Progress 09/01/19 to 08/31/24

Outputs
Target Audience:Our Target audience includes the payers, patients who need our device, and Doctors who prescribe our device. As described in our Accomplishments section TO 1, AVT reached out to Dr.McBane for guidance about what his patients need and want (determining factors in a doctor's decision to prescribe a therapeutic device) through in-person meetings, teleconferences, and emails to best direct AVT's device development. We greatly appreciate the expertise he has shared solely for his patients' benefit as he has never received any funds or reimbursement from AVT to date. AVT will continue to do this and reach out to him as soon as we have the final results from our FDA pre-submission meeting in 2025 as he directed. Brian Mullinax (2020 reimbursement specialist referred to in accomplishments TO 3) provided AVT insight into the payers' needs to direct compliance feedback concerns in both the home and clinical markets to validate reimbursement & make the device more affordable. Changes/Problems:GMI's dedicated subcontractor, Jake Flagle & his company 316 Product Development (316PD) who are experts in medical device alpha & beta development became our manufacturing consultants. The predominant problems AVT encountered were availability including supply chain limitations & inflationary cost increases caused by COVID. We were able to communicate with Dr. McBane to move the project forward & transfer the prototype to 316PD. AVT continued to strive for an on-time project completion but needed no-cost extensions that the USDA graciously granted. AVT continued to balance project scope & cost to maintain the stated project Technical Objectives (TO) as best possible. If AVT had not been diligent & creative in this effort, the project would have easily exceeded the original budget early on. We verified with our National Program Leader, DR Keith Harris that it was acceptable to raise separate funds to help offset cost increases. AVT received a $10,000 INTAP grant from Indiana for additional software features & a $15,000 INTAP grant to subsidize the cost of custom cases. The PHI pneumatic compression device (PCD) that was further developed in PHII, maintained all the stated goals & exceeded expectations. This model is referred to as the proof of concept model (POC). Taking AVT's POC to the manufacturer is where much change had to occur to make it repeatable, starting with several iterations of the alpha model before a production-quality beta PCD could be built for FDA testing & first sales. The first major manufacturing change was using foam for ducts & the adaptation of the valve for significant cost savings. The custom case was a large cost item in the budget costing $150,000 in injection molds. Injection molding requires very large expensive multipart molds that material is injected into at high temperatures but is very common in manufacturing. Knowing our budget problems because of Covid, AVT looked for & found a good alternative called thermal vacuum-formed molding. We were able to find an available subcontractor (CHellis in Indianapolis, IN) that could manufacture our custom case using this technology & also able to fabricate all of AVT's foam needs. The funds saved in this reduced tooling cost were used for much-needed hardware (HW) & software (SW) expense increases. Genesis Plastics (GP) had estimated $50,000 total to make our cuff. With Covid (more orders than engineers) they said engineering alone would exceed $125,000. This was replicated at most alternative companies. We were Blessed to find Masson INC. (Indianapolis, IN) who developed and made the first beta cuff ready for production for nearly 10% of what GP now suggested. We eliminated the USB dealer key & interface and switched it to a better value-adding cloud validation that was more flexible & cost-effective using cell & Wi-Fi connection. This allowed for user real-time revocable validation through the cloud to enable rights & access changes to both the machine for setup & patient compliance for appropriate prescribing doctors, clinics, & payers - all via the web. This would keep logins up-to-date & provide for greater patient safety and will be included in the final beta. We eliminated speaking interaction for times & state of the treatment that was part of the PHI PCD but will reconsider as sales begin & revenue is available. A "buzzer" was replaced with a further cost-saving "Alert" that greatly reduced test requirements. At the halfway point, AVT still had funds left as the project director (PD) & program manager (PM) worked for a stipend & AVT's in-house computer science (CS) programmer provided much volunteer effort as a lab assistant. Whenever AVT switched from its lab to a legitimate manufacturer, the typical manufacturing cost rose to $175/hour for engineering & SW programming. This was concerning. In 2022, AVT's first & persistent problem was both logistical & financial. Covid has significantly made it more difficult to get the correct parts & greatly increased manufacturing costs from the 2019 grant budget. We were running the project in parallel. SW consultants were waiting for HW consultants to be completed, & then there were HW problems, & the SW consultants were waiting again, & so on - not allowing work on other client's projects. This was the quickest way to complete the project but with funds running so short, was unacceptable. The burn rate (over $30,000/month) would deplete the grant funds well before completion. We switched to work in series (completing one segment before starting the next) to avoid wasting money. This takes much longer waiting for the next segment to be completed & then waiting for the expert to come back when available & the iteration repeats. We needed to cut costs further & hire engineers & consultants for $50-$75/hour to further reduce cost. This was hard as most said it was less than they make from their full-time employer. They already had full workloads so it made them even less available to do AVT work but it still seemed the only path to accomplish our project. Surprisingly, people perform differently if their livelihood depends on their work versus part-time contributions. AVT is only working with kind people trying to do good things but understandably, discretionary time is hard to come by. Our first Electrical Engineer (EE), a university professor who designed & redesigned our PCB had personal issues & the second iteration went from 2 weeks to over 9 months with no progress. Finding someone to finish another's work was difficult. We were able to find a replacement EE that works remotely from TX & has been able to complete the PCB redesign. Separately, our first software consultants E-gineering (EG) said they would stick to their original software budget even with Covid. They changed their minds & wanted to charge more at a much higher rate (> $175/hour) which was already more than AVT could afford. The good news is their lead software developer, (Bryan Varner who had worked with us & had experience in medical devices) left EG. His new job allowed him to work with AVT after hours at $50/hour but with very limited hours. Bryan thought he could easily find an extra 10 hours a week of work for AVT. However, He was quickly promoted to management at his new job & had trouble providing 10 hours per month but is sticking with us & we are grateful. There are many issues with the Digi single board computer (SBC) manufacturer but they have tried hard to assist & we are grateful. John Lockwood (our regulator consultant) left Pearl Pathways during Covid to form his own company. John Lockwood worked with us from the start & led our FDA pre-submission & will make our full 510K submission. As AVT only made an FDA pre-submission currently, much of the original budgeted consulting costs were saved. In 2022, Jake Flagle (316PD) started deeply discounting labor costs to help AVT & continues to provide oversight for this project. Our Product development engineer, Mike Hoffa & Program Manager, Kathryn Logan declined a grant salary starting 9/1/21 to reduce cost. AVT's computer science (CS) expert, John Paul Logan has agreed to help as a technician to do the HW & SW work with the PD Kerry Logan at a reduced, or no cost to complete the project. The PD worked for Stipent & stopped charging AVT in 2024. In 2024, the IRS stopped deducting expenses to offset grant funding directly & only over 5 years of amortization, resulting in a large tax burden for a pre-revenue small business. Additionally, John McNett (AVT's patent lawyer) retired but he left AVT with a very competent replacement, Scott Collins, to continue our current patent effort that is pending appeal. What opportunities for training and professional development has the project provided? 9/21/2023 RAQU Quality Systems - Pre-submission and Preeminence (Allison Komiyamo) 12/19/2023 Indiana Small Business - Optimizing Your Website for Maximum Impact 4/18/2024 NIH - Extramural Changes Coming to Applicants and Peer Review in 2025 4/22/2024 Small Business Administration - Completing a Quad Chart 4/27/2024 Ivy Tec - 2024 INTAP 5/9/2024 Overview of the Quality System Regulations - Tonya Walbon 7/1/2024 Larta - Non-dilutive Funding Through NIH Grants 7/16/2024 Attended SBIR Roadshow in Indianapolis, IN How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? Technical Objective (TO) 1: Advanced Vascular Therapies (AVT) started this project just before Covid causing many cost & availability issues. AVT received input from DR McBane to guide our PHII pneumatic compression device (PCD) development to benefit his patients & our customers. He liked the modified PHI secure website tracking compliance data example we provided & the added setting to help prevent deep vein thrombosis (DVT). He recommended we raise the default DVT prevention pressure to 55 mm of HG, within range of the other predicate devices. DR McBane's approval of the modified PHI POC with all his recommended changes initiated AVT's transition to the Alpha 1 device iteration. He was very pleased with AVT's reconfigured valve. The compressions were very rapid with low backpressures. We demonstrated an innovative 2'- 6' collapsible hose that would stay expanded until a minimum force is applied avoiding volume change during use & making for easy storage. DR McBane was concerned different sized cuffs would complicate the clinician's or patient's choices so AVT optimized the broadest fitting cuff possible (up to size 15 shoe). The calf part of the cuff is adjustable with Velcro & does not need to be re-adjusted for the same patient. It fully encloses the calf & foot & a zipper makes for easy limb insertion. It still avoids pressure points & provides for a numbered protocol for installation (DR McBane wanted). Because DR McBane was concerned about cuff replacement cost, AVT will use inexpensive disposable impervious sterile stockinet (Medline NON22535) separating the patient from the PCD cuff, simplifying regulatory biocompatibility & cleaning concerns while reducing patient cost. DR McBane would like to see our PCD after the FDA has answered all our pre-sub questions. TO 2: The alfa valve design that our manufacturer 316 Product Development (316PD) provided had to be redesigned again for greater durability with no loss of efficacy. AVT received from 316PD five printed circuit boards (PCB) that we then tested, modified, & tested again - until meeting design requirements. This was a large iterative process including many circuit & component changes. We now have a PCB reduced to a repeatable design that works & is ready to manufacture in large lots when funds are raised. A large alfa 1 case & foam set made by 316PD was too large & noisy. They suggested making it even larger to make it quieter. AVT went through a long iteration process spanning more than 6 months, utilizing all the things we learned from PHI & more, and made it smaller & quieter - roughly comparable to the PHI PCD. We then sent it to CH Ellis to produce the beta production quality case & foam sets. The production quality parts in our beta units need to be made with SLA & SLS 3D printers. This is ideal for FDA testing & low volume sales & allows for revision. TO 3: Except for changes already referred to (or required), AVT will retain all settings & defaults of the PHI PCD with a simple touch-to-pause screen. AVT added software/hardware fail-safes to prevent discomfort to the patient. Dr. McBane & Brian Mullinax (reimbursement specialist) agreed compliance feedback is essential to home & clinical users, as it directs treatment plans, validates reimbursement, & makes the device more affordable. Many protocols were added to make this work over WiFi or cell connections. AVT created a new dealer-settings device menu. AVT will create a secure, encrypted subscriber website. All PCDs will have factory software set serial numbers & all data changes will be logged. All subscribers - dealers, prescribing doctors & patient's clinics will have a revocable account, validated over the cloud before being given access. Dealers will be able to access patient billing information (web-based), & doctors & clinics will access their patient's medical data (web-based). We greatly reduced cost by utilizing the graphic user interface (GUI) of the POC that AVT was able to create in their lab. This GUI will be almost unchanged in the beta that is being completed but will still require more testing. Our lead programmer Bryan (Robust Systems, LLC) spent long hours trying to get our Digi single board computers (SBC) working with their tech support to communicate properly & consistently with their modem. Finally, AVT communicated with an executive engineer at Digi & learned there was a production change just before Covid, & there was no model change designated except the date of manufacture that they never shared with AVT. During Covid, it appears the SBCs were scarce & they shipped the older units without our realizing it. This caused all AVT's modem problems. Digi graciously provided replacement SBCs for the retired manufacturer dated ones that would now communicate with their modem. While they provided remote management to provide updates, firmware change to use the modems required much of AVT's code (firmware) to be rewritten. This is pretty hard to come back from in the last 4 months of a project with part-time help. That said, Bryan has the firmware operating again & communicating with the Xbee modem correctly (Bryan having only 10 hours per month to give) & John Paul (our in-house part-time CS) has been reworking the GUI to replicate the original POC & has it close. New software always needs testing to get the bugs out. We have avoided restarting the administrative & subscriber web page & database as security is such an issue (See TO 5). With the start of commercialization soon, AVT decided to wait until we can get more funding & hire a Quality Assurance (QA) person to help in creating the final SW test needed for FDA passage & guide our web pages & database creation for best security. TO 4: Based on AVT's alpha #2 case & foam set successfully developed in AVT's Lab, we have 10 beta production quality cases purchased & being built with a 2-month lead-time with one coming soon. It will be a thermal vacuum molding custom case using black ABS material built by CH Ellis in Indianapolis, IN. It will be close in quality to the originally planned injection molded one, but much cheaper. We need both the design flexibility & these savings to cover cost increases. The beta case size is 23" tall x 15.5" wide x 14.5" deep. We have also ordered the first beta foam set fabricated & pending results more will come. Masson INC. in Indianapolis, IN worked with AVT through several iterations to create the final cuff design & a production quality beta model based on DR McBane's input. As soon as new funds are raised, AVT will create tooling & start manufacturing in large lots at reduced cost & then perform FDA-required tests. TO 5: John Lockwood our regulatory consultant made our pre-submission to the FDA, to better guide our path to obtain final 510K approval of our device. We had several questions. Can we use two predicates with the same or very similar Intended use, but with different indications of use as a broader basis for predicate justification for AVT's device that has more indications for use than any one previous predicate? They are still evaluating this question. Another question was about AVT using commercially available sterile impervious stockinet to separate the patient from our device. The FDA supported that this would eliminate AVT's cuff needing extensive biocompatibility testing (very expensive). AVT would still need correct labeling requiring proper wound dressing if there is breached tissue present. The rest of our conversation with the FDA regarded needed tests. Specific EMF emitter testing & cybersecurity requirements were identified. Much testing will be needed to receive an FDA 510K approval & will require additional funds.

