60128 
NOTICES 
Note.— If the agenda for an RAC meeting 
Is modified. ORDA shall make the revised 
agenda available to anyone, upon request, at 
least 72 hours in advance of the meeting. 
IV-E-3-c-<5). Publish the Recombin- 
ant DNA Technical Bulletin', and 
IV-E-3-c-<6). Serve as executive sec- 
retary to the RAC. 
IV-E-4. Other N1H Components. 
Other NIH components shall be re- 
sponsible for: 
IV-E-4-a. Awarding no grant or con- 
tract involving recombinant DNA 
techniques unless a properly executed 
MUA has been received; 
IV-E-4-b. Certifying P4 facilities, in- 
specting them periodically and inspec- 
tion other recombinant DNA facilities 
as deemed necessary; and 
IV-E-4-c. Announcing and distribut- 
ing certified HV2 and HV3 host-vector 
systems (see Section II-E-3). 
(See Administrative Practices Sup- 
plement for additional information on 
the administrative procedures of 
ORDA and other NIH components.) 
IV-F. Registration 
IV-F-1. Required Registration. Insti- 
tutions receiving NIH funds for recom- 
binant DNA projects shall inform NIH 
of all recombinant I>NA projects at 
the institution. A non-NIH project, 
after approval by the Institutional 
Biosafety Committee, shall be regis- 
tered with NIH within 30 days of initi- 
ation. Applications for NIH projects 
must be accompanied by a Memoran- 
dum of Understanding and Agreement 
(MUA). 
For information on MUAs or equiva- 
lent documents that must be submit- 
ted for registration of recombinant 
DNA projects, see the Administrative 
Practices Supplement (APS). 
IV-F-2. Federal Agency Registration. 
Institutions at which recombinant 
DNA research projects funded by 
other Federal agencies are conducted 
need not register such projects with 
NIH when the Federal agency main- 
tains a registry and provides such in- 
formation to NIH. Registration of 
non-NIH-funded research with the 
NIH Office of Recombinant DNA Ac- 
tivities (ORDA) is described in the 
APS. (The information required is 
similar to that in an MUA for NIH- 
supported research.) 
IV-F-3. Voluntary Registration and 
Certification. Any institution that is 
not required to comply with the 
Guidelines may nevertheless register 
recombinant DNA research projects 
with NIH by submitting the appropri- 
ate information to ORDA. NIH will 
accept requests for certification of 
host-vector systems proposed by the 
institition. The submitter must agree 
to abide by the physical and biological 
containment standards of the NIH 
Guidelines. 
IV-F-4. Disclosure of Information. 
Institutions are reminded that they 
FEDERAL 
should consider applying for a patent 
before submitting information to 
DHEW which they regard as poten- 
tially prpprietary. (Provisions for pro- 
tection of proprietary information as 
permitted under current DHEW au- 
thorities will be proposed as a future 
supplement to these Guidelines.) 
IV-G. Compliance. As a condition 
for NIH funding of recombinant DNA 
research, Instititions must ensure that 
such research conducted at or spon- 
sored by the Instititon, irrespective of 
the source of funding, shall comply 
with these Guidelines. The policies on 
noncompliance are as follows: 
IV-G-1. All NIH-funded projects in- 
volving recombinant DNA techniques 
must comply with the NIH Guidelines. 
Noncompliance may result in (1) sus- 
pension, limitation, or termination of 
financial assistance for such projects 
and of NIH funds for other recombin- 
ant DNA research at the Institution, 
or (ii) a requirement for prior NIH ap- 
proval of any or all recombinant DNA 
projects at the Institution. 
IV-G-2. All non-NIH-funded pro- 
jects involving recombinant DNA tech- 
niques conducted at or sponsored by 
an Institution that receives NIH funds 
for projects involving such techniques 
must comply with the NIH Guidelines. 
Noncompliance may result in (i) sus- 
pension, limitation, or termination of 
NIH funds for recombinant DNA re- 
search at the Institution, or (ii) a re- 
quirement for prior NIH approval of 
any or all recombinant DNA projects 
at the Institution. 
IV-G-3. Information concerning 
noncompliance with the Guidelines 
may be brought forward by any 
person. It should be delivered to both 
NIH (ORDA) and the relevant Institu- 
tion. The Institution, generally 
through the IBC, shall take appropri- 
ate action. The Institution shall for- 
ward a complete report of the incident 
to ORDA, recommending any further 
action indicated. 
