1. In the name of God

2. Cover Letter

5. ICH CTD Format for Marketing Authorization Application

6. CTD
The common technical document (CTD) is an international standard for the structure of applications for marketing authorization of a medical product
The CTD is the outcome of the ICH process
The CTD is mandatory since 01/July/2003
The CTD does not define the scientific content of the dossier

7. CTD OBJECTIVES
CTD presents the agreed common format for preparation of a well-structured dossier that will be submitted to regulatory authorities.
A common format for the technical documentation will significantly reduce the time and resources needed to compile applications for registration and will ease the preparation of electronic submissions.

8. ICH/CTD
The Common Technical Document (CTD) is organized into 5 modules.

9. Documents in each Module
Information 1
Administrative and prescribing information (region specific) 2
Summaries and overview 3
quality 4
Non-clinical study reports 5
Clinical study reports

10. Relationship between CTD and old EU Format
Module 1 < > Part IA/B
Module 2 < > Part IC
Module 3 < > Part II
Module 4 < > Part III
Module 5 < > Part IV

11. ICH/CTD Module 1
Administrative Information and Prescribing Information

12. 1. Module 1: ADMINISTRATIVE AND PRESCRIBING INFORMATION
1.1 Table of contents.
1.2. Administrative information
Drug submission application
Drug submission fee application
Submission certification
IRC Number
Establishment licensing information
GMP certification
International registration status
Other application information
1.3. product labeling
Summary of product characteristics.
product monograph
Instruction for medical use

13. 1. Module 1: ADMINISTRATIVE AND PRESCRIBING INFORMATION
Draft for all inner and outer labels
Specimen
1.4. Bioequivalence studies summaries
1.5. Information about the expert
1.5.1 Information about the independent experts:
Information about the quality expert.
Information about the non clinical expert.
Information about clinical expert.
1.6. Environmental risk assessment
Annex

20. Summary of product characteristic
SPC
Summary of product characteristic

21. SPC Generic name/Trade name Qualitative and quantitative composition
Pharmaceutical form and strengths
Clinical particulars

22. SPC
4.1. Therapeutic indications 4.2. Route of administration 4.3. Contra indications 4.4. Special warnings and precautions for use 4.5. interaction with other medicinal products and other forms of interaction 4.6. Pregnancy and lactation 4.7. Effects on ability to drive and use machines 4.8. Undesirable effects 4.9. Overdose

23. SPC
5. Pharmacological properties 5.1. Pharmacodynamic properties 5.2. Pharmacokinetic properties 5.3. Pre clinical safety data

24. SPC
6. Pharmaceutical particulars 6.1. List of excipients 6.2. Incompatibility 6.3. Shelf life 6.4. Special precautions for storage 6.5. Nature and contents of container 6.6. Special precautions for disposal and other handling

25. SPC
Administrative data 7. MARKETING AUTHORIZATION HOLDER 8. MARKETING AUTHORIZATION NUMBER(S) 9. DATE OF FIRST AUTHORIZATION/RENEWAL OF THE AUTHORIZATION 10. DATE OF REVISION OF THE TEST

26. Quality Expert
Name
Experience
Education
Position held

27. Module 2: Overviews and Summaries
2.1 CTD TOC Modules Introduction 2.3 Quality Overall Summary 2.4 Nonclinical Overview 2.5 Clinical Overview 2.6 Nonclinical Summary 2.7 Clinical Summary

28. 2.2 Introduction
• One page dealing with – Pharmacological class – Mode of action – Proposed clinical use

29. 2-3. QOS Quality Overall Summary
2.3. Introduction 2.3.S (active substances) 2.3.P (finished product) 2.3.A Appendixes 2.3.R Regional information

30. 2.3. QOS
Marketing Authorization holder Manufacturer (S) Formula Introduction Dosage Form Packaging Salt Reproducibility of product’s quality

