Statement of Work-75N95021R00051.pdf

STATEMENT OF WORK

RFP 75N95021R00051

“Development and Maintenance of a Multigenotypic Aged Mouse Colony”

BACKGROUND

Current and projected experiments using rodents to model the aging processes and age-related diseases in humans require animals of defined genotype and health status that are reared and aged under controlled environmental conditions. Therefore, a continuous supply of genetically defined, well characterized inbred and hybrid laboratory animals is essential for a program of research on aging.

OBJECTIVE(S)

The objective is to develop, maintain and distribute a standing colony of aged, genetically defined, specific pathogen free, laboratory mice for use by investigators in studies of aging.

This colony is to be developed and maintained within controlled and defined barrier environments where animals are monitored and characterized for disease status and markers of genetic purity.

WORK TO BE PERFORMED

Independently, and not as an agent of the government, the Contractor shall furnish all necessary services, qualified personnel, materials, facilities and equipment not otherwise provided by the Government as needed to perform the work described below.

The Contractor shall develop, maintain and distribute a standing colony of aged mice of the National Institute on Aging (NIA)-specified genotypes for use by investigators in studies of aging. The expected duration of this colony, and therefore of this contract, is ten years.

During years 1 and 2, foundation stock shall be re-derived, and animals shall be entered into the colony, but few animals shall be removed from the colony except for the purposes of monitoring health and genetic purity. However, if the need should arise, animals may be distributed from the colony at any time at the direction of the Contracting Officer’s Representative (COR).

During years 3 through 7, animals shall continue to be entered into the colony and animals shall be distributed to investigators. This should be a period of stable operation such that by year 4 animals will be entering the colony at approximately the same rate as animals leave the colony due to distribution and normal attrition. The final three year period, years 8 through 10, will serve as the colony close-out period. Animals shall be maintained and disbursed, but entry of animals shall cease at the beginning of year 8 or when entries begin in a renewal contract colony. Thus, the population in this contract colony will decline over the last three year period to a point of zero or very few animals at the end of year 10. The colony population at the end of each year of the ten year period should be approximately as shown in Table 1.

Table 1. Approximate annual animal population levels at end of year.

YEAR 1 17,000 YEAR 5 105,000 YEAR 9 35,000

YEAR 2 68,000 YEAR 6 105,000 YEAR 10 Near 0

YEAR 3 105,000 YEAR 7 105,000

YEAR 4 105,000 YEAR 8 68,000

Task Area 1. Provision of Barrier Environment

a) This animal colony shall be divided into at least two, approximately equal, separate segments. Each segment shall be maintained behind a totally independent barrier, specific pathogen- and parasite free, for the entire contract period. All segments shall specifically be helicobacter-negative. The purpose of colony division is to insure the survival of at least one half of the colony in the event of pathologic breach of a barrier, mechanical failure of environmental maintenance systems, or accidental disaster such as fire, or flood. Total independence of colony segments therefore means separation of buildings, power systems and back-up systems, environmental controls (heat, air conditioning, and air filtration) and breeding stock. Each barrier shall have an independent back-up generator and alarm system in case of loss of power.

b) The total monthly entry level for each strain shall be divided approximately equally amongst the barriers. Exceptions might be made for strains with very low entry levels, but such exceptions shall require written approval from the COR.

c) Each colony segment shall be maintained solely within its barrier facility without intermingling. Exceptions may be granted but each exception shall require the prior written approval of the COR.

Task Area 2. Supply of the Mouse Genotype

a) Within 60 calendar days of the start date of the associated task order, the Contractor shall acquire the genotypes (foundation stock) described herein and as directed by the COR.

