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

Outputs
Target Audience:We have shared information on the radiation attenution glove and the need for specialty natural ruber latex production to support intial establishment of domesiic rubber crops to 398 potential investorsand several manufacturing companies interested in developing or using domestic sources of alternative natural rubber production. We also won a USDA grant to support a conference on Domestic Natural Rubber which was held in October 2021 and attracted over 50 attendees from industry, government and academia. This conference has led to a recurring bimonthly meeting among these stakeholders, with the goal of garnering interagency support. In October 2021, EnergyEne was invited to participate in the OSU portfolio of technologies. This contribution led to OSU's selection as a source of relevant innovations applicable to both DoD and commercial markets. EnergyEne was then selected to participate in the summer 2022 10 week NSIN (National Security Innovation Network) Emerge Accelerator. and received a $15,000 grant which should lead to new opportunities for guayule latex in critical military applications. This includedpreparingand presenting a DOD-focused 5 minute pitch and a two page visual "handout". EnergyEne was selected for a mainstage presentation which was given by our CEO. About 50 registrants attended this presentation. We completed the glove durability tester and demonstrated this virutally to the ASTM D11 Committee on Rubber and Rubber-like Materials, subcommittee D11.40 Consumer and Medical Products June meeting which included representives of numerous manufacturers. Changes/Problems:We have received a 12-monthno cost extension. this was required becasue of FDA delays in responses to questions,and becasue our identified toll manufacturer back out at the last minute. It took some time to find a replacement company but this has now been acheived. What opportunities for training and professional development has the project provided?We have trained a high school graduate with austic spectrum disorderto provide technical support to our research techician. How have the results been disseminated to communities of interest?We participated in 2022COSI Science festival as part of the OSU Rubber Bandits booth (one of 103 booths). Among many activities, we demonstrated the glove durability tester and presented glove latex gloves as well as poorer perfoming glvoes from other materials.This event had 25,000 attendees. The COSI 2022 Impact Report describes 95,000 people reached and 2.6 million impressions. What do you plan to do during the next reporting period to accomplish the goals?We have received a 12 month no-cost extension of this project. this will aloow us to complete the toll manufacturing run, use the 500 gloves to accumulaet all the data required by FDA and submitt our formal 510(k) premarket approval application.

