ARTB Statement of Work.pdf

STATEMENT OF WORK ATTACHMENT 1

STATEMENT OF WORK

Aged Rodent Tissue Bank

Development and Maintenance of an Aged Rodent Tissue Bank

I. BACKGROUND

The National Institute on Aging (NIA) supports basic biomedical research through several programs that require animal models of aging. NIA also maintains through contracts large colonies of aged mice and rats for use in research on aging (Aged Rodent Colonies). While some investigators need live animals for their research, others simply need biospecimens (tissue or body fluids) for their experiments. The purpose of this contract to develop and maintain an Aged Rodent Tissue Bank (ARTB) is to provide a source of biospecimens, mostly fresh frozen or fixed and embedded tissue, suitable for multiple experimental protocols, from the NIA colonies of aged mice and rats. This constitutes a mechanism for multiple investigators to share tissue from a single animal, allowing more studies to be carried out with existing resources, optimizing the value of the rodent colonies, increasing the efficiency and cost effectiveness of aged tissue collection. This requirement is a follow-on to contract 75N95021C00008. The ARTB currently consists of approximately 40,000 frozen biospecimens stored at -70 to -80°C, and 800 tissue and tissue array blocks stored at room temperature. Approximately 1,500 biospecimens are shipped each year to approximately 25 investigators.

II. OBJECTIVES

The objective of the ARTB is to collect, store and distribute biospecimens (tissues and fluids) from mice and rats from the NIA Aged Rodent Colonies. Biospecimens are flash-frozen, or fixed and embedded in paraffin, to meet the requirements of a wide-range of molecular and histochemical protocols. In addition, tissue arrays designed in agreement with the Contracting Officer’s Representative (COR) will be assembled starting from paraffin blocks. Vital statistics information will be compiled to accompany the corresponding biospecimens.

III. WORK TO BE PERFORMED

Independently, and not as an agent of the Government, the Contractor shall provide all necessary services, qualified personnel, facilities, material and equipment (except for those to be furnished by the Government as specified elsewhere in the contract agreement) to perform the work required by this Statement of Work as set forth below.

The Contractor shall receive mice and rats selected by the COR (strain, age and sex) from the NIA Aged Rodent Colony and shipped at no cost to the Contractor. Upon receipt, live animals will be housed by the Contractor in an approved animal facility before biospecimen collection. The Contractor will assign a unique identification number to each received animal, record vital statistics, collect and process selected tissues and fluids for storage (flash freeze or fix for subsequent embedding or otherwise as directed by the COR), collect sections on slides, label all biospecimens, record them in an inventory and store them under appropriate conditions. The Contractor shall ship biospecimens to investigators at the direction of the COR. The number of animals sent to the Contractor for tissue collection shall be approximately 150 per year, in groups of 5-10 animals per week, according to a schedule established by the COR in consultation with the Contractor. Approximately ninety percent (80%) of the collections shall be “basic collections” and twenty percent (20%) shall comprise “extended” and “comprehensive” collections (see Task Area 2c). Occasionally, “custom” collections shall be performed at the direction of the COR and after establishing the Contractor’s technical capabilities.

TASK AREA 1: Initial Transition – Transfer of Existing Aged Rodent Tissue Bank

Holdings

If necessary, the Contractor shall transfer the existing tissue biorepository from the current Contractor’s facility to the new Contractor’s facility in a safe and secure manner that prevents thawing of any frozen samples and maintains the integrity and organization of all samples. Transfer of biospecimen inventories and Vital Statistics Information Sheets shall happen concurrently. The transfer shall be accomplished within thirty (30) calendar days from the start of the Contract. The successor contractor will have up to ninety (90) days upon award of the contract to perform a full inventory of the tissue bank holdings.

