02_Basics of Application Filing

7/29/2019 02_Basics of Application Filing

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All Rights Reserved 2008 Health Sciences Authority | 2

Basics of ApplicationFiling

Ms Jalene Poh

Senior Regulatory Specialist

Pharmaceuticals & Biologics BranchTherapeutics Products Division

Health Products Regulation Group

Health Sciences Authority




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

HSA’s commitment:Make quality, safe and effective medicines

available in Singapore in a timely manner

Need Pharma’s cooperation and support

Help Us Help You !




Screening Process

Application Submission

Screening

Issue Deficiency Letter

YOUR Stop-Clock

Screen Response

Acceptance

Join Evaluation Queue

Non-Acceptance

MajorDeficiencies

25 w.d.

Receipt of Complete Dossier




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-SubmissionPreparations




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 Preparations

• Pre-submission inquiry:

[email protected]• For issues on MIV submissions

– MIV Filing and Submission Inquiry Form (App 13)

– Include a copy of the Inquiry form in the MIVsubmission

• Pre-submission consultation

– For more complex issues

– Prior to a full dossier submission– Request via email to

[email protected]




New Drug Application

Generic Drug Application

- PRISM Application




PRISM Application

• Online applications via PRISM

(Pharmaceutical Regulatory and InformationSystem)

• Separate application form required for:

– Each pharmaceutical dosage form and strength

– Powder for injections containing different amountsof drug substance per container

– Concentrates for reconstitution labelled with theactual amount of drug substance before

reconstitution

– Pre-filled syringes

Pg13




PRISM Application

400 iu/4 ml

Submit as 2 separate applications:One as NDA-1/GDA-1 and the other as NDA-3/GDA-2

100 iu/mlPre-filledsyringe

5

Submit as a single application with two pack

sizes (i.e., 5ml and 10ml)

2mg/ml: presented

in 5ml vial and 10mlvial

Concentrate4

20mg/10ml


10mg/5mlConcentrate3

2mg/ml pre-filled

syringe


2mg/ml in a vialSolution forInjection

2

50mg/vial


25mg/vialPowder forInjection

1

Application typeLabelled strengthbefore

reconstitution

Examples




Section 1: Company particulars

Section 2: Applicant particulars

Pg14

Company address

may be entered

Direct telephone and faxnumbers in companymay be entered

PRISM Application




Section 3: Application details

PRISM ApplicationPg15




Section 3: Application details (cont’d)

• 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-1to GDA-1)

¨ Application to be withdrawn and submit newapplication

PRISM Application




PRISM Application

Section 3: Application details (cont’d)

• Reference Product (3.3):– NDA-3 application not submitted at the same time

as the NDA-1/2 application

¨ state NDA-1/2 product’s SIN no.

– All GDA applications¨ state Singapore Reference Product’s SIN no.

– GDA-2 application not submitted at the same timeas the GDA-1 application

¨ state both Singapore Reference Product andGDA-1 product’s SIN nos




Section 4: Product Information

Section 4.1: Product Name

• Product’s trade name shown on product labelling

ABC Injection 5mg/ml USP

ProductStandard(optional)

ProductStrength

PharmaceuticalDosage Form

Product Name

PRISM Application

Pg17




Trans-Patch® 24mg/24 hrsState the amount of activeingredient released in 2 4

h o u r s

Transdermal patches

Ingredient® 300mg per vialState the amount of activeingredient b e f o r e

reconstitution or dilution

Powder forreconstitution, injectionor infusion

Antibiotic® 200mg/5mLState the concentration a f t e r

reconstitutionPowder forreconstitution, oral

per mL, per puff, per drop,per kg, per m2, etc.

State the concentrationMulti-dose preparation

Ingredient® 300mg per vialState the amount of activeingredient per unit dose

Single-dose preparation,total use

Multi-Tab® Tablet

100mg/25mg

Strength of each active

ingredient separated by a ‘/’

Fixed-combination

ExampleFormatProduct

PRISM Application




Section 4.2: Product Formula





Section 4.2: Product Formula (cont’d)

• Ingredients related to pharmaceutical dosage form

Film coating ingredient

Printing ink

PRISM Application





• Active substance present in the form of a salt

Enter the strengthof the a c t i v e

s u b s t a n c e b a s e

here.

