Braeburn Pharmaceuticals Inc.: BRIXADI

Therefore, final approval of your application under section 505(c)(3) of the Act [21 U.S.C. 355(c)(3)] may not be granted before the period has expired.

In addition to a safety update, the amendment should also identify changes, if any, in the conditions under which your product was tentatively approved, i.e., updated labeling; chemistry, manufacturing, and controls data; and risk evaluation and mitigation strategy (REMS).

Section 505(0)(3) of the FDCA authorizes FDA to require holders of approved drug and biological product applications to conduct postmarketing studies and clinical trials for certain purposes, if FDA makes certain findings required by the statute.

Therefore, based on appropriate scientific data, FDA has determined that if your application is approved, you will be required to participate in the conduct of the following postmarketing studies:

It is, therefore, anticipated that clinicians may elect to accelerate the initiation of BRIXADI treatment by omitting the titration over the first week.

Therefore, based on appropriate scientific data, FDA has determined that you are required to conduct the following trial:

Therefore, no additional data are required, but the findings must be included in labeling.

If this application is ultimately approved, submit the protocols to your IND 114082, with a cross reference letter to this NDA. Submit all final reports to your NDA. Prominently identify the submission with the following wording in bold capital letters at the top of the first page of the submission, as appropriate:

If your application is ultimately approved, your REMS must be fully operational before you introduce BRIXADI into interstate commerce.

Act for BRIXADI (buprenorphine extended-release) injection for subcutaneous use, 8 mg, 16 ing, 24 mg, 32 mg weekly; 64 mg, 96 mg, 128 mg a monthly.

Provide additional data ©® or withdraw it from the application.

For example, the response to the November 16, 2017, information request (IR) about Subject HS-11-421who appeared to have two doses of study drug on the first day of treatment, noted that the subject received the SL BPN test doses and one dose of the 16 mg weekly formulation.

3. The Summary of Clinical Safety and the Clinical Study Report for Study HS-11-421 did not include an evaluation of dose-response for either efficacy or safety, nor an analysis of whether any dose-related risks were balanced by incremental increases in efficacy.

Provide a revised Summary of Clinical Safety and Summary of Clinical Efficacy that includes analysis and discussion of the dose-response relationships and how they inform the overall balance of risk and benefit.

Use the results of the extraction studies to assure that you are adequately monitoring the drug product stability samples for potential leachables from the primary or secondary container closure systems and from your analysis of data from any upstream manufacturing processes that suggest the potential for additional leachable compounds in the final drug product formulation.

8. You have not provided adequate pharmacokinetic data to appropriately calculate exposure margins for buprenorphine in your labeling.

The exposure margins based on AUC in the labeling are to be based on the worst-case exposures in humans over the treatment period at steady state.

Provide mean partial AUC (24-hour interval) data in humans at steady state that represents the highest exposures over any given 24-hour period to inform labeling.

As discussed at the February 24, 2015, End-of-Phase 2 meeting, provide data to support your conclusion that the DAG oil tested in these publications contains GDO at levels which provide an adequate characterization of the effects of GDO on these required studies.

Valley (FEI: 1000513101) testing facility for this application, our field investigator conveyed deficiencies to the facility.

Pharmaceutics International, Inc. (Pii) must resolve these issues before this application may be considered for approval.

19. The information concerning container-closure integrity testing (CCIT) of postapproval stability samples provided in your submission dated December 8, 2017, is acknowledged.

These deficiencies must be adequately addressed before this application can be approved.

IFU used during the HF validation study, however, Figure 5 remained unchanged in the IFU included in the November 30, 2017 draft submission of the proposed intend-to-market IFU.

28. We reserve further, more detailed comment on the proposed labeling until the application is otherwise adequate.

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)].

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

In accordance with section 505-1 of the FDCA, we have determined that a REMS is necessary for BRIXADI, if it is approved, to ensure that the benefits of the drug outweigh the risk(s) of serious harm or death that could result from intravenous (IV) self-administration.

The REMS must include the following ETASU: healthcare settings and pharmacies that dispense BRIXADI must be certified.