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CTD Dossier Preparation
Sr.Manager-Regulatory Affairs
Medreich LimitedMedreich Limited
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CTD D o s s i e r P r e p a r a t i o n CTD D o s s i e r P r e p a r a t i o n
CTD (Common Technical Document)contains 5 modules o u e
Module 2
Module 3
Module 4
Module 5
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DMF
Drug Master File (DMF) is a submission to theFood and Drug Administration (FDA) that may
information about facilities, processes, orarticles used in the manufacturing, processing,
,drugs. The information contained in the DMF
may be used to support following, ,
New Drug Application (NDA),
Abbreviated New Drug Application (ANDA),
Export Application.
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ANDA:
An Abbreviated New Drug Application (ANDA)is an application for a U.S. generic drugapprova or an ex st ng cense me cat on orapproved drug.
The ANDA contains data which when submittedto FDA's Center For drug Evaluation andResearch (CDER), Office of Generic Drugs,rovides for the review and ultimate a roval
of a generic drug product. Once approved, anapplicant may manufacture and market theeneric dru roduct to rovide a safe
effective, low cost alternative to the Americanpublic.
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Module 1 (e.g. EU)
Module-1: Administrative Information and
Prescribing Information
.
1.1 Comprehensive Table of Content1.2 Application Form
. ro uc n orma on
1.3.1 SPCs, Labelling and Packaging
1.3.2 Mock-Up
1.3.3 Specimen
1.3.4 Consultation with target patient group
. .
states
1.3.6 Braille
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Module - 1
1.4 Information about the Experts
1.5 Specific Requirements for differenttypes of applications
1.6 Environmental Risk Assessment
1.7 Information relatin to Or han MarketExclusivity
1.8 Information relating to
Pharmacovigilance1.9 Information relating to Clinical Trials
1.10 Information relating to Pediatrics
1.11 Response to Queries
1.12 Additional Data
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Module - 2Module - 2: CTD Summary
. a e o on en ompre ens ve
2.2 Introduction (general introduction to thepharmaceutical, including its pharmacology class,mo e o ac on, an propose c n ca use
2.3 Quality Overall Summary
2.4 Non-clinical Overview2.5 Clinical Overview
2.6 Non-clinical Written and Tabulated Summaries
2.7 Clinical summary
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Module - 2
2.4 Non-clinical Overview
2.4.1 General As ects2.4.2 Content and Structural Format
2.5 Clinical Overview
2.5.1 Product Development of Content Rationale2.5.2 Overview of Biopharmaceutics. .
2.5.4 Overview of Efficacy
2.5.6 Benefits and Risks Conclusions
2.5.7 Literature References
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Module - 22.6 Non-clinical Written and Tabulated Summaries
2.6.1 Pharmacology
. . armaco ne cs
2.6.3 Toxicology
.
2.7.1 Biopharmaceutic Studies and Associated
Analytical Methods2.7.2 Clinical Pharmacology Studies
2.7.3 Clinical Efficacy
. . nca a e y2.7.5 Literature References
. .
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Module - 3
Module 3: ualit
3.1 Table of Contents3.2 Bod of Data
3.2.S Drug Substance
3.2.S.1 General Information3.2.S.1.1 Nomenclature
3.2.S.1.2 Structure
. . . .
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Module - 33.2.S.2 Manufacture
3.2.S.2.1 Manufacturer Details
3.2.S.2.2 Description of Manufacturing Process andProcess Controls
. . . .
3.2.S.2.4 Controls of Critical Steps and
Intermediates. . . . rocess a a on an or va ua on
3.2.S.2.6 Manufacturing Process Development
3.2.S.3 Characterisation
3.2.S.3.1 Elucidation of structure and otherCharacteristics
3.2.S.3.2 Im urities
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Module - 33.2.S.4 Control of Drug Substance
3.2.S.4.1 Specification of Drug Substance
3.2.S.4.2 Analytical Procedures
3.2.S.4.4 Batch Analyses
3.2.S.4.5 Justification of Specification. . . r r r r
3.2.S.6 Container Closure System
3.2.S.7 Stability
3.2.S.7.1 Stability Summary and Conclusions3.2.S.7.2 Post-approval Stability Protocol and
3.2.S.7.3 Stability Data
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Module - 33.2.PDrug Product
3.2.P.1 Description and Composition of the DrugProduct
. . . armaceu ca eveopmen
3.2.P.2.1 Components of Drug Product
. . . .
