appendix 3 application checklist actd

GUIDANCE ON MEDICINAL PRODUCT REGISTRATION IN SINGAPORE JANUARY 2009– APPLICATION CHECKLIST (ACTD)

APPENDIX 3 APPLICATION CHECKLIST (ACTD)

This Application Checklist should be used to ensure submission of a complete dataset in the ASEAN CTD format.

To use this Checklist, check against the dossier and application type for your submission.

For NDA and MAV-1 applications, the document shown in the second column has to be submitted if the symbol representing the dossier type viz. full dossier represented by , abridged dossier by and verification dossier by , and “ *” (under application type) appear on the same row. For GDA and MAV-2 applications, the “Dossier Type” column does not apply.

Application Type NDA GDA MAV-1 MAV-2

Dossier Type Full dossier Abridged dossier Verification dossier

Note: without the asterisk * indicates that the document shown in the second column of the same row may be optional depending on the application type/product/change concerned.

Please refer to the Guidance on Medicinal Product Registration in Singapore and the ASEAN guidance on ACTD for explanatory notes on the preparation of documents for a submission in ACTD format.

HEALTH SCIENCES AUTHORITY – HEALTH PRODUCTS REGULATION GROUP Appendix 3 - of 16


Part I – Administrative Documentation

Section Documents Dossier Type

Application Type ACTDVol/Page

(Vol __ Page __ to __)NDA MAV-1 GDA MAV-2

1.1 Comprehensive Table of Contents * * * *

Include a complete list of all documents provided in the application dossier by Part

The location of each document should be identified by the Part number

For hardcopy submissions, the location of each document should be identified by the volume number and tab identifiers (name of document or section heading according to ACTD format)

1.2 Introduction * * * *

Provide a concise and precise summary of the application

Justify the lack of certain documents and deviation(s) from guidelines

1.3 PRISM Application Form * * * *

1.3.1 Section 1: Company Particulars * *

Company shall be based and registered in Singapore

1.3.2 Section 2: Applicant particulars * * * *

Applicant must be a permanent staff of the company and is residing in Singapore. If the person making the application / correspondence person is an external party (consultant) engaged by the applicant company, an original letter of authorization from the applicant company must be submitted.

Company address and contact details can be entered instead of personal residential address and contact details

1.3.3 Section 3: Application Details

3.1 Type of Application * * * *

3.2 Type of Product * *

3.3 Reference Product *

All GDA applications – Specify Singapore Reference Product’s SIN number






If GDA-2 application not submitted at the same time as GDA-1 application – Specify both the Singapore Reference Product’s and the GDA-1 product’s SIN numbers

If NDA-3 applications not submitted at the same time as NDA-1/2 application – Specify the NDA-1/2’s SIN number

3.4 Product intended for export * *

3.5 Type of Dossier * *

3.6 Type of Format * *

1.3.4 Section 4: Product Information

4.1 Product name * *

Enter in the following format: Product Name - Dosage Form – Product Strength

Refer to Guidance document section 6.1.4 for additional pointers

4.2 Product Formula * *

Include the full composition of all active substances and excipients (including water) that are present in the final pharmaceutical dosage form

Ingredients related to the pharmaceutical dosage form, such as tablet film coating or capsule shell, should be indicated within parentheses before the ingredient name, e.g. (Film coating) Ingredient Z

For active ingredients presented in the form of salts and chelate, the quantity should be clearly stated, e.g., XX phosphate 32 mg (equivalent to XX)






Information on residual amounts of certain materials, such as antibiotics, thiomersal and materials of biological origin (e.g. human serum albumin), added or present in the drug product must be declared. Information to declare includes the following:o the material’s name – enter ‘(Residual)’, followed by the

material’s name in the Name of Substance field;o the material’s grade, if applicable;o the material’s limit in the product – enter ‘≤’, followed by the limit

in the Strength field.

