Registrations arrive in the Biosafety Office by campus mail, US mail, FAX, or hand delivery. Incoming Registrations are screened by the Biosafety Office to determine:

1. Has the registration been completed correctly?
2. Is the registration signed?
3. Does the registration indicate the use of agents that have not been registered by the PI? For example, propagation of adenoviral vectors is frequently done with HEK293 cells, a human cell line. Thus, any investigator that registers adenoviral vectors is checked for human tissue registration. If none is noted, the investigator is queried as to whether human cells will, indeed, be utilized. Likewise, Recombinant or Synthetic Nucleic Acid Molecules Registrations that indicate transduction of cells are cross-checked for registered viral vectors and the investigator queried if none are found.

Once a registration is determined to be complete, the registration is coded for entry into the database and a letter is sent to the investigator indicating the status of the registration. The following code letters precede the registration numbers transmitted to investigators:

• DE - Recombinant or Synthetic Nucleic Acid Molecules Registration exempt from formal IBC review as defined in section III-E of the NIH Guidelines                                                  
• DN - Recombinant or Synthetic Nucleic Acid Molecules Registration subject to formal IBC review
• P - Infectious Agent/Pathogen registration. All are reviewed by the IBC.
• T - Toxin registration. All are reviewed by the IBC.
• GT - Clinical Research involving Gene Therapy, the introduction of Recombinant or Synthetic Nucleic Acid Molecules, potential Infectious Agents/Pathogens, or Biological Toxins into human subjects. All are reviewed by the IBC.
• BC - Human tissue registration for clinical studies. Reviewed by the Biosafety Office.
• B - Human tissue registration for laboratory-based studies. Reviewed by the Biosafety Office.

Submissions for IBC review should be mailed, faxed or otherwise delivered to the Biosafety Office at the following address:

Fax: 410-955-5929

Because of the nature of the submission, the IBC requires the investigator to submit 14 copies of any study involving human subjects that requires IBC review and approval.

Johns Hopkins Bloodborne Pathogen Module - links to the Johns Hopkins Bloodborne Pathogens Online Training Module. This course is intended for those individuals who can not attend the instructor-led course offered quarterly by HSE.

• Centers for Disease Control - links to the homepage of this agency.
• CDC Office of Health and Safety - provides excellent links to information regarding the Select Agent program, transport of biologicals, and Biosafety.
• CDC/NIH Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th (New) Edition.
• NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules
• NIH Database on Human Gene Transfer Trials
• NIH Office of Biotechnology Activities
• FDA Center of Biologics Evaluation and Research
• Johns Hopkins School of Medicine IRB Office
• Bloomberg School of Public Health IRB
• Homewood IRB

All research involving Recombinant or Synthetic Nucleic Acid Molecules (naturally-derived or synthesized DNA or RNA) on campus must be accompanied by a valid Recombinant or Synthetic Nucleic Acid Molecules Registration. This is an NIH Requirement. An investigator does not need to file a separate registration for every project performed or funded in the laboratory if the projects involve similar recombinant or synthetic nucleic acid molecule activities. Clearly distinct projects such as "expression of signal transduction molecules in cell lines to assay function" and "expression of modified viral stocks to assay modes of infection" would require separate registrations. Be advised, however, that the NIH expects the investigator to identify the genetic elements or nucleic acid molecules that will be inserted into a given vector or host and to report the identity of constructs designed to replicate or express recombinant protein.  Recombinant or Synthetic Nucleic acid Molecules that can be used to express a biological toxin must also be registered for that toxin (see below).  Experiments involving Recombinant or Synthetic Nucleic Acid Molecules that are not exempt as defined in the NIH Guidelines are submitted to the Institutional Biosafety Committee (IBC) for review and assignment of Biosafety Containment Levels (BSL levels). IBC approval must be received prior to the commencement of the research project.

All Infectious Agents and Pathogens on campus must be registered through the Biosafety Office. Organisms listed as Select Agents may require additional effort (see Select Agent Policy, HSE 505 for details) This is a JHI Policy requirement. Each pathogen should be registered on a separate form. The only pathogens that can be combined on a single form are "like agents". For example, an investigator wishing to study Methicillin-resistant Staphylococcus may register this strain and a control strain of Staphylococcus on one registration. Likewise, someone wishing to register multiple forms of lentiviral vectors may register all on a single form. One may not, however, register lentiviral vectors and adenoviral vectors on the same form. All Infectious Agent/Pathogen registrations are reviewed by the IBC for the use of appropriate safety procedures and facilities. IBC approval and designation of appropriate BSL levels is necessary before commencement of the research project.

