Electronic Common Technical Document (eCTD)

Pharmaceutical Product Registration by eCTD

1. Presented by Md. ZakariaFaruki
Asst. Manager, Quality Assurance
OPL
Training on
Electronic Common Technical
Document (eCTD)

2. The ICH
TheInternationalConferenceonHarmonisation(ICH)wasformedin
April1990hostedbyEFPIA(EuropeanFederationofPharmaceutical
IndustriesandAssociations)inBrusselsasajointregulatory
consortiumtobringtogetherthetechnicalrequirementsofrespective
regulatoryagenciesandstandardizethecommonportionsofdrug
applications.
Observers
OPL

3. Common Technical Document (CTD)
Representatives of the regulatory agencies and industry
associations of EU, Japan and the US.
OPL

4. eSubmissionsHistory
Beganinlate80’sbutinsufficientITcapabilities
1995–FDAusedPDFfileswithhyperlinks
1997–CTDtopicofICH4
2001–firsteCTDguideline
2003–CTDmandatoryinEUandfirsteCTDssubmitted
2006–lifecyclemanagementachallenge
In2007,eCTDsrepresented10%oftotalsubmissionstoCDER.
2008–onlyelectronicsubmissionsaccepted(eithereCTDornon-eCTD)
2009–stronglyrecommendonlyeCTDformatelectronicsubmissionstobe
accepted.PaperandotherelectronicformatstobeexceptionintheEMEA
It is expected that by the end of 2012, eCTDsubmissions may represent 40 or 50%
of total submissions to CDER (Center for Drug Evaluation and Research).
OPL

5. What does eCTDconsist of?
Folder or tree structure
XML backbone file is Table of Contents
Additional information (Document type definition –rule book
for tags and attributes)
Regional information and files
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6. Folder Structure
Sections with specific
information in folder names
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7. Preparing documents
Templates should be used where possible
Documents to be:
technically correct
have the right granularity
conform to external regulations/guidelines
consistent with internal standards and styles –naming
conventions, etc.
‘intelligent’ PDF files
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8. Concept of Reuse
Submit a document once, never submit again.
Concept ofGranularity
Authoringinsmallerpieces(granules),allowsforgreater
flexibilityandreuseinthecontextofsubmissions.
IfdocumentsareformattedaccordingtoICHgranularityand
contentneedstochange,onlythosedocumentsthatcontainnew
contentwillneedtobereplaced(orappended)andsubmitted
nottheentiresectionorstudyreport.
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9. What is XML?
ExtensibleMarkupLanguage(XML)isanelectronic
documentanddataexchangestandard.
XML vs. HTML?
XMLdescribesandfocusesondata.Itisinformation
wrappedintagsthatrequiresanotherpieceofsoftwareto
send,receiveordisplayit.Thetagsarenotpredefined.XML
isacomplementtoHTML.
HTMLdisplaysdataandfocusesontheappearanceofdata.
Tagsarepredefined.
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10. DTD
ThepurposeoftheDTDistodefinethebuildingblocksthat
canbeusedinanXMLdocument.Itdefinesthenamestobe
usedforthedifferenttypesofelements,aswellaswherethey
mayoccurandhowtheyallfittogether.
XSL
Stylesheets,orExtensibleStyleSheetLanguage(XSL),
arefilesthatdefinethelookofthecontent,includingfontsizes,
colors,margins,etc.
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11. Metadata
Regional Information
Company Name
Application Number
Date of Submission
Product Name and Type
Application Type
Submission Type
ICH Information
Product, Dosage Form,
Manufacturer, Excipient
Substance & Manufacturer
Indication
Novel Excipient
OPL

12. 012345
util
style
ich-ectd-3-2.dtd
dtd
0000
M1
M2
M3
M4
M5
ich-stf.dtd
us-regional-v2-01.dtd
ectd-1-0.xsl
ich-stf-stylesheet.xsl
us-regional.xsl
index.xml
index-md5.txt
eCTDFolder
Structure
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13. M1M1 M1
M2
M3
M4
M5
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14. Each Section/Tab represents a PDF File
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15. X
M
L
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16. OPL

17. OPL

18. eCTDSoftware Vendors
1)Extedo/IABGLifeSciences-:
eCTDmanagerisanoff-the-shelfsubmissionmanagementsystemofhighestquality
andfunctionality.ItprovidestheeCTDfunctionsofbuilding,viewing,validatingand
publishing(electronicandpaper)andenablestheeasy-to-usecompilationof
compliantelectronicdossiersbasedonCTD,eCTDandotherdossierstructures.
2)eCTDXpress:
eCTDXPressisISI’slatestweb-basedsolutionforcreating,managingeCTDlifecycles,
andreviewingeCTDsubmissions.Theapplicationsatisfiesbothregulatoryagencies’
andindustrysponsors’requirementsforreviewing,compiling,publishingand
archivingofmulti-regioneCTDsubmissions.eCTDXPressallowsuserstoseparate
technologyfromcontent,whichimprovesproductivityandtime-to-market.
3)SubmissionAcceleratorforeCTD:
ItisacomplimentarymoduleforCoreDossier®--automatestheassemblyand
publishingofcomplianteCTDdossiers,includingtheXMLbackbonesforregional
content.
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19. 012345
0000
M1
M2
M3
M4
M5
util
index.xml
Index-md5.txt OPL

20. 0000
0001
0002
012345
M1
M2
M4
util
0003
0004
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21. Granularity
Defineshowthecompleteddocumentisbrokendown,
taggedandstoredforreuse
Determinessmallestpieceofinformationthatisreusable
Changinggranularityduringlifecycleisdifficult,therefore
mustbeplannedatthebeginning.
FDAGuidance
Eachdocumentshouldbeprovidedasaseparatefile
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22. ‘intelligent’ PDF files
A file converted to special PDF format enabling links and
bookmarks to be applied, and hence is searchable.
Cross referencing documents
Intradocumentlinks –bookmarks
Most intradocumentlinks can be automatically set using
templates
To set each link manually would take MANY hours
Interdocumentlinks
Cross reference documents in context of other documents.
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23. Cross referencing submissions
Intersubmissionlinks
Crossreferencesofsubmissionsincontextofother
submissions,e.g.variations.
Time frames
Oncealldocumentsarewritten,checkedandformatted
settingbookmarksandlinkstakefrom2to12weeks.
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24. Eye openers
Globalapplication
Lifecyclehistoryeasilyaccessible
Easeofcompilationandreviewoncesystemisupandrunning
Intersubmissionchecksmadepossiblebybothapplicantand
reviewer
Authenticityofdocumentationeasytoverify.
bombshell
Extensivesoftwareprogrammeneededtosupportthesystem
SoftwareprogrammeusedinEUcosts€20,000perUSER
ExtensiveITsupportneededbyapplicantandregulator.
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25. Comparing paper CTD and eCTD
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26. Conclusion
Greatideabutneedintermediatestepstogetthere
CTDformattobeadoptedimmediately
NeeSininterim
Essentialtojoinelectronicbandwagon
ToexplorethestagesofdevelopinganeCTDstrategyand
approach.
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27. Strategy & Approach
Save a Tree!!
•NCE is approx 240,000 pages, Paper for this would be 672 kg, Equivalent to ONE
average tree.
•An entire tree is required to submit a single copy of the application form one
applicant to one health authority
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28. OPL