TASK AREA 2: Receipt of Animals, Collection of Tissue and Records

a. Shipping of mice and rats to the Contractor is established by the COR in consultation with the contractor with the intent to maintain a full catalog of biospecimens available for distribution to the investigators. The Contractor shall maintain the animals at least three days after arrival to allow them to recover. Animals shall be housed in such way not to expose them to other animals or disease and shall be monitored. Any animal that exhibits signs of illness or distress shall not be used for tissue collection and shall be euthanized in accordance with the Board on Animal Health Sciences, Conservation, and Research (BAHSCR) guidelines (see reference below). Animals shall be maintained in filtered cages, no more than 3 rats or 5 mice per cage, with ad libitum food and water, a temperature range of 70-75°F and 12/12-hour light/dark cycle. NIH31 laboratory diet or equivalent, water and cage bedding shall be autoclaved. Cages shall meet BAHSCR minimum floor space requirements per animals and population size as stated in the “Guide for the Care and Use of Laboratory Animals” (Eighth Edition). Necropsy shall be performed within a consistent 4-hour window of time (e.g., between 9:00AM and 1:00PM) not earlier than the third day after receipt of the animals.

b. The contractor shall record on the Vital Statistics Information Sheet, in a format to be approved by the COR, the date of accession, strain, sex, age, weight, stage of estrous cycle for females as needed, barrier of origin, special notes such as caloric restriction and general conditions including visible lesions. The identification number (ID) is assigned at this time and linked to the Vital Statistics Information Sheet for each animal. ID format shall be approved by the COR.

c. The contractor shall euthanize each animal individually by CO2 asphyxiation and immediately collect, freeze or fix, post-process and store the designated biospecimens. Three alternative collection schedules – basic, extended, and comprehensive – will be used for frozen biospecimen collection. The list of tissues may be changed as directed by the COR, for example when collecting tissues from female breeders or for “custom” collections.

Individual fluids/tissues are to be abbreviated using the abbreviations in parentheses below:

Basic collection

• Serum (SRM), stored in 200 ul aliquots at -70 to -80°C, up to a maximum of 5 vials per animal

• Blood (BLO), whole, collected in EDTA-coated tubes stored in 200 ul aliquots at -70 to -80°C, up to a maximum of 1 vial per animal

• Heart (HRT), whole, rinsed in Phosphate Buffered Saline (PBS), flash frozen in LN2 and stored at -70 to -80°C

• Brain (BR), whole, flash frozen in liquid Nitrogen (LN2) and stored at -70 to -80°C

• Liver (LVR), whole, flash frozen in LN2 and stored at -70 to -80°C

• Kidney (KDN), pair, whole, flash frozen in LN2 and stored at -70 to -80°C

Extended collection

• Basic collection plus:

• White adipose tissue (WAT), abdominal subcutaneous, flash frozen in LN2 and stored at -70 to -80°C

• Brown adipose tissue (BAT), scapular subcutaneous, flash frozen in LN2 and stored at -70 to -

80°C

• Muscle (MSC), total thigh, individual, flash frozen in LN2 and stored at -70 to -80°C

• Lung (LU), whole, flash frozen in LN2 and stored at -70 to -80°C

Comprehensive collection

• Extended collection plus:

• Small intestine (SINT), whole, rinsed in PBS, flash frozen in LN2 and stored at -70 to -80°C

• Spleen (SPL), whole, flash frozen in LN2 and stored at -70 to -80°C

• Ovary or Testes (OV or TST), pair, whole, flash frozen in LN2 and stored at -70 to -80°C

• Pancreas (PAN), whole, flash frozen in LN2 and stored at -70 to -80°C

• Prostrate (PST), whole, flash frozen in LN2 and stored at -70 to -80°C

• Skin (SKN), shaved, from flank, 1x1 cm square, flash frozen in LN2 and stored at -70 to -80°C

• Thymus (THY), whole, flash frozen in LN2 and stored at -70 to -80°C

• Adrenal gland (ADR), pair, whole, flash frozen in LN2 and stored at -70 to -80°C

• Eyes (EYE), pair, whole, flash frozen in LN2 and stored at -70 to -80°C

i. Brain, heart, liver, spleen, lungs, kidneys, and reproductive organs shall be frozen within 5 minutes of anoxia, and all other tissues shall be frozen within 10 minutes of anoxia. The Vital Statistics Information Sheet shall list the time from anoxia to freezing for brain, heart, liver, spleen, lungs, kidneys, and reproductive organs and the total time elapsed between anoxia and freezing of the last tissue specimen from that animal. Wet weight of brain, heart, liver, spleen, lungs, kidneys, reproductive organs, white and brown adipose tissue and muscle shall be recorded on the Vital Statistics Information Sheet.

ii. The Contractor shall collect, flash freeze in LN2 and store individually at -70 to -80°C, any tissue mass (potential tumors) found. The contractor shall note the type and location of the mass on the animal’s Vital Statistics Information Sheet, and append the suffix “TMR” on the animal’s ID.

iii. For frozen biospecimens, the Contractor shall use packaging materials and labels that withstand storage at -80°C and shipping in dry ice without loss of integrity or label.

