Reference Medicinal Products

Compiled by Real Generics Ltd.
www.rgenerics.com
August 2015

A reference product is required whenever an applicant refers to data in someone else's dossier rather than the applicant's own data or data in the public domain.

A reference product is required for:

• All generics
• All hybrids (which include some safety and/or efficacy studies generated by the applicant)
• Some fixed dose combinations

The problem:
How do you select a reference medicinal product for an abridged application in Europe?

In the United States you just go for the RLD (reference listed drug)...

... but there is no RLD concept in Europe.

So how do you find an appropriate reference product?

Use this EMA guideline to search for possible reference products in each target country, or a European Reference Product

Features of an appropriate reference product...

Supported by a complete dossier:

Authorised via Articles 8(3), 10(a, b or c), possibly 10(3),
NOT via Article 10(1)

No longer protected by data exclusivity

(Authorised for at least 8 years in the EEA, possibly more in certain cases)

No need to worry about:

• Patent linkage - you can refer to a product even if it is still protected by patents

No need to worry about:

• Dosage form or strength. Refer to any product in the global marketing authorisation - it's the DRUG SUBSTANCE that counts

No need to worry about:

• Whether the product is still authorised or on the market BUT reference products for bioequivalence studies must be sourced from the EEA AND public health concerns due to lack of pharmacovigilance data may prevent granting of authorisation

Info to collect about the reference product:

Name, strength, dosage form

Authorisation date, number, holder

Authority granting the MA

Source country if used as reference in bioequivalence study

References

• Directive 2001/83/EC (16-Nov-12)
• Eudralex Volume 2B, Application Form (Jun-15)
• Eudralex Volume 2A, Chapter 1 Marketing Authorisation (Jul-15)
• EMA/33143/2009 Rev. 1 (16-Mar-15)