Preparing a drug registration for the US and the EU: Parallel or sequential applications? – Part 2

Nathalie Boeglin, Alice Rolland, Frederic Pailloux, David Uguen

Published in Regulatory Rapporteur, June 2015

CONTENTS

01 Introduction 3

02 Example: Comparison of US CTD Module 1 versus EU CTD Module 1 4

03 Voisin Consulting Life Sciences 5

04 Additional information 6

Introduction

How do the differences between EU and US applications impact the application strategy?

This article, the second in a two-part paper highlights the potential differences in the content of the safety/nonclinical, efficacy/clinical and administrative/regional sections of the common technical document (CTD) between the US and the EU. It provides applicants with an overview of the main challenges faced by submission teams targeting a global fi ling, during the conversion of a registration dossier from one region to the other, and proposes methods to help decide whether the applications should be prepared in a sequential or a parallel manner.

The first part of this paper, published in Regulatory Rapporteur in February 2015, focused on the Quality/CMC (chemistry, manufacturing, and controls) sections of the EU and US CTDs.

The purpose of this second part of the paper is to clarify the nature of the differences which exist between the two regions, especially with regards to the Safety sections (Module  2.4 – Nonclinical Overview, Module  2.6 – Nonclinical Summaries and Module 4), Efficacy sections (Module 2.5 – Clinical Overview, Module 2.7 – Clinical Summaries and Module 5), and the administrative/regional sections (Module 1) of the applications. The pros and cons of the parallel versus sequential approaches for the preparation of the CTD as a whole are also discussed.

US CTD Module 1 EU CTD Module 11.1 Forms 1.0 Cover Letter1.2 Cover Letters 1.1 Comprehensive Table of Contents1.3 Administrative Information 1.2 Application Form1.4 References 1.3 Product Information1.5 Application Status 1.3.1 SPC, Labelling and Package Leaflet1.6 Meetings 1.3.2 Mock-up1.7 Fast Track 1.3.3 Specimen1.8 Special Protocol Assessment Request 1.3.4 Consultation with Target Patient Groups1.9 Pediatric Administrative Information 1.3.5 Product Information already approved in the Member States1.10 Dispute Resolution 1.3.6 Braille1.11 Information Amendment: Information Not Covered Under Modules 2 To 5

1.4 Information about the Experts

1.12 Other Correspondence 1.4.1 Quality1.13 Annual Report 1.4.2 Non-Clinical1.14 Labeling 1.4.3 Clinical1.14.1 Draft Labeling 1.5 Specific Requirements for Different Types of Applications1.14.2 Final Labeling 1.6 Environmental Risk Assessment1.14.3 Listed Drug Labeling 1.7 Information relating to Orphan Market Exclusivity1.14.4 Investigational Drug Labeling 1.8 Information relating to Pharmacovigilance1.14.5 Foreign Labeling 1.8.1 Pharmacovigilance System1.14.6 Product Labeling For 2253 Submissions 1.8.2 Risk-management System1.15 Promotional Material [Promotional-Material-Audience-Type] 1.9 Information relating to Clinical Trials1.16 Risk Management Plan 1.10 Information relating to Paediatrics1.16.1 Risk Management (Non-REMS)1.16.2 Risk Evaluation And Mitigation Strategy (REMS)1.17 Post-Marketing Studies 1.18 Proprietary Names

Prescribing information

Information related to paediatric development

Information related to risk management

Example: Comparison of US CTD Module 1 versus EU CTD Module 1

Discussion

Although a drug registration application in the EU and the US may include the same core data, the Agencies’ regulatory requirements, regulations/guidelines and medical practices may be quite different across the two regions. Consequently, for a same product, there are generally substantial differences in the content and presentation of data in the US and the EU CTD dossiers, particularly in the Quality (CMC), the Clinical and the “Administrative” modules.

Pros Cons

Parallel preparation (preparation of once core dossier, then adapted to regional considerations)

Optimisation of the use of resourcesIn fine, quicker global registration

Early and thorough anticipation of all regional specificities along drug

development

The time spent on the conversion or adjustments of the

dossiers should never be

underestimated. Converting a NDA into a MAA (or vice

versa) requires several months of

work

Sequential preparation(preparation of the application

for the first region, then conversion to meet

requirements of the second region)

Feedback from the first Agency allowing some adjustments of the

dossier prior to its submission in the second region

Gap analysis to determine adjustments required from the first

applicationRecommendations to involve – even partially – the same team

members on the preparation of the 2 applications

Voisin Consulting Life Sciences

Cambridge, MA, San Francisco, CA & Somerville, NJ, USA London, UK Paris & Rennes, France Lausanne, Switzerland Bangalore, India

Founded in 1997 by Dr. Emmanuelle M. Voisin, VCLS is a team of over 100 life science professionals located in the US, Europe and Asia.

VCLS supports Biotech, Pharma and Medtech manufacturers to:• Design global product development

strategies• Engage with local regulators & payers

We believe that product development must be driven by a solid understanding of the environment within which the product will be launched, and the criteria by which elements of the development will be assessed by both regulators and payers.

VCLS partners with life science companies across European, North American and international markets.

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Nathalie Boeglin, Pharm. D, Ph. D., is a Director at VCLS, specialized in registration procedures, notably in Europe. She has over 10 years of experience in the pharmaceutical industry and 6 as a regulatory

consultant, leading over 20 successful MAA submissions. Learn more about her

VoisinConsulting.com

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