4.3 Ingredients derived from human blood or animal sources * *

Information to be provided in the following format: (Species & product) – (In manufacturing/drug substance/excipient) – (Country)

4.4 ATC Code * *

4.5 Dosage Form * *

4.6 Route of Administration * *

Include all routes of administration proposed for the product

4.7 Packaging, Shelf Life & Storage Condition * *

Where more than one drug component is included in a drug product (e.g., powder for injection with solvent as composite pack) and each component has a different shelf life, the shorter shelf life is to be used as the shelf life of the composite pack

4.8 Forensic Classification * * *

4.9 Registration Status in Other Countries * * *

For each country - State the application status and status date

For country of origin and all reference agencies - State the application status, status date, application details and forensic classification

For products approved via an appeal process, following either a negative opinion/rejection/non-approvable decision or an approvable/conditional approvable decision – Provide reasons for the initial regulatory decision along with the subsequent approval






For applications submitted to the European Union agencies, the type of application – i.e. centralised, decentralised, mutual recognition or national, should be identified; For decentralised and mutual recognition applications, the reference member state should be indicated

For applications approved by the UK MHRA – Indicate whether approval was granted through national procedure or whether MHRA acted as RMS or CMS for decentralised and mutual recognition procedures in European Union

For NDA & GDA, the registration status of the product in other countries should be entered into PRISM

In the event that the PRISM text space does not allow input of full details of the indication(s), dosing regimen(s), and/or reason(s), a brief description may be entered; The full details should be attached in softcopy (PDF) in PRISM section 7 (Supporting Attachments) and in hardcopy in section 1.16 of the CTD Part 1

For MAV-1, the registration status should be attached in softcopy (PDF) in PRISM section 7 (Supporting Attachments) and in hardcopy in section 1.16 of the CTD Part 1

4.10 Product Owner * *

1.3.5 Section 5: Manufacturer’s Particulars * *

All manufacturers of active substance(s), drug product and diluent used to reconstitute the product (if packed and sold together with the drug product) must be declared

For secondary packagers, enter ‘(Secondary packager)’ after the name of the manufacturer

All manufacturers’ names and addresses should be consistent throughout all of the documents submitted in the application, such as GMP certificates, CPPs, Letters of authorisation, Part II of the CTD and so forth

1.3.6 Section 6: Batch Release Details * *

If there are multiple companies responsible for batch release, the applicant must declare all of the sites

1.3.7 Supporting Documents * * * *






Attach all documents relating to Part I of the CTD

Other Parts – Either attach in full in this PRISM section or submit soft copies in CD

1.4Labelling and PI/PIL proposed & currently approved in Singapore. For NDA and GDA only proposed labelling and PI/PIL need to be submitted Labelling must be in English; If non-English text is included in the labelling, applicants

must provide an official statement to declare that the non-English text is complete, accurate and unbiased information and is consistent with the English text

Highlight any non-English country-specific labelling requirements on the artwork/drafts if the labelling is shared with other countries

1.4.1 Outer/Carton Labels * *

1.4.2 Inner/Blister Labels * *

1.4.3 Package Insert (PI) 1.4.4 Patient Information Leaflet (PIL) *

1.5 Approved SmPC/PI/PIL

1.5.1 SmPC/PI/PIL approved by HSA’s reference regulatory agencies *

The approved SmPC / PI / PIL currently approved by each of HSA’s reference agencies should be submitted, where applicable

1.5.2 SmPC/PI/PIL approved by Country of Origin/Country of Manufacture 1.5.3 PI / SmPC / PIL approved by other regulatory agency

The approved SmPC / PI / PIL from the drug regulatory agency that issued the proof of approval, if different from the Country of Origin

1.5.4If applicable: declaration that the translation of the SmPC/PI/PIL conforms to the SmPC/PI/PIL currently approved

1.6Assessment report issued by HSA’s reference regulatory agency: (Please specify)

* *

1.7 Description of batch numbering system * *






1.8

Proof of Approval from: Country of Origin Reference Agency Others:

__________________________________________________ * * *

1.9

Proof of Approval from at least 2 of HSA’s reference regulatory agenciesPlease specify issuing agencies: __________________________________________________ * *

1.10 Authorisation Letters

All submitted authorisation letters shall be hardcopy originals on the authorising company’s (i.e. Product Owner’s) letterhead, dated and signed by the designated authorised person in the company

The names and addresses stated in the letters should be consistent with the information provided in application form and dossier

1.10.1 Authorisation Letter from Product Owner to the Applicant firm * *

This letter authorises the local applicant firm to apply for and be the Product Licence Holder for a specific medicinal product

1.10.2 Authorisation Letter from Product Owner to the Manufacturer(s) * *

This letter authorises the specified manufacturer to produce, pack and/or label the drug product intended for Singapore

