The Food and Drug Administration (FDA) is a federal agency of the United States Department of Health and Human Services, that regulates the use of drugs within the United States. As per FDA mission statement, “the Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of our nation’s food supply, cosmetics, and products that emit radiation.” Its primary responsibility is ensuring the protection of human subjects who participate in clinical studies testing new drugs such as Investigational New Drug (INDs).
Patient safety evaluation during clinical studies is a critical component in all stages of the drug development life-cycle. Pharmaceutical sponsors need to adequately characterize the safety profile of the drug in order to obtain regulatory approval and marketing authorization.
IND Safety Reports
In the US, prior to the initiation of a first in human clinical trial, pharmaceutical sponsors must submit an Investigational New Drug (IND) application to the FDA as required by law. The FDA reviews the IND (typically within 30 calendar days) for safety to ensure that research subjects will not be subjected to unreasonable risk.
Under 21 of the code of federal regulations (CFR) 312.32(c), the sponsor is required to notify FDA and all participating investigators in an IND safety report (i.e., 7-or15-day expedited report) of serious and unexpected suspected adverse reactions from clinical trials or any other source as soon as possible, but no later than 15 calendar days after the sponsor receives the safety information and determines that the information qualifies for reporting. If applicable, relevant follow-up information to an initial safety report must be submitted as a Follow-up Safety Report as well.
Any adverse event associated with the use of an IND drug in humans should be reported as soon as possible, whether or not considered drug related, including:
- Use in professional practice
- Overdose (intentional and accidental)
- Abuse
- Withdrawal
- Failure of expected pharmacological action (lack of effect)
Electronic Submission Of IND Safety Reports To FAERS
According to the FDA, all sponsors who conduct clinical trials under an IND are required to submit IND safety reports as per 21 CFR 312.32 for suspected adverse reactions (AE) that are observed in the clinical study, at domestic or foreign study sites.
These reports have traditionally been submitted to FDA on MedWatch Form FDA 3500A or on a Council for International Organizations of Medical Sciences (CIOMS) I Form or other narrative forms. Currently these IND safety reports for sponsors of commercial INDs are submitted in eCTD format (electronic common technical document) generally as PDFs, FDA takes this data forms and converts into the International Conference on Harmonisation (ICH) E2B (an international standard for transmitting medicine adverse event reports) to FDA Adverse Event Reporting System (FAERS), which is a very inefficient and labor-intensive process to both tracking review, and regulatory agencies. It is also lack of universal tracking system.
To address these problems, in October 2019, the FDA is establishing a new submission process for investigational new drug application (IND) safety reports when they electronically submit to the FDA FAERS, focusing particularly on this important safety information as structured data. FDA takes this data forms and convert into E2B to FAERS, then further develop some of the technical specifications around the particular data elements in E2B that are required for IND safety reports for the post-market. The new submission process will allow for use of data visualization and analytic tools for review and tracking.
It is also leverages existing processes that are used in the post-market safety reporting such as the ICH E2B data standard and also FDA submission pathway such as the gateway and the safety reporting portal. It also complies with existing FDA Federal Regulations surrounding IND safety reports on 21 CFR 312.32.
The new guidance will improve FDA’s ability to review and track saf...
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