFORMATION)

3 1. Package insert 2. Summary of Product Characteristics Product Data Sheet 3. Patient Information Leaflet (PIL)

Package insert

1. (Product name) 2. (Name and strength of active ingredient (s)) 3. ( product description ) 4. / (Pharmacodynamic/Pharmacokinetics) 5. (Indication) 6. (Recommended Dose) 7. (Mode of Administration ) 8. ( Contraindication ) 9. (Warning and Precaution) 10. ( Interactions with Other Medicaments) 11. ( Pregnancy and Lactation) 12. (Undesirable Effects) 13. (Overdose and Treatment) 14. ( Storage Condition) 15. (Dosage Forms and Packaging Available) 16. (Name and Address

of Manufacturing / Marketing Authorization Holder) 17. (Date of revision of package insert)

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(Summary of Product Characteristics Product Data Sheet)

1. Name of the Medicinal Product 1.1 (Product Name) 1.2 (Strength) 1.3 ( Pharmaceutical Dosage Form)

2. ( Quality and Quantitative Composition) 2.1 (Qualitative Declaration)

INN hydrate form

2.2 (Quantitative Declaration) 1 ( per dosage unit) ( For metered dose inhalation product, per puff)

3. ( Pharmaceutical Form)

100 4. ( Clinical Particulars) 4.1 (Therapeutic indication) 4.2 (Posology and method of adminnistration) 4.3 (Contraindication) 4.4 (Special warning and precautions for use) 4.5 (Interaction with other medicinal products and

other forms of interactions) 4.6 (Pregnancy and lactation) 4.7 (Effects on ability to drive and use

machine) 4.8 (Undesirable effects) 4.9 (Overdose)

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5. ( Pharmacological Properties) 5.1 (Pharmacodynamic Properties) 5.2 (Pharmacokinetic properites) 5.3 (Preclinical Safety data)

6. ( pharmaceutical Particulars) 6.1 (List of excipient) 6.2 (Incompatibilities) 6.3 (Shelf life)

6.4 (Special precautions for storage) 6.5 (Nature and contents of container)

7. (Marketing Authorization

Holder) 8. ( Marketing Authorization Numbers) 9.(Date of authorization) 10. (Date of revision of the text)

Patient Information Leaflet PIL

1. ( Name of Product) 2. ( Description of Product) 3. ( What is in the medicine?) 4. (Strength of the medicine) 5. (What is this medicine used for?) 6. ( How much and how often should you use this

medicine?) 7. (When should you not take this medicine?) 8. (Undesirable effects) 9. (What other medicine or food

should be avoided whilst taking this medicine?)

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10. (What should you do if you miss a dose?) 11. (How should you keep this medicine?) 12. (Sign & Symptom of over dosages) 13. (What to do when you taken more than the

recommended dosage?) 14. / //

(Name / logo of manufacturer/ importer/ marketing authorization) 15. (Care that should be taken when taking this medicine?) 16. (When should you consult your doctor?) 17. (Date of revision of PIL)

36

... . . . . / 1 1. / ... /./. .... .. .....

.. (...)

...... .. ..

... (....)

...... .. ..

(New Drugs)

... .......

37

. . 1. () () () 2. (Safety Monitoring Programme) (Protocol) 3. () 4.

.. 2510 ( 5) .. 2530

().. (.... )

...... .. .. ().. (...)

38 ...... .. ..

... ..

Country Approval Date

Category / Condtion of

Approval

Indication Registration Name

Remark

() USA Canada UK Sweden Australia Japan

.. .

.

.

. .

Remark 1. Non Approval 2. Non Application

().. ()

...... .. .. () (....)

...... .. ..

. (Patent) (Non Patent)

39

Country Application Date Date of Patent granted Term of Protection

(Expiry Date) ()

.

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...... .. .. () (....)

...... .. ..

40 1.

2. 1 2529-30 2534 3.

41

.. / .. . () .

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42

5 : (checklist)

. ND1 . ND2 . ND3 . ND4

43 . ND 1 1

U (New Drugs) ASEAN HARMONIZATION.

1.

New Chemical Entity (NCE) New Indication (NI) New Combination (NCO) New Delivery System (ND)

New Route of Administration (NR) New Dosage form of Approved NCE (NDOS) New Strength of Approved NCE (NS)

2.

