4.7 Risks and Discomforts 
Risks associated with blood drawing may include transient pain, bruising or 
lightheadedness, and a modest risk of infection. Risks associated with product injections 
include local pain, inflammation, erythema, swelling, itching, tenderness, skin 
discoloration, skin breakdown, regional lymphadenopathy, and possibly even granuloma 
formation at the injection site. Serious inflammation is not anticipated; however, should 
this occur, symptomatic treatment will be provided. Other clinical manifestations that could 
result from product administration include fever and chills, diaphoresis, mild 
gastrointestinal distress, allergic reactions which may include rash, decrease in blood 
pressure, shortness of breath and/or syncope, and remotely, anaphylaxis. 
There are several theoretical safety concerns related to the use of retrovirally vector- 
mediated gene transfer^. These are summarized in Section 4.7.1 through 4.7.5. 
4.7.1 Production of Replication Competent Virus Through Recombination 
4.7 . 1 . 1 The risk of producing replication-competent retrovirus through 
recombination is remote since (1) All known human endogenous 
retroviruses have multiple disruptions in their coding sequences and 
Southern blot analysis of human genomic DNA, probed with the HIV-1 
env gene, has failed to demonstrate any significant homology, (2) The 
canine packaging cell utilized in HTV-IT (V) production has been 
engineered to minimize the possibility of generating replication- 
competent retrovirus *7; (3) A split genome approach to produce the 
packaging cell line predicts that three separate recombination events 
would be required in order to produce a replication competent murine 
virus', (4) Quality Control testing using the S + L' extended assay to 
detect amphotropic and xenotropic retroviruses will be performed on 
HIV-IT (V) prior to Quality Control release for injection^. 
^Cometta K. et a], Human Gene Therapy, 2:5-14, 5-15, (1991). 
^Abraham, G.N. and Khan, A.S., Clin. Immunol. &. Immunopath., 56:1-8 (1990). 
^See Drug Master File It BB-MF4452, Section IV.B.3.b. (p.57) and IV.B.4.c.(5)(a) (p69). 
^Miller, D.A., Human Gene Therapy, 1:5-14 (1990). 
^Bassin, R.H., et al, Int. J. Cancer, 6:95-107 (1970). 
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