19778 
Federal Register / Vol. 56, No. 82 / Monday. April 29, 1991 / Notices 
Category of Experiments: Experiments 
that require RAC review and NIH and 
IBC approval before Initiation. Section 
III-A-2 curently reads: 
Ill-A-2. Deliberate release into the 
envirotunent of any organism containing 
recombinant DNA except those listed below. 
The term 'deliberate release' is defined as a 
planned introduction of recombinant DNA- 
containing microorganisms, plants, or 
animals into the environment 
ni-A-Z-a. Introductions conducted under 
conditions considered to be accepted 
scientihc practices in which there is adequate 
evidence of biological and/or physical 
control of the recombinant DNA-containing ’ 
organisms. The nature of such evidence is 
described in appendix L 
m-A-Z-b. Deletion derivatives and single 
base changes not otherwise covered by the 
Guidelines. 
m-A^2-c. For extrachromosomal elements 
and microorganisms (including viruses), 
rearrangements and amplifications within a 
single genome. Rearrangements involving the 
introduction of DNA from different strains of 
the same species would not be covered by 
this exemption. 
It is proposed to delete this Section 
III-A-2 in its entirety. 
VL Amend the “Points to Consider in the 
Design and Submbsion of Protocols for 
the Transfer of Recombinant DNA into 
the Genome of H uman Subjects” 
A. Review Process 
In a memorandum dated April 6, 1991, 
from Dr. W. French Anderson of the 
National Institutes of Health, he 
proposes that the Human Gene Therapy 
Subcommittee be eliminated from the 
review process involving human gene 
iherapy protocols. These review 
responsibilities would be totally 
transferred to the parent committee, the 
Recombinant DNA Advisory Committee. 
In his letter, he states: 
Over the past year the RAC has 
undertaken a review of its mission. Many of 
its earlier duties are no longer required, but 
human gene therapy remains as a major 
responsibility. The RAC has been acquiring 
over the past several years the expertise to 
review chnical protocols and, in fact, there is 
now almost a duplication of review, in some 
cases by the same people (there are seven 
individuals who sit on both the Subcommittee 
and the RAC). I believe that the 
Subcommittee has now fulfilled its role and 
should be dissolved. However, the expertise 
of the Subcommittee members should not be 
lost Accordingly, those Subcommittee 
members with unexpired terms could serve 
as ad hoc consultants to the RAC until their 
appointments are completed. By having the 
national review limited to the RAG time 
would be saved in the review process and 
duplication would be avoided. If the number 
of RAC meetings were increased to four per 
year, then the total number of meetings 
would be reduced from six to four, and the 
length of the review process would be 
decreased. Local review, RAC national 
review, and FDA ongoing review would 
appear to be more than adequate to insure a 
thorough oversight It would seem to be 
timely for the RAC to consider this 
possibility. 
The proposed amendment to the 
Introduction, section 4, 6. 7, 9, 10, 12 of 
the Points to Consider deletes all 
references to the Subcommittee. The 
text reads as follows: 
(4) A proposal will be considered by the 
RAC only ^ter the protocol has been 
approved by the lo<ial Institutional Biosafety 
Committee (IBC) and by the local 
Institutional Reriew Board (IRB) in 
accordance with Department of Health and 
Human Services (DHHS) Regulations for the 
Protection of Human Subjects (45 Code of 
Federal Regulations, Part 46). (If a proposal 
involves children, special attention should be 
paid to subpart D of these DHHS regulations.) 
The IRB and EBC may, at their discretion, 
condition their approval. on further specific 
deliberation by the RAG Consideration of 
proposals by tiie RAC may proceed 
simultaneously with review by any other 
involved federal agencies * provided that the 
RAC is notified of the simultaneous review. 
Meetings of the Committee will be open to 
the public except where trade secrets or 
propriety information would be disclosed. 
The committee prefers that the first {M-oposals 
submitted fc«RAC review cont^ no 
proprietary information or trade secrets, 
enabling ^ aspects of the review to be open 
to the public, ^e public review of these 
protocols will serve to inform the public not 
only on the technical aspects of the proposals 
but also on the meaning and significance of 
the research. 