IV-G-4. In cases where NIH pro- 
poses to suspend, limit, or terminate 
financial assistance because of non- 
compliance with the Guidelines, appli- 
cable DHEW and Public Health Serv- 
ice procedures shall govern. 
V. Footnotes and References 
1. The reference to organisms as Class 1, 
2, 3. 4, or 5 refers to the classification In the 
publication Classification of Etiologic 
Agents on the Basis of Hazard, 4'th Edition, 
July 1974; U.S. Department of Health, Edu- 
cation, and Welfare, Public Health Service, 
Center for Disease Control, Office of Biosa- 
fety. Atlanta, Georgia 30333. The list of or- 
ganisms in each class, as given in this publi- 
cation, is reprinted in Appendix B to these 
Guidelines. 
The Director, NIH. with advice of the Re- 
combinant DNA Advisory Committee, may 
designate certain of the agents which are 
listed as Class 2 in the Classification of 
Etiologic Agents on the Basis of Hazard, 4th 
REGISTER, VOL. 43, NO. 247— FRIDAY, DECEMBER 
[ 50 ] 
Edition. July 1974. as Class 1 agents for the 
purposes of these Guidelines (see Section 
IV-E-l-b-(2)-<d)). An updated list of such 
agents may be obtained from the Office of 
Recombinant DNA Activities (ORDA). Na- 
tional Institutes of Health, Bethesda, Mary- 
land 20014. 
The entire Classification of Etiologic 
Agents on the Basis of Hazard is in the proc- 
ess of revision. 
One exception to the prohibition of for- 
mation of recombinant DNAs derived from 
Class 3. 4. or 5 agents is that the formation 
of recombinant DNAs derived from Vesicu- 
lar Stomatitis Virus (VSV) is not prohibited. 
The reason for this is explained in the “De- 
cision Document" accompanying the pro- 
posed revised guidelines published in the 
Federal Register on July 28, 1978. Howev- 
er, as noted in Appendix B, a permit from 
the U.S. Department of Agriculture is re- 
quired for the import or interstate transport 
of VSV. This can be obtained form USDA- 
APHIS, Veterinary Service. Federal Build- 
ing. Hyattsville. Maryland 20782. 
2A In Parts I and III of the Guidelines, 
there are a number of places where Judg- 
ments are to be made. These include: "cells 
known to be infected with such agents" 
(Section I-D-ll; “toxins potent for verte- 
brates" (Section I-D-2); "beyond that which 
occurs by natural genetic exchange" (Sec- 
tion I-D-3); "known to acquire it naturally" 
(Section I-D-5); "known to produce a potent 
polypeptide toxin • * • or known to carry 
such pathogens * * * not likely to be a prod- 
uct of closely linked eukaryote genes • • • 
shown not to contain such agents” (Section 
III-A-l-a-<5)-(a)); "shown to be free of dis- 
ease causing microorganisms" (Section III- 
A-l-a-(5)-(b)): "close relatives” (Section III- 
C-3); and "produce a potent polypeptide 
toxin” (Footnote 34). 
In all these cases the principal investiga- 
tor is to make the initial judgment on these 
matters as part of his responsibility to 
“make the initial determination of the re- 
quired levels of physical and biological con- 
tainment in accordance with the Guide- 
lines" (Section IV-D-7-a). In all these cases, 
this Judgment is to be reviewed and ap- 
proved by the Institutional Biosafety Com- 
mittee as part of its rsponsibility to make 
“an independent assessment of the contain- 
ment levels required by these Guidelines for 
the proposed research" (Section IV-D-3-a- 
(1)). If the IBC wishes; any specific cases 
may be referred to the NIH Office of Re- 
combinant DNA . Activities as part of 
ORDA s functions to “provide advice to all 
within and outside NIH” (Section IV-E-3), 
and ORDA may request advice from the Re- 
combinant DNA Advisory Committee as 
part of the RAC's responsibility for "inter- 
esting and determining containment levels 
upon request by ORDA” (Section IV-E-l-b- 
(2Ma». 
3. The following types of data should be 
considered in determining whether DNA re- 
combinants are "characterized” and the ab- 
sence of harmful sequences has been estab- 
lished: (a) The absence of potentially harm- 
ful genes (e.g., sequences contained in indig- 
enous tumor viruses or sequences that code 
for toxins, invasins, virulence factors, etc., 
that might potentiate the pathogenicity or 
communicability of the vector -and/or the 
host or be detrimental to humans, animals, 
or plants); (b) the types(s) of genetic infor- 
mation on the cloned segment and the 
nature of transcriptional and translation 
gene products specified; (c) the relationship 
22, 1978 
i 
