02 - Basics of Application Filing

Basics of Application Filing
Ms Jalene Poh Senior Regulatory Specialist Pharmaceuticals & Biologics Branch Therapeutics Products Division Health Products Regulation Group Health Sciences Authority
All Rights Reserved 2008 Health Sciences Authority | 2
Agenda
Introduction Pre-submission Preparations New Drug/Generic Drug Applications
PRISM Application Dossier Requirements Submission Requirements Documentary Requirements
Post-Approval Variation Applications

PRISM Application Dossier & Submission Requirements Documentary Requirements
Final Note
Introduction
Medicinal Product Registration

HSAs commitment: Make quality, safe and effective medicines available in Singapore in a timely manner Need Pharmas cooperation and support Help Us Help You !
Screening Process
Application Submission Receipt of Complete Dossier Screening 25 w.d. Issue Deficiency Letter Non-Acceptance YOUR Stop-Clock Screen Response Acceptance Join Evaluation Queue
Major Deficiencies
Importance of a Proper Submission

Importance of getting the application submission right the first time
Prevent non-acceptance Reduce YOUR screening deficiencies Reduce YOUR stop-clock time
Reduce overall processing timeline for YOUR application Familiarise yourself with the requirements Consult HSA
Pre-Submission Preparations
Compiling all necessary documents Organise in CTD format Discuss with HSA:
Clarifications/questions Difficulties in meeting requirements Alternative proposals Pg12
Pre-submission inquiry: HSA_MedProd_Registration@hsa.gov.sg For issues on MIV submissions
MIV Filing and Submission Inquiry Form (App 13) Include a copy of the Inquiry form in the MIV submission
Pre-submission consultation
For more complex issues Prior to a full dossier submission Request via email to HSA_MedProd_Registration@hsa.gov.sg
New Drug Application Generic Drug Application - PRISM Application
PRISM Application
Pg13
Online applications via PRISM (Pharmaceutical Regulatory and Information System) Separate application form required for:
Each pharmaceutical dosage form and strength Powder for injections containing different amounts of drug substance per container Concentrates for reconstitution labelled with the actual amount of drug substance before reconstitution Pre-filled syringes
PRISM Application
Examples Labelled strength before reconstitution 25mg/vial 50mg/vial 2 Solution for Injection 2mg/ml in a vial 2mg/ml pre-filled syringe 3 Concentrate 10mg/5ml 20mg/10ml 4 Concentrate 2mg/ml: presented in 5ml vial and 10ml vial 100 iu/ml 400 iu/4 ml Application type 1 Powder for Injection Submit as 2 separate applications: One as NDA-1/GDA-1 and the other as NDA3/GDA-2 Submit as 2 separate applications: One as NDA-1/GDA-1 and the other as NDA2/GDA-1 Submit as 2 separate applications: One as NDA-1/GDA-1 and the other as NDA3/GDA-2 Submit as a single application with two pack sizes (i.e., 5ml and 10ml) Submit as 2 separate applications: One as NDA-1/GDA-1 and the other as NDA3/GDA-2
Pre-filled syringe
PRISM Application
Section 1: Company particulars Section 2: Applicant particulars
Pg14
Company address may be entered
Direct telephone and fax numbers in company may be entered
PRISM Application
Section 3: Application details
Pg15
PRISM Application
Section 3: Application details (contd) Type of application (3.1):
Change within same application type (e.g. NDA-2 to NDA-3) Input request to amend Change to a different application type (e.g. NDA-1 to GDA-1) Application to be withdrawn and submit new application
PRISM Application
Section 3: Application details (contd) Reference Product (3.3):
NDA-3 application not submitted at the same time as the NDA-1/2 application state NDA-1/2 products SIN no. All GDA applications state Singapore Reference Products SIN no. GDA-2 application not submitted at the same time as the GDA-1 application state both Singapore Reference Product and GDA-1 products SIN nos
PRISM Application
Section 4: Product Information
Pg17
Section 4.1: Product Name