PRISM Application




This strengthwill actually beentered here


• Information on residual amounts of certain materials,such as antibiotics, thiomersal and materials of biological origin (e.g. human serum albumin), added orpresent in the drug product must be declared

PRISM Application




• Refer to Appendix 10 & 11 for details on datarequirements

PRISM Application

Section 4.3: Ingredients derived from Human

Blood/Animal Sources

Pg20




• Section 4.4: Pharmacotherapeutic group

• Section 4.5: Dosage form

• Section 4.6: Route of administration





PRISM Application

Section 4.7: Packaging, Shelf-life & StorageConditions

Pg23




PRISM Application




Section 4.8: Forensic Classification

• Prescription Only Medicine (POM)

• Pharmacy only medicine (P)

• General Sales List medicine (GSL)





PRISM Application Pg25

Section 4.9: Registration Status in Other Countries




State the expectedsubmission date

-PENDINGSUBMISSION

State the expected

regulatory decision date,if applicable

State the submission

date

PENDING

EVALUATION

For allreferenceagencies andcountry of origin (if

applicable)

State the approvedindication(s) and dosingregimen(s)

State the approvaldate

APPROVAL

State the reason(s)State the date of

deferment

DEFERRAL

State the reason(s)State the date of rejection/withdrawal

REJECTION orWITHDRAWAL

-State the approvaldateAPPROVALFor ALLcountries

Application DetailsStatus DateApplicationStatus

Country

PRISM Application




PRISM Application




Section 4.9: Registration Status in OtherCountries (cont’d)

• In the event that the PRISM text space does not allowinput of full details of the indication(s), dosingregimen(s), and/or reason(s), a brief description maybe entered

• The full details should be attached in softcopy (PDF) inPRISM section 7 (Supporting Attachments) and inhardcopy in section 1.16 of the CTD Module 1/Part 1

PRISM Application




POMAdjuvant treatment of colorectal cancer stage III(Dukes C) following complete removal of primary

tumour.Notice of Compliance with Conditions issued on 16April 2003 based on promising efficacy results withcondition to furnish confirmatory efficacy data

21 Nov 2004ApprovedCountry 4

POMAdjuvant treatment of colorectal cancer stage III(Dukes C) following surgery.

Submitted:15 Jun 2005

PendingCountry 5

POMIndication submitted ‘Adjuvant treatment of colorectalcancer’. Withdrawn due to insufficient long-term

efficacy data (only phase II data submitted). Re-submitted on 16 June 2005 with completed phase IIIdata for ‘Adjuvant treatment of colorectal cancerfollowing surgery’.

14 April 2002Withdrawnby applicant

Country 3

POMAdjuvant treatment of colorectal cancer followingsurgery

2 Feb 2006ApprovedCountry 2

POMAdjuvant treatment of colorectal cancer stage III

(Dukes C) following complete resection of primarytumour.

12 Jan 2005ApprovedCountry 1

Approvedforensic

classification

Approved application indication/dosing regimendetails

Status DateApplicationStatus

Country

PRISM Application




Section 4.10: Product Owner Information

– Input the full name and address of the legallyregistered owner of the product formulation, i.e.the drug product





PRISM Application

Section 5: Manufacturers’ Particulars

Pg29




Section 5: Manufacturers’ Particulars (cont’d)

• Enter information on all manufacturers of activesubstance(s), drug product and diluent used toreconstitute the product (if packed and sold togetherwith the drug product)

• For secondary packagers, enter ‘(Secondary packager)’

after the name of the manufacturer

• All manufacturers’ names and addresses should beconsistent throughout all of the documents submittedin the application, such as GMP certificates, CPP’s,

Letters of Authorisation, Module 3/Part II of the CTDand so forth

PRISM Application




Section 6: Batch Release Details





Section 7: Supporting Documents

• Before completion of the application, applicants mustattach all Module 1/Part 1 documents into this PRISMsection

• Notes:

– Use Portable Document Format (PDF) whenever possible

– Do not combine documents if the content is unrelated

– Ensure that the documents are appropriately named foreasier recognition to facilitate screening

