Attach_3_-_SOW_3-8-18_Final.pdf

ATTACHMENT 3

Statement of Work for Provisions for Barrier Reared and Maintained, Rats, Mice, Hamsters, Gerbils, and Guinea Pigs, and Specialized Animal Services

Dated March 8, 2018

A. Background Information

The Comparative Medicine Branch (CMB), Animal Resources Section (ARS), is responsible for the centralized ordering of rodents and for the National Institute of Environmental Health Sciences (NIEHS). The ARS maintains procurement mechanisms with a broad range of commercial contractors for laboratory animals and animal services to support the research requirements of investigators within the NIEHS Intramural Research Program. This centralized purchasing mechanism is used for the following functions:

• To provide an efficient and cost effective centralized purchasing mechanism that can maintain uninterrupted support of the research animal needs of NIEHS intramural investigators;

• To provide monitoring and oversight of the genetic quality and health status of research animals introduced into the NIEHS animal facilities;

• To provide monitoring and oversight of the genetic quality and health status of NIEHS-owned research animals housed and maintained offsite at the commercial contractor’s facilities;

• To maintain compliance with various federal, state, local laws and NIH & NIEHS regulations affecting the use of laboratory animals; and

• To ensure that NIEHS Principal Investigators and the Comparative Medicine Branch have authorized the placement of individual animal procurement requests.

B. Objectives

The objective of this contract is to provide quality laboratory rodents and animal services to the NIEHS Intramural Research Program.

C. Mandatory Compliance and Accreditation

This contract shall be conducted in compliance with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals, the Animal Welfare Act Regulations and the current edition of the “Guide for the Care and Use of Laboratory Animals”, and all local, state, or federal regulations.

The Contractor shall have a PHS Assurance from the NIH Office of Laboratory Animal Welfare (OLAW) at the time of contract award, and shall be accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC). If animal species regulated https://olaw.nih.gov/policies-laws/phs-policy.htm https://olaw.nih.gov/policies-laws/phs-policy.htm https://www.nal.usda.gov/awic/animal-welfare-act https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwi00Y-HxojbAhURPN8KHSxvC1AQFggnMAA&url=https%3A%2F%2Fgrants.nih.gov%2Fgrants%2Folaw%2FGuide-for-the-care-and-use-of-laboratory-animals.pdf&usg=AOvVaw0YtvzGCfOn_DG3aE9LZtKK https://olaw.nih.gov/ by the United States Department of Agriculture (USDA) are involved, the contractor shall be registered with the Secretary of Agriculture of the United States in accordance with the following Federal regulations 7 U.S.C 2136 and 9 CFR sections 2.25-2.28 respectively. In addition, the Contractor shall comply with all applicable laws, regulations and standards governing animal welfare while performing under this contract.

All facilities, practices and procedures of husbandry, care and maintenance of animals used in the performance of this contract shall be in accordance with the current edition of the “Guide for the Care and Use of Laboratory Animals.”

Animal experimental protocols approved by the Contractor’s Institutional Animal and Use Committee (IACUC), shall be deliverables to the NIEHS Contracting Officer Representative (COR) prior to the commencement of work. These contractor-approved protocols shall also be made available to the NIEHS ACUC.

D. Services to be Performed

Independently, and not as an agent of the Government, the Contractor shall furnish all the necessary services, qualified personnel, materials, equipment and facilities, needed to perform the Statement of Work below:

1. General Requirements

General requirements include the following:

a. Commercial Animal Purchases

(1) Various strains and stocks of barrier-reared and maintained rats, mice, hamsters, gerbils, and/or guinea pigs, which meet the specific genotype, health status, sex, age, weight, and/or pregnancy requirements and surgical manipulations, as included in the vendors’ commercial catalogues, websites, or notifications of availability; and

(2) Various blood, tissues, organs, and other biological specimens

b. Specialized Animal Services

(1) Various specialized animal services, which may include, but not limited to:

rederivation, cryopreservation, cryopreservation storage, quarantine, customized breeding, colony development, production and maintenance, animal health surveillance and diagnostic testing; genetic monitoring, diagnostic, and testing services, veterinary services, customized research protocols, and rodent export and import services, as included in the vendor’s commercial catalogues, websites, or notifications of availability;

(2) The Contractor shall be regularly engaged in the breeding, raising, and shipping of the animals described. The animals, tissues, organs, and blood or serum supplied under this contract shall be maintained and collected in the Contractor’s facilities.