Publications

Progress 09/01/22 to 08/31/23

Outputs
Target Audience:We have updated Dr. McBane by phone and email. He directed the continued efficacy and ease of use of our device as most important, then noise level for his patients, and finally its size. He wants to see our device as soon as it is final, to evaluate the results. We hope this will be Spring 2024. Changes/Problems:When AVT exceeded its budgeted burn rate, our main contractor, 316 Development was more than kind and started charging AVT the actual cost (no mark-up) of his services to help, and still continues to provide oversight for this project. Our software consulting firm, E-gineering had originally said they would hold the cost to their original estimate. COVID overwhelmed their ability to do this and E-gineering felt they had to increase their estimate. Their programmer availability was nil and their labor rate went up greatly with inflation. AVT could no longer afford them. The good news is that one of their lead software developers, (Bryan Varner who had worked with us before and had experience in medical devices) left E-gineering. His new job allows him to work with AVT after hours. He is currently working with JP Logan, AVT's programmer to further reduce costs. Bryan's time is limited but he is graciously working for AVT as a consultant for near ¼ the rate E-gineering was charging. They continue progressing on software revision. Our regulatory consultant John Lockwood stopped working for Pearl Pathway even as a contractor. He is prevented from working further with AVT because of his contract's non-compete clause with Pearl Pathways, at least until next year. This has precipitated several questions about the regulatory path and a possible new consultant needed. Based on input from 4 different regulator consultants we have interviewed and are considering, a pre-submission to the FDA would still benefit our full submission effort. We are still determining the best candidate and are planning on a pre-submission to the FDA early in 2024. What opportunities for training and professional development has the project provided?1/11/2023 Purdue Research Foundation - Accounting 101 1/12/2023 Indiana SBC - INTAP 2023 Launch 3/23/2023 BidSpeed - Traning: Navigating Federal Contracts 7/11/2023 Elevate - Non-Dilutive Funding How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?AVT will continue the interactive series progression of software and hardware revision to ensure efficacy and safety are maintained until we can make the alfa design final. The final iteration of printed circuit boards will be created. Our foam and case are designed but further revision is possible if results can be improved before made final. AVT has worked hard to create the cuff that was approved by Dr. McBane to survive many uses to reduce patient costs and the need for frequent replacements. We don't want to just sell more cuffs. After continued testing, Dan Marsh (President of Masson INC) has determined we can improve the cuff's longevity more by adding a small sewn addition on the top of the ankle or shin of the boot. This modification has not been enacted yet but will be going forward and further testing and possible revision done until final. Once we have the alpha final, we will show it to Dr. McBane for his guidance and start working on a pre-FDA submission early in 2024. The case will likely require an expensive reusable mold to form so it will be created last to allow for any changes. AVT thinks the cost can be reduced further by using production quality 3D printed parts where feasible that will give the desired test results at reduced cost, in small quantities. The AVT team worked hard and diligently during this project to manage the scope, to satisfy the stated Technical Objectives of this PHII project on a 2019 pre-COVID budget, and is still constantly seeking ways to make our device better for doctors and their patients in need. The USDA has helped in every way it could and is an incredible group of caring people. AVT's goal has always been to get our device FDA-approved so we can get good funding and validating research to help patients who need it and maintain the efficacy of our device. AVT will continue to seek other non-dilutive funding options that might help us get as close as possible to making a full FDA submission and getting FDA approval. We will be reaching out to Program Directors for guidance for this and other parts of the project. Once FDA approval is granted, we will seek a large multi-site study for our device to resolve any question of efficacy on patients. This is especially important where limbs are in jeopardy from poor arterial circulation. We hope this could be funded through an SBIR or STTR NIH grant.

Impacts
What was accomplished under these goals? The effects of COVID and inflation for everyone continue to increase the cost and time necessary to complete the project, as well as reduce the availability of parts and manufacturing services. AVT would like to acknowledge the USDA's kindness in allowing several No Cost Extensions which have allowed AVT to successfully switch from working in parallel (all working at the same time) to series (finish one part and then go to the next and back again when needed) to significantly reduce cost. AVT is very Grateful. Based on Dr. McBane's guidance after efficacy, noise and size were the most important factors. AVT used the data and observations from PHI to guide noise reduction. We learned the most effective sound blocking occurs from large changes in density between layers, or using large amounts of foam. With varying frequencies, sound absorption occurs best with the optimal density of foam being present. AVT first addressed noise and size of the repeatable and manufacturable design using ducting based on multiple foam layers and good manufacturing practices. This involved technical objective (TO) # 1, 2, 4 and 5. AVT's manufacturer's design PHII alpha #1 was 28x21x17 inches, 50 lbs with an average 82 dB noise level at 3 feet, which was much larger and noisier than our handmade PHI proof of concept (POC) model. The easiest solution to reduce noise was to add even more foam and thus increase weight and size. Instead, we worked in our AVT lab for more than 6 months, hampered by foam and parts availability and limited funds. We managed to find and use only UL-listed foam though to avoid regulatory issues. PHI taught AVT, that foam changes density when compressed. Even dense foam's (less dense much more) acoustics are changed when compressed to some degree. A uniform way of compressing the assembly of foam in the correct amount was needed. Less dense foam absorbed noise but denser foam blocked noise better. (Proprietary Information in Bold) The layers of foam were made airtight by being compressed sufficiently and glued. AVT found commercially available nylon bead ties (tiny beads molded on a string) and created 2-inch nylon disks to slide and lock on the beads to hold the layers together with just the correct amount of force, using only 6 bead ties. Strategic layers of polycarbonate (PC) sheets were used between layers of correct-density foam. The thickest PC (which became our chassis) was used in the center of foam layers to mount the blower and all components, including the valve and printed circuit board (PCB). We made the top foam layers removable to expose all the working parts mounted on the chassis. This chassis can be removed separately for easy repair. We added a top and bottom layer of PC with ½ low-density foam to make the force more uniform and improve acoustics. Lateral noise (perpendicular to the layers from the sides of the unit) was a big sound issue. Gluing foams laterally was also a manufacturing problem but stacking and cutting were not. AVT found the noisiest foam layer was at the valve, straight from the blower. To help with lateral noise, we used denser foam here but wanted absorption as well. We drilled holes in that denser foam layer's inner perimeter touching layers above and below, effectively reducing density on the inside laterally, but maintaining density on the outside of that layer. This didn't affect vertical density from assembly compression. It was also necessary to add an ½ inch layer of very low-density foam bonded to a very thin PC to the external case sides to absorb and block lateral noise. This still allowed the foam assembly to be dropped into the case and easily removed the same way. AVT's lab produced a handmade demo case with optimized components to use in a PHII manufacturable alfa #2 unit that measures 24x16x16 inches & weighs 32 lbs. with an average 66 dB noise level at 3 feet. This is much smaller & lighter, and 16 dB quieter (6 dB is considered twice/half as loud to the human ear) than AVT's PHII manufatureable previous alpha #1 (See above). This PHII alpha #2 is one lb. heavier and also close in size to AVT's PHI POC - but a little quieter. AVT circled back to PCB testing again. This involved TO 3, 4, and 5. We had done an initial test on our first commercially made PCB. Normally, any PCB interim design changes would require the remanufacturing of completely new PCB iterations to test over and over at a large cost. Instead, in the AVT lab, we did this with small patch boards made by hand and created new wiring harnesses, and altered old ones, (keeping documentation up to date) modifying the first PCB iteration. Then these changes could be incorporated into the second (think final) PCB commercial iteration when ready, for almost no cost. All these changes to the design including sensors, alerts, and other parts were done to broaden compatibility with available components and solve software (SW) and hardware (HW) performance issues, found after other series steps were done. We then turned over our work to our SW consultant Bryan Varner (Robust Systems, LLC) for SW revision to retest. This involved TO 2, 3, 4, and 5. In working together with him, AVT found a glitch in the previous SW that allowed our device to stay compressed longer than intended which could cause patient discomfort. Our HW safety system went into fail-safe (FS) mode to protect the patient but the flaw could not be allowed. AVT discovered it was SW pulse width modulation (PWM), thought to be sufficient, was causing the single board computer (SBC) to be overworked. The SW PWM was responsible for regulating power and time of compression of our device. In our PHI POC device, AVT used HW PWM built into the SBC to avoid this. Industrial-grade SBC choices and availability were limited by COVID during PHII. Our contractor thought the SBC they chose was (and still is) the best available even though it had no HW PWM built into it. Working with 316 Product Development's engineer and both our SW consultants, AVT found an addable HW PWM chip with SW drivers available to solve the problem. This was successfully tested and will be incorporated in our second PCB revision. Without SW causing FS we circled back to retest HW. This involves TO 2, 4, and 5. Our valve was completely redesigned in PHII from our POC in PHI. We discovered the new valve was sticking after about ten hours of use - a problem our PHI POC did not have after thousands of hours of use. We are currently working on this new design to solve the problem, but are convinced it to be entirely mechanical and solvable. These all demonstrate the series iteration process we have been following.