The Government may alter the number of entries of particular genotypes and change genotypes as research demands change during the performance period. Alterations in the number or genotype of mice entered require the specific written approval of the Contracting Officer. Alterations in genotypes might require the Contractor to acquire new foundation stock during the course of the contract performance period.

b) The foundation stock shall be re-derived by caesarean re-derivation or embryo transfer prior to development of the breeding colony. Discrete space within the re-derivation area shall be provided for re-derivation of the mice. No other animals shall be housed within an isolator housing the mice from this contract, other than this contract’s animals and foster mothers. The animals shall remain in the isolators until transfer to the barriers for development of the breeding colonies. Foster mothers shall be of a strain that is easily distinguished from the subject genotype by color and/or genetic markers. The choice of strains(s) to be used for foster mothers shall require approval from the COR. Use of foster mothers with different coat color is preferred when possible.

c) The Contractor shall provide the COR with documentation of the health status and genetic purity of the re-derived stock within 120 calendar days after the birth of the re-derived litters.

Task Area 3. Development of Breeding Colonies

a) The Contractor shall develop breeding colonies consisting of two or three tiers:

foundation colony, and expansion and/or production colonies, dependent on the entry levels required for the aging colonies. The numbers of breeding mice to be maintained shall be at a level that permits the addition of male and female weanling mice at the rate required for each colony segment. The number of mice of each sex and genotype to be entered into the aging colony each month shall be defined in each Task Order Statement of Work (TO SOW).

b) After the foundation stock animals for each colony segment have been re-derived, they shall be entered from isolators into the barrier system without contamination by pathogens or parasites and shall be maintained as such. All offspring, whether part of the breeding colony or the aging colony, shall be considered Government owned property.

Animals shall be removed from the barrier only for shipment to investigators, for monitoring of genetic purity or colony health or for other purposes as directed by the COR. In all colony segments, no other types of animals and no other types of activity other than that defined in the work-scope shall be permitted in the barrier rooms used to rear and maintain the mouse genotypes specified.

c) Breeding and recording of pedigrees of animals shall conform to the standards established for laboratory mouse strains by the Institute for Laboratory Animal Resources (ILAR) 2010

"GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS"

https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals

d) Litters larger than 8 shall have the smallest pups culled within 5 calendar days of birth to bring the litter size down to 8; animals from litters smaller than 3 shall be excluded from introduction into the aging colony.

e) Mice shall be weaned at 3-4 weeks of age and entered into the aging colony.

https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals

f) Mating, isolation, and primary enclosures shall meet or exceed minimum floor space requirements per mouse, and population size per cage as stated in the ILAR "Guide for the Care and Use of Laboratory Animals". All primary enclosures shall require the prior approval of the COR. Mating cages shall be numbered consecutively. The type of cage bedding is subject to review and approval by the COR within 60 calendar days of award of contract.

g) Records of date of birth, health, breeding, environment, and colony monitoring shall be maintained by the Contractor and shall be supplied to the COR upon request.

h) The Contractor shall provide discrete production space for each breeding colony segment within the barrier or isolation area for that segment. This space shall be defined within each unit, and the animals held therein until the authorized removal or expiration of the animals. Facilities set aside for these colonies shall be provided with all equipment, materials, and supplies necessary to maintain these animals effectively within the barrier enclosure in a stable condition and environment.

i) No animal shall be medicated during any part of the breeding, rearing, or maintenance period except on specific instruction of the COR.

j) The Contractor shall provide for quarterly positive assurance of genetic quality control on mice from 35% of the nucleus breeding colonies of the inbred strains and 50% of the nucleus breeding colony of the hybrid strain, including histocompatibility antigen and/or micro-satellite testing of a sample of breeder mice of each genotype to detect genetic contamination. Procedures for genetic quality control are subject to the prior written approval of the COR.

k) Upon obtaining pathologic or other evidence that a barrier has been breached, the

Contractor shall notify the COR and the Contracting Officer by telephone and/or email within four (4) hours of discovery of the breach. The COR might request a teleconference or meeting of the Contractor's representative, the COR, and the Contracting Officer as soon as practicable, or might request emailed reports at specified intervals, to determine an appropriate course of action. Such action may range from medication to reestablishment of the colony in newly constituted barrier facilities. Final determination of the appropriate course of action will be made by the COR. Potentially affected investigators shall be notified by written notice approved by the COR.

