Investigators intending to administer or treat live animals with hazardous materials must submit a copy of their Institutional Animal Care and Use Committee (IACUC) animal protocol review form (Form A) to EHRS for review and approval before the IACUC will give its full approval to the protocol. To expedite the review process, a copy of Form A should be simultaneously submitted to EHRS in addition to the form submitted to ORA (See Procedure below).

More detailed information on the classification of hazardous materials is available in University's Biological Safety Manual, Chemical Hygiene Plan and Radiation Safety User's Guide. Investigators who are uncertain about the classifications of the specific hazardous materials should contact EHRS.

Investigators intending to work with radioactive materials in research must be licensed to do so. License applications, obtained from EHRS, are reviewed and approved by the University's Radiation Safety Committee. A Protocol Summary Form must be submitted to EHRS for protocols involving the use of radioactive materials in animals and may require a license amendment if the room(s), isotope(s), and activity were not previously approved.

Investigators should consult the Chemical Hygiene Plan for handling procedures when using potentially hazardous chemicals. Investigators must include descriptions of appropriate safeguards, such as the use of personal protective equipment, proper handling of contaminated bedding, cages, water bottles and carcasses and proper labeling of cages/facilities.

When biohazardous material is used in animals, investigators are required to work under the containment conditions appropriate for the specific agent. Infectious agents are classified according to risk. Investigators are expected to understand the risks associated with a proposed agent and to use practice and procedures appropriate for the activity to be conducted, based on biosafety containment criteria described in CDC/NIH Biosafety in Microbiological and Biomedical Laboratories, 4th ed. and the University's Biological Safety Manual.

After a protocol is fully approved by the IACUC, investigators must notify ULAR and EHRS in writing or by email and consult with each office, prior to initiating work on an animal protocol involving hazardous materials. In addition, on certain animal protocols (i.e., Animal Biosafety level 2 or higher, or administration of certain hazardous chemicals or radioisotopes), investigators are required to brief the ULAR staff, prior to starting work in the animal facility. See procedures below.

back to top



II. NON PROTOCOL DRIVEN, SPECIES SPECIFIC, OCCUPATIONAL RISKS

In addition to protocol-specific occupational hazards, there are some occupational risks that are intrinsic to individual species. Mitigation of these risks are handled as part of the species-specific training that is required for all researchers, and are not the subject to the procedures outlined below.

ULAR, in consultation with EHRS, developed policies to protect animal care and research staff from possible exposure to potentially infectious agents that research animals may harbor (such as rabies, cercopithecine herpesvirus type 1 [formerly monkey B virus], Coxiella burnetti). Investigators should review these policies with their staff and follow them when working with animals that may harbor these agents.

All faculty and staff working in research laboratories must attend required Introduction to Laboratory Safety, Biological Safety and Bloodborne Pathogens at Penn Training and annual online update training thereafter.

Procedure

1. The Office of Regulatory Affairs (ORA) provides EHRS with IACUC protocols that will be reviewed at upcoming meetings. Investigators may also submit IACUC Form A to EHRS electronically via approvals@ehrs.upenn.edu or through intramural mail.
2. An EHRS professional staff member reviews the protocol and determines the nature of the hazard(s).
3. An EHRS administrative assistant logs in the protocol, obtains an IACUC protocol number from the ORA and checks health and safety training records of all protocol participants named, including the investigator.
4. The protocol is distributed to EHRS staff member(s) who specialize in the risk assessment of the specific hazard(s). If multiple hazard reviews (biological, radiation, chemical) are required the protocol may be reviewed by as many as three different reviewers.
5. If issues arise that require clarification, the reviewer contacts the investigator.
6. Once issues are resolved, an EHRS full approval letter is generated. The letter may contain the following, depending on circumstances described in the animal protocol:
   1. Assignment of appropriate Biosafety level(s) for animal and laboratory work.
   2. Special handling and husbandry procedures for animals exposed to hazardous chemicals or radioactive materials.
   3. Transport guidelines for infectious materials/animals between the animal facility and the laboratory.
   4. Recommendations related to respirator fit testing if respiratory protection is required.
   5. Vaccination requirements, if relevant.
   6. The requirement that the PI must notify and consult with ULAR and EHRS in advance of starting protocols
      1. assigned to Biosafety Level 2 or higher,
      2. involving the administration of hazardous chemicals.
7. When there are issues that are not resolved in the short term, EHRS issues provisional approval letters. Once the issues in the provisional approval letter are addressed, the investigator is asked to FAX back a signed copy of the letter, at which time EHRS issues a full approval letter.
8. Approval letters are sent directly to the investigator, with copies to the Co-Investigators, ORA, and the director of ULAR. Copies of the letters may also be sent to the attending veterinarians as well.

