33052 
NOTICES 
• General Applicability 
• Prohibitions 
• Exemptions 
• General Definitions 
It should be noted that the Prohibi- 
tions appear before the Exemptions. 
This will again emphasize the fact 
that the latter provisions cannot be 
used to claim relief from the former. 
II. Containment 
The object of these revised guide- 
lines is to Insure that experimental 
DNA recombination will have no ill ef- 
fects on the researchers, on the gener- 
al public, or on the environment. The 
essence of their construction, as in the 
case of the 1976 Guidelines, is subdivi- 
sion of potential experiments by class, 
and assignment to these of certain 
procedures for containment. 
Containment is both physical and 
biological. Physical containment in- 
volves the isolation of the research by 
procedures that have evolved over 
many years of experience in laborato- 
ries studying infectious micro-organ- 
isms. PI containment— the first physi- 
cal containment level— is that used In 
most routine bacteriology laboratories. 
P2 and P3 afford increasing isolation 
of the research from the environment. 
P4 represents the most extreme meas- 
ures used for containing virulent path- 
ogens. and permits no escape of con- 
taminated air. wastes, or untreated 
materials. Biological containment is 
the use of biological agents that are 
crippled by mutation so as to be in- 
capable of surviving under natural 
conditions. 
PHYSICAL CONTAINMENT 
Review of RAC- Proposed Guidelines 
Two major changes were proposed in 
the physical containment section of 
the PRO-RAC. One deals with the or- 
ganization of the section: the other in- 
corporates into the PRG-RAC the 
philosophy and guidance of the report 
of the NIH European Molecular Biol- 
ogy Organization (EMBO) Workshop 
on parameters of physical contain- 
ment.* 
Physical containment requirements 
for each P level have been organized 
under the topic headings Laboratory 
Practices, Containment Equipment, 
and Special Laboratory Design. This 
was done to emphasize the importance 
of laboratory practices and contain- 
ment equipment in achieving the de- 
sired safety objective. 
Other revisions contained in the 
"Physical Containment" section re- 
•The Report of the NIH/EMBO Work- 
shop (Parameters of Physical Contain- 
ment)" may be obtained from the Office of 
Research Safety. National Cancer Institute. 
Room 3E47, Building 13. National Institutes 
of Health. 9000 Rockville Pike, Bethesda, 
Md 20014. 
fleet a conscious effort to encourage 
international uniformity with respect 
to recombinant DNA guidelines. This 
has been achieved by revising the con- 
tainment descriptions so that they are 
consistent with the guidance provided 
in the NIH/EMBO report. In addition, 
some statements have been rewritten 
and others added in order to clarify 
the basic requirements for each level 
of containment. The most significant 
clarifications were made in the areas 
on containment equipment and special 
facility design. The revisions, however, 
have not resulted in changing the pur- 
pose or Intent of the physical contain- 
ment descriptions in the 1976 Guide- 
lines. 
Two specific additions to the Guide- 
lines that originated from the NIH/ 
EMBO report are particularly notable. 
The first is that Tables I and II have 
been added to the P3 and P4 sections, 
respectively. These tables show combi- 
nations of safeguards that provide 
similar protection. The combinations 
are dependent on the level of biologi- 
cal containment. This approach allows 
flexibility in selecting containment 
equipment for a particular study with- 
out compromising safety. 
The second specific addition is the 
inclusion of laboratory design criteria 
for an area in which personnel wear 
positive-pressure suits ventilated by 
life-support systems. This added ap- 
proach provides a level of physical 
containment equivalent to that afford- 
ed by the glove-box cabinet require- 
ment at the P4 level. 
Other important changes are sum- 
marized below: 
• Certain specific microbiological 
practices are mandated at the PI level 
in the PRG-RAC (whereas in the 1976 
Guidelines they were merely encour- 
aged); 
• At the P2 level, prohibitions 
against eating, drinking, smoking, and 
storage of foods have been extended 
from the work area to the entire labo- 
ratory; 
• The universal biohazard sign is 
now required at the P2 level. Use of 
these signs has been extended to 
equipment such as freezers and refrig- 
erators in which organisms containing 
recombinant DNA molecules are 
stored; 
• Access procedures in controlled 
areas adjacent to P3 laboratories have 
been specified; 
• Installation of foot-, elbow-, or 
automatically-operated facilities for 
washing hands is now required in PS- 
level laboratories; 
• Specific guidance on containment 
equipment appropriate for laboratory 
animals has been added to the P3 and 
P4 sections: 
• The labeling requirements for 
shipment of etiologic agents now 
apply to all organisms containing re- 
combinant DNA molecules. Thus, the 
Center for Disease Control, U.S. 
Public Health Service, must be noti- 
fied in the event of any accidental 
breakage during shipment. Also, 
agents requiring P4 containment must 
be packaged according to strict Feder- 
al standards and be shipped by regis- 
tered mail or an equivalent system 
that provides for notifying the shipper 
upon delivery. 
I have carefully reviewed the recom- 
mendations of the PRG-RAC relating 
to physical containment and propose 
to adopt them with certain modifica- 
tions. The modifications, based on 
issues raised by the Director's Adviso- 
ry Committee and public commenta- 
tors. are discussed below. 
Review of comments and NIH-pro- 
posed guidelines 
As reported in the "Decision Docu- 
ment" which accompanied the release 
of the 1976 guidelines, comments on 
the containment provisions of the 
original Guidelines were directed to 
the definitions of both physical and 
biological containment and to the 
safety and effectiveness of the pre- 
scribed levels. Several commentators 
at that time found the concept of 
physical containment imprecise and 
subject to human error. Others ques- 
tioned the concept of biological con- 
tainment in terms of its safety and 
purported effectiveness in averting po- 
tential hazards. The commentators 
were divided on which method of con- 
tainment would provide the most ef- 
fective and safe system. 
Several suggested that each of the 
physical levels be explained more 
fully. The physical containment sec- 
tion of the 1976 guidelines— and now 
of the PRG-NIH— is directly respon- 
sive to many of these commentators. 
In addition, the PRG-NIH takes into 
account the more recent comments re- 
lated to standards for physical and 
biological containment. Commentators 
on the PRG-RAC have expressed par- 
ticular concern over (1) the flexibility 
which allows various combinations of 
containment safeguards, (2) the design 
of containment systems, and (3) the 
adequacy of training in laboratory 
safety practices. The Standing Adviso- 
ry Committee on Recombirant DNA 
Research of the European Molecular 
Biology Organization (EMBO) made a 
number of recommendations that NIH 
has considered, and public commenta- 
tors have proffered additional sugges- 
tions relating to specific levels of phys- 
ical containment and to shipment of 
recombinant DNA materials. These 
are examined below. 
Concept of "Flexibility. ” Some com- 
mentators have expressed concern 
over the flexibility provided in Tables 
I and II that allows