Impacts
What was accomplished under these goals? Objective 1: Optimize curing protocols for two hand-specific and one ambidextrous guayule natural rubber latex radiation attenuation gloves. The final curing protocol of 91°C for 85 minutes previously selected for manufacture of GNRL RA examination gloves containing 150 PHR Bi2O3 was adjusted because, when a new shipment ofBi2O3 ,arrived the formulation had to be adjusted to maintain glove quality and to remove bubbles. A low concentration of carboxymethyl cellulose was added to stablilze the suspension ofBi2O3 in the guayule latex. Objective 2: Produce sufficient gloves for testing to ensure product integrity and safety, in support of one submission for a radiation attenuation examination glove to FDA for market clearance. Kent Elastomeric Productsunexpectedly backed out of their agreement to toll manufacture our guayule radiation attentiation gloves. Fortunately, we have been able to recruit DipTech, Kent, Ohio. We have run on site dipping tests at DipTech and haveensuredthat the necessary compounding ingredients have been purchased. Our latex drums have been rolled to ensure that the latex isfully suspended in advance of the toll manufacturing run. Objective 3: Determine effect of gamma sterilization on glove physical properties. This objective will be performed on gloves from the toll manufacturing run during our no-cost extension Year 3. This was delayed because Kent Elastomeric Products backedout of their agreement (see Objective 2) Objective 4: Submit application to FDA for a non-sterile, hand-specific RA examination glove and obtain clearance to market from FDA. EnergyEne determined FDA's "current thinking" on glove submissions to formulate a strategy for market clearance by the FDA. Our TABA conustant, Donna DiGangi, has participated in team meetings and has worked with EnergyEne to provide advice on claims substantiation, and help develop and train the team on the design control process, EnergyEne's submitted the Q-submission (a written request for feedback) to FDA . EnergyEne requested additional information to determine whether a510(k) submission or a De Novo submission willb e required. This led to a virtual conference with FDA personnel in which FDA directed us to use the guayule latex examination glove as the predicate dievice and then add radiation attention properties to this predicate andfile a 510(k), not a de novo submission. Objective 5: Design, manufacture, and validate a glove durability testing device. The glove durability testing device has been completed and hasbeen demonstrated to ASTM and to the general public (COSI event - see Communities of Interst below)). .ASs we precviulsy reported, an invention disclosure application was submitted and accepted by the Ohio State University's Innovate IP program on May 6, 2021 - it is still unclear if OSU will submit a patent application. Since EnergyEne is an OSU spin-off and its CEO Dr. Katrina Cornish is an OSU Professor, anything she "touches" has to first pass through OSU's Office of Technology andCommercialization. If OSU declines to submit, EnergyEne may then do so.Dr. Cornish's OSU Ph. D. student has been a key researcher on the tester construction and on the published paper. She is extending her research on glove durability using this device - and has proven that EnergyEne's guayule radiation attenuation glove outlasts several radiation gloves currently in the marketplace. We have made 50+ gloves in-house and bought the other gloves fordirect comparison. Objective 6: Introduction of a new ASTM Glove Durability Standard, which will enhance the marketability of Guayule Latex Gloves. EnergyEne presented the glove durability tester design and initial data at the ASTM meeting in June 2021. Sub-committee D11.40 agreed to start work on a new standard once the test is demonstrated at the in person Dec 2021 meeting. However, due to the spread of new COVID-19variants this meeting was changed to a virtual meeting.The June 2022 meeiting was held in Seattle in person but we decided not to risk transporting the device while there is only one. ASTM and the glove industry are still discussing the funding of multiple testers because new standards require round robin testing so that required precision andbias statements can be prepared. Objective 7: Competitive analysis and market research. Other companies involved in guayule rubber globally are mostly tire companies using multiple organic solvents to extract and purify rubber targeted to the solid rubber market, especially for tires. Although this is the largest market, it also has the lowest profit margins. EnergyEne is the only company currently capable of producing guayule latex using water-based extraction technology, which is suitable for the high margin consumer and medical latex markets. We have tested the guayule radiation attenuation glove for durability agains several commercially available gloves and have sent sample to MD Anderson to confirm the attenuation efficiency of all these gloves and test their mechanical performance. This will allow us to refine our labelling claims for the 510(k) submission as well as our marketing materials - centered around making the only natural latex examination glove also able to attenuate radiation sufficiently be used by itself (without double-gloving i.e., two gloves on each hand). The COVID-19 pandemicdoubled medical glove demand to 600 billion/year. As the COVID-19 pandemic wanes it is predicted that demand will settle to about 450 billion/year.Manufacture and sale of first-to-market, high profit margin guayule latex products, like our new glove, can be addressed with latex production from small acreages and pilot plant production. Discussions revealed that weshould continue to develop a sterile surgeon's glove and a super-attenuating examination glove. In addition, market research at MD Anderson has revealed a need for a disposal RA glove. We predict that a single-use RA medical glove that meets the radiation attenuation standard but is much thinner than any RA glove currently in the marketplace may have real utility and rapidly gain market share. In addition, MD Anderson medical personnel have requested additional medical devices made from guayule latex, such as an NMR imagable, isotope and metal dosed GNRL brachytherapy seed. Also, Balloon Maestro has approached us, representing a cadre of balloon artists in need of a high-performance allergy-safe balloon. - another example of a premium, low volume, market. Objective 8: Partner with Kent Elastomer Products to make the Radiation Attenuation Gloves in the US, with a EnergyEne private label. Kent Elastomer Products unexpectedly backed out of their agreement to currently schedule their toll run of 500 guayule latex RA exam gloves. This caused a serious delay in manufacture. However, we are now working with Diptech, Kent, OH and have run intial tests at their facility and so expect the toll run to occur this year. Objective 9: Investigate licensing glove production rights to select partners. EnergyEne will discuss this option with at least 4 glove companies, including Ansell HealthCare, US Medical Glove, Medline and FLC, after the initial mechanical testing of the toll gloves. Letters of intent and take off agreements will be discussed to support major investment into guayule latex manufacture. These companies are already aware that we are preparing for a 510(k) submission and are waiting for that to be cleared before proceeding further.

