How Do You Translate Your Non-EU Dossier For The EU Market?

The issues faced when translating a non-EU dossier for the EU market is covered in this blog by the CMC team at Acorn Regulatory.

Any regulatory professional will tell you that when you’re developing your new medicinal product your developmental R&D strategy should have your regulatory strategy firmly in sight. This is an ideal that many larger companies successfully perform with ease whereby they develop a global product that has an individualised regulatory strategy for each region firmly embedded in the development process.

How does the smaller company achieve this when they have limited resources and perhaps limited regulatory expertise?

The answer:  “it’s possible to achieve this, however, you will need correct advice”

Smaller companies and SME’s tend to develop a product with one region or market in mind and then when they achieve regulatory approval in that market their focus moves to registration in a different region. SME’s are then left with the task of trying to tailor their existing dossier for the proposed region. This can be a daunting task but with the correct regulatory assistance, it can be done successfully.

Legal Basis of the Application

In Europe, the first step for any new registration is “what is the proposed legal basis of the application”. The legal basis will dictate the dossier content, market exclusivity, and paediatric requirements in a very profound way. Directive 2001/83/EC as amended outlines the various “legal basis” that a new application can adopt. It is also important to note that in Europe your legal basis is independent of the procedural route that your company wishes to take. Whether you decide the Centralised, Decentralised, or National route your choice in a legal basis will remain the same.

In the majority of circumstances, only one legal basis will be appropriate whereby your product only fits into one category. But what happens when your product doesn’t fit nicely into one of the legal basis categories. You can be left navigating the depths of Directive 2001/83/EC and coming up with more questions than answers. When your product is an established active substance where there is no current patent but includes a new dosage form, strength, route of administration, a new indication, or any combination of these, your product cannot be considered as a generic medicine. Three possible legal bases may be open to you:

  • Article 8 (3) Full Dossier Mixed Marketing Authorisation
  • Article 10 (a) Full Dossier Well established use
  • Article 10 (3) Abbreviated Dossier (hybrid application)

Knowing the requirements and limitations to each option will help you determine which is the best approach or appropriate choice for you and your business. The table below outlines various differences in the dossier requirements between each legal basis.

Article 8 (3) Full Dossier Mixed Marketing AuthorisationArticle 10 (a) Full Dossier Well Established UseArticle 10 (3) Abbreviated Dossier (hybrid application)
Dossier Requirements·         Company’s own studies + published peer-reviewed literature

·         No reliance on EU Reference product.

·         Paediatric regulation 1901/2006 is applicable

·         PIP/waiver must be submitted

·         Advantages due to certain data protection and market exclusivity

·         Must demonstrate “well established use” of the active substance in the community over a 10 year period. This use must also demonstrate that the active substance has a recognised efficacy and an acceptable level of safety.

·         Proposed indication must be aligned with the existing recognised indication within the EU

·         Risk of rejection in certain member states if an alternative route of administration is proposed

·         No reliance on an EU reference product

·         Paediatric regulation 1901/2006 is not applicable

·         No PIP/waiver is required

·         EU reference product is required and must be referenced in the dossier

·         Company’s own studies which must have been conducted using the EU reference product (i.e. bioequivalence)

·         Reference is made in the dossier to the Non-clinical and Clinical data of the EU reference product

·         Paediatric regulation 1901/2006 is not applicable

·         No PIP/waiver is required

Once your legal basis is decided upon it will direct what clinical and non-clinical sections (Modules 4 and 5) of the dossier need to be revised.

Module 1

Another area that can present problems for companies who are inexperienced in the EU regulatory process is Module 1. Module 1 is crucial to the successful validation of any procedure within Europe and requires time to compile and generate properly. It is important that you identify what documents you will require in Module 1 and that is largely based on your proposed legal basis. Documents that require planning at an early stage are outlined below.

  1. Section 1.3.4 Consultation with Target Patient Groups (PIL User Testing)
  2. Section 1.6 Environmental Risk Assessment
  3. Section 1.8.1 Pharmacovigliance System
  4. Section 1.8.2 Risk Management System
  5. Section 1.10 Paediatrics (PIP/Waiver)
  6. Section 1.2 Application Form eAF

While the eAF is not a difficult document to complete it prompts the user regarding the associated documentation for the Annex. All the GMP and Quality related documents are contained there. If the applicant starts generating this document early in the regulatory process it allows adequate time to request English translations etc.

Module 2

Module 2 is generic across all the proposed legal basis and all documentation should be supplied as outlined in the eCTD guidelines.

Module 3

While the large proportion of any Module 3 dossier is consistent no matter where the dossier is registered it is important to note the following points:

  • All non-EU references must be removed and replaced with the EU equivalent (e.g. USP to Ph.Eur.)
  • Appropriate EU Guidance documents must be referred too throughout each document in module 3
  • European specifications and associated limits as detailed in the various EMA guidance documents must be adhered to

In conclusion, obtaining an EU authorisation for a US product is certainly possible and while it takes careful planning it is achievable for the SME style company.

If you would like assistance with translating a Non-EU dossier for the EU market you can talk to us.  We have an experienced team in our pharmaceutical services team that can help you every step of the way.  To find out more just call us on 00353 52 61 76 706 or complete the form below and we will get back to you.

Further Reading from Acorn Regulatory

Veterinary Clinical Trials: New EU Law & Global Approaches

Clinical studies are intended to advance animal health care by identifying the most effective therapies and practices for a given condition, or by advancing our basic understanding of the disease. Much like a clinical study in the human population, a veterinary clinical study involves research that gains information from animal patients.

Read more here.

Pharmacovigilance & Social Media in 2020

We have been tracking the role of social media in pharmacovigilance in social media since 2015.  We first wrote about it here.  5 years on, we are glad to say that the field has moved on substantially in terms of research into the practical applications of social media in Pharmacovigilance. Regulatory guidance for the industry, however, has yet to be updated.

Read the full article here.

Download Our Clinical Trials E-Book

Acorn Regulatory is a leading regulatory, pharmacovigilance, and clinical consultancy company headquartered in Ireland.  Our Clinical & Medical team works with the largest and the leading companies in life sciences to assist them in bringing their products to market.  The team, led by Dr. Danica Cvetkovic, has written extensively on the issue.  In the latest e-book from Acorn Regulatory, we look at the best and most popular articles from our Clinical & Medical team.

Download the e-book here.

A Practical Approach to Risk Management Plans

Writing a risk management plan (RMP) for the first time can be a daunting task. The RMP is a legally binding regulatory document submitted to health authorities and is a mandatory commitment for all Marketing Authorisation Holders in the European Union. The goal of the RMP is to improve the benefit-risk balance of a medicinal product by combining risk assessment and risk minimisation. The RMP is a complex document, but with the revised RMP module (March 2017), comes the revised EU template for RMPs (rev 2 format) and the RMP is now structured in a clear manner with less repetition and with attention to detail.

Read more here.


About the Author
Gemma Robinson, PhD
Managing Director
As Managing Director of Acorn Regulatory, Gemma Robinson is actively involved on client projects on a day to day basis and she leads a team of respected pharmaceutical, medical device, pharmacovigilance and clinical trial experts.  Gemma is also an active contributor to developing and promoting standards in the regulatory affairs profession and she has worked with a number of academic and not for profit organisations to encourage individuals to pursue a career in regulatory affairs and the broader STEM subjects. You can read more articles by Gemma by clicking the link below.
Other articles by Gemma Robinson PhD