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Issue 2021/02
April 2021

Category: Regulatory, Nucleic Acid-Based Therapies

Classification of Borderline Products in the EU: Are all nucleic acid-based products gene therapies?

By Anika Schroeter

Nucleic Acid-based products are gene therapies, aren’t they? The answer to this question is not as straight forward as one might think, but will substantially influence the overall development strategy of a product candidate. Indeed, in the past, European regulators classified nucleic acid-based products either as gene therapy or as small molecule / biologic or as vaccine based on the current definition laid out in EU Directive 2001/83/EC. However, a discussion on the European level is ongoing indicating a change and streamlining in the current thinking.

Nucleic acid-based drugs represent a highly diverse and very promising product class including coding (e.g., DNA or mRNA) as well as non-coding (e.g., siRNA, miRNA) product types, with further innovating ideas being on the horizon (e.g., extrachromosomal DNA). While a range of non-coding RNA-based products were already approved in the European Union, mRNA-based products reached the market only very recently (i.e., as preventive vaccines against COVID-19). Despite these achievements, there is an ongoing debate and uncertainty about the formal classification of those products: Are nucleic acid-based products considered gene therapies, biologics, small molecules or vaccines? The answer to this question is essential as it will impact the overall developmental strategy of any nucleic acid-based program.

The European Medicines Agency (EMA) offers support in this regard. A formal and straightforward classification procedure can be sought by companies providing clarity on the classification of their product early on in development (CAT, 2013). The outcome of such classification procedures is published by EMA. In 2017 for example, an siRNA was not classified as gene therapy (CAT, 2017), while mRNA-based products were considered as gene therapy (CAT, 2021a). To complicate matters even more, definition of gene therapies as provided in EU Directive 2001/83/EC explicitly excludes vaccines against infectious diseases from the umbrella of gene therapies (EC, 2001). Thus, the recently approved mRNA-based products from Moderna (COVID-19 Vaccine Moderna) and BioNTech/Pfizer (Comirnaty) are considered vaccines and not gene therapies.

This view might, however, change in the near future, as a debate is currently ongoing on the European regulatory level. Indeed, EMA is discussing an update of the definition of gene therapies, as the definition planned to be included in the upcoming ICH S12 guideline (Non-clinical biodistribution studies for gene therapy products) seems to deviate from the current definition provided in EU Directive 2001/83/EC (EMA, 2021). Specifically, it is mentioned that “a discussion took place on the difference between the definition in the glossary of the draft S12 guideline and the EU GTMP definition: inclusion of genome editing technologies; exclusion of direct effect of recombinant nucleic acids on the therapeutic effect (only genetic material active in transcriptional/translations ways); unclarity if vaccines against infectious diseases are included classification” (CAT, 2021b). No further details are available at the moment, but more information is expected to be released soon.

MC Toxicology Consulting was successfully involved in non-clinical development of various nucleic acid-based products including EMA classification procedures and will keep you updated on this burning topic! Stay tuned to not miss substantial changes, which might impact the non-clinical development of your ongoing and future nucleic acid-based products!


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