Bacteriophage therapy
pre- established regulatory framework, the ‘prêt -à- porter’ approach remains the more preferred model by most regulatory agencies, which is manifested by the completion of the first large-scale and systematic clinical trial of fixed 12- phage cocktails from 2015 to 2017 under the EU’s medicinal regulatory standards – PhagoBurn. 61 However, it is still likely that, in the foreseeable future, many start- ups or even major pharmaceutical companies may eventually succeed in producing and marketing fixed phage cocktails under the ‘prêt -à- porter’ concept, despite assimilating phages to antibiotics and consequently resulting in the de facto commodification of dynamic life-like biological entities. Changes to the regulatory paradigms are also taking place within a certain range of limited flexibility, and the specific regulations regarding phages differ in different countries. In Poland, therapeutic phages are permitted for clinical applications as per Polish Law Gazette Number 29 of 1997 and the Declaration of Helsinki. Meanwhile, in the United States, a new type of emergency investigational new drug (eIND) pathway of the FDA has been made available to patients on compassionate grounds. 62 A similar model has also been adopted in France, where the French regulatory agency Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) permits the compassionate uses of phages under the system of nominative Temporary Authorization for Use in exceptional cases after discussions and a successful validation with the ANSM and a special committee. 63 The magistral model of phage therapy in Belgium exhibits superior flexibility and adaptability, in which the concept of magistral preparations is adopted. 64 According to EU and Belgian law, the definition of magistral preparations (equivalent to compounded prescription drugs in the US) is ‘a ny medical product prepared in a pharmacy in accordance with a medical prescription for an individual patient’. 65 Under this framework of ‘sur - mesure’ phage therapy, pharmacists are permitted to mix different constituent ingredients for a given patient following a professional prescription and appropriate magistral standards. Phages have also been re-classified as active pharmaceutical ingredients (APIs), which allows for the greater flexibility required by personalized phage therapy . 66 A series of authorizations is also required from the Federal Agency for Medicines and Health Products (FAMHP), the Belgian regulatory agency and may also be required from the Ministry of Public Health. The phage APIs must also be produced from accredited Belgian approved laboratories for quality control. In Belgium, a large collection of phages, known as a ‘phage bank’, has also been established and regularly updated for efficient phage selection (e.g., at the Queen Astrid military hospital (QAMH) in Brussels). As described b y Pirnay et al. (2018), ‘the resulting Belgian ‘ magistral phage medicine ’ framework will be flexible enough to exploit and further explore the specific nature of phages as co- evolving antibacterials whilst giving precedence to patients’ safety’. Notwithsta nding that the sustainability and several other aspects of Belgium’s magistral framework for phage therapy are still in question, it may still be further considered as a practical approach to personalized medicine on a larger international scale by other regulatory authorities.
Future prospects of phage therapy
Recent successful human applications of therapeutic phages have rekindled a widening public interest in this old practice in the new context of AMR. There has been clear evidence that phage therapy is
61 Jault at el. 2019. 62 Schooley et al. 2017. 63 Brives & Pourraz 2020. 64 Häusler 2021. 65 Directive 2001/83/EC of the European Parliament and of the Council 2001; Law of 25 March 1964 Concerning the Medicinal Products 1964. 66 Pirnay et al. 2018.
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