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Federal Register / Vol. 58, No. 28 / Friday, February 12, 1993 / Notices 
7. Among other factors to be 
considered by the Director of NIH, is the 
consanguinity of the new protocol to 
existing protocols. 
8. The NIH will report to the RAC 
following its internal review. 
9. Protocols that are deferred or not 
approved by the RAC in its normal 
review process, are not eligible for 
expedited review. 
10. In the development of any 
documents that are a part of this policy 
statement, the terms, compassionate use 
and compassionate treatment, will be 
deliberately avoided. 
The Recombinant DNA Advisory 
Committee will be further developing 
this policy statement for inclusion in 
the Points to Consider document. 
XIII. Amendment to the Points to 
Consider Regarding Safety of Delivery/ 
Expression Systems and Report on 
Murine Replication-Competent 
Retrovirus (RCR) Assays. 
During the September 14-15, 1992, 
RAC meeting, there was a discussion 
regarding requirements for the assays of 
replication-competent retrovirus in 
vector supernatants. In the Points to 
Consider (March 1, 1990, 55 FR 7445), 
it states: 
“I. Description of Proposal.* * * 
"B. Research design, anticipated risks, 
and benefits.* * * 
“2. Preclinical studies, including risk 
assessment studies. * * * 
"c. Laboratory studies pertaining to 
the safety of the delivery/expression 
system. 
*‘(l) If a retroviral system is used: 
* • * 
"(b) How stable are the retroviral 
vector and the resulting provirus against 
loss, rearrangement, recombination, or 
mutation? What information is available 
on how much rearrangement or 
recombination with endogenous or 
other viral sequences is likely to occur 
in the patient’s cells? What steps have 
been taken in designing the vector to 
minimize instability or variation? What 
laboratory studies have been performed 
to check for stability, and what is that 
sensitivity of the analyses? * * * 
"(e) Has a protocol similar to the one 
proposed for a clinical trial been carried 
out in non-human primates and/or other 
animals? What were the results? 
Specifically, is there any evidence that 
the retroviral vector has recombined 
with any endogenous or other viral 
sequences in the animals?” 
The recommended assays for 
detecting the presence of adventitious 
agents, including replication-competent 
retroviruses (RCR) have evolved as the 
RAC has gained experience in the 
review and approval of human gene 
transfer/therapy protocols. Recently, the 
Food and Drug Administration has been 
considering additional tests to increase 
the sensitivity of detection of RCR in 
vector supernatant preparations. 
Since it is very important that 
retroviral vectors be free of RCR, it is 
important to quantitate the relative 
safety margin afforded by the assay 
systems used. To confirm that this 
safety margin is adequate, the RAC will 
discuss specific assay requirements and 
minimal levels of detection for possible 
inclusion in the Points to Consider. 
During the Recombinant DNA 
Advisory Committee meeting on 
December 3-4, 1992, Drs. W. French 
Anderson, National Institutes of Health. 
Bethesda, Maryland; Gerard J. 
McGarrity, Genetic Therapy, Inc., 
Gaithersburg, Maryland; and Robert 
Moen, Genetic Therapy, Inc., 
Gaithersburg, Maryland, submitted a 
Report on Murine Replication- 
Competent Retrovirus (RCR) Assays. At 
the meeting, it was agreed that a 
modification of the report was 
warranted. The committee will be 
discussing the modified report during 
the March 1-2, 1993, meeting. 
XTV. Amendment to the Points to 
Consider Regarding the Separation of 
the Gene Marking Informed Consent 
Document from die Therapeutic 
Informed Consent Documents. 
During the September 14-15, 1992, 
RAC meeting, Dr. Leonard Post 
requested that when a gene transfer 
protocol is submitted as an additibn to 
a therapeutical protocol, the principal 
investigator should submit two separate 
informed consent documents, one for 
the gene marking portion and one for 
the therapeutic portion of the protocol. 
In the Points to Consider, Part I-D — 
Informed Consent (March 1, 1990, 55 FR 
7446), a new sentence would be added 
to the introductory paragraph: 
"When gene transfer is a procedure 
separate from the therapeutic protocol, 
an informed consent document should 
be submitted for both the gene marking 
end therapeutic procedures.” 
OMB’s "Mandatory Information 
Requirements for Federal Assistance 
Program Announcements” (45 FR 
39592, June 11, 1980) requires a 
statement concerning the official 
government programs contained in the 
Catalog of Federal Domestic Assistance. 
Normally, NIH lists in its 
announcements the number and title of 
affected individual programs for the 
guidance of the public. Because the 
guidance in this notice covers not only 
virtually every NIH program but also 
essentially every Federal research 
program in which DNA recombinant 
molecule techniques could be used, it 
has been determined not to be cost 
effective or in the public interest to 
attempt to list these programs. Such a 
list would likely require several 
additional pages. In addition, NIH could 
not be certain that every Federal 
program would be included at many 
Federal agencies, as well as private 
organizations, both national and 
international, have elected to follow the 
NIH Guidelines. In lieu of the 
individual program listing, NIH invites 
readers to direct questions to the 
information address above about 
whether individual programs listed in 
the Catalog of Federal Domestic 
Assistance are affected. 
Dated: February 4, 1993. 
Jay Moskowitz, 
Associate Director for Science Policy an d 
Legislation, NIH. 
fFR Doc. 93-3433 Filed 2-11-93; 8:45 ami 
BttJJNQ COOE 4140-01-41 
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