Progress 09/01/19 to 08/31/23

Outputs
Target Audience:The ability to spawn fish in captivity is extremely important to three major industries, food and bait fish aquaculture, ornamental fish aquaculture, and aquatic conservation. Technical and scientific workers within these industries, specifically those tasked with reproducing these species in captivity for either production or research, are the target audience for this project. Both domestic and international audiences would benefit from the commercialization of this work. Changes/Problems:This project had way more than its fair share of delays. COVID and its burden on the FDA to fast track COVID drugs, completely stopped any and all dialogue with what experiments we would need to carry out to gaindrug approvals. And the supply chain interruption, both in raw materials and utilization of FDA approved drug labs for trials, caused massive delays in producing prototype implants for use in required research trials and analytics. When the FDA finally re-opened to non-human drugs, we were hit with the indexing expansion. While this ultimately benefited this project and drug, it caused a complete closure in paperwork submissions until the rule change could go through, which took upwards to 18 months. Finally, when we were on the road to making great headway, NIFA personnel changes and associated communication barriers, caused our last $98k in funds to be withheld until the last month of the project. This caused considerable stress on a project already at the limit of its no-cost-extension. However, me made it in under the wire. What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?For each year of the project, we have attended the Annual Aquaculture Drug Approval Coordination Workshop and have had numerous conversations with the FDA in varioius departments. We have also presented numerous times at Aquaculture America, part of the World Aquaculture Society Conferences, describing our work on development and commercial approval of a spawning implant for fish. These conference presentations have been reported elsewhere in this report and past reports. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? This project successfully identified an analogue of hormone that works best for a very wide variety of species of fish. It developed a new implant applicator gun that can be easily 3d printed from biodegradable materials, can be sterilized between use, and is very easy for the user to operate. Finally we worked on a huge step in gaining FDA approvals for marketing and sales. The last of our successes, FDA approvals, as can be imagined was not easy or quick. Over seven years we have worked with various departments of the FDA to gain approvals and investigate the best pathways forward. Fortunately during the course of this project, an alternative pathway called indexing was expanded to include the drugs used on brood fish, such as our spawning implant. This pathway requires passing of three steps. The first, and argueably the hardest, is eligibilty for indexing where the applicant lays out a huge amount of information including indication for use, need, environmental safety regulations, and, most expensive and intensive, chemical manufacturing and controls protocols. We passed this step and have since moved on to step 2 which is where an expert panel evaluates existing and new literature to judge if the drug meets target animal safety and efficacy standards. We are currently undergoing this step. Finally, in step three, the packaging and warnings need to be approved. Each step cannot proceed until the step prior is fully approved. So we anticipate full indexing within the next year.

Publications

• Type: Conference Papers and Presentations Status: Published Year Published: 2023 Citation: Kirchhoff, N.T. (2023) Summary of Application Process with Spawning Implant for Indexing. Presentation, Aquaculture America 2023, World Aquaculture Society, Feb 23-26, 2023, New Orleans.

Progress 09/01/21 to 08/31/22

Outputs
Target Audience:Small marine finfishare economically important for three main industries, marine baitfish for recrecational fishing live bait, the ornamental aquarium trade, and conservation dependent species for aquariums and restocking. All three industries are target for the work completed in this project. Changes/Problems:We were forced to request another extension of this project, which was accepted. There were signficant delays due to COVID that continued to cause supply chain and government delays within the FDA. Supply chain, meaning it took us nearly 18months to obtain one of our major ingredients for our implants due to COVID supply chain disruption, as well as delays in some of the instruments needed to manfacture the drug. Government delays also included the over ayear long lock-out of the drug application submission system while a decision was made regarding the expansion of indexing to include finfish broodstock. What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?We attended the 28th Annual Aquaculture Drug Approval Coordination Workshop in Bozeman, Montana. This included private meetings with the AADAP team as well as more open discussions with some potential customers (such as the Fish and Wildlife Service) and CVM members. We updated all members on the progress of our drug and our intent to submit for index approval. We also attended Aquaculture America Conference in San Diego, California. This is a very large aquaculture industry conference where we had several private meetings with potential customers and government officals regarding our drug approval applicationexperience, progress, and intent to have a product on the market soon. We also did a presentation to the audience at large regarding our entire business, i.e. hatchery and drug, including the development of this spawning implant. What do you plan to do during the next reporting period to accomplish the goals?During this next reporting period we aim to (1) submit our application for Indexing of our spawning implant. This is a three step process and we hope to have at least 2 of the three steps submitted and accepted by end of this reporting period. This includes the intend to index document as well as our expert panel findings. We have already chosen, contacted, and have our expert panel on hold for the second step in this process. (2) we also aim to finish analytics on our drug ingredients, batch validation, and final methodology completed to FDA standard.This includes getting some implants manufactured under the slighly new methology and ingredient sourcing to trial side-by-side with our origional formulation to ensure maintained efficacy. (3) we will manufacture a few more prototypes of our applicator gun and provide them to our two origional farm trial partners for feedback.

