Federal Register / VoL 59. No. 29 / Friday, February 11, 1994 / Notices 
6707 
(No Changes — Parts II through II— B.) 
(Delete — Part III. Requested 
Documentation. In addition to responses to 
the questions raised in these Points to 
Consider, please submit the following 
materials:) 
(Delete— Part IIl-A. Your protocol as 
approved by your local IRB and IBC) 
(Delete — Part Ul-8. Results of local IRB 
and LBC deliberations and recommendations 
that pertain to your protocol.) 
(Delete — Part Ill-C A ooe-page scientific 
abstract of the protocol.) 
(Delete — Part UI-D. A one-page description 
of the proposed experiment In nontechnical 
language.) 
(Delete— Part E-E. Curricula vitae for key 
professional personnel.) 
(Delete — Part E-F. An Indication of other 
federal agencies to which the protocol is 
being submitted for review.) 
(Delete — Part E-G. Any other material 
which you believe wE aid in the review.) 
(Renumbered/ Amended) "Ptirt 111. 
Guidelines for the Submission of Human 
Gene Transfer Protocols" 
(Additiool “For consideration of human 
gene transfer protocols under Section E-A- 
3 and E-B-2 of the NIH Guidelines the 
following criteria will apply;" 
(Renumbered) “Part E-A. Investigator- 
Submitted Mater^” 
(Renumbered/ Amended) “Part E-A-1. 
Written proposals must be submitted in the 
following order (l) Scientific abstract — 1 
page: (2) non -technical abstract — 1 page; (3) 
institutional Biosafety Committee (IBG) and 
lostitutional Review Board (IRB) approvals 
and their deliberations pertaining to your 
protocol; (4) Points to Consider (Parts 1 and 
II) — 5 pages; (6) protocol (as approved by the 
local IRB and IBC} — 20 pages excluding 
appendices; (7) Informed Consent 
Doctimont — approved by the IRB; (8) 
appendices including tables, figures, and 
manuscripts; (9) Curricula vitae — 2 pages in 
Biographical sketch format; and (10) an 
indication of other Federal agencies to which 
the protocol is being submitted for review " 
[Renumbered) “Part 111— A-2. When a 
proposal has been submitted previously, 
there should be a short section (5 200 words) 
immediately following the abstracts that 
summarues the major revisions since the last 
review." 
(Renumbered) “Part E— A-3. Data provided 
must Include: (i) A description of the 
elements in the vector. (Uj the source of that 
information, (tli) the method by which 
sequence data were compiled, and (iv) three 
3V2 inch diskettes with the vector sequence 
in ASen format" 
(Renumbered) “Part E-A— 4. Time Frame 
for Submissions." 
(Added) “Note; Time frames are applicable 
only to protocols that are determined by NTH 
(OI^A) to require full RAC review and NIH 
Director approval. Times frames do not apply 
to Accelerated Review human gene transfer 
experiments (see Section E-B-2 of the NTH 
Guidelines) or those that only require 
registration with NIH (ORDA) (see Section 
E-C-6 of the NTH Guidelines)." 
(Renumbered) “Part Ill-A— 4-a. Written 
material from PI must be submitted at least 
6 weeks before the RAC meeting at which it 
will be reviewed." 
(Renumbered) "Part E-A— 4-b. Written 
cominculs from the primary reviewers to the 
PI must be submitted at least 4 weeks before 
tlie RAC meeting at which it will be 
reviewed." 
(Renumbered) “Part Ill-A— 4— c. Written 
responses (including critical data in response 
to the primary reviewers' comments) must be 
submitted by the Principal Investigators to 
ORDA at least 2 weeks before the RAC 
meeting." 
I Renumbered) "Part E-A -5. Oral 
Responses to the RAC" 
(No changes] “Principal Investigators must 
limit their oral responses to the RAC only to 
those questions that are raised during the 
meeting. Oral presentations of previously 
submitted material and/or critical data that 
was not submitted at least 2 weeks prior to 
the RAC meeting is prohibited." 
(Renumbered) “Part E-B. Primary 
Reviewers' Responses." 
(Renumbered] “Part E-B— 1. Primary • 
Reviewers' Written Comments." 
(No changes) “The primary reviewers' 
written comments on a proposal should 
Include the following:" 
(Renumbered) “Part E-B-l-a. Emphasize 
the Issues related to gene marking, gene 
transfer, or gene therapy." 
(Renumbered) "Part Dl-B-l-b. State 
explicitly whether the Points to Consider 
have been addressed satisfactorily." 
(Renumbered) “Part E-B-l-c. Examine 
the scientific rationale, scientific context 
(relative to other proposals reviewed by the 
RAC), whether the preliminary in vitro and 
in vivo data were obtained in appropriate 
models and are sufficient, and wheffier 
questions related to safety, efficacy, and 
social and ethical context have been 
resolved." 