(3) The Contractor shall operate any and all proposed facilities for services related to rederivation of animal models for the elimination of the vertical and horizontal transfer of pathogens, parasites and other undesired organisms, cryopreservation of mouse and/or rat embryos or germplasm, and colony production and maintenance. However, with the Government’s approval, some or all of the long-term storage of cryopreserved embryos (repository functions) may be subcontracted.

(4) The Contractor shall meet all mandatory compliance and accreditation requirements provided in Section C herein.

(5) The Contractor shall have an active pest control program to prevent the introduction of pathogenic agents from wild rodents to research animals housed in the production facilities.

2. Disease Prevention and Health Status for Rodent Colonies Maintained Specifically for

NIEHS

The Contractor shall have health surveillance and disease control programs that meet or exceed NIEHS requirements (see Attachment A - NIEHS Defined SPF). The Contractor shall be responsible for the cost of the testing. Oversight of these programs shall be developed, administered, and directed by a veterinarian who is board certified or eligible for certification by the American College of Laboratory Animal Medicine. The veterinarian may be a full-time member of the Contractor’s staff or an adjunct consultant.

The microorganisms that shall be monitored, the required specimens, and type of testing and reporting are outlined by species in Attachment A - NIEHS Defined SPF. The organisms and tests outlined in the NIEHS Defined SPF represent a minimal characterization of the colony. The Contractor shall, using trained staff under the direction of the veterinarian, examine sick and dead animals and collect appropriate specimens from these animals for further study by the veterinarian or other designated qualified individuals. Colony morbidity and mortality data shall be captured, (quarterly at minimum) tracked, and a report made available for review by the Contracting Officer Representative (COR) and Government site inspectors upon request. This data shall contain the number of colony deaths by age, genotype, number of necropsies performed, and a summary of the necropsy findings.

All health surveillance test results shall be clearly identified with:

a. Date of report

b. Date specimen collected;

c. Number of animals examined;

d. Species and strain or stock examined;

e. Age or date of birth;

f. Source of animal or specimen (e.g., building and room number/isolator, if available, include the cage or pen number), and;

g. Agent tested for and test used.

The required testing specified herein shall be performed by a diagnostic laboratory, approved by the COR. The diagnostic laboratory staff shall be qualified by training and/or experience and shall have demonstrated the capability to perform the required tests.

The diagnostic laboratory may be owned and operated independently of the Contractor, or it may be owned and operated by the Contractor. The COR shall have the right to require confirmatory testing at a lab of their specification and at the Contractor’s expense. Results of the required tests shall be provided directly to the COR and their designees.

The Contractor shall notify the COR and their designees within twenty-four hours of receiving any positive test result and/or confirmation of a pathogen within the colony.

Whenever test results are positive for any of the disease entities listed in the attached NIEHS Defined SPF, the Contractor shall be responsible for conducting appropriate additional testing to confirm the results within 72 hours. During this period animals from the suspected room(s) shall not be used for this contract. Following the 72 hour period the COR and their designees shall be notified if the original results are confirmed as positive or if the confirmatory tests are still pending. Notification shall be made by E- Mail and telephone with a written notice to follow. The Government retains the right to order or reject animals from the Contractor’s colonies that have tested positive for any of the disease entities listed Attachment A - NIEHS Defined SPF.

Additional Rejection Considerations

Any physical event which, either potentially or directly, could adversely influence the health status of animals in the production colonies shall be reported to the COR within 24 hours of the occurrence. Examples of such events include, but are not limited to, problems with environmental control equipment or transportation of animals, extremes in weather conditions, sanitation/sterilization procedures and contamination of isolators, feed, bedding or water.

All animals shall be delivered in physically sound and healthy condition (except those animal models that exhibit clinical signs appropriate to their genetic makeup) and shall be free of wounds (except those related to requested surgical modifications), scars, and clinical signs of disease. Animals prone to fighting shall be physically separated.

