**Kent D. McClure**

General Counsel

April 2, 2007

Regulatory Analysis and Development,

Policy Program and Development (PPD)

Animal and Plant Health Inspection Service (APHIS)

Station 3A--03.8

4700 River Road Unit 118

Riverdale, MD 20737--1238

> **Re: Docket No. APHIS -- 2006-0079**

The [Animal Health Institute]{.smallcaps} ("AHI") submits these comments
to Docket No. APHIS 2006-0079 regarding standard requirements for live
vaccines. AHI is the national trade association representing
manufacturers of animal health products \-- the pharmaceuticals,
biological products and feed additives used in modern food production,
and the medicines that keep livestock and pets healthy. AHI member
companies represent the majority of animal health products utilized in
the United States, as well as serving a significant segment of the world
market. This also includes over 95% of the domestic veterinary biologics
market. As such we have a tremendous interest in the development of
policy affecting veterinary vaccines.

We support APHIS' decision to eliminate the requirement to repeat
immunogenicity studies for Master Seed bacteria and viruses at post
completion of the initial immunogenicity study. The Master Seeds have
demonstrated long term immunogenicity. The elimination of this
requirement represents good science. While viewed individually, any
single study or test requirement may not seem overly burdensome,
cumulatively they represent tremendous cost and use of animals. APHIS
should continually review its requirements with an eye to refining or
eliminating those that are no longer necessary or no longer fit their
purpose.

We also support the elimination of the required mouse safety test by
intracerebral inoculation, as well as allowing for use of either, but
not both, proposed methods (intraperitoneally or subcutaneously) with a
single group of eight mice. We have long worked with APHIS to decrease
unnecessary or duplicative animal testing.

We offer one comment with respect to the proposed subcutaneous route of
administration. The proposed rule calls for 0.5 milliliters to be
administered. We understand that this is consistent with other APHIS
regulatory provisions for vaccines, and appears to have been utilized
without significant issue. However, it is unclear whether the rule would
allow for the 0.5 mL inoculate to be divided among more than one
injection site. The Association for Assessment and Accreditation of
Laboratory Animal Care (AAALAC) recommends as "good practice" for
subcutaneous injection the use of a volume of 0.1 ml/10 g BW with a
\"possible maximal dose volume\" listed at 0.4 ml/10 g. However, there
is also a caveat for non-aqueous injectates and multiple injection
sites. The AAALAC reference is *A good practice guide to the
administration of substances and removal of blood, including routes and
volumes*. J Appl Toxicol 21(1):15-23. Diehl KH, Hull R, Morton D,
Pfister R, Rabemampianina Y, Smith D, Vidal JM, van de Vorstenbosch C
(European Federation of Pharmaceutical Industries Association and
European Centre for the Validation of Alternative Methods) 2001. We
request APHIS consider revisiting the volume requirement and
specifically provide for the option to split the injection volume among
more than one injection site.

Sincerely,

Kent D. McClure