If there are multiple drug product manufacturers, the applicant may opt to submit one authorisation letter which clearly states all of the manufacturers (names and addresses) and their responsibilities related to the drug product

For biologic drug products, an additional authorisation letter from the Product Owner to the Drug Substance Manufacturer is required

1.10.3 Authorisation Letter from Product Owner to the Batch Releaser * *

This letter authorises the specified company to test and batch release the drug product

1.11GMP certification/proof of GMP compliance for each finished product manufacturer inclusive secondary packer(s) * *

For biologics: GMP certification/proof of GMP compliance for each drug substance manufacturer must be provided






Proof of GMP compliance must not expire within 6 months from the time of submission to HSA

Diluents used for reconstituting the drug product and are packaged together with the drug product will be considered as part of the final drug product; Manufacturer(s) of the supplied diluent(s) will follow the same requirements applicable to the drug product – e.g. proof of GMP compliance

The names and addresses of manufacturer(s) / repacker(s) should be consistent with information provided in application form

1.12 Patent declaration form * *

The Patent Declaration form is required for each NDA and GDA

Under “Applicant Particulars”, name & address of the local applicant firm to be stated

Under “Product Particulars”, the product name is stated and it should be consistent with that stated in PRISM, the application form, all product labelling and all other relevant documents in the dossier

Under “Declaration”, the patent declaration must be signed by the Company Director, Company Secretary as registered with ACRA, or equivalent

1.13 Declaration on rejection, withdrawal and deferral * * *

1.14Declaration that Singapore product is identical to current approved product by reference agency *

Applies only to NDA verification dossier

1.15Registration Status in Other Countries as separate attachment in PRISM under [7] “Supporting Attachments” *

For NDA & GDA, registration status should be entered into PRISM section 4.9; In the event that the PRISM text space does not allow input of the full details of the indication(s) and/or reason(s), a brief description may be entered; The full details should then be attached in softcopy (PDF) in this PRISM section (“supporting attachments”) and in hardcopy in section 1.15 of the CTD Part 1

FOR MAV-1, registration status should be attached in this PRISM section (“supporting attachments”) and in hardcopy in section 1.15 of the CTD Part 1



Part II – Quality

Section DocumentDossier

Type

Application TypeACTD Vol /

Page (Vol __ Page __ to __)NDA MAV-1 GDA

For verification dossier – The submission should include Part II dossier as originally submitted to the reference agency, and any documentations submitted to the same reference agency in subsequent variations to the quality aspects of the product.

A Table of Contents of Part II * *

B Singapore Quality Overall Summary (QOS) & QOS in other format, if available * *

C Body of Data

Drug Substance (Active substance)

S1 General Information

S1.1 Nomenclature * *

S1.2 Structure * *

S1.3 General Properties * *

S2 Manufacture

S2.1 Manufacturer(s) * *

S2.2 Description of Manufacturing Process and Process Controls * *

S2.3 Control of Materials * *

S2.4 Controls of Critical Steps and Intermediates * *

S2.5 Process Validation and/or Evaluation * *

S2.6 Manufacturing Process Development * *

S3 Characterisation

S3.1 Elucidation of Structure and other Characteristics * *

S3.2 Impurities * *

S4 Control of Drug Substance

S4.1 Specification of Drug Substance * *




Type



S4.2 Analytical Procedures * *

S4.3 Validation of Analytical Procedures * *

S4.4 Batch Analyses * *

S4.5 Justification of Specification * *

S5 Reference Standards or Materials * *

S6 Container Closure System * *

S7 Stability

S7.1 Stability Summary and Conclusions * *

S7.2 Post-approval Stability Protocol and Stability Commitment * *

S7.3 Stability Data * *

Drug Product

P1 Description and Composition of the Drug Product * *

P2 Pharmaceutical Development

P2.1 Information on Development Studies * *

P2.2 Components of the Drug Product

P2.2.1 Active Ingredients * *

P2.2.2 Excipients * *

P2.3 Finished Product

P2.3.1 Formulation Development * *

P2.3.2 Overages * *

P2.3.3 Physicochemical and Biological Properties

P2.4 Manufacturing Process Development * *

P2.5 Container Closure System * *

P2.6 Microbiological Attributes * *




Type



P2.7 Compatibility * *

P3 Manufacture

P3.1 Batch Formula * *

P3.2 Description of Manufacturing Process And Process Controls * *

P3.3 Controls of Critical Steps and Intermediates * *

P3.4 Process Validation and/or Evaluation * *

P4 Control of Excipients

P4.1 Specifications * *

P4.2 Analytical Procedures * *

P4.3 Excipients of Human and Animal Origin * *

P4.4 Novel Excipients * *

P5 Control of Drug Product (Finished Product)