Animals provided under this contract shall not have been subject to previous experimental use of any type or kind. They shall not have been reared, housed, or transported in contact with animals of a different health status.

Animals provided under this contract shall not have been treated with any medication without prior approval from the COR. If medication of the animals is agreed to, monthly reports concerning such use shall be submitted to the COR.

Genetic Integrity

The Contractor shall have documented breeding schemes used to produce genetically defined animals. These schemes shall be designed to assure the homozygosity of inbred strains, the heterogeneity of outbred stocks, and the requested genotype of genetically engineered models (GEM). The structure of the colony shall be detailed, and no more than five (5) generations should elapse between the foundation and production colonies.

The Contractor shall have a documented genetic quality control program to assure the genotype of the animal models. Testing shall be conducted as needed for genetically engineered models and at least semi-annually for commercial colonies. A copy of the genetic results including the genetic profile and at least 20 microsatellite markers shall be provided semi-annually to the COR and shall be included with animal shipments for standing orders. The latest genetic profile results shall be available to the NIEHS investigators or the COR at the beginning of a study. Results of the testing from the genetic quality control program shall be available to the COR. Evidence of any genetic contamination shall be reported to the COR within two (2) business days and additional testing shall be conducted to determine the cause and source of the contamination.

Results of the testing and a plan for correction shall be provided to the COR.

The Contractor shall have a qualified animal geneticist review the management of the colonies as needed (GEM) and at least once per annum (commercial colonies). This individual shall have a Ph.D. degree in animal genetics or a related field and at least two years professional experience with laboratory animal species. The geneticist shall be either a full-time member of the Contractor’s staff or a consultant. If a consultant, the time spent inspecting the facilities and reviewing the management procedures shall be described. A report of the geneticist findings regarding the genetic integrity of the Contractor’s colonies shall be furnished to the COR, within 30 business days of the completion of the review.

3. Additional Services to be Provided by the Contractor

a. Surgery Services

As required, the Contractor shall provide surgically modified animals. All surgery performed under this contract shall be performed in compliance with the “Guide for the Care and Use of Laboratory Animals.”

b. Specialized Animal Services

(1) General Requirements

(a) As required by the COR, the Contractor shall prepare a price quote for specialized animal services.

(b) As required by the COR, the Contractor shall prepare in writing a detailed “project description” that may include, but not limited to: project goals, milestones, specialized animals services required, timeline, breeding schemes, genotyping details, estimated costs, etc.

(c) The Contractor shall obtain project approvals from the COR before new projects or amendments to ongoing projects are implemented.

(d) The Contractor shall provide project status updates, at least quarterly, to the COR. As required, the COR may request that additional project details be provided by the Contractor.

(e) The Contractor shall obtain from the COR animal health and shipping approvals before any animals that have been housed at the Contractor’s site for animal services are shipped to NIEHS.

(f) Disposition of NIEHS animals at vendor’s facility shall require approval by the COR.

https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwi00Y-HxojbAhURPN8KHSxvC1AQFggnMAA&url=https%3A%2F%2Fgrants.nih.gov%2Fgrants%2Folaw%2FGuide-for-the-care-and-use-of-laboratory-animals.pdf&usg=AOvVaw0YtvzGCfOn_DG3aE9LZtKK https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwi00Y-HxojbAhURPN8KHSxvC1AQFggnMAA&url=https%3A%2F%2Fgrants.nih.gov%2Fgrants%2Folaw%2FGuide-for-the-care-and-use-of-laboratory-animals.pdf&usg=AOvVaw0YtvzGCfOn_DG3aE9LZtKK

(2) Services to Eliminate the Transmission of Specific Pathogens, Parasites and Organisms specified on the contract agent lists

As required, the Contractor shall provide rederivation services for the purpose of eliminating the transmission of specified pathologic agents.

The Contractor shall establish and maintain records of the process of rederivation and colony expansion. This includes the number, sex, and genotype of all animals, any treatments (e.g., superovulation, health, etc.), number of embryos/pups recovered, number of embryos transplanted, number of litters and pups successfully weaned, morbidity/mortality, adverse phenotype observed, and any other information requested by the individual order.

