- E&L Study
- E&L case study
- USP 1663
- USP 1664
- USP 1664.1
- ICH Q3E
- Medical Device
CENTER FOR DRUG EVALUATION AND RESEARCH
Approval Package for:
Referance : 4720395
page1 : Results of ongoing stability studies should be submitted throughout the dating period, as they become available, including the results of stability studies from the first three production lots.
page8 : To perform extractables/leachables studies and risk assessments to evaluate leachables from the container closure system(s) and manufacturing product conduct surfaces of ansuvimab drug substance and drug product and assess the potential impact of leachables on product quality at the end of drug product shelf-life. The analyses will be performed using drug substance and drug product lot(s) and/or representative samples (e.g.___________ if justified) analyzed at appropriate time points, including at the end of drug product shelf life. Appropriate methods will be used to detect, identify, and quantify organic non-volatile, volatile and semi-volatile species, and metals. Characterization of the potential impact on product quality will be assessed using adequate analytical methods. Complete data and the risk evaluation for the potential impact of leachables on product safety and quality will be provided in the final study report per 21 CFR 601.12.
Referance : 4285070
Extractables Testing Strategy: The Sponsor conducted an extractables study with two pre-filled glass syringes. The study was performed for another Sandoz Biopharmaceutical product (using the same syringe) and were applied to GP2017. Placebo solution was provided by the Sponsor for the extractables study. An extractables screening was conducted for known and unknown compounds present in the two different rubber materials of the syringe and in the needle adhesive. The core part of the study consisted of a set of forced extraction experiments followed by subsequent analyses of the extracts by GC/MS with and without derivatization (for semi- volatiles compounds), by HPLC/UV/MS (for non-volatile and polar compounds), by headspace-GC/MS (for volatile compounds), and by ICP-MS (for elemental analysis). The study utilized guidelines of Product Quality Research Institute (PQRI) best practices for extractable and leachable studies for orally inhaled and nasal products.
LEACHABLES ASSESSMENT :
A general screening of leachables was conducted to determine the risk of exposure to the patient. No single compounds were identified in the extractables evaluation for further testing in the leachables studies. The SCT was converted into an AET based on the number of doses per day. All compounds over the AET were toxicologically evaluated. Only two leachables were detected in stability studies covering up to 32 months of storage at intended conditions.
대한민국 식품의약품 안전처 MFDS
Extractables and Leachables 자료제출 (원액 / 완제 용기적합성)