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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
`Food and Drug Administration
`Rockville, MD 20857
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`NDA 20-845/S-004
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`INO Therapeutics, Inc.
`Attention: Mary Ellen Zamstein
`Senior Director, Regulatory Affairs
`6 State Route 173
`Clinton, NJ 08809
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`Dear Ms. Zamstein:
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`Please refer to your supplemental new drug application dated March 21, 2007, submitted under section 505(b) of
`the Federal Food, Drug, and Cosmetic Act for INOmax (nitric oxide) for Inhalation.
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`We acknowledge receipt of your submission dated October 30, 2007.
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`This supplemental new drug application provides for labeling revised as follows:
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`1. The Carcinogenesis, Mutagenesis, Impairment of Fertility section has been changed from:
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`Nitric oxide has demonstrated genotoxicity in Salmonella (Ames Test), human lymphocytes, and after
`in vivo exposure in rats. There are no animal or human studies to evaluate nitric oxide for effects on
`fertility or harm to the developing fetus.
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`To:
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`No evidence of a carcinogenic effect was apparent, at inhalation exposures up to the recommended dose
`(20 ppm), in rats for 20 hr/day for up to two years. Higher exposures have not been investigated.
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`Nitric oxide has demonstrated genotoxicity in Salmonella (Ames Test), human lymphocytes, and after
`in vivo exposure in rats. There are no animal or human studies to evaluate nitric oxide for effects on
`fertility.
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`2. The copyright date has been revised.
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`We have completed our review of this supplemental new drug application. It is approved, effective on the date
`of this letter, for use as recommended in the final printed labeling (FPL) submitted on October 30, 2007.
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`If you issue a letter communicating important information about this drug product (i.e., a “Dear Health Care
`Professional” letter), we request that you submit a copy of the letter to this NDA and a copy to the following
`address:
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`MEDWATCH
`Food and Drug Administration
`5515 Security Lane
`HFD-001, Suite 5100
`Rockville, MD 20852
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`NDA 20-845/S-004
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`We remind you that you must comply with the requirements for an approved NDA set forth under 21 CFR
`314.80 and 314.81.
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`If you have any questions, please call Mr. Russell Fortney, Regulatory Project Manager, at (301) 796-1068.
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`Page 2
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`Sincerely,
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`{See appended electronic signature page}
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`Norman Stockbridge, M.D., Ph.D.
`Director
`Division of Cardiovascular and Renal Products
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
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` /s/
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`Norman Stockbridge
`12/4/2007 04:42:28 PM
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