505(b)(2) For the approval of a clinically significant improvement to a previously approved drug by allowing for the use of data not developed by the NDA applicant (without having to repeat all the drug development work done for the initial indication). Thus, potentially offering significant drug development and marketing advantages.

505(b)(2) submissions can be advantageous because they can often lead to a faster route to approval when compared to traditional development pathways such as 505(b)(1) NDA, while creating new, differentiated products with commercial value. A 505(b)(2) application can be utilized for a variety of different marketing applications, including:

• Drugs with new indications
• New combination products

505(b)(2) Pre-IND Meeting

The pre-investigational drug application involves a pre-IND meeting with the FDA before the eventual IND filing. The pre-IND process for the 505(b)(2) vs. 505(b)(1) pathways differs greatly. Major distinctions include:

• Order of steps: Unlike the 505(b)(1) process, 505(b)(2) is initiated with the pre-IND meeting, moving into formulation development and additional studies (if deemed necessary), and concluding with the IND filing.
• Goals and strategy of the pre-IND meeting: The objective of a 505(b)(2) pre-IND meeting is to gain input from the FDA and concurrence with the studies, clinical research plans, and chemistry, manufacturing and controls (CMC) strategy in order to minimize the number of new studies required for approval. Obtaining this input from the FDA can be vital to securing investments for many companies.
• Number and type of required studies: The ability to use public data or previous FDA findings through the 505(b)(2) pathway may allow for programs to conduct bridging studies, preventing the need for some clinical or nonclinical studies traditionally required for a 505(b)(1).
• Timing of CMC work: The clinical trial materials for Phase 1 studies should be representative of the commercial manufacturing process (including packaging) for a 505(b)(2) product. Generally, the three stability batches to be used for the determination of shelf-life are to be prepared at this time as well. As a result, a great deal of CMC work must be completed prior to the initiation of studies, even for Phase 1.
• Timing of studies: Due to the reliance on pre-existing data, clinical studies can be started simultaneously and developed in parallel. With the reliance on pre-existing data, a Phase 3 study can be initiated before completing all the Phase 1 studies and without having to conduct a Phase 2 study, which saves time and money.
• NIV’s strategy: Use pharmacology (i.e., combination drugs) to enhance the brain neuroplasticity, promote more neuron growth and rewiring, and improve a patient’s functional recovery
• NIV-001 commercial sales to begin after Phase III Trials, around year 5, and generate EBITDA (cash flow) of $30 million after 12-24 months of commercialization