Text from EMA Qualification Opinion on In-vitro hollow fiber system model of tuberculosis (HSF-TB)
…
4.3 Proposed Use of HFS-TB in Drug Development
The HFS-TB can: (1) mimic the concentration-time profiles of antibiotics observed in TB patients, (2) mimic the metabolic and physiologic behavior of Mtb populations commonly encountered in infected patients with pulmonary TB and the intracellular Mtb characteristic of disseminated TB and (3) quantify the sensitivity and resistance of these Mtb populations to various doses and combinations of antibiotic agents over time. When these outcomes are correctly achieved, the results can then be used in Monte Carlo simulations to identify
(i) optimal doses of drugs,
(ii) drug combinations which are most likely to achieve desired microbial outcomes,
(iii) expected response rates from a drug or combination regimen,
(iv) expected rates of and time to resistance emergence in patients and
(v) susceptibility breakpoints based on a minimum inhibitory concentration (MIC) above which therapy by a specific drug will fail.

The HFS-TB is proposed for use in optimization of drug regimens and dose selection to maximize the bactericidal and sterilizing effect rates and minimize the emergence of resistance. When used early in the drug development cycle as a complementary and additional tool to existing methodologies, information regarding optimal dose selection, dosing schedules and potential combination therapies can be obtained. Additionally, the HFS-TB can be used in a post-approval setting to optimize currently used drug regimens (for both dose and dosing schedule) for drug-susceptible and drug-resistant TB. Therefore, the results obtained by the HFS-TB are expected to support trial design for Phase I, II, III and IV clinical trials.