– During scanning of documents, applicants are advised

not to break seals of authenticated documents as this willrender them invalid





PRISM Application






- Dossier Requirements




• The submission of the complete dossiershould take place within 2 working days afterthe PRISM application submission to preventdelays in processing of the application

• The date of submission will be defined as the

date when HSA receives the complete datasetfor the application

• Dossier requirements for each applicationtype & dossier type

– Main guidance document

– Application Checklists (Appendix 2/3)

Dossier RequirementsPg31




Dossier Requirements






- Submission Requirements




Submission Requirements

Requirement of both hard and soft copiesof submission dossier

Default: Electronic Copy Only




• An electronic copy of the complete CTDdossier is to be submitted with the application

– Module 1/Part 1 in PRISM section 7

– Remaining Modules/Parts in PRISM or CD

Don’t combine PRISM attachments with a CDsubmission

• Hardcopy submission of all admin documentsin CTD Module 1/Part 1 still required

• When applicable, upon acceptance, additional

copy(ies) of clinical documents (in CD) maybe requested

Submission RequirementsPg37




• Do’s

– Ensure that e-copies for scanned documents are

legible

– For CD submission, organise the dossier in the CTDformat, using folders and subfolders and includebookmarks

– Ensure access to CD is not restricted (or providepassword for access)

– Electronic copies are identical to the hardcopydocuments (for admin documents)

Submission Requirements






- Documentary Requirements

D t R i t




1.1: Comprehensive Table of Contents

1.2: Introduction

1.3: Application form

1.4: Labelling, PI, PIL

– Separate drafts for each different pack size

– Must be in English; If not, provide an officialstatement to declare that the non-English text iscomplete, accurate and unbiased information and isconsistent with the English text

– Refer Appendix 6 for specific details of labellingrequirements

Documentary Requirements

- Administrative DocumentsPg40

D t R i t




1.5: Approved SmPC/PI/PIL

– Country of Origin

– Agency that issued proof of approval (if not COO)

– Each of HSA’s reference agencies (if approved)

1.6: Assessment report from Reference Agency

1.7: Description of Batch Numbering System1.8, 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– Section 2: Product Particulars

Product name is stated and it should be consistent with thatstated in PRISM, all product labelling and all other relevantdocuments in the dossier

– Section 8: Declaration

Signed by person authorised to make the declaration onbehalf 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 thecompany, or an extract of the relevant portion of thecompany’s articles of association







1.13: Declaration on rejection, withdrawal and

deferral

1.14: Declaration for NDA verification

– Only for NDA verification dossiers

1.15: Registration status in other countries


- Administrative Documents Pg44





• CTD Overview and Summaries

– Module 2 of the ICH CTD

– Relevant sections in Part 2, 3 and 4 of the ACTD

• Quality Documents

– Complete Module 3/Part 2

• Non-clinical Documents (NDAs only)

– Full dossier: Complete set of Module 4/Part 3

– Other dossier types: Non-clinical overview


- Technical DocumentsPg44

Pg48





• Clinical (NDAs only)

– Full dossier: Complete Module 5/Part 4

– Other dossier types: Study reports of pivotal clinicalstudies

Studies should be conducted using the proposedcommercial formulation, and in the appropriate

patient population for the proposed indication(s) anddosing regimen

Biopharmaceutic study reports are required if thecommercial formulation differ from the clinical trialformulation used in the pivotal clinical studies


- Technical DocumentsPg49




Post-ApprovalVariation Application




PRISM Application• Similar to NDA/GDA application

• Some fields would not be editable dependingon the application type

• Detail all proposed change(s) in theAmendment Summary section

Pg54




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 newapplication

Pg52




Submission Requirements• The submission of the complete dossier should take

place within 2 working days after the PRISM application

submission to prevent delays in processing of theapplication

• The date of submission will be defined as the datewhen 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




Screening Process


Screening

Issue Deficiency Letter

YOUR Stop-Clock

Screen Response

Acceptance


Non-Acceptance

MajorDeficiencies

25 w.d.


Screening Process




Sc ee g ocess


Screening

Acceptance


25 w.d.





Thank You

02_Basics of Application Filing

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