Thus, within the current scope of NIH guidelines, the RAC should adopt safety reporting guidelines that harmonize with the IND reporting rules and format outlined in 21 CFR 312 and current international standards. As noted, those regulations require sponsors to notify FDA of any serious and unexpected adverse event associated with the use of the drug being tested in the clinical trial within 7 days if the event was fatal or life-threatening, or 15 days for other serious and unexpected events. This process ensures that federal officials have the information they need to make a timely determination about the progress of a trial and whether patients’ safety is in danger. In addition, it protects patients’ privacy rights and maintains the integrity of the drug development process. Harmonization with the FDA requirements would simplify the reporting requirement and would lead to increased compliance.
Coordinating the procedures of the FDA and NIH will also help ensure a discussion between the two agencies as they interpret the data. It is essential that the review and interpretation of submitted safety data be coordinated between FDA and NIH to ensure a single, agreed-upon interpretation of those data. Specifically, if after an initial review, the RAC feels there may be potential safety concerns, we recommend a joint evaluation of the data between the RAC and the FDA. The results of these joint deliberations could form the basis of public discussion at the RAC meeting. Prior to any presentation of the conclusions from this assessment, however, the sponsor should be made aware of the findings, and have the opportunity to provide additional information or comment. Sponsors should also have the opportunity to present data at the RAC meeting.
Although the NIH guidelines and FDA reporting requirements would coincide, the respective roles of the agencies would remain the same. FDA would remain the only agency with regulatory authority and the ability to approve a trial or put a trial on hold. The RAC would maintain its role as an educational advisory body.
Reporting of adverse events to NIH/RAC in addition to FDA is only acceptable to BIO in the case of gene therapy because of the established role that NIH has to oversee novel human gene therapy experiments. Our proposed reporting structure is not applicable to the development process for other drugs and biological products.
The industry’s willingness to provide adverse event data to the RAC is contingent upon an agreement between NIH and industry that would memorialize how the data will be used. OBA would be responsible for ensuring that patient privacy rights are protected and that trade secret data remains confidential. How will the agency carry out that mission? What patient data will become public? How will the RAC ensure that confidential commercial and financial information from companies will not be disclosed? How will the RAC use this data to complement the oversight role of the FDA? We call upon the OBA to develop a proposal that would answer these questions. OBA should work with FDA and industry to develop a process that will provide the RAC with adverse event data it needs to do its job effectively, but also will ensure that this information will be used appropriately. The industry stands ready to work with OBA and FDA on this matter. We look forward to this collaboration.
Once the RAC, FDA, and industry agree to a reporting structure, BIO recommends that the process have a life span of one year. At the end of that year, industry will, in consultation with RAC and FDA, evaluate the system to determine if it should continue or if it needs modification.
The initial promise of gene therapy technology has not yet been realized. Despite the recent tragedy at UPenn, data obtained in gene therapy trials thus far are encouraging, and it is BIO’s belief that gene therapy currently has a good safety profile, as determined by more than a decade of pre-clinical and human clinical data. The biotechnology and pharmaceutical industry involved in gene therapy development fully supports presenting to the public a practical and balanced assessment of the benefits and risks of the technology.
The organizations represented by BIO remain fully committed to providing the resources necessary to fully realize the promise of gene therapy for the treatment of serious medical conditions such as cancer, cardiovascular disease, and genetic and metabolic diseases. It is vital that patients with these conditions have access to novel and innovative therapies. To meet that end, gene therapy research and clinical trials must be regulated in an efficient, thorough, and expeditious manner, in accordance with clear federal statutes and guidelines.