Packaging and labeling materials shall be approved by the COR at the beginning of the contract and whenever changes are implemented.

iv. For fixed and paraffin embedded tissues, the Contractor shall establish tissue preparation protocols that are most suitable for a wide array of histological analyses (including but not limited to immunohistochemistry and in situ RNA/DNA hybridization). Collection schedules and collected tissues shall be established in agreement with the COR. Fixed tissue should be embedded in paraffin within 24 hours of collection to avoid over fixing. Tissue blocks shall be used to generate sections and produce slides or shall undergo further processing to generate materials for the assembly of master blocks of tissue arrays.

TASK AREA 3: Biospecimen Storage and Inventory

a. The Contractor shall maintain frozen tissues in three freezers, each equipped with an independent alarm system and back-up generator. Biospecimens from each sample cohort (same strain, age, sex) shall be separated approximately in half and maintained in two independent freezers.

b. Tissue and array blocks shall be stored at room temperature in dedicated cabinets and sectioned onto glass slides upon request. Quality control of tissues, blocks and slides shall be completed and recorded in the biorepository database.

c. The Contractor shall maintain an electronic inventory of all biospecimens, including those transferred to the Contractor at the beginning of the contract and those collected during the Contract period of performance. Separate inventories shall be maintained for frozen, fixed/paraffin embedded and tissue array biospecimens. Currently, the biospecimen inventory is formatted as an Excel spreadsheet. As an option, the inventory may be transferred to a new database system (for data storage, retrieval and query.) The Contractor shall catalog and store Vital Statistics Information Sheets in electronic and hard copy.

Updated frozen biospecimen inventories shall be submitted to the COR via email any time that biospecimens are added or shipped or monthly, whatever comes first. Similarly, updated inventories of fixed tissues and tissue arrays shall be submitted when samples are added or shipped or every six months, whatever comes first. Access to the inventory system should be restricted to the Contractor, the COR and any other individual approved by the COR. The inventory system shall be approved by the COR prior to implementation.

TASK AREA 4: Ship Tissues to Investigators

a. The contractor shall section fixed, embedded tissues and tissue arrays onto slides at the direction of the COR upon approval of incoming requests by investigators.

b. The contractor shall ship frozen biospecimens, tissue and array slides to investigators at the direction of the COR or authorized representative thereof following the approval of incoming requests by investigators. A copy of the Vital Statistics Information Sheet for each animal shall be included in each shipment. Frozen biospecimens shall be shipped on dry ice by overnight carrier unless otherwise specified. Slides with fixed sections and tissue arrays shall be shipped in appropriate protective containers at room temperature by overnight carrier unless otherwise specified. Biospecimens obtained from “custom” collections shall be shipped according to instructions provided by the COR in consultation with the requesting investigator.

c. The Contractor shall communicate directly with the investigators keeping the COR always informed for example when biospecimen requests need clarification, the inventory does not carry all requested biospecimens or in case of “custom” collections.

d. The Contractor shall bear the costs for providing the biospecimens to investigators at this time. However, the Contractor shall have in place a mechanism for invoicing the investigator (including but not limited to industry, for profit and international users) for the cost of shipping the biospecimens and/or a nominal service fee set by the COR and be prepared to implement such invoicing should the Government direct it.

e. The Contractor shall provide the COR with updated monthly shipping schedules and regularly update the ARTB Request Log currently maintained as a shared Excel spreadsheet.

f. The Contractor shall dispose of undistributed biospecimens only with the consent of the

COR.

