Paving The Way for Operation Warp Speed
2019 Removal of the NIH Recombinant DNA Advisory Committee (RAC) from routine biosafety oversight
Coincidence or just another piece of OPERATION COVID?
I am talking about Revision of the NIH Guidelines FOR RESEARCH INVOLVING RECOMBINANT OR SYNTHETIC NUCLEIC ACID MOLECULES in April 2019 altered federal oversight of HGT clinical research , with the removal of the NIH Recombinant DNA Advisory Committee (RAC) from routine biosafety oversight of clinical and nonclinical research.
Until 2016, every HGT trial subject to the NIH Guidelines had a prereview by the RAC, which were the national and world level experts in gene transfer and biosafety, before a trial ever came to the local committees.
The RAC was renamed and repurposed in 2019 and no longer conducts routine reviews of clinical trials.
The amount of biosafety review that now takes place is not always clear and not always public. The RAC meetings were public.
Before 2019, Institutional Biosafety Committees (IBCs ) also reviewed risks to the trial participant. So, the informed consent document had to be reviewed by both the IBCs and IRBs. Then the FDA and the NIH decided in 2018 that IRBs could review them on their own, and the IBCs did not have to evaluate such risk.
Strikes me as clearing the minefields for the Operation Warp Speed Tanks that were to deliver their payload into billions of arms
This is the current NIH guideline
https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.pdf
What did RAC do? This paper from 2014 explains.
At the behest of a RAC member in the early 1990s, the RAC began to review adverse event reports as part of semiannual reviews of NIH data management reports on gene transfer trials. Since 1997, tables of adverse event reports from gene transfer trials have been posted with the RAC meeting minutes.
In 1995, an ad hoc committee appointed by the director of NIH to advise on the future role of the RAC concluded that gene transfer research was different enough from other research to deserve continued public scrutiny. The committee concluded that the RAC should, however, no longer review every protocol; rather, its reviews should focus on protocols raising special concerns (e.g., those using novel vectors) (Verma, 1995).
NIH and FDA agreed in 1995 that NIH would limit its public reviews to novel protocols, while FDA would assume primary responsibility for reviewing gene therapy protocols (Rainsbury, 2000; Wolf et al., 2009).
The RAC's public reviews are selective, limited to protocols that present certain safety or ethical issues.
The current charter of the RAC describes its role as providing “advice to the Director, NIH, on matters related to: (1) the conduct and oversight of rDNA, including the content and implementation of the NIH Guidelines for Research Involving Recombinant DNA Molecules, as amended, and (2) other NIH activities pertinent to rDNA technology” (NIH, 2011, p. 1).
The current guidelines also specify that 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 (human gene transfer) are to be subject to a review process involving both NIH/OBA and the RAC (NIH, 2013c).
Within the entire gene transfer research oversight system, the RAC is the only oversight or regulatory body that provides a public venue for the review of a protocol. FDA, IRBs, and IBCs all convene in private; however, IRBs and IBCs often include nonscientists as members of their committees.
Currently, the RAC is “a panel of up to 21 national experts representing various fields of science, medicine, genetics, ethics, and patient perspectives that considers the current state of knowledge and technology regarding research with recombinant or synthetic nucleic acid molecules” (NIH, 2013a, p. 2).
A majority of the 21 voting members must have expertise in relevant scientific fields, such as molecular genetics, molecular biology, and rDNA research, including clinical gene transfer research. Further, at least four voting members must have expert knowledge in fields dealing with public health and safety, such as human subjects protection, environmental safety, ethics, and law. An FDA CBER representative is also an ex-officio member of the RAC.
Terms for the chair and committee members, who are appointed by the director of NIH, are 4 years. The RAC meets in person quarterly in an open forum, with a webcast of the full meeting and the meeting transcript later posted online.
Gene Transfer Safety Assessment Board consists of clinical members of the RAC who meet quarterly to review all serious adverse events that may possibly be trial-related as well as summaries of more than 400 amendments and annual reports filed on active protocols (Corrigan-Curay, 2013).
The safety board reviews safety information from gene transfer trials for the purpose of assessing toxicity and safety data across trials and identifying significant trends or single events, and it reports such findings and aggregated trend data to the full RAC (Corrigan-Curay, 2013; NIH, 2013c).
OBA considers this role as being akin to a “national Data Safety Monitoring Board,” responding in real time to emerging information (Corrigan-Curay, 2013).
According to OBA, protocol review by the RAC serves many functions (Corrigan-Curay, 2013), including
optimizing clinical trial design, increasing safety for research subjects, and, in some instances, strengthening biosafety protections necessary for researchers, health care workers, and close contacts of research subjects;
improving the efficiency of gene therapy research by allowing scientists to build on a common foundation of new knowledge emanating from a timely, transparent analytic process; and
informing the deliberations of FDA, the NIH Office of Human Research Protections (OHRP), IRBs, IBCs, and other oversight bodies, whose approval is necessary for gene therapy research projects to be undertaken
There are policy exemptions in place for certain types of human gene transfer protocols that are exempt from the RAC review. Appendix M Section VI-A of the NIH Guidelines details exemption for protocols for certain gene transfer vaccines against infectious diseases, specifically, those using plasmids and other vectors that usually do not persist (e.g., adenoviral vectors) and usually are administered intradermally or intramuscularly. The RAC does, however, review vaccine protocols that include a recombinant or synthetic construct that is not a microbial antigen, such as a gene to express a cytokine
https://www.ncbi.nlm.nih.gov/books/NBK195894/
Its not clear if mRNA Vaccines would have been exempt since the modified mRNA is a synthetic construct and the vector is a novel LNP assembly
Trials that fit the characteristics described in Appendix M-VI-A of the NIH Guidelines, however, are exempt from the RAC review and OBA reporting requirements set forth in Appendix M-I.
Exempt from Appendix M-I are:
• Experimental vaccines studied in humans in which induction or enhancement of an immune response to a vector-encoded microbial immunogen is the major goal.
• Immune response to the experimental vaccine has been demonstrated in model systems, and
• The persistence of the vector-encoded immunogen is not expected.
In order to avoid delays in the protocol development process the protocol team should determine early on whether a protocol should undergo RAC review. RAC meets only 4 times a year and submissions need to be received by OBA eight weeks prior to the scheduled public RAC meetings. The protocol team will document this decision in the minutes of the protocol team meeting and will promptly notify the manufacturer of the product of this decision for timely preparation of the RAC submission material.
Submission of protocol for RAC review
If a new vaccine candidate is not exempt according to the above criteria (appendix M-VI-A of the NIH guidelines for research involving recombinant DNA molecules), the protocol team and the manufacturer of the product must prepare and submit a package of information for RAC review.
• The documents required for this submission are:
• A cover letter signed by the principal investigator and co-investigators that :
o Acknowledge that the documentation complies with the requirements outlined in appendix M-I-A.
o Identify the IBC and IRB that are responsible for approval of the protocol.
o Acknowledge that no enrollment will take place until RAC review is completed, IBC and IRB approval is obtained and the protocol is considered safe to proceed by the FDA.
• A scientific abstract.
• A non-technical abstract.
• The proposed clinical protocol, including tables, figures and relevant manuscript.
• The proposed informed consent document.
• CVs for the principal investigator(s).
https://rsc.niaid.nih.gov/sites/default/files/IBCReqsRecombinantDNA.pdf
Oh well, I guess we will never know if it would have made a difference. Probably not given Operation Warp Speed was a Militarized Project and seemingly prioritized Speed over Safety.