Approval Letter Other 210526 (Jan 1, 2022)

During a recent inspection of the Tris Pharma, Inc. (FEI: 3004712471) manufacturing facility for this application, our field investigator conveyed deficiencies to the representative of the facility. Satisfactory resolution of these deficiencies is required before this application may be approved.

Recommended response: Address and resolve all deficiencies identified during the manufacturing facility inspection. Provide documentation of satisfactory resolution to the agency.

The 505(b)(2) application relies upon the Agency’s finding of safety and effectiveness for NDA 011522 for Adderall Tablets, for which a Paragraph IV certification was submitted. However, documentation of receipt by each person identified in 21 CFR 314.52(a) of the required notice for the ‘020 patent has not been provided. Acceptable forms of documentation are described in 21 CFR 314.52(e). Notification to FDA within 14 days of any legal action filed within 45 days of receipt of the notice of Paragraph IV certification is also required per 21 CFR 314.107(f)(2).

Recommended response: Provide complete documentation of receipt of the Paragraph IV certification notice as per 21 CFR 314.52(a) and (e). Ensure timely notification to FDA regarding any legal actions related to the Paragraph IV certification.

Cited: 21 CFR 314.52(a), 21 CFR 314.52(e), 21 CFR 314.107(f)(2)

Comment on the proposed labeling is reserved until the application is otherwise adequate. The sponsor is encouraged to review labeling review resources on PLR Requirements for Prescribing Information and Pregnancy and Lactation Labeling Final Rule websites, including regulations and related guidance documents and the Selected Requirements for Prescribing Information (SRPI) checklist. Any revised labeling must conform with format items in regulations and guidances and include updated content of labeling [21 CFR 314.50(l)(1)(i)] in structured product labeling (SPL) format.

Recommended response: Review and revise the proposed prescribing information according to PLR requirements, Pregnancy and Lactation Labeling Final Rule, and SRPI checklist. Submit updated content in SPL format.

Cited: 21 CFR 314.50(l)(1)(i)

The established name on the revised container labels is too prominent relative to the proprietary name. The size of the established name must be decreased so that it is ½ the size of the proprietary name. Consideration should be given to increasing the size of the proprietary name while decreasing the size of the established name.

Recommended response: Adjust the font size of the established name on carton and container labels to be half the size of the proprietary name, potentially by increasing the proprietary name's size.

The bolded statement 'ATTENTION PHARMACIST: Each patient is required to receive the enclosed Medication Guide.' or an appropriate alternative must be added to the carton and container labels per 21 CFR 208.24(d).

Recommended response: Add the specified Medication Guide statement to carton and container labels as required by 21 CFR 208.24(d).

Cited: 21 CFR 208.24(d)

The proposed proprietary name, Dyanavel XR, was found acceptable pending approval of the application in the current review cycle. It must be resubmitted when responding to the application deficiencies.

Recommended response: Resubmit the proposed proprietary name, Dyanavel XR, along with the complete response to all other deficiencies.

A comprehensive safety update, as described at 21 CFR 314.50(d)(5)(vi)(b), is required. This update must include data from all nonclinical and clinical studies/trials regardless of indication, dosage form, or dose level. Specific requirements include: detailed description of significant safety profile changes, incorporation of new safety data into adverse event sections (including combined tabulations and comparisons), retabulation of premature trial discontinuations, provision of case report forms and narrative summaries for deaths and serious adverse events, description of changes in common adverse event incidence, updated exposure information, a summary of worldwide safety experience, and English translations of current approved foreign labeling not previously submitted.

Recommended response: Prepare a comprehensive safety update as per 21 CFR 314.50(d)(5)(vi)(b), incorporating all new nonclinical and clinical safety data, detailed adverse event analyses, updated exposure information, worldwide safety experience, and English translations of foreign labeling.

Cited: 21 CFR 314.50(d)(5)(vi)(b)