El CTD consta de cinco módulos.

• El Módulo 1 no es común a las tres regiones ICH y lo define la Comisión

Europea en consulta con las autoridades de los Estados Miembros
y la Agencia Europea del Medicamento. Los Módulos 2, 3, 4 y 5 son
comunes a las tres regiones ICH. Veamos el contenido de cada Módulo
de manera resumida.
• El Módulo 1 contiene los datos administrativos junto con la información
específica a nivel regional o nacional. Contiene el formulario de
solicitud, el resumen de las características de producto o ficha técnica,
prospecto y etiquetado, etc.
• El Módulo 2 contiene los resúmenes de los tres módulos siguientes. Es
decir, los resúmenes de la información de Calidad, información Preclínica
y la información Clínica así como los resúmenes tabulados de los
estudios preclínicos y clínicos realizados. Estos resúmenes tienen que
ser elaborados por expertos que los firmaran y acreditaran su experiencia
en el área correspondiente.
• El Módulo 3 contiene la información química, farmacéutica y biológica.
Es necesario seguir las recomendaciones de la directriz ICH M4Q (revisión
1) para completar la información de toda la estructura del CTD.
• El Módulo 4 contiene la información de los estudios preclínicos que
deben presentarse en el orden que dispone la directriz ICH M4S (revisión
2).
• El Módulo 5 contiene la información de los estudios clínicos llevados
a cabo con el medicamento. Esta información se incluirá en el expediente
del dossier de registro siguiendo el orden marcado por la
directriz ICH M4E (revisión 2).

Como hemos comentado anteriormente, el CTD está pensado para ser

utilizado con cualquier tipo de medicamento así como cualquier tipo
de solicitud. No obstante, en función del tipo de solicitud esté formato
puede sufrir modificaciones. En el caso de no disponer de información
o de que esta no proceda, no podemos eliminar el apartado/sección del
CTD, sino que se mantendrá el apartado/sección correspondiente pero
se indicará como “No procede” o “No relevante”. En el resumen
correspondiente del Módulo 2 justificaremos la ausencia de información o la
carencia de relevancia.

Veamos algunos ejemplos:

• Solicitud de acuerdo al Artículo 8(3): se presentará un dossier con
datos administrativos, de calidad, preclínicos y clínicos. Todos los
módulos tienen que presentarse en la solicitud con datos propios
del medicamento.

• Solicitud de acuerdo al artículo 10(1): solicitud de un genérico; de

acuerdo al artículo 10(3): solicitud de un híbrido o de acuerdo al
artículo 10(4): solicitud de un biosimilar. En todas ellas, el Módulo
1 contendrá la información del medicamento de referencia. En los
tres casos, el Módulo 2 llevará los resúmenes de Calidad, Preclínico
y Clínico. No es necesario incluir los resúmenes de los estudios en
formato tabular a no ser que se incluyan estudios propios. El Módulo
4 puede ser sustituido por referencias bibliográficas o estudios preclínicos
propios (como puede ocurrir en las solicitudes híbridas).
En el caso de la solicitud de un genérico, el Módulo 5 constará del
estudio de bioequivalencia únicamente.

• Solicitud de acuerdo al artículo 10a: solicitud de uso bien establecido.

Los Módulos 4 y 5 pueden ser referencias bibliográficas.
A continuación, veremos de manera esquemática las secciones incluidas
en los cinco Módulos y que se deben completar con la información del
medicamento en cualquier tipo de solicitud y procedimiento:

