10 
Or. Miller pointer! out that vaccines are biological systems and are covered by 
the FDA staff manual. Dr. Grobstein replied that vaccines are developed for 
administration to large numbers of healthy school children. Human gene therapy 
presents a very different case; procedures ethically unacceptable if administered 
to healthy children might be used to treat seriously afflicted, critically ill 
individuals for when no other therapy is possible. 
Ms. Areen said RAC and its working groups may be replacing the FEA in reviewing 
human gene therapy protocols arri should pro/ide regulatory guidance for 
investigators. Dr. Murray and Mr. Capron said RAC would not be replacing the 
FDA in this area; they felt the concerns addressed in the alternative document 
proposed by Dr. Miller and Ms. Areen wore the responsibility of local IRBs. 
They argued that the working group should not duplicate the responsibilities of 
IRBs but rather should address novel issues vshich might develep with human 
gene therapy. 
Dr. Walters asked the working group to continue evaluating the working group 
draft document (Attachment II). He called the attention of the group to Section 
I-A-2, Research Methods . Mr. Capron said this section of the document should 
have a short preamble vhich requests the rationale and objectives of the 
proposal. Dr. Varmus said a preamble could offer ideas without stating specific 
informational requirements; he thought at this time the working group is not 
aware of all of the data which might be required for case-by-case ra/iew. He 
suggested a preamble might suggest same important considerations for use of 
retroviral systems and cell culture or animal system testing. 
Dr. Anderson suggested a preamble to this section should ask about the delivery 
system, the introduced gene, and the effectiveness of introducing the gene. He 
suggested the scientists on the working group develep appropriate language for 
this section before the next meeting of the working group. 
Dr. Varmus suggested Item I-A-2-(5) should ask vhat will be done to "assess" 
that contaminants are absent from the cultures rather than to "demonstrate" their 
absence . 
Dr. Grobstein asked how "stability" is defined in Item I-A-2-(4); does this 
item refer to the stability of the DNA, to the stability of the integration, or 
to both? 
Dr. Varmus said Sections I-A-2-a, Characterization of vector and inserted DMA , 
and I-A-2-b, Prior laboratory research ask the same questions. He suggested 
these sections be combined into a single section. Dr. Gottesman said this 
single section should address the following questions: How do you knew vhat 
you have? How do you knew it will stay that way? Hew do you knew it won't 
spread? 
Dr. Varmus questioned whether Item I-A-2-b-( 1 ) (a) should request characterization 
of the integration site. He said the possibility exists that chance integration 
of a retrovirus in certain sites might cause neoplastic change. Dr. Anderson 
said this is a key issue. Dr. Gottesman wondered vhether tissue culture or 
animal test data might address this question and provide this typo of data. 
[ 98 ] 
