Attachment II - Page 46 
50900 Federal Register / Vol. 49, No. 252 / Monday, December SI, 1984 / Notices 
the nucleotide sequence, and the 
restriction endonuclease digestion map. 
A vector is a cloning vehicle which 
provides a suitable origin of replication 
necessary for production of foreign 
DNA. Such replicons may be derived 
from plasmids, bacteriophages, or 
viruses such as vaccinia, bovine 
papillomavirus, adenoviruses, of SV40. 
A restriction endonuclease map of the 
vector construct describing structural 
genes, regulatory or promotor regions, 
insert orientation, and a description of 
readily detectable phenotypic traits on 
host cells will be required as supporting 
data. 
Production of functional gene 
products depends on the efficient 
expression of cloned DNA-vector 
complexes in suitable host organisms. 
Tissue culture cells, bacteria, yeasts, 
and other cells may be used as hosts for 
replication of vectors. The mechanisms 
of transfer, the copy number, and the 
physical state of the constructed vector 
inside the host cell, integrated or 
extrachromosomal, should be described. 
USDA's licensing policy for veterinary 
biological products derived from 
recombinant DNA technology is 
evaluated on a product-by-product 
basis. USDA requires all licensed 
applicants or products derived from 
DNA technology to comply with the NIH 
Guidelines for research involving 
recombinant DNA molecules. 
APHIS has executed a Memorandum 
of Understanding with the Food and 
Drug Administration to resolve 
jurisdictional or definitional questions 
regarding animal biologic products 
subject to the VST Act or as drugs under 
the Food, Drug, and Cosmetic Act (21 
USC 301 et seq.). This memorandum was 
published on June 8, 1982, at 47 FR 
26458. 
2. Chemically Synthesized Antigens. 
When the product consists of chemically 
synthesized polypeptides, the 
appropriate amino acid sequences will 
mimic the antigenic site or epitope found 
in the native antigen where one exists. 
Supporting data shall include type, 
degree, and persistence of the immune 
response following administration of the 
synthetic peptide. Procedures used to 
increase or prolong an antibody 
response such as coupling to carrier 
proteins or addition of adjuvants, must 
also be described. 
3. Monoclonal Antibody Products. The 
specificity and potency of monoclonal 
antibody products will be compared 
with that of similar polyclonal antibody 
products where appropriate. The 
specificity and sensitivity of monoclonal 
antibody products must be at least equal 
to that of antibody products of 
traditional polyclonal nature. 
Monoclonal antibody products must 
be derived from Master Cell Stocks 
which meet the requirements of 9 CFR 
113.52. Description of cell cloning 
procedures, preparation, and 
characterization of cell passages must 
also be provided. 
The Outline of Production must 
provide a description of all processes 
including scale-up, ascites fluid or cell 
culture supernatant preparation, 
purification, concentration, and 
inactivation. Mouse colonies must be 
screened to demonstrate freedom from 
adventitious agents, especially those 
detected by the mouse antibody 
production (MAPJ test If the MAP test 
discloses the presence of adventitious 
agents, the product shall not be released 
unless inactivation procedures approved 
by Veterinary Services have been 
performed. 
4. Master Seeds. Bacterial or viral 
seed stocks used to prepare veterinary 
biological products must meet 
established procedures used to certify 
Master Seeds for biological products (9 
CFR 101.7). 
The Master Seed for recombinant 
DNA derived products may consist of a 
plasmid or virus carrying the inserted 
gene. This constructed plasmid is then 
introduced into the appropriate 
eukaryotic or prokaryotic expression 
system selected for vaccine production. 
Genomic DNA may also be transfected 
directly into a variety of mammalian 
cells. Alternatively, in such cases, the 
stable transfected cell could be 
considered as the Master Seed. 
The establishment of a Master Seed of 
constructed plasmids or transferred 
cells requires submission of background 
information concerning the recombinant 
DNA procedures used to isolate, purify, 
and identify genetic material from one 
source and the modification used for 
Insertion of this material into a new 
host. Data from cloning, isolation, 
proliferation, and selection of 
genetically unique cells would be 
retained by licensed applicants. 
Tissue culture-propagated cells. from 
vertebrate animals used for vector 
propagation and antigen production 
must meet the requirements of 9 CFR 
113.51 or 113.52. 
If a Master Seed has been accepted by 
Veterinary Services for use in a licensed 
product, further genetic modifications 
may be approved with reduced 
requirements for additional host animal 
efficacy studies. 
Product and Serial Release 
Each Outline of Production shall be 
prepared in accordance with 9 CFR 
114.9. Outlines must include procedures 
to ensure consistency in production and 
recovery of specific antigenic material. 
Recovery procedures must include 
removal or excessive antibiotic levels (9 
CFR 114.10] and undesirable 
fermentation byproducts such as 
excessive levels of bacterial endotoxins. 
Serial release tests for purity, safety, 
and potency with appropriate 
techniques will be required. 
Pursuant to the Act of February 2, 
1903, (21 USC 111), USDA has authority 
to make such regulations and take such 
measures as may be deemed proper to 
prevent the introduction or 
dissemination of the contagion of any 
contagious, infectious, or communicable 
disease of animals and/or live poultry 
from a foreign country into the United 
States or from one State or territory of 
the United States or the District of 
Columbia. Under this authority and the 
VST Act, the importation into the United 
States or interstate shipment of 
organisms and vectors is regulated 
under Title 9, Code of Federal 
Regulations, 9 CFR Part 122. Organisms 
and vectors are defined in 9 CFR 122.1 
as entities which may introduce or 
disseminate any contagious or infectious 
disease of animals. Such substances 
may not be shipped interstate or 
imported without a permit. Permit 
applications must provide a complete 
description of the substances, intended 
use, location of the permittee, and 
safeguards to be observed. When 
appropriate, a review is conducted by 
the Administrator's Parent Committee 
on Organisms and Vectors. Members of 
this committee have wide expertise in 
evaluating safety. Clearance may also 
require testing in high security facilities 
at the Veterinary Services Foreign 
Animal Disease Diagnostic Laboratory, 
Plum Island, New York. 
C. Plants and Plant Products 
Pursuant to authority granted by the 
Federal Plant Pest Act of May 23, 1957, 
as amended (7 USC 150 aa through 150 
jj), and the Plant Quarantine Act of 
August 20, 1912, as amended (7 USC 151 
through 164, 166, and 167), USDA has 
regulatory authority over the movement 
into and through the United States of 
plants, plant products, plant pests, and 
any product or article which may 
contain a plant pest at the time of 
movement. These articles are regulated 
in order to prevent the introduction, 
spread or establishment of plant pests 
new to or not widely prevalent in the 
United States. The regulations 
implementing this statutory authority 
are found in 7 CFR Parts 300 through 
339. 
The Federal Plant Pest Act and the 
Plant Quarantine Act would be 
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