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EU Regulatory FAQs
Common questions on the three parts of Directive 2001/83/EC that shape most EU dossiers: hybrid applications, well-established use applications and the expert who signs the Clinical and Nonclinical Overviews.
Hybrid applications
Article 10(3) questions.
What is a hybrid application under Article 10(3)?
A hybrid application relies partly on the published safety and efficacy data of a reference medicinal product and partly on new data that supports changes to it. Typical changes include a new strength, a new pharmaceutical form, a new route of administration or a new indication.
When should I file a hybrid rather than a generic application?
A generic application under Article 10(1) is for a product with the same active substance, essentially the same qualitative and quantitative composition, pharmaceutical form and conditions of use as the reference product. Once your product differs in a way that needs new data, such as a new indication or a new route, you move to a hybrid application under Article 10(3).
What new data does a hybrid application require?
It depends on the change. New indications usually need clinical data for the new use. New strengths or pharmaceutical forms may need bridging bioequivalence or pharmacokinetic data. The Nonclinical Overview assesses whether the safety data of the reference product still applies to your product.
How does data exclusivity affect a hybrid application?
The reference product's data exclusivity period must have expired, or its holder must consent to the use of the data, before a hybrid application can rely on it. Check the exclusivity status of the reference product in each Member State before committing to the route.
What must the Clinical Overview cover in a hybrid application?
It must justify each difference from the reference medicinal product and critically assess the data that bridges the reference product's safety and efficacy to your product. Assessors read this section first, and gaps in the justification are a common ground for objection.
Well-established use
Article 10a questions.
What is a well-established use application?
A bibliographic application under Article 10a where the active substance has a well-established medicinal use in the EU for at least ten years, with recognised efficacy and an acceptable level of safety. Instead of your own full data package, you build the dossier on published scientific literature.
What does the ten-year requirement actually mean?
You must demonstrate at least ten years of well-established medicinal use in the EU. That means published literature and regulatory or clinical use documentation covering a decade or more, for the active substance in the claimed indication, not simply that the substance has existed for ten years.
Can I combine literature with my own data?
Yes. Article 10a allows a mixed application where published literature is combined with your own preclinical or clinical data. This is common when you have new strengths, new formulations or additional data that strengthen the case.
Do I still need nonclinical data for a well-established use application?
The published literature may replace much of the nonclinical package, but the Nonclinical Overview still has to demonstrate that the safety profile is adequately covered. Environmental risk assessment and certain quality related nonclinical topics remain mandatory.
Does a well-established use application depend on a reference product?
No. Unlike generic and hybrid applications, a well-established use application is free standing and does not rely on a reference product or its data exclusivity. Any applicant can use the route when the ten-year use requirement is met.
The expert requirement
Article 12 questions.
Who must sign the Module 2 Overviews?
Article 12 of Directive 2001/83/EC requires the Clinical Overview (2.5) and Nonclinical Overview (2.4) to be drawn up and signed by a Clinical Expert and a Nonclinical Expert with the necessary technical or professional qualifications. A brief statement and CV from each expert are part of the dossier.
What qualifications must the expert have?
The directive requires experts with the necessary technical or professional qualifications. In practice, national authorities expect senior scientists or physicians with relevant specialisation, a track record in the therapeutic area and experience with the dossier type.
Can one person act as both Clinical and Nonclinical Expert?
Yes, where one person genuinely holds the qualifications for both roles, but the two statements are made separately and each must stand on its own. Many sponsors appoint two experts so each overview has a clearly accountable specialist.
Can we appoint an expert from outside our company?
Yes, and most sponsors do. The expert must be able to provide an independent, critical assessment of the dossier rather than simply endorse the development story, which is why an external named expert is common.
Can we change the expert after submission?
Yes. If an expert becomes unavailable, a new qualified expert can review the overviews, sign a new statement and CV, and take over responsibility for the dossier. The change should be notified through the appropriate procedure.
Expert reports
Need a named expert for your dossier?
Neta Kela, PhD writes and signs the Clinical Overview (2.5) and Nonclinical Overview (2.4) as named Clinical and Nonclinical Expert for full, hybrid and well-established use applications and variations.
Always confirm current requirements in EMA and national competent authority guidance before filing.