Impacts
What was accomplished under these goals? We are continuing to work on clarifying the pathway forward for FDA approvals. This included conducting some more animal efficacy trials, refine the applicator gun as well as aiding the expansion of drug Indexing as a pathway for broodstock fish drug approval. We conducted a few more spawning trials on fish at our hatchery utilizing the spawning implants we are aiming to get FDA approval for sale as well as the applicator gun we developed. The gun required some refining to ensure best user safety and ease of use and cleaning. Most of this reporting period included refining the pathway forward for FDA approvals. This included (1) working with our consultants and manufacturing analytics company to validate major and minor ingredient sourcing and purity. We were forced to swap out some ingredient manufactures or even whole ingredients due to updated FDA and industry guidence. This required finding new sources, prices, protocols on validating purity, etc. And refinement of required FDA analytics required to be collected for shelf-life, batch validation, etc. for continued drug commercialization and approval.(2) working with the Aquatic Animal Working Group, Minor Use and Minor Speices (MUMS), FDA and the Center for Veterinary Medicine (CVM) to expand the guidence document on indexing of some animal drugs to include broodstock finfish. This included several meetings, webinars, facilitating favorable public comments to be submitted by potential customers and industry members, etc.This was a huge milestone as it significantly streamlined the approval process and trials required to get our product to commerical sales. However, this step was not with its own set of delays. As once the guidence document was sent out for public comment and then internal evaluation, all we could do was wait. Meaning no finfish broodstock drug applications could be submitted in any form until a decision was made. Fortunately a decision was made in late summer 2022 and it allowed for indexing expasion to include finfish broodstock.

Publications

• Type: Conference Papers and Presentations Status: Accepted Year Published: 2022 Citation: Kirchhoff, Nicole T. (2022) Advancing marine fin fish aquaculture: an international journey from academia to business owner. Women of the Water, Mote Marine Lab. 14-15 June 2022
• Type: Conference Papers and Presentations Status: Accepted Year Published: 2022 Citation: Kirchhoff, Nicole T. (2022) OPERATING A MARINE BAITFISH AND FOOD FISH HATCHERY: TRIALS, TRIBULATIONS, AND OUTLOOK FOR THE FUTURE. Aquaculture America, San Diego, CA 28 Feb- 4 Mar 2022.

Progress 09/01/20 to 08/31/21

Outputs
Target Audience:Covid put a substantial delay on my project, with restriction of travel, cancelling of trade events, and temporary closure of some offices including FDA. However, we were able to make commercializationprogress with discussion of our product with several potentialmanufacturers, FDA regulatory authorities and participated in an electronic meeting of the Aquatic Animal Drug Partnership this past July. We are anxious to get our product moving through approvals and manufacturing now that most places are at least somewhat open and paperwork has started moving forward again. We have also been in constant contact with several potential customers including private aquaculture facilities, universities, NGOs and government labs. They are very anxious for our product as current there are none approved on the market and the one research only product is no longer available. Changes/Problems:As explained earlier, COVID caused significant delays to our progress this past year. In addition to to normal delays business have faced due to the pandemic. Our product requires working closely with the FDA and pharma manufacturers to gain approval and commercialized product, respectively. Both FDA and pharma were sidelined due to the pandemic and manufacturing vaccines and treatments. In addition, the USA election and transitioning to a new FDA director and administration also caused delays. What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?We have participated in the Aquatic Animal Drug Partnership online meeting this past July. And have been marketing our product to both customers and potential investors through word of mouth, restricting information so that IP production can be maintained. We are currently working on an investor pitch deck and plan for final commercialization steps now that we have more information regarding regulatory and manufacturing hurdles that must be overcome. And have recieved guidence on this document from several business coaches. What do you plan to do during the next reporting period to accomplish the goals?We hope to finish Objective 2, with guidence from FDA regarding the studies that must be completed for product approval. We also hope to finalize Objective 3 applicator gun with completion of customer on-farm trials and optimization. Finally, we also hope to identify, sign and start CMC with a manufacturer, sign on several investors to fill the funding gaps andgaining inventory within the next year. We are working with our business coaches and TABA consultants on this task.

Impacts
What was accomplished under these goals? During this period we completed Objective 3design of our application gun utilizing 3d printing technology and are currently trialling the applicator gun at several partner facilities for optimization. We have also worked with the FDA to identify what chemical manufacturing controls (CMC) they will require for the manufacturing of our product. And we have recieved several quotes from manufacturers to work on the initial analytics required by FDA for production of our product. Due to Covid related delays, we are still waiting for more information through the FDA application process regarding what other studies may be required for approval of our product (Objective 2).

Publications

Progress 09/01/19 to 08/31/20

Outputs
Target Audience:Year one of the project was examining active ingredients and their ability to work across a large range of finfish species. We also aimed to begin our application process with the FDA to get our drug product approved. Theactive ingredient examination occurring with two potential customers; allowing for honest feedback for continued product development. And FDA application is well underway, with several meetings with FDA project managers and my consultants to assist with the application process. We have also identified several potential manufacturers. Changes/Problems:Our FDA application process has been significantly sidelined and delayed due to COVID and the Presidential election. We have actually hit a point where we are not allowed to submit any more paperwork until Spring 2021. This will delay our approval time and we are considering asking for a no-cost extension for this reason. What opportunities for training and professional development has the project provided? Nothing Reported How have the results been disseminated to communities of interest?Currently, this project is still under IP protection as our FDA application is underway. However, we have been discussing our product development with several potential customers under NDA agreements. What do you plan to do during the next reporting period to accomplish the goals?We are going to continue working with the FDA to develop our application for drug approval. This will include more information on what, if any, additionalexperiments we may need to complete for approval to commercialize our product. We will also continue working with potential manufacturers to develop the best manufacturing and application method of our product, hopefully trialling some prototypes with our commercial partners.

Impacts
What was accomplished under these goals? At the completion of year one, we have completed objective (1.) optimization of the hormone active ingredient to be used in the final implant formulation. And we have begun working with the FDA to examine experiments that may need to be completed for objective (2). We have also started working with manufacturers and have re-evaluated our application gun design for objective (3) given new information about manufacturing methodology of the final commercial product.

Publications