Products trade name shown on product labelling
Product Name Pharmaceutical Dosage Form Product Strength Product Standard (optional)
ABC
Injection
5mg/ml
USP
PRISM Application
Product Fixed-combination Format Strength of each active ingredient separated by a / State the amount of active ingredient per unit dose State the concentration Example Multi-Tab Tablet 100mg/25mg Ingredient 300mg per vial
Single-dose preparation, total use Multi-dose preparation
per mL, per puff, per drop, per kg, per m2, etc. Antibiotic 200mg/5mL
Powder for reconstitution, oral Powder for reconstitution, injection or infusion Transdermal patches
State the concentration after reconstitution State the amount of active ingredient before reconstitution or dilution State the amount of active ingredient released in 24 hours
Ingredient 300mg per vial
Trans-Patch 24mg/24 hrs
PRISM Application
Section 4.2: Product Formula
Pg18
PRISM Application
Section 4.2: Product Formula (contd)
Ingredients related to pharmaceutical dosage form
Film coating ingredient
Printing ink
PRISM Application
Active substance present in the form of a salt
Enter the strength of the active substance base here.
PRISM Application
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
This strength will actually be entered here
PRISM Application
Pg20
Section 4.3: Ingredients derived from Human Blood/Animal Sources

Refer to Appendix 10 & 11 for details on data requirements
PRISM Application
Section 4.4: Pharmacotherapeutic group Section 4.5: Dosage form Section 4.6: Route of administration
Pg21
PRISM Application
Section 4.7: Packaging, Shelf-life & Storage Conditions
Pg23
PRISM Application
PRISM Application
Section 4.8: Forensic Classification
Prescription Only Medicine (POM) Pharmacy only medicine (P) General Sales List medicine (GSL)
Pg24
PRISM Application
Pg25
Section 4.9: Registration Status in Other Countries
PRISM Application
Country For ALL countries Application Status APPROVAL REJECTION or WITHDRAWAL DEFERRAL For all reference agencies and country of origin (if applicable) APPROVAL Status Date State the approval date State the date of rejection/withdrawal State the date of deferment State the approval date State the submission date State the reason(s) State the reason(s) State the approved indication(s) and dosing regimen(s) State the expected regulatory decision date, if applicable State the expected submission date Application Details
PENDING EVALUATION PENDING SUBMISSION
PRISM Application
PRISM Application
Section 4.9: Registration Status in Other Countries (contd)
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 Module 1/Part 1
PRISM Application
Country Application Status Approved Status Date Approved application indication/dosing regimen details Adjuvant treatment of colorectal cancer stage III (Dukes C) following complete resection of primary tumour. Adjuvant treatment of colorectal cancer following surgery Indication submitted Adjuvant treatment of colorectal cancer. Withdrawn due to insufficient long-term efficacy data (only phase II data submitted). Resubmitted on 16 June 2005 with completed phase III data for Adjuvant treatment of colorectal cancer following surgery. Adjuvant treatment of colorectal cancer stage III (Dukes C) following complete removal of primary tumour. Notice of Compliance with Conditions issued on 16 April 2003 based on promising efficacy results with condition to furnish confirmatory efficacy data Adjuvant treatment of colorectal cancer stage III (Dukes C) following surgery. Approved forensic classification POM Country 1 12 Jan 2005
Country 2 Country 3
Approved Withdrawn by applicant
2 Feb 2006 14 April 2002
POM POM
Country 4
Approved
21 Nov 2004
POM
Country 5
Pending
Submitted: 15 Jun 2005
POM
PRISM Application
Section 4.10: Product Owner Information
Pg28
Input the full name and address of the legally registered owner of the product formulation, i.e. the drug product
PRISM Application
Section 5: Manufacturers Particulars
Pg29
PRISM Application
Section 5: Manufacturers Particulars (contd)
Enter information on all manufacturers of active substance(s), drug product and diluent used to reconstitute the product (if packed and sold together with the drug product) 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, Module 3/Part II of the CTD and so forth
PRISM Application
Section 6: Batch Release Details
Pg29
PRISM Application
Section 7: Supporting Documents
Pg30
Before completion of the application, applicants must attach all Module 1/Part 1 documents into this PRISM section Notes:
Use Portable Document Format (PDF) whenever possible Do not combine documents if the content is unrelated Ensure that the documents are appropriately named for easier recognition to facilitate screening During scanning of documents, applicants are advised not to break seals of authenticated documents as this will render them invalid
PRISM Application
New Drug Application Generic Drug Application - Dossier Requirements
Dossier Requirements
Pg31
The submission of the complete dossier should take place within 2 working days after the PRISM application submission to prevent delays in processing of the application The date of submission will be defined as the date when HSA receives the complete dataset for the application Dossier requirements for each application type & dossier type
Main guidance document Application Checklists (Appendix 2/3)
New Drug Application Generic Drug Application - Submission Requirements
Submission Requirements
Requirement of both hard and soft copies of submission dossier