Publications

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

Outputs
Target Audience:Our Target audience includes the payers, patients who need our device, and doctors that prescribe our device. AVT continues to update DR McBane through email and will interact directly after our alpha prototype is final and we are prepared for FDA - pre-submission. We will pursue relationships with our payers as we near FDA clearance and utilize future patient feedback to continue to grow and improve. Changes/Problems:AVT's first and persistent problem is both logistical and financial. Covid has significantly made it more difficult to get the correct parts and greatly increased manufacturing costs from the 2019 grant budget. As previously discussed, AVT has balanced scope and time to try to keep this project in line and believes to have done a good job. Early this year we saw there was going to be more balancing needed and will try to accurately describe these changes below for transparency. We started running the project in parallel. Software contractors were waiting for hardware contractors to be completed, and then there were hardware problems, and the software contractors were waiting again and so on - not allowing work on other client's projects. This may have been the quickest way to complete the project but with funds running so short, was unacceptable - so we have since tried to work in series (completing one segment before starting the next) as much as possible to avoid wasted time and money. This takes longer since you still wait for the next segment to be completed, but additionally wait for the expert to come back when they become available. AVT asked The USDA for a time extension which they graciously provided. This allowed us to then complete hardware to a point, and then call in the software contractors to work - but our burn rate was still over $30,000 per month which would deplete the grant funds before completion. We then verified with our National Program Leader, DR Keith Harris that it was acceptable to raise additional funds to cover our shortfall. Next, AVT successfully pursued a $10,000 INTAP grant from Indiana for additional software features we needed that were not part of our original submission. See "Accomplishments." Separately, our software contractor (E-gineering) first said they would stick to their original software budget but with time increases and other commitments cannot. This stretched our budget further. AVT's product development contractor, Jake Flagle (President of 316 Product Development - numerous engineers and experts in diverse fields) provided his best future cost analysis. He feels strongly if AVT takes on as much additional direct work as possible under 316's direction with Jake's personnel doing what AVT cannot, the project will be at least $87,000 behind to complete. He is deeply discounting their labor cost to help AVT. We are currently pursuing a crowdfunding page called "GiveSendGo.com" to raise additional funds and will consider partnering, investing, and grant opportunities as necessary and available. Our Product development engineer, Mike Hoffa has declined a grant salary starting 9/1/21 and only receives $1000 from AVT (separate from grant funds) to cover expenses for the year. Our PM, Kathryn Logan has agreed to do the same to reduce costs. AVT's Computer science expert, John Paul Logan has agreed to help as a technician to do the hardware and software work with the PD, Kerry Logan, at a reduced or no cost to complete the project. What opportunities for training and professional development has the project provided?Time for training has been more limited but focused this reporting period, because of our intimate manufacturing efforts. We participated live and recorded webinars from Elevate (focused on helping Indiana companies grow) and Bidspeed (focused on women-owned Hubzone companies). 4/19/22 - Elevate: Tuesday Talk - Slicing Equity between Founders 4/27/22 - Bidspeed: Doing Business with the VA, Department of 5/10/22 - Elevate: Tuesday Talk - Fundraising 101 5/12/22 - Elevate: NIH - SBIR/STTR Deep Dive with Stephanie Fertig How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?Starting with our PHI device that achieved all the TOs described in that completed project and going on in the PHII project, AVT continues to work even closer with our product development manufacturer (316 Product Development) and update our final production manufacturer (GMI) to make changes to benefit the design and reduce cost. Covid still limits the availability of supply and increases the cost and time to complete. See "Changes." Our first milestones will be to get a final alpha prototype, get prepared for a pre-FDA submission, and consult further with DR McBane to determine if any final trade-offs or improvements are needed. We have the initial testing of our first iteration of alfa PCBs done and need to test in a closer and closer near-use environment. To do this we have to create foam passages refined to design specifications that minimize noise and promote airflow and create new test cases and enclosures. The foam we need is in short supply and more than doubled in cost. We were unable to get the correct foam from the foam manufacturer (Zotefoams) but found a stockpile at a different fabrication manufacturer (Technifab) in Avon, OH who allowed us to personally drive and pick up a large sample to experiment on. Technifab thinks more will be available in the future at that location. AVT will validate the boards further when in place in the test alfa system to assure everything works correctly when all together in use. Once that is done, we will turn them over to AVT's software contractor Bryan Varner (Senior Software Consultant at E-gineering) for further development of their software for use on our PCBs in our finished device. Bryan thinks this could take 3 months and will update our web software to include any changes needed. If it were not for cost limitations, AVT would be starting to produce beta cases and enclosures at this point through our case and foam manufacturer (C.H. Ellis). We can create test alpha cases and enclosures in-house at greatly reduced cost and if changes are still needed, they can still be cheaply made. We will reserve the beta case for after the design is final and testing begins to save cost. AVT has talked to our manufacturer and team as well as our regulatory consultant and decided that only 5 (instead of up to 10 anticipated) production quality beta units will be required for FDA testing. This will reduce cost, leaving more funds to get closer to FDA passage - the most important milestone for commercialization. If FDA passage can be obtained, we believe funding will be no problem as our company value will go up sharply after this milestone. As stated in our PHII submission, we will begin sales as soon as we have FDA approval and seek an NIH study for validation and a new reimbursement code for our technology. AVT is sorry to be in a post-Covid environment where the budget and time have become such great issues. We are very grateful for the USDA's patience and continued support of this project, without which this device would never get to the patients that need it. Thank you, Kerry Logan

