Streamlining Regulatory Processes: Converting IMPD to eCTD

Efficient regulatory submissions are pivotal in the pharmaceutical industry's journey from development to market access. In this guide, we'll explore the conversion of an Investigational Medicinal Product Dossier (IMPD) to electronic Common Technical Document (eCTD), specifically focusing on the crucial step of mapping IMPD sections to eCTD's Chemistry, Manufacturing, and Controls (CMC) sections. By aligning IMPD content with the structured framework of eCTD, pharmaceutical companies can ensure regulatory compliance across regions while gaining efficiency.

IMPD and eCTD/CMC Basics

Let's start with defining IMPD and eCTD/CMC and their purposes.

What is an IMPD?

The Investigational Medicinal Product Dossier (IMPD) contains essential data on the quality, manufacture, and control of an investigational medicinal product. It encompasses preclinical and clinical trial information, serving as a foundational document for regulatory submissions outside of the United States (i.e., Canada and Europe).

What is eCTD?

Electronic Common Technical Document (eCTD) is a standardized electronic format for regulatory submissions, providing a structured framework for organizing documents defined by the International Council for Harmonisation (ICH). It comprises modules covering various aspects of drug development, including Chemistry, Manufacturing, and Controls (CMC), among others.

What is CMC?

CMC sections within eCTD focus on the pharmaceutical development and manufacturing processes, encompassing information related to drug substance, drug product, manufacturing process, and controls. eCTD's CMC sections contain information similar to the Quality Sections of an IMPD.

Legacy IMPD Structure vs. eCTD Structure

Below, you can see how the legacy IMPD structure aligns with the modern eCTD structure.

