SOLICITATION NOTICE
B -- Recombiant E-Selectin - Solicitation
- Notice Date
- 7/8/2014
- Notice Type
- Combined Synopsis/Solicitation
- NAICS
- 325412
— Pharmaceutical Preparation Manufacturing
- Contracting Office
- Department of Health and Human Services, National Institutes of Health, National Institute on Drug Abuse, Station Support/Simplified Acquisitions, 31 Center Drive, Room 1B59, Bethesda, Maryland, 20892
- ZIP Code
- 20892
- Solicitation Number
- HHS-NIH-NIDA-(SSSA)-14-349
- Archive Date
- 8/22/2014
- Point of Contact
- Brian Lind, Phone: 3014021635
- E-Mail Address
-
lindbj@nida.nih.gov
(lindbj@nida.nih.gov)
- Small Business Set-Aside
- N/A
- Description
- Attachment Number Four - Section K Attachment Number Two - Proposal Intent Form Attachment Number One - Proposal Packaging Instructions Attachment Number Three - Statement of Work Solicitation - HHS-NIH-NIDA(SSSA)-14-349 E-Selectin The National Institutes of Health (NIH) is the nation's leading medical research agency and the primary Federal agency whose mission is to seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability, conducting, supporting and making medical discoveries that improve people's health and save lives. The National Institute of Neurological Disorders and Stroke (NINDS) is a part of the National Institutes of Health (NIH), conducting research into the causes, treatment, and prevention of neurological disorders and stroke. The NINDS mission is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. The NlNDS currently has planned two (2) trials; a Phase 1 safety trial and a Phase 2 proof of concept trial assessing the safety and efficacy profiles of intranasally instilled rhE-selectin. The patients in these trials will be diagnosed with Binswanger Disease, involving progressive impairment of cognition. The progressive cognitive impairment derives from a stroke like etiology. The illness begins with impairments of gait and balance, focal neurologic findings, and executive dysfunction. The disorder is progressive and leads to further lacunar recurrent strokes with increasing functional disability that is both motor and cognitive. Despite the use of antithrombotic drugs for the prevention of recurrent strokes, 10% of patients who experience any cerebral ischemic event will go on to have a stroke within 90 days. The development of new treatment strategies for prevention of the various forms of recurrent stroke is an important issue for modern medicine. The principle for the use of E-selectin is the increasing evidence that a state of chronic, subtle immune dysregulation that leads to inflammation at the sites of endothelial activation plays an important role in the pathogenesis of strokes. Control of such molecular inflammation at the sites of endothelial activation can be achieved by induction of mucosal tolerance. The induction of mucosal tolerance by repeated low-dose intranasal administration of E-selectin causes a shift of the immune response. T -cells tolerized to E-selectin become circulating regulatory cells that release anti-inflammatory, immunosuppressive cytokines locally when these T-cells encounter E-selectin in activated blood vessel segments. The local release of these cytokines suppresses the vessel activation and prevents local thrombosis or hemorrhage. This approach to stroke prevention differs from conventional measures. It will very likely synergize with existing clinical regimens for prevention of stroke and will stimulate a great deal of research in this under-explored area. Statement of Objectives The purpose of the acquisition is to attain clinical grade production of recombinant human E-selectin (rhE-selectin) within Good Laboratory Practice (GLP) or current good manufacturing practices (cGMP) standards in sufficient quantities for use in multiple animal studies and two human clinical trials. This acquisitions objective is to: (1) obtain a sufficient amount of rhE-selectin for use in nonclinical animal studies; followed by, but contingent upon the results of the toxicology animal study, under either GLP or cGMP guidelines for use in two human clinical trials; and (2) obtain regulatory meeting support for the pre-IND and IND filing for use of E-selectin in the treatment of Binswanger Disease. Written reports to be in eCTD format; and the regulatory meeting support will include a contractor representative to field questions from the FDA before and after the IND filing process. (3) full CMC section report, per FDA requirements, in writing. Scope of Work This acquisition will permit production of the recombinant protein at the right quality in the shortest possible time. Background material in support of desired outcomes consists only of high level descriptions of the most likely process and analytical method parameters. Sponsor wishes to allow Contractor to optimize or further develop and improve on existing methods to meet Sponsor's desired outcomes as described later in this document. However, all changes must be discussed with and receive prior approval from Sponsor. The scope of work includes: a) Cloning and small scale expression, purification, and preliminary characterization of a 282 amino-acid truncated version of human E-selectin by inserting DNA coding sequences optimized to yield a stable and highly expressing selected Baculovirus insect cell expression single clone producing the native 282 amino-acid recombinant protein and demonstrating its bioactivity using a cell adhesion potency assay. b) Creation, characterization, and maintenance of a stable GLP Master Cell Bank and possibly an optional Working Cell Bank using selected clone. c) Develop, characterize, optimize, and establish written procedures describing