Impacts
What was accomplished under these goals? Technical Objective (TO) # 1: DR Robert McBane still wants to see in person our device again to evaluate any final changes once we have an alfa prototype completed and pre-FDA submission ready. AVT is still working hard to complete the alfa to prepare for this pre-FDA submission. We have kept DR McBane up to date on our progress and changes and continue to act on his previous directions. TO # 2 and # 4: Parts procurement remains a real issue. Even worse, parts may be available now only in limited quantities. They may need to be substituted later with equivalence proven if more is needed after FDA passage. An example is sensors. They are often difficult to get with the accuracy desired and at even greater expense than in the past. AVT started with our first iteration of 5 development printed circuit boards (PCB) commercially created and propagated for our alpha prototype which our contract manufacturer created. AVT then began basic testing of these PCBs and made needed modifications to make them functional and meet design specifications. We first did this on two PCB boards with the documentation needed for certification. We discovered weak solder joints, incorrect component values, and incorrect sensors. Additional wiring and new and modified circuits were needed on this first iteration. Using these base results we continued on the next 3 PCB boards that now appear fully functional, but the first two have not been updated yet. AVT had to develop a "state diagram" describing how our device worked for our software contractor who used this diagram to create the drivers and a basic operating system to utilize the components for simple testing. Once this was done, AVT then had to modify the software and hardware further to test the boards closer to a nearer-use environment to get more detailed results. This is a progressive iterative process. To create this nearer-use environment the first foam we created for demonstration and testing is refined over and over to closer meet design requirements. As previously stated noise increased significantly as the size was reduced. We have been balancing that while trying to create the alpha test environment we need. The blower was "choppy" at low-duty cycles. AVT resolved this by adding an RC filter circuit to the trigger for setting the blower control. Separately, the manufacturer (Ametek) suggested an optional larger external line filter in preference to blower disassembly to add needed parts, if AVT needs to reduce the EMF of the blower further. Final EMF testing has not been done yet so we are still using the original line filter until more data is obtained. AVT could not get the exact valve motor used in the original device. During testing, the substituted valve motor damaged components because it was slightly different. We substituted correct replacement components with no further issues and improved the design at the same time based on the manufacturer's recommendations. We replaced a micro switch in the valve with a sensor (a "hall effect" transistor with a magnet) for greater longevity but circuitry had to be modified. We had to determine the correct placement for both this sensor and a magnet within our 3D printed valve and will include this position in the next iteration of the valve. Both the mechanical hardware failsafe pressure sensor and the software interfaced pressure sensor had to be calibrated for accuracy using an HG Monometer. The results were very consistent. AVT worked with Dan Marsh (President of Masson INC - cuff manufacturer) further to develop a good protocol for the patient usage and limb insertion of AVT's cuff and numbering system that will simplify and clarify the repeatable method we desired per DR McBane's suggestions. We also worked on ideas to improve the cuff's durability for longer life. TO # 3: AVT was concerned with the availability of key components. The single board computer (SBC) is an example. We were able to purchase 30 of these SBCs, spread out over the last year (limit of 5 per order) and they are currently out of stock and on backorder. The drawback is you have to decide a lot of things before the devices are all actually utilized. We involved multiple engineers and our software contractor to make good choices. These SBCs solve stability issues we had to work around in our PHI device, such as data loss when power was turned off. Currently, no SBCs meeting our needs that would be appropriate in an FDA device can be found in stock at a reasonable price. We had an issue with the SBC's hardware pulse width modulation (PWM). Most SBCs have this built-in to reduce the CPU workload and increase reliability when controlling motors, but they are very SBC-specific. The SBC we chose had one but required very specific ports that we already were using and was not flexible enough. AVT's software contractor developed a driver for us that created a timed software PWM that minimized any CPU loading. It made the software more universal so it would more easily adapt if we needed to use a different SBC because of limited availability during later production. AVT was able to get 30 of the correct universal cell modems for our SBC to provide internet access through numerous providers (ATT, Tmobile....) for greater access to our device. We found displays for our device with "water glove" sensitivity (being able to work with a wet exam glove) available in small quantities (AVT purchased 5.), but long-term availability and cost are not stable. We also found alternate displays that were substantially equivalent to these that had "optically bonded" screens that are significantly more durable and more available from different countries. These screens often required different supply voltages so we will add optional voltage supplies to AVT's next iteration PCBs for these displays to increase future production stability, so we can use any of the best screens available when needed. There were numerous interaction issues between the PCBs and the SBCs. Preboot SBC values cause false failsafe and misreadings. States had to be altered for the available sensors. External circuits had to be designed and made. These will be incorporated in the next iteration of PCBs. All these issues are currently resolved. AVT's software team determined what revisions would be needed in our secure subscriber web space for patient data, such as a better log system to report changes for regulatory transparency and best protocols. It was also determined keeping software on the device up to date was essential. This could result in patient loss of use if not implemented. We do not have extra resources. See "Changes." We received an Indiana grant (INTAP) to cover this additional cost to make our device even better. We won this grant but have not yet enabled these automatic software updates. Our software contractor has been contracted to do so. TO # 5: AVT continues to be guided by our regulatory consultant John Lockwood and our product development manufacturer (316 Product Development) and seeks new ways to reduce the very large development and testing cost for regulatory clearance. This is even more vital with our limited budget. See "Changes." We had been diligent in keeping the cost for our "Alarm" system at a minimum by using pre-certified "Alarms" for example. We thought it was time to consult the actual independent testing labs (F2LABS) that would later certify our devices for the FDA to see if there were any variables we had missed. It was surprising what we found. The lab felt strongly our device is non-invasive and minimal threat to a patient. AVT's device is only connected to the patient by an air passage and separated from the patient by a sterile sleeve. They recommended we remove our "Alarm" and substitute it with an "Alert" that has far fewer testing requirements and will reduce the final cost. We did this in our last efforts and hope this will help reduce the budget further.