All Biological Toxins, organisms that generate Biological Toxins, and recombinant or synthetic nucleic acid molecules that can be used to express Biological Toxins must be registered through the Biosafety Office. Registration of Select Agent Toxins is mandatory and may require additional effort including CDC notification (see Select Agent Policy, HSE 505 for details). All Biological Toxin registrations are reviewed by the IBC and approval is necessary before commencement of the research project.

Human Subjects Research Involving the Introduction of Recombinant or Synthetic Nucleic Acid Molecules, Potential Infectious Agents or Pathogens, or Biological Toxins in Human Subjects

Investigators who wish to introduce recombinant or synthetic nucleic acid molecules, potential infectious agents or pathogens, or biological toxins into human subjects must receive IBC approval in addition to IRB approval. The IBC evaluates the protocol for patient, staff, and environmental safety issues in their review. The following documents are required by the IBC for review of a Human Subject protocol:

1. Recombinant or Synthetic Nucleic Acid Molecules registration form, if applicable.
2. Infectious Agent/Pathogen registration form, if applicable.
3. Biological Toxin registration form, if applicable
4. Human tissue registration form.
5. Investigator's brochure (usually the same one submitted to the IRB)
6. Sponsor's Protocol
7. Appendix M, if applicable, with Hopkins-specific responses. Please note that many studies include an Appendix M written by the sponsoring company for a PI at some other institution. The answers provided (who is doing the work, where will it be done, how many patients, etc.) may or may not reflect what will be done here at JHMI. In these cases, the IBC requests that the investigator provide answers to the Appendix M questions that specifically address the Hopkins component(s) of the project.
8. Any RAC communications/approvals
9. Any FDA communications/approvals
10. IRB comments/approvals

See Links section above for further information from the BSPH, JHMI, and Homewood IRB websites regarding research involving human subjects.

OSHA requires bloodborne pathogen training for all individuals who may come in contact with human blood, bloodborne pathogens, and other potentially infectious materials (29CFR part 1910.1030). Other potentially infectious materials are defined by OSHA as:

1. The following human body fluids:
   semen, vaginal secretions, cerebrospinal fluid, synovial fluid, pleural fluid, pericardial fluid, peritoneal fluid, amniotic fluid, saliva in dental procedures, any body fluid that is visibly contaminated with blood, and all body fluids in situations where it is difficult or impossible to differentiate between body fluids.
2. Any unfixed tissue or organ (other than intact skin) from a human (living or dead).
3. HIV-containing cell or tissue cultures, organ cultures, and HIV- or HBV-containing culture medium or other solutions; and blood, organs, or other tissues from experimental animals infected with HIV or HBV.

Human Tissue Registrations are reviewed upon receipt by Biosafety Office personnel. Investigators should expect to receive written confirmation of human tissue registration within a week of document delivery to the Biosafety Office.

Human tissues and body fluids in the clinical setting are handled under "Universal Precautions" or "Standard Precautions". These definitions do not neatly fit into the common biosafety containment levels of laboratory-based research. For this reason, clinical human tissue registrations are handled as a separate category. A clinical researcher only needs to possess one clinical research registration. There is no need to complete a registration for every clinical study as long as the list of personnel on the registration who may come in contact with the human tissues is inclusive for all studies.

Since Question 8 of the Human Tissue Registration Form deals specifically with personnel, it is important that this section is filled out completely and accurately. The PI's name should always be listed. Then, if the blood draw/sample acquisition is done by the GCRC or Express Testing, or the nursing staff on CMSC 9 (for example) the PI can enter this on the next line of question 8. If the PI has an assistant or assistants who will handle or ship the tissue, these names should be listed in question 8 along with any additional investigators who may come in contact with the human tissue. Since human samples in clinical research are derived in standardized manners (blood draws, tissue samples, etc.), Clinical investigators do not need to complete question 9a-f of the form.

Human tissues (including human-derived cell lines) and human body fluids used in the laboratory setting are handled with BSL2 containment practices which include the use of a biosafety cabinet (or other approved containment procedures) for manipulation of the material.  An investigator only needs to have one human tissue registration for laboratory-based research. Investigators who maintain research laboratories and also oversee clinical studies should maintain a clinical-focus and a laboratory-focus registration given the differences between BSL2 and universal or standard precautions. Since research laboratory practices are not standardized and prone to creative influence, laboratory-focus human tissue registrations must include answers to question 9a-f.