3.2.P.2.3 Manufacturing Process
Develo ment
3.2.P.2.4 Container Closure System
3.2.P.2.5 Microbiological Attributes
3.2.P.2.6 Compatibility
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. . . anuac ure
3.2.P.3.1 Manufacturer
. . . .
3.2.P.3.3 Description of Manufacturing Process
and Process Controls3.2.P.3.4 Controls of Critical Steps and
Intermediates
. . . .
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. . .
3.2.P.4.1 Specifications
. . . .
3.2.P.4.3 Validation of Analytical
3.2.P.4.4 Justification of Specifications
. . . . Origin
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. . . on ro o rug ro uc
3.2.P.5.1 Specification of Drug Product
. . . .
3.2.P.5.3 Validation of Analytical Procedures
3.2.P.5.5 Characterisation of Impurities
3.2.P.5.6 Justification of Specification
3.2.P.6 Reference Standards or Materials
3.2.P.7 Container Closure System
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3.2.P.8 Stability3.2.P.8.1 Stability Summary and
onc usions
3.2.P.8.2 Post-approval Stability
Commitment
. . . .
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Module - 33.2.A Appendices
3.2.A.1 Facilities and Equipment
3.2.A.2 Adventitious Agents Safety Evaluation
. . .
3.2.RRegional Information/ Requirements
3.2.R.1 Process Validation and or Evaluation
3.2.R.2 Medical Device
3.2.R.3 Restricted part of DMF
. . . e c na pro uc s con a n ng or us ng nthe manufacturing process materials of
animal and / or human origin.
3.3 List of Literature References
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-Module - 4: Non-clinical Stud Re orts
4.1 Table of contents4.2 Study Reports
. .
4.2.1 Primary Pharmacodynamic
4.2.2 Secondary Pharmacodynamic. . a e y p armaco ogy
4.2.4 Pharmacodynamic drug
interactions
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Module - 44.2.2 Pharmacokinetics
4.2.2.1 Analytical Methods and
validation Reports
. . .
4.2.2.3 Distribution
4.2.2.4 Metabolism4.2.2.5 Excretion
4.2.2.6 Pharmacokinetic Drug
Interactions4.2.2.7 Other Pharmacokinetic studies
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Module - 4
4.2.3 Toxicology
-. . .
4.2.3.2 Repeat-dose toxicity4.2.3.3 Genotoxicit
4.2.3.4 Carcinogenicity
4.2.3.5 Reproductive and developmentalox c y
4.2.3.6 Local tolerance
. . .
4.3 Literature References
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Module - 5 o u e - : n ca u y epor s
5.1 Table of Contents
5.2 Tabular Listings of All Clinical Studies
5.3 Clinical Study Reports
5.3.1.1 Bioavailability (BA) study Reports
5.3.1.2 Com arative BA andBioequivalence study reports
5.3.1.3 In-vitro In-vivo Correlation study
5.3.1.4 Reports of Bioanalytical andAnalytical methods
. . .Reports
5.3.2.2 Reports of Hepatic metabolism
5.3.2.3 Reports of Studies Using human
Biomaterials
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Module - 5. . . ea y u ec an n a
Tolerability study reports
5.3.3.2 Patient PK and Initial Tolerabilit
study reports.5.3.3.3 Intrinsic Factor PK study reports
. . . xtr ns c actor stu y reports
5.3.3.5 Population PK study reports
. . .study reports
5.3.4.2 Patient PD and PK/PD study
reports5.3.5.1 Study reports of controlled clinical
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Module - 5
5.3.5.2 Study reports of Uncontrolled clinical
5.3.5.3 Reports of Analyses of data frommore than one study
5.3.5.4 Other clinical study reports
5.3.6 Reports of Post-Marketingxper ence
5.3.7 Case report forms and Individual
5.4 List of Key Literature References
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eCTDeCTD(Version 3.2.2)(Version 3.2.2)
06.05.201106.05.2011
K. Srikantha ReddyK. Srikantha ReddySr. ManagerSr. Manager--Regulatory AffairsRegulatory Affairs
[email protected]@medreich.com
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eCTD electronic Common Technical Document
.