Publications

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

Outputs
Target Audience:Part of our target audience (not including the payers) is the doctors that prescribe our device to their patients and their patients, who need treatments. As described in our Accomplishments section under technical objectives # 1, AVT has reached out to Dr.McBane by teleconference and in person for guidance of what he and his patients need and want, and how we can best direct the development of our device. Changes/Problems:The USDA kindly granted AVT a PHII project time extension of one year ending now in August 31, 2022. We needed this delay because of the ongoing cost increases and supply chain limitation caused by Covid. We have continued to balance project scope and cost to maintain the stated project Technical Objectives (TO) due to these circumstances which are beyond AVT's control (See Accomplishments). If we had not been diligent and creative in this effort, the project would have easily exceeded our original budget & been unable to complete. The PHI pneumatic compression device (PCD) produced in AVT's lab that was further developed in PHII, maintained all the stated goals and exceed expectations. This model is referred to as the proof of concept model (POC). Taking the POC to the manufacturer is where much change had to occur to make it repeatable, starting with several iterations of the alpha model until final. We are not through this process yet. After the final alpha, a production quality beta will be built, and tested and FDA approved for sale. ***The following contains proprietary/privileged information that AVT requests not be released to persons outside the Government, except for purposes of review & evaluation.*** The first major manufacturing change was using foam for ducts and the adaptation of the valve for significant costs savings (See Accomplishments TO # 2 & 4).*** The custom case was a large cost item in the budget costing $150,000 in injection molds. Knowing our budget problems because of Covid, AVT looked for and found a good alternative called thermal vacuum formed molding. Injection molding requires very large expensive multipart molds that material is injected into at high temperatures but is a very common manufacturing solution. Thermal vacuum molding uses a simple mold that can be shaped out of wood for low volume and the material is heated and laid, under vacuum over the mold to shape the material to exact specifications. This greatly reduced our custom case cost with only minor alterations. We were able to find an available subcontractor (CHellis in Indianapolis, IN) that could manufacture our custom case using this technology and also fabricate all of AVT's foam needs. The funds saved in this reduced tooling cost can be used for much needed software expense (See Accomplishment TO # 3 & 4). We had planned for Genesis Plastics to make our cuff with an initial estimate from them for $50,000 total. With Covid, they only had one engineer working and a minimum crew and were vastly overbooked. Genesis said engineering alone without fabrication would exceed $125,000 currently. This was replicated at most of the cuff contractors we found available and most were not available at all. We were Blessed to find Masson, INC in Indianapolis, IN that was shorthanded but able to do the cuff development and manufacture. They estimated they could create our cuff at, or possibly below the original budgeted amount. Masson made the alpha cuff DR. McBane was so pleased with (See Accomplishments TO # 1, 2 & 4). We eliminated the USB dealer key and interface because of cost. We switched it for a better value adding cloud validation that was more flexible and cost effective using cell and Wi-Fi connection to the cloud. This additional software work allowed AVT to add and develop a user real-time revocable validation through the cloud to enable rights and access changes to both the machine for setup and patient compliance for appropriate prescribing doctors, clinics and payers via the web. This would keep logins up-to-date and provide for greater patient safety. This significant software work was additional, but a major benefit to our customers and our commercialization (See Accomplishments TO # 3 & 4). AVT very much wants to reduce patient cost. Providing accurate verifiable usage validation will help get payers (Medicare and insurance) to pay for this service, especially after efficacy is proven through usage and studies. We eliminated speaking interaction for times and state of the treatment because of regulatory and validation high cost (several languages) but will reconsider as sales begins and revenue is available. As a result, an FDA pre-certified buzzer with already enhanced visual display for warnings will be used. Pearl Pathways has seen numerous personnel changes through this Covid Pandemic and some were people we work with. One such person is John Lockwood. He has worked with us from the start and will handle our 510K FDA submission. John left Pearl but they assured us he can continue to work with AVT through Pearl as an independent contractor and has been doing so. He recently told us a pre-submission would be helpful to determine and make any needed changes before the final submission and would be cost effective. We have been told by John after he checked with Andrea Mackie (Sales and Marketing Development Manager at Pearl Pathways) that the cost for this submission will be on the high end of the original estimate. With the work already paid for, we should be able to complete a pre-submission and a 510K submission with the $45,000 remaining of $55,000 original maximum budgeted. AVT will provide Pearl and John needed technical support documents that he will use. John feels AVT's submission will likely be successful based on all current information and his interaction, but of course no guarantee can be made of an FDA response. AVT still has funds left from the first half of the project in our ASAP account but will soon need the second half of funds to continue. While we could have done even more if not for Covid, AVT and its team still expect to complete this project and stated Technical Objectives by August 31, 2022 with the changes we have described. We will continue to update the USDA and are incredibly grateful for all your support. What opportunities for training and professional development has the project provided?Training opportunities from the project: AVT was able to participate live and through recordings in several Larta, Bidspeed, KENX, NIH and Purdue webinars that will help our company commercialize as we go forward. Larta is an incredible resource and provided free for the USDA grant recipients. Bidspeed is provided for Women owned Hub zone companies thru the SBA. KENX, NIH, and Purdue webinars were provided complementary. AVT is very grateful for all these opportunities to grow and learn. Sep 15 / 20 - KENX - Managing FDA inspections Oct 20 / 20 - Larta - Project Portfolio Management 101 Oct 27 - 30 / 20 - NIH - Virtual Seminar on Program Funding and Grants Administration - Not all booths Jan 12 / 21 - Bidspeed - Focus on New Opportunity Searches Jan 13 / 21 - Bidspeed - How to Prepare for 2021 in the Federal Market Jan 20 / 21 - Bidspeed - How, Where and Who to Market in the Federal Government Jan 20 / 21 - Purdue - Startup Financing Tools and the Impact of Dilution How have the results been disseminated to communities of interest?See TO #1 in Accomplishments above about interacting with Dr. Robert McBane to address patient and physician concerns. What do you plan to do during the next reporting period to accomplish the goals?Technical Objectives (TO) # 1: AVT will continue to interact with Dr. McBane. Approach - After the alpha is final and the FDA 510K pre-submission is completed, we will show the alpha to Dr. McBane for his final approval. AVT will interact on any FDA responses and Dr McBane's further input before proceeding to the beta production model. Expected Outcomes - We will resolve any issues then. We will proceed with beta production and submission of a PHI NIH grant to start validating our pneumatic compression device. After 510K passage is approved, AVT will continue to interact with Dr. McBane on the NIH study and our further development. TO # 2, 4: We will work with our manufacturer to continue to develop our device. Approach - AVT will begin validating the first 5 circuit boards that have already been propagated and then build and validate their wiring harnesses for transfer to the software developers so they can start initial test of the software (TO # 3, 4 below) they have developed. While this is going on, AVT will resolve the sound issue discovered in downsizing the foam model. As soon as we can make the foam final, we will know exact size and shape. AVT can then start the final case development that will take a couple of months. It will be used in the last alpha model and all the beta models. When this all comes together, AVT will start internal test on the alpha and start taking all the manufacturing technical documentation to John Lockwood for his pre-submission work (TO # 5 below). After the