Fürst-Wilmes Miriam, Respondek Vanessa, Lilienthal Nils, Buss Katrin, Düchting Anja
Fachgebiet Infektiologie, Dermatologie, Allergologie, HNO, Zulassung 3, Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn, Deutschland.
Fachgebiet Pharmazeutische Biotechnologie, Genetische und Reproduktionstoxikologie, Zulassung 2, Bundesinstitut für Arzneimittel und Medizinprodukte, Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Deutschland.
Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2025 May 5. doi: 10.1007/s00103-025-04060-2.
Due to their biological properties, bacteriophages represent a regulatory peculiarity and a challenge for drug approval. Adopted European guidelines on pharmaceutical quality, preclinical, and clinical development are only partially applicable to phage products. The increasing threat of infections with multi-resistant pathogens has not only given a major boost to the development of bacteriophages for the treatment of bacterial infections in recent years but has also led to major progress in the adaptation of regulatory requirements. This review article presents these recent developments and the current status of regulatory requirements for phage therapeutics.In 2024, harmonised quality criteria for phage products and active pharmaceutical ingredients have been implemented in the European Pharmacopoeia for the first time. Both the EU pharmaceutical reform and the national Medical Research Act should enable exemptional regulations taking into account the special features of phage therapeutics and allow novel regulatory pathways. Although increasing clinical data on the use of phage therapeutics have been published, the desired breakthrough in the form of proof of efficacy in randomised controlled clinical trials has not yet been achieved. However, the growing knowledge on phage preparations could be used to adjust the regulatory requirements. The next and decisive step on the path to approval of a defined phage product is the evidence-based proof of efficacy and safety in a randomised controlled clinical trial.
由于其生物学特性，噬菌体代表了一种监管上的特殊性以及药物审批方面的一项挑战。欧洲采用的关于药品质量、临床前和临床开发的指导原则仅部分适用于噬菌体产品。近年来，多重耐药病原体感染带来的威胁日益增加，这不仅极大地推动了用于治疗细菌感染的噬菌体的开发，也在监管要求的调整方面取得了重大进展。这篇综述文章介绍了这些最新进展以及噬菌体治疗的监管要求现状。2024年，噬菌体产品和活性药物成分的统一质量标准首次在《欧洲药典》中实施。欧盟药品改革和国家医学研究法案都应考虑到噬菌体治疗的特殊特征，从而实现豁免规定，并允许采用新的监管途径。尽管关于噬菌体治疗应用的临床数据不断增加，但在随机对照临床试验中尚未取得作为疗效证据的理想突破。然而，对噬菌体制剂日益增长的了解可用于调整监管要求。在明确的噬菌体产品获批道路上的下一个决定性步骤，是在随机对照临床试验中以循证方式证明其疗效和安全性。