Task Area 4. Aging Colony Development

a) The Contractor shall provide discrete production space for each colony segment within the barrier or isolation area for that segment. This space shall be defined within each unit, and the animals held therein until the scheduled removal or expiration of the animals.

Facilities set aside for these colonies shall be provided with all equipment, materials, and supplies necessary to maintain these animals effectively within the barrier enclosure in a stable condition and environment. The weanling mice shall be from barrier maintained parents and shall be maintained within the barrier until scheduled for removal (shipment or sacrifice) or natural expiration of the animal. The numbers of mice of each strain that shall be entered into the aging colony each month shall be defined in each Task Order SOW, as described under the Task 3.a. No change in the entry level shall be made without written authorization from the Contracting Officer.

b) All cages of mice shall be permanently identified by their genotypes, sex, and age. Age shall be denoted as month/year of birth with the additional notation on the cage card of the week of the month when born, such as week 1, week 2, etc. Recombination or consolidation of cages is prohibited unless approved in writing by the COR.

c) Each mouse shall be permanently marked by tail tattoo to identify month (2 digits) and year (2 digits) of birth (a mouse born in August of 2021 would receive the tattoo 0821).

d) No animal shall be medicated during any part of the breeding, rearing, or maintenance period except on specific instruction of the COR.

e) The Contractor shall periodically submit members of this colony for independent evaluation by a qualified animal diagnostic center as instructed by the COR (with shipping and laboratory fees being charged to the contract).

f) All spontaneous deaths in the aging colony shall be reported by strain, sex, and age in the semiannual progress reports (Task 7.c., in table form) and on the weekly inventory report (Task 7.d.). Necropsies shall not be performed on mice found dead in the colony unless there is an unusual pattern of animal deaths or upon the direction of the COR. Postmortem findings in such cases shall be tabulated, summarized, and provided to the COR within 60 calendar days of the death. Primary and secondary lesions possibly attributable to cause of death are to be described. Differences in strain specific or colony wide findings between colony segments shall be identified and reported in the semiannual progress report.

g) Routine monitoring for disease and post mortem examinations are to be performed by either an independent laboratory approved by the COR or the Contractor if Contractor plans, personnel and facilities are approved by the COR. Selection of animals for monitoring shall be evenly divided between colony segments and represent all genotypes and sexes which are maintained in each segment. Numbers of each genotype and sex submitted for monitoring shall reflect the proportion of that genotype/sex in the colony.

A minimum of sixty (60) mice shall be submitted for routine health monitoring each quarter unless otherwise specified by the COR. Mice to be submitted for routine monitoring shall be a minimum of four (4) months old, except during colony start up when younger animals may be submitted. Approximately half of the mice tested each quarter shall be 4-12 months old and the other half 12-20 months old. The schedule for removal shall be developed by the Contractor and shall require the approval of the COR.

h) Routine clinical and postmortem evaluation shall include:

1. Descriptive clinical condition of the animals including general condition, weight, and visible lesions and symptoms; gross pathologic observations of body tissues and organs;

2. Microbial, parasitological, and serological evaluation necessary and approved by the COR to monitor effectiveness of the barrier system and animal health;

3. Histopathology of major organs and systems.

i) Mice shall be monitored for wounds and open lesions caused by fighting or excessive scratching and for visible tumors. Mice shall be euthanized when wounds or tumors are extreme enough to cause pain, wasting, inability to eat or decreased mobility of the animal, or when tumors reach 1 cm in diameter. Unless the COR instructs the Contractor to perform necropsies on animals that are euthanized, the Contractor is free to dispose of the carcasses in any manner they deem appropriate, including donation to raptor rescue groups or zoos and contribution of the carcasses to academic researchers for research purposes at no cost to the Government.

