Inadequate validated leachable data for container closure system
Severity: majorYou have not provided adequate validated leachable data to permit a substantive toxicological risk assessment for the proposed container closure system. This includes characterizing trends over shelf-life and assessing compounds over 5 mcg/day. A full leachable profile with data collected on a fresh batch of drug product at multiple time points using well-validated methods is needed.
Recommended response: Submit a revised toxicological risk assessment based on validated leachable data that characterizes the trends in leachables over the course of the proposed shelf-life, including later timepoints. Submit a risk assessment for any compound present over 5 mcg/day. Provide a full leachable profile with data collected on a fresh batch of drug product, at 0, 3, 6, 9, and 12-month time points using well-validated methods.
Missing complete accelerated stability data for drug product batches
Severity: majorModule P.8.3. states that 6 month accelerated studies under 40° ± 2°C/ NMT 25% RH were provided for 2019 batch stability samples 1907059, 1907060, and 1907061. However, this information cannot be located.
Recommended response: Provide the complete data for at least three batches of drug product stored under accelerated conditions.
Photostability study report incomplete (missing table)
Severity: minorTable 2 in the Photostability study report ARL/STDR/0066/19 was not included in the report.
Recommended response: Provide this information in your resubmission.
Prescribing Information not adequate
Severity: majorComment on the proposed labeling is reserved until the application is otherwise adequate. The sponsor is encouraged to review PLR requirements, Pregnancy and Lactation Labeling Final Rule, and SRPI checklist.
Recommended response: If you revise labeling, use the SRPI checklist to ensure that the Prescribing Information conforms with format items in regulations and guidances. Your response must include updated content of labeling in structured product labeling (SPL) format.
Cited: 21 CFR 314.50(l)(1)(i)
Strength presentation on labeling is error-prone
Severity: majorThe strength (1,000 mg) is presented as “1000 mg” (without a comma), which may be misinterpreted as hundreds “100”.
Recommended response: Present numbers greater than or equal to 1,000 with a comma.
Expiration date and lot number format/location not specified on container label
Severity: majorThe location and format of the expiration date and lot number is not specified, which can lead to confusion, medication errors, and dispensing errors.
Recommended response: Designate an area for inclusion of the expiration date and lot number on the container label. Ensure the expiration date is clearly differentiated and identify the format (e.g., YYYY-MM-DD or YYYY-MMM-DD).
Cited: 21 CFR 201.17
Expiration date format not specified on overwrap label
Severity: minorThe format of the expiration date on the overwrap label is not specified, which can lead to confusion and risk for deteriorated drug medication errors.
Recommended response: Identify the expiration date format you intend to use. FDA recommends YYYY-MM-DD or YYYY-MMM-DD.
Net quantity statement competes for prominence with product strength on overwrap label
Severity: majorThe net quantity (100 mL) statement competes for prominence with the product strength and could be misinterpreted as a strength statement (100 mg).
Recommended response: Reduce the prominence of the net quantity statement.
Missing temperature units on carton labeling
Severity: minorThe units of temperature measurement (Centigrade and Fahrenheit symbols) are missing after the first numbers in the temperature ranges (e.g., '20' and '68'), potentially leading to overlooked lower temperatures.
Recommended response: Add the Centigrade symbol (C) following the 20 and the Fahrenheit symbol (F) following the 68 within the storage statement (e.g., '20°C to 25°C (68°F to 77°F)').
Product strength (1,000 mg per 100 mL) missing on carton labeling
Severity: majorThe product strength (1,000 mg per 100 mL) is not included on the carton labeling; only the quantity per milliliter ('10 mg/mL') is present. This is required by regulation.
Recommended response: Add the proposed product strength, '1,000 mg per 100 mL' to the carton labeling (e.g., '1,000 mg per 100 mL (10 mg/mL)').
Cited: 21 CFR 201.57(c)(17)(i)
Route of administration missing on carton labeling
Severity: majorThe route of administration is missing from the carton labeling, posing a risk of product administration errors.
Recommended response: Add the route of administration statement without abbreviations to the carton labeling, consistent with the container label (e.g., 'For Intravenous Use Only').
Cited: 21 CFR 201.100(b)(3)
Misleading quantity statement on carton labeling
Severity: minorA quantity statement, (b)(4), may be interpreted as one infusion bag per carton, which is misleading and incorrect.
Recommended response: Delete the misleading quantity statement, (b)(4).
