Masterstudiengang "Drug Regulatory Affairs"


Evaluation and consideration of resistance data on the licensing process of antibiotics ***

Dr. Daniela Lieder (Abschlußjahr: 2005)

The discovery of antimicrobial agents over 50 years ago has been one of the greatest achievements of medicine. Antibiotics have been used to treat diseases in humans and have revolutionized the treatment of bacterial infections, protecting previously vulnerable populations against painful, debilitating, and even life-threatening illness. The success of antibiotic treatment is now reduced and bacterial resistance is becoming a major and growing problem in health care. However, the current level of antibiotic-resistant bacteria is attributed to the overuse and abuse of antibiotics. The emergence of resistance has limited the number of effective antimicrobial agents available for therapy of common infections that were once easily treated by antibiotics. The transfer of genetic material between bacterial species provides an easy and efficient way to multiply and spread of resistance against several antibiotics at one time.

In recent years guidance documents have been established by the CHMP for the improvement of market authorisations and product information of antimicrobial drugs. One key guideline [CPMP/EWP/558/95 rev.1] has come into effect in October 2004. One purpose of this document is to provide guidance on the principles on the development of antibacterial drugs under the aspect to minimise resistance development and to encourage prudent use of antimicrobials in medicine. The guideline also contains new requirements for the format and structure of the pharmacodynamic section of the SPC, particularly details on resistance information. This section should include a brief description of the mode of resistance mechanism(s), the information about the susceptibility of bacteria (MIC breakpoints) and a table that display information on the species-specific prevalence of the resistance to the drug. The new recommendation comprises to subdivide the resistance rates of bacterial species into three susceptibility categories, because resistance data provide useful information about patterns of emerging resistance, which in turn can guide the physicians by treatment decisions. Different national and international surveillance systems aiming to collect comparable resistance data represent one tool to get sufficient data to analyse the current resistance situation and to give a well-established overview.

Because information concerning resistance changes chronologically and geographically, it needs to be updated within the scope of regulatory activities like compilation of PSURs, renewal procedure, and whenever a significant change in sensitivity profile is found.

This thesis concentrates on the new requirements of antibacterial SPCs relating resistance information. The requirements are discussed in detail -under involvement of scientific, therapeutic and regulatory aspects- and are exemplified. The impact of the changing resistance situation and some of the challenges derived thereof are pointed out.

Pages: 59