Task Area 5. Environmental and Husbandry Requirements

a) Weaned mice assigned to the aging colony shall receive a laboratory animal feed, the formulation of which is consistent with NIH31 diet with regard to ingredients, both in kind and amount. The kind of ingredients shall be absolute; the percentage of the kinds of ingredients may vary dependent on nutrient content provided the final formulation remains consistent with NIH31 diet. The laboratory animal feed formulation shall be reviewed and approved by the COR.

b) The barrier system or isolation room shall be operated and constructed to effectively exclude pathogens, ecto-, endo-parasites as well as vermin. Personnel shall follow the sanitary and/or sterile practices and techniques that have been established for the maintenance of barrier-sustained animals as described in the 2010 ILAR "GUIDE FOR THE CARE AND USE OF LABORATORY ANIMALS" https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals.

c) The following items shall be controlled within the ranges specified: temperature (72- 79oF), humidity (40-70%), light cycles (12/12 hours), air circulation (0.25m/hr/animal) and filtration (HEPA), and water chlorination and acidification (water shall be chlorinated and the pH controlled so as to not exceed pH 7.3 and 7-8 PPM chlorination at discharge end).

A maximum of 25% re-circulated air within the barrier is allowed. The COR shall be notified immediately if the ambient temperature remains outside the above noted temperature range for a period in excess of four (4) hours or if there is a loss of animals due to a breakdown of environmental controls.

https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals.

https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals.

d) Current ILAR https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals and Department of Health and Human Services (DHHS) guidelines (https://olaw.nih.gov/policies-laws/phs-policy.htm) for breeding, care and maintenance of laboratory mice shall apply where specifications have not been detailed.

e) If requested by the COR, the Contractor shall measure food intake in the first cohort (DOB), or subset thereof, of each strain and gender entered into the aging colony, to verify that food intake in the new colony is consistent with the levels on which the feeding protocol is based. Food intake shall be measured by providing an excess number of food pellets of known total weight each day and weighing the food remaining the next day. Food intake shall be measured daily for the entire cohort from the age of 5 weeks through the age of 12 weeks. The data shall be compiled in an Excel spreadsheet and the up-dated spreadsheet shall be provided to the COR weekly.

Task Area 6. Shipment of Animals to Investigators

a) Animals from the aging mouse colony shall be distributed to investigators or laboratories only as specified by the COR or the designated representative of the COR. A copy of the most recent Health Evaluation Summary for the animals prepared under Task 7.e. shall be sent with each order.

b) The aged mice shall be shipped in containers:

1. Made of new materials that are non-reusable and non-returnable;

2. The design and fabrication of which are approved by the COR;

3. With filters for ventilation openings of a type approved by the COR;

4. Designed so stacking will not interfere with air circulation through the container;

5. Containing food and a water source in each compartment; aged mice shall be shipped with excess food.

c) The number of mice per container shall not exceed 10 animals. If animals from different cages are shipped in the same container, the container shall be sub-divided into compartments, each compartment containing only cage-mates, and all compartments in the crates shall be of the same age and sex. Special provisions may be specified by the COR as needed, such as shipping male BALB/c mice singly in individual compartments.

d) The Contractor shall report to the COR or the designated representative of the COR within 12 hours of expected delivery time if there are delays in the shipment of animals.

e) Shipment via dedicated, climate-controlled truck is the preferred method. The Contractor shall bear responsibility for the cost of animals and shipping charges for replacing animals or providing credits for animals that die during shipment or within 48 hours of delivery, or that are unacceptable to the consignee due to breached or crushed shipping containers.

The Contractor shall be responsible for the cost of replacing orders not filled correctly https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals https://www.nationalacademies.org/our-work/update-of-the-guide-for-the-care-and-use-of-laboratory-animals https://olaw.nih.gov/policies-laws/phs-policy.htm according to the instructions provided by the COR or the representative designated by the

COR.

f) When shipment by dedicated, climate-controlled truck is not possible, air freight shall be used. The Contractor shall take all necessary precautions to assure expedient delivery of animals shipped by air freight, by advising the recipient of expected arrival time, mode of transport and carrier number, and any responsibility the consignee has for pick-up at the point of arrival. When the consignee is notified that they are required to meet animals at point of arrival, late or delayed pick up of animals shall constitute neglect by recipient and Contractor is relieved of all replacement or reimbursement obligations.

g) Mice produced under this contract shall be made available to investigators under conditions as stated herein or as otherwise specified by the COR.

