EMA proposes new guideline establishing therapeutic equivalence for nasal products
The European Medicines Agency (EMA) has proposed developing a new guideline addressing the data generic drug manufacturers should submit to demonstrate therapeutic equivalence (TE) for nasal products compared to the reference product, a topic that is “insufficiently covered” in existing guidelines.These plans were announced in a concept paper published on 25 July. The agency noted that nasal treatments can be used to treat the common cold, for allergic rhinitis or serve as an alternative to injections. EMA said that demonstrating TE will differ depending on whether the product is used for local or systemic treatment.
EMA anticipates that a forthcoming guidance could be modeled after its guideline on establishing TE for orally inhaled products for treating asthma and chronic obstructive pulmonary disease (COPD) in adults and children. This guideline was released in April 2024, along with another guideline addressing the quality of inhalation and nasal products. (Euro Roundup: EMA seeks feedback on quality, therapeutic equivalence of inhaled drugs, Regulatory Focus 18 April 2024)
The April TE guideline “presents a stepwise approach with a list of in vitro criteria to be fulfilled and of additional PK [pharmacokinetic] studies to be conducted in case not all in vitro criteria are fulfilled.”
EMA said such a guideline is necessary as the only reference made to TE for nasal products is in the other April guideline on establishing pharmaceutical quality for inhalation and nasal medicinal products. A paragraph in the guideline states that demonstrating TE for these products “may depend on the intended site of action of the active substance(s) i.e., whether the effect is locally or systemically mediated.”
EMA said several in vitro parameters could be considered in establishing such TE with a reference product. This can include a product’s qualitative and quantitative composition, actuation volume, droplet size distribution, mass of droplets smaller than 10 µm, particle size distribution and morphological form of active substance for suspensions, spray pattern, rheological properties, surface tension, density, osmolality, and buffer capacity.
The agency states that “all these parameters might not be relevant for all formulations, and other parameters may be applicable depending on the finished medicinal product characteristics, it would still be of value to discuss these in more detail and set acceptance criteria for similarity. Thereby, data requirements on TE based on in vitro data only would be clearly set.”
In vivo data “would be warranted” if TE cannot be concluded from vitro data unless the product is reformulated to fit the in vitro criteria.
For systemically active substances, the data could include comparable bioavailability/bioequivalence data as outlined in the January 2010 guideline on bioequivalence investigations. EMA said that for locally active substances there is “currently no consensus on in vivo study designs and endpoints.”
The guideline would be drafted by EMA’s Rheumatology and Immunological Working Party. The agency plans to release the guideline in the third quarter of 2024 for a three-month public consultation.
The deadline for sending comments is 31 October 2024
Concept paper
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