31. 2.3.S QOS: Drug Substance
1. General information 2. Manufacture – Flow diagram 3. Characterisation - Tabulated summary of data, including graphical representation 4. Control of drug substance – Tabulated summary of batch analysis data, with graphical representation

32. 2.3.S QOS: Drug Substance
5. Reference standards or materials 6. Container closure system (CCS) 7. Stability – Tabulated summary of study results, graphical representation

33. 2.3 P QOS: Drug Product
1. Description and composition 2. Pharmaceutical development – Tabulated summary of composition of formulations, dissolution profiles 3. Manufacture - Flow diagram 4. Control of excipients 5. Control of drug product – Tabulated summary of batch analysis data, graphical representation

34. 2.3 Drug Product
6. Reference standards or materials 7. Container closure system (CCS) 8. Stability – Tabulated summary of stability data, graphical representation

35. 2.3.A Appendices
1. Facilities and equipment – Biotech: with summary 2. Adventitious agents safety evaluation – Measures to control adventitious agents in production – Summary of reduction factors • Novel excipients 2.3.R Regional information

36. ICH/CTD Module 2 (Summaries)
Quality (Module 3) Overall Summary,
Non-clinical (Module 4) Overview/Summaries, and
Clinical (Module 5) Overview/Summaries.

37. ICH/CTD Module 3 (Quality)
Documentation of
Chemical and
Pharmaceutical on
active substance and/or medicinal product is provided in Quality Report, Module 3.

38. ICH/CTD Module 3 (Quality)
3.1 Table of Contents
3.2 Body of Data
3.3 Literature References

39. Module 3 (Quality) Module 3: Quality 3.1 Table of Contents
3.2 Body of Data
3.2.S Drug Substance
3.2.P Drug Product
3.2.R Regional Information
3.2.A Appendices
3.3 Literature References

40. Module 3 (Quality) 3.1. Table of contents
The first document in this module should be a TOC listing all of the documents provided for module 3.

41. Module 3 (Quality) 3.2. Body of data
Each individual sub-section related to the drug substance and drug product should be provided as:
an individual document either
bound separately, or
divided by tab identifiers,

43. Module 3 (Quality) 3. 2. Body of data 3. 2. S. Drug Substance 3. 2. S
Module 3 (Quality) Body of data 3.2.S. Drug Substance 3.2.S.1 General Information
3.2.S.1.1 Nomenclature
INN
Compendial name if relevant
Chemical name(s)
3.2.S.1.2 Structure
3.2.S.1.3 General Properties
– International Non-Proprietary Name (INN),
– National Approved Names,
– US Adopted Name (USAN),
– British Approved Names (BAN)
– Laboratory Code(s),
– Systematic Chemical Name(s), IUPAC
– Other Names (e.g. Proprietary).
– CAS registry number;

44. 3.2.S.1.3 General Properties
Appearance, physiochemical characteristics
Category
Absorption, toxicity, protein binding
Half life, organism affected

45. Module 3 (Quality) 3. 2. Body of data 3. 2. S. Drug Substance 3. 2. S
Module 3 (Quality) Body of data 3.2.S. Drug Substance 3.2.S.2 Manufacture
3.2.S.2.1 Manufacturers [name, manufacturer]
3.2.S.2.2 Manufacturing Process and Process Controls
3.2.S.2.3 Control of Materials
3.2.S.2.4 Controls of Critical Steps and Intermediates
3.2.S.2.5 Process Validation and/or Evaluation
3.2.S.2.6 Manufacturing Process development

46. Module 3 (Quality) 3. 2. Body of data 3. 2. S. Drug Substance 3. 2. S
Module 3 (Quality) Body of data 3.2.S. Drug Substance 3.2.S.3 Characterization
3.2.S.3.1 Elucidation of Structure and other Characteristics
3.2.S.3.2 Impurities

