Federal Register / Vol. 44, No. 232 / Friday, November 30, 1979 / Notices 
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for NIH projects must be accompanied 
by a Memorandum of Understanding 
and Agreement (MUA). 
For information of MUAs or 
equivalent documents that must be 
submitted 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 maintains a 
registry and provides such information 
to NIH. Registration of non-NIH-funded 
research with the NIH Office of 
Recombinant DNA Activities (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 appropriate information 
to ORDA. NIH will accept requests for 
certification of host-vector systems 
proposed by the institution. 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 
should consider applying for a patent 
before submitting information to DHEW 
which they regard as potentially 
proprietary. (Provisions for protection of 
proprietary information as permitted 
jnder current DHEW authorities are 
discussed in Part VI of these 
Guidelines.) 
IV-G. Compliance. As a condition for 
NIH funding of recombinant DNA 
research, Institutions must ensure that 
such research conducted at or 
sponsored by the Institution, 
irrespective of the source of funding, 
shall comply with these Guidelines. The 
policies on noncompliance are as 
I follows: 
IV-G-1. All NIH-funded projects 
involving recombinant DNA techniques 
i must comply with the NIH Guidelines. 
Noncompliance may result in (i) 
i suspension, limitation, or termination of 
financial assistance for such projects 
and of NIH funds for other recombinant 
DNA research at the Institution, or (ii) a 
! requirement for prior NIH approval of 
any or all recombinant DNA projects at 
1 the Institution. 
IV-G-2. All non-NIH-funded projects 
involving recombinant DNA techniques 
I 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) 
suspension, limitation, or termination of 
NIH funds for recombinant DNA 
research at the Institution, or (ii) a 
requirement 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 Institution. 
The Institution, generally through the 
IBC, shall take appropriate action. The 
Institution shall forward a complete 
report of the incident to ORDA, 
recommending any further action 
indicated. 
IV-G— 4. In cases where NIH proposes 
to suspend, limit, or terminate financial 
assistance because of noncompliance 
with the Guidelines, applicable DHEW 
and Public Health Service procedures 
shall govern. 
IV-G-5. Voluntary Compliance. Any 
individual, corporation, or institution 
that is not otherwise covered by the 
Guidelines is encouraged to conduct 
recombinant DNA research activities in 
accordance with the Guidelines, through 
the procedures set forth in Part VI. 
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. 4th Edition. July 1974; 
U.S. Department of Health. Education, and 
Welfare, Public Health Service, Center for 
Disease Control. Office of Biosafety, Atlanta, 
Georgia 30333. The list of organisms in each 
class, as given in this publication, is 
reprinted in Appendix B to these Guidelines. 
The Director, NIH, with advice of the 
Recombinant 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, 4 th 
Edition, July 1974, as Class 1 agents for the 
Purposes of these Guidelines (see Section IV- 
E— 1— b— {2)(d)J. An updated list of such agents 
may be obtained from the Office of 
Recombinant DNA Activities (ORDA), 
National Institutes of Health, Bethesda, 
Maryland 20205. 
The entire Classification of Etiologic 
Agents on the Basis of Hazard is in the 
process of revision. 
2. One exception to the prohibition of 
formation of recombinant DNAs derived from 
Class 3, 4, or 5 agents is that the formation of 
recombinant DNAs derived from Vesicular 
Stomatitis Virus (VSV) is not prohibited. The 
reason for this is explaned in the "Decision 
Document" accompanying the proposed 
revised guidelines published in the Federal 
Register on July 28, 1978. However, as noted 
in Appendix B, a permit from the U.S. 
Department of Agriculture is required for the 
import or interstate transport of VSV. This 
can be obtained from USDA— APHIS, 
[ 215 ] 
Veterinary Service, Federal Building, 
Hyattsville, Maryland 20782. 
2A. In Parts I and III of the Guidelines, 
there are a number of places where 
judgments are to be made. These include: 
"cells known to be infected with such agents” 
(Section I-D-l); "toxins potent for 
vertebrates" (Section I— D— 2); “beyond that 
which occurs by natural genetic exchange" 
(Section 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 product of closely linked 
eukaryote genes . . . shown not to contain 
such agents” (Section HI— A— 1— a— (5) — (a)); 
"shown to be free of disease causing 
microorganisms" (Section III— A— 1— a— (5) — (b)): 
"close relatives" (Section III— C— 3): and 
“produce a potent polypeptide toxin” 
(Footnote 34). 
In all these cases the principal investigator 
is to make the initial judgment on these 
matters as part of his responsibility to “make 
the initial determination of the required 
levels of physical and biological containment 
in accordance with the Guidelines" (Section 
IV-D-7-a). In all these cases, this judgment is 
to be reviewed and appoved by the 
Institutional Biosafety Committee as part of 
its responsibility to make "an independent 
assessment of the containment levels 
required by these Guidelines for the proposed 
research" (Section IV-D-3-a-(l)). If the IBC 
wishes, any specific cases may be referred to 
the NIH Office of Recombinant 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’ Recombinant DNA 
Advisory Committee as part of the RAC's 
responsibility for “interpreting and 
determining containment levels upon request 
by ORDA" (Section IV-E-l-b-{2Ha)). 
3. The following types of data should be 
considered in determining whether DNA 
recombinants are "characterized" and the 
absence of harmful sequences has been 
established: (a) the absence of potentially 
harmful genes (e.g., sequences contained in 
indigenous 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 type(s) of genetic information 
on the cloned segment and the nature of 
transcriptional and translation gene products 
specified; (c) the relationship between the 
recovered and desired segment (e.g., 
hybridization and restriction endonuclease 
fragmentation analysis where applicable); (d) 
the genetic stability of the cloned fragment; 
and (e) any alternations in the biological 
properties of the vector and host 
4. In Section I-E, "exemptions" from the 
Guidelines are discussed. Such experiments 
are not covered by the Guidelines and need 
not be registered with NIH. In Section I-D on 
“prohibitions," the possibility of "exceptions" 
is discussed. An “exception” means that an 
experiment may be expressly released from a 
prohibition. At that time it will be assigned 
an appropriate level of physical and 
biological containment. 
5. Care should be taken to inactivate 
recombinant DNA before disposal. 