P5.1 Specification of Drug Product * *

P5.2 Analytical Procedures * *

P5.3 Validation of Analytical Procedures * *

P5.4 Batch Analyses * *

P5.5 Characterisation of Impurities * *

P5.6 Justification of Specifications * *

P6 Reference Standards or Materials * *

P7 Container Closure System * *

P8 Stability

P8.1 Stability Summary and Conclusions * *

P8.2 Post-approval Stability Protocol and Stability Commitment * *

P8.3 Stability Data * *




Type



P9 Product Interchangeability *

D Key Literature References *

Q Country-specific Quality Requirements

Q1 Checklist for Human Blood Product with the required supporting documents

Q2 TSE Checklist with the required supporting documents

Q3 Blank Production Batch Record

Q4 Appendices

A.1 Facilities and Equipment

A.2 Adventitious Agents Safety Evaluation

A.3 Novel Excipients



Part III – Non-clinical Data


Type



A Table of Content of Part III *

B Non-clinical Overview *

B1 General Aspect *

B2 Content and Structural Format *

C Non-clinical Summary (Written and Tabulated)

C1 Non-clinical Written Summary

C1.1 Pharmacology *

C1.2 Pharmacokinetics *

C1.3 Toxicology *

C2 Non-clinical Tabulated Summaries *

D Non-clinical Study Report

D1 Table of Content *

D2 Pharmacology

D2.1 Primary Pharmacodynamics *

D2.2 Secondary Pharmacodynamics *

D2.3 Safety Pharmacology *

D2.4 Pharmacodynamics Drug Interactions *

D3 Pharmacokinetics

D3.1 Analytical Methods and Validation Reports *

D3.2 Absorption *

D3.3 Distribution *

D3.4 Metabolism *

D3.5 Excretion *




Type



D3.6 Pharmacokinetics Drug Interaction (non-clinical) *

D3.7 Other Pharmacokinetics Studies *

D4 Toxicology

D4.1 Single-Dose Toxicity *

D4.2 Multiple-Dose Toxicity *

D4.3 Genotoxicity *

D4.4 Carcinogenicity *

D4.5 Reproductive and Developmental Toxicity *

D4.6 Local Tolerance *

D4.7 Other Toxicity Studies *

E List of Key Literature References *



Part IV – Clinical Data


Type


Page (Vol __ Page __ to __)NDA MAV-1 GDA MAV-2

A Table of Content of Part IV * *

B Clinical Overview * *

C Clinical Summary

C1 Summary of Biopharmaceutic Studies and Associated Analytical Methods *

C2 Summary of Clinical Pharmacology Studies *

C3 Summary of Clinical Efficacy * *

C4 Summary of Clinical Safety * * *

C5 Synopses of Individual Studies * *

D Tabular Listing of All Clinical Studies * *

E Clinical Study Reports

E1 Reports of Biopharmaceutic Studies

For Abridged and Verification Dossiers: only final study report(s) of biopharmaceutic studies to establish bioequivalence between commercial product formulation and clinical trial formulation used in pivotal studies should be submitted, if applicable

For Full Dossier, all biopharmaceutic study reports are required

E2 Reports of Studies Pertinent to Pharmacokinetics using Human Biomaterials *

E3 Reports of Human Pharmacokinetic (PK) Studies *

E4 Reports of Human Pharmacodynamic (PD) Studies *

E5 Reports of Clinical Efficacy and Safety Studies * *

For Full Dossier, reports of all clinical trials should be submitted, including the appendices & tables

For Abridged and Verification Dossiers, only study reports of pivotal or relevant clinical trials should be submitted (appendices & tables are required upon request by HSA)

E6 Reports of Post-marketing Experience *




Type


Page (Vol __ Page __ to __)NDA MAV-1 GDA MAV-2

E7 Case Reports Forms and Individual Patient Listing (required upon request by HSA)

F List of Key Literature References * *

G Other Supporting Documents


appendix 3 application checklist actd

Documents

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introduction formcheckbox

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application dossier

application details

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applicant company