GeNO LLC: GENOsyl™ ©®

Please refer to your New Drug Application (NDA), originally submitted March 20, 2012, our refuse to file letter dated May 18, 2012. and your resubmission dated August 31, 2012. under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act for GENOsyl™ ©® (nitric oxide for inhalation).

We recommend demonstrating that the specification limits be correlated to performance that ensures that the cartridges meeting release and stability specifications when used under conditions representing projected use at minimum convert the contents of one cylinder of 800 ppm nitrogen dioxide © to acceptable levels of output for nitric oxide and nitrogen dioxide.

We find your proposed studies to demonstrate cartridge capacity (time to cartridge failure) under simulated real conditions (tandem cartridges on the MVG-2000 delivery system) adequate.

2000 to prevent microbiological contamination of the breathing air, and to prevent particulates from the cartridges and MVG-2000 system from entering the patient.

The following comments are not requirements for the complete response to this application, but they are recommendations to assist in more efficient review of the application:

The Agency expects all facilities involved in the manufacture, processing, packing or holding, which includes packaging and labeling operations, testing and quality control, of the drug product to be ready for inspection at the time of application submission.

After you submitted your 505(b)(2) application, the NDA holder for INOmax (nitric oxide) for inhalation, 100 and 800 ppm, timely filed information on U.S. Patent No. 8,431,163 ('163 patent) for listing in the Orange Book.

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

© have a high potential of affecting the quality of nitric oxide and eventually the final drug product delivered to the patient.

Within 30 days of the date of this letter, you may request in writing a meeting about our refusal to file the application.

To file this application over FDA's protest, you must avail yourself of this informal conference.

Tf, after the meeting, you still do not agree with our conclusions, you may request that the application be filed over protest.

In that case, the filing date will be 60 days after the date you requested meeting.