pre-submission using any FDA and Dr. McBane feedback, AVT will make design final and start beta production of first units and testing for FDA passage. With limited supply chain we are trying to pre-order essential components in advance to avoid shortages where possible. Expected Outcomes - We will interact on any issues that arise. Once testing is completed successfully and FDA approves our beta, AVT will make remaining beta units for patient use. TO# 3, 4: Software and smart features we will develop. Approach - The software is currently being developed for both the web and device use. The hardware circuitry is needed to implement the device software for testing before further development. Expected Outcomes - We will interact on any issues that arise. All the needed features will be reviewed and evaluated against design specification and the alpha carefully tested and then the beta tested for FDA passage. TO # 5 and beyond: FDA approval will be sought. Approach - After the alpha is final and a few months of interaction with AVT John Lockwood will pre-submit our 510K submission. The FDA response should inform any further development that is necessary before final 510K FDA submission at the end of the project. Expected Outcomes - We will resolve any issues then. After final submission is completed, John Lockwood will help AVT by providing labeling information needed going forward. With FDA approval, AVT will proceed with the commercialization plan and start sales.

Impacts
What was accomplished under these goals? Technical 0bjective (TO) # 1 & Technical Questions (TQ) # 1, 2 & 3: We consulted with Dr. Robert Bane in person & through teleconference. Our PCD treats 4 different circulatory ailments for home & clinical use with compliance feedback for prescribing doctors, clinics & payers. Dr. McBane liked we were able to maintain all these features. He was very pleased with AVT's reconfigured valve. The compressions were very rapid with low backpressures. Talking with him, we raised the default deep vein thrombosis (DVT) prevention pressure to 55 from 46 mm of HG, staying within the operating range of other predicate devices. We demonstrated an innovative 6' collapsible hose that reduced to 2' for storage & would stay expanded until a minimum force is applied. This avoided volume change during use. Dr. McBane liked it but was concerned it might waste air volume. AVT will continue testing this issue. AVT will use an inexpensive disposable sterile sockinet separating the patient from the PCD cuff. The sockinet provides a sterile environment for wounds. The cuff does not touch the patient, simplifying FDA cuff passage. Also, largely eliminating cuff cleaning between treatments allows easy reuse of the cuff reducing cost. Dr. McBane felt this solved a number of problems & was delighted. We showed the Medline NON22535 sockinet that offers a soft fabric lining against the patient that absorbs moisture & an impervious thin TPE skin that protects the patient from outside danger, packaged individually sterile. Dr. McBane felt the TPE skin clung slightly to our cuff material during insertion but thought acceptable. When possible, we will seek a sockinet with different skin & add texture to our cuff to reduce clinging. Dr. McBane was quite pleased with our new cuff saying it felt like a comfortable boot one might normally wear. It inserted easily & zipped up in the back & he said, "We checked all the needed boxes." He especially liked the way we avoided pressure points, like our inner bladder extending behind / across the back zipper to the other side to retain uniform compression & avoid any zipper danger. Dr. McBane did have some concerns about AVT's cuff: 1) During compression of the cuff, the foot tends to rise towards the leg slightly reducing the ankle angle. For patient comfort, he directed during compression of the limb the ankle angle should not be less than 90 degrees. We will include this design requirement. 2) He also suggested holding the overlapping bladders behind the zipper at top of cuff together with Velcro to help prevent misalignment of the bladder overlaps. We added this design requirement but have not determined the exact implementation. 3) He thought that many multiple sized cuffs could be confusing. It took the clinician's time to choose, & whenever a new cuff was needed, the wrong size was available. AVT's concern was wasted air in too large a cuff reduces efficacy & too small of size cuff can cause discomfort. To address Dr. McBane's concerns, AVT optimized the broadest fitting cuff possible. It can fit a typical patient with 10" - 21" circumference calf & any shoe size up to 15 for a 5' - 6' 1" tall patient. The calf part of the cuff can be easily adjusted with Velcro after being zipped up & not needed to be re-adjusted for the same patient but adjusted each time for a new patient. TO # 2 & 4 & TQ # 1, 4 & 5: AVT's proof of concept (POC) was handmade in our lab & is now being developed to be repeatably made in two design sprints through our contractors with our input. The alpha model is refined over & over until it meets all final established design requirements & can easily & exactly be reproduced. The production quality beta model is then built & will be tested & certified for FDA requirements. AVT's POC's ducting was cost prohibitive to manufacture. ***The following contains proprietary/privileged information that AVT requests not be released to persons outside the Government, except for purposes of review & evaluation.*** So instead, AVT will use layers of foam with channels cut to form ducting reducing cost & improving flexibility & manufacturability, but requiring component repositioning & possible larger size & other issues described later. *** The valve was reconfigured to fit in these foam layers & still maintain activation speed, reliability & efficacy while reducing back pressure. Our manufacturers (GMI with subcontractor 316 Product Development & others) had to start with a much larger standard case & foam to reduce experimental cost. They designed (now in testing) all our circuitry on one board to reduce cost & created a cooling path in the foam with easy access to all components. The results of the larger foam and case were good. The final smaller case could not be made until final alpha because of cost. Test with the smaller foam were more noisy than expected. We will start with the blower, valve & air turbulence finding ways to block sound transmission that are manufacturable. We will use a thermal vacuum molding custom case built by CHellis in Indianapolis, IN. It will be close in quality to the original injection molded one, but much cheaper. We need this savings to cover cost increases (See Changes). Masson, INC in Indianapolis, IN developed the alpha cuff that Dr. McBane liked so much at similar cost to original estimates from Genesis Plastics (See Changes). TO # 3 & 4 & TQ # 1, 4 & 5: All PCDs will have factory software set serial numbers and all data changes will be logged. All subscribers - dealers, prescribing doctors & patient's clinics will have a revocable account, validated over the cloud before given access. Dealers can access their PCD's set up (directly) & patient billing information (web-based), & doctors & clinics can access their patients' medical data (web-based). The signup & validation is all being added to the alpha model, not developed in the POC that used an encrypted key and fixed password. This is possible because of the further software development of our cell (default) & Wi-Fi connectivity, & further web development as an alternative to a USB interface for the benefit of the patient, doctor, & payer (See Changes). New protocols are needed restricting AVT to only changing human input errors with written authorization & preventing the change of any device data outputs. We greatly reduced cost by utilizing the graphic user interface (GUI) of the POC that AVT was able to create in their lab. This GUI is almost unchanged in the alpha being developed. Covid caused several new features to be out of scope including diagnostic codes, automatic updating, enhanced Wi-Fi setup (switching & finding) & controlled shutdown. AVT will still achieve the project TOs. TO # 5 & TQ # 6: AVT's regulatory consultant Pearl Pathway - John Lockwood (formerly a Pearl employee, See Changes) feels AVT is correctly placed with multiple predicates & a planned pre-submission. While on the high side of budget ($45K remaining of $55K total), John feels we can still complete final submission with AVT contributing the technical documentation. Parts substitution because of limited supply chain can be replaced with more desired parts after submission with minimal documentation & testing required. Pre-submission will begin after alpha is final, likely the beginning of 2022. If there is any money left in the budget after completion of the project we will pursue FDA certified & tested packaging allowing us to ship, & not hand deliver our PCDS. We originally understood hand delivery would avoid this need for the first 22 units but John has expressed concern whether this additional FDA packaging & testing could be a requirement.

