49604 . 
NOTICES 
IV. Holes and Responsibilities 
Safety In research Involving recombinant 
DNA molecules depends upon how the re- 
search team applies these guidelines. Moti- 
vation and critical Judgment are necessary, 
In addition to specific safety knowledge, to 
ensure protection of personnel, the public, 
and the environment. 
The Guidelines given here are to help the 
principal investigator determine the nature 
of the safeguards that should be Implement- 
ed. These Guidelines will be Incomplete In 
some respects because all conceivable experi- 
ments with recombinant DNAs cannot be 
anticipated. Therefore, they cannot substi- 
tute for the Investigator’s own knowledge- 
able and discriminating evaluation. When- 
ever this evaluation calls for an Increase In 
containment over that Indicated In the 
Guidelines, the Investigator has a responsi- 
bility to Institute such an Increase. In con- 
trast, the containment conditions called for 
In the Guidelines may not be decreased with- 
out review and approval at the Institutional 
and/or NTH levels. 
The following roles and responsibilities de- 
fine an administrative framework In which 
safety Is an essential and Integrated func- 
tion of research Involving recombinant DNA 
molecules. 
A. Principal investigator. Each principal 
Investigator shall have had adequate train- 
ing In good microbiological techniques. The 
principal Investigator has the primary re- 
sponsibility for: (1) Determining the real 
and potential biohazards of the proposed 
research, (11) determining the appropriate 
level of biological and physical containment, 
(111) selecting the microbiological practices 
and laboratory techniques for handling re- 
combinant DNA materials, (lv) preparing 
procedures for dealing with accidental spills 
and overt personnel contamination, (v) se- 
curing approval of the proposed research 
prior to Initiation of work, (vl) submitting 
Information on purported HV2 and HV3 sys- 
tems to the NTH Recombinant DNA Mole- 
cule Program Advisory Committee and mak- 
ing the strains available to others, ( vll) re- 
porting to the Institutional biohazards com- 
mittee and the NTH Office of Recombinant 
DNA Activities new Information bearing on 
the Guidelines, such as technical Informa- 
tion relating to hazards and new safety pro- 
cedures or Innovations, (vlll) applying to 
the Institutional biohazards committee and/ 
or to the NTH Office of Recombinant DNA 
Activities for approval to lower containment 
levels when a cloned DNA recombinant de- 
rived from a shotgun experiment has been 
rigorously characterized and there Is suffi- 
cient evidence that It Is free of harmful 
genes, and (lx) packaging and distributing 
organisms and viruses containing recom- 
binant DNA In accordance with the speci- 
fications set forth In Section II., C. (Ship- 
ment) . 
Before work Is begun, the principal Inves- 
tigator Is responsible for: (1) Making avail- 
able to program and support staff copies of 
the approved protocols that describe the bio- 
hazards and the precautions to be taken, (11) 
advising the program and support staff of 
the nature and assessment of the real and 
potential biohazards, (111) Instructing and 
training this stafr In the practices and tech- 
niques required to ensure safety, and In the 
procedures for dealing with accidentally cre- 
ated biohazards, and (lv) Informing the stafr 
of the reasons and previsions for any advised 
or requested precautionary medical prac- 
tices, vaccinations, or serum collection. 
During the conduct of the research, 
the principal Investigator Is responsible 
for: (1) Supervising the safety perform- 
ance of the stall to ensure that the re- 
quired safety practices and techniques 
are employed, (11) investigating and re- 
porting In writing to the NIH Office of 
Recombinant DNA Activities, the Institu- 
tional biological safely officer (where 
applicable), and the Institutional bio- 
hazards committee any serious or ex- 
tended illness of a worker or any accident 
that results In <&> Inoculation of recom- 
binant DNA materials through cutaneous 
penetration, (b) Ingestion of recombi- 
nant DNA materials, (c) probably Inha- 
lation of recombinant DNA materials 
following gross aerosollzation, or (d) any 
Incident causing serious exposure to per- 
sonnel or danger of environmental con- 
tamination, (111) Investigating and re- 
porting In writing to the NIH Office of 
Recombinant DNA Activities, the Insti- 
tutional biological safety officer (where 
applicable), and the institutional bio- 
hazards committee any significant prob- 
lems pertaining to operation and imple- 
mentation of biological and physical 
containment safety practices and pro- 
cedures, or equipment or facility failure, 
(lv) correcting work errors and condi- 
tions that may result in the release of 
recombinant DNA materials, and (v) en- 
suring the Integrity of the physical con- 
tainment (e.g., biological safety cabinets) 
and the biological containment (e.g., 
genotypic and phenotypic characteris- 
tics, purity, etc.) . 