(3) Cryopreservation and Banking Services for Germplasm (sperm, ovaries, embryos, etc.)

As required by the COR, the Contractor shall provide services to establish a bank of cryopreserved germplasm or establish living offspring from banked germplasm to include ovary or oviduct removal, embryo or sperm collection and cryopreservation, storage of cryopreserved germplasm, thawing, and rederivation of Specific Pathogen Free (SPF) offspring from banked germplasm (refer to Attachment A - NIEHS Defined SPF).

The Contractor shall have the capability of long-term storage of cryopreserved germplasm, to include:

(a) the distribution of banked germplasm in two or more liquid nitrogen freezers;

(b) the storage of banked germplasm at a remote site to protect against local disaster at the primary storage site;

(c) an inventory control system;

(d) equipment and procedures to ensure continuous low temperatures when banked germplasm is shipped;

(e) alarms to monitor continuous low temperatures and physical security of storage freezers, and;

(f) a documented plan of action to safeguard the cryopreserved germplasm in the event of a storage freezer failure.

The Contractor shall establish and maintain the following records, which shall be made available to the COR upon request:

(a) Physical conditions of each cryopreservation run, including the protocol used for cryopreserving the germplasm and the results of random viability tests carried out to confirm success;

(b) Genetic identification of banked germplasm. The strain, genotype and pedigreed number(s) of donor(s). For any germplasm cryopreserved from a pedigreed stock, information shall be recorded to enable its ancestry to be traced to the colony from which it was derived;

(c) Storage location of banked germplasm. The type and code number of the container in which the germplasm are contained and the precise location in the liquid nitrogen refrigerators shall be recorded along with the amount of germplasm and an indication of whether embryos were obtained by gonadotropin-induction or spontaneous ovulation of the donor female, and;

(d) Thawing and recovery data for banked germplasm. Provide the number of containers and embryos thawed and success of each step in the process including quality control procedures used to rederive live-born mice.

(4) Quarantine, Customized Breeding, and Colony Development, Production and

Maintenance Services

As required by the COR, the Contractor shall receive, house, breed, genotype, and perform health diagnostic testing and surveillance on NIEHS- provided rodents. The NIEHS- provided animals received by the Contractor may have a SPF status (refer to Attachment A - NIEHS Defined SPF), may harbor organisms that are listed on the attachment, or may be of an unknown disease status.

As required by the COR, the Contractor shall perform customized colony development, breeding and maintenance, which may include: genetically-modified mouse lines; knockout and conditional knockout mouse lines; and transgenic mouse lines.

As required by the COR, the Contractor shall perform backcrossing of animals which may be performed by conventional backcrossing or accelerated backcrossing.

The Contractor shall maintain detailed breeding records to include, in part:

Animal IDs, mating schemes, parental information, genotyping results, generation number, quantity/sex/age/DOB/zygosity of animals per cage, litters and pups, deaths, and health monitoring results.

The Contractor shall notify and request approval from the COR when additional animals need to be added to an existing NIEHS isolator/colony.

(5) Animal Health Surveillance and Diagnostic Testing

As required by the COR, the Contractor shall perform NIEHS customized animal health surveillance and diagnostic testing for the pathogens listed in Attachment A - NIEHS Defined SPF.

(6) Genetic Monitoring and Testing and Veterinary Services

As required by the COR, the Contractor shall provide genetic and veterinary services on NIEHS-provided animals. Comprehensive diagnostic testing may include genetic monitoring of transgenic and knockout laboratory mice.

(7) Customized Research Protocols

As required by the COR, the Contractor shall perform NIEHS customized research studies according to NIEHS-specific protocols. Sample protocols may include, but not limited to: provision of special diets, dosing, sample collection, and aging studies.

(8) Rodent Import and Export Services

As required by the COR, the Contractor shall perform domestic and international rodent export and import services of NIEHS-provided animals to and from the contractor’s facilities. The Contractor shall obtain Shipping Courier approval from the COR when SPF, NIEHS animals are shipped from the contractor’s facilities. The Contractor shall notify the COR when NIEHS animals are received into their facility or shipped to NIEHS or to a NIEHS collaborator.

