Inactive

Description: This is a Research and Development (R & D) Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is... Description: This is a Research and Development (R & D) Small Business Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified small business sources to perform a potential R & D requirement. The purpose of this notice is to obtain information regarding: (1) the availability and capability of qualified small business sources; (2) whether they are small businesses; HUBZone small businesses; service-disabled, veteran-owned small businesses; 8(a) small businesses; veteran-owned small businesses; woman-owned small businesses; or small disadvantaged businesses; and (3) their size classification relative to the North American Industry Classification System (NAICS) code for the proposed acquisition. Your responses to the information requested will assist the Government in determining the appropriate acquisition method, including whether a set-aside is possible. An organization that is not considered a small business under the applicable NAICS code should not submit a response to this notice. This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only. Background: The National Institute of Neurological Disorders and Stroke (NINDS) Epilepsy Therapy Screening Program (ETSP), until recently known as the Anticonvulsant Screening Program (ASP), was established in 1975 to address a critical need for new anti-seizure medications and to promote industry interest in their development. The screening process involves researchers from academia and industry in the U.S. and abroad (“ETSP participants”) submitting compounds to the ETSP for investigation in a series of animal (rodent) acute and chronic seizure models. These tests are performed blinded by the contract laboratory and on a confidential basis through a written agreement between the NINDS and the ETSP participant at no cost to the ETSP participant. The NINDS ETSP program office reports test results to participants and provides advice on future steps for promising compounds, while protecting confidentiality and intellectual property. Over 32,000 compounds have been screened to date, and the ETSP has contributed to bringing 11 anti-seizure drugs to market since 1990, with a major role in some and a minor role in others. The ETSP was reviewed by Working Groups commissioned by the National Advisory Neurological Disorders and Stroke (NANDS) Council in 2011, 2014 and most recently in 2020. The Working Groups’ recommendations were consistent in each review in favor of prioritizing the identification of treatments for drug resistant epilepsy, epileptogenesis, and disease modification over the identification of additional undifferentiated anti-seizure drugs. The new name of the program (ETSP) is meant to emphasize that a major focus is going beyond the symptomatic treatment of seizures to identifying agents that have the potential to prevent their development. Additional details on the reports containing the Working Groups’ recommendations are available for review at https://www.ninds.nih.gov/Current-Research/Focus-Research/Focus-Epilepsy/ETSP. Purpose and Objectives: The NINDS is interested in identifying sources with the requisite capabilities and qualifications to perform annually various preclinical pharmacological evaluations of investigational compounds as potential therapies for the treatment of epilepsy disorders. Contractor will also conduct pharmacokinetic studies using normal and epileptic animals. Epilepsy model development and validation will be conducted on an as needed basis. Project requirements: The NINDS envisions awarding a contract to support the conduct of preclinical pharmacological evaluations of investigational compounds as potential therapies for the treatment of epilepsy and related disorders. This contract shall require the contractor to conduct studies including, but not limited to, the following performance areas: anti-seizure screening in acute and chronic seizure models, models of anti-epileptogenesis and disease modification, models of special epilepsy populations, models and endpoints associated with neurological assessment and recognized co-morbidities of epilepsy. The contract shall also require the performance of pharmacokinetic and potentially some ADME studies. Initial in vivo testing will routinely utilize male rodents but female animals will also be required on specified candidate compounds and models. Major technical requirements are listed under the Information sought section below. Technical deliverables will include data reports for all completed studies submitted in compliance with Section 508 for the Rehabilitation Act of 1973, quarterly progress reports, Standard Operating Procedures (SOPs) and tables for comparative assessments for all major testing performed in the preclinical pharmacological evaluations. Anticipated period of performance: The anticipated period of performance is a base period of 12 months (1 year) with four successive 12-month term options for a total possible performance period of five (5) years. Capability statement /information sought. 