SOURCES SOUGHT
A -- The Identification and Characterization of Therapeutics to Prevent, Modify and Treat Resistant Epilepsy: Neuroprotectants as Countermeasures to Chemical Threats
- Notice Date
- 10/6/2010
- Notice Type
- Sources Sought
- NAICS
- 541711
— Research and Development in Biotechnology
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute of Neurological Disorders and Stroke, 6001 Executive Boulevard, Neuroscience Center, Suite 3287, MSC 9531, Bethesda, Maryland, 20892-9531
- ZIP Code
- 20892-9531
- Solicitation Number
- NIH-NINDS-10-03
- Archive Date
- 11/6/2010
- Point of Contact
- Helene C Braun, Phone: 301 496-1813
- E-Mail Address
-
hb106s@nih.gov
(hb106s@nih.gov)
- Small Business Set-Aside
- N/A
- Description
- PURPOSE: The National Institute of Neurological Disorders and Stroke (NINDS) is interested in identifying sources with the requisite capabilities and qualifications to provide multiple pharmacological screening services directed at discovery of interventions in disease processes of seizure progression, new therapeutics for patients with epilepsy, resistant epilepsy and as countermeasures to damage resultant from possible exposures to chemical nerve agents. The NINDS envisions awarding a contract for comprehensive in vitro and in vivo screening services in models/assays designed to identify and evaluate both the potential efficacy and toxicities of candidate compounds intended as lead therapeutics against resistant forms of epilepsy, interventions in disease processes of seizure progression and as countermeasures to possible exposure to chemical nerve agent induced damage. Hundreds of small molecules are submitted to the Anticonvulsant Screening Program (ASP) annually with the intent to assess their bioactivity for further translation of compounds possessing sufficient potency, efficacy, and drug-likeness (lead compounds) into late stage preclinical safety (absorption, distribution, metabolism, and excretion (ADME)) studies prior to investigational new drug (IND) application. BACKGROUND: The ASP was initiated in 1975 in response to a congressional inquiry on therapeutic development strategies for the epilepsies. Since inception over 30T compounds have been evaluated for their potential as therapeutics to treat patients with epilepsy and other related Central Nervous System (CNS) disorders. For over three decades the ASP has contributed to the discovery, optimization and translation of candidate compounds resulting in FDA approvals for ten currently marketed AEDs, eight in various stages of clinical development and 100s of others currently undergoing preclinical testing and development. The ASP coordinates the activities of more than 500 domestic and international public/private research partnerships in areas of chemistry, pharmacology, model development and drug testing directed at epilepsy and related CNS research as well as countermeasures to chemical nerve agents. Summarily, hundreds of small molecules are submitted by ASP participants around the world which are then screened for both efficacy and neurotoxicity. The resulting leads are used to support participating sponsors with critically relevant preclinical evidence used for long-term toxicology studies required for submission of Investigational New Drug Applications (INDs) to the Food & Drug Agency (FDA). An in-house NINDS stepwise decision making process involving expert pharmacologists, chemists and toxicologist are utilized to make interim selections on the most active compounds. Compounds are advanced through a unique multistage screening and analysis process. When a therapy is finally chosen its pharmacokinetic and pharmacodynamic profile is compared to that of known drugs as well as those still under development. This intensive process assures that products being proposed for human trials provide a clear treatment advantage over existing therapies. INFORMATION REQUESTED: With consideration to the above, the NINDS is requesting the following specific information as part of our market research in support of this program. It is mandatory that your response demonstrate your technical abilities and related scientific and managerial experience in a requirement-specific Capability Statement to: 1) quantitatively validate complete anticonvulsant pharmacological profiles for the 20 approved antiepileptic drugs (AEDs) prior to screening of novel candidates. The profiles require: ED& TD50s, Std. Error of the mean, 95% confidence intervals, slopes of the regression lines, using both mice and rats by various routes of administration (i.p., p.o., s.c. and some i.c.v.) performed in the models noted below. Quantitative calculations must include at least three different doses using a minimum of eight rats and eight mice per dose per test. Testing must have been done in the range of models currently accepted as standard preclinical assays predictive of human efficacy. This requirement must be fulfilled and satisfactorily demonstrated before screening of novel candidate drugs can take place. 