E. Additional Requirements – Feed, Bedding, Water, Packaging, Shipping

1. Feed and Bedding

The Contractor shall have a documented quality assurance program for laboratory animal feed and bedding. Autoclaved or irradiated feed and bedding shall be provided to all animals. Also, feed/bedding shall meet the specific requirements for nutrients, chemical and microbial contaminants as specified in the “Guide for the Care and Use of Laboratory Animals.” The quality assurance program shall include, at minimum, a nutrient and contaminant analyses of representative feed samples on a quarterly basis. The Contractor shall submit copies of the analyses to the COR upon request. The Contractor shall provide feed and bedding samples to the NIEHS COR upon request. The Government reserves the right to perform any quality assurance assays when such actions are deemed necessary by the Government to assure conformation with prescribed requirements.

The quality assurance program shall include, but not be limited to Standard Operating Procedures for the following feed and bedding operations:

a. Dietary regimens for each animal species;

b. Receipt of feed and bedding;

c. Storage and handling of feed in animal rooms;

d. Maintenance of storage areas;

e. Feed and bedding inventory, and:

f. Storage of bagged feed and bedding in the warehouse.

Upon request, the Contractor shall provide the COR with the supplier name, product name, ingredient list, and nutrient concentrations of the diets fed to animals purchased by or maintained for NIEHS. Upon request, the Contractor shall provide the COR with the supplier name and product name of the bedding used in and under the cages of the animals purchased by or maintained for NIEHS. The Contractor shall notify the COR in writing before there is a change in feed or bedding used for animals purchased by or maintained for NIEHS.

The Contractor shall notify the COR within 24 hours if it is determined that the feed is deficient or toxic in any nutrient or contaminated by pathogens or any chemical compounds known to be undesirable. The Contractor shall notify the COR within 24 hours if it is determined that the bedding used for animals purchased by or maintained for NIEHS is contaminated by pathogens, chemicals or any toxic compounds at levels known to be undesirable.

2. Water Quality

Animals shall have continuous access to fresh, potable, uncontaminated drinking water, according to their requirements.

The Contractor shall have a documented water and watering devices quality assurance program. The quality assurance program shall include monitoring water for pH, hardness, and microbial and chemical contamination on a quarterly basis. The Contractor shall submit copies of the analyses to the COR upon request.

The Contractor shall notify the COR within 24 hours if it is determined that the water and/or the watering devices used for animals provided under this contract is contaminated by pathogens, chemicals or any toxic compounds at levels known to be undesirable.

3. Packaging, Marking, and Shipping

a. Packaging

Animals shall be delivered in properly ventilated, filtered, escape proof containers furnished by the Contractor. If the container is constructed with cardboard, the cardboard should be of sufficient strength to withstand 50 lbs pressure without damaging the integrity of the container. Each order shall be boxed separately. Containers should be divided into compartments to reduce the number of animals that can congregate at ventilation openings and to separate animals from fighting. Windowed crates shall be used for international shipments.

b. Marking

The containers shall be labeled “RUSH - LIVE ANIMALS” and “AVOID EXTREME TEMPERATURES AND DIRECT SUNLIGHT” in bold contrasting letters with up directional arrows.

At a minimum, the packing slip accompanying the shipment shall contain the following information:

(1) NIEHS Release #

(2) Species

(3) Strain

(4) Date of Birth (if applicable)

(5) Weight range (if applicable)

(6) Delivery location

(7) Facility Area

(8) Investigator’s Name

(9) Quantity per Sex/Age

(10) Surgical Manipulation with Date (if applicable)

c. Shipping

(1) The Contractor shall follow all applicable federal, state and local laws and regulations affecting the transportation of animals and comply with the most recent edition of “The Guide for the Care and Use of Laboratory Animals”, the “PHS Policy on Humane Care and Use of Laboratory Animals”, the Institute of Laboratory Animal Resources (ILAR) Guidelines, and the International Air Transport Association (IATA) Regulations for transport of live animals.

