Adapting drug approval pathways for bacteriophage-based therapeutics

The global rise of multi-drug resistant bacteria has resulted in the notion that an antibiotic apocalypse is fast approaching. This has led to a number of well publicized calls for global funding initiatives to develop new antibacterial agents. The long clinical history of phage therapy in Eastern...

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Main Authors: Callum Cooper, Mohammadali Khan Mirzaei, Anders S Nilsson
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-08-01
Series:Frontiers in Microbiology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01209/full
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spelling doaj-9ee52cc9b10a4c1981883ba09acf38472020-11-24T22:33:50ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2016-08-01710.3389/fmicb.2016.01209211741Adapting drug approval pathways for bacteriophage-based therapeuticsCallum Cooper0Mohammadali Khan Mirzaei1Mohammadali Khan Mirzaei2Anders S Nilsson3Stockholm UniversityStockholm UniversityMcGill UniversityStockholm UniversityThe global rise of multi-drug resistant bacteria has resulted in the notion that an antibiotic apocalypse is fast approaching. This has led to a number of well publicized calls for global funding initiatives to develop new antibacterial agents. The long clinical history of phage therapy in Eastern Europe, combined with more recent in vitro and in vivo success, demonstrates the potential for whole phage or phage based antibacterial agents. To date, no whole phage or phage derived products are approved for human therapeutic use in the EU or USA. There are at least three reasons for this: (i) phages possess different biological, physical and pharmacological properties compared to conventional antibiotics. Phages need to replicate in order to achieve a viable antibacterial effect, resulting in complex pharmacodynamics / pharmacokinetics. (ii) The specificity of individual phages requires multiple phages to treat single species infections, often as part of complex cocktails. (iii) The current approval process for antibacterial agents has evolved with the development of chemically based drugs at its core, and is not suitable for phages. Due to similarities with conventional antibiotics, phage derived products such as endolysins are suitable for approval under current processes as biological therapeutic proteins. These criteria render the approval of phages for clinical use theoretically possible but not economically viable. In this review, pitfalls of the current approval process will be discussed for whole phage and phage derived products, in addition to the utilization of alternative approval pathways including adaptive licensing and Right to try legislation.http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01209/fullBacteriophagephage therapyPharmaceutical regulationAdaptive pathwaysalternative licensing
collection DOAJ
language English
format Article
sources DOAJ
author Callum Cooper
Mohammadali Khan Mirzaei
Mohammadali Khan Mirzaei
Anders S Nilsson
spellingShingle Callum Cooper
Mohammadali Khan Mirzaei
Mohammadali Khan Mirzaei
Anders S Nilsson
Adapting drug approval pathways for bacteriophage-based therapeutics
Frontiers in Microbiology
Bacteriophage
phage therapy
Pharmaceutical regulation
Adaptive pathways
alternative licensing
author_facet Callum Cooper
Mohammadali Khan Mirzaei
Mohammadali Khan Mirzaei
Anders S Nilsson
author_sort Callum Cooper
title Adapting drug approval pathways for bacteriophage-based therapeutics
title_short Adapting drug approval pathways for bacteriophage-based therapeutics
title_full Adapting drug approval pathways for bacteriophage-based therapeutics
title_fullStr Adapting drug approval pathways for bacteriophage-based therapeutics
title_full_unstemmed Adapting drug approval pathways for bacteriophage-based therapeutics
title_sort adapting drug approval pathways for bacteriophage-based therapeutics
publisher Frontiers Media S.A.
series Frontiers in Microbiology
issn 1664-302X
publishDate 2016-08-01
description The global rise of multi-drug resistant bacteria has resulted in the notion that an antibiotic apocalypse is fast approaching. This has led to a number of well publicized calls for global funding initiatives to develop new antibacterial agents. The long clinical history of phage therapy in Eastern Europe, combined with more recent in vitro and in vivo success, demonstrates the potential for whole phage or phage based antibacterial agents. To date, no whole phage or phage derived products are approved for human therapeutic use in the EU or USA. There are at least three reasons for this: (i) phages possess different biological, physical and pharmacological properties compared to conventional antibiotics. Phages need to replicate in order to achieve a viable antibacterial effect, resulting in complex pharmacodynamics / pharmacokinetics. (ii) The specificity of individual phages requires multiple phages to treat single species infections, often as part of complex cocktails. (iii) The current approval process for antibacterial agents has evolved with the development of chemically based drugs at its core, and is not suitable for phages. Due to similarities with conventional antibiotics, phage derived products such as endolysins are suitable for approval under current processes as biological therapeutic proteins. These criteria render the approval of phages for clinical use theoretically possible but not economically viable. In this review, pitfalls of the current approval process will be discussed for whole phage and phage derived products, in addition to the utilization of alternative approval pathways including adaptive licensing and Right to try legislation.
topic Bacteriophage
phage therapy
Pharmaceutical regulation
Adaptive pathways
alternative licensing
url http://journal.frontiersin.org/Journal/10.3389/fmicb.2016.01209/full
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