VACCINE CLINICAL TRIALS:

Transcription

1 VACCINE CLINICAL TRIALS: What triggers an IBC review? Marcia Finucane, MS, CBSP Biological Safety Officer Environmental Health and Safety June 2, 2015

2 NIH GUIDELINES FOR RESEARCH INVOLVING RECOMBINANT OR SYNTHETIC NUCLEIC ACID MOLECULES Each institution (and the Institutional Biosafety Committee acting on its behalf) is responsible for ensuring that all research with recombinant or synthetic nucleic acid molecules conducted at or sponsored by that institution is conducted in compliance with the NIH Guidelines

3 IBC REVIEWS: All research with recombinant or synthetic nucleic acid molecules All research with infectious agents of risk group 2 or above All research with potential for occupational exposure to zoonotic disease All research with Select Agents or Toxins

4 NIH GUIDELINES FOR RESEARCH INVOLVING RECOMBINANT OR SYNTHETIC NUCLEIC ACID MOLECULES Section III-C & Appendix M : Human Gene Transfer Trials Research proposals involving the deliberate transfer of recombinant or synthetic nucleic acid molecules, or DNA or RNA derived from such nucleic acid molecules, into human subjects

5 VACCINE EXEMPTION: ONLY FROM APPENDIX M-I OF NIH GUIDELINES ALL OTHER REQUIREMENTS OF THE NIH GUIDELINES APPLY VACCINE EXEMPTION WAS INTENDED TO STREAMLINE THE DEVELOPMENT OF NEW VACCINES AGAINST INFECTIOUS DISEASES

6 EXEMPTION REQUIRES THAT ALL THREE OF THE FOLLOWING CONDITIONS ARE MET: The major goal is the induction or enhancement of an immune response to a vector-encoded microbial immunogen Such an immune response has been demonstrated in model systems The persistence of the vector-encoded immunogen is not expected

7 EXEMPTION MEANS PROTOCOL DOES NOT: Have to be registered with NIH OBA Undergo RAC review Have to adhere to reporting requirements under Appendix M-I of the NIH Guidelines It still requires LOCAL IBC review / approval before research participants are enrolled

8 Examples of trials which DO NOT fall under the vaccine exemption: The principal goal of the study is to treat a precancerous or cancerous lesion Not infectious disease Administration of a microbial immunogen in combination with recombinant DNA that encodes for a cytokine or other immune stimulant, for example recombinant interleukin-2 recombinant DNA encoding the cytokine is not of microbial origin

9 CAN BE SUBMITTED ON A VOLUNTARY BASIS Particularly if the investigator believes that a clinical trial involving the administration of recombinant DNA presents scientific, safety, or ethical issues that would benefit from RAC review Investigators who submit trials voluntarily will be expected to comply with all aspects of the protocol review and reporting requirements

10 WHAT DOCUMENTS ARE SENT TO THE IBC? New submission: IBC form (EHS webpage/forms/biosafety)) Investigator s Brochure Protocol Informed Consent Any correspondence from NIH or RAC Preferably sent to IBC before COMIRB review Amendment or renewal: Everything that is sent to COMIRB Simultaneous with COMIRB review

11 WHAT DOES THE IBC REVIEW? Public Health Considerations Risk of transmission (horizontal or vertical), environmental Precautions/mitigation against transmission Personnel involved with protocol Training, expertise, medical surveillance, vaccinations Adequacy of laboratory, pharmacy, clinical facilities How will safety reporting be handled? Informed consent specific to UCD sites involved Release of information, patient privacy, long-term followup, autopsy

12 RED FLAG WORDS: MAY NEED IBC REVIEW Recombinant Viral Vector (adenovirus/-al, lentivirus/-al, etc.) Plasmid(s) Live or attenuated vaccine DNA vaccine Human gene transfer (HGT) RNA, DNA, synthetic nucleic acid molecules Transduction, transfection Autologous, allogenic transplantation (in combination with recombinant or transduction/transfection)

13 DOES NOT REQUIRE IBC REVIEW: Inactivated vaccines Pathogen inactivated May take several doses because of weaker immune system response Subunit vaccines May use rdna technology to express antigenic molecules in yeast/bacteria Traditional vaccines May not work against all viral pathogens which need cell mediated immunity to clear virus

14 FYI: HUMAN GENE TRANSFER VS THERAPY Transfer: broad category, introducing a genetic sequence with any function, i.e. fluorescent protein marker Therapy: clinical application of transfer technology, with the intent to produce beneficial health consequences Reserved for product/intervention with demonstrated safety & efficacy Not for interventions still being investigated

15 REFERENCES NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules Select Agents and Toxins CDC/NIH: Biosafety in Microbiological and Biomedical Laboratories,

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