Preparing the IMPD: Investigational Medicinal Product Dossier

Introduction

The Investigational Medicinal Product Dossier (IMPD) is a critical document required for clinical trial applications in the EU. It provides comprehensive information about the quality, manufacture, control, and safety of investigational medicinal products used in clinical trials.

What is the IMPD?

The IMPD is required for clinical trial applications (CTA) in the EU and provides detailed information about the investigational medicinal product. It follows a structure similar to Module 3 of the CTD but adapted for investigational products.

IMPD Structure

The IMPD consists of several key sections:

Part I: Quality (Pharmaceutical Documentation)

This is the main section containing:

S. Drug Substance (Active Pharmaceutical Ingredient)

• General information and nomenclature
• Manufacture and characterization
• Control of drug substance
• Reference standards
• Container closure system
• Stability data

P. Drug Product (Finished Dosage Form)

• Description and composition
• Pharmaceutical development
• Manufacture
• Control of excipients
• Control of drug product
• Reference standards
• Container closure system
• Stability

A. Appendices

• Facilities and equipment
• Adventitious agents safety evaluation
• Novel excipients

R. Regional Information

• Manufacturing authorization
• GMP certificates
• Batch analysis certificates

Part II: Non-Clinical Documentation

Summary of non-clinical pharmacology and toxicology data supporting the clinical trial.

Part III: Clinical Documentation

Summary of previous clinical experience with the investigational product or similar products.

IMPD Preparation Best Practices

1. Start Early

Begin IMPD preparation during product development to ensure all necessary data is generated and documented appropriately.

2. Follow EudraLex Guidelines

Refer to EudraLex Volume 10 and the detailed guidance on IMPD preparation provided by the European Commission.

3. Use the IMPD Template

Utilize the official IMPD template (available from EMA) to ensure all required sections are included and properly formatted.

4. Ensure GMP Compliance

Manufacturing of investigational products must comply with GMP requirements. Include appropriate GMP certificates and manufacturing authorizations.

5. Justify the Clinical Trial

The IMPD should support the rationale for the clinical trial and demonstrate that the quality of the investigational product is adequate for the intended use.

Common Challenges

Challenge: Determining Level of Detail

Solution: Consider the phase of development, known risks, and regulatory precedents. Early phase trials may require less detail than late-phase trials.

Challenge: Managing Updates

Solution: Establish version control procedures and clearly document all changes to the IMPD throughout the clinical development program.

Challenge: Coordinating Multiple Sources

Solution: Designate a qualified person to coordinate IMPD preparation and ensure consistency across all sections.

Common Technical Document (CTD) for Pharmaceuticals

The CTD is an internationally harmonized format for preparing regulatory submissions for pharmaceutical products. It consists of five modules:

• Module 1: Regional administrative information
• Module 2: Common Technical Document summaries
• Module 3: Quality (Chemistry, Manufacturing, and Controls)
• Module 4: Nonclinical study reports
• Module 5: Clinical study reports

MDR Technical Documentation for Medical Devices

Under the EU Medical Device Regulation (MDR 2017/745), manufacturers must compile comprehensive technical documentation that demonstrates conformity with regulatory requirements. The structure includes:

• Device description and specifications
• Information supplied by the manufacturer
• Design and manufacturing information
• General safety and performance requirements
• Benefit-risk analysis and risk management
• Product verification and validation
• Clinical evaluation
• Post-market surveillance

Comparative Analysis

Clinical Evidence Requirements

CTD: Requires extensive clinical trial data with detailed Clinical Study Reports following ICH E3 guidelines. Emphasis on randomized controlled trials demonstrating efficacy and safety.

MDR: Clinical evaluation can include clinical investigations, literature reviews, and post-market clinical follow-up. Equivalence to existing devices may be demonstrated in some cases.

Quality Documentation

CTD Module 3: Detailed chemistry, manufacturing, and controls information including drug substance and drug product specifications, manufacturing processes, and stability data.

MDR: Design and manufacturing information including materials, manufacturing processes, quality management system, and compliance with harmonized standards (e.g., ISO 13485).

Risk Management

CTD: Risk management integrated into Module 2.5 (Clinical Overview) and Module 2.7 (Clinical Summary) as part of benefit-risk assessment.

MDR: Comprehensive risk management file required following ISO 14971, with detailed risk analysis, evaluation, and control measures as a standalone section.

Post-Market Requirements

CTD: Post-marketing data included in periodic safety update reports (PSURs) and risk management plans (RMPs), submitted separately from the initial CTD.

MDR: Post-market surveillance plan and post-market clinical follow-up plan must be included in the initial technical documentation and continuously updated.

Similarities

• Both require comprehensive safety and performance data
• Both emphasize risk-benefit analysis
• Both require quality management system documentation
• Both need to demonstrate compliance with applicable standards
• Both require ongoing post-market monitoring

Practical Implications

For Combination Products

Products that combine drugs and devices (e.g., drug-eluting stents, prefilled syringes) must address requirements from both frameworks. The primary mode of action determines which regulation takes precedence, but documentation must satisfy both sets of requirements.

For Companies Working Across Sectors

Organizations operating in both pharmaceutical and medical device sectors should:

• Develop expertise in both regulatory frameworks
• Establish separate but coordinated documentation processes
• Leverage common elements (e.g., quality systems, risk management)
• Ensure teams understand the distinct requirements