CENTER FOR DRUG EVALUATION AND RESEARCH

APPLICATION NUMBER: 125320

CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICS REVIEW(S)

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7 pages(s) have been Withheld in Full immediately following this page as B4

(CCI/TS)

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3 pages(s) have been Withheld in Full immediately following this page as B4

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CLINICAL PHARMACOLOGY AND BIOPHARMACEUTICSFILING FORM/CHECKLIST FOR NDA/LA or Supplement

General

18 Are the clincal pharmacology and biopharmaceutics studies of appropriatedesign and breadth of investigation to meet basic requirements fora rovabili of ths roduct?

19 Was the translation (of study reports or other study inormation) fromanother Ian a e needed and rovided in ths submission?

x

x

is THE CLINICAL PHARMCOLOGY SECTION OF THE APPLICATION FILEABLE? Yes

If the NDAILA is not fileable from the clincal pharmacology perspective, state the reasons and providecomments to be sent to the Applicant.

. N/A

Please identify and list any potential review issues to be forwarded to the Applicant for the 74-day letter.

· We acknowledge the submission of the comparability studies in your submission. We notice the followingand these wil be review issues:

o There is no direct bridging between the ATO vial and the ACO PFS formulation.

o Pharmacodynamics comparabilty in target population needs to be assessed.

· We remind you that bioanalytical method validation reports for all analytes (i.e., biomarkers) assessed tosupport this application need to be submitted.

· We recommend that you assess denosumab 's effect on CYP activities in vitro.

~.~Reviewing Clincal Pharm ologist

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Date

Tea~ Leader/Supervsor

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