What did the FDA's first letter on VP-102 object to?

FDA Complete Response Letter, July 13, 2020 · page 12

Please refer to your new drug application (NDA) dated and received September 13, 2019, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act for cantharidin topical solution, 7%. We have completed our review of this application and have determined that we cannot approve this application in its present form. We have described our reasons for this action below and, where possible, our recommendations to address these issues.

FDA Complete Response Letter, July 13, 2020 · page 12

The proposed drug product specification does not include test to assure the drug product can be safety and accurately expelled onto the lesion area and avoid the adjacent healthy skin. The specification for the final assembled drug product should be revised to include the following: a. A test for the crushing force of the glass ampule. b. A leakage test after ampule crushing to assure there is no drug leakage at release and during shelf-life. c. A droplet test to demonstrate that the users are capable of dispensing various amount of drug product as needed to the affected skin area while avoiding the adjacent healthy skin.

FDA Complete Response Letter, July 13, 2020 · page 14

We note your heuristic analysis submitted on April 10, 2020 indicates that the average palmar pinch force (grip used to break an ampule) for adult females is 16 lbs. and that the average force to break the ampule with paperboard sleeve on is 19 lbs.

FDA Complete Response Letter, July 13, 2020 · page 14

As we previously communicated, our review of the human factors (HF) validation study data noted use errors and difficulties with the critical task- ‘Break the Ampule’. We note one use error and three difficulties with the critical task. The use error occurred when the user removed the cap and paperboard sleeve, tipped the applicator upside down and broke the ampule with two hands. Additionally, three other users had difficulty breaking the ampule, which required two hands to break. Of these three use difficulties, one user also tilted the applicator horizontally. Based on your use-related risk analysis (URRA), this task is considered critical because premature cap removal and incorrect applicator orientation can lead to accidental exposure to the patient or healthcare provider’s (HCP’s) mouth or eyes leading to serious harm. Despite the use error and difficulties with critical task, you did not propose any additional mitigation strategies to address the use issues (e.g., reducing the force required to break the ampule).

FDA Complete Response Letter, July 13, 2020 · page 15

We recommend you submit your revised HF validation study protocol for feedback from the Agency before commencing the study. Please note we will need 60 days to review and provide comments on the HF validation study protocol. Plan your development program timeline accordingly.

FDA Complete Response Letter, July 13, 2020 · page 15

We also reviewed your April 10, 2020 threshold/comparative analyses with Eskata and Levulan Kerastick; products with some similarities to the proposed product in this review. We determined that the Levulan Kerastick has a different user interface than your proposed product because the Levulan Kerastick includes the Kerastick Krusher device as a means of breaking the ampule prior to administration. This difference may impact performance of the critical task of breaking the ampule. Furthermore, with respect to the comparative analyses to the Eskata product, we note postmarketing medication error cases that report accidental exposure to patient and health care professionals when using the product. Given some of the similar design attributes with your proposed product, we are concerned that accidental exposure can occur with cantharidin topical solution, which may present a different risk. As such, we have determined that a leveraging approach for your proposed product is not appropriate and the residual risk with your product is unacceptable.

FDA Complete Response Letter, July 13, 2020 · page 15

In summary, we remain concerned that your proposed cantharidin combination product is not safe for use by HCPs. We are concerned that the risk of accidental exposure will outweigh the benefit of the treatment with this combination product. Inherent design issues exist with this product that may contribute to serious harm if accidental exposure occurs during use. Thus, additional mitigation strategies are needed and could include the need for device design changes to optimize applicator use along with other revisions to the product user interface taking into consideration our previously identified concerns and the data collected from your HF validation study. After you implement additional risk mitigation strategies/modifications, we recommend you conduct an additional HF validation study to ensure that these modifications address the observed use errors and use difficulties and do not introduce any new risks.

FDA Complete Response Letter, July 13, 2020 · page 15

there is a potential that users will struggle to break the glass ampule due to the amount of force required. There is risk that some users may remove the paperboard sleeve in order to try and break the glass ampule. There is also potential for users to utilize other means to break the ampule if they are unable to generate enough force with their hands.”