EA Review #1, NDA 20-358

Page 10

A discussion of any deviations from EATAD 3.04 should be included.

DEFICIENT.

The octanol/water partition coefficient was determined in 1976, prior to the availability of the FDA Technical Assessment Handbook.  This method is described on page 44 and involved four (4) single determinations at four (4) different pH conditions.  The results have been recorded in the scientific literature and are thus considered to be adequate and scientifically valid.  All of the resulting log Kow values are less than 2, the threshold value for Tier 2.

A literature reference for the publication of the log Kow of the drug substance should be provided together with any supportive data obtained or appearing since 1976.

DEFICIENT.

The vapor pressure of drug substance was determined by (whited out) as described in FDA EATAD 3.03 in compliance with FDA Good Laboratory Practice regulations.  The vaopr pressure was 3.74 x 10^-7 torr, below the Tier 3 threshold value.

Adequate.

Based on the values presented for the physical properties of the drug substance, the assessment concluded that further assessment of the drug substance in the air or terrestrial compartment wre not warranted.

Adequate.

Tier 1 Attributes (see Attachment 4)

Aerobic biodegradation of the drug substance in water was tested by (whited out) as desribed in EATAD 3.11 in compliance with FDA Good Laboratory Practice regulations.  The substance did not degrade over a 14-day period.

Adequate.

Aqueous photodegradation of the drug substance was determined by (whited out) according to EATAD 3.10 in compliance with FDA Good Laboratory Practice regulations.