47. 3.2.S.3.1
S UV S IR S NMR S HPLC S Mass spectrometry

48. S.3.2 Impurity
starting material S process intermediate during the process degradation S Residual solvent 2.3 control of impurity 2.4 impurity structure

49. Module 3 (Quality) 3. 2. Body of data 3. 2. S. Drug Substance 3. 2. S
Module 3 (Quality) Body of data 3.2.S. Drug Substance 3.2.S.4 Control of Drug Substance
3.2.S.4.1 Specification
3.2.S.4.2 Analytical Procedures
3.2.S.4.3 Validation of Analytical Procedures
3.2.S.4.4 Batch Analyses
3.2.S.4.5 Justification of Specification

50. 3.2.S.5 Reference Standards or Materials [name, manufacturer]
Module 3 (Quality) Body of data 3.2.S. Drug Substance 3.2.S.5 Reference Standards or Materials
3.2.S.5 Reference Standards or Materials [name, manufacturer]

51. Module 3 (Quality) 3. 2. Body of data 3. 2. S. Drug Substance 3. 2. S
Module 3 (Quality) Body of data 3.2.S. Drug Substance 3.2.S.6 Container Closure System
3.2.S.6 Container Closure System [name, manufacturer]

52. s.6 container closure system
S.6.1 summary of primary and secondary packaging 6.2 suitability of container closure system 6.3 specification of C.C & COA 6.4 shematic drawing (if necessary)

53. Module 3 (Quality) 3. 2. Body of data 3. 2. S. Drug Substance 3. 2. S
Module 3 (Quality) Body of data 3.2.S. Drug Substance 3.2.S.7 Stability
3.2.S.7.1 Stability Summary and Conclusions
3.2.S.7.2 Post-approval (on going) Stability Protocol and Stability Commitment
3.2.S.7.3 Stability Data

55. Module 3 (Quality) 3.2. Body of data 3.2.P Drug Product

56. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data P Drug Product P.1 Description and Composition of the Drug Product
Description of the dosage form
Composition (i.e., list of all components, amount on a per unit basis (including overages, if any) their function, and a reference (e.g., compendial monographs or manufacturer’s specifications)
Description of accompanying reconstitution diluents
Type of container and closure used for the dosage form

57. Composition of Lamivudine Tablets 150 mg
Strength mg
Ingredients
Quality
standard
Unit composition
Function in the
Formulation mg %
Lamivudine (as API)
USP 34-NF29
150 50
Active Ingredient
Microcrystalline Cellulose
108 36
Diluent & Disintegrant
Pregelatinized Starch
25.5
8.5
Binder/Disintegrant
Sodium Starch Glycolate 12 4
Disintegrant
Magnesium Stearate
1.5
0.5
Lubricant
Sodium Lauryl Sulfate
EP 2010 3 1
Total
300
100

58. Composition of Lamivudine Tablets 150 mg
Strength mg
Composition of tablet
coating
Quality
standard
Unit composition
Function in the
Formulation mg %
HPMC (6cp)
USP 34-NF29
9.43
66.77
Film-forming Agent
Polyethylene Glycol 4000
2.35
16.63
Titanium Dioxide
White Pigment & Opacifier
Isopropyl Alcohol
0.038 mL
-----
Solvent
Purified Water
0.1 mL
Solvent & Vehicle
Total
14.13
100

59. Tips on Composition
Constituents including those removed during processing, e.g. granulation solvents:
should be clearly identified by means of a pharmacopoeia monograph name if one exists,

60. Tips on Composition
Colouring materials should be identified by the EC code number if appropriate.
It is recognised that for multi-national companies wish to use coloring materials approved elsewhere than the EU to allow use of the same dosage form in all centers.

61. Dosage Form Composition to be expressed as:
Solid Dosage Forms: Tablets, Capsules and Boluses: Quantity per unit dose
Oral liquids, Syrups and Suspensions:
Quantity per unit dose (usually 5mL)
Aerosols Quantity per unit dose, puff

62. Dosage Form Composition to be expressed as:
Injectable Preparations:
mg per in the unit container or
usable volume of the product, w/v), or
I.U. of active constituents in the
unit container (taking into account
usable volume of the product).

