FDA CRL - TEVA Pharmaceuticals USA, Inc.

The FDA issued a Complete Response Letter (CRL) for Teva Pharmaceuticals USA, Inc.'s New Drug Application (NDA 210063) for Fulvestrant Injection, 250 mg/5 mL, initially submitted on December 28, 2016, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The agency determined the application could not be approved due to deficiencies across nonclinical, product quality, and combination product aspects. Key nonclinical issues included inadequate justification for the safety of the medium chain triglycerides (MCT) excipient for intramuscular injection, particularly regarding local tissue toxicities. Teva must provide robust safety justification and submit a GLP nonclinical bridging toxicology study comparing their formulation to the reference drug, Faslodex, assessing local effects and toxicokinetics. Product quality concerns involved the absence of long-term leachability data and safety evaluations for syringe components, missing specifications for plunger rod tensile and elongation properties, and incomplete extractables/leachables study reports. Significant issues were also identified with the combination product (prefilled syringe and safety needle), including a lack of design requirements and specifications for the syringe's essential performance (e.g., expelled volume and forces). For the included SafetyGlide needle, Teva failed to provide design specifications, a Letter of Authorization to review the referenced 510(k) (K951254), a clinical use study for sharps injury prevention, and a complete biocompatibility evaluation addressing endpoints like cytotoxicity and sensitization. Teva must address these comprehensive information gaps to support approval.