U.S. Food and Drug Administration Center for Devices and Radiological Health Document Control Center 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 FDA Pre-Submission Cover Letter QSub Type: PreSubmission Modern Medical Equipments​​ will share current product development plans. We look forward to feedback from the FDA. Device name: ​Osteoporosis Micro-needle Patch Company Partners: ​Ammar Sheikh, Abdulrahman Sindi, Deanna-Nicole Busog , Ansam Alkhafaji. Mailing address: Catholic University of America 620 Michigan Ave NE, Washington, DC 20064 Table of Contents I. II. Device Description Proposed Intended Use III. New Modification IV. Product Classification V. VI. VII. VIII. IX. Submission Type Product Code CFR Regulation Number Overview of Product Development Specific Questions X. Feedback XI. References I. Description Technological advancements have seen the formulation of concepts that are much smaller in size and efficient as compared to the older conventional ways. Microneedle patches comprise of microneedles less than a millimeter long and are intended to deliver drug substances and vaccinations into the skin (Arya et al.). In the event of administering the patch, the microneedles dissolve in the skin within a short time, preferably twenty minutes or so. This process helps to see that the drug is delivered into the body. Typically, the patches may contain coated microneedles or dissolving microneedle patches containing solid metal. Microneedle patches are aimed at replacing or instead substituting the conventional needle-and-syringe injections. II. Proposed Intended Use: Meant as an alternative to the use of needles to administer drugs through the skin, through the dissolution of the coating on the microneedle patches, or the dissolution of water-soluble microneedles. The target population for this device are patients living with osteoporosis. Our microneedle patches can treat osteoporosis through the delivery of the parathyroid hormone.The microneedle patches can be placed on different parts of the body including arms, abdomen, and thighs. This device is meant to be used by caregivers, including doctors, nurses, and clinic staff, and can also be self-administered by the patient. Each patch is intended for single use drug administration. Our device is intended for prescription use. Each of our patches will have a set amount of the parathyroid hormone, which we will still have to determine, but the dosage, prescription, and number of patches for daily patient use will be determined by the caregiver. III. New modification The micro-needle patch is a new device. It cannot be easily used by patients themselves and are therefore utilized primarily in the clinic or at home by patients who have received special training on correct injection method. Rather than avoiding needles, it is proposed shrinking the needle to micron dimensions in order to make use of its powerful delivery capabilities while improving patient compliance and safety. As a micron-scale device, a microneedle should be large enough to deliver almost any drug or small particulate formulation, but still be small enough to avoid pain, fear and the need for expert training to administer. Microneedles can generally be classified into four types according to drug delivery methods: solid, coated, dissolving, and hollow microneedles. Each type of microneedle has pros and cons. A solid microneedle punctures the surface of the skin and applies the drug to the skin layer, allowing the drug to slowly diffuse through the holes. It has the advantage of preventing pathogenic infection but the drug delivery effect is low. Coated microneedle is typically coated with a water-soluble drug. The microneedle is attached to the skin, the drug is quickly delivered to the skin, and then the microneedle is removed. It has an advantage of delivering a very small fixed amount of drug. Unlike other types of microneedle, the dissolving microneedles are made of water-soluble materials. When the microneedle is pushed into the skin, the microneedle melts in the skin, releasing the drug in the microneedle (​Ki Mun). IV. Product Classification: ● Class: II V. Submission Type: ● 510(k) #K874024 VI. Product Code: ● FMI VII. CFR Regular number: ● 880.5570: ​Hypodermic Needle VIII. Overview of Product Development The studies performed were done on human subjects to test tolerability, usability and self-administration capabilities of our microneedle patches, and were not yet filled with any drugs. Our studies were performed on 15 participants, eligibility to enter the studies included an age range from 18-57 years. Participants were also required to have normal skin with no allergies to materials used in our patches, or had been previously exposed to any microneedle patches. The patches we used in this study were made out of biocompatible and water-soluble materials; polyvinyl alcohol and sucrose. Since we are also testing to make sure our patches can be self-administered, the patches had a grade tape that made a clicking sound, acting as force-feedback, when a sufficient force was applied. Unlike