CENTER FOR DRUG EVALUATION AND RESEARCH

APPLICATION NUMBER:

125554Orig1s000

CHEMISTRY REVIEW(S)

2

Evaluation of criteria that may warrant inspection

1. The manufacturer does not hold an active U.S. license, or in the case of a contract manufacturer, is not approved for use in manufacturing a licensed product.

BMS-Manati is currently approved under license 1713 for manufacture of three sterile biologics: Orencia (abatacept, BLA 125118), Yervoy (ipilimumab, BLA 125377), and Nulojix (belatacept, BLA 125288). These products are manufactured in the same Parenteral Vial Area proposed for Nivolumab manufacture.

2. FDA has not inspected the establishment in the last 2 years.

The facility was last inspected by SJN-DO from May 5-16, 2014 and classified NAI. This was a routine cGMP surveillance inspection covering biotech drug product manufacturing operations, and included inspection of the Parenteral Vial Area proposed for Nivolumab manufacture. The profile was updated and is acceptable.

3. The previous inspection revealed significant GMP deficiencies in areas related to the processes in the submission (similar processes) or systematic problems, such as QC/QA oversight.

The previous inspection on May 5 – 16, 2014 covered Profile Class and was classified NAI.

4. The establishment is performing significant manufacturing step(s) in new (unlicensed) areas using different equipment (representing a process change). This would include areas that are currently dedicated areas that have not been approved as multi-product facilities / buildings / areas.

The Parenteral Vial Area at BMS-Manati proposed for Nivolumab manufacture is currently approved for manufacture of Orencia, Yervoy, and Nujolix .

5. The manufacturing process is sufficiently different (new production methods, specialized equipment or facilities) from that of other approved products produced by the establishment.

The proposed manufacturing scheme for Nivolumab is similar to the approved process for Yervoy liquid injectable. It is also similar to the approved processes for Orencia and Nujolix

Reference ID: 3639584

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---------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signedelectronically and this page is the manifestation of the electronicsignature.---------------------------------------------------------------------------------------------------------/s/----------------------------------------------------

STEVEN FONG10/06/2014

PATRICIA F HUGHES TROOST10/10/2014

JOEL T WELCH10/10/2014

KATHLEEN A CLOUSE STREBEL10/10/2014

ZHIHAO PETER QIU10/10/2014

Reference ID: 3639584

---------------------------------------------------------------------------------------------------------This is a representation of an electronic record that was signedelectronically and this page is the manifestation of the electronicsignature.---------------------------------------------------------------------------------------------------------/s/----------------------------------------------------

JOEL T WELCH09/19/2014

LAURIE J GRAHAM09/22/2014

KATHLEEN A CLOUSE STREBEL09/22/2014

Reference ID: 3631139