IMPD	eCTD
1. INTRODUCTION	m2 Summaries / 2.2 Introduction
2.1 CHEMICAL PHARMACEUTICAL DATA	m3 Quality / 3.2 Body of data
2.1.S ACTIVE SUBSTANCE	3.2.S Drug substance [name, manufacturer]
2.1.S.1 General Information	3.2.S.1 General information
2.1.S.1.1 Nomenclature	3.2.S.1.1 Nomenclature
2.1.S.1.2 Structure	3.2.S.1.2 Structure
2.1.S.1.3 General Properties	3.2.S.1.3 General properties
2.1.S.2 Manufacture	3.2.S.2 Manufacture
2.1.S.2.1 Manufacturer(s)	3.2.S.2.1 Manufacturer(s)
2.1.S.2.2 Description of Manufacturing Process and Process Controls	3.2.S.2.2 Description of Manufacturing Process and Process Controls
2.1.S.2.3 Control of Materials	3.2.S.2.3 Control of Materials
2.1.S.2.4 Controls of Critical Steps and Intermediates	3.2.S.2.4 Controls of Critical Steps and Intermediates
2.1.S.2.5 Process Validation and/or Evaluation	3.2.S.2.5 Process Validation and/or Evaluation
2.1.S.2.6 Manufacturing Process Development	3.2.S.2.6 Manufacturing Process Development
2.1.S.3 Characterisation	3.2.S.3 Characterization
2.1.S.3.1 Elucidation of Structure and Other Characteristics	3.2.S.3.1 Elucidation of Structure and other Characteristics
2.1.S.3.2 Impurities	3.2.S.3.2 Impurities
2.1.S.4 Control of Active Substance	3.2.S.4 Control of drug substance
2.1.S.4.1 Specification	3.2.S.4.1 Specification
2.1.S.4.2 Analytical Procedures	3.2.S.4.2 Analytical Procedures
2.1.S.4.3 Validation of Analytical Procedures	3.2.S.4.3 Validation of Analytical Procedures
2.1.S.4.4 Batch Analyses	3.2.S.4.4 Batch Analyses
2.1.S.4.5 Justification of Specification	3.2.S.4.5 Justification of Specification
2.1.S.5 Reference Standards or Materials	3.2.S.5 Reference standards or materials
2.1.S.6 Container Closure System	3.2.S.6 Container closure systems
2.1.S.7 Stability	3.2.S.7 Stability 3.2.S.7.1 Stability Summary and Conclusions 3.2.S.7.2 Post Approval Stability Protocol and Stability Commitment 3.2.S.7.3 Stability Data
2.1.P DRUG PRODUCT (This section can be repeated for a Placebo Product using numbering 2.1.Q.)	3.2.P Drug product [name, dosage form, manufacturer] (This section can be repeated for a Placebo Product using the same numbering with the appropriate metadata mirrored in the brackets.)
2.1.P.1 Description and Composition of the Investigational Medicinal Product	3.2.P.1 Description and composition of the drug product
2.1.P.2 Pharmaceutical Development	3.2.P.2 Pharmaceutical development
2.1.P.3 Manufacture	3.2.P.3 Manufacture
2.1.P.3.1 Manufacturer(s)	3.2.P.3.1 Manufacturer(s)
2.1.P.3.2 Batch Formula	3.2.P.3.2 Batch Formula
2.1.P.3.3 Description of Manufacturing Process and Process Controls	3.2.P.3.3 Description of Manufacturing Process and Process Controls
2.1.P.3.4 Controls of Critical Steps and Intermediates	3.2.P.3.4 Controls of Critical Steps and Intermediates
2.1.P.3.5 Process Validation and/or Evaluation	3.2.P.3.5 Process Validation and/or Evaluation
2.1.P.4 Control of Excipients	3.2.P.4 Control of excipients [name]
2.1.P.4.1 Specification	3.2.P.4.1 Specification(s)
2.1.P.4.2 Analytical Procedures	3.2.P.4.2 Analytical Procedures
2.1.P.4.3 Validation of Analytical Procedures	3.2.P.4.3 Validation of Analytical Procedures
2.1.P.4.4 Justification of Specifications	3.2.P.4.4 Justification of Specifications
2.1.P.4.5 Excipients of Human or Animal Origin	3.2.P.4.5 Excipients of Human or Animal Origin
2.1.P.4.6 Novel Excipients	3.2.P.4.6 Novel Excipients
2.1.P.5 Control of the Investigational Medicinal Product	3.2.P.5 Control of drug product
2.1.P.5.1 Specification	3.2.P.5.1 Specification(s)
2.1.P.5.2 Analytical Procedures	3.2.P.5.2 Analytical Procedures
2.1.P.5.3 Validation of Analytical Procedures	3.2.P.5.3 Validation of Analytical Procedures
2.1.P.5.4 Batch Analyses	3.2.P.5.4 Batch Analyses
2.1.P.5.5 Characterization of Impurities	3.2.P.5.5 Characterization of Impurities
2.1.P.5.6 Justification of Specification	3.2.P.5.6 Justification of Specification(s)
2.1.P.6 Reference Standards or Materials	3.2.P.6 Reference standards or materials
2.1.P.7 Container Closure System	3.2.P.7 Container closure system
2.1.P.8 Stability	3.2.P.8 Stability 3.2.P.8.1 Stability Summary and Conclusion 3.2.P.8.2 Postapproval Stability Protocol and Stability Commitment 3.2.P.8.3 Stability Data
2.1.A APPENDICES	3.2.A Appendices
2.1.A.1 Facilities and Equipment	3.2.A.1 Facilities and Equipment [name, manufacturer]
2.1.A.2 Adventitious Agents Safety Evaluation	3.2.A.2 Adventitious agents safety evaluation [name, dosage form, manufacturer]
2.1.A.3 Novel Excipients	3.2.A.3 Novel excipients
2.1.A.4 Solvents for Reconstitution and Diluents	3.2.R Regional information
2.2 NON-CLINICAL PHARMACOLOGY, PHARMACOKINETICS AND TOXICOLOGY 2.2.1 Test Materials used in Toxicity Studies 2.2.2 Integrated Assessment of the Data Package 2.2.3 List of studies Conducted & References 2.2.4 GLP statement and Bioanalytical Methods	m2 Summaries / 2.4 Nonclinical Overview
2.3 CLINICAL DATA 2.3.1 Clinical Pharmacology 2.3.2 Clinical Pharmacokinetics 2.3.3 Human Exposure 2.4 BENEFITS AND RISKS ASSESSMENT	m2 Summaries / 2.5 Clinical Overview
REFERENCES	3.3 Literature references

Benefits of IMPD to eCTD Alignment

IMPDs can use eCTD numbering, and by doing so, there are efficiencies to be gained.

Granular Documents for Simultaneous Submissions

By splitting an IMPD into granular format based on FDA's granularity index, you can simultaneously author both the IMPD and future US IND CMC documents. While the granular versions can be submitted to the IND, the IMPD can be compiled into a submission-ready PDF for ex-US submissions.

Efficiency for Future IMPD / eCTD Updates

When it comes time to update the IMPD, only the necessary granular documents will need to be updated, rather than working with a large, easily corrupted Word document. This reduces the potential for formatting errors and speeds time to compilation and submission. This also allows updates to be aligned between US and ex-US submissions rather than having to update two versions of the same information.

SWOT IMPD to eCTD Services

Whether you're creating your first set of CMC or IMPD documents or looking to streamline your legacy process, The Sugar Water Operations Team can help. We'd love to talk to you about what we can do to meet your needs. And while you're there, sign up for our newsletter so you never miss an update!