title: Access to bacteriophage therapy: discouraging experiences from the human cell and tissue legal framework.
abstract: Cultures of human epithelial cells (keratinocytes) are used as an additional surgical tool to treat critically burnt patients. Initially, the production environment of keratinocyte grafts was regulated exclusively by national regulations. In 2004, the European Tissues and Cells Directive 2004/23/EC (transposed into Belgian Law) imposed requirements that resulted in increased production costs and no significant increase in quality and/or safety. In 2007, Europe published Regulation (EC) No. 1394/2007 on Advanced Therapy Medicinal Products. Overnight, cultured keratinocytes became (arguably) 'Advanced' Therapy Medicinal Products to be produced as human medicinal products. The practical impact of these amendments was (and still is) considerable. A similar development appears imminent in bacteriophage therapy. Bacteriophages are bacterial viruses that can be used for tackling the problem of bacterial resistance development to antibiotics. Therapeutic natural bacteriophages have been in clinical use for almost 100 years. Regulators today are framing the (re-)introduction of (natural) bacteriophage therapy into 'modern western' medicine as biological medicinal products, also subject to stringent regulatory medicinal products requirements. In this paper, we look back on a century of bacteriophage therapy to make the case that therapeutic natural bacteriophages should not be classified under the medicinal product regulatory frames as they exist today. It is our call to authorities to not repeat the mistake of the past.
authors.affiliation: Laboratory for Molecular and Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium Faculty of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium Department of Behavioural Sciences, Royal Military Academy, Renaissancelaan 30, 1000 Brussels, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Verbeken
authors.affiliation: Faculty of Pharmaceutical and Pharmacological Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium KU Leuven Centre for IT & IP law, Sint Michielsstraat 6, box 3443, 3000 Leuven, Belgium isabelle.huys@kuleuven.be.
authors.forename: I
authors.initials: I
authors.lastname: Huys
authors.affiliation: Laboratory for Molecular and Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium Department of Behavioural Sciences, Royal Military Academy, Renaissancelaan 30, 1000 Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: De Vos
authors.affiliation: Department of Dermatology, University Hospital Brussels (UZ Brussel), Free University Brussels, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: De Coninck
authors.affiliation: Department of Dermatology, University Hospital Brussels (UZ Brussel), Free University Brussels, Laarbeeklaan 101, 1090 Brussels, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Roseeuw
authors.affiliation: Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Kets
authors.affiliation: Laboratory for Molecular and Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Vanderkelen
authors.affiliation: Laboratory for Molecular and Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Draye
authors.affiliation: Laboratory for Molecular and Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Rose
authors.affiliation: Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Jennes
authors.affiliation: Department of Behavioural Sciences, Royal Military Academy, Renaissancelaan 30, 1000 Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Ceulemans
authors.affiliation: Laboratory for Molecular and Cellular Technology, Burn Wound Centre, Queen Astrid Military Hospital, Bruynstraat 1, 1120 Brussels, Belgium.
authors.forename: J P
authors.initials: JP
authors.lastname: Pirnay
mesh_terms: D001424:Bacterial Infections / Q000382:microbiology / Q000628:therapy*; D001435:Bacteriophages / Q000254:growth & development / Q000302:isolation & purification; D001691:Biological Therapy / Q000266:history / Q000592:standards*; D005060:Europe; D000069467:Fecal Microbiota Transplantation; D033161:Government Regulation / Q000266:history; D049673:History, 20th Century; D006801:Humans; D015603:Keratinocytes
keywords: Advanced Therapy Medicinal Products; bacteriophage therapy; biological medicinal products; hospital exemption; keratinocytes; regulatory