()

(Volume)

(Page) 1 (Part 1) : (ADMINISTRATIVE DATA AND PRODUCT INFORMATION)

A (Section A) : (Introduction) B (Section B) : ( Table of Contents) C (Section C) :

1. 1.1 ( .1) 1.2 ASEAN HARMONIZATION( .1)

2. (Certificates) 2.1

2.1.1 2.1.2 GMP

2.2 2.2.1

44 . ND 1 2

()

(Volume)

(Page) 2.2.2 (Certificate of Pharmaceutical Product)

2.2.3 GMP ( 2.2.2)

3. (Labeling) 4. (Product Information)

4.1 Summary of Product Characteristics (SPC) Product Data Sheet

4.2 (Package Insert, PI) 4.3 (Patient Information Leaflet, PIL)

5. / 5.1 ( .8)

5.2 ( .8)

6. (Applicant Declaration) 6.1 6.2 6.3 6.4 6.5 () 6.5.1

6.5.2 (/ )

6.5.3 6.5.4 ( )

6.5.5

45 . ND 1 3

()

(Volume)

(Page) 7. ( )

8. -

9. 2 (Part 2) : (QUALITY DOCUMENT)

3 (Part 3) : (NONCLINICAL DOCUMENT)

4 (Part 4) : (CLINICAL DOCUMENT)

___________________________

( )

___________________

*

*

*

*

*

*

*

*

*

*

46 . ND 1 4

1

...

...

...

...

...

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( )

___________________

2

...

...

...

...

__________________________

( )

___________________

. ND 2 1

47

U U(Checklist of ASEAN Common Technical Document : Part Quality)

1.



2.

()

(Volume)

(Page) A (Section A) : (Table of Contents) B (Section B) : (Quality Overall Summary)

S (Drug Substance) S1 (General Information)

S.1.1 (Nomenclature) S.1.2 (Structure) S.1.3 (General Properties)

S2 (Manufacture) S.2.1 () (Manufacturer(s)) S.2.2 (Description of Manufacturing Process and Process Controls)

S.2.3 (Control of Materials) S.2.4 (Controls of Critical Steps and Intermediates)

S.2.5 / (Process Validation and/or Evaluation)

. ND 2 2

48

()

(Volume)

(Page) S.2.6 (Manufacturing Process Development)

S3 (Characterisation) S.3.1 (Elucidation of Structure and Other Characteristics)

S.3.2 (Impurities) S4 (Control of Drug Substance)

S.4.1 (Specification) (Certificate of Analysis)

S.4.2 (Analytical Procedure) S.4.3 (Validation of Analytical Procedures)

S.4.4 (Batch Analysis) S.4.5 (Justification of Specification)

S5 (Reference Standards or Materials)

S6 (Container Closure System) S7 (Stability)

P (DRUG PRODUCT) P1 (Description and Composition) P2 (Pharmaceutical Development)

P.2.1 (Information on Development Studies)

P.2.2 (Components of the Drug Product)

P.2.3 (Finished Product) P.2.4 (Manufacturing Process Development)

P.2.5 (Container Closure System) P.2.6 (Microbiological Attributes) P.2.7 (Compatibilty)

. ND 2 3

()

(Volume)

(Page) P3 (Manufacture)

P.3.1 (Batch Formula) P.3.2 (Manufacturing Process and Process Controls)

P.3.3 (Controls of Critical Steps and Intermediates)

P.3.4 / (Process Validation and/or Evaluation)

P4 (Control of Excipients) P.4.1 (Specifications) (Certificate of Analysis)

P.4.2 (Analytical Procedure) P.4.3 (Excipients of Human or Animal Origin)

P.4.4 (Novel Excipients) P5 (Control of Finished Product)

P.5.1 (Specification) (Certificate of Analysis)

P.5.2 (Analytical Procedure) P.5.3 (Validation of Analytical Procedures)

P.5.4 (Batch Analyses) P.5.5 (Characterisation of Impurities)

P.5.6 (Justification of Specifications)

P6 (Reference Standards or Materials)

P7 (Container Closure System) P8 (Stability) P9 (Product Interchangeability Equivalence Evidence)

49

. ND 2 4

()

(Volume)

(Page) C (Section C) : (Body of Data) S (Drug Substance) S1 (General Information)

S.1.1 (Nomenclature) S.1.2 (Structure) S.1.3 (General Properties)

S2 (Manufacture) S.2.1 () (Manufacturer(s)) S.2.2 (Description of Manufacturing Process and Process Controls)

S.2.3 (Control of Materials) S.2.4 (Controls of Critical Steps and Intermediates)

S.2.5 / (Process Validation and/or Evaluation)

S.2.6 (Manufacturing Process Development)

S3 (Characterisation) S.3.1 (Elucidation of Structure and Other Characteristics)

S.3.2 (Impurities) S4 (Control of Drug Substance)

S.4.1 (Specification) (Certificate of Analysis)

S.4.2 (Analytical Procedure) S.4.3 (Validation of Analytical Procedures)

S.4.4 (Batch Analysis) S.4.5 (Justification of Specification)

50

. ND 2 5

()

(Volume)

(Page) S5 (Reference Standards or Materials)

S6 (Container Closure System) S7 (Stability)

P (DRUG PRODUCT) P1 (Description and Composition) P2 (Pharmaceutical Development)

P.2.1 (Information on Development Studies)