Módulo 1:
1.0 Cover Letter
1.1 Comprehensive Table of Contents
1.2 Application Form
1.3 Product Information
1.3.1 SPC, Labelling and Package Leaflet
1.3.2 Mock-up
1.3.3 Specimen
1.3.4 Consultation with Target Patient Groups
1.3.5 Product Information already approved in the
Member States
1.3.6 Braille
1.4 Information about the Experts
1.4.1 Quality
1.4.2 Non-Clinical
1.4.3 Clinical
1.5 Specific Requirements for Different Types of Applications
1.5.1 Information for Bibliographical Applications
1.5.2 Information for Generic, ‘Hybrid’ or Bio-similar Applications
1.5.3 (Extended) Data/Market Exclusivity
1.5.4 Exceptional Circumstances
1.5.5 Conditional Marketing Authorisation
1.6 Environmental Risk Assessment
1.6.1 Non-GMO
1.6.2 GMO
1.7 Information relating to Orphan Market Exclusivity
1.7.1 Similarity
1.7.2 Market Exclusivity
1.8 Information relating to Pharmacovigilance
1.8.1 Pharmacovigilance System
1.8.2 Risk-management System
1.9 Information relating to Clinical Trials
1.10 Information relating to Paediatrics
Responses to Questions
Additional Data

Módulo 2: resúmenes del Documento Técnico Común

2.1 Common Technical Document Table of Contents (Module 2 – 5)
2.2 Introduction
2.3 Quality Overall Summary (QOS)
Introduction
2.3.S DRUG SUBSTANCE (NAME, MANUFACTURER)
2.3.S.1 General Information (name, manufacturer)
2.3.S.2 Manufacture (name, manufacturer)
2.3.S.3 Characterisation (name, manufacturer)
2.3.S.4 Control of Drug Substance (name, manufacturer)
2.3.S.5 Reference Standards or Materials (name, manufacturer)
2.3.S.6 Container Closure System (name, manufacturer)
2.3.S.7 Stability (name, manufacturer)
2.3.P DRUG PRODUCT (NAME, DOSAGE FORM)
2.3.P.1 Description and Composition of the Drug Product (name,
dosage form)
2.3.P.2 Pharmaceutical Development (name, dosage form)
2.3.P.3 Manufacture (name, dosage form)
2.3.P.4 Control of Excipients (name, dosage form)
2.3.P.5 Control of Drug Product (name, dosage form)
2.3.P.6 Reference Standards or Materials (name, dosage form)
2.3.P.7 Container Closure System (name, dosage form)
2.3.P.8 Stability (name, dosage form)
2.3.A Appendices
2.3.A.1 Facilities and Equipment (name, manufacturer)
2.3.A.2 Adventitious Agents Safety Evaluation (name, dosage form,
manufacturer)
2.3.A.3 Excipients
2.3.R Regional Information
2.4 Nonclinical Overview
2.5 Clinical Overview
2.6 Nonclinical Summary
2.7 Clinical Summary