Regulatory Perspective
The eCTD is defined as an interface for industry to
agency transfer of regulatory information while at
the same time takin into consideration thefacilitation of the creation, review, lifecycle
management and archival of the electronic
.
Common structure for Modules 2 through 5
Agency specific requirements for Modules 1
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eCTD
Technical Perspective
containing PDFs and SAS files (Statistical AnalysisSoftware) on a CD/DVD (Can also be submitted
through Agency web portals)
The eCTD backbone is an XML file (Extensiblear up anguage represen ng e s ruc ure o e
submission, it includes links to files and other
metadata such as check sum information. The
schema for the XML is very rigid.
PDF hyperlinks
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eCTD
Granularity of files submitted is small (there are no longer
issues of creating large volumes of PDFs).
Increased potential for reusing the same submissioncontent across agency submissions.
The standard, and many of the modules have been agreed
upon by the main worldwide agencies.
Once a submission is sent in eCTD format all future
submissions for the application should be in eCTD format.
ppor un y o use ar omp an ec ron cSignatures.
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Easy to distribute and review
More efficient use of resources, less cost and stress to
the organization
Highly organized electronic table of contents
Searchable Self-validating
Integrated document and life-cycle management
Cross submission integration
New, replace, append & delete
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Overall Table of contents provided in XML (Extensible
Markup Language)
Utility files to enable technical conformance and
viewing
Submission Folders, XML and Utility Files are createdau oma ca y an e u er s use .
Generally high level of granularity in documents
Structure is more precise
Lifecycle Management of the submission is easier.
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Jan 1, 2008, eCTD became CDERs standard for
electronic submission.
FDA has made it mandatory for all ELECTRONIC
submissions to be in eCTD format since 2007-08.
However, paper copies are still accepted. Suitable
waivers will have to be taken before hand.
The number of ANDA submissions to FDA has
increased from 72 in the year 2006 to 1550 in 2009
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eCTD Implementation - EU
(http://esubmission.emea.europa.eu/)
Requirements on Electronic submissions (Nees (Non-eCTD electronic
submission, Version 2.0 March-2010) and eCTD) and paper documentation for
New Application within MRP, DCP or National procedure Refer CMDh/085/2008/Rev7 October 2010)
rom s u y , e v . mus e use or a
eCTD submissions for all European procedures,
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eCTD Implementation - MHRA
p: www.m ra.gov.u armaceu ca n us ry ar e ngau or sations/index.htm
The preferred format for new marketing authorization (MA)
app cat ons s t e e ectron c Common Tec n ca Doss er eCTD
eCTD applications must be created according to the current
specifications: eCTD specification v 3.2.2
MHRA will accept applications in PDF-only format (Note that all PDFfiles included in an eCTD (irrespective of the module) should be v1.4, except
where there is an agency-specific requirement for a later version (e.g. for anapplication form)).
The Summary of Product Characteristics (SmPC) will need to be
prepared using the Word template.
Use the MHRA Adobe Application form which is available via the
MHRA Portal. This will produce an XML file that MHRA can upload
.
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When making an electronic submission, each document
should be rovided as a se arate file.
The documents, whether for a marketing application, aninvestigational application, or a related submission,
should be organized based on the five modules in the
CTD:
Module 1 includes administrative information and
prescribing information,
o u e nc u es summary ocumen s,
Module 3 includes information on quality,
Module 4 includes the nonclinical study reports, and
Module 5 includes the clinical study reports.
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eCTD Screen Shot of Module 3
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eCTD Screen Shot of Module 4
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eCTD Screen Shot of Module 5
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eCTD Screen Shot of Module 5
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eCTD Screen Shot of Module 5
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eCTDXPress Image Solutions http://www
.
MasterControl Submissions Gateway - Master
, . .
Liquents EZsubs software solution,
htt ://www.li uent.com/
Data Farm, http://www.datafarminc.com/
. .
Lorenz Life Sciences : www.lorenz.cc
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SRIKANTH.K