Development and eCTD submission Process & Contents

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Rajeev Kashyap TIPT

Time

Personnel

Methods Materials

Environment Communication

Initiating Process Planning Executing

Cost cutting &Processing Time

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The XML eCTD DTD describes the hierarchical structure according to the CTD as defined by the ICH M4 Expert Working Group.

The XML eCTD instance covers the entire submission including all hierarchical levels and includes references to each individual file.

The submission should include a Style sheet that supports presentation of the XML

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Directory Structure: A structure of directory and files

XML eCTD: Intention to have links from leaf element. eCTD empty template included in ICH Web site be available for 50 years in PDF –XML(Extensible mark-up language) and the graphics in JPEG, PNG,SVG, GIF format. eCTD should have checksums for each file. Contents file.

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The number of eSubmissions to the FDA now over 60,000 . Regulatory agencies in the U.S., EU, Japan, and Canada in

the areas of eSubmission strategy, document and records management,

Compliance software integration.• Efficiency• Problems with paper• Industry and modern trends• Competitive edge • FDA “encouragement”

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• New Drug Applications (NDAs)• Supplemental NDAs (sNDAs)• Investigational New Drug

Exemptions (INDs)• Clinical Trial Authorization

(CTAs) filed in EU

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Electronic versions of Agency-Required Regulatory Submissions

• IND, NDA, BLA, Correspondences, Safety Reports

• CTA - other marketing apps… • eCTD vs. hybrid esub• Format: PDF, XML, SAS, MSWord, JPG

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ICH - guidelines The eCTD has five modules 1 Administrative Information and

Prescribing Information 2 Common Technical Document

Summaries 3 Quality 4 Nonclinical Study Reports 5 Clinical Study Reports

There are two categories of modules:

Regional module: 1 (different for each region; i.e., country)

Common modules: 2-5 (common to all the regions)

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Not part of the eCTD

Regional Administrative information

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Rajeev Kashyap TIPT

Regional guidance will provide the specific instructions on how to provide the administrative forms and detailed prescribing information.

There will be local requirements for both the content and electronic component of module 1.

The eCTD backbone was developed to enable the transfer of the regional information included in a regulatory dossier

A description of the submission including appropriate regulatory information.

A listing of the sections of the submission filed as paper, electronic, or both paper and electronic.

A description of the electronic submission including type and number of electronic media,

Approximate size of the submission, and if appropriate, characteristics concerning the media (e.g.,format used for DLT tapes) .

A statement that the submission is virus free with a description of the software used.

The regulatory and information technology points of contact for the submission

Administrative Information & Prescribing Information.

Cover LetterForm 356hlabelling information (Draft)Cartoon and Containers LabelsClinical Trials label.Pack insertsInvestigator BoucherFinancial DisclosureExclusivity CertificatePatent certificateRisk management plan

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Rajeev Kashyap TIPT

A document can be equated to a file for an electronic submission .

A document is defined for a paper submission as a set of pages, numbered sequentially and divided from other documents by a tab

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The granularity of the paper and electronic submissions should be equivalent, although if a paper submission is updated to be an electronic submission, some changes in granularity could be introduced to facilitate on-going lifecycle management.

Optionality of granularity for the Quality Overall Summary is provided in order to accommodate different levels of complexity of products. The applicant can choose the level at which the QOS is managed.

One document should be submitted for each drug substance For a drug product supplied with reconstitution diluent(s), the

information on the diluent(s) should be provided in a separate part “P” document

One document for each indication should be submitted, although closely related indications can be within a single document

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<m3-2-s-2-manufacture> <m3-2-s-2-1-manufacturer> <leaf ID="xxx" operation = "new" xlink:type =

"simple“ checksum-type="md5" checksum= "xxx" xlink:href =

"m3/32-body-data/32s-drug-sub/xxx/32s2-manuf/xxx" application-version = "xxx">

<title>xxx</title> </leaf> </m3-2-s-2-1-manufacturer>

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Building blocks: PDF files for text* MD5 transport files for checksum data*

Connected through XML backbone Looks like a web page Viewing Links and bookmarks Search keywords, metadata Managing lifecycle (Append, Replace, Delete)

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• Document Storage and Transfer

• EDMS v/s file system

• Balance version control, security and flexibility

• Acrobat

• Conversion from MSWord

• PDF version compatibility

• Plug-in Tools

• Publishing PDF docs

• Bookmarks, links, …

• In addition to esub tools:

• eCTD Compiler Tool• Major IT project!• Validation/upgrade• Migration• Implementation• External Links

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• Regulatory submission strategy and technology

• Electronic and paper submissions to Regulatory Agencies for drug registration

• Template for authoring regulatory docs

• eCTD, hybrid electronic submissions

• Liaise with FDA on Esub requirements

• SPL - Structured Product Labeling

• Gateway implementation

• Fill able forms + Digital Sigs: 356h, 1571…

• Submission lifecycle tracking + archiving

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• Drive electronic submission acceptance and adoption within company

• Lead software implementation projects

• Cross functional training and awareness of Esub initiatives

• Esub guidance and specification interpretation

• Keep Upper Management informed of:

• new regulatory submission requirements

• how to adopt new technology and processes to sustain competitive advantage

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PAPER V/S PAPER V/S EESUB COMPARISONSUB COMPARISON

• E-publishing software

• Authoring templates - MSWord

• Volumization

• Volume TOC creation

• Overlays: page stamps, master headers/footer info

• Print: multiple copies

• E-publishing software

• Still based on e-templates

• Document info, descriptive metadata*

• PDF Table of contents creation*

• Navigation: Bookmarks, links (automation key)

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• Clinical QC √-list• Medical Writing √-list• QA reports• Publishing work practices• CLINICAL SUMMARY REPORTS Publishing

work practice• CSR Appendix √-list• Electronic PDF √-list• Guide for eSub ready Docs• Scanned Document √-list• eQC √-list

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• eCTD Taskforce: Reg Ops, Reg Affairs, Medical Writing, and other functional group representation

• Company-wide “awareness”

• Presentations at Project Team meetings

• Templates and Training

Process Agreements

• eCTD Task force

• Med Writing – Reg. Ops – Data Mgt – other functional group reps

• File Transfer• EDMS• File share• eRooms• eArchival

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STRENGTHS WEAKNESS

OPPORTUNITIES THREATS

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• Electronic Submissions Gateway• created as required by [The

Prescription Drug User Fee Act ] PDUFA IV legislation as the single point of entry for the receipt and processing of electronic submissions to the FDA

PDUFA enable FDA to accelerate its drug evaluation process without compromising review quality.  

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New Drug Applications (NDAs)CDER Central Document Room:FDA/Center for Drug Evaluation and Research (CDER)Central Document Room (CDR)5901-B Ammendale RoadBeltsville, MD 20705-1266

Abbreviated New Drug Applications (ANDAs)Office of Generic Drugs7500 Standish PlaceRockville, MD 20855

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Rajeev Kashyap TIPT

ICH Website: http://www.ich.org/cache/compo/276-254-1.html SPL Resources: http://www.fda.gov/oc/datacouncil/spl.html

CPage:  http://www.fda.gov/cder/regulatory/ersr/ectd.htm Submit electronically via the Gateway: http://www.fda.gov/esg/CDER's eCTD Validation Criteria:  http://www.fda.gov/cder/regulatory/ersr/validation_specs.htm

Daily Med Approved Labels: http://dailymed.nlm.nih.gov/dailymed/drugList.cfm?startswith=T CDISC Standards:

http://www.cdisc.org/models/def/v1.0/index.html

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Rajeev Kashyap TIPT