Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
7/13/12
303030
Contents:
ICH Objectives Introduction To CTD Significance Of CTD Organization Of CTD eCTD References
7/13/12
303030
22
ICH M4- COMMON TECHNICAL DOCUMENT FOR THE REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE:
International Conference on Harmonisation (ICH) was created in 1990.
Agreement between the EU, Japan and the USA to harmonize different regional requirements for registration of pharmaceutical drug products.
A Unique approach because joint effort by regulators and associated pharmaceutical industry trade associations.
7/13/12 303030 33
ICH Objectives
Identification and elimination of the need to duplicate studies to meet different regulatory requirements.
Quicker access for patients to deliver safe and effective new medicines.
7/13/12
303030
44
Working Groups
SAFETY QUALITY
EFFICACY
MULTIDISCIPLINARY
STEERING COMMITTEE
Endorses topics, guidelines and monitors 7/13/12 303030 55 progress
BACKGROUND
Through
the
ICH
process,
considerable
harmonization has been achieved among the three regions in the technical requirements for the registration of pharmaceuticals for human use.
However,
until
now, of the
there
has
been of
no the
harmonization
organization
registration documents. Each region has its own requirements for the organization of the technical reports in the submission and for the preparation of the summaries and303030 tables. 7/13/12
66
The U.S. FDA has guidance regarding the format To avoid the need to generate and compile
different registration dossiers, this guideline describes a format for the Common Technical
7/13/12
303030
77
Regulatory Communication
ICH
has
sought
to
enhance
regulatory
Standardized data elements, example: E2B Controlled vocabularies, example: MedDRA Common format for drug registration: CTD Electronic specifications and standards for the transmission
303030
of
such
information,
88
7/13/12
Regulatory Communication
Benefits:
Speak
same
language:
promotes
communication
Quality,
accuracy
and
consistency
of
information
Improve
timeliness
of
communications
(electronic transmission)
7/13/12
ORIGIN OF CTD
ICH
EWG
WAS OFFICIALLY SIGNED OFF IN NOVEMBER 2000,
CTD
7/13/12
303030
1010
CTD
WHAT IS IT?
IT IS :
A common harmonized FORMAT for applications for preparing marketing authorizations in the three ICH regions. A TEMPLATE for presenting data in the dossier.
7/13/12
IT IS NOT:
303030 1111
CTD
CTD IS A JOINT EFFORT OF 3 REGULATORY AGENCIES: 1.European Medicines Agency (EMEA, Europe), 2. Food and Drug Administration (FDA, USA) and 3. Ministry of Health, Labour and Welfare (MHLW,Japan). It has been adopted by several other
7/13/12
Any guideline which is given by ICH passes through different steps. These different steps are called STATUS of that GUIDELINE.
FUNCTIONALITY Development of Consensus Text released for consultation Consultation outside ICH ICH guideline finalized Implementation Status of CTD STEP 4 STATUS ACHIEVED IN NOV.2000 IN 5TH ICH CONFERENCE IN STEP 5 STATUS SANDIEGO.. ACHIEVED IN MAY.2001 IN ICH MEETING IN TOKYO. GUIDANCE MADE AVAILABLE TO INDUSTRY IN OCTOBER 16,2001 BY FDA.
1313
7/13/12
303030
SIGNIFICANCE OF CTD
Avoid generating and compiling different registration dossiers Common format will significantly reduce the time and resources Facilitates simultaneous submission in three regions Facilitates exchange of information among regulatory authorities Faster availability of new medicines
7/13/12
STRUCTURE OF CTD:
Divided into various modules having different contents
7/13/12
303030
1515
Module 1 Module 2
Nonclinical Overview Quality Overall Summary Nonclinical Summary Clinical Overview Clinical Summary Clinical Study Reports
The CTD
7/13/12
Module 3
Qualit y
303030
Module 4
Module 5
1616
Numbering System
1.0 Regional Administrative Information 1.1 ToC of Module 1 or overall ToC, Module including Module 1 1 1. 2.1 ToC of the CTD (Mod 0 2,3,4,5) 2.2 Introduction 2. 1 2.3 Quality Overall 2. Summary 2 2.4 Nonclinical 2. 2. Overview 2.5 Clinical 5 4 Overview 2. 2. 2.6 Nonclinical 6 7 Summary 2.7 Clinical Module Module 4 Nonclinica 5Clinical Summary Study l Reports Study 303030 1717 5.0
Prescribing Information
application
303030
forms,
prescribing
1818
information)
Module 2: Common Technical Document Summaries 2.1 CTD Table of Contents 2.2 CTD Introduction 2.3 Quality Overall Summary 2.4 Nonclinical Overview 2.5 Clinical Overview 2.6 Nonclinical Written and Tabulated Summary Pharmacology Pharmacokinetics Toxicology 2.7 Clinical Summary Biopharmaceutics and Associated Analytical Methods Clinical Pharmacology Studies Clinical Efficacy Clinical Safety 303030 7/13/12 1919 Synopses of Individual Studies
Module 3: Quality 3.1 Module 3 Table of Contents 3.2 Body of Data 3.3 Literature References Module 4: Nonclinical Study Reports 4.1 Module 4 Table of Contents 4.2 Study Reports 4.3 Literature References Module 5: Clinical Study Reports 5.1 Module 5 Table of Contents 5.2 Tabular Listing of All Clinical Studies 5.3 Clinical Study Reports 5.4 Literature References
7/13/12 303030 2020
The sequence of M4 Common Technical Document for the Registration of Pharmaceuticals for Human Use is:
M4 Document
M4 Quality - Quality overall summary and CTD Quality M4 Safety - Nonclinical Summaries and
7/13/12 303030 Organization of Module 4 2121
Industry
Although the CTD is organized by modules, the guidance for industry that provide recommendations for applicants on preparing the CTD have been organized by topic: Quality, Safety, and Efficacy. As a result, guidance discussing Module 2 is divided among three guidance.
