EMA Works On Definition To Support Similarity Assessments For Orphan Drugs
This article was originally published in SRA
The European Medicines Agency is working on a definition for 'principal molecular structural features'- a term in the EU orphan drugs legislation for determining the similarity between a drug in the pre-authorization phase and a drug that has already received orphan designation or market authorization.
The definition is being drawn up at the request of the European Commission1, which is currently considering changes to the 16-year-old orphan drugs regulatory framework2. Once ready, the definition is expected to help further clarify the requirements of the orphan drugs legislation, under which sponsors developing orphan drugs must assess whether there are similar orphan drugs already designated or authorized for a condition related to their proposed therapeutic indication, and submit a similarity report where needed.
The EMA told Scrip Regulatory Affairs that it was aiming to provide a definition to the commission in the "near future" and that it was currently holding discussions on the topic with its relevant committees and working parties.
Assessing similarity is important as the legislation offers a 10-year marketing exclusivity for authorized orphan drugs. During this period, the EMA and EU member states cannot accept or grant another marketing authorization for a "similar product" for the same therapeutic indication unless the sponsor can prove that its product is subject to certain derogations, such as if the new drug is more effective, safer or otherwise clinically superior to the one already authorized.
The legislation defines "similar active substance" as an identical active substance or an active substance with the same principal molecular structural features (but not necessarily all of the same molecular features) and which acts via the same mechanism. This, in turn, means that the similarity assessment of the new and authorized/designated orphan drug should depend on: principal molecular structural features; mechanism of action; and the therapeutic indication.
While the legislation introduced the concept of principal molecular structural features, it offered no definition for this term, an EMA spokesperson told SRA. "Over the last 16 years, experience has been gathered with the application of the definition of 'similar active substance' and it was felt useful to clarify the meaning of the [term principal molecular structural features] and include a definition together with an update of the examples… to take into account the technological and scientific advances since this piece of legislation was adopted," the spokesperson added.
The commission has proposed changes to the main orphan drugs law (Regulation (EC) No 141/2000), which introduced incentives for the research, development and marketing of medicinal products for rare diseases. It is also considering revisions to a related implementing regulation (Regulation (EC) No 847/2000), which lays down the provisions for implementing the criteria for designating a medicinal product as an orphan medicinal product and offers definitions for "similar medicinal product" and "clinical superiority".
In addition, the commission is considering a review of its "communication" on Regulation (EC) No 141/2000. The communication was issued in 2003 in response to a number of requests for interpretation of and clarification on matters relating to the implementation of the orphan designation and market exclusivity provisions.
Stakeholder feedback on the commission's proposal to revise the orphan drugs framework was made public on March 23.
References
1. Minutes of CHMP meeting held on 25-28 January 2016, posted online March 4, 2016, www.ema.europa.eu/docs/en_GB/document_library/Minutes/2016/03/WC500202684.pdf
2. European Commission Seeks To Facilitate Innovative Orphan Drug Entry; Avoid Delays For Generics, Scrip Regulatory Affairs, Oct. 1, 2015
3. Responses to the public consultations on notice from the Commission on aspects of the application of Article 3, 5 and 7 of Regulation (EC) N° 141/2000 on orphan medicinal products, http://ec.europa.eu/health/human-use/orphan-medicines/developments/2015_11_pc_orphans_en.htm