Notice of Intent: In vitro cell permeation model and drug classification for the prediction of drug transfer into human milk

This synopsis is hereby issued in accordance with FAR Part 5.203 and FAR 13.501(a) in response to the mandatory requirement for a 15-day notification. The purpose of this synopsis is to announce the Food and Drug Administration's (FDA) intent to negotiate a Firm Fixed Price sole source contract with Husson University- School of Pharmacy., located at 1 College Circle, Bangor, Maine 04401 to develop and validate a human mammary epithelial permeability assay and use in vitro to in vivo extrapolation (IVIVE) approach to predict the amount of drug transfer into human milk. The Government intends to negotiate solely with Husson University, as the only source capable of performing this work. The tasks to be performed under the anticipated award are as follows: 1. To develop and validate a human mammary epithelial permeability assay for mammary drug transport. 2. To assess expression levels of xenobiotic transporters in established human mammary epithelial permeability model and human breast tissues. 3. To facilitate developing physiologically based pharmacokinetic (PBPK) modeling based in vitro to in vivo extrapolation (IVIVE) approach. Husson University, School of Pharmacy is the only source capable of performing the work above based on the following unique qualifications/capabilities- 1. The capability to culture an immortal human MEC line to form integral tight junctions with TEER values > 1000 ??cm2 (1000-2000 ??cm2); Characterized the tight junction formation and extensively assessed various culturing conditions; Tight junctions maintained for 2-3 h when human breast milk was used during incubation 2. Experience of establishment and characterization of CloneticsTM human corneal epithelial (cHCE) cell line as a corneal permeability model for in vitro permeability assay and to predict corneal permeability of topically administered compounds (Xiang, Batugo et al. 2009) 3. Characterization, quantitation and functional analysis of CYP450, nuclear receptors, and common xenobiotic transporters in preclinical species and human ocular tissues and cells (Zhang, Xiang et al. 2008, Lam, Jiang et al. 2010) 4. In vitro permeability assay of drug candidates across Caco-2 cells, in vitro transport assay in stably expressed and over-expressed human transporter cell lines. (Several years' industrial experience in Novartis Institutes for Biomedical Research) 5. Extensive hands-on experience in PK analysis, PBPK modeling and PK/PD modeling to establish IVIVE, predict human drug concentrations in different populations, and a master user of several PK modeling and simulation software (Simcyp, Gastroplus, Phoenix WinNonlin, etc.)(Xia, Barve et al. 2014, Zhang 2015, Zhang, Heimbach et al. 2015, Conner, Nikolian et al. 2018, Conner, Reed et al. 2018) 6. Unique experience in culturing more than ten different breast normal and cancer cell lines, and optimizing culturing systems for monolayer, mammosphere and colony formation 7. Sandwich-culture of human primary hepatocytes, CYP450 inhibition and induction assays using human liver microsome, cDNA recombinant CYP450 isoenzymes and hepatocytes of lead compounds of MDM2 inhibitors (e.g. MI-219). (Poser presentation at FIP Pharmaceutical Sciences 2010 World Congress in Association with the AAPS Annual Meeting Nov 14-18, 2010 New Orleans, LA) The anticipated period of performance is for one (1) base year and one (1) twenty-four (24) month option period. The anticipated dollar value (inclusive of options) of this purchase is $ 264,880.00 THIS NOTICE IS NOT A REQUEST FOR COMPETITIVE PROPOSALS, however, interested firms may submit a capability statement in response to the above requirement with pricing information by June 29th, 2019 Local Time to Christopher McGucken, Contracting Officer, Phone: (240) 402-7566, Email: Christopher.McGucken@fda.hhs.gov. A determination not to open competition based responses to this notice is solely within the discretion of the Government.