Quality Overall Summary (QOS), and Module 3) can be found in the guidance for industry M4Q: The CTD Quality.
Nonclinical Overview and the Nonclinical Written and Tabulated Summaries, and Module 4) can be found in the guidance for industry M4S: The CTD Safety.
7/13/12 303030 2222
GENERAL PRINCIPLES
Throughout the Common Technical Document, the display of information should be unambiguous and transparent, in order to facilitate the review of the basic data and to help a reviewer become quickly oriented to the application contents. Text and tables should be prepared using margins that allow the document to be printed on both A4 paper (E.U. and Japan) and
8.5 x 11 paper (U.S.). The left-hand margin should be sufficiently large that information is not obscured by the method of binding.
Font sizes for text and tables should be of a style and size that are large enough to be easily legible, even after photocopying.
7/13/12
303030
2323
eCTD
Six months behind CTD, the eCTD was a transport format to be moved into an agencys review environment.
Electronic Common Technical Document (e-CTD) submission protocol is designed by the ICH to facilitate regulatory submissions to US, EU and Japan, in electronic format.
7/13/12
303030
2424
e-CTD issues.
as
methodology
of
regulatory
document
One to solve the issue of managing colossal paper documentation at the receiving end (i.e. USFDA, EMEA) & other to solve the major issue of managing the life-cycle of the drug approval documentation." This will automatically improve the throughput of the approval process at the FDA, which logically should also result in improved approval cycle timelines.
Paper CTD
1 oc D c2 Do 3 oc D c4 Do
eCT D
File 1 File 2
File 3
File 4
7/13/12
303030
2626
Developed by M2 EWG (Multidisciplinary 2 Expert Working Group) of ICH. Industry <-----> Message <------> Agency Paper submission has been replaced by electronic submission
7/13/12
303030
2727
Characteristics of eCTD:1. Files Referenced in the XML Backbone(s) (Extensible Markup Language) REASONS: 1. It manages the large data for the entire submission and for each document within the submission. 2. This 303030 backbone allows the eCTD XML 2828
7/13/12
2.The file formats that can be included in the eCTD are Portable Document Format (PDF) and XML. However other formats can be used for graphs and images. JPEG PNG GIF
7/13/12
7/13/12
Company Name
303030
3030
27-clin-sum
7/13/12
303030
3131
7/13/12
303030
3232
Summary
CTD was introduced with the aim to harmonize submission of technical data for registration of human use in different regions. The CTD is not a Global Dossier!
Content different for US, EU and Japan based on individual regulations , Some regulations never covered in ICH. It is an agreed upon common format for the modular presentation of summaries, reports and data. After 10 years of implementation of CTD, we can say that considerable harmonization has been achieved in various regions for submission of technical data.
7/13/12 303030 3333
REFERENCES:
www.ich.org http://www.fda.gov/cder/regulatory/ersr/ectd.htm http://esubmission.eudra.org/ http://www.fda.gov/cder/guidance/index.htm European Medicines CPMP/ICH/2887/99 Agency; February 2004;
Guidance For Industry On Preparation Of Common Technical Document For Import / Manufacture And Marketing Approval Of New Drugs For Human Use; Central Drugs 303030 Standard Control Organization; 7/13/12 3434
7/13/12
303030
3535