Publications

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

Outputs
Target Audience:Target Audience: Part of our target audience is doctors that prescribe our device to their patients. As described in our Accomplishments section, we have reached out to Dr.McBane for guidance what his patients need and want. Changes/Problems:Problems/Change: We did not encounter obstacles that were prohibitive to accomplishing the technical objectives. GMI's dedicated subcontractor, Jake Flagle, and his company 316 Product Development--experts in medical device Alpha development--are now part of our GMI team. Additionally, we were blessed to receive TABA funds to be applied to the manufacture of 12 additional prototypes for promotion or sales. The predominant problems AVT encountered in meeting the technical objectives were beyond AVT's control and included: funding delays resulting from the USDA move to Kansas and both delays and procedural workarounds caused by COVID-19. As such, AVT delivered our prototype to GMI approximately 9 months later than expected. COVID-19 related issues included connecting with Dr. McBane, who is in Rochester, MN. While we were able to communicate well virtually, COVID-19 restrictions, Mayo Clinic furloughs, and civil unrest made travel unfeasible. Further Dr. McBane was quarantined due to exposure to a COVID-positive patient. Due to the nature of the project, in-person and hands-on consultation are hugely beneficial. That said, despite these limitations and the resulting delays, we were able to communicate with Dr. McBane and move the project forward and transfer the prototype to GMI. Additionally, multiple members of AVT's team, including our programmer, project director, and project manager were COVID-positive or had exposure to COVID-positive individuals and required either quarantine or isolation and, where feasible, remote work, which resulted in additional delays. AVT continues to strive for an on-time project completion but may need an extension. It is too early to tell if that will be necessary; everyone is doing their best to move the project forward. What opportunities for training and professional development has the project provided?Training opportunities from the project: We were able to participate in several Larta webinars and two Venture Club webinars that will help our company commercialize as we go forward. Larta is an incredible resource and provided free for the USDA grant recipients. We are very grateful. 11/20/2019 - Larta "Seed and Series A Financing 101" 2/18/2020 - Larta "Business Strategy" 3/17/2020 - Larta "Navigating the Regulator Journey to Commercialization" 4/15/2020 - Venture Club "Covid Impact on Startups" 4/21/2020 - Larta "Building Digital Solutions" 4/30/2020 - Larta "Market Research / Competitive Landscape" 5/7/2020 - Venture Club "Alternate Financing Obstacles for Startups" 8/18/2020 - Larta "Licensing 101: Term Sheets and Royalty Modeling" How have the results been disseminated to communities of interest? Nothing Reported What do you plan to do during the next reporting period to accomplish the goals?Going Forward: AVT has largely accomplished Technical Objectives (TO) #1-3. TO #4 is in process and will be completed by GMI; the prototype was delivered to GMI 8/13/2020.TO #5 will be done by Pearl Pathway with GMI's help. AVT will follow the work plan in the original submission with the exceptions of the delay described in the Problem/Change section and the addition of Jake Flagel et al to the GMI team. Technical Objective 4: Transfer the PHI prototype to GMI and ramp-up manufacturing for home and clinical sales. We are working with GMI's dedicated subcontractor Jake Flagle, and his company 316 Product Development, experts in medical device Alpha development. GMI will oversee this process through Alpha 1 and 2, and all billing and management will be through GMI. GMI will directly provide all Beta development. Currently, AVT and Jake are collaborating to transfer prototype documentation and models to determine design specifications for Alpha 1. Upon team review and approval, Jake will build Alpha 1. After review and design specification changes, Alpha 1 will be modified to create a refined Alpha 2 prototype. The cycle will repeat until a final design is identified. Once final, GMI will produce up to 10 Beta units. Approach. Continuing the existing successful relationship, AVT, GMI and Jake will review requirements and complete two design sprints, which will include assessment interviews to determine critical production requirements, priority design features, and necessary changes to ensure efficacy, device comfort (including cuff design by Genesis Plastics), and cost-effectiveness. Genesis will collaborate with GMI and AVT to integrate the newly designed cuff into each prototype design. AVT will procure all materials and oversee the design and assembly. Once the two Alpha prototypes are completed, the team (AVT, GMI and Genesis Plastics) will collectively review and revise the designs to determine a Beta prototype design. GMI will produce up to 10 Beta units. Expected Outcomes, Potential Pitfalls and Alternative Strategies. Jake and GMI will track and log specifications on a Design Requirements document that will be reviewed and approved by AVT. To ensure the Alpha 1 prototype is in line with end-user requirements, Alpha prototypes will be evaluated against the Design Requirements document. With the development of each prototype design features will be evaluated against the Design Requirements document until the Beta design is finalized and up to 10 prototypes developed. GMI will manage change control procedures. AVT will continue to manage the project and ensure quality control. One potential pitfall is that it may be necessary to make design and/or feature compromises during this process. If the team encounters this challenge, GMI is highly experienced in identifying priorities and alternative solutions to meet design needs. Technical Objective 5: Prepare for FDA passage and regulatory clearance. AVT will complete verification and validation activities in preparation for beginning the FDA 510(k) clearance process. Approach. Through AVT's contract with GMI, a third-party testing firm will be identified and contracted for formalized testing of the Beta prototype units to ensure compliance with verification and validation protocols necessary for FDA 510(k) clearance. AVT will work with Pearl Pathways to begin the process necessary to obtain FDA 510(k) clearance. Expected Outcomes, Potential Pitfalls and Alternative Strategies. The verification and validation activities will be reported, approved, and controlled via Design Verification and Validation reports. AVT will work with Pearl Pathways to respond to all FDA requests for information and feedback for the clearance application. Final FDA testing and evaluation costs and timelines cannot be guaranteed. As AVT is seeking 510(k) clearance using predicates, no issues are anticipated. However, should a study be required, AVT is submitting a proposal for an NIH SBIR grant (expected submission date 2021--COVID-19 may affect this date) to fund and meet this requirement. If the FDA requires unanticipated steps, such as approving AVT's website and software separately, additional delays and resulting expenses may result. In that event, additional sources of funding will be pursued."

