Impact of Erythropoiesis Stimulating on Malignant Tumor Growth

This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6, in conjunction with Far 13.5 as applicable and as supplemented with additional information included in this notice. This announcement constitutes the only solicitation. This is a Request for Quotations (RFQ); a written solicitation will not be issued. The Food and Drug Administration, Center for Drug Evaluation and Research has a requirement for the services below: Objective: The objective of this contract is to collaborate on the development of a three part study for assessing the Impact of Erythropoiesis Stimulating on malignant tumor growth. B.2 - Compensation - Fixed-Price Schedule - A. As consideration for the services described in C-I, "Scope of Work," the Government shall pay to the Contractor the fixed price of $________________. B. Base Period (October 1, 2008 through September 30, 2009) Description Quantity Unit Unit Price 1. Sample and reservation of tissue and related clinical data 1 JOB $_______ 2. Establishment of Ventana staining protocols for Ki67 and Caspases 3/7 1 JOB $________ 3. Preparation of primary colon cancer cells and corresponding tissue grant access and use 1 JOB $_________ 4. Preparation of primary colon cancer cells and corresponding tissue grant of access and use 1 JOB $__________ C-1 - Description/Specifications/Work Statement Independently and not as an agent of the Government, the Contractor shall furnish all necessary personnel, materials, services and otherwise do all things necessary for or incident to the performance of the work as described below: In preparation for this project, significant work towards fulfillment of Part I of this study has already been performed by Indivumed, such as standardized tissue collection, comprehensive data accrual by interviewing patients, data validation by our documentation assistants and the establishment of various protocols for Ventana-Immunohistochemistry staining. Part I - determine expression of erythropoietin receptor (EpoR) and erythropoietin (Epo) by immuno-histochemical staining of tissue samples collected under the - Indivumed-Standard. The Indivumed standard refers to Indivumed's highly standardized bio-specimens and clinical data collection protocol which is ensured by the fact that Indivumed personnel 1) have full control over all steps of tissue collection, and 2) document accurately a variety of pre-, intra- and postsurgical factors that might impact molecular reality in tissue samples. For example, Indivumed tissues are characterized by a very short and exactly documented cold ischemia time of less than 12 min. This may be of importance, as it is known that EpoR expression is related to tissue hypoxia. For this study, we will use tissue samples with an average cold ischemia time of 8 (+/- 4) minutes. We will prepare a Tissue-Micro-Array (TMA) that consists of tumor specimens from 50 patients with colorectal cancer and 50 patients with breast cancer. Tumor stage and grad will be distributed equally. As a control, we will use a TMA consisting of corresponding normal tissues from the same patients. For immunohistochemistry staining we will establish a protocol for the Ventana-technology platform which we use for automated routine tissue staining. In addition to EpoR and Epo, we will immuno-histochemically analyze the expression of Ki67 (proliferation rate), caspase 3/7 (apoptotic rate), and Stat5 (total and phosphoprotein levels). All expression data will be correlated with clinical data such as hemoglobin level, tumor stage and tumor grading, age, gender and, if required, up to 300 additional individual data points already available from data base for each patient. Part II - determine the role of Epo and EpoR in activation of signaling pathways and growth/proliferation of tumor cells, e.g. via defining and Epo dose response in primary tumor cells. Indivumed has already prepared various colorectal cancer primary cell cultures that grow by nature continuously in vitro. For these cells Indivumed still has the corresponding original primary tumor available that allows comparative analysis of the expression profile. Determine the expression profile of Epo and EpoR by immunostaining and possibly, RT-PCR in cells and primary tumor tissue. If comparable, we will continue to analyze the impact of Epo on cell growth (proliferation/apoptosis) and signaling pathways (MSD-technology). Also, establish a model for inhibiting Epo effects by adding various dilutions of soluble Epo-R (sEpo-R). sEpo-R which will be provided by collaborators of the FDA. To perform these studies we will use at least one primary cancer cell line which was established and characterized. Part III - Functional analysis of the Epo/EpoR interaction using molecular drug profiling platform. This technology is based on instantly cultivated tumor tissue (vital tissue slices of 200-400 um) which is incubated with a compound of interest and