Módulo 3: Calidad
3.1. TABLE OF CONTENTS OF MODULE 3
3.2. BODY OF DATA
3.2.S DRUG SUBSTANCE (NAME, MANUFACTURER)
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 (name, manufacturer)
3.2.S.2 Manufacture (name, manufacturer)
3.2.S.2.1 Manufacturer(s) (name, manufacturer)
3.2.S.2.2 Description of Manufacturing Process and Process
Controls (name, manufacturer)
3.2.S.2.3 Control of Materials (name, manufacturer)
3.2.S.2.4 Controls of Critical Steps and Intermediates (name,
manufacturer)
3.2.S.2.5 Process Validation and/or Evaluation (name, manufacturer)
3.2.S.2.6 Manufacturing Process Development (name, manufacturer)
3.2.S.3 Characterisation (name, manufacturer)
3.2.S.3.1 Elucidation of Structure and other Characteristics (name,
manufacturer)
3.2.S.3.2 Impurities (name, manufacturer)
3.2.S.4 Control of Drug Substance (name, manufacturer)
3.2.S.4.1 Specification (name, manufacturer)
3.2.S.4.2 Analytical Procedures (name, manufacturer)
3.2.S.4.3 Validation of Analytical Procedures (name, manufacturer)
3.2.S.4.4 Batch Analyses (name, manufacturer)
3.2.S.4.5 Justification of Specification (name, manufacturer)
3.2.S.5 Reference Standards or Materials (name, manufacturer)
3.2.S.6 Container Closure System (name, manufacturer)
3.2.S.7 Stability (name, manufacturer)
3.2.S.7.1 Stability Summary and Conclusions (name, manufacturer)
3.2.S.7.2 Post-approval Stability Protocol and Stability Commitment
(name, manufacturer)
3.2.S.7.3 Stability Data (name, manufacturer)
3.2.P DRUG PRODUCT (NAME, DOSAGE FORM)
3.2.P.1 Description and Composition of the Drug Product (name,
dosage form)
3.2.P.2 Pharmaceutical Development (name, dosage form)
3.2.P.2.1 Components of the Drug Product (name, dosage form)
3.2.P.2.1.1 Drug Substance (name, dosage form)
3.2.P.2.1.2 Excipients (name, dosage form)
3.2.P.2.2 Drug Product (name, dosage form)
3.2.P.2.2.1 Formulation Development (name, dosage form)
3.2.P.2.2.2 Overages (name, dosage form)
3.2.P.2.2.3 Physicochemical and Biological Properties (name,
dosage form)
3.2.P.2.3 Manufacturing Process Development (name, dosage form)
3.2.P.2.4 Container Closure System (name, dosage form)
3.2.P.2.5 Microbiological Attributes (name, dosage form)
3.2.P.2.6 Compatibility (name, dosage form)
3.2.P.3 Manufacture (name, dosage form)
3.2.P.3.1 Manufacturer(s) (name, dosage form)
3.2.P.3.2 Batch Formula (name, dosage form)
3.2.P.3.3 Description of Manufacturing Process and Process Controls
(name, dosage form)
3.2.P.3.4 Controls of Critical Steps and Intermediates (name, dosage
form)
3.2.P.3.5 Process Validation and/or Evaluation (name, dosage form)
3.2.P.4 Control of Excipients (name, dosage form)
3.2.P.4.1 Specifications (name, dosage form)
3.2.P.4.2 Analytical Procedures (name, dosage form)
3.2.P.4.3 Validation of Analytical Procedures (name, dosage form)
3.2.P.4.4 Justification of Specifications (name, dosage form)
3.2.P.4.5 Excipients of Human or Animal Origin (name, dosage form)
3.2.P.4.6 Novel Excipients (name, dosage form)
3.2.P.5 Control of Drug Product (name, dosage form)
3.2.P.5.1 Specification(s) (name, dosage form)
3.2.P.5.2 Analytical Procedures (name, dosage form)
3.2.P.5.3 Validation of Analytical Procedures (name, dosage form)
3.2.P.5.4 Batch Analyses (name, dosage form)
3.2.P.5.5 Characterisation of Impurities (name, dosage form)
3.2.P.5.6 Justification of Specification(s) (name, dosage form)
3.2.P.6 Reference Standards or Materials (name, dosage form)
3.2.P.7 Container Closure System (name, dosage form)
3.2.P.8 Stability (name, dosage form)
3.2.P.8.1 Stability Summary and Conclusion (name, dosage form)
3.2.P.8.2 Post-approval Stability Protocol and Stability Commitment
(name, dosage form)
3.2.P.8.3 Stability Data (name, dosage form)
3.2.A APPENDICES
3.2.A.1 Facilities and Equipment (name, manufacturer)
3.2.A.2 Adventitious Agents Safety Evaluation (name, dosage form,
manufacturer)
3.2.A.3 Excipients
3.2.R REGIONAL INFORMATION
3.3 LITERATURE REFERENCES