(Renumbered) "Part E-B-l-d. Whenever 
possible, criticisms of Infonned Consent 
documents should include suggested 
revisions for the RAC to consider, provided 
as written altemativ’es." 
(Renumbered) "Part E-B-l-e. I^rimary 
reviews should also state whether the 
proposal is; (i) Acceptable as written, (ii) 
expected to be acceptable with specific 
revisions or after satisfactory responses to 
specific questions raised on review, or (iii) 
unacceptable in its present form." 
(Remunbered) "Part E-B-2. Oral 
Discussions by Ternary Reviewers at the RAC 
Meeting." 
(Renumbered) “Part E-B-2-a. It should be 
possible for most primary reviewers to 
present their oral reviews in 5 minutes or 
less." 
(No changes — Part VI through Vl-B.) 
(Delete — Part V. Minor Modifications to 
Human Gene Transfer Experiments 
Approved by the RAC and NIH Director 
Under Section E-A-3 of the NTH Guidelines. 
A minor modification in a protocol approved 
by the RAC and NIH Director under Section 
E-A-3 (see Section IV-C-l-b-1 — Major . 
Actions) is a change that does not 
significantly alter the basic design of a 
protocol and that does not increase risk to the 
subjects). If the change has been approved 
by the relevant IRB and IBC, then the Chair 
of the RAC may give approval. It is expected 
that the Chair will consult with one or more 
members of the committees, as necessary. 
The RAC Chair will report on any such 
approvals at the next regularly scheduled 
RAC meeting.) 
(Addition) “Part V. Procedures to be 
Followed for Accelerated Review of Human 
Gene Trai^sfer Expieriments by NIH (ORDA) 
Under Section Dl-B-2 of the NIH 
Guidelines," 
(Addition) “Part V— A. Human gene transfer 
experiments in this category must be in 
accordance with the provisions of Section 
E-®-2 of the NIH Guidelines. If the h uman 
gene transfer protocol does not qualify for 
Accelerated Review (see Section E-B-2 of 
the NIH Guidelines) as determined by NIH 
(ORDA), then the PI must submit the 
experiment lor full RAC review and NIH 
approval in accordance with Section E-A- 
3 of the NTH Guidelines." 
(Addition] “Part V-B. No protocol shall be 
considered without IBC and IRB approval." 
(Addition) “Part V-C At this time, all gene 
transfer protocols must be considered 
experimental." 
lAdditionl "Part V-O-1. Pis requesting 
Accelerated Review (see Section ID-B-2 of 
the NTH Guidelines), must submit the, 
relevant documentation In accordance with 
Part E of the Points to Consider. NIH 
(ORDA) wE liotify the investigator whether 
the proposed study qualifies for the 
Accelerated Review process. If NIH (ORDA) 
determines that an experiment does not 
qualify for the Accelerated Review process 
the PI must submit the proposal for full'RAC 
review at least 8 weeks prior to the next 
schedEed RAC meeting." 
(Addition) “Part V-R It is expected that 
NIH (ORDA) wE consult wiE Ee RAC Chair 
end one or more RAC members, as necessary, 
when considered Accelerated Review human 
gene transfer protocols (see Section E-B-2 of 
Ee NIH Guidelines — 
(Addition) “Part V-F. The Chair of Ee 
RAC wdll provide a report on all human gene 
transfer protocols that have been approv^ by 
NIH (OE)A) at Ee next regularly s<Eeduled 
RAC meeting." 
(Additionl "Part V-F-1. In accordance 
wiE Part VI. Reporting Requirements, of Ee 
Points to Consider, any adverse effects of Ee 
treatments should be reported in writing 
immediately to boE the local IRB and the 
NIH Office for Protection fiom Research 
Risks, and Ee report shoEd also be 
forwaitkd to NIH (ORDA)." 
(AdEtion) "Part V-F-2. E accordance 
wiE Part IV, Reporting ReqiEements, of Ee 
Points to Consider, reports regarding Ee 
general progress of patients shoEd be filed 
wiE both Ee local IRB and ORDA wiEln six 
monEs of Ee commencement of the 
experiments and at slx-monE Intervals. In 
Ee event of a patient's deaE, a summary of 
Ee specid pok-mortem stiidies and 
statement of Ee cause of deaE should be 
submitted to the IRB and ORDA. if' 
available." 
(Amended) “Part VL Procedures to be 
Followed for Expedited RAC Review and 
NIH Approval of Single-Patient Human Gene 
Transfer Protocols Considered Under Section 
IIl-A-3 (see Section IV-C-l-b-(l)-(d) of Ee 
NIH Guidelmes)." 
(Amended] “Part Vl-A. An mvestigator 
submitting a request to NIH (ORDA) for 
Recombinant DNA Research, Volume 19 
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