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Review
. 2020 Dec 8:15:1177271920974652.
doi: 10.1177/1177271920974652. eCollection 2020.

Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape

Mariya Gromova  1 , Annegret Vaggelas  1 , Gabriele Dallmann  1 , Diane Seimetz  1
Affiliations
Review

Biomarkers: Opportunities and Challenges for Drug Development in the Current Regulatory Landscape

Mariya Gromova et al. Biomark Insights. .

Abstract

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.

Keywords: Biomarker; EMA; FDA; companion diagnostics; drug approval; drug development; qualification; regulatory landscape.

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Conflict of interest statement

Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Figures

Figure 1.
Figure 1.
Drug discovery and development processes with a potential to benefit from biomarkers phase I, II and III refer to clinical trial phases. NDA, new drug application (FDA); BLA, biological license application (FDA); MAA, marketing authorisation application (EU).
Figure 2.
Figure 2.
EMA novel methodologies qualification procedure. QT, qualification team; LoQ, list of questions; LOI, Letter of Intent; SAWP, scientific advice working party; CHMP, Committee for Medicinal Products for Human Use; Figure created based on the information provided in EMA guidance to applicants ‘Qualification of novel methodologies for drug development’.
Figure 3.
Figure 3.
Possible outcomes of the EMA Novel Methodologies Qualification procedure. Figure created based on the information provided in EMA guidance to applicants ‘Qualification of novel methodologies for drug development’.
Figure 4.
Figure 4.
FDA Biomarker Qualification Program procedure. DDT, Drug Development Tools; LOI, Letter of Intent, Figure created based on the information provided in FDA draft guidance for industry and FDA staff ‘Qualification process for drug development tools’.
Figure 5.
Figure 5.
EMA and FDA drug approvals with and without biomarkers between 2015 and 2019.
Figure 6.
Figure 6.
Selected EMA drug approvals with and without biomarkers between 2015 and 2019 by pharmacotherapeutic group.
See this image and copyright information in PMC

References

    1. Ghasemzadeh N, Zafari AM. A brief journey into the history of the arterial pulse. Cardiol Res Pract. 2011;2011:164832. - PMC - PubMed
    1. Booth J. A short history of blood pressure measurement. Proc R Soc Med. 1977;70:793-799. - PMC - PubMed
    1. Institute of Medicine (US) Forum on Drug Discovery Development and Translation. 1. Introduction. In: Steve O, Sally R, Robert G, et al., eds. Accelerating the Development of Biomarkers for Drug Safety: Workshop Summary. National Academies Press (US); 2009: 1-6. - PubMed
    1. Seimetz D. The key to successful drug approval: an effective regulatory strategy. In: Becker J, Villinger TR, eds. Life Science Venturing. Springer Fachmedien Wiesbaden GmbH; 2017: 139–147.
    1. EMA. Glossary: biomarker. 2020. Accessed February 23, 2020 https://www.ema.europa.eu/en/glossary/biomarker