5 
Dr. Anderson said a reference to "toxic chemicals" should not be included in 
the working group document as experts reading the document would doubt the 
working group's competence if the points to consider clearly did not apply to 
hunan gene therapy procedures. 
Dr. Anderson suggested language might be added to the introduction indicating 
the points to consider document addresses laboratory scale procedures and not 
industrial manufacturing processes. He volunteered to draft this language. 
Dr. Gottesman asked why Dr. Miller was concerned that penicillin or beta- lactam- 
containing antibiotics might be used in human gene therapy. Dr. Anderson said 
antibiotics are used in same industrial production processes to protect against 
bacterial contamination. Antibiotics would not, however, be used in the labora- 
tory scale tissue culture systems producing retroviral vectors for human gene 
therapy since antibiotics do not control myccplasma contamination. Indeed, 
use of antibiotics to control bacterial Contamination would be cointerproductive 
since bacterial contamination frequently occurs concomitantly with myccplasma 
contamination and can be an indicator of this contamination . 
Dr. Walters questioned whether Er. Miller's concern with product potency, 
consistency of product lots and product stability were valid. Er. Anderson 
said the FDA deals with large-scale systems in which the product is perhaps 
one part in a million of the culture system. It has not dealt with the system 
that will be employed in hunan gene therapy protocols. Product potency is not 
an issue in human gene therapy except in terms of viral titer. Certainly, there 
will be no product lot considerations in the initial protocols. In human gene 
therapy, the cell line producing the retrovirus vector will be constructed in the 
laboratory and then frozen. When budding particles containing the retrovirus 
vector are needed, cells will be thawed, plated out in tissue culture medium, 
and used. The viral particles will bud fran the tissue culture cells. Bone 
marrow cells will be taken from the subject and introduced into the tissue 
culture medium. The bone marrow cells, which float in the medium, will be 
exposed to the virus particles. The bone marrow cells wall then be harvested 
and introduced into the patient. "There is, thus, no product in the FDA sense. 
The questions Dr. Temin drafted for Section I-B-2-c-(b) of the document are 
exactly the questions which should be posed for retro/iral vectors produced by 
budding particles. These questions address the issue in great detail and are 
more than adequate. 
Dr. Murray said Dr. Miller is not familiar with this area. His experience 
appears to be in the area of drugs and biologicals, and he continues to think 
of human gene therapy in those terms. 
Dr. Welters called the attention of the subworking group to Dr. Miller's comment 
on Section I-B-2-a-(2) of the working group document. Dr. Miller felt the term 
"adequate" as used in this section is vague and undefined, and he suggested the 
sec±ion be revised. 
Dr. Gottesman suggested "adequate" might be defined in terms of the insertion 
frequency of the retroviral vector in bone marrow cells. Dr. Anderson felt 
the current language is acceptable, but said he would draft a clause to clarify 
[ 5 ] 