various controls. Cultivate and treat tissue slices from 20 breast cancer patients. In addition, EpoR and Epo expression as well as expression of Epo signaling pathway molecules (e.g. Stat5) will be determined in instantly fixed tumor tissue and compared to cultivated tissue slices. This is done to exclude or at least determine variations of the expression profile due to the cultivation process. Slices will be treated with: 1. Epo 2. Epo + different dilution of sEpo-R 3. Negative control 1 (medium only) 4. Negative control 2 (Epo-solvent, e.g. DMSO) 5. Camptothecin (toxic control) Tissue slice analysis will include: 1. Viability (ATP assay) 2. Apoptotic rate (Caspase assay) 3. Analysis for Epo-related pathway molecules (MSD technology) 4. Expression of Epo, Epo-R, Ki67 (proliferation rate) and Epo-related phosphor-proteins (need to be determined) by using Ventana-technology for immunohistochemistry. The solicitation number is FDA-SOL-08-00846. Quotations are September 3, 2008, by 1:00 p.m. Central Daylight Time in Jefferson, AR; at Food and Drug Administration, OC/OSS/OFFAS, Attention: Sandra Davis, 3900 NCTR Rd., Jefferson AR 72079-9502. The North American Industry Classification System (NAICS) Code is 541990 and the size standard is $6.5 million. The award will be made on the basis of full and open competition from among all responsible business concerns submitting offers. All responsible sources may submit a quotation, which if received timely, shall be considered by the Agency. Offers must reference solicitation number FDA-SOL-08-00846. Contract Type: Commercial-Item Firm Fixed Price, using simplified acquisition procedures. FOB Point of Delivery for equipment and supplies provided will be Food and Drug Administration, Regulatory Information Management, 8800 Rockville Pike, Bethesda, MD 20892. Offerors must include a completed copy of the provisions at FAR 52.212-3, Offeror Representations and Certifications - Commercial Items with its offer. Applicability of FAR Provisions: the following Federal Acquisition Regulation (FAR) provisions and clauses apply to this request for quotes and are incorporated by references. The solicitation document and incorporated provisions and clauses are those through Federal Acquisition Circular (FAC) 2005-26 dated June 12, 2008. COMMERCIAL CLAUSES IN ACCORDANCE WITH FAR PART 12 - INCORPORATED IN FULL TEXT: 52.212-1 Instructions to Offerors'Commercial Items (June 2008) 52.212-2 - Evaluation - Commercial Items (JAN 1999) (a) The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors shall be used to evaluate offers: Technical, Price and Past Performance. Technical and past performances, when combined, are equal to cost. The technical quotations will receive paramount consideration over cost and past performance; however, cost will be evaluated for price reasonableness. Each offeror must (1) submit written information that pertains to their capability to supply the required equipment, (2) identify two sources for which the offeror has provided the same or similar items that are required herein (include contracts within the past two years, Points of contact and telephone numbers). The Government may make its decision on the basis of initial quotations received and not have discussions. Therefore, each initial quotation should contain the offeror's best terms from both a price and technical standpoint. Offerors shall include technical specifications, descriptive material, literature, brochures and other information corresponding to each minimum required item, which demonstrates the capabilities of the offeror. The Government is not responsible for locating or securing any information, which is not identified in the proposal. Before the offer's specified expiration time, the Government may accept the offer (or part of an offer), whether or not there are negotiations after its receipt, unless a written notice of withdrawal is received before award. 52.212-3 - Offeror Representations and Certifications - Commercial Items (June 2008) 52.212-4 - Contract Terms and Conditions'Commercial Items (Feb 2007) 52.212-5 - Contract Terms and Conditions Required to Implement Statutes or Executive Orders'Commercial Items (June 2008): The following additional FAR clauses cited in this clause are applicable: 52.222-3; 52.222-21; 52.222-26; 52.222-35; 52.222-36; 52-222-37; 52.222-50 and 52.232-33 Clause and provisions can be obtained at http://www.acquisition.gov. CCR Requirement - Offeror's must be registered in the Central Contractor Registration (CCR) before an award can be made. If offeror's are not registered in CCR, they may do so by accessing the CCR web site at: http://www.ccr.gov. Period of Performance - Performance of this order shall begin on October 1, 2008 and continue through September 30, 2009. A standard commercial warranty on parts and workmanship is required. The Defense Priorities and Allocation System (DPAS) and assigned rating are not applicable to this solicitation notice.