Impacts
What was accomplished under these goals? TO #1: Dr. McBane's analysis, approval & ongoing support in Technical Objective (TO) #1 below answer technical questions 1-3. TO #2 & 3 carry them out. Because of Dr. McBane's concern that an external Secure Digital (SD) card for storage could be easily lost, AVT opted for internal storage. AVT secured the operating system (OS) using 2 different internal SD cards-1 for system files & 1 for data. AVT determined Samsung SD cards were the most reliable. AVT created an overlay system to protect the Raspberry PI OS data integrity--preventing data from writing to the long-term system SD card. It also transfers the basic system to random volatile memory, avoiding damage to the long-term internal SD card storage, if shutdown incorrectly. Data only transfers to long term SD card storage via WiFi or cell connection to AVT's secure website (TO #3). AVT added visual warnings to prevent shutdown during upload. Internal storage requires a secure method to change settings (encrypted & password protected USB set-up key) & backup data (blank USB key when Wi-Fi or cell communication not available), so AVT added an external USB port, which will be limited to these uses on the final model. AVT created a 5-second shutdown delay to allow time for data transfer & system shutdown when switched off. We added an "ON" light to the power switch to signal shutdown during the delay. AVT communicated via web & telecommunications with Dr. McBane to ensure his satisfaction with improvements made to our PHI prototype, especially those improving patient ease of use (design modifications to the interface, display & setting options); weight, size & noise reductions; & home device speaking. He is very pleased with the secure website tracking compliance data & added settings to prevent deep vein thrombosis (DVT) (TO #3). Dr. McBane liked AVT's cuff benefits to patient comfort & convenience but is concerned with cuff costs, as they are replaced by clinicians after each clinical application. Competitor cuffs cost $200-300 each. While the AVT feels its cuff is better designed, work will continue to minimize patient cost & maintain efficacy. Dr McBane's approval of the current prototype initiated the transition to the GMI Alpha 1 iteration (TO #4). Dr. McBane is eager to see Alpha 1. TO #2: Because of delays (see Changes/Problems), AVT completed more research prior to a delayed hand-off to GMI. AVT determined a revised PHI blower remains the best option. GMI will further reduce circuitry & improve manufacturing efficiency. During PHI, AVT disassembled the blower to remove the internal cooling fan, to avoid backpressure & maintain cooling. Internal bolts were installed to solve EMF & add thermal protection. This could create additional manufacturing expense & reliability issues. To avoid disassembly, fan removal & reduce costs, AVT redirected airflow external to the original blower, supplementing airflow from the internal fan. An added external metal strap (placed by the internal coil of the blower motor) secures the EMF solution & thermal protection. This was accomplished without increased backpressure, temperature, EMF, or significant additional noise. AVT modified the cuff using optimally thin & flexible materials--a fine nylon fabric bonded to thin vinyl--to minimize discomfort, avoiding elasticity (preventing wasted airflow or hampered near-instant compression), and deadening noise. This material comprises the majority of the external air chamber surface, wraps over the cuff top to the internal air chamber surface, which is in contact with the limb, and is reinforced by a 2-inch overlap. A soft, clear vinyl, flat-bottomed shoe completes the cuff's external air chamber surface. A large hose quick-disconnect is positioned on the shoe toe box. The internal air chamber surface is made of very thin vinyl to ensure comfort when in contact with the contours of the limb. Elastic anchors were added internally at the toe & heel to prevent crowding or misalignment of the foot (due to poorly adjusted Velcro) & to maintain uniform compression. AVT added Velcro strips to the cuff front & a rear zipper for limb insertion, which was accomplished without interrupting the air chamber. The zipper was inserted with sealed sewing & adhesives. A flap was inserted in the air chamber to protect the patient's skin & avoid pressure points. TO #3: Per Dr. McBane's approval, AVT retained all settings & defaults; added a DVT prevention mode, which includes a voice alert to inform home patients with limited vision of current treatment status & time remaining & corresponds with a simple touch-to-pause screen. AVT added software/hardware fail-safes, such as a software-generated signal, periodically checked by hardware, to verify critical code that activates compression. If a signal is not detected, the blower stops preventing harm to the patient. Dr. McBane & Brian Mullinax (reimbursement specialist) agreed compliance feedback is essential to home & clinical users, as it directs treatment plans, validates reimbursement & makes the device more affordable. We consulted John Lockwood (Pearl Pathway-regulatory), Device IQ Software (medical device expertise) & our programmer to determine key factors to consider: 1) FDA requirements, 2) best software & protocol solutions, 3) HIPAA, 4) medical record & medical record number (MRN) format variances between clinics. Based on the above, the device only stores & transmits non-patient identifiable data. It initiates any secured, encrypted & verified transmission to our password-protected website. It accepts no transmission from outside except overhead response to these transmissions. Without validation of the transmission, it continues to store the data internally until successfully transmitted. The final model will feature a "nag" screen prompting data upload to a USB drive at one month & requiring it after 2 months without. The USB key will be mailed to AVT's compliance subscription service, which will be secured with national provider identifier (NPI) credentials for each account. Access to the device settings is restricted to those with encrypted dealer USB key & password. AVT created a new dealer-settings device menu & a secure, encrypted subscriber website. The settings screen features prescriber, clinic & dealer NPIs, patient MRNs, WiFi & cell information. The website includes multiple compliance data points referring to the patient MRN & machine serial number & allows access only to appropriate NPIs. The website has "search & sort" abilities, a "more" option & a dealer-only page with reimbursement interest highlighted. The larger clinics, with internal IT departments, will directly download patient compliance feedback from AVT's site. TO #4: GMI will address technical questions 4-5. We began transferring AVT's prototype development to GMI mid-August 2020 (Change/Problem). The progression from AVT's PHI prototype impressed GMI. We are working with GMI dedicated subcontractor & medical device Alpha development expert Jake Flagle (316 Product Development) to oversee the Alpha 1 & 2 development process. GMI will oversee all billing, management & Beta development. Current prototype documentation & models needed for Alpha 1 design requirements are being transferred. No substantive changes to the original statement of work is expected. TO #5: Pearl Pathways will answer technical question 6 when FDA clearance of AVT's Beta begins. The regulatory process started with Pearl Pathways' John Lockwood prior to & during PHII. He has guided all AVT FDA regulatory questions along the way, including compliance feedback. AVT plans a continued partnership with John during Alpha & Beta development and FDA submission.

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