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1. CTD and eCTD
Prepared by : Gaurav R. Panchal Guided by : Ms. Hardi Joshi
M.Pharm QA (sem 1) Assisstant Professor, GSP-GTU
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2. CTD (Common Technical Document)
• The Common Technical Document is a set of specification for application
dossier for the registration of medicines.
• It is an internationally agreed “well structured common format” for the
organization of the technical requirement authority as an application for the
registration of pharmaceuticals for human use in all three ICH regions (USA,
Europe, Japan).
• It was agreed in Nov. 2000 in San Diego. USA.
• In July 2003, CTD became mandatory format for new drug application in the
EU and Japan, and strongly recommended the format of choice of NDAs
submitted to the FDA.US.
• It is maintained by ICH (International Council on Harmonization).
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3. CTD
Need for CTD :
• Substantial documentation and data are required in submission for import
/manufacture and marketing approval of drugs for human use, resulting in
large, complex applications.
• Till date, applicants have used many different approaches in organizing the
information and difference in organization of data in each application has
made reviewing more difficult and can lead to omission of critical data or
analyses.
• Such omissions can result in unnesccesary delays in approvals.
• Thus, a common format of submission will help in overcoming these
hurdles.
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4. CTD
Need for CTD :
• Prior to the implementation of the Common Technical Document (CTD) in
2002, each of the three major regulatory regions (European Union (EU),
USA, and Japan) had its own set of guidelines and format for the
submission of a regulatory dossier to obtain marketing approval for a new
drug or a variation to the licensing of an existing drug.
• In Japan, the GAIYO was required, which organised and presented a
summary of the technical information; in Europe, Expert Reports and
Tabulated Summaries were required and Written Summaries were
recommended; and in the USA, the Food and Drug Administration (FDA)
had guidance documents regarding the format and content of the New
Drug Application (NDA).
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5. CTD
Need for CTD (Contd.) :
• To avoid the need to generate and compile different registration dossiers,
this guideline describes a format for the Common Technical Document that
will be acceptable in all three regions..
• In 2000, representatives from the European Medicines Agency (EMA), the
USA FDA, and the Ministry of Health, Labour, and Welfare in Japan
developed a set of guidelines defining the structure and content of the
dossier for an application for the registration of a new medicine that could
be used across all three regions.
• Now it is adopted by Switzerland(SwissMedic), Canada(Health Canada),
Australia(TGA), etc.
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6. CTD
Scope :
• This guideline primarily addresses the organisation of the information to be
presented in registration applications for new pharmaceuticals (including
biotechnology-derived products).
• This guideline is not intended to indicate what studies are required.
• It merely indicates an appropriate format for the data that have been
acquired.
• Applicants should not modify the overall organisation of the Common
Technical Document as outlined in the guideline.
• However, in the Nonclinical and Clinical Summaries, applicants can
modify individual formats if needed to provide the best possible
presentation of the technical information, in order to facilitate the
understanding and evaluation of the results
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7. CTD
Objectives :
• Avoid duplicate animal and human testing.
• More economical use of human, animal and material resources.
• Elimination of unnecessary delays in global development
• Fast availability of new medicines
• Maintain safeguards on quality, safety, efficacy and regulatory obligations
to protect public health.
• Reduce time and resources used to compile applications
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8. CTD
Organisation :
Module 1: Administrative information and prescribing information
Module 2: Overviews and Summaries of Modules
Module 3: Quality (pharmaceutical documentation)
Module 4: Non-clinical reports (pharmacology/ toxicology)
Module 5: Clinical study reports (clinical trials).
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9. CTD
• CTD Triangle :
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10. CTD
Module : 1 Administrative and prescribing information
• It contains documents specific to each region.
• Eg. Application form regarding the prescribing information, proposed
label.
• This module is not part of CTD.
• The content and format of this module can be specified by the relevant
authorities.
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11. CTD
Module : 1 (contd.)
1. Cover Letter
2. Comprehensive Table of Content
3. Application Form
4. Product information
a) SPC’s, Labelling and Packaging
b) Mock-up
c) Specimen
d) Consultation of target special group
5. Information about the Experts
6. Specific Requirements for different types of application
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12. CTD
7. Environmental Risk Assessment
8. Information relating to Orphan Market Exclusivity
9. Information relating to Pharmacovigilance
10. Information relating to clinical trials
11. Information relating to pediatrics
12. Response to Queries
13. Additional data
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13. CTD
Module : 2 Quality Overall Summaries (QOS)
• It contains seven sections that should be maintained in following order :
1. Table of contents
2. Introduction
3. Quality Overall Summary
4. Non-clinical Overwiew
5. Clinical Overview
6. Non – clinical Written and tabulated Summaries
7. Clinical Summary
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14. CTD
Module 2 (contd.) :
• The quality overall summary (QOS) is a summary of the chemical and
pharmaceutical data in the dossier (including data for
biological/biotechnological products).
