NOTICES 
33127 
this part of the PRG-RAC was de- 
signed to proride an adrninistrative 
framework for implementation. 
Institution 
In the PRG-RAC as compared with 
the current Guidelines. several 
changes were proposed in the respon- 
sibilities of the institution. Responsi- 
bilities that were added or further de- 
tailed included: (l)a requirement for 
insuring the training of research per- 
sonnel and the use of good microbiolo- 
gical technique, and (2) a requirement 
to determine the need for medical pro- 
cedures, with recommendations of pos- 
sible specific practices. 
Institutional biosafety committees 
Membership of the IBC's was clari- 
fied by a recommendation to include 
other than scientific members. In the 
PRG-RAC, institutional biosafety 
committees (called ’ ‘biohazards com- 
mittees” in the current Guidelines) 
are given the discretion to approve 
single-step reductions in containment 
levels for experiments with character- 
ized clones and purified DNA. The 
IBC's would be required to notify the 
NIH Office of Recombinant DNA Ac- 
tivities ORDA) of these approvals. 
Biological safety officer 
Institutions at which P3 and P4 level 
recombinant DNA work is conducted 
would tr required to have a biological 
safety officer, whose specific roles and 
responsibilities are outlined. 
Principal Investigator. The role and 
responsibilities of the principal investi- 
gator would remain basically the same, 
except for the important addition of a 
requirement for training in microbio- 
logical techniques. Responsibility for 
the determination of the practices nec- 
essary for medical surveillance would 
be relocated to the institution. 
NIH responsibilities 
Office of the Director. The responsi- 
biii :es of the Director remain un- 
changed. A sentence has been added 
that clarifies the Director’s authority 
to implement the Guidelines and to be 
the final arbiter in their interpreta- 
tion. 
Recombinant advisory committee 
There were no changes in the cur- 
rent responsibilities of the RAC. 
There were, however, clarifications of 
the scope of some duties — for example, 
the certification process. The language 
of the 1S76 Guidelines caused some 
confusion about the certification of 
EK2 (HV2) and EK3 (HV3) host- 
vector systems. In practice, the certifi- 
cation process, clarified in the PRG- 
RAC, involves a two-step procedure: 
(1) The RAC's recommendation to the 
Director, NIH, that a particular host- 
vector system be certified; and (2) cer- 
tification of the system by the Direc- 
tor. The rationale for the procedure is 
that it allows the Director to solicit 
the opinions of additional experts 
before making a financial decision on 
certification. 
The RAC's authority to recommend 
exceptions from the prohibitions was 
also clarified. The 1976 version of the 
Guidelines envisioned the possibility 
of the RAC's recommending an excep- 
tion to the 10-liter limit on culture 
volume for recombinant DNA’s known 
to make harmful products. The pro- 
posed revision would extend the possi- 
bility of an exception to the five other 
classes of currently prohibited experi- 
ments. 
The general rationale for this addi- 
tion is twofold: the RAC's inability to 
foresee all possible future circum- 
stances and its desire to specify, 
within the limits of strict safeguards, 
the possibility of an exception for 
compelling social or scientific reasons. 
A more immediate and specific justifi- 
cation for the paragraph on excep- 
tions from the prohibitions is that the 
risk-assessment studies necessary for a 
clearer understanding of the potential 
biohazards of recombinant DNA re- 
search may be technically prohibited 
by the current Guidelines, unless 
there is a mechanism for approving 
exceptions. 
Alternatives: Public Commentators 
Institutional responsibilities 
This section of the Guidelines drew 
considerable comment directed to the 
roles and responsibility of the local in- 
stitution and its several constituents. 
Generally, commentators requested 
more information and greater clarifi- 
cation of the structure and operation 
of the IBC, the function of the biologi- 
cal safety officer, and the duties of the 
institution. The suggestions and com- 
ments were carefully considered, in 
view of the importance of this section 
to successful implementation of the 
Guidelines and therefore safe conduct 
of the research. 
NTH has a special responsibility for 
leadership in developing and promot- 
ing safety programs relevant to recom- 
binant DNA experiments. Accordingly, 
as in 1976, another committee chaired 
by Dr. W. Emmett Barkley, Director 
of the National Cancer Institute’s 
Office of Research Safety, was con- 
vened to address concerns raised. As a 
result, and in response to a number of 
commentators’ requests, the substance 
of Appendix D has been revised and 
republished as a supplement to the 
Guidelines. The revised Guidelines 
also retain requirements for emergen- 
cy plans to cover accidents and 
strengthen the requirement for train- 
ing of all recombinant DNA research- 
ers in safe laboratory procedures. 
The intent of this section, as before, 
is to integrate safety practice into the 
conduct of recombinant DNA research 
and to assign responsibilities for this 
to the principal investigator, institu- 
tion, IBC, and biological safety officer. 
It is important that these responsibil- 
ities be stated in an unambiguous 
manner. In response to many commen- 
tators. Part IV has been restructured 
to present some of these functions in 
greater detail and clarity. The appen- 
dices contain additional complemen- 
tary information on roles and respon- 
sibilities. including material for IBC’s 
and biological safety officers. 
Expanded Responsibilities. In re- 
sponse to several comments, the 
review of research has been broadened 
in the PRG-NIH to cover all recom- 
binant DNA research at an institution 
receiving NTH funds for this purpose, 
whether or not the specific recombin- 
ant DNA project is funded by NTH. 
While this increases the responsibility 
of the institution and the IBC, it is be- 
lieved that the overall safety of recom- 
binant DNA research will be en- 
hanced. To reflect more closely the 
spirit of the Guidelines, the name "in- 
stitutional biohazards committee” is 
proposed to be changed to "institu- 
tional biosafety committee.” 
Several generic comments deserve to 
be highlighted, as they represent sig- 
nificantly increased authority to be 
delegated to the institution. In 1976 
the RAC did not accept commentators' 
suggestions to require local commit- 
tees to make an independent evalua- 
tion of the containment levels re- 
quired by the Guidelines for individual 
research projects. It was therefore 
stated in the 1976 Decision that NIH 
would not require local institutions to 
have their committees perform this 
function, although they would not be 
prohibited from doing so. Commenta- 
tors have now noted that an IBC, in 
order to to accomplish its mandated 
responsibilities under the 1976 Guide- 
lines, including the review and approv- 
al of recombinant DNA research pro- 
jects, must implicitly determine con- 
tainment conditions. In order to clari- 
fy the committee’s role, the assess- 
ment of appropriate containment 
levels is now made an explicit respon- 
sibility of the IBC. 
In addition, institutions through 
their biosafety committees would be 
given increased responsibility for pri- 
mary overview of this research, as 
they have been delegated the authori- 
ty to approve or disapprove proposed 
recombinant DNA projects. NIH, 
through ORDA, will conduct a review 
of institutions’ actions, upon registra- 
tion of the projects, to ensure compli- 
ance with the NIH Guidelines, thereby 
maintaining a national standard. This 
action has been in response to several 
comments calling for increased local 
responsibility and a simpler adminis- 
FEDERAl REGISTER. VOL 43, NO. 146— FRIDAY, JULY 28, 1978 
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