(6) Following the Introduction, this 
document is divided into four parts. Part I 
requests a description of the protocol with 
special attention to the short-term risks and 
benefits of the pressed research to the 
patient 4 and to other people, the selection of 
patients, informed consent, and privacy and 
confidentiality. In part n. investigators are 
requested to address special issues pertaining 
to the free flow of information about the 
clinical trials. Hiese issues lie outside the 
usual purview of IRBs and reflect general 
public concenu about biomedical research. 
Part m sununarizes other requested 
documentation that will assist the RAC in its 
review of tiie proposals. Part IV specifies 
reporting requirements. 
(7) The RAC will not at present entertain 
proposals for gerin line alterations but will 
consider for approval protocols involving 
somatic cell gene therapy. The purpose of 
somatic cell gene therapy is to treat an 
individual patient, e.g„ by inserting a 
properiy functioning gene into a patient's 
somatic cells. In germ line alterations, a 
sp>ecific attempt is made to introduce genetic 
changes into the germ (reproductive) cells of 
an individual, with the aim of changing the 
set of genes passed on to the individual's 
offspring.' 
(9) In their evaluation of proposals 
involving the transfer of recombinant DNA 
into human subjects, the RAC will consider 
w'hether the design of such experiments 
offers adequate assurance that their 
consequences will not go beyond their 
purpose, which is the same as the traditional 
purpose of all clinical investigations, namely, 
to protect the health and well-being of the 
individual subjects being treated while at the 
same time gathering generalizable 
knowledge. 
Two possible imdesirable consequences of 
the transfer of recombinant DNA would be 
unintentional: (1) vertical traiumisslon of 
genetic changes from an individual to his or 
her offspring or (2) horizontal transmission of 
viral Infection to other persons with whom 
the indiridual comes in contact Accordingly, 
this dociunent requests Information that 
enable the RAC to assess the possibility that 
the proposed experiments will inadvertently 
affect reproductive cells or lead to infection 
of other people (e.g., treatment personnel or 
relatives). 
(10) In recognition of the social concern 
that surrounds the subject of gene transfer, 
the RAC will cooperate with other groups in 
assessing the possible long-term 
consequences of the transfer of recombinant 
DNA into human subjects and related 
laboratory and animal experiments in order 
to define appropriate human applications of 
this emerging technology. 
(12) Inves^atofs should indicate points 
which are not applicable with a brief 
explanatloiL Investigators submitting 
proposals that employ essentially the same 
vector systems (or with minor variatioiu), 
and/or tiiat are based on the same preclinlcal 
testing as proposals previously reviewed by 
the Recombiiumt DNA Advisory Committee 
(RAC), may refer to preceding documents 
without having to rewrite suc^ niateriaL'' 
This proposed amendment will be 
considered during the Recombinant 
DNA Advisory Committee May 30-31, 
1991, meeting. 
B. PrecUnical Studies 
In a letter dated March 4, 1991, Dr. R. 
Scott Mclvor of the University of 
Minnesota proposed having more 
explicit directives for animal model 
systems and ceH culture studies in 
Section 1-6-2 of the Points to Consider. 
Section I-B-2 in the Points to 
Consider currently reads: 
2. Preclinlcal studies, including risk- 
assessment studies. 
Describe the experimental basis (derived 
fit>m tests in culhued cells and animals) for 
claims about the efScacy and safety of the 
proposed system for gene delivery and 
explain why the model(s) chosen is (are) the 
most appropriate. 
During the Human Gene Therapy 
Subcommittee meeting of April 5, 1991, the 
subcommittee recommended the following 
text change in the Points to Consider 
1-^2. Preclinical studies, including risk 
assessment studies. Provide results that 
demonstrate the safety, efficacy, and 
feasibility of the proposed procedures using 
animal and/or cell culture model systems, 
and explain why the models chosen are the 
most appropriate. 
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Recombinant DNA Research, Volume 14 
