4. Regulation of Phage-Based Products
4.噬菌体产品的监管
The recent return of interest in phage therapy increases the importance of legal regulation of phage-based products. Current legislation for pharmaceuticals is defined for industrially manufactured drugs, which can be difficult to relate to phage therapy, considered as a type of evolutionary or personalized medicine due to its unusual pharmacokinetics and evolutionary considerations, posing a major challenge for regulators. The EU is not open to a change in legislation, which is an obstacle to the expansion of new, less conventional therapies [87].
最近对噬菌体疗法的兴趣的回归增加了对基于噬菌体的产品的法律的监管的重要性。目前的药品立法是针对工业生产的药物定义的，这可能很难与噬菌体治疗相关，由于其不寻常的药代动力学和进化因素，噬菌体治疗被认为是一种进化或个性化的药物，这对监管机构构成了重大挑战。欧盟不接受立法的改变，这是扩大新的、不太传统的疗法的障碍[ 87]。
In some Eastern countries, phage therapy practices have never been abandoned, such as in Russia [88] or Georgia [89], and their regulations are being reviewed by some Western countries, making new forms of regulation possible [87]. In Belgium, the first steps are being taken for the regulation of phage therapy by establishing two bases: the elaboration of extended documentation on the phage to be used in the phage product to ensure its quality and the availability of authorized laboratories with phage stock that can ensure that phages raise the quality standards according to technical and scientific knowledge [90]. On the other hand, in France, a specialized committee issued some recommendations for the use of phage-based products according to the Temporary Authorization for Use (ATUn). This is an exceptional procedure allowing the use of a medical product without marketing authorization in the absence of an alternative treatment [91]. In the U.S., owing to the special interest acquired by phages during pandemics for fighting MDR bacteria in hospitals [92], the Food and Drug Administration (FDA) has recently approved phage therapy for COVID-19 patients as a compassionate treatment due to the lack of clinical trials [93]. Regarding their use in animals, phages do not easily fit into existing EU regulations regarding the use of food additives or food processing aids, which is a major obstacle [94]. The EU legislation on veterinary medicinal products and food and feed safety considers different authorizations for substances such as pesticides, biocides, feed additives, or veterinary medicinal products but does not relate to the type of substance. Because of this, phage applications may get different authorizations depending on their application [95].
在一些东方国家，噬菌体治疗实践从未被放弃，例如在俄罗斯[ 88]或格鲁吉亚[ 89]，一些西方国家正在审查其法规，使新的监管形式成为可能[ 87]。在比利时，通过建立两个基础，正在采取第一步来规范噬菌体治疗：详细说明噬菌体产品中使用的噬菌体的扩展文件，以确保其质量，以及拥有噬菌体库存的授权实验室的可用性，可以确保FDA根据技术和科学知识提高质量标准[ 90]。另一方面，在法国，一个专门委员会根据临时使用授权（ATUn）发布了一些使用噬菌体产品的建议。这是一个例外程序，允许在没有替代治疗的情况下使用未经上市许可的医疗产品[ 91]。在美国由于噬菌体在大流行期间获得了在医院中对抗MDR细菌的特殊兴趣[ 92]，由于缺乏临床试验，食品和药物管理局（FDA）最近批准了用于COVID-19患者的噬菌体疗法作为同情治疗[ 93]。关于其在动物中的使用，益生菌不容易符合现有的关于使用食品添加剂或食品加工助剂的欧盟法规，这是一个主要障碍[ 94]。关于兽药产品和食品与饲料安全的欧盟立法考虑了农药、杀生物剂、饲料添加剂或兽药产品等物质的不同授权，但与物质类型无关。因此，噬菌体应用程序可能会根据其应用程序获得不同的授权[ 95]。
The lack of specific regulation limits the development of phage therapy, which, at the same time, does not incentivize the interest of the authorities to elaborate these regulations. This increases the importance of research and more clinical trials [87].
缺乏具体的监管限制了噬菌体疗法的发展，同时，这也没有激励当局制定这些监管的兴趣。这增加了研究和更多临床试验的重要性[ 87]。