• The structure of the QOS broadly follows the structure of the data included
in Module 3.
• The QOS should not include information that has not already been
included in Module 3 or in other parts of the CTD.
• The aim of the QOS is to discuss the critical parameters of the product, but
it should also address issues that arose during development and provide
justification for instances where guidelines were not followed etc.
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15. CTD
Module 2 (contd.) :
• The main purpose of the Non-Clinical Written and Tabulated Summaries is
to provide a comprehensive factual summary of the non-clinical
information on pharmacology, pharmacokinetics, and toxicology.
• The interpretation of the data, the clinical relevance of the findings, any
association between non-clinical findings and quality aspects of the IMP,
and any implications of non-clinical findings for the safety of the IMP in
humans should be addressed in the Non-Clinical Overview.
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16. CTD
Module 2 (contd.) :
• Clinical Overview is a key document in the CTD dossier. The Clinical
Overview is divided into six sections: product development rationale,
biopharmaceutics, clinical pharmacology, efficacy, safety, and risk/benefit
conclusions.
• The Clinical Summary is divided into sections covering biopharmaceutics
and associated analytical methods, clinical pharmacology, efficacy, and
safety.
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17. CTD
Module 3 :
• It presents the chemistry, manufacturing, and controls reports for the
product included in the registration dossier.
• The section of the application covering chemical and pharmaceutical data
for biological/biotechnological products.
• Information on quality should be presented in structure and format.
• The Quality section of CTD provides a harmonized structure and format
for presenting (CMC) information in registration dossier.
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18. CTD
Module 3 (contd.) :
• The main headings in this section are as follows:
1. Table of Content
2. Body of Data
a) Drug Substances
b) Drug Product
3. Literature References
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19. CTD
Module 4 :
• It presents the non-clinical reports included in the dossier.
• The structure and content of Module 4 is specified in the ICH M4S
guidelines.
• The main headings in this section are as follows:
1. Table of contents of Module 4
2. Study reports
a) Pharmacology
b) Pharmacokinetics
c) Toxicology
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20. CTD
Module 5 : Clinical Study reports
• Module 5 presents the clinical reports included in the dossier.
• The structure and content of Module 5 is specified in the ICH M4E
guidelines.
• main headings in this section (that must not be altered) are as follows:
1. Table of contents of Module 5
2. Tabular listing of all clinical studies
3. Clinical study reports
a) Reports of biopharmaceutic studies
b) Reports of studies pertinent to pharmacokinetics using human
biomaterials
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21. CTD
Module 5 (contd.) :
c) Reports of human pharmacokinetic (PK) studies Reports of human
pharmacodynamic (PD) studies
d) Reports of efficacy and safety studies
e) Reports of post-marketing experience
f) Case report forms and individual patient listings
3) Literature references
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22. eCTD (Electronic Common Technical Document
• After decades of using paper, the goal is the electronic transfer of drug
application and their review across submission formats, procedures, and
reasons came in electronic technical document.
Defination :
“eCTD is an interface and international specification for the pharmaceutical
industry to agency transfer of regulatory information.”
• The focus of the specification is to provide the ability to transfer the
registration application electronically from industry to regulatory authority.
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23. eCTD
Reasons :
• Manages the large data for entire sybmission and for each document within
the submission.
• XML backbone allows the eCTD submission to be viewed via a web
browser and canbe loaded on a web server.
• The file formats that can be included in the eCTD are Portable document
Format (pdf) and XML.
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24. eCTD
eCTD submission are accepted for :
• Investigational New Drug (INDs)
• New Drug Application (NDAs)
• Abbreviated New Drug Applications (ANDAs)
• Biologics License Application (BLAs)
• All the application following the submission of the above stated
applcations.
• All the Master Files which are part of any above mentioned applications
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25. eCTD
Advantages :
• Allows agencies to upload sequences automatically with the help of XML
backbone.
• Reviewers can refer the information easily with of hyperlinks
• No need to scan, copy or store paper documents.
• Changes and updates made to the dossiers can be easier identified.
• Easy product lifecycle tracking.
• Simultaneous accessibility of documents is possible.
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26. Thank you
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