Publications

• Type: Journal Articles Status: Published Year Published: 2022 Citation: Ramirez-Cadavid, D.A., Layman, R.R., Nishino, T., Slutzky, J.L., Li, Z., Cornish, K., Characterization of Guayule Natural Rubber Latex and Bi2O3 films for X-Ray Attenuating Medical Gloves, Special Issue, Radiation Shielding Materials, Materials 15: 1184-1207, 2022. DOI: 10.3390/ma15031184
• Type: Journal Articles Status: Published Year Published: 2022 Citation: Venturini, A., Pancake, M., VanCleave, W., Wan, Y., Cornish, K., Invention of a Medical Glove Durability Assessment Device, Inventions 7:62-77, 2022

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

Outputs
Target Audience:Information was shared with industrial representatives and scientists during the 2021 International latex conference. Additionally, we have shared information with potential investors interested in developing a domestic source of alternative natural rubber production. Also, various FDA officials and conferences such as (International elastomer conference, ASTM 11.40, Bio environmental polymer society, Rubber and Plastics News Health care elastomers, and NSF convergent accelerator workshop). Changes/Problems:The interaction between FDA and EnergyEne is taking longer than planned, which is understandable because of the pandemic. EnergyEne does not believe that there is any cost impact to the project. The delays will continue but it believed that these can be managed. The above normal heat in Northeast Ohio has made it necessary to thin the latex to avoid clotting.A minor delay occurred when we observed that some drums of latex had "clotted" (not coagulated). This required that 1/5th of the volume from the top of each drum was removed, remixed with 20% volume of stabilization buffer, and then mixed back into the latex remaining in the drum adn rolled with a drum roller for 5 hours. This small dilution requires a reduction in the volume of added buffer in the glove formulation, to ensure that the final recipe remains the same as the optimized formulation. This has delayed the delivery to the toll manufacturer, but no long-term delays and/ or costs are anticipated. The development of the device has been delayed due to staffing changes at OSU's CDME. The current target completion date is October 31, 2021 What opportunities for training and professional development has the project provided?The training of EnergyEne's processing staff (2 people, including a recent career center high school graduate) developed improved dippingtechniques and testing procedures. How have the results been disseminated to communities of interest?Information was shared with industrial representatives and scientists during the 2021 International latex conference. Additionally, we have shared information with potential investors interested in developing a domestic source of alternative natural rubber production. Also, various FDA officials and conferences such as (International elastomer conference, ASTM 11.40, Bio environmental polymer society, Rubber and Plastics News Health care elastomers, and NSF convergent accelerator workshop). What do you plan to do during the next reporting period to accomplish the goals?EnergyEne will make any necessary changes to the glove dipping procedures and/or latex formulation based upon the test results adn will develop a sterile surgeon's glove and a super-attenuating examination glove. In addition, market research at MD Anderson has revealed a need for a disposal RA glove. We predict that a single-use RA medical glove that meets the radiation attenuation standard but is much thinner than any RA glove currently in the marketplace may have real utility and rapidly gain market share. In addition, MD Anderson medical personnel have requested additional medical devices made from guayule latex. In one example, brachytherapy seed are typically titanium with an implanted radioactive material (Pd-103, I-125, etc.) but the titanium could be replaced with a polymer such as GNR and solve clinical problems. The selection of the radioisotope controls the radiation dose rate and particle range. The seeds are then implanted into a tumor to deliver the radiotherapy. They can be left in the patient permanently or removed after a period. The clinical challenge is that the titanium they are made with causes image artifacts (streaks and signal void (Fig. 10). This creates challenges to ensure placement, evaluate the tumor after therapy for response assessment, etc. Questions to answer are durability of GNR during radiation and how to implant. Besides removing the image artifacts, there is an opportunity to make the GNR version imageable using bismuth (as in our RAG), iodine or gadolinium, all of which are excellent for MR imaging. Furthermore, Balloon Maestro has approached us, representing a cadre of balloon artists in need of a high-performance allergy-safe balloon. - another example of a premium, low volume, market. We may make prototypes for them as time permits. The toll manufacture will produce 500 radiation attenuation gloves. The gloves wilol be tested using standard trensiometrty and the Glove Durability tester to provide data for the FDA 501K submission. Market research and competitive analysis will be continued.