(2) Each shipping container shall be provided with accessible transport water kit or moisture/nutrient gel with appropriate moisture content to meet the needs of the species transported. The Contractor shall be responsible for meeting all requirements associated with the shipment of laboratory animals to the NIEHS.

It is recognized that breeder and suppliers of laboratory animals have no direct control or jurisdiction over public carriers used for transporting animals.

However, they shall maintain close liaison with carrier personnel in order to assure their cooperation for proper care of animals during transit.

(3) The Contractor should ensure that the secondary enclosure (delivery vehicle) is loaded on a last in/first out basis (according to the delivery schedule) to avoid the unnecessary movement out of animals within or outside of the vehicle.

Animal shipping cartons shall not be placed outside of the vehicle (street, sidewalk, or concrete loading dock surface, etc.) while sorting through the containers to identify those to be delivered at the designated building.

(4) All vehicles used in transporting animals under this requirement shall be heated

/ air-conditioned when necessary to provide an ambient temperature between 68° and 78° F and must be sanitizable. The Contractor may authorize an agent or delivery agency to make deliveries to air carriers if the vehicle and drivers meet the specifications stated herein. The period before loading when an animal’s environment is not controlled shall be held to a minimum.

https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0ahUKEwid_6HNiIvbAhXLqFkKHX61BGkQFggnMAA&url=https%3A%2F%2Fgrants.nih.gov%2Fgrants%2Folaw%2FGuide-for-the-care-and-use-of-laboratory-animals.pdf&usg=AOvVaw0YtvzGCfOn_DG3aE9LZtKK https://olaw.nih.gov/policies-laws/phs-policy.htm http://www.iata.org/whatwedo/cargo/live-animals/Pages/index.aspx http://www.iata.org/whatwedo/cargo/live-animals/Pages/index.aspx

(5) In hot weather (greater than 78°F), floor space per animal shall be increased by up to 50% by reducing the number of animals in each shipping container.

(6) Each driver or assistant shall be qualified to handle and care for the species of laboratory animals being transported and to provide needed service in emergencies.

(7) Animals shall be delivered by the Contractor, or his designee, to the designated destination detailed on each order. Animals shall be delivered no earlier than 7:00 a.m. and no later than 2:00 p.m. on the date specified.

(8) This delivery service may involve (1) truck or van delivery from the Contractor’s premises to the consignee or (2) air freight shipment to a local airport plus an approved local delivery service to NIEHS or (3) the service of an acceptable air freight forwarding company. Temperature controlled facilities as stated above for proper storage of animals received after hours must be available if (2) or (3) are used.

(9) The Contractor is responsible for ensuring that the animals are delivered to the designated building and room designated by the order form, or to one, two, or both of the designated animals receiving locations for that facility.

Each animal delivery shall be made to the representative of the designated destination facility. A signature shall be obtained upon delivery.

Attachment A NIEHS Defined Specific Pathogen Free (SPF) Agent Exclusion List

The NIEHS reserves the right to alter this exclusion list based on emerging pathogens or changes in agent pathogenicity.

RANK TESTING

FREQUENCY

NIEHS ORGANISM LIST RECOMMENDED TEST

OR SPECIMEN

1 4 wks Minute Virus of Mice (MVM) Serology, IFA, PCR or Western Blot 1 4 wks Mouse Hepatitis Virus (MHV) Serology, IFA, PCR or Western Blot 1 4 wks Mouse Norovirus (MNV) Serology, IFA or PCR or Western Blot 1 4 wks Mouse Parvovirus (MPV) Serology, IFA, PCR or Western Blot

(see additional requirements in SOW)

1 4 wks Rota Virus (Enzootic Diarrhea of Infant Mice - EDIM)

Serology, IFA, PCR or Western Blot

1 12 wks Cilia-Associated Respiratory (CAR) Bacillus

Serology, IFA, PCR or Western Blot

1 12 wks Citrobacter rodentium Fecal Culture/PCR

1 12 wks Clostridium piliforme Serology, PCR, Histopathology (if indicated)

1 12 wks Corynebacterium kutscheri Tracheal/Oral/Nasopharyngeal Culture

1 12 wks Ectoparasites Low Power Microscopic Examination of Fur and Skin; PCR

1 12 wks Giardia muris Proximal Small Intestine 1 12 wks Helicobacter sp. (if positive, speciate) PCR and/or Culture

