Federal Register / Vol. 44, No. 232 / Friday. November 30. 1979 / Notices 
69231 
recommendations on handling the viruses 
themselves. 
40. HVlCV means the use of an HVl host 
and a vector certified for use in an HV2 
system. 
41. The DNA preparation is defined as 
“purified" if the desired DNA represents at 
least 99% (w/w) of the total DNA in the 
preparation, provided that it was verified by 
mort than one procedure. 
42. The lowering of the containment level 
when this degree of purification has been 
obtained is based on the fact that the total 
number of clones that must be examined to 
obtain the desired clone is markedly reduced. 
Thus, the probability of cloning a harmful 
gene could, for example, be reduced by more 
than 10-fold when a nonrepetitive gene from 
mammals was being sought. Furthermore, the 
level of purity specified here makes it easier 
to establish that the desired DNA does not 
contain harmful genes. 
43. This is not permitted, of course, if it 
falls under any of the Prohibitions of Section 
I-D. Of particular concern here is prohibition 
l-D-5, i.e., "Deliberate transfer of a drug 
resistance trait to microorganisms that are 
not known to acquire it naturally, if such 
acquisition could compromise the use of a 
drug to control disease agents in human or 
veterinary medicine or agriculture." 
44. Because this work will be done almost 
exclusively in tissue culture cells, which have 
no capacity for propagation outside the 
laboratory, the primary focus for containment 
is the vector. It should be pointed out that 
'risk of laboratory-acquired infection as a 
consequence of tissue culture manipulation is 
very low. Given good microbiological 
practices, the most likely mode of escape of 
recombinant DNAs from a physically 
contained laboratory is carriage by an 
infected human. Thus the vector with an 
inserted DNA segment should have little or 
no ability to replicate or spread in humans. 
For use as a vector in a vertebrate host cell 
system, an animal viral DNA molecule should 
display the following properties: 
(1) It should not consist of the whole 
genome of any agent that is infectious for 
humans or that replicates to a significant 
extent in human cells in tissue culture. If the 
recombinant molecule is used to transform 
nonpermissive cells (i.e., cells which do not 
produce infectious virus particles), this is not 
a requirement 
(ii) It should be derived from a virus whose 
epidemiological behavior and host range are 
well understood. 
(iii) In permissive cells, it should be 
defective when carrying an inserted DNA 
segment (I.e., propagation of the recombinant 
DNA as a virus must be dependent upon the 
presence of a complementing helper genome). 
In most all cases this condition would be 
achieved automatically by the manipulations 
used to construct and propagate the 
recombinants. In addition, the amount of 
DNA encapsidated in the particles of most 
animal viruses is defined within fairly close 
limits. The insertion of sizable foreign DNA 
sequences, therefore, generally demands a 
compensatory deletion of viral sequences. It 
may be possible to Introduce very short 
Insertions (50-100 base pairs) without 
rendering the viral vector defective. In such a 
situation, the requirement that the viral 
vector be defective is not necessary, except 
in those cases in which the inserted DNA 
encodes a biologically active polypeptide. 
It is desired but not required that the 
functional anatomy of the vector be known — 
that is, there should be a clear idea of the 
location within the molecule of: 
(i) the sites at which DNA synthesis 
originates and terminates, 
(ii) the sites that are cleaved by restriction 
endonucleases, and 
(iii) the template regions for the major gene 
product. 
If possible the helper virus genome should: 
(i) be integrated into the genome of a stable 
line of host cells (a situation that would 
effectively limit the growth of the vector 
recombinant to such cell lines) or 
(ii) consist of a defective genome, or an 
appropriate conditional lethal mutant virus, 
making vector and helper dependent upon 
each other for propagation. 
However, neither of these stipulations is a 
requirement 
45. Review by NIH on a case-by-case basis 
means that NIH must review and set 
appropriate containment conditions before 
the work may be undertaken. NIH actions in 
such case-by-case reviews will be published 
in the Recombinant DNA Technical Bulletin. 
46. Provided the inserted DNA sequences 
are not derived from eukaryotic viruses. In 
the latter case, such experiments will be 
evaluated on a case-by-case basis. 
47. >99% pure; otherwise as for shotgun 
experiments. 
VI. Voluntary Compliance 
VI-A. Basic Policy. Individuals, 
corporations, and institutions not 
otherwise covered by the Guidelines are 
encouraged to do so by following the 
standards and procedures set forth in 
Parts I-IV of the Guidelines. In order to 
simplify discussion, references hereafter 
to "institutions" are intended to 
encompass corporations, and 
individuals who have no organizational 
affiliation. For purposes of complying 
with the Guidelines, an individual 
intending to carry out research involving 
recombinant DNA is encouraged to 
affiliate with an institution that has an 
Institutional Biosafety Committee 
approved under the Guidelines. 
Since commercial organizations have 
special concerns, such as protection of 
proprietary data, some modifications 
and explanations of the procedures in 
Parts I-IV are provided below, in order 
to address these concerns. 
VI-B. IBC Approval. The NIH Office 
of Recombinant DNA Activities (ORDA) 
will review the membership of an 
institution's Institutional Biosafety 
Committee (IBC) and, where it finds the 
IBC meets the requirements set forth in 
Section IV-D-2, wall give its approval to 
the IBC membership. 
It should be emphasized that 
employment of an IBC member solely 
for purposes of membership on the EBC 
does not itself make the member an 
institutionally affiliated member for 
purposes of Section IV-D-2-a. 
Except for the unaffiliated members, a 
member of an IBC for an institution not 
otherwise covered by the Guidelines 
may participate in the review and 
approval of a project in which the 
member has a direct financial interest, 
so long as the member has not been and 
does not expect to be engaged in the 
project. Section IV-D-2-d is modified to 
that extent for purposes of these 
institutions. 
VI-C. Registration. Upon approval of 
a recombinant DNA research project by 
the IBC, an institution may register the 
project by submitting to ORDA the 
information required in the 
Administrative Practices Supplement. 
VI-D. Certification of Host-Vector 
Systems. A host-vector system may be 
proposed for certification by the 
Director, NIH, in accordance with the 
procedures set forth in Section II-D-2-a. 
Institutions not otherwise covered by 
the Guidelines will not be subject to 
Section II-D-3 by complying with these 
procedures. 
In order to ensure protection for 
proprietary data, any public notice 
regarding a host-vector system which is 
designated by the institution as 
proprietary under Section VI-F-1 will be 
issued only after consultation with the 
institution as to the content of the 
notice. 
VI-E. Requests for Exceptions, 
Exemptions, Approvals. Requests for 
exceptions from prohibitions, 
exemptions, or other approvals required 
by the Guidelines should be requested 
by following the procedures set forth in 
the appropriate sections in Parts I-IV of 
the Guidelines. 
In order to ensure protection for 
proprietary data, any public notice 
regarding a request for an exception, 
exemption, or other approval which is 
designated by the institution as 
proprietary under Section VI-F-1 will be 
issued only after consultation with the 
institution as to the content of the 
notice. 
VI-F. Protection of Proprietary Data. 
In general, the Freedom of Information 
Act requires Federal agencies to make 
their records available to the public 
upon request. However, this requirement 
does not apply to, among other things, 
"trade secrets and commercial and 
financial information obtained- from a 
person and privileged or confidential.” 
18 U.S.C. 1905, in turn makes it a crime 
for an officer or employee of the United 
States or any Federal department or 
agency to publish, divulge, disclose, or 
make known "in any manner or to any 
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