Impacts
What was accomplished under these goals? Objective 1: Optimize curing protocols for two hand-specific and one ambidextrous guayule natural rubber latex radiation attenuation gloves. An extensive round of curing protocol variations (temperature and time) was tested using die D, to maximize the number of formulations and tensiometer tests possible. The best curing protocols were used to make radiation attenuation gloves and their mechanical performance was retested with Die C dumbells, the ASTM-recommended die size for latex glove films. A final curing protocol of 91°C for 85 minutes was selected for manufacture of GNRL RA examination gloves containing 150 PHR Bi2O3. Objective 2: Produce sufficient gloves for testing to ensure product integrity and safety, in support of one submission for a radiation attenuation examination glove to FDA for market clearance. Kent Elastomeric Products, Inc, is currently scheduling the toll manufacturing run. We are ensuring that the necessary compounding ingredients are purchased in advance and that the drums are latex are fully suspended in advance of the run. Objective 3: Determine effect of gamma sterilization on glove physical properties. This objective will be performed on gloves from the toll manufacturing run, in Year 2 of the project. Objective 4: Submit application to FDA for a non-sterile, hand-specific RA examination glove and obtain clearance to market from FDA. EnergyEne determined FDA's "current thinking" on glove submissions to formulate a strategy for market clearance by the FDA. Ou TABA conustant, DiGangi, has participated in team meetings and has worked with EnergyEne to provide advisory on claims substantiation, develop and train the team on the design control process, EnergyEne's submitted the Q-submission (a written request for feedback) to FDA. EnergyEne requested additional information that will direct preparation of either a 510(k) submission or a De Novo submission. Objective 5: Design, manufacture, and validate a glove durability testing device. The design for the new prototype was based on an undergraduate Capstone project completed at the Ohio State University in 2017. This prototype was used to collect baseline data for comparison with the data collected using the new automated prototype. Medical and surgical gloves are an important line of defense in preventing the spread of healthcare-associated infections (HAIs) between caregivers and their patients. Unfortunately, the American Society for Testing and Materials (ASTM) does not currently have a minimum standard for the durability of medical gloves once they are removed from their packaging and, as a result, the quality of gloves varies widely among manufacturers. In addition, the current ASTM standard test for punctures in medical gloves consists of filling a glove with water and manually observing if any leaks are present, which is highly inefficient. Therefore, a medical glove durability testing device was developed with the goal of proposing a standard for glove durability to ASTM. The device will also be implemented as a required part of the glove manufacturing process, once approved by ASTM, and adopted by FDA. The glove durability testing device was disclosed at the ASTM D11 meeting, which occurred online on June 7, 2021. An invention disclosure application was also submitted and accepted by the Ohio State University's Innovate IP program on May 6, 2021. Objective 6: Introduction a new ASTM Glove Durability Standard, which will enhance the marketability of Guayule Latex Gloves. EnergyEne presented the glove durability tester design and initial data at the ASTM meeting in June 2021. Sub-committee D11.40 agreed to start work on a new standard once the test is demonstrated at the Dec 2021 meeting. Objective 7: Competitive analysis and market research. Other companies involved in guayule rubber globally are mostly tire companies using multiple organic solvents to extract and purify rubber targeted to the solid rubber market, especially for tires. Although this is the largest market, it also has the lowest profit margins. EnergyEne is the only company currently capable of producing guayule latex using water-based extraction technology, which is suitable for the high margin consumer and medical latex markets. The COVID-19 pandemic has doubled medical glove demand. Although unsustainable nitrile latex has made up about 100 billion gloves, 200 billion are outstanding requiring one million tons of natural latex, while global latex production dropped by 10% (1.4 million tons) due to leaf drop blights, extreme weather events and pandemic induced labor shortages. Latex manufacturers have only small inventories of latex on hand. Hevea latex has a shelflife of only a few months, and so manufacturers buy frequent shipments, untiull recently often under annual contracts. Latex shortfalls have led the producers and distributers to refuse long term contracts and US manufacturers are currently forced to buy essential supplies under rapidly increasing spot pricing. Manufacture and sale of first-to-market, high profit margin guayule latex products, like our new glove, can be addressed with latex production from small acreages and pilot plant production. Discussions revelatd that we should continue to develop a sterile surgeon's glove and a super-attenuating examination glove. In addition, market research at MD Anderson has revealed a need for a disposal RA glove. We predict that a single-use RA medical glove that meets the radiation attenuation standard but is much thinner than any RA glove currently in the marketplace may have real utility and rapidly gain market share. In addition, MD Anderson medical personnel have requested additional medical devices made from guayule latex, such as an NMR imagable, isotope and metal dosed GNRL brachytherapy seed. Also, Balloon Maestro has approached us, representing a cadre of balloon artists in need of a high-performance allergy-safe balloon. - another example of a premium, low volume, market. Objective 8: Partner with Kent Elastomer Products to make the Radiation Attenuation Gloves in the US, with a EnergyEne private label. Kent Elastomer is currently scheduling their toll run of 500 guayule latex RA exam gloves. Current estimate is late September or October. Objective 9: Investigate licensing glove production rights to select partners. EnergyEne will discuss this option with at least 4 glove companies, including Ansell HealthCare, US Medical Glove, Medline and FLC, after the initial mechanical testing of the toll gloves. Letters of intent and take off agreements will be discussed to support major investment into guayule latex manufacture.

Publications