Question 5A asks investigators to specify infectious or transmissible agents (See Appendices 1-6 of the Biological Safety Manual); human source material (human blood, body fluids, tissues or cell lines); tumor cell lines and recombinant DNA administered or used to treat live animals.

If infectious or transmissible agents are specified, the Biosafety Officer identifies the risk group of the agent and specifies the biocontainment level required for work with the agent(s). If recombinant and/or replication-defective agents are specified, risk assessment includes the nature of the vector, its insert(s) and the potential for replication competent virus to be produced and shed.

If a vaccine is available, it is recommended that all personnel handling the agent or animals infected with the agent be offered vaccination far enough in advance of handling infected animals to be afforded protection. Occupational Medicine administers the vaccinations, available through the medical surveillance program for University personnel. For example, investigators intending to work with vaccinia virus must be approved by EHRS to do so. They are advised to follow the specific University protocol to work with this virus. Staff is offered small pox vaccine based on Centers for Disease Control and Prevention recommendations. Laboratory faculty and staff as well as animal care personnel who fall in this category must be counseled by Occupational Medicine in the Hospital of the University of Pennsylvania and offered vaccination before being allowed to handle vaccinia virus or infected animals.

Laboratory personnel working with human source materials are advised to treat all human blood, blood products, body fluids or tissues as if they are potentially infectious and handle them accordingly. All animal research using human source material is conducted at Animal Biosafety Level 2, which is consistent with the concept of Standard (formerly Universal) Precautions. Free Hepatitis B vaccination is made available to all at-risk personnel through Occupational Medicine. All personnel working with human source material are advised they must attend annual required bloodborne pathogens training offered by EHRS before the animal protocol is approved. In addition, each laboratory using human source material is advised to complete an Exposure Control Plan and have it available for reference purposes.

Investigators who generate recombinant DNA must register the recombinant work with Institutional Biosafety Committee. If the recombinant work indicated in the protocol is not registered, investigators are contacted by phone or email and ask to complete a recombinant DNA registration document. Protocol approval does not proceed until this has occurred.

Question 7 requires investigators to get written permission to transport infected animals through human patient areas. At Penn, laboratory animal facilities used for studies of infectious or non-infectious disease are physically separate from clinical laboratories and patient care areas. Occasionally, a protocol may involve a procedure that requires the investigator to bring animals into human hospital spaces. If this occurs, the investigator must consult with the Hospital Epidemiologist and have specific written approval to work in a clinical area before the work begins. EHRS reminds investigators of this responsibility through the protocol approval process.

Question 8 deals with removal of animals from the facility. EHRS may provide transport guidelines for infected animals in response to answers to questions 7 and 8.

Question 13 deals with the production or use of transgenic animals. Investigators who intend to create transgenic animals must register the recombinant work with Institutional Biosafety Committee before starting experiments. If transgenics are to be developed by a Transgenic Core Facility, investigators must register the work with the Institutional Biosafety Committee before the core facility creates the transgenic animal. In addition, EHRS must approve the relevant animal protocol before the Animal Care and Use Committee gives the protocol its full approval.

back to top



IV. CHEMICAL TECHNICAL REVIEW PROCESS

Protocols involving animals and the use of hazardous chemicals are reviewed by an EHRS Industrial Hygienist. Question 5 B1 of the IACUC Form A requires the investigator to list the dose and route of administration of any potentially hazardous substance (including approved or experimental pharmaceutical products, hormones, laboratory chemicals, inhalation anesthetics, and the injectable anesthetics Urethane and Chloralose) to live animals and indicate if this process results in the animals, their bedding or cages posing a hazard to animal handlers. If the investigator answers in the affirmative they must explain the hazard in section 5 B2 and describe how it will be controlled. When inhalation anesthetics are used, the investigator must describe how waste anesthetic gases will be scavenged in section 5 B3.

