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02.0 EMUA

The EMUA provides the means for a authorized MUA (PI in most cases) to register etiological agents with EH&S and gain approval from the IBC for safety procedures that will be followed to ensure the health and well-being of lab staff, housekeepers, waste handlers, animal health staff, and spill response teams.

An EMUA is required for:

  1. All work covered by the NIH guidelines, including exempt work excluding the purchasing of transgenic animals.
  2. Work with any infectious material in Risk Group 1, 2, 3 or 4 (as defined by the NIH Guidelines) or which is known to be infectious to humans, plants, or animals in lab, culture, or with the animals;
  3. Recombinant DNA (including gene transfer) use in human subjects to be administered at the Center;
  4. Work with recombinant DNA or RNA or pathogens in labs or animals;
  5. Handling and use of registered toxins (see section 11);
  6. Handling and use of select agents as defined by CDC;
  7. Production of transgenic animals; or
  8. Xenotransplantation;
  9. Work with human cells, tumor cells or cell lines;
  10. xNon-human primate cells.

Use of non-infected blood, human tissue, or body fluids does not require an EMUA. Researchers should handle these using universal precautions as addressed under in Section 7, Bloodborne Pathogens.

Purposeful isolation and amplification of an etiologic agent from blood, tissue or body fluids does require an EMUA. Non-human primate blood and tissue does require an EMUA.

An approved EMUA must be obtained prior to commencement of work with infectious agents or recombinant DNA/RNA (rDNA). The EMUA is submitted to EH&S for review to ensure all safety aspects of the project have been adequately addressed. The IBC reviews and approves all projects working at Biosafety Levels 2, 3 or 4.

An EMUA for work with non-rDNA projects which have a maximum Biosafety Level of 1 (BSL-1) can be approved by the BSO. Work with rDNA which is exempt from the NIH Guidelines can also be approved by the BSO. The BSO can defer any approval to the IBC. A PI submitting his or her first EMUA application must also submit the Training and Experience form. This form is not required for renewals.

EMUAs must be renewed every five years; this is done by submitting an EMUA Application Form. Any change in etiological agent, labs used, staff, or procedures requires the submission of an EMUA Amendment Form (see Section 2.3, Use of Human Subjects).

All EMUA and biosafety related forms can be obtained from EH&S.

New grants and contracts submitted for funding which involve the use of infectious agents or recombinant DNA are not required to have a pre-approved EMUA at the time of grant submission. Once a grant is funded, the PI is responsible for submitting an EMUA or amendment to cover the research. For Competing and Non-Competing Renewal submissions, the PI must have a previously approved EMUA covering the grant on file with EH&S, which will be verified by ensuring the project title is listed on the PI's EMUA. New projects may be quickly added to an existing EMUA using an EMUA Amendment Form as along as there is no increase in biosafety level. Change in biosafety level requires IBC approval.

The following criteria must be met before an EMUA can be approved:

  1. The EMUA is complete and provides an adequate description of safety procedures;
  2. The PI has sufficient training, experience, and competence with the proposed level of biological safety to handle the agent safely;
  3. Staff are trained in biological safety (and if necessary, offered vaccinations) so that it is safe to perform the work in the lab; and
  4. The lab facilities are adequate for the level of containment required.
  5. Work which is exempt from the NIH Guidelines must be identified by the PI, along with supporting documentation.

After submission of an EMUA, the BSO will review and contact the PI for additional information if the EMUA is not complete and or does not meet the above criteria.

Revisions to an existing EMUA must be submitted to the BSO via an EMUA Amendment Form (available online or from EH&S directly). Amendments must be made for the following protocol modifications:

  1. A new project title (or any change in title);
  2. Use of a new infectious agent or registered toxin;
  3. Use of new labs or change in room numbers;
  4. Addition or removal of workers from the project;
  5. Change in procedure that increases risk to staff;
  6. Addition of new transgenic animal or plant production or xenotransplants; or
  7. Adding work with animals.

Amendments to EMUAs for work at a biosafety level no greater than BSL-1 or are exempt from the NIH guidelines, that remove a lab or add or remove personnel can be approved by the BSO. Any increase in biosafety level must be approved by the IBC.