Default: Electronic Copy Only
Pg37
An electronic copy of the complete CTD dossier is to be submitted with the application
Module 1/Part 1 in PRISM section 7 Remaining Modules/Parts in PRISM or CD
Dont combine PRISM attachments with a CD submission
Hardcopy submission of all admin documents in CTD Module 1/Part 1 still required When applicable, upon acceptance, additional copy(ies) of clinical documents (in CD) may be requested
Dos
Ensure that e-copies for scanned documents are legible For CD submission, organise the dossier in the CTD format, using folders and subfolders and include bookmarks Ensure access to CD is not restricted (or provide password for access) Electronic copies are identical to the hardcopy documents (for admin documents)
New Drug Application Generic Drug Application - Documentary Requirements
Documentary Requirements - Administrative Documents

1.1: 1.2: 1.3: 1.4: Comprehensive Table of Contents Introduction Application form Labelling, PI, PIL
Pg40
Separate drafts for each different pack size Must be in English; If not, provide an official statement to declare that the non-English text is complete, accurate and unbiased information and is consistent with the English text Refer Appendix 6 for specific details of labelling requirements

1.5: Approved SmPC/PI/PIL
Pg41 Country of Origin Agency that issued proof of approval (if not COO) Each of HSAs reference agencies (if approved)
1.6: Assessment report from Reference Agency 1.7: Description of Batch Numbering System 1.8, 1.9: Proof of Approval 1.10: Authorisation Letters 1.11: GMP Certification
Must not expire within 6 months from the time of submission

1.12: Patent Declaration Form
Section 1: Applicant Particulars
Name & address of local applicant firm Product name is stated and it should be consistent with that stated in PRISM, all product labelling and all other relevant documents in the dossier Signed by person authorised to make the declaration on behalf of the applicant ,e.g. the Company Director, Company Secretary as registered with ACRA, or equivalent Evidence of authorisation to be submitted, e.g. resolution of board of directors, resolution of a general meeting of the company, or an extract of the relevant portion of the companys articles of association
Pg43
Section 2: Product Particulars
Section 8: Declaration

1.13: Declaration on rejection, withdrawal and deferral 1.14: Declaration for NDA verification
Only for NDA verification dossiers
Pg44
1.15: Registration status in other countries
Documentary Requirements - Technical Documents

CTD Overview and Summaries
Module 2 of the ICH CTD Relevant sections in Part 2, 3 and 4 of the ACTD Pg44
Quality Documents
Complete Module 3/Part 2 Pg48
Non-clinical Documents (NDAs only)

Full dossier: Complete set of Module 4/Part 3 Other dossier types: Non-clinical overview
Documentary Requirements - Technical Documents

Clinical (NDAs only)
Pg49 Full dossier: Complete Module 5/Part 4 Other dossier types: Study reports of pivotal clinical studies
Studies should be conducted using the proposed commercial formulation, and in the appropriate patient population for the proposed indication(s) and dosing regimen Biopharmaceutic study reports are required if the commercial formulation differ from the clinical trial formulation used in the pivotal clinical studies
Post-Approval Variation Application
PRISM Application
Pg54
Similar to NDA/GDA application Some fields would not be editable depending on the application type Detail all proposed change(s) in the Amendment Summary section
PRISM Application
Section 3.1: Type of Application
Change from MIV to MAV-1, MIV-2 to MIV-1, or vice versa Application to be withdrawn and submit new application
Pg52
The submission of the complete dossier should take place within 2 working days after the PRISM application submission to prevent delays in processing of the application The date of submission will be defined as the date when HSA receives the complete dataset for the application An electronic copy of the CTD dossier is to be submitted with the application
Module 1/Part 1 in PRISM section 7 Remaining Modules/Parts in PRISM or CD
Hardcopy submission of all admin documents in CTD Module 1/Part 1 still required
Documentary Requirements
MAV-1
Detailed in the Application Checklists (Appendix 2/3)
MAV-2
Detailed in Section 10.3.2 (page 59-60)
MIV-1/MIV-2
Detailed in Minor Variation Guidelines (Appendix 14/15)
Final Note
Screening Process
Application Submission Receipt of Complete Dossier Screening 25 w.d. Issue Deficiency Letter Non-Acceptance YOUR Stop-Clock Screen Response Acceptance Join Evaluation Queue
Major Deficiencies
Screening Process
Application Submission Receipt of Complete Dossier Screening 25 w.d.
Acceptance Join Evaluation Queue

