Drug reformulations and repositioning in the pharmaceutical industry and their impact on market access: regulatory implications

Abstract

BackgroundRepurposing has become a mainstream strategy in drug development, but it faces multiple challenges, amongst them the increasing and ever changing regulatory framework. This is the second study of a series of three-part publication project with the ultimate goal of understanding the market access rationale and conditions attributed to drug repurposing in the United States and in Europe. The aim of the current study to evaluate the regulatory path associated with each type of repurposing strategy according to the previously proposed nomenclature in the first article of this series.MethodsFrom the cases identified, a selection process retrieved a total of 141 case studies in all countries, harmonized for data availability and common approval in the United States and in Europe. Regulatory information for each original and repurposed drug product was extracted, and several related regulatory attributes were also extracted such as, designation change and filing before or after patent expiry, among others. Descriptive analyses were conducted to determine trends and to investigate potential associations between the different regulatory paths and attributes of interest, for reformulation and repositioning cases separately.ResultsWithin the studied European countries, most of the applications for reformulated products were filed through national applications. In contrast, for repositioned products, the centralized procedure was the most frequent regulatory pathway. Most of the repurposing cases were approved before patent expiry, and those cases have followed more complex regulatory pathways in the United States and in Europe. For new molecular entities filed in the United States, a similar number of cases were developed by serendipity and by a hypothesis-driven approach. However, for the new indication's regulatory pathway in the United States, most of the cases were developed through a hypothesis-driven approach.ConclusionThe regulations in the United States and in Europe for drug repositionings and reformulations allowed confirming that repositioning strategies were usually filed under a more complex regulatory process than reformulations. Also, it seems that parameters such as patent expiry and type of repositioning approach or reformulation affect the regulatory pathways chosen for each case.

Unlocking the potential of established products: toward new incentives rewarding innovation in Europe

“…After its initial approval for metastatic colorectal cancer (mCRC) in January 2005, nine more indications were launched over the following seven-year timespan; four in the year 2007 (breast cancer, non-small cell lung cancer, renal cell cancer and a different treatment regimen for mCRC), one in 2009 (a different treatment regimen for breast cancer), three in 2011 (ovarian, fallopian tube or peritoneal cancer and two different treatment regimens for breast cancer) and one in 2012 (different stage of ovarian, fallopian tube or peritoneal cancer). [26] The work of Murteira et al [25] revealed that such a strategy is commonly practised. The majority of repositioning cases 2 2

Repositioning is defined as the process of finding a new therapeutic use for an already known drug.

analysed in this study, i.e.…”

On-Label or Off-Label? Overcoming Regulatory and Financial Barriers to Bring Repurposed Medicines to Cancer Patients

“…In certain cases, medicine developers may choose to reformulate, protect (e.g., through second medical use patents) and rebrand an established medicinal product to create sufficient legal and strategic protection from generic competitors (Smith, 2011;Novac, 2013;Dilly and Morris, 2017). For developers other than the original marketing authorization holder, a new full marketing authorization application may even offer a 10-year period of data and marketing protection for the repurposed product (Murteira et al, 2014a).…”

“…Repurposing of existing medicines can be particularly useful in areas with high unmet needs, for example to treat patients with rare diseases (Norman, 2013;Murteira et al, 2014a). In fact, studies have shown that about one in five orphan medicinal products are established medicines that were repurposed for a new indication (Davies et al, 2017).…”

The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

“…This refers to the exploitation of known drugs for new indications [ 7 ]. Repurposing receives attention in both the United States and Europe, although differences exist between both continents with respect to policies for repurposing of medicinal products [ 8 ]. Several initiatives have been created to identify possible targets for drug repositioning [ 7 ].…”