Any recombinant DNA research performed at the Hutchinson Center involving the use of human subjects requires IBC approval. Research involving human subjects must also be approved by a qualified Institutional Review Board (IRB). Human gene transfer protocols may require review by the National Institutes of Health (NIH) Recombinant DNA Advisory Committee (RAC). If so, the RAC review must take place prior to review by the Center IBC. No research participant may be enrolled in a clinical study until the IBC and IRB approvals are obtained. A study already reviewed and approved by another IBC or human subjects committee must still be approved by the Center IBC if the Center is a clinical trial site.

For these protocols, the PI must submit the following information to the Center IBC:

  1. The IBC Research Review Submission Form;
  2. Complete IRB application packet and supporting documents that include at least the following:
    1. The proposed protocol (and amendments, if applicable),
    2. The investigator’s brochure,
    3. A proposed consent form(s),
    4. FDA Form 1572, and
    5. A biographical sketch or curriculum vitae (CV) for all staff listed on the FDA Form 1572, including the principal investigator;
  3. Responses to NIH Guidelines Appendices M-II through M-V: Points to Consider;
  4. RAC-sponsor/PI correspondence pertaining to this gene transfer product and clinical trial; and
  5. If the study required public RAC review, include the PI's response to RAC recommendations made during the public review meeting.

The completed review package (four copies) must be sent to EH&S (J3-200) at least two weeks prior to the next IBC meeting. Incomplete or late review packages will be postponed until the next IBC meeting. The review of the above material will generate a Gene Transfer MUA (GMUA), to differentiate it from other biological hazards.

2.3.1 Seattle Cancer Care Alliance (SCCA)

If you will be conducting a study involving the administration of recombinant DNA (rDNA) into human subjects at the SCCA or a UW clinic, the protocol must be reviewed and approved by the IBC for that institution. For additional information, contact EH&S, or call the Human Protections Coordinator at SCCA at 206.288.1287. For studies done at UW facilities, contact the UW BSO at 206.583.7278.

Laboratories at the SCCA will follow the same requirements as noted in this chapter.

2.3.2 Adverse Event Report Requirements for Human Gene Transfer Studies

The NIH Guidelines require immediate reporting of serious adverse events (SAEs) associated with human gene transfer clinical research; see NIH Guidelines, Appendix M for details.

A serious adverse event is defined as any expected or unexpected adverse event, related or unrelated to patient treatment, occurring at any dose that results in any of the following outcomes:

  1. Death;
  2. A life-threatening event (real risk of dying);
  3. In-patient hospitalization (not required as part of the treatment) or prolongation of existing hospitalization;
  4. A persistent or significant disability or incapacity;
  5. A congenital anomaly or birth defect; or
  6. A diagnosis of cancer.

Certain medical events that may not result in death, be life-threatening, or require hospitalization, may also be considered a serious adverse event when appropriate medical or surgical intervention is necessary to prevent one of the outcomes listed above.

2.3.3 SAE Reporting Requirements

Principal investigators who have received approval from the IRB to initiate recombinant DNA use in humans protocol must report any serious adverse event (SAE) immediately upon awareness to the Center IBC, via the BSO (call EH&S or mail your report to J3-200). The PI is responsible for all other SAE notifications required by the NIH Guidelines.

Any recombinant DNA or infectious materials research performed at the Hutchinson Center involving the use of animals requires an approved EMUA. Research involving animals must also be approved by the Center's Institutional Animal Care and Use Committee (IACUC). Any research involving the use of fresh animal tissues originating from non-commercial sources may require investigators to attend Animal Health Resources (AHR) training on zoonotic diseases. Contact AHR for training requirements.

2.4.1 Transgenics

Any new production of transgenic animals or plants must be registered with the IBC. Contact the BSO for more information on registration.

Any transplantation of tissue from one species into a different species should have IBC review and approval. Primary concern is human tissue into an animal model or animal tissue into a human, which requires IBC approval. Contact the BSO for more information on registration.