Thank You

02 - Basics of Application Filing

Încărcat de

Informații document

Titlu original

Drepturi de autor

Formate disponibile

Partajați acest document

Partajați sau inserați document

Opțiuni de partajare

Vi se pare util acest document?

Este necorespunzător acest conținut?

Drepturi de autor:

Formate disponibile

02 - Basics of Application Filing

Încărcat de

Drepturi de autor:

Formate disponibile

Basics of Application Filing

All Rights Reserved 2008 Health Sciences Authority | 2

Post-Approval Variation Applications

All Rights Reserved 2008 Health Sciences Authority | 4

Medicinal Product Registration

All Rights Reserved 2008 Health Sciences Authority | 5

Importance of a Proper Submission

All Rights Reserved 2008 Health Sciences Authority | 7

All Rights Reserved 2008 Health Sciences Authority | 8

All Rights Reserved 2008 Health Sciences Authority | 9

All Rights Reserved 2008 Health Sciences Authority | 10

New Drug Application Generic Drug Application - PRISM Application

All Rights Reserved 2008 Health Sciences Authority | 11

All Rights Reserved 2008 Health Sciences Authority | 12

All Rights Reserved 2008 Health Sciences Authority | 13

Company address may be entered

Direct telephone and fax numbers in company may be entered

All Rights Reserved 2008 Health Sciences Authority | 14

All Rights Reserved 2008 Health Sciences Authority | 15

All Rights Reserved 2008 Health Sciences Authority | 16

All Rights Reserved 2008 Health Sciences Authority | 17

Section 4.1: Product Name

All Rights Reserved 2008 Health Sciences Authority | 18

Single-dose preparation, total use Multi-dose preparation

Ingredient 300mg per vial

Trans-Patch 24mg/24 hrs

All Rights Reserved 2008 Health Sciences Authority | 19

All Rights Reserved 2008 Health Sciences Authority | 20

Film coating ingredient

All Rights Reserved 2008 Health Sciences Authority | 21

Enter the strength of the active substance base here.

All Rights Reserved 2008 Health Sciences Authority | 22

This strength will actually be entered here

All Rights Reserved 2008 Health Sciences Authority | 23

Section 4.3: Ingredients derived from Human Blood/Animal Sources

All Rights Reserved 2008 Health Sciences Authority | 24

All Rights Reserved 2008 Health Sciences Authority | 25

All Rights Reserved 2008 Health Sciences Authority | 26

All Rights Reserved 2008 Health Sciences Authority | 27

All Rights Reserved 2008 Health Sciences Authority | 28

Section 4.9: Registration Status in Other Countries

All Rights Reserved 2008 Health Sciences Authority | 29

PENDING EVALUATION PENDING SUBMISSION

All Rights Reserved 2008 Health Sciences Authority | 30

All Rights Reserved 2008 Health Sciences Authority | 31

All Rights Reserved 2008 Health Sciences Authority | 32

Approved Withdrawn by applicant

2 Feb 2006 14 April 2002

Submitted: 15 Jun 2005

All Rights Reserved 2008 Health Sciences Authority | 33

All Rights Reserved 2008 Health Sciences Authority | 34

All Rights Reserved 2008 Health Sciences Authority | 35

All Rights Reserved 2008 Health Sciences Authority | 36

All Rights Reserved 2008 Health Sciences Authority | 37

All Rights Reserved 2008 Health Sciences Authority | 38

All Rights Reserved 2008 Health Sciences Authority | 39

New Drug Application Generic Drug Application - Dossier Requirements

All Rights Reserved 2008 Health Sciences Authority | 40

All Rights Reserved 2008 Health Sciences Authority | 41

All Rights Reserved 2008 Health Sciences Authority | 42

All Rights Reserved 2008 Health Sciences Authority | 43

New Drug Application Generic Drug Application - Submission Requirements

All Rights Reserved 2008 Health Sciences Authority | 44