previous studies performed, high-velocity insertion devices were not used here, devices which are typically used to ensure that the needles are penetrated adequately into the skin. Instead, pressure from the thumbs of administers are being used. The patches were stored for approximately four weeks, and observations under a microscope were done to ensure their viability before carrying out of the research. For the 15 eligible participants, the experiment first involved a briefing on the procedures. A short instructional presentation was first made on self-administration. Later, each participant received three patches; one which was to be self-administered, and two which were to be investigator-administered. Each arm where a patch was placed received markings, made by staining the site on the skin, to help in usability measurement. A survey was later conducted to gauge the tolerability of the patches by the participants. Days later, visits to the study site were made for tolerability measurements, which involved checking for pain, tenderness and size and grade of swelling (erythema) on the skin. Once the experiments were completed, assessments of the results were made. Skin tolerability studies were established to recognize and categorize reactions in the skin. Tolerability of the skin is dependent on the process of administration of the patch and the excipients left in the skin once the dissolution of the microneedles takes place. Interestingly, only one out of the fifteen participants reported tenderness at the skin site on the material day, but the pain was no more on the second day (Arya et al. 3). Apart from this finding, none of the subjects indicated swelling of the skin site; the patches were tolerated appropriately with only relative transient erythema that was no more by the seventh day (Arya et al. 3). The usability of the microneedle patches was determined, by checking the reliability in the manner in which it dissolved in the skin. Self-administration after very brief training on the same was also identified, and it was noted that the usability was identical between investigator and self-administration and the patches were adequately dissolved into the skin. We also found that the average wear time would be about 20 minutes, which is the time it took for the patches to dissolve into the skin. Acceptability reports indicated that majority preferred microneedle patch administration over the conventional way of needle injections. Further Development: In order to facilitate the delivery of the entire intended drugs dose into the skin, some modified fabrications need to development . These include micro molding of arrowhead dMNs mounted on mechanically strong shafts or dMNs presenting an elongated base increasing the needle length . There is some modification which include patch pillars to improve the delivery efficiency. After patch application into the skin, dMNs separate from the pillars due to a tensile breaking force of the fibrous sheet between the pillar and the dMN. This allows a proper implantation of the dMNs into the skin and removal of the remaining back plate without the need to wait dMN dissolution ​(R. Prausnitz). IX. Questions ● The study was conducted on a group of 15 participants in the age of 18-57 years old. What would be a better age range that can participate in the same study to provide an adequate feedback? ● Other than the conventional needle-and-syringe injections, what would be the best medical device to compare our product with, in terms of safety and effectiveness? ● Does the FDA have any feedback regarding the studies we have conducted to further develop the safety and effectiveness of our product? X. Feedback ● Preferred methods to receive feedback: - E-mail: ​asheikh1417@gmail.com - Phone : +1(202)999-5523 - Mailing address: Catholic University of America 620 Michigan Ave NE, Washington, DC 20064 ● Meeting request dates and times: - October 24th 2018, at 2:30pm - November 1st 2018, at 9:00am - November 10th 2018, at 11:00am XI. References ● FDA.(2017).​Guidance for industry and food and drug administration staff.​ Retrived from https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidanced ocuments/ucm575923.pdf ● FDA. ​510(k) access data. R ​ etrived from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpcd/classification.cfm?id=2529 ● Arya, Jaya, and Mark R. Prausnitz. “Microneedles for Drug and Vaccine Delivery.” Journal of Controlled Release : Official Journal of the Controlled Release Society,​ U.S. National Library of Medicine, 28 Oct. 2016, www.ncbi.nlm.nih.gov/pmc/articles/PMC4871790/​. ● Kwon, Ki Mun, et al. “Microneedles: Quick and Easy Delivery Methods of Vaccines.” Clinical and Experimental Vaccine Research​, The Korean Vaccine Society, July 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5540964/​. ● Arya, Jaya, et al. “Tolerability, Usability and Acceptability of Dissolving Microneedle Patch Administration in Human Subjects.” ​Biomaterials​, vol. 128, 2017, pp. 1–7., doi:10.1016/j.biomaterials.2017.02.040.
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