63. Dosage Form Composition to be expressed as:
Topical preparations Percentage:
Ointments, Creams and Gels %w/w
Toothpaste %w/w, Lotions %w/v
Eye & Nasal Drops: % w/v
Oral Drops: mg in ml

64. Tips on Composition
Exact quantities are not required for constituents used in:
Tablet coating, or
Capsule shells although the qualitative formulation of these must be declared.

65. Tips on Composition
For excipients where a slight variation in quantities may be required from batch to batch:
These may be expressed in the formula as a range (and justified in the Development Pharmaceutics section).

66. Overage
The inclusion of an overage normally applies only to active constituents, preservatives, etc.
Where an overage is included it must be stated whether this is intended to cover:
losses during manufacture,
loss of potency on storage or both.

67. Overage
Justification for an overage should be provided in the Development Pharmaceutics section.

68. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data P Drug Product P.2 Pharmaceutical Development
information on the development studies conducted to establish that the dosage form, the formulation, manufacturing process, container closure system, microbiological attributes.

69. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data P Drug Product P.2 Pharmaceutical Development
Process attributes (critical parameters) that can influence batch reproducibility, product performance, and drug product quality.

70. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data P Drug Product P.2 Pharmaceutical Development
The compatibility of the drug substance with the excipients.
Additionally, key physicochemical characteristics (e.g., water content, solubility, particle size distribution, polymorphic or solid state form) of the drug substance that can influence the performance of the drug product should be discussed.

71. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data P Drug Product P.2 Pharmaceutical Development
3.2.P.2.1 Components of the Drug Product
3.2.P Drug Substance
For a drug product supplied with reconstitution diluents, information on the diluents should be provided in a separate part P.
For combination products, the compatibility of drug substances with each other should be discussed.

72. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data 3.2.P Drug Product P.2 Pharmaceutical Development
3.2.P Excipients
The choice of excipients listed in 3.2.P.1,
their concentration, and
the characteristics that can influence the drug product performance should be discussed relative to their respective functions.

73. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data P Drug Product P.2 Pharmaceutical Development
3.2.P.2.2 Drug Product
3.2.P Formulation Development
3.2.P Overages [name, dosage form]
3.2.P Physicochemical and Biological Properties
3.2.P.2.3 Manufacturing Process Development
3.2.P.2.4 Container Closure System
3.2.P.2.5 Microbiological Attributes

74. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data 3.2.P Drug Product P.3 Manufacture
3.2.P.3.1 Manufacturers
3.2.P.3.2 Batch Formula
3.2.P.3.3 Description of Manufacturing Process and Process Controls
3.2.P.3.4 Controls of Critical Steps
3.2.P.3.5 Process Validation and/or Evaluation

75. Batch Formula (core) Strength 150 mg Batch Size 450000 tablets
Ingredients
Quality
standard
Unit composition
Batch quantities mg % kg
Lamivudine (as API)
USP 34-NF29
150 50
67.5
Microcrystalline Cellulose
108 36
48.6
Pregelatinized Strach
25.5
8.5
11.475
Sodium Strach Glycolate 12 4
5.4
Magnesium Stearate
1.5
0.5
0.675
Sodium Lauryl Sulfate
EP 2010 3 1
1.35
Total
300
100
135

76. Batch Formula (coat) Strength 150 mg Composition of tablet coating
Quality
standard
Unit composition
Batch quantities mg % kg
HPMC (6cp)
USP 34-NF29
9.43
66.77
4.2435
Polyethylene Glycol 4000
2.35
16.63
1.0575
Titanium Dioxide
Isopropyl Alcohol
0.038 mL
-----
17.1 L
Purified Water
0.1 mL
45 L
Total
14.13
100
6.3575

77. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data 3.2.P Drug Product P.4 Control of Excipients
3.2.P.4.1 Specifications
3.2.P.4.2 Analytical Procedures
3.2.P.4.3 Validation of Analytical Procedures
3.2.P.4.4 Justification of Specifications
3.2.P.4.5 Excipients of Human or Animal Origin
3.2.P.4.6 Novel Excipients

78. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data 3.2.P Drug Product P.5 Control of Drug Product
3.2.P.5.1 Specifications
3.2.P.5.2 Analytical Procedures
3.2.P.5.3 Validation of Analytical Procedures
3.2.P.5.4 Batch Analyses
3.2.P.5.5 Characterization of Impurities
3.2.P.5.6 Justification of Specifications

79. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data 3.2.P Drug Product P.6 Reference Standards
3.2.P.6 Reference Standards or Materials

80. 3.2.P.7 Container Closure System
Module 3 (Quality) Body of data P Drug Product P.7 Containers
3.2.P.7 Container Closure System
Containers <661>
Permeation <671>
Biological reactivity test, in vitro <87>
Biological reactivity test, in vivo <88>

81. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data P Drug Product P.7 Containers
A brief description of the containers to be used should be given.
It is also helpful if any outer packages to be used are also mentioned in appropriate cases e.g. cardboard cartons to provide light protection for photosensitive material packed in clear glass ampoules.

82. Module 3 (Quality) 3. 2. Body of data 3. 2. P Drug Product 3. 2. P
Module 3 (Quality) Body of data 3.2.P Drug Product P.8 Stability
3.2.P.8.1 Stability Summary and Conclusion
3.2.P.8.2 Post-approval Stability Protocol and Stability Commitment
3.2.P.8.3 Stability Data

84. Module 3 (Quality) 3.3. Literatures
3.2.R. REGIONAL INFORMATION
3.2.A. APPENDICES
A1 Facilities and Equipment
A2 Adventitous Agents Safety Evaluation
A3 Novel Excipients
3.3 LITERATURE REFERENCES

85. For non-viral adventitious agents:
Detailed information should be provided on the avoidance and control of non-viral adventitious agents (e.g., transmissible spongiform encephalopathy agents, bacteria, mycoplasma, and fungi).
This information can include, for example, certification and/or testing of raw materials and excipients, and control of the production process, as appropriate for the material, process and agent

86. For viral adventitious agents:
Detailed information from viral safety evaluation studies should be provided in this section.
Viral evaluation studies should demonstrate that the materials used in production are considered safe, and that the approaches used to test, evaluate, and eliminate the potential risks during manufacturing are suitable.

87. A3 Novel Excipients For excipient(s) used for the first time in a drug
product or by a new route of administration, full details of manufacture, characterisation, and controls, with cross references to supporting safety data (nonclinical and/or clinical) should be provided according to the drug substance format

88. 3.2.R Regional information: EU
• Process validation scheme for the drug product
• Medical device
• Certificate(s) of suitability (CEP)
Medicinal products containing or using in the manufacturing process materials of animal and/ or human origin

89. Module 4 Module 4: Nonclinical Study Reports 4.2 Study Reports
4.1 Table of Contents
4.2 Study Reports
4.2.1 Pharmacology
4.2.2 Pharmacokinetics
4.2.3 Toxicology
4.3 Literature References

90. Module 5 Module 5: Clinical Study Reports
5.1 Table of Contents
5.2 Tabular Listing of All Clinical Studies
5.3 Clinical Study Reports
5.4 Literature References

91. Module 5 Invitro Invivo PSUR Bioequivalency Irritation test (Human)
Irritation test (Animal) > Module 4
Module 5

92. ICH/CTD Guidance M4: Organization of the CTD M4Q: The CTD — Quality
M4S: The CTD — Safety
M4E: The CTD — Efficacy.

93. Thanks for your
kind attention