DURECT Corporation: POSIMIR

August, 20, September 3, 10, and 25, October 23, November 6 and 26, and December 6, 20, 30, and 31, 2013, and January 16 and February 3, 2014.

1. The application does not contain sufficient information to demonstrate that POSIMIR is safe when used in the manner described in the proposed label.

There were insufficient data due to the limited number of subjects and the lack of an appropriate comparator to permit a determination of whether SABER-bupivacaine causes adverse reactions affecting the joint or the surrounding structures to a clinically relevant greater extent than either bupivacaine HCI or a non-SABER containing placebo.

SABER-placebo) substantially more often than following administration of bupivacaine HCL.

SABER containing placebo following the surgical procedures studied and whether the risk was greater with only certain surgical procedures.

There were insufficient data to determine whether the risk is greater with SABERbupivacaine than for either bupivacaine HCI or a non-SABER containing placebo following each of the surgical procedures studied and clinical impact of these reactions, e.g., whether they delayed discharge from the post-anesthesia care unit or affected time to ambulation.

The treatments need to include SABER-bupivacaine and either bupivacaine HCL or anon-SABER containing placebo (or both).

8. Provide English translations of current approved foreign labeling not previously submitted.