Clinical and Regulatory Development of Antibiofilm Drugs: The Need, the Potential, and the Challenges - Antibiofilm Agents: From Diagnosis to Treatment and Prevention - page 462

that the novel, high-potential antibiofilm strategy for treatment of infection faces so
many barriers and challenges to clinical implementation.

4 Current Regulatory Guidances: Emphasis on New
Treatments for Serious, Antibiotic-Resistant Infections,
But No Provision for Antibiofilm Mechanism

While there are a series of FDA clinical/antimicrobial guidances related to the
development of antibacterials for the treatment of a variety of infections ( FDA
website: Guidance Compliance Regulatory Information, Guidances), none of the
guidances address the development of antimicrobial drugs targeting biofilms or any
other specific microbial targets (e.g., virulence factors). Likewise, the European
Medicines Agency document titled “Guideline on the evaluation of medicinal
products indicated for the treatment of bacterial infections” (European Medicines
Agency website) also does not address the issue of the treatment of infections
related to biofilms.
Even so, the July 2013 FDA guidance titled “Guidance for Industry:
Antibacterial Therapies for Patients with Unmet Medical Need for the Treatment
of Serious Bacterial Diseases” (FDA 2013 ) provides a discussion that indicates
(a) the urgent unmet need for new antibacterial drugs, (b) the difficulty in carrying
out antimicrobial regulatory studies, and (c) the effort that the FDA is making to
encourage antimicrobial drug development, particularly for

life-threatening

infections.
Over the past few decades, efforts to develop new antibacterial drugs have declined
substantially. Over this same time period antibacterial drug resistance has become more
common even in settings in which attempts were made to slow the rate at which bacterial
pathogens become resistant, such as the prudent use of antibacterial drugs and adherence to
infection control procedures. As a result, an increasing number of patients are suffering
from bacterial diseases that do not respond to currently available antibacterial drugs, with
serious consequences, including increased mortality.

Clinical trials for antibacterial drugs can be challenging for a number of reasons, including:
(1) for a serious bacterial disease, there is a need to urgently initiate empiric antibacterial
drug therapy, which may obscure the effect of the antibacterial drug under study because
patients receive effective antibacterial therapy before enrolling in the trial; (2) patients with
serious acute bacterial diseases can be acutely ill (e.g. delirium in the setting of acute
infection) and obtaining informed consent and performing other trial enrollment procedures
in a timely fashion may be difficult; (3) there may be diagnostic uncertainty with respect to
the etiology of the patients' underlying disease, including identifying a bacterial etiology;
and (4) there may be a need for concomitant antibacterial drug therapy with a spectrum of
activity that may overlap with the antibacterial drug being studied.

A decreased rate of antibacterial drug development poses a significant public health
concern. As bacteria continue to develop resistance because of selection pressures from
empiric and/or inappropriate use of currently available antibacterial therapies, increased