(specify screening method in health reports)

1 12 wks Lymphocytic Choriomeningitis Virus

(LCMV)

Serology, IFA, PCR or Western Blot

1 12 wks Mycoplasma pulmonis Tracheal/Oral/Nasopharyngeal Culture, Serology, IFA, or /PCR

1 12 wks Other Intestinal Helminths Fecal Concentration 1 12 wks Pasteurella pneumotropica Tracheal/Oral/Nasopharyngeal

Culture or PCR 1 12 wks Pneumonia Virus of Mice (PVM) Serology, IFA, PCR or Western Blot 1 12 wks Reo Virus - Strains 1-3 Serology, IFA, PCR or Western Blot 1 12 wks Rodentolepsis nana Fecal Concentration 1 12 wks Salmonella species Fecal Culture

1 12 wks Sendai Virus Serology, IFA, PCR or Western Blot 1 12 wks Spironucleus muris Proximal Small Intestine Wet Mount 1 12 wks Streptobaccillus moniliformis Tracheal/Oral/Nasopharyngeal Culture

1 26 wks Ectromelia Virus Serology, IFA, PCR or Western Blot 1 26 wks Encephalitozoon cuniculi Serology, IFA, PCR or Western Blot

1 26 wks Hanta Virus (Testing quarterly for international shipments or animals imported from outside sources)

Serology, IFA, PCR or Western Blot

1 26 wks Lactate Dehydrogenase-Elevating Virus (LDHV)

Serology, IFA, PCR or Western Blot

1 26 wks Mouse Adenovirus (MAV) Serology, IFA, PCR or Western Blot 1 26 wks Mouse Cytomegalovirus (MCMV) Serology, IFA, PCR or Western Blot

1 26 wks Mouse Thymic Virus (MTV) Serology, IFA, PCR or Western Blot 1 26 wks Polyoma Virus Serology, IFA, PCR or Western Blot 1 necessary only if ectoparasites present

Eperythrozoon coccoides Stained Blood Smears, Smears prepared from splenectomized mice

1 necessary only if ectoparasites present

Hemobartonella muris Stained Blood Smears, Smears prepared from splenectomized mice

2 12 wks Klebsiella oxytoca Tracheal/Oral/Nasopharyngeal Culture; PCR

2 12 wks Klebsiella pneumoniae Tracheal/Oral/Nasopharyngeal Culture; PCR

2 12 wks Streptococcus Sp. Tracheal/Oral/Nasopharyngeal Culture or PCR

2 12 wks Other Protozoa Fecal Wet Mounts 2/3 12 wks Bordatella bronchiseptica Tracheal/Oral/Nasopharyngeal

Culture or PCR 2/3 12 wks Corynebacterium bovis Skin culture or PCR 2/3 12 wks Coagulase (+) Staphylococcus species Tracheal/Oral/Nasopharyngeal Culture or PCR

2/3 12 wks Pseudomonas aeruginosa Tracheal/Oral/Pharyngeal Culture and Fecal Culture or PCR

2/3 12 wks Pneumocystis murina/carinii (immuno-deficient mice)

Lung, Histopathology or Immunochemistry or PCR; Serology (if available)

RANKING CATEGORY AS IT APPLIES TO ISSUING ANIMALS TO ANY NIH DELIVERY ADDRESS

1 Vendor shall not issue animals to NIEHS from rooms/units/barriers positive for these agents without a specific written request demonstrating acceptance from the ICD Veterinarian acknowledging the positive status on the face of the order.

2 Vendor may issue animals, with pre-approval from NIEHS COR or designee, from areas known to be positive for these agents if no alternate clean source is available unless a specific request for animals free of these agents are present on the face of the order form. (Vendors shall continue to emphasize maintenance of colonies free of these agents.)

3 For Immunodeficient animals, these agents shall be interpreted at the criteria stated in ranking category 1.

* Four weeks may be interpreted as monthly, twelve weeks may be interpreted as quarterly, twenty-six weeks may be interpreted as semi-annually, and 52 weeks may be interpreted as annually.