Federal Register / Vol. 50, No. 160 / Monday. August 19. 1985 / Notices 
33463 
III. Proposed Amendments of Appendix 
C— III of the NIH Guidelines 
BioTeehnica International. 
Cambridge. Massachusetts, proposes 
the following amendments to 
Appendix 0— III of the Nil I Guidelines. 
The first paragraph of Appendix C— III 
would be amended to read as follows: 
Experiments which use Soocho nxm yevs 
cerevhioe host-vector systems, with the 
exception of experiments listed below, are 
exempt from these Guidelines. 
This amendment would extend the 
current exemption to include strains 
other than "laboratory strains.” 
A new second paragraph would be 
added to Appendix C— III to read as 
follows: 
Experiments which use Sacchammyces 
iivarum host-vector systems, with the 
exception of experiments listed below, nre 
, exempt front these Guidelines. 
The company has provided 
information concerning this request to 
ORDA. 
IV. Points To Consider in the Design and 
Submission of Human Somatic-Cell 
Gene Therapy Protocols 
Proposed "Points to Consider in the 
Design and Submission of Human 
Somatic-Cell Gene Therapy Protocols" 
were published for comment in the 
Federal Register of January 22. 1985 (50 
FR 2940). Readers are referred to that 
| announcement for detailed background 
information and the roster of the RAC 
Working Group on I luman Gene 
Therapy. Fifteen letters were received 
during the comment period. Based on 
; those comments, the RAC Working 
*| Group on Human Gene Therapy met on 
April 1. 1985. and prepared a revised 
proposed Points to Consider. The 
revised proposed Points to Consider and 
I letters of comment were reviewed by 
the full RAC at its meeting on May 3. 
1985. After extensive discussion, the 
RAC voted to incorporate changes 
suggested at the meeting, to accept the 
revised Points to Consider as a working 
j document, and to republish the 
document for further comment. An 
additional section, entitled 
"Applicability." has been added to 
emphasize that the Points to Consider 
apply only to institutions receiving 
support for recombinant DNA research 
from the NIH. 
The following Points to Consider 
document incorporating the 
recommended Changes is now published 
for public comment. Comments received 
will be circulated to all RAC and 
working group members. The Points to 
Consider document and the public 
comments received will be considered 
at the next RAC meeting on September 
23. 1985. 
NATIONAL INSTITUTES OF HEALTH 
POINTS TO CONSIDER IN THE 
DESIGN AND SUBMISSION OF 
HUMAN SOMATIC-CELL GENE 
THERAPY PROTOCOLS 
Working Group on Human Gene 
Therapy NIH Recombinant DNA 
Advisory Committee 
Outline 
Applicability 
Introduction 
I. Description of Proposal 
A. Objectives and Rationale of the 
Proposed Research 
U. Research Design. Anticipated Risks and 
Benefits 
t. Structure and Characterislka of the 
Biological System 
2. (‘Technical Studies. Including Risk- 
Assessment Studies 
3. Clinical Procedures. Including Patient 
Monitoring 
4. Public-Health Considerations 
5. Qualifications of Investigators. 
Adequacy of Laboratory and Clinical 
Facilities 
C. Selection of Patients 
D. Informed Consent 
E. Privacy and Confidentiality 
II. Special Issues 
A. Provision of Accurate Information to the 
Public 
B. Timely Communication of Research 
Methods and Results to Investigators and 
Clinicians 
III. Requested Documentation 
A. Original Protocol 
B. IRB and IBC Minutes and 
Recommendations 
C. One-Page Abstract of Gene Therapy 
Protocol 
D. One-Page Description of Proposed 
Experiment in Non-Technical Language 
E. Curricula vitae for Professional 
Personnel 
F. Indication of Other Federal Agencies To 
Which the Protocol Is Being Submitted 
G. Other Pertinent Material 
IV. Reporting Requirements 
Applicability 
These "Points to Consider" dpply only 
to research conducted at or sponsored 
by an institution that receives any 
support for recombinant DNA research 
from the National institutes of Health 
(NIH). This includes research performed 
by NIH directly. 
Introduction 
(1) Experiments in which recombinant 
DNA 1 is introduced into cells of a 
1 Section ni-A-4 applies to both recombinant 
DNA and DNA derived from recombinant DNA. 
human subject with the intent of stably 
modifying the subject's genome are 
covered by Section III— A— 4 of the NIM 
Guidelines for Research Involving 
Recombinant DNA Molecules (49 FR 
46260). Section III— A— 4 requires sudh 
experiments to be reviewed by the NIH 
Recombinant DNA Advisory Committee 
(RAC) and approved by the NIH. RAC 
consideration of each proposal will be 
on a case-by-caes basis and will follow 
publication of a precis of the proposal in 
the Federal Register, an opportunity for 
public comment, and a review of the 
proposal by the working group of the 
RAC. RAC recommendations on each 
proposal will be forwarded to the NIH 
Director for a decision which will then 
be published in the Federal Register. In 
accordance with Section I V-C-l-b of 
the NIH Guidelines, the NIH Director 
may approve proposals only if he finds 
that they present “no significant risk to 
health or the environment.” 
(2) In general, it is expected that 
somatic-cell gene therapy protocols will 
not present a risk to the environment as 
the recombinant DNA is expected to be 
confined to the human subject. 
Nevertheless. Section I-B— 4-b of the 
"Points to Consider" document asks the 
researchers to address specifically this 
point. 
(3) This document is intended to 
provide guidance in preparing proposals 
for NIH consideration under Section ’HI— 
A— 4 of the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
Not every point mentioned in the 
“Points to Consider" document will 
necessarily require attention in every 
proposal, it is expected that the 
document will be considered for 
revision at least annually as experience 
in evaluating proposal accumulates and 
as new scientific developments occur. 
(4) A proposal will be considered by 
the RAC only after the protocol has 
been approved by the local Institutional 
Biosafety Committee (IBC) and by the 
local Institutional Review Board (IRB) in 
accordance with Department of Health 
and Human Services (DHHS) 
Regulations for the Protection of Human 
Subjects (45 CFR Part 46). If a proposal 
involves children, special attention 
should paid to subpart D of these DHHS 
regulations. The IRB and IBC may, at 
their discretion, condition their approval 
on further specific deliberation by the 
RAC and its working group. 
Consideration of gene therapy proposals 
by the RAC may proceed simultaneously 
with review by any other involved 
federal agencies 1 provided that the RAC 
’The Food and Drug Adm tnt 8 1 ration (FDA) has 
jurisdiction over dreg products intended for use In 
Continued 
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