Teva Pharmaceuticals USA: Fulvestrant

Federal Food, Drug, and Cosmetic Act for Fulvestrant Injection, 250 mg/5 mL.

We also acknowledge receipt of your amendment dated October 23, 2017, which was not reviewed for this action.

1. The safety of the proposed level of the medium chain triglycerides (MCT) excipient in the drug product to be administered by intramuscular injection was not adequately justified.

Therefore, these studies were inadequate to assess the safety of intramuscular injection of the proposed levels of MCT present in your to-be-marketed Fulvestrant Injection drug product.

You state that the BD Safety Glide™ Needle, is a Class II, 510(k) Medical Device cleared by the Center Devices and Radiological Health, U.S. FDA CDRH, under 510(k)#: K951254 and that therefore, no letter of access is needed for a 510(k) cleared Medical Device.

Sharps Injury Prevention Features," dated August 9, 2005. A sample size of 500 with zero failures of the protection feature is recommended.

As your device is intended to deliver fluids systemically, the Agency recommends that the following endpoints are addressed: cytotoxicity, sensitization, and irritation, acute systemic toxicity, hemolysis, and material-mediated pyrogenicity.

1. We note that you have not submitted a comprehensive risk analysis or your justification for not conducting a Human Factors (HF) validation study.

We recommend you conduct a comprehensive use-related risk analysis if you have not already completed one.

The comprehensive use-related risk analysis should include a comprehensive and systematic evaluation of all the steps involved in using your product (e.g., based on a task analysis) the errors that users might commit or the tasks they might fail to perform and the potential negative clinical consequences of use errors and task failures.

If models of the same or similar combination products exist, your use-related risk analysis should incorporate applicable information on known use-related problems with those products.

Cosmetic Act for Romidepsin Injection, solution, 10 mg/2 mL (5 mg/mL).

Please refer to your New Drug Application (NDA) dated and received November 30, 2015, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act (FDCA), for buprenorphine and naloxone sublingual film, 16 mg/4 mg.

Satisfactory inspection is required before this application may be approved.

Section 505-1 of the FDCA authorizes FDA to require the submission of a risk evaluation and mitigation strategy (REMS) if FDA determines that such a strategy is necessary to ensure that the benefits of the drug outweigh the risks [section 505-1(a)].

Guide, elements to assure safe use, an implementation system and a timetable for submission of assessments of the REMS.

REMS will be necessary for buprenorphine and naloxone sublingual film if it is approved, to ensure that the benefits of the drug outweigh the risk(s) of misuse, abuse and accidental overdose.

The REMS, should it be approved, will create enforceable obligations.

Cosmetic Act for Romidepsin Injection, 10 mg/2 mL (5 mg/mL).

We acknowledge your March 28, 2016 response to the information request dated March 14, 2106.

2. Include sterility information for the drug product in the carton container.