Investigational New Drug (IND) Application is submitted to the FDA if an unauthorized drug is intended to be used for clinical investigation or treatment in the US. INDs come under the regulation of Title 21, Code of Federal Regulations, Part 312.
Individualized ASO INDs are classified as research INDs (as against commercial, where drugs of commercial intent are being developed). Electronic submissions of IND applications and use of data standards are encouraged, however eCTD formatting is not mandatory for non-commercial INDs. Prior to any N-of-1 patient receiving an ASO treatment, research INDs need to be filed and approved by the FDA.
The number of subjects enrolled has no bearing on whether the study is subject to IND regulations. So even for N-of-1 trials, INDs are still required. When reviewing and approving N-of-1 INDs for individualized ASOs, the FDA’s primary objective is to assure the safety and rights of human subjects in the study and a safety threat is the only reason for clinical hold for this type of IND.
The IND application should be submitted by the sponsor of the application. For individualized ASOs, the clinician responsible for administering the ASO formulation to the patient and tracking treatment progress would be the sponsor and is referred to as the sponsor-investigator.
Early FDA Interaction
FDA recommends that sponsors request a pre-investigational new drug application (pre-IND) meeting with the appropriate review division as soon as a participant and at least one potential individualized ASO drug product (for which there are convincing proof-of-concept data) are identified.
The primary purpose of this meeting is to review and obtain feedback on the design of preclinical studies, the design of the initial IND study, and product manufacturing and quality controls needed to initiate human studies.
Upon receipt of the IND by FDA, an IND number will be assigned, and the application will be forwarded to the appropriate reviewing division. The reviewing division will send a letter to the Sponsor-Investigator providing notification of the IND number assigned, date of receipt of the original application, address where future submissions to the IND should be sent, and the name and telephone number of the FDA person to whom questions about the application should be directed. Studies shall not be initiated until 30 days after the date of receipt of the IND by FDA unless you receive an earlier notification by FDA that studies may begin.