Biomarkers are widely used at every stage of drug discovery and development. Utilisation of biomarkers has a potential to make drug discovery, development and approval processes more efficient. An overview of the current global regulatory landscape is presented in this article with particular emphasis on the validation and qualification of biomarkers, as well as legal framework for companion diagnostics. Furthermore, this article shows how the number of approved drugs with at least 1 biomarker used during development (biomarker acceptance) is affected by the recent advances in the biomarker regulations. More than half of analysed approvals were supported by biomarker data and there has been a slight increase in acceptance of biomarkers in recent years, even though the growth is not continuous. For certain pharmacotherapeutic groups, approvals with biomarkers are more common than without. Examples include immunosuppressants, immunostimulants, drugs used in diabetes, antithrombotic drugs, antineoplastic agents and antivirals. As a conclusion, potential benefits, challenges and opportunities of using biomarkers in drug discovery and development in the current regulatory landscape are summarised and discussed.

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Aspergillus fumigatus and A. flavus are the fungal pathogens responsible for most cases of invasive aspergillosis (IA). Early detection of the circulating antigen galactomannan (GM) in serum allows the prompt application of effective antifungal therapy, thus improving the survival rate of IA patients. However, the use of monoclonal antibodies (mAbs) for the diagnosis of IA is often associated with false positives due to cross-reaction with bacterial polysaccharides. More specific antibodies are therefore needed. Here we describe the characterization of the Aspergillus -specific mAb AP3 (IgG1κ), including the precise identification of its corresponding antigen. The antibody was generated using A. parasiticus cell wall fragments and was shown to bind several Aspergillus species. Immunofluorescence microscopy revealed that AP3 binds a cell wall antigen, but immunoprecipitation and enzyme-linked immunosorbent assays showed that the antigen is also secreted into the culture medium. The inability of AP3 to bind the A. fumigatus galactofuranose (Gal f )-deficient mutant Δ glfA confirmed that Gal f residues are part of the epitope. Several lines of evidence strongly indicated that AP3 recognizes the Gal f residues of O -linked glycans on Aspergillus proteins. Glycoarray analysis revealed that AP3 recognizes oligo-[β-D-Gal f -1,5] sequences containing four or more residues with longer chains more efficiently. We also showed that AP3 captures GM in serum, suggesting it may be useful as a diagnostic tool for patients with IA.

In March 2017, the US FDA introduced the new Regenerative Medicine Advanced Therapy (RMAT) designation thus recognizing the enormous potential of these medicines and the need for efficient regulatory tools to accelerate their development and their commercial availability. The development of regenerative medicines is very challenging because of their complex and unique nature, especially to the rather unexperienced small- and medium-sized developing enterprises. With the new RMAT designation, FDA aims at providing intensive support to companies developing cell- and tissue-based therapies, tissue-engineering products, and combination treatments. This may also include cell-based products where the genome has been edited by emerging technologies such as CRISPR-Cas9. This article presents the newly launched "Regenerative Medicine Advanced Therapy" (RMAT) designation, outlines existing FDA regulatory tools aiming at expediting approval, and discusses the overall value of these programs. Additionally, recommendations are provided for companies developing these very specific and complex therapies on how and when to consider these tools for an integrated development and regulatory strategy.