Complete details on CTD format along with document list for submission in DRAP

1. Written by
Aqsa Tufail
Research and development officer
Zaka health care

2.  A common harmonized Format/set of
technical documents for preparing
marketing authorization of Pharmaceutical
products in three regions define by ICH.
 It is not a statement of data requirements
for applications.
 FDA characterized CTD as: An information
package of clinical, non clinical ,
manufacturing technical data in the same
format and with the same content that
would be submitted for registering new drugs
in all three ICH regions.

3.  it is firstly introduced by industries in 1995-
1996
 ICH did not approve its format and advise
more practical approach on CTD.
 In year 2000 CTD was officially approved By
ICH in U.S.A
 Following three regulatory agencies are
involved in this process
 US-FDA
 European medicine agency EMA –Europe
 Ministry of Health Labour and welfare Japan

4.  CTD consist on five modules
 Module 1 Administrative and prescribing
information
 Module 2 Overview and summery of module 2
and 3
 Module 3 Quality ( documentation)
 Module 4 safety toxicology study
 Module 5 Efficacy clinical studies

6.  Administrative information and prescribing
information
 Should contain documents specific to regions
 This module is not a part of CTD
 The content and format of this module can
be specified by the relevant regularity
authority e.g. Application form , proposed
label for use in the region, registration
certificates, COAs, COPP, DML, form 29

7.  It contain 7 sections in the following order
 CTD TOC
 CTD introduction
 Quality overall summery
 Non-clinical overview
 Clinical overview
 Non-clinical summery
 Clinical summery

8.  The individual organization of these
summaries is describes in three separate
documents
 M4 Q The CTD Quality
 M4 S The CTD Safety
 M4 E The CTD Efficacy
 M4 Q The CTD Quality : This section
provide structure and format for presenting
CMC (Chemistry , manufacturing , control)
information in dossier
 The table of content section includes Drug
substance and drug product information

9.  M4 S The CTD Safety
This portion provide complete detail on Non-
clinical data , it also linked with Module 4 i.e.
Non-clinical study reports
Non-clinical data overview: should present an
integrated and clinical assessment of
pharmacological, pharmacokinetic , and
toxicological evaluation of pharmaceutical
products ( it should not exceed 30 pages)
 Non-clinical written summaries provide more
extensive knowledge of Non-clinical
information on pharmacological,
pharmacokinetic , and toxicological evaluation
( it should not exceed 100-150 pages)

10.  M4 E The CTD Efficacy : Includes structure
and format of clinical data in an application
including summaries and detailed study
reports .

11.  Quality
 TOC of module 3
 Body of data
 Drug substances
 Drug products
 Appendices
 Regional Information
 Literature reference

12. Module 3
3.2 Body of data
3.2.S DRUG SUBSTANCE
3.2.S.1 General information (name, manufacturer)
3.2.S.1.1 Nomenclature (name, manufacturer)
3.2.S.1.2 Structure (name, manufacturer)
3.2.S.1.3 General properties
3.2.S.2 Manufacturer of drug substance (name, manufacturer)
3.2.S.2.1 Manufacturer
3.2.S.2.2 Description of manufacturing process and process
control data
3.2.S.2.3 Control of materials
3.2.S.2.4 Control of critical steps and intermediates
3.2.S.2.5 Process validation/Evaluation
3.2.S.2.6 Manufacturing process development

13. Module 3 Cont…
3.2.S.3 Characterization of drug substances
3.2.S.4 Quality control parameters of drug substances
3.2.S.5 Reference standards/materials
3.2.S.6 Details on container closure system
3.2.S.7 Stability study data of drug substances
3.2 P DRUG PRODUCT
3.2 P.1 Description and composition of drug product
3.2 P.2 Pharmaceutical development
3.2 P.3 Manufacturer of drug product
3.2 P.4 Control of excipients
3.2 P.5 Control of drug products
3.2 P.6 Reference standard or materials
3.2 P.7 Container closure system
3.2 P.8 Stability of drug product

14.  TOC of module 4
 Study reports
 Pharmacology
 Pharmacokinetics
 Toxicology
 Literature review

15.  TOC of module 4
 Tabular listing of module 5
 Clinical study reports
 Reports of biopharmaceutical studies
 Reports of pharmacokinetic (biomaterial) studies
 Reports of pharmacokinetic (PK) studies
 Reports of pharmacodynamic (PD) studies
 Reports of safety and efficacy studies
 Reports of post-marketing experience
 Case reports forms and individual patient listings
 Literature references

16.  Documents required by DRAP as per Form 5F CTD
 DMF
 Product development document
 BMR of Trial Batches
 critical steps in manufacturing process
 Manufacturing process validation
 Excipient control document
 API and Excipients supplier/company COA
 Analytical validation of finished product
 Stability protocol, summery , conclusion, post
approval stability protocol, stability
commitment, three batches stability data on
long term and accelerated conditions.

17.  API working standard certificate
 Container closure system packaging material
spec. COA and analytical procedure
 BA/BE studies comparative study if bio
wavier is available

18.  To make reviewing of each application more
easily
 To save time and resources
 Appropriate format for data
 Easy to understand and evaluation of data
 Applicable to all types of products (vaccines,
radiopharmaceuticals, herbal etc)
 Facilitate electronic submission

19.  CTD is only a format , its not a single dossier
with single contents.
 Legal requirements differ in different
regions.
 ICH guidelines have not yet harmonized in all
requirements.
 Pharmacopoeias are not harmonized.
 Applicants may have regional preferences.

20.  https://www.ich.org/products/guidelines/m
ultidisciplinary/article/multidisciplinary-
guidelines.html
 https://www.ema.europa.eu/en/documents
/presentation/common-technical-document-
quality-ctd-q-george-wade_en.pdf
 https://en.wikipedia.org/wiki/Common_Tec
hnical_Document