OVERVIEW OF COMMON TECHNICAL DOCUMENT (CTD)

The Common Technical Document

The agreement to assemble all the Quality, Safety and Efficacy information in a common format (called CTD – Common Technical Document) has revolutionized the regulatory review processes, led to harmonized electronic submission that, in turn, enabled implementation of good review practices.

For industries, it has eliminated the need to reformat the information for submission to the different ICH regulatory authorities.

The CTD is organized into five modules. Module 1 is region specific and Modules 2, 3, 4 and 5 are intended to be common for all regions.

In July 2003, the CTD became the mandatory format for new drug applications in the EU and Japan, and the strongly recommended format of choice for NDAs submitted to the FDA.

Purpose of CTD

Organization of the CTD

CTD is divided into 5 modules:

Detailed Structure of CTD

Module 1: ADMINISTRATIVE INFORMATION

• 1.1 Table of contents.
• 1.2. Application form.
• 1.3. Summary of product characteristics, labelling and instructions for medical use:
• 1.3.1. Summary of product characteristics.
• 1.3.2. Labelling.
• 1.3.3. Instructions for medical use.
• 1.3.4. Mock-ups and specimens.
• 1.3.5. Summary of product characteristics already approved in the manufacturer/applicant-country.
• 1.4. Information about the independent experts:
• 1.4.1. Information about the quality expert.
• 1.4.2. Information about the pre-clinical expert.
• 1.4.3. Information about clinical expert.
• 1.5 Specific requirements for different types of applications.
• Annex to Module 1. Environmental risk assessment

MODULE 2: CTD SUMMARY

• 2.1. Table of contents of Modules 2 – 5.
• 2.2. Introduction.
• 2.3. Quality overall summary.
• 2.4. Pre-clinical overview:
• 2.5. Clinical overview
• 2.6. Pre-clinical summary
• 2.6.1. Pharmacology written summary.
• 2.6.2. Pharmacology tabulated summary.
• 2.6.3. Pharmacokinetics written summary.
• 2.6.4. Pharmacokinetics tabulated summary.
• 2.6.5. Toxicology written summary.
• 2.6.6. Toxicology tabulated summary.
• 2.7. Clinical summary:
• 2.7.1. Summary of biopharmaceutical studies and associated analytical methods.
• 2.7.2. Summary of clinical pharmacology studies.
• 2.7.3. Summary of clinical efficacy.
• 2.7.4. Summary of clinical safety.
• 2.7.5. Literature references.
• 2.7.6 Synopses of individual studies.

MODULE 3: QUALITY

CHEMICAL, PHARMACEUTICAL AND BIOLOGICAL INFORMATION

• 3.1. Table of contents.
• 3.2. Basic data.
• 3.2.S. Active substance(s).
• 3.2.S.1. General information: Nomenclature, Structure, General properties
• 3.2.S.2. Manufacture: Manufacturer(s), Process, Control of materials, Critical steps, Process validation, Manufacturing process development.
• 3.2.S.3. Characterization: Elucidation of structure, Impurities.
• 3.2.S.4. Control of active substance: Specification, Analytical procedures, Validation, Batch analyses, Justification.
• 3.2.S.5. Reference standards or materials.
• 3.2.S.6. Container/closure system.
• 3.2.S.7. Stability: Summary, Post-approval protocol, Stability data.
• 3.2.P. Finished medicinal product:
• 3.2.P.1. Description and composition.
• 3.2.P.2. Pharmaceutical development: Composition, Formulation development, Overages, Physicochemical properties, Manufacturing process development, Container, Microbiological attributes, Compatibility.
• 3.2.P.3. Manufacture: Manufacturer(s), Batch formula, Process description, Critical steps, Process validation.
• 3.2.P.4. Control of excipients: Specifications, Analytical procedures, Validation, Justification, Human/animal origin, Novel excipients.
• 3.2.P.5. Control of medicinal product: Specification(s), Analytical procedures, Validation, Batch analyses, Impurities, Justification.
• 3.2.P.6. Reference standards and materials.
• 3.2.P.7. Container/closure system.
• 3.2.P.8. Stability: Summary, Protocol, Data.
• 3.2.A. Appendices: Facilities, Adventitious agents safety evaluation, Novel excipients.
• 3.2.R. Additional information.
• 3.3. Literature references.

Module 4: PRE-CLINICAL STUDY REPORTS

• 4.1. Table of contents.
• 4.2. Study reports.
• 4.2.1. Pharmacology: Primary pharmacodynamic, Secondary pharmacodynamic, Safety pharmacology, Pharmacodynamic interactions.
• 4.2.2. Pharmacokinetics: Analytical methods, Absorption, Distribution, Metabolism, Excretion, Interactions, Other studies.
• 4.2.3. Toxicology: Single-dose, Repeated dose, Genotoxicity, Carcinogenicity, Reproductive and developmental, Local tolerance, Other toxicity.
• 4.3. Literature references.

MODULE 5: CLINICAL STUDY REPORTS

• 5.1. Table of contents.
• 5.2. Tabular listing of all clinical studies.
• 5.3. Clinical study reports:
• 5.3.1. Reports of biopharmaceutical studies.
• 5.3.2. Reports of studies pertinent to pharmacokinetics using human biomaterials.
• 5.3.3. Reports of human pharmacokinetic studies.
• 5.3.4. Reports of human pharmacodynamic studies
• 5.3.5. Reports of efficacy and safety studies.
• 5.3.6. Reports of post-registration experience.
• 5.3.7. Samples of case reports forms and individual patient listings.
• 5.4. Literature references.

Note: This is as per ICH CTD guidelines. For industries, CTD eliminated the need to reformat for different ICH authorities. Module 1 is always region specific (US, EU, Japan).

About the Author

Mahummed Asif is a experienced pharmaceutical Quality Assurance professional and publisher of Pharmashare. He has worked with leading Pharmaceutical organizations and has developed extensive expertise in Quality Assurance, deviation management, investigations, CAPA, QMS, Product Life Cycle Management, change control, risk management, validation, product complaints, product recalls, and regulatory compliance. He is passionate about sharing practical pharmaceutical knowledge with professionals, students, and quality practitioners across the industry.