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 expertise and managerial experience in a requirement-specific Capability Statement. Demonstrate evidence of proficiency in conducting studies with different rodent species by various routes of administration [oral gavage (p.o.), intraperitoneal (i.p.), subcutaneous (s.c.), and intracerebroventricular injection (i.c.v.)] performed in acute and chronic seizure models as follows. These include electrical stimulation models (maximal electroshock test mouse and rat, 6 Hz seizure test mouse and rat, mouse corneal kindled seizure test and rat pharmacoresistant amygdala kindled seizure test) and chemoconvulsant models (metrazol-, pilocarpine-, focal- and systemic kainic acid-) induced epilepsy. Provide data tables demonstrating quantitative pharmacological profiles for at least 10 clinically approved anti-seizure drugs (ASDs) by i.p. route of administration. The profiles require the following: ED50s & TD50s determinations, 95% confidence intervals, quantitative calculations must include at minimum eight rats or mice per test dose. Quantitation must be provided for both mouse and rat maximal electroshock tests, mouse 6 Hz seizure test and mouse corneal kindled seizure test. TD50 values (TD= “toxic dose”) must be based on assessment of motor impairment in mice (rotarod test) and rats (assessment of minimal motor impairment). Provide data tables demonstrating quantitative pharmacological profiles for at least 6 clinically approved anti-seizure drugs (ASDs) by i.p. route of administration. The profiles require ED50s determinations in a pharmacoresistant amygdala kindled seizure test and a chronic mouse model of mesial temporal epilepsy (mTLE) induced by focal administration of a chemoconvulsive agent. Demonstrate capacity to perform annually the following quantitative screening of novel investigational compounds. Include technical staff, laboratory, animal and surgical facilities and equipment to handle concurrent testing requirements. At minimum 120 compounds in the mouse 6 Hz and maximal electroshock tests. At minimum 40 compounds in the rat 6 Hz and maximal electroshock tests. At minimum 40 compounds in the mouse corneal kindled seizure test. At minimum 20 compounds in a rat model of pharmacoresistant amygdala kindled seizures and a mouse model of mesial temporal lobe epilepsy. At minimum 15 compounds screened in post-status epilepticus epileptic rats measuring spontaneous recurrent seizures chronically by video-EEG monitoring. This must include the capability of administering test compounds in food via an automated feeder system. Capability to screen a minimum of 15 investigational compounds in acute rodent hippocampal slice preparation determining concentration response activity against spontaneous bursting. At minimum 10 compounds in a model of infection-induced epilepsy At minimum 5 compounds evaluated in a rodent model of drug refractory status epilepticus. A minimum of 5 compounds evaluated for anti-epileptogenic or disease modifying effects in a status epilepticus-induced chronically epileptic rat by assessing the development of spontaneous recurrent seizures recorded by video-EEG monitoring. Demonstrate capability to perform pharmacokinetic studies in mice and rats on a investigational minimum of 15 compounds. Demonstrate experience in setting-up and validating new models in-house for screening investigational compounds for the treatment of pharmacoresistant epilepsy, disease modification and epileptogenesis. Demonstrate capabilities to receive and store hundreds of investigational small and large molecules and biologicals including Drug Enforcement Agency (DEA) Scheduled compounds (must possess DEA license for schedule I-V drugs). Capability to prepare dosing formulations and properly dispose of investigational compounds. 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, accreditation by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) and approved Animal Welfare Assurance for the Office of Extramural Research (OER), Office of Laboratory Animal Welfare (OLAW), Office of the Director, NIH as required by Section 1-43-30 of the PHS Policy on Humane Care and Use of Laboratory Animals. Report-writing, data collection capabilities and record storage for up to ten years. Provide evidence of capabilities for IT security, and networking support for managing data and interface with NIH network. Provide evidence of scientific expertise of the principle investigator in the evaluation of investigational compounds in models of epilepsy, epileptogenesis and disease modification and the development and validation of rodent seizure models (demonstrated by peer reviewed scientific publications and invited speaker invitations) and broad knowledge in the epilepsy research field. Provide profile of compay management team and their experience in management of epilepsy therapy screening business. The respondent must also provide their DUNS number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements. The information submitted must be must be in an outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein. A cover page and an executive summary may be included but is not required. The response must include the respondents’ technical and administrative points of contact, including names, titles, addresses, telephone numbers, and e-mail addresses. All responses to this notice must be submitted electronically to the Contract Specialist, Sneha Singh, at sneha.singh@nih.gov. Facsimile responses are NOT accepted. The response must be received on or before February 8, 2021 at 5:00 p.m., Eastern Standard Time. “Disclaimer and Important Notes: This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization’s qualifications to perform the work. Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in betaSAM. However, responses to this notice will not be considered adequate responses to a solicitation. Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).”