3. Module 2

The respective experts will also produce the various summaries in Module 2. Summaries should make it easier for assessors at the regulatory agencies to get an overview of the application. Again, the regulatory affairs professionals are involved.

Module 2 contains seven sections:
2.1 Table of contents
2.2 Introduction
2.3 Quality Overall Summary
2.4 Non-clinical Overview
2.5 Clinical Overview
2.6 Non-clinical Written and Tabulated Summaries
2.7 Clinical Summary.

Section 2.3 The Quality Overall Summary (QOS):

  • a summary that follows the scope and the outline of the body of data in Module 3.
  • should not include information, data or justification that was not already included in Module 3 or in other parts of the CTD.
  • should include sufficient information from each section to provide the Quality reviewer with an overview of Module 3.
  • should emphasize critical key parameters of the product and provide, for instance, justification in cases where guidelines were not followed.
  • should include a discussion of key issues that integrates information from sections in the Quality Module and supporting information from other Modules (e.g., qualification of impurities via toxicological studies discussed under the CTD-S module).

Section 2.4 Non-clinical Overview:

  • should present an integrated and critical assessment of the pharmacologic, pharmacokinetic, and toxicologic evaluation of the pharmaceutical.
  • where relevant guidelines on the conduct of studies exist, any deviation from these guidelines should be discussed and justified.
  • the nonclinical testing strategy should be discussed and justified.
  • should contain a comment on the GLP status of the studies submitted.
  • any association between nonclinical findings and the quality characteristics of the human pharmaceutical, the results of clinical trials, or effects seen with related products should be indicated, as appropriate.
  • should include assessment of the impurities and degradants present in the active substance and product along with what is known of their potential pharmacologic and toxicologic effects.
  • the implications of any differences in the chirality, chemical form, and impurity profile between the compound used in the nonclinical studies and the product to be marketed should be discussed.

Section 2.5 Clinical Overview should:

  • provide a critical analysis of the clinical data in the CTD
  • provide a succinct discussion and interpretation of the clinical information in the CTD together with any other relevant information (e.g., pertinent animal data or product quality issues that may have clinical implications).
  • present the strengths and limitations of the development program and study results, analyse the benefits and risks of the medicine in its intended use, and describe how the study results support critical parts of the prescribing information.
  • describe and explain the overall approach to the clinical development of a medicine, including critical study design decisions;
  • assess the quality of the design and performance of the studies, and include a statement regarding GCP compliance;
  • provide a brief overview of the clinical findings, including important limitations
  • provide an interpretation of how the efficacy and safety findings support the proposed dose and target indication and an evaluation of how prescribing information and other approaches will optimise benefits and manage risks;
  • address particular efficacy or safety issues encountered in development, and how they have been evaluated and resolved;
  • explore unresolved issues, explain why they should not be considered as barriers to approval, and describe plans to resolve them;

Section 2.6 Non-clinical Written and Tabulated Summaries:

  • guidance, not intended to indicate what studies are required. It merely indicates an appropriate format for the non-clinical data that have been acquired.
  • brief information concerning the medicine’s structure (preferably, a structure diagram should be provided) and pharmacologic properties;
  • information on the medicine’s proposed clinical indication, dose, and duration of use.
  • whenever appropriate, age- and gender-related effects should be discussed.
  • relevant findings with stereoisomers and/or metabolites, as appropriate.
  • in the Discussion and Conclusion sections, information across studies and across species; exposure in the test animals should be related to exposure in humans given the maximum intended doses.

Section 2.7 Clinical Summary:

  • intended to provide a detailed, factual summary of all of clinical information in the CTD.
  • includes information provided in ICH E3 clinical study reports; information obtained from any meta-analyses or other cross-study analyses for which full reports have been included in Module 5; and post-marketing data for products that have been marketed in other regions.
    • the comparisons and analyses of results across studies should focus on factual observations.

The bulk elements of the documentation for quality, safety and efficacy are in Modules 3 – 5. This documentation is produced by various functions in the company, each expert in their field. The Regulatory Affairs (RA) professionals ensure that the documentation is in line with all relevant regulations, directives and guidelines.