TASK AREA 5: Promote the ARTB resource

a. The Contractor shall inform investigators of the publication policy as provided by the COR and maintain a list of all peer-reviewed manuscripts, pre-publications (e.g., BioRxiv), conference abstracts, conference posters, conference presentations, and grant numbers resulting from the use of tissues provided by the ARTB. This information shall include what is reported to the Contractor by the ARTB users surveyed on a yearly basis and/or what the Contractor finds through searches of PubMed and other publication databases.

b. The contractor shall promote the ARTB to the scientific community through dissemination of information by a variety of means, including but not limited to, publications about the collection, platform presentations at scientific sessions, and two (2) persons participation in up to one (1) scientific conference held in the continental USA per year with the option to sponsor a booth. The meetings must be approved in advance by the COR.

TASK AREA 6: Final Transition

a. If necessary, prepare and transfer the ARTB biorepository, biospecimen inventory and Vital Statistics Information Sheets to a new Contractor at the end of the contract period of performance following the COR’s instructions. The successor Contractor shall be responsible for all transfer arrangements.

IV. Period of Performance The anticipated period of performance will consist of a base period and four(4) option periods as follows:

Base Period: 3/15/2026 - 3/14/2027 Option Period 1: 3/15/2027 - 3/14/2028 Option Period 2: 3/15/2028 - 3/14/2029 Option Period 3: 3/15/2029 - 3/14/2030 Option Period 4: 3/15/2030 - 3/14/2031

V. REQUIRED REPORTS/DELIVERABLES

All submitted electronic reports shall be compliant with Section 508 of the Rehabilitation Act of 1973. Additional information about testing documents for Section 508 compliance, including guidance and specific checklists, by application, can be found at:

http://www.hhs.gov/web/508/index.html under “Making Files Accessible.

In addition to those reports required by the other terms of this contract, the Contractor shall prepare and deliver the following progress reports:

a. Monthly frozen biospecimen inventory updates in electronic format shall be provided to the NIA, reflecting the most recent shipments or additions of tissues. Biospecimen inventory updates shall also be provided to the COR concomitant with any new tissue shipment or collection.

b. Quarterly tissue block and array inventory updates in electronic format shall be provided to the COR, reflecting the most recent changes and additions. Tissue block and array inventory updates shall also be provided to the COR concomitant with any new collection or addition.

c. Monthly updates shall be performed of the Vital Statistics Information Sheets collection for all animals represented in the bank inventory. An electronic copy of the Vital Statistics Information Sheets for each animal shall be transferred to a shared folder accessible by the Contractor and the COR (e.g., NIH Box folder). An electronic copy as well as a hard copy of the same file shall be maintained by the Contractor.

d. Semi-annual progress reports shall be submitted to the COR and the Contracting Officer within thirty (30) calendar days of the end of the period covered by the report. The initial report shall be submitted for the first full six (6) months of the contract performance including any fractional part of the initial month. Thereafter, the reporting period shall consist of six

(6) full calendar months. A semi-annual report will not be required for the period when the final report is due. Semi-annual progress reports shall detail the number, sex, strain and age of animals received for tissue banking, the number of orders filled and the number and type of biospecimens delivered to investigators. The number of animals culled due to illness shall also be included.

e. A final report shall be submitted to the COR and the Contracting Officer on or before the expiration date of this contract. The final report shall include a summation of the work performed under the entire contract period of performance, including the number and details of biospecimens collected and of those shipped to investigators.

VI. CONTRACT CLOSEOUT

Contract Closeout. In accordance with FAR 4.804-5, within sixty (60) days of contract expiration/completion, the Contractor shall be responsible for and provide the following items:

a. Indirect cost rate proposals for all years (in which a proposal was not previously submitted);

b. Final property inventory (excluding intellectual property) and Standard Forms 1428 and 1429 (if applicable);

c. Settling all subcontract costs and any issues thereunder;

d. Subcontracting compliance reports for all years to the electronic subcontract reporting system at http://www.esrs.gov (if applicable);

e. Final patent and royalty reports;

f. A Contractor's release of claim, i.e., Contractor's closing statement; and Contractor's

Assignment of Refunds, Rebates, and Credits; and

g. A final invoice or completion voucher.