B. Institution. Since In almost all cases 
NIH grants are made to Institutions 
rather than to Individuals, all the re- 
sponsibilities of the principal investiga- 
tor listed above are the responsibilities of 
the institution under the grant, fulfilled 
on Its behalf by the principal Investiga- 
tor. In addition, the institution Is re- 
sponsible for establishing an Institutional 
biohazards committee “to: (1) Advise the 
Institution on policies, (11) create and 
maintain a central reference file and 
library of catalogs, books, articles, news- 
letters, and other communications as a 
source of advice and reference regarding, 
for example, the availability and quality 
of the safety equipment, the availability 
and level of biological containment for 
various host-vector systems, suitable 
training of personnel, and data on the 
potential biohazards associated with cer- 
tain recombinant DNAs, and (ill) develop 
a safety and operations manual for any 
P4 facility maintained by the Institution 
and used In support of recombinant DNA 
research. 
Each Institution has the responsibility for 
ensuring that research personnel have been 
adequately trained In, and consistently em- 
ploy, good microbiological technique. The In- 
stitution shall certify to the NIH on applica- 
tions for research support and annually 
thereafter, that facilities, procedures, and 
practices and the training and expertise of 
the personnel Involved have been reviewed 
and approved by the Institutional biohazards 
committee. 
Each Institution shall also determine the 
necessity of various medical procedures for 
research personnel, arrange for these neces- 
sary procedures, and regularly review the re- 
sults. For example, such procedures might In- 
clude pre-employment or pre-assignment his- 
tory and physical examination to detect rele- 
vant medical situations, such as steroid ther- 
apy, Immunosuppression, pregnancy, gastro- 
intestinal disorders, Including achlorhydria, 
or stomach or bowel resection or disorders 
which may require the use of antibiotics or 
large doses of antacids. Individuals receiving 
Antibiotics should not work with prokaryotic 
hos-vector systems during therapy nor for 
seven days thereafter. The obtaining of one 
or more serum samples for analysis or storage 
may also be Indicated, as may specific Im- 
munizations. Periodic examinations subse- 
quently, as well as following any accidental 
exposure, may also be wise, as may be the 
maintenance by the Institution of a registry 
of Individuals Involved In recombinant DNA 
research. 
The biohazards committee must be suffi- 
ciently qualified through the experience and 
expertise of Its membership and the diver- 
sity of Its membership to ensure respect for 
Its advice and counsel. Its membership 
should Include individuals from the Institu- 
tion or consultants, selected so as to provide 
a diversity of disciplines relevant to recom- 
binant DNA technology, biological safety, and 
engineering. Tn addition to possessing the 
professional competence necessary to assess 
and review specific activities and facilities, 
the committee should possess, or have avail- 
able to It. the competence to determine the 
acceptability of Its findings In terms of ap- 
plicable laws, regulations, standards of prac- 
tice, community attitudes, and health and 
environmental considerations. The commit- 
tee shoud, therefore, Include persons whose 
concerns are In these areas. 
Minutes of the meetings should be kept 
and made available for public Inspection. 
The Institution Is responsible for reporting 
names of and relevant background Informa- 
tion on the members of Its biohazards com- 
mittee to the NIH. 
In addition, each Institution In which re- 
combinant DNA research at a P3 or P4 con- 
tainment level Is being conducted shall des- 
ignate a biological safety officer. The safety 
officer, who may be a member of the Insti- 
tutional biohazards committee, shall be an- 
swerable to the responsible officer of the 
Institution, and shall work In close cooper- 
ation with the Institutional biohazards com- 
mittee. The officer's duties shall Include, but 
not be limited to, the following: (1) Verify- 
ing that all research personnel have been 
adequately trained In good microbiological 
techniques; (11) ensuring through periodic 
Inspections that laboratory safety standards 
are rigorously followed; (111) Investigating 
all laboratory accidents: (lv) reviewing the 
results of histories, physical examinations, 
and monitoring of laboratory personnel: and 
(v) providing advice on laboratory security. 
C NIH initial review groups < study sec- 
tions) — The NIH study sections, In addition 
to reviewing the scientific merit of each 
grant application Involving recombinant 
DNA molecules, are responsible for ; (1) Mak- 
ing an Independent evaluation of the con- 
tainment levels required for the proposed 
research by these Guidelines. (11) determin- 
ing whether the proposed physical contain- 
ment safeguards certified by the Institu- 
tional biohazards committee are adequate, 
(111) determining whether the proposed bio- 
logical containment safeguards are ade- 
quate. (lv) referring to the NIH Recombi- 
nant DNA Molecule Program Advisory Com- 
mittee or the NIH Office of Recombinant 
DNA Activities those problems pertaining to 
assessment of biohazards or safeguards de- 
termination that cannot be resolved by the 
study sections. 
The membership of the study sections will 
be selected In the usual manner Biological 
safety expertise, however, will be available 
to the study sections for consultation and 
guidance. 
D. N1R Recombinant DNA Molecule Pro- 
gram Advisory Committee — The Recombl- 
FEOERAl REGISTER, VOL 42, NO. 187— TUESOAY, SEPTEMBER 27, 1977 
[ 172 ] 