Módulo 4:
4.1 TABLE OF CONTENTS OF MODULE 4
4.2 STUDY REPORTS
4.2.1 Pharmacology
4.2.1.1 Primary Pharmacodynamics
4.2.1.2 Secondary Pharmacodynamics
4.2.1.3 Safety Pharmacology
4.2.1.4 Pharmacodynamic Drug Interactions
4.2.2 Pharmacokinetics
4.2.2.1 Analytical Methods and Validation Reports (if separate
reports are available)
4.2.2.2 Absorption
4.2.2.3 Distribution
4.2.2.4 Metabolism
4.2.2.5 Excretion
4.2.2.6 Pharmacokinetic Drug Interactions (nonclinical)
4.2.2.7 Other Pharmacokinetic Studies
4.2.3 Toxicology
4.2.3.1 Single-Dose Toxicity (in order by species, by route)
4.2.3.2 Repeat-Dose Toxicity (in order by species, by route, by
duration; including supportive toxicokinetics evaluations)
4.2.3.3 Genotoxicity
4.2.3.3.1 In vitro
4.2.3.3.2 In vivo (including supportive toxicokinetics evaluations)
4.2.3.4 Carcinogenicity (including supportive toxicokinetics evaluations)
4.2.3.4.1 Long-term studies (in order by species; including
range-finding studies that cannot appropriately be included
under repeat-dose toxicity or pharmacokinetics)
4.2.3.4.2 Short- or medium-term studies (including range-finding
studies that cannot appropriately be included under repeat
dose toxicity or pharmacokinetics)
4.2.3.4.3 Other studies
4.2.3.5 Reproductive and Developmental Toxicity (including range-
finding studies and supportive toxicokinetics evaluations) (If modified study
designs are used, the following sub-headings
should be modified accordingly.)
4.2.3.5.1 Fertility and early embryonic development
4.2.3.5.2 Embryo-fetal development
4.2.3.5.3 Prenatal and postnatal development, including maternal
function
4.2.3.5.4 Studies in which the offspring (juvenile animals)
are dosed and/or further evaluated.
4.2.3.6 Local Tolerance
4.2.3.7 Other Toxicity Studies (if available)
4.2.3.7.1 Antigenicity
4.2.3.7.2 Immunotoxicity
4.2.3.7.3 Mechanistic studies (if not included elsewhere)
4.2.3.7.4 Dependence
4.2.3.7.5 Metabolites
4.2.3.7.6 Impurities
4.2.3.7.7 Other
4.3 LITERATURE REFERENCES

Módulo 5:
5.1 Table of Contents of Module 5
5.2 Tabular Listing of All Clinical Studies
5.3 Clinical Study Reports
5.3.1 Reports of Biopharmaceutic Studies
5.3.1.1 Bioavailability (BA) Study Reports
5.3.1.2 Comparative BA and Bioequivalence (BE) Study Reports
5.3.1.3 In vitro-In vivo Correlation Study Reports
5.3.1.4 Reports of Bioanalytical and Analytical Methods for Human
Studies
5.3.2 Reports of Studies Pertinent to Pharmacokinetics using Human
Biomaterials
5.3.2.1 Plasma Protein Binding Study Reports
5.3.2.2 Reports of Hepatic Metabolism and Drug Interaction Studies
5.3.2.3 Reports of Studies Using Other Human Biomaterials
5.3.3 Reports of Human Pharmacokinetic (PK) Studies
5.3.3.1 Healthy Subject PK and Initial Tolerability Study Reports
5.3.3.2 Patient PK and Initial Tolerability Study Reports
5.3.3.3 Intrinsic Factor PK Study Reports
5.3.3.4 Extrinsic Factor PK Study Reports
5.3.3.5 Population PK Study Reports
5.3.4 Reports of Human Pharmacodynamic (PD) Studies
5.3.4.1 Healthy Subject PD and PK/PD Study Reports
5.3.4.2 Patient PD and PK/PD Study Reports
5.3.5 Reports of Efficacy and Safety Studies
5.3.5.1 Study Reports of Controlled Clinical Studies Pertinent to
the Claimed Indication
5.3.5.2 Study Reports of Uncontrolled Clinical Studies
5.3.5.3 Reports of Analyses of Data from More Than One Study
5.3.5.4 Other Clinical Study Reports
5.3.6 Reports of Post-Marketing Experience
5.3.7 Case Report Forms and Individual Patient Listings