Regulatory Approaches to the Development Programme for Medicines Used to Treat Infectious Diseases

In February 2017 the World Health Organization first published the list of antibiotic-resistant «priority pathogens» — a catalogue of 12 species of bacteria that pose the greatest threat to human health. The list highlights the danger posed by Gramnegative bacteria that are resistant to multiple antibiotics. Thus, the development of new antimicrobial medicines is becoming a pressing issue. The list is an important reference point and incentive to secure and guide research and development related to new antibiotics that will help solve the issue of growing global resistance to antimicrobial medicines. The aim of the study was to determine the main regulatory approaches to planning preclinical and clinical development programmes for new antimicrobial medicines. On the basis of current requirements and recommendations in force in the Russian Federation and guidelines of the European Medicines Agency, the issues of planning antimicrobial drug development programs were considered. The autors analysed the main stages and aspects of preclinical studies of medicines for infectious diseases (specific activity in vitro and in vivo, PK-PD modeling), as well as requirements for the clinical trial stage, including the rationale for the choice of clinically relevant efficacy and safety endpoints, study design, and statistical methods.

1. Shallcross LJ, Davies SC. The World Health Assembly resolution on antimicrobial resistance. J Antimicrob Chemother. 2014;69(11):2883—5. https://doi.org/10.1093/jac/dku346

2. Magiorakos AP, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18(3):268—81. https://doi.org/10.11117j.1469-0691.2011.03570.x

3. Reshetko OV, Yakimova YuN. New systemic antimicrobials. Klinicheskaya mikrobiologiya i antimikrobnaya khimioterapiya = Clinical Microbiology and Antimicrobial Chemotherapy. 2015;17(4):272-85 (In Russ.)

4. Asin-Prieto E, Rodriguez-Gascon A, Isla A. Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents. J Infect Chemother. 2015;21(5):319-29. https://doi.org/10.1016/j.jiac.2015.02.001