2) Demonstrate capabilities to accept, store, prepare and annually screen 750 to 1000 small molecules in the battery of in vivo and in vitro epilepsy models/assays utilized in the ASP, 3) obtain, adequately house and maintain hundreds of mice and rats for periods of weeks to months between and during test cycles providing evidence of meeting all IACUC and PHS animal certification requirements, 4) provide laboratory space, equipment, to adequately handle the large volume of molecules and simultaneous testing requirements, 5) demonstrate evidence of in-house expertise and competency in handling different rodent species, slice & cell culture preparations, experience using chemical chemo-toxins (i.e. metrazol, bic, pic, NMDA and KA) & proficiency in use of electrical stimulation models (MES, 6 Hz and kindling paradigms-hippocampal & amygdala rat and corneal mouse, (note MES & 6Hz testing is approx 750 annually while kindling is 300 candidates annually, testing requires both qualitative and quantitative assessment), culture preparation and chronic EEG electrographic monitoring for chronic antiepileptogenic and disease modification studies and evaluations (15-20 annually), 6) Provide evidence of possessing resources & competency in using patch clamping techniques, 7) surgical skills using whole animals for kindling, electrographic monitoring & interpretation of recordings necessary to differentiate candidate compounds, 8) report-writing and data collection capabilities 9) Other specific modeling requirements include: a) Morris Water Maze - forced swim with chronic dosing to test for cognitive impairment, depression (20-30 compounds annually), b) neuroprotection screening using organotypic hippocampal brain slices to against various excitotoxins (KA & NMDA - note: must possess medium throughput capabilities for screening 500-600 candidates annually) c) both qualitative & quantitative efficacy and toxicity testing using the pilocarpine resistant status rat models (600 compounds annually) and d) Chung and formalin model of pain e) sciatic nerve ligation model of neuropathic pain (200 compounds annually). 10) Provide evidence and examples of design, development and validation of new screening paradigms. 11) in vitro CYP inhibition studies (100 annually), & metabolic gene induction studies using reporter cell lines (100 annually), 12) genetic model of epilepsy (Fring mouse - approx. 60 annually) and finally 13) evidence of capability to perform in vitro mechanism of action studies for both inhibition and excitation studies (GABA, NMDA and channels). Please submit 4 copies of your response to the attention of Helene Braun, Contract Specialist, at the address provided by 4:00 PM Local Time on October 22, 2010. In lieu of hard copies, electronic submittal will also be accepted at hb106s@nih.gov (please format for printing). You are encouraged to limit you response to fewer than 15 pages and must specifically address each of the requirement specific items stated above. Generic marketing brochures will not be considered further. This Announcement is for information and planning purposes only and shall not be construed as a solicitation or as an obligation on the part of the Government. The Government does not intend to award a contract on the basis of responses nor otherwise pay for the preparation of any information submitted or the Government's use of such information. Acknowledgment of receipt of responses will not be made, nor will respondents be notified of the Government's evaluation of the information received. However, should such a requirement materialize, no basis for claims against the Government shall arise as a result of a response to this announcement or the Government's use of such information as either part of our evaluation process or in developing specifications for any subsequent requirement. Responses will be held in a confidential manner. Any proprietary information should be so marked. All respondents are asked to indicate the type and size of your business organization, e.g., Large Business, Educational Institution, Small Business, Veteran-Owned Small Business, Service-Disabled Veteran-Owned Small Business, HUBZone Small Business, Small Disadvantaged Business, Women-Owned Business, 8(a). If submitting hard copies, please send to: Helene Braun, Contract Specialist, National Institutes of Health, NINDS R&D Contracts Management Branch, CMB, 6001 Executive Blvd., Suite 3287, Bethesda, MD 20892-9531 or via courier to Rockville, MD 20852. THIS ANNOUNCEMENT IS NOT A REQUEST FOR PROPOSALS. Once a determination is made regarding the suitability of this future requirement for a small business set-aside or an open competition to include both large and small business, a separate Pre-Solicitation Announcement will be issued in advance of the release of a Request for Proposals. The applicable North American Industry Classification System (NAICS) code for this requirement is 541711. Therefore, the small business size standard for this announcement is 500 or fewer employees. Please note that in order to qualify as an eligible small business for purposes of a small business set-aside, at least 50% of the direct labor cost must be in-house. Specifically, FAR 52-219-14 - Limitations on Subcontracting states that at least 50 percent of the cost of contract performance incurred for personnel shall be expended for employees of the concern. Submitted Capability Statements must address how the business meets the applicable size standard designated for this project.
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