Drug reformulations and repositioning in pharmaceutical industry and its impact on market access: reassessment of nomenclature

Abstract

Background: Medicinal products that have been developed and approved for one disease may be the object of additional clinical development in other disease areas or of additional pharmaceutical development for new and different formulations. The newly developed products can be named as repositioned or reformulated products, respectively. Market access of repositioned or reformulated products in Europe and the United States is an interesting object of study as it may provide clarity about which parameters are assessed and considered to bring added value, other than the molecule itself. As such, we aim to evaluate if the added value of repositioned or reformulated medicinal products can be systematically described, quantified, and predicted. As a first step toward investigating the impact of market access on drug research and development trends for repositioned and reformulated products, it is necessary to have consistency in the designations for the case studies evaluated in this project. In an attempt to achieve that consistency, the current study aims to propose harmonized definitions for the repositioning and reformulation strategies and to propose a taxonomy for the medicinal products derived thereof.

Methods: A systematic literature review was conducted to collect information on existing cases of repositioning or reformulation. A search strategy was developed by defining the search objectives, targeted data sources, search keywords, and inclusion/exclusion criteria for the retrieved documents.

Results: A total of 505 publications were retrieved through a search of the main data sources. The screenings and the ad hoc search led to a total of 56 publications to be used for the case study data extraction. In total, 87 repositioning and/or reformulation cases were found described in the literature, 23 of which presented different definitions and/or classifications by different authors.

Conclusion: Given the disparity and inconsistency of terminologies and classifications in the literature, a harmonized nomenclature for drug repositioning, reformulation, and combination cases will allow for a robust analysis of the added value and market access conditions attributed for each strategy and case type as assessed by regulators and payors in Europe and the United States. After evaluation of the existing terminologies and given the absence of clear and consistent definitions for drug reformulation and repositioning in the literature, we propose a global terminology and taxonomy in order to cover all of the previously unclear definitions and classifications for repositioned and reformulated products.

Keywords: classification; combination; lifecycle management; market access; reformulation; repositioning; repurposing; taxonomy.

Fig. 1

Flow diagram of reviewed publications. The diagram shows the number of selected publications at the different search phases, including the Embase search results, and the additional articles retrieved using the ad hoc search.

Fig. 2

Overview of selected publications. (A) Distribution of publications by year of publication. (B) Distribution of publications by scope: The selected publications are distributed depending on their scope as attributed by us during the data extraction phase. The scope can be drug reformulation, drug repositioning, or both. (C) Distribution of publications by reason of selection; during the screening phases of the search, reasons for selection were recorded and we attributed five categories covering the overall search objectives: Background information, including definitions and general information; Approaches, any description of strategies for reformulations or repositioning; Cases, all case studies or examples of repositioned or reformulated products; Regulations, any regulatory implication; Pricing, pricing and market access of repositioned and reformulated products. (D) Distribution of publications by reason for selection and year of publication. (E). Distribution of publications by year of publication and scope (reformulation, repositioning, or both).

Fig. 3

Classification algorithm for drug repurposing. Drug repurposing strategies (i.e., repositioning, reformulations, and combination) are illustrated as three distinct lines. Under each of these strategies, the cases can be classified according to specific criteria.

Fig. 4

Classification tree for repositioning of drugs. Cases of drug repositioning are classified according to the parameters mentioned in the algorithm (Fig. 3). The presented tree is only a partial illustration of the classification.

Fig. 5

Classification tree for drug reformulation. Cases of drug reformulation are classified according to the parameters mentioned in the algorithm (Fig. 3). The presented tree is only a partial illustration of the classification.

Fig. 6

Classification tree for drug combination. Cases of drug combination are classified according to the parameters mentioned in the algorithm (Fig. 3). The presented tree is only a partial illustration of the classification.