Corium, Inc.: ADLARITY

If significant changes are made to the product (e.g., in formulation, design, and size) to address the Complete Response deficiencies identified below, additional studies such as in vivo adhesion studies, other clinical assessments, and/or redevelopment of some quality test methods and acceptance criteria may be necessitated.

2. There is an overarching concern that the drug product on release is not equivalent to the drug product after long-term storage.

It is also unclear whether the donepezil salt:base ratio changes during storage.

To demonstrate the product at the beginning of shelf life is equivalent to product at the end of shelf life, you should conduct a bioequivalence study on product near the beginning of shelf life comparing it to product near the end of the proposed shelf-life.

Alternatively, you should develop a formulation which exhibits greater stability with respect to excipient degradation, migration, ® etc. We also refer you to Complete Response deficiency #3, which recommends a new bioequivalence study with oral Aricept, and Complete Response deficiency #1, which may result in a reformulation.

Bioequivalence (BE) and Registration Product Comparison, compared batches with different manufacturing processes, active product ingredient particle sizes, storage times, and storage temperatures in addition to scale changes.

To address this concern, you should conduct a new bioequivalence (BE) study with oral Aricept utilizing the proposed commercial product/manufacturing process.

Satisfactory resolution of these deficiencies is required before this application may be approved.

The following comments are not approvability issues, but should be addressed in the resubmission of this application.

3. The amendment to the NDA, submitted on April 28, 2020, included an unsolicited facility submission.

Perform an in-use stability study to demonstrate that the drug product quality remains unaffected through the longest expected period of use (7 days) at lowest dose (5 mg/day).

The clinical relevance of these lower concentrations is not known, and to ensure clinical benefit, oral supplementation with 5 mg/day ARICEPT may be required during the first 2 weeks of oral-totransdermal system switch.

Moreover, the errors observed in this study indicate the labeling did not provide assurance that patients and caregivers could adequately identify adhesive squares that remained on the skin or on the liner.

The Agency recommends that the human-readable expiration date on the product package label include a year, month, and non-zero day.

Additionally, the Agency recommends that the expiration date appear in YYYY-MM-DD format if only numerical characters are used or in YYYY-MMM-DD if alphabetical characters are used to represent the month.

201.55. We recommend that you revise the container labels and carton labeling to read: "Recommended dosage: See prescribing information and Instructions for Use for dosing and application instructions."

"Keep ADLARITY in the individual sealed pouch until use" to the storage statement on the labels and labeling.