the downstream processing/purification of the 282 amino-acid rhE-selectin protein. d) Develop, optimize, and establish written procedures of analytical test methods and procedures to extensively characterize the identity, purity, sterility, stability, dose concentration, and potency of recombinant human E-selectin during in-process production and for final release testing requirements. e) Develop, designate and maintain a well characterized Reference Standard of the 282 amino-acid rhE-selectin that can be used to qualify production lots for final lot release testing. f) Design and establish manufacturing scale-up procedures consistent with a stable and optimized manufacturing process plan. g) Demonstrate procurement and receipt of all necessary and qualified raw materials, maintenance of appropriate inventory control, consistent with a recognized and compliant in-house Quality Assurance System. h) Demonstrate qualification of all critical raw material vendors and any testing sub-contractors. i) Produce GLP or cGMP grade truncated rhE-selectin protein using a Baculovirus Expression Vector System (BEVS) in an insect cell platform in amounts to be specified: • The amount of rhE-selectin required will be presented in the final contract. The working estimates are that at a 1000 mg ±10% scale will be required from early batch for rodent model studies, another 2,000 mg ±10% scale for additional animal toxicology studies and research studies, and another 2,000 mg ±10 % scale for human clinical studies. It is anticipated that these materials will be derived from distinct production lots to demonstrate the reproducibility of the production process and reliability of analytical release criteria. • Specifically, the 282 amino acid rhE-selectin that (i) contains a secretory signal peptide, which is removed during secretion, (ii) has complete homology to the human E-Selectin sequence except for a signal peptide and the two amino acid residues (Arg-Ser) at the carboxy terminus, which are derived from the translation of linker sequence in the baculovirus expression vector (according to current immunological data, two amino acid residues are not capable of inducing humoral, cellular, or mucosal immune responses). There are significant advantages in recombinant protein quality, productivity, post-translational processing and biological activity, and therefore we expressly require, that the expression be done in insect cells. Molecular mass specifications include the 282 amino acid sequence of the amino terminal of the extra membranous domain of human E-selectin comprised of lectin, epidermal growth factor, and complement regulatory factor repeats beginning with ‘WSYNT...' and ending with ‘....CKAVT'. The full sequence will be provided in the contract. j) Perform final product release testing and provide a Certificate of Analysis (COA) for each recombinant human E-selectin production lot using analytical tests and preliminary acceptance criteria specified in Table 3. k) Design and perform stability testing (real-time and accelerated) of purified rhE-selectin protein. In addition, assess any variability of dose concentrations due to potential protein aggregation, precipitation, or adsorption to cryovial and nasal spray device surfaces, using assays specified in Table 3 and 5. l) Able to provide a fraction of first rhE-selectin production lot, successfully release tested as compared against the reference standard, cross-linked with a radiolabelled isotope for use in sponsor's animal PK studies: approximately 60-70 mg. Details to be specified in contract. m) Facilitate access to experienced regulatory staff to work in collaboration with sponsor and contractor to prepare for, and write the CMC-related section of the pre-IND meeting package; and prepare for and write the CMC section of the IND in eCTD format. Regulatory staff should also be available and participate in any required written or verbal interaction with FDA before and after filing of the IND. n) Able to provide deliverables that include human E-selectin product in a time frame allowing for the start of Good Laboratory Practice (GLP) animal toxicology and immunotoxicology testing in twelve to fifteen months, or sooner, from time of contract release. o) Has experience and potential capability in developing formulations of recombinant proteins for long-term stability should variability of dose concentrations be observed due to protein aggregation or adsorption to storage container or nasal delivery device surfaces. p) Delivery of product to be delivered in aliquoted cryogenic vials, to avoid degradation of product due to freeze thaw impact on bioactivity. Quantity per vial to be determined. q) Able to provide sterile placebo vials of PBS without protein or other contaminants, amounts and volume per vial to be given at time of contract. r) Prepare and approve all necessary GLP or cGMP documentation consistent with a compliant Quality System and maintain this Quality System necessary to support GLP or cGMP manufacturing compliance requirements and CMC section write-ups. Please refer to the attached solicitation and related documents for the complete details and specifications for this requirement.
- Web Link
-
FBO.gov Permalink
(https://www.fbo.gov/spg/HHS/NIH/NIDA-2/HHS-NIH-NIDA-(SSSA)-14-349/listing.html)
- Place of Performance
- Address: National Institutes of Health, National Institute on Neurological Disorders and Stroke, 35 Center Drive, Building 35, Bethesda, Maryland, 20892, United States
- Zip Code: 20892
- Zip Code: 20892
- Record
- SN03418204-W 20140710/140708235552-4abd32f4398ed2479cc7ac6f3e597128 (fbodaily.com)
- Source
-
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