Task Area 7. Reporting Requirements and Other Deliverables

a) Post-re-derivation Health and Genetic Monitoring Report. The Contractor shall provide to the COR a report documenting the health status and genetic purity of the re-derived foundation stock within 120 calendar days after the birth of the re-derived litters.

b) Breeding Colony Development Report. Monthly reports shall be provided during the development of the breeding colony, providing the date the foundation stock was received, updates on the re-derivation progress, the numbers of mice produced each month for the breeding colony for each strain and the target number of breeder mice for each strain, any problems encountered with breeding the mice or litter size/survival, and the anticipated date for entries into the aging colony to begin and how that estimate has changed since the previous month’s report. Any change in the trajectory for the breeding colony development that has cost implications for the contract shall be noted in the report. The breeding colony development report shall be provided to the COR by email within seven (7) calendar days from the end of the reporting period. The first reporting period for the breeding colony development report shall be due thirty (30) calendar days after the associated task order award and the reports shall continue until all strains have begun entries into the aging colony.

c. Semi-Annual Progress Reports. Semi-annual progress reports shall include the number of mice shipped from each barrier during the reporting period, the number of mortalities in each barrier, and any problems involving the colony, colony health, environment or environmental control. The report shall include the results of routine genetic monitoring and all laboratory tests executed either by Contractor as a routine part of the protocol or results from tests that have direct implication for colony health or development. All deaths or sacrifices from the colony shall be accounted for by strain, gender and age of the animal sacrificed or expired. Unusual problems with the potential to impact the colony, colony health or genetic purity shall be reported to the COR immediately. Semi-annual progress reports shall be submitted to the COR within fifteen (15) calendar days of the end of each reporting period of the associated task order. The initial reporting period shall consist of 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.

Electronic transmission of progress reports is acceptable as long as they contain the Principal Investigator’s signature (ex. .PDF format).

d) Weekly Inventory Report. A weekly inventory report shall be submitted to the COR in accordance with a format approved by the COR. Electronic transfer of the inventory in Excel spreadsheet format is the preferred means. The weekly inventory report is due to the COR no later than one (1) week (seven (7) calendar days) from date of inventory.

Access to a “real-time” electronic inventory would take the place of the weekly inventory report subject to approval by the COR.

e) Health Monitoring Reports. Quarterly health monitoring reports shall be submitted to the

COR no later than three (3) months from the date the animals were submitted for evaluation. Semiannual summaries of these reports shall be furnished as a part of 7.c above. Real time access to the health monitoring reports as the results come in is an acceptable alternative for these reports.

f) Genetic Monitoring Reports. Results of the genetic monitoring of the foundation stock and quarterly genetic monitoring of the breeding colonies shall be reported to the COR no later than sixty (60) calendar days from the date the animals were submitted for evaluation. Semi-annual summaries of these reports shall be furnished as a part of 7.c above. Real time access to the genetic monitoring reports as the results come in is an acceptable alternative for these reports.

g) Individual Postmortem Reports. Complete postmortem reports on individual animals chosen for additional health monitoring independent of the quarterly health monitoring shall be submitted to the COR no later than sixty (60) calendar days from the date of death.

h) Final Report. A final report shall be submitted to the COR on or before the completion date of the associated task order. The final report shall include a summation of the work performed and results obtained for the entire associated task order period of performance. This report shall be submitted on or before the associated task order completion/expiration date.

i) Summary of Salient Results. The Contractor shall submit, with the Final Report, a summary

(not to exceed 200 words) of salient results achieved during the performance of the associated task order.

j) Contract Closeout. In accordance with FAR 4.804, within 60 calendar days of the contract task order expiration/completion, the Contractor shall be responsible for and provide the following items:

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

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

3. Settling all subcontract costs and any issues thereunder;

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

5. Final patent and royalty reports;

6. A contractor’s release of claims, i.e., contractor’s closing statement; Contractor’s

Assignment of Refunds, Rebates, and Credits; and

7. A final invoice or completion voucher.

http://www.esrs.gov/