INTRODUCTION Support Services.doc · Web viewTABLE OF CONTENTS TABLE OF merican Health Research Institute (AHRI) serves both Government and Industry through a broad range of scientific

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AMERICAN HEALTH RESEARCH INSTITUTE, INC. Animal Support and R&D Services

TABLE OF CONTENTS

merican Health Research Institute (AHRI) serves both Government and Industry through a broad range of scientific disciplines including Animal Support Services, Diagnostic Testing, Clinical Laboratory Testing, Physician Services, Magnetic Resonance Imaging (MRI), Echocardiology, Lithotripsy, Breast Imaging, Synthesis of Drugs (anti-AIDS and anti-Cancer) and Immunological and Toxicological evaluation of drugs (research and development). AHRI is currently performing Animal Husbandry Services for the CDC’s NIOSH facility in Morgantown, West Virginia.

Section I – Introduction Page 1CDC Recommendation Letter Page 2

Section II – General Services Page 3Waste DisposalOrdering and Supply InventoryOrdering, Receipt and Delivery of AnimalsAnimal Feeding and Watering PracticesAnimal Health MonitoringAnimal Holding and RestraintEquipment Maintenance and OperationQuality Assurance Program

Page 5Page 6Page 8Page 10Page 11Page 13Page 14Page 15

Section III – Research and Development Page 16Tumor Biomarker StudiesCytokine Production/Clinical TrialsCustom Radiolabelling/Hybridoma ProductionChemistry SynthesisForensic Toxicology/Drugs of AbuseRadioimmunologyVeterinary Pathology & ToxicologyMolecular BiologyEnvironmental ToxicologyChemoprevention

Page 18Page 19Page 20Page 21Page 22Page 23Page 24Page 25Page 26Page 27

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INTRODUCTION

AHRI’s Laboratory Animal Science Division offers a comprehensive range of services in animal care and research. AHRI staff is knowledgeable and experienced with laboratory animal regulations (PHS Policy on Humane Care and Use of Laboratory Animals by Awardee Institutions, Animal Welfare Assurance and the Guide for the Care and Use of Laboratory Animals); acceptable animal care procedures and practices; basic scientific concepts; comparative anatomy; normal physiology and disorders, administration, management and record keeping. AHRI staff is also skilled in equipment design and maintenance, animal husbandry and animal health surveillance procedures, transportation of animals, intake procedures, sanitation, hygiene, safety, nutrition, metabolism, genetics and mating, and types of housing for a wide variety of experimental and surgical techniques. They are also familiar with appropriate types of housing for a wide variety of experimental animals ranging from mice to primates. AHRI’s staff has expert relevant knowledge of radiology, animal health and disease, veterinary pharmacology, anesthesia and euthanasia, and the use of inhalation chambers. On the following page is a reference letter AHRI’s staff received for our on-going NIOSH Animal Husbandry contract.

AHRI’s focus is on the growing need for support services. AHRI recognizes the Government's needs to cut back expenses and AHRI specializes in a "best value" approach to doing business with the Government.

AHRI is capable of mobilizing rapidly to perform work with extraordinary skill and efficiency and has done so. AHRI supports and makes every effort to provide further employee education and technical training. All supervisory employees are encouraged to attend professional training seminars, higher education classes and certification courses.

AHRI has always been proud of its leadership in the development, application, and management of state-of-the-art technology. Many of our Corporate Projects involve the cooperative effort of the scientists, veterinarians, pathologists, technicians, engineers, and regulatory personnel in order to achieve work of the highest quality and client satisfaction.

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GENERAL SERVICES

Routine Animal Care and Husbandry

An important, and often overlooked, component of biomedical research is the animal care and husbandry practices for the research animals. We define laboratory animal care as the optimum husbandry of the animals -- providing a clean, environmentally stable living area and a healthy, stress-free existence. The animals must have access to fresh, clean feed and water, have ample cage space for routine movement and activities, and be maintained in a rigidly controlled environment. Inconsistencies in the environment can have detrimental effects on research. Our animal care procedures are based upon the guidelines established in the HHS Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy on the Humane Care and Use of Laboratory Animals, the USDA Animal Welfare Act, and ALOSH Standard Operating Procedures.

Emergency services are provided during the contract. A list of emergency phone numbers is provided to the Project Officer for use during such times. There may be times when animal care staff may stay beyond normal business hours to complete necessary work. Often animal deliveries arrive late in the day and require either the technician or the technologist to remain at the facility to process the incoming animals.

The following are examples of typical “routine’ services that are performed:

Sanitation and Husbandry Procedures Facility Sanitation Monitoring Animal Room Environment Cage Monitoring and Room Checks Moribund or Dead Animals VCL Units Cage Changes

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Cagewashing and Sanitizing

The Animal Technologist has the primary responsibility for monitoring cagewash operations. He will work closely with the technicians to ensure adherence to established schedules and the proper operation of and maintenance of all equipment. When equipment failures have occurred, the Animal Technologist will notify the Project Officer immediately and requests repair. In some instances, the Animal Technologist’s experience with the equipment may enable him to complete minor repairs himself.

The following items/equipment have specific cagewashing procedures that are strictly followed:

Cabinet washer Feeders, Bottles and Sipper Tubes Caging (Bedding) Monitoring Cagewash Temperature

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WASTE DISPOSAL AND PEST CONTROL

Disposal of Biological Waste and Dead Animals

Because the majority of animals wastes are from "clean" or noninfectious animals, contents of dirty cages, including litter and feed, is be dumped into a plastic lined barrel and sealed. Bags and/or liners are placed in the area dumpster outside the building. Biological waste is disposed of at the end of each day. Animals that have been dead for a period of time may be carried (after double bagging) directly to a dedicated chest freezer in a cold room. All dead animals are kept here for transport to the incinerator for burning. Project staff generally transport the animals on each Friday in a government provided vehicle.

Refuse Practices and Pest Control

AHRI maintains the animal holding rooms and support facilities in such a way that they will not harbor pest or other vermin. Vermin control, all administrative (trash) and animal (feed, waste, bedding) organic waste or refuse is carried to a dumpster on a daily basis. This includes:

Daily removal of all trash; Ensuring that all doors and windows are closed to prevent fly infestation; Securing lids to trash, food, and feed containers when not in use Removal of spilled and excess feed as quickly as possible; Flushing animal room drains with a disinfectant solution after cleaning; Moving feed to storage areas immediately upon receipt; and Wipe down hallways and support areas.

Currently, the pest control program requires the use of sticky pest traps that are placed in each animal room for monitoring. Each trap is checked weekly for signs for roaches, beetles, mites, or other common pests. Upon discovery of a contaminated trap, it is replaced and noted in the room log by the attending technician. Pesticides are never used within the animal quarters.

Disposal of Hazardous Wastes

The Animal Technologist notifies the Project Officers of any reported hazardous waste for explicit direction on disposal. All hazardous waste is bagged and autoclaved before disposal. After sterilization, the waste is moved for pickup or as directed.

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ORDERING AND SUPPLY INVENTORY

Ordering and Inventory Procedures

The Animal Technologist, who performs weekly inventories of these items, maintains a list of supplies. The list is maintained in the facility office for review and inspection. Supply ordering is the responsibility of the Animal Technologist.

Logistical Support

AHRI provides all logistical support as required to meet the animal care and research needs of the investigators at the facilities. This includes, but is not limited to, maintaining inventories, properly storing supplies, alerting the Project Officer when additional equipment, animal feed and bedding, and other animal care supplies are required. The Animal Technologist keeps the Project Officer updated on animal care equipment and supplies.

Ordering

Supplies orders are given to the Project Officer, who goes through the government procurement process. The Animal Technologist places feed and bedding orders directly with the suppliers.

Receipt

AHRI staff receives, stocks, and maintains inventories of all supplies and equipment required for performance of the project requirements. As items are received, they are visually inspected and any damage noted and reported to the Project Officer. Any discrepancies between what was ordered and received is reconciled. Without authorization from the Project Officer, staff members will not receive items not related to the contract, such as drugs and medical supplies. All feed is closely inspected for mill date.

Storage

All supplies are stored in dedicated storage room located in a clean room. The Animal Technologist responds accordingly, ensuring that all supplies are properly stored and the area kept in a neat and organized manner and the room disinfected monthly.

After the feed has been accepted and unloaded, the feed or bedding is immediately taken to the dedicated storage room where the Animal Technologist or technician stack the feed and bedding on pallets in such a way as to be kept a minimum of 1 inch from the closest walls.

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Feed and bedding is stored so that different types (species, certified, etc.) and shipments of feed and bedding are physically separated. Both feed and bedding will be used on a first-in, first-out (FIFO) basis to ensure that the oldest feed/bedding is used first. This ensures that feed is not used after expiration dates have passed and that animals will continually receive fresh feed.

Feed that has exceeded the allowable expiration date is discarded because the nutrient quality may be reduced due to the degradation of the less stable nutrients. The technician does not transfer feed barrels between animal rooms. The feed container is cleaned and emptied of all feed prior to filling with new feed. The lot number of the feed used to fill the container is documented. All barrels are labeled with the milling and receipt date (recommended).

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ORDERING, RECEIPT AND DELIVERY OF ANIMALS

AHRI feels that one of the most critical procedures with an animal research program is their procurement, which encompasses the ordering, receipt, and delivery of the animals to the requesting researcher.

Animal Ordering

A researcher using a form in standard memorandum format generally initiates orders for research animals. Each request must have an approved protocol number or it will be returned and the Project Officer notified.

Animal Receipt

When animals are received, they are delivered/received at the loading dock. Upon arrival, the Animal Technologist is notified of the arrival and transports a cart to the dock for moving the animals in their boxes. At the dock, the information of the boxes are verified against the order and then inspected for damage. Wet, torn, or damaged boxes are not accepted. Boxes in acceptable condition and with animals in agreement with the original order are then signed for and accepted.

All incoming animals will be observed for disease and other abnormal conditions by our staff. These include, but are not limited to:

Heat prostration Dehydration Wounds or skin trauma Abscesses Abnormal discharges (e.g., ocular, nasal) Diarrhea Poor hair coat Ear/skin parasites Overgrown teeth or toenails Animal posture

Any abnormalities that are observed are immediately reported to the Project Officer or designate such at the attending Veterinarian. Any animals that are rejected, regardless of cause, are identified and the Project Officer notified immediately. Dead animals are double bagged, a mortality form completed and filed, and the animals either moved to the pathology lab or to the freezer for incineration. Morbid animals may be euthanized or treated as determined by the attending veterinarian. A morbidity report is completed and filed in the office. Final determinations are entered on the mortality or morbidity reports and are filed along with any pathologist reports.

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Healthy animals are placed in disinfected cages bedded with autoclaved or sterilized bedding. Rats are given autoclaved ARodent Blox 3500 and sterilized water bottles filled with tap water. Guinea Pigs feed hoppers are filled with Agway Guinea Pig feed and bottles filled with tap water added to each cage.

Entries are made into the room logs, trash removed, and the room swept. Shipping receipts and Viral Antibody Profiles labels are properly filed and the USDA forms for guinea pigs completed and mailed.

Animal Stabilization

After the animals have been properly placed in cages, fed, watered, and placed in a LAF unit, all animals are not moved for a period of 1 week. This period allows the animals to stabilize before being moved to other caging, LAF unit, or to a lab.

Animal Identification

Identification of the research animals is accomplished through the use of cage cards, which are placed directly on the cage into a dedicated holder, and the use of the LAF Identification form.

The cage cards contain the following information:

animal order number species strain sex weight date of birth source

date received number of animals per cage LAF unit number cage number investigator’s name section

The Facility LAF identification is a master log that identifies all animals and the LAF unit where they are housed. As animals are received or removed from the cages, the Facility LAF form is updated to reflect these changes. The form is posted on the bulletin in the main corridor for quick reference and then filed when replaced by a revised log.

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ANIMAL FEEDING AND WATERING PRACTICES

The following presents some common practices employed by AHRI involving animal feeding and watering

Animal Feeding Practices

Research animals are fed in accordance with protocol requirements and the appropriate SOP for each species housed. Animal care technicians checks all feeders throughout the day, taking special care during room checks in the morning and afternoon.

Animal Watering Practices

All animals (except those on water restriction protocols) must have constant access to clean, fresh, potable water. The exception would be as part of a research protocol, which is documented in writing. Automatic watering systems is checked daily (as discussed earlier). Individual lixits are touch tested for proper functioning. If a lixit is found not functioning or if the animal appears dehydrated, a water bottle will be provided immediately for as long as necessary to replace or repair the lixit and the Project Officer then notified. Automatic watering lines are flushed daily.

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ANIMAL HEALTH MONITORING

The results of biomedical research involving laboratory animals are dependent on maintaining healthy animals for the duration of the experiments. A properly executed animal health surveillance program will verify and document the health status of the animal colonies involved in biomedical research programs as well as alert the facility veterinary staff of any potential disease outbreak. Currently, the Animal Care Technician and the Animal Technologist conducts the daily activities.

The following activities are performed:

Daily Health Checks

All animals are observed a minimum of two times each day for mortality, morbidity and clinical signs of disease. During cage changes a thorough health check is done during transfer and handling of the animals. The Project Officer or attending Veterinarian (as directed) and researcher are notified of any animals requiring their attention immediately following completion of the inspection. AHRI animal care technician and technologist continue to observe the following:

Food or water consumption Presence of masses Blood or mucous in feces and urine Discharge from the eyes, nose, mouth, or other orifices Abnormal or moribund behavior Posture and gait Skin and coat condition Respiration Tumors Weight loss.

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Administering Drugs and Routine Treatments

When required, AHRI’s animal care technicians will administer medical treatments to animals requiring such care. Current treatments are administered by injection, mixed with the feed or water, or applied by topical application. The Project Officer or Veterinarian must authorize all treatments in writing, and all treatments must be properly documented.

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ANIMAL HANDLING AND RESTRAINT

AHRI is committed to providing proper care and humane treatment of all animals. This includes handling and restraining the animals for use in specific research protocols. Only properly trained technicians are assigned to assist in the restraint of the laboratory animals. All methods of restraint whether physical, chemical or mechanical are performed only by experienced staff and conducted in accordance with ALOSH SOP and techniques promoted by the American Association of Laboratory Animal Science (AALAS).

New employees are trained to handle and restrain laboratory animals according to the AALAS Laboratory Animal Technician Certification Program as described in the Manual for Laboratory Animal Technicians.

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EQUIPMENT MAINTENANCE AND OPERATION

Equipment Maintenance

The laboratory animal equipment represents resources that must be properly cared for and managed. All equipment is maintained in a clean, sanitary condition. In addition, care is taken while cleaning, handling, storing, or using a piece of equipment to prolong its usable life. Proper and careful handling extends life and reduces costs (repair or replacement). Standard procedures on the use of specific animal care equipment is observed and followed. All equipment used is maintained according to the operating manuals and appropriate operating instructions.

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QUALITY ASSURANCE PROGRAM

To monitor and assure the quality of health, a sentinel program is implemented in the animal quarters. The program requires serum samples to be taken from incoming animals and animals housed for extended periods of time. Serum samples are taken by the staff and sent for testing. Results are sent to the Facility Veterinarian for review and eventually filed in the facility office. Positive test results will require the Project Officer and facility veterinarian to determine a plan of action, including sacrificing infected animals. Manufacturers are required to perform bi-monthly inspections of equipment.

A more comprehensive QA Program Plan can be provided upon request.

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RESEARCH AND DEVELOPMENT

AHRI provides R&D in the following areas:

Immunological and Toxicological Evaluation of Xenobiotics, Drugs

and other agents Tumor Immunology Transplant Immunology Immune Complex Rectors Drugs: Immune Response Chemical Carcinogenesis and

Chemoprevention Recombinant DNA Gene Therapy Cytokine Studies Hybridoma Studies Animal Toxicology

AHRI utilizes state-of-the-art equipment in its laboratory and is dedicated to performing only work of the highest quality. In addition, AHRI has been performing Small Business Innovative Research awards from the National Institutes of Health (NIH).We currently have three full-time, one part-time, and six consulting veterinarians on our team staff. We have the knowledge and expertise in our company to provide and/or develop appropriate veterinary medical care to provide Research Support Services and Laboratory Animal Care to the U.S. Government Agencies.

AHRI team members currently provides rodent surgical models to the research community. These models are prepared by trained technicians under veterinary supervision in our dedicated surgical facilities. We understand the requirements and needs for the conduct of aseptic surgery in facilities intended for that purpose to include separate support area, preparation area, operating(s), and an intensive care and supportive treatment of animals.

We currently have the resources to provide colony maintenance, hysterectomy and/or embryo cyropreservation, and animal transportation services for transgenic and knockout mice. Animals are either returned to the clients or other as needed to meet their research requirements. Animals are also manipulated per investigators’ approved experimental protocols. We have consultants in cryobiology and microinjection who could provide support if needed.

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AHRI’s team maintains large breeding colonies of disease-free, genetically defined inbred and outbred mouse and rat stocks and strains. These animals are produced in maximum barrier buildings or in flexible-film isolators. Our personnel are highly skilled and experienced in maintaining and providing a wide variety of strains to worldwide biomedical research. We routinely meet special research requirements in delivering animals of the appropriate stock/strain, sex, age, number, size, and pregnancy status. We also provide special services or techniques to meet investigator and/or approved protocol requirements.

Our molecular biologist has worked on various techniques in the areas of autoradiography, electrophoresis, in situ hybridization and sample analysis. We currently perform DNA fingerprint and polymerase chain reaction techniques.

Our staff has extensive experience in pathological investigation, microdialysis, protein expression and cardiac manipulation techniques.

Capabilities of some of our investigators are enclosed.

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R&D CAPABILITIES IN TUMOR BIOMARKER STUDIES

Special Interest/Area:

In vitro and vivo evaluation of anti-angiogenic agents (synthetic and natural) In vitro biological assays for screening potential anti-proliferation and anti-tumor

compounds. Analysis of tumor biomarkers (oncogenes, growth factors, cell surface receptors)

in human tissue/cells. Cell activation, differentiation and transformation analysis using in vitro coculture

protocols. Experimental metastasis model for testing anti-invasion and anti-metastasis

agents.

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R&D CAPABILITIES IN CYTOKINEPRODUCTION/CLINICAL TRIALS


Analysis of Human Anti-Mouse Antibodies and Cytokines (Interleukins, Interferons, growth factors and colony stimulating factors).

Design of specific Assays for clinical trials. Long term storage of clinical samples. Clinical trial technical support. Delayed hypersensitivity. Cytokine production in Mycoplasmal Pulmonary Disease. Cytokine Assays for studying the effects of drugs on Cytokine Expression. Immunological evaluation of Osteoarthritis.

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R&D CAPABILITIES IN CUSTOMRADIOLABELLING/HYBRIDOMA PRODUCTION


Human response to Monoclonal Antibodies. Hybridoma Studies. Iodine Radiolabelled Monoclonal Antibodies used in clinical trials for cancer

patients. 125I-antibody of known specific activity. Chimeric Monoclonal Antibodies. Design customized assays for clinical trials. Custom Radiolabelling.

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R&D CAPABILITIES IN CHEMISTRY SYNTHESIS


Synthesis of Hetrocyclics as Psychopharmacological Agents (Indoles, Spiroindoles, Benzodiazepines).

Carbohydrates (Sialic Acid Derivatives). Radiolabeled compounds (up to 12-step synthesis). 14c Pyrazolo Pyridines 14c Pyridazinothiadiazoles 14c Pyrimidine Organometallic Compounds. Custom synthesis of Histamines, Peptides, Phenothiazine Phenylalanines,

Phenylalkylamines, Pteridines Purine and Pyrimidine Tryptamines. Synthesis of Anti-viral compounds, Potential Prophylactic Agents, Naphlhalene-

Hydroxynapthalene Polymer Compounds, Anti-tumor agents, Mitotic and Folate Inhibitors, Disulfonic Stilbene Derivatives.

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R&D CAPABILITIES IN FORENSICTOXICOLOGY/DRUGS OF ABUSE


Drugs of Abuse: Qualitative and Quantitative approach using Gas Chromotography/Mass Spectrometry, Nuclear Magnetic Resonance Spectroscapy Liquid Chromatography & HPLC

Drug Metabolites: Digestion, Extraction, Derivatization and Analysis of Drugs of Abuse

Synergistic Effects of Drugs of Abuse: Toxicological Evaluation

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R&D CAPABILITIES IN RADIOIMMUNOLOGY


Thermotolerence and Heat Shock Proteins. Natural killer cells, Inferon. Monoclonal Antibodies: Inhibition of Moloney Sarcoma growth in-viro. Biology, pathology and ultrasound studies of solid tumors. Preparation and measurement of Interleukin–2 receptors.

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R&D CAPABILITIES IN VETERINARYPATHOLOGY & TOXICOLOGY


Retinoids Synthesis. Retinoids Evaluation/Immunology-Toxicology Mechanism of Retinoids Potentiation. Immune Functional Studies.

Animal Support:

Diplomate: American College of Veterinary Pathology Diplomate: American College of Laboratory Medicine

Center for Disease Control, Atlanta, Georgia:

Provides Clinical and Anatomic Pathology Diagnostic Services for Animal Resources Branch.

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R&D CAPABILITIES IN MOLECULAR BIOLOGY


Cloning and characterization of human and rat cDNA clines. Recombinant DNA. Mapping of genes. Screening of Genomic and cDNA libraries. Sequencing of DNA and RNA using chain termination and chemical methods.

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R&D CAPABILITIES IN ENVIRONMENTAL TOXICOLOGY


Role of Nonhistone Proteins in homral Carcinogenesis. Geotoxicity of Na-o-phenylphenol. Inhibition of estrogen-induced carcinogenesis by turmeric. Determination of Mutagenic potential of Na-o-phenylphenol. Mechanism of o-phenylphenol-induced bladder cancer. Phase 1 and Phase 2 Clinical trials of New Chemopreventive Agents. Toxicology and Carcinogenicity of environmental estrogens. Free Radical generation of redox cycling of estrogens.

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R&D CAPABILITIES IN CHEMOPREVENTION


In vitro testing and pharmacokinetics of chemopreventive agents (synthetic and natural).

Evaluation of potential anti-tumor compounds using carcinogen-induced animal tumor models.

Analysis and detection of early and late tumor biomarkers in human tissues/cells. Cell phenotype analysis (differentiation, transformation and apoptosis). Evaluation of dietary factors (amino acids, fatty acids, vitamins for

chemoprevention and cancer therapy).

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Documents

INTRODUCTION Support Services.doc · Web viewTABLE OF CONTENTS TABLE OF merican Health Research Institute (AHRI) serves both Government and Industry through a broad range of scientific