P.2.2 (Components of the Drug Product)

P.2.3 (Finished Product) P.2.4 (Manufacturing Process Development)

P.2.5 (Container Closure System) P.2.6 (Microbiological Attributes) P.2.7 (Compatibilty)

P3 (Manufacture) P.3.1 (Batch Formula) P.3.2 (Manufacturing Process and Process Controls)

P.3.3 (Controls of Critical Steps and Intermediates)

P.3.4 / (Process Validation and/or Evaluation)

P4 (Control of Excipients) P.4.1 (Specifications) (Certificate of Analysis)

P.4.2 (Analytical Procedure) P.4.3

51

. ND 2 6 52

(Excipients of Human or Animal Origin)

()

(Page) (Volume)

P.4.4 (Novel Excipients) P5 (Control of Finished Product)

P.5.1 (Specification) (Certificate of Analysis) P.5.2 (Analytical Procedure) P.5.3 (Validation of Analytical Procedures) P.5.4 (Batch Analyses) P.5.5 (Characterisation of Impurities)

P.5.6 (Justification of Specifications)

P6 (Reference Standards or Materials)

P7 (Container Closure System)

P8 (Stability) P9 (Product Interchangeability Equivalence Evidence)

D (Section D) : () (Key Literature Reference, if applicable)

___________________________

( )

___________________

* * * *

. ND 2 7 53 * ** 1

...

...

...

...

...

__________________________

( )

___________________

2

...

...

...

...

__________________________

( )

___________________

54 . ND 3

1 U

U(Checklist of ASEAN Common Technical Document : Part Nonclinical) 1.


New Route of Administration (NR) New Strength of Approved NCE (NS) New Dosage form of Approved NCE (NDOS)

2.

()

(Volume)

(Page) A (Section A) : (Table of Contents) B (Section B) : (Nonclinical Overview)

1. (General Aspects) 2. (Content and Structural Format)

C (Section C) : (Nonclinic Summary : Written and Tabulated)

1. (Nonclinical Written Summary )

1.1U (Pharmacology)U 1.1.1 (Primary Pharmacodynamics)

1.1.2 (Secondary Pharmacodynamics)

1.1.3 (Safety pharmacology)

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1.1.4 (Pharmacodynamic Drug Reactions)

1.2 U (Pharmacokinetics) U 1.2.1 ( Absorption) 1.2.2 ( Distribution) 1.2.3 (Metabolism) species ( inter species comparison)

1.2.4 (Excretion) 1.2.5 ( ) Pharmacokinetic Drug Interaction (Non-clinical)

1.2.6 (Other Pharmacokinetics Studies)

1.3 U (Toxicology)U 1.3.1 (Single Dose Toxicity )

1.3.2 ( Repeat Dose Toxicity )

1.3.3 ( Genotoxicity) 1.3.4 (Carcinogenicity) 1.3.5 (Reproductive and developmental Toxicity)

1.3.5.1 (Fertility and Early Embryotic Development)

1.3.5.2 - (Embryo-fetal Development)

1.3.5.3 (Pre-Natal and Post-Natal Development including Maternal Function )

1.3.6 ( Local Tolerance) 1.3.7 (Other Toxicity Studies, if available)

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(Page) 2. (Nonclinical Tabulated Summaries)

D (Section D) () (Nonclinical Study Report ( As requested))

1. (Table of Content) 2. (Pharmacology)

2.1 (Primary Pharmacodynamics) 2.2 (Secondary Pharmacodynamics) 2.3 (Safety Pharmacology) 2.4 (Pharmacodynamics Drug Interactions)

3. (Pharmacokinetics) 3.1 (Analytical Methods and Validation Reports)

3.2 (Absorption) 3.3 (Distribution) 3.4 (Metabolism) 3.5 (Excretion) 3.6 () Pharmacokinetics Drug Interaction (non-clinical)

3.7 (Other Pharmacokinetics studies)

4. (Toxicology) 4.1 (Single dose toxicity)

4.2 (Repeat dose toxicity) 4.3 (Genotoxicity)

4.3.1 (in vitro) 4.3.2 (in vivo)

4.4 (Carcinogenicity) 4.4.1 (Long-term studies)

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4.4.2 (Short or medium term studies)

4.4.3 (Other studies) 4.5 (Reproductive and developmental Toxicity)

4.5.1 (Fertility and Early Embryotic Development)

4.5.2 - (Embryo-fetal Development)

4.5.3 (Pre-Natal and Post-Natal Development including Maternal Function )

4.5.4 / (Studies in which the offspring are dosed and/or further evaluated)

4.6 ( Local tolerance) 4.7 ( ) (Other toxicity studies, if available)

4.7.1 (Antigenicity) 4.7.2. (Immunotoxicity) 4.7.3 (Dependence) 4.7.4 (Metabolites) 4.7.5 (Impurities) 4.7.6 (Other)

E (Section E) ( List of Key Literature Reference)

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59 . ND 4 1

U U(Checklist of ASEAN Common Technical Document : Part Clinic)

1.



2.

()

(Volumn)

(Page)

A (Section A) : (Table of Contents)

B (Section B) : (Clinical Overview)

1. (Product Development Rationale)

2. (Overview of Biopharmaceutics) 3. (Overview of Clinical Pharmacology)

4. (Overview of Efficacy) 5. (Overview of Safety) 6. (Benefits and Risks Conclusions)

C (Section C) :

(Clinical Summary)

1. (Summary of Biopharmaceutic Studies and Associated Analytical Method)

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(Volumn)

(Page) 1.1 (Background and Overview)

1.2 (Summary of Results of Individual Studies)

1.3 (Comparison and Analyses of Results Across Studies) 1 (Appendix 1)

2. (Summary of Clinical Pharmacology Studies)

2.1 (Background and Overview)

2.2 (Summary of

Results of Individual Studies)

2.3

(Comparison and Analyses of Results Across Studies)

2.4 (Special Studies) 2 (Appendix 2)

3. (Summary of Clinical Efficacy)

3.1

(Background and Overview of Clinical Efficacy)

3.2 (Summary of Results of Individual Studies)

3.3

(Comparison and Analyses of Results Across Studies)

3.4

(Analysis of Clinical Information Relevant to Dosing

Recommendations )

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3.5 /

(Persistence of Efficacy and/or Tolerance Effects)

3 ( Appendix 3)

4. (Summary of Clinical Safety)

4.1 (Exposure to the Drug)

4.2 (Adverse Events)

4.3 (Clinical Laboratory Evaluations)

4.4 , ,

(Vital Signs, Physical Findings,

and Other Observations Related to Safety )

4.5 (Safety in Special Groups and Situations)

4.6 (Post-marketing Data)

4 (Appendix 4)

5. (Synopses of Individual Studies)

Section D. ( Tabular Listing of All Clinical Studies)

Section E. (Clinical Study Reports (if applicable)

1. (Reports of Biopharmaceutic Studies)

1.1 BA (BA Study Reports)

1.2 BA BE (Comparative BA or BE Study Reports)

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1.3

(In vitro-In vivo Correlation Study

Reports)

1.4

(Reports of Bioanalytical and Analytical

Methods for Human Studies)

2. (Reports of Studies Pertinent to Pharmacokinetics using Human Biomaterials)

2.1 (Plasma

Protein Binding Study Reports)

2.2

(Reports of Hepatic Metabolism and Drug Interaction

Studies)

2.3 (Reports of

Studies Using Other Human Biomaterials)

3. (Reports of Human Pharmacokinetic (PK) Studies

3.1 PK

(Heatthy Subiect PK and Initial Tolerability Study Reports)

3.2 PK (Patient PK and Initial Tolerability Study Reports)

3.3 PK (Population

PK Study Reports)

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(Page) 4. (Reports of Human Pharmacodynamic (PD) Studies)

4.1 PD PK/PD

(Healthy Subject PD and PK/PD Study Reports)

4.2 PD PK/PD (Patient PD

and PK/PD Study Reports)

5. (Reports of Efficacy and Safety Studies)

5.1

(Study Reports of Controlled Clinical

Studies Pertinent to the Claimed Indication)

5.2

(Study Reports of Uncontrolled Clinical Studies

5.3

(Reports of Analyses of Data from More Than One Study,

Including Any Formal Integrated Analyses, Meta-analyses,

and Bridging Analyses )

5.4 (Other Clinical Study

Reports)

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6. (Reports of Post-Marketing Experience)

7. (Case Report Forms and Individual Patient Listing)

Section F. (List of Key Literature References)

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A (Introduction) NCE*NI*NCO*ND*NR*NDOS*NS*

.1

1. (DETAILS OF APPLICANT AND MANUFACTURER) ................................. ......................... ................................. ......................... ................................. ......................... 2. (DETAILS OF PRODUCT) 2.1 (Product Name, Dosage Form and Strength) (Generic Name)Quantity/unit dose

Explanatory notes

3 (LABELLING) (UNIT CARTON) INNER LABEL

(BLISTER/STRIPS) (PRODUCT INFORMATION)

4 .

4 .

1. (Table of Content)2.4 (Pharmacodynamics Drug Interactions) 3. (Pharmacokinetics) 4. (Toxicology)4.2 (Repeat dose toxicity)4.3 (Genotoxicity)

1 2

A (Section A) : (Table of Contents) B (Section B) : (Clinical Overview) C (Section C) : (Clinical Summary)

Section D. ( Tabular Listing of All Clinical Studies) Section E. (Clinical Study Reports (if applicable)

2

2

1 2

. 1

7. .. 7