If the hazard control procedures in sections 5 B2 or 5B 3 are not adequate, the investigators are contacted to discuss their research and EHRS provides specific hazard abatement instructions in the protocol letter. If the procedures outlined in sections 5 B2 or 5B 3 are adequate or if the chemicals listed in section 5 B1 do not pose a hazard, the protocol is approved as written.

back to top



V. RADIATION TECHNICAL REVIEW PROCESS

Protocols involving animals and the use of radioactive materials, irradiators or x-ray machines are reviewed by an EHRS Health Physicist. Investigators are advised to follow procedures outlines in the Radiation Safety User's Guide, Irradiator's User's Guide, X-ray Diffraction User's Guide, X-ray User's Guide as well as those specified in their University license.

The Principal Investigator may be asked to amend his/her license to include the isotopes and rooms where the animal work is performed, including the ULAR facility if the animal will contain radioactive material while being housed there. Imaging locations are included as well.

The Radiation Safety User's Guide gives specific instruction that in the animal facility, animal care is the responsibility of the licensee while the animals are radioactive. Directions for labeling of radioactive cages, rooms and waste containers; monitoring of contaminated cages, equipment and rooms; radioactive waste disposal; and transport of animals containing radioactivity are also provided.

back to top



VI. AMENDMENTS

To add biohazardous materials, hazardous chemicals or radioactive material use to an approved protocol, investigators may submit an Animal Use Protocol Amendment Form. Risk assessment processes outlined above are followed, depending on the nature of the hazard involved.

Letters of approval for amendments are sent to the investigator, with copies to the Co-Investigators, ORA and ULAR. Investigators may be required to amend their license for radioactive material use in animals if the room(s), isotope(s), and activity were not previously approved.

back to top



VII. POST APPROVAL RISK INFORMATION IMPLEMENTATION

As stated above, after a protocol is fully approved by the IACUC, investigators are required to notify ULAR and EHRS in writing or by email and consult with each office, before beginning work on an animal protocol involving radioisotopes, work at Animal Biosafety Level 2 or 3, certain hazardous chemicals or any combination thereof. This is to ensure that proper housing is available and all required safeguards and animal husbandry procedures are in place before experiments begin.

ULAR will not allow animals to be ordered if EHRS approval is required and has not been received. ULAR assigns animal housing to protocols, based on EHRS containment criteria and husbandry recommendations. In addition, on certain animal protocols (i.e., Animal Biosafety level 2 or higher, or administration of certain hazardous chemicals or radioisotopes), investigators are required by ULAR to brief the ULAR staff, prior to starting work in the animal facility.

back to top



VIII. POST APPROVAL RISK MITIGATION

EHRS audits laboratories regularly through its lab audit programs.

EHRS participates in animal facility audits when invited by the director of ULAR or when notified of IACUC inspections by ORA. These audits are performed on an as-needed basis and as staffing allows.

EHRS also responds when made aware of health and safety concerns by the ULAR staff or others users of the animal facility.

back to top



IX. REVIEW EFFECTIVENESS

The review process is effective when investigators properly identify and evaluate all of the hazard(s) in their protocol, ensure that all lab staff is up to date in health and safety training and submit the properly completed forms to the appropriate offices.

The review of protocols involving biological hazards provides the investigator and ULAR with specific biosafety guidelines for work in the laboratory and in the animal facility. It is the responsibility of the investigator to inform laboratory staff who work with research animals of EHRS recommendations and to ensure laboratory staff adhere to those recommendations as well as the policies and procedures established by ULAR while working the animal facility.

If the investigators use hazardous materials in their animal research but do not complete section 5 of IACUC Form A, the protocol may not be reviewed by EHRS. The IACUC reviewers may or may not recognize a potential hazard prior to giving a protocol full approval.

back to top



X. REVIEW TIMELINESS

EHRS reviewed over 600 animal protocols in 2005.

Time is lost when:

1. The investigator does not realize the need for EHRS review of the protocol.
2. The investigator provides inadequate information.
3. Recombinant materials or transgenic animals have not been registered with the Institutional Biosafety Committee.
4. The investigator fails to respond or comply with a request from the EHRS reviewer(s).
5. An IACUC protocol number has not been assigned to the protocol. Because of the large number of similar animal protocols, EHRS approval letters are not sent to ORA until ORA assigns a protocol number.
6. Forms are incomplete.
7. Old forms that are no longer accepted by ORA are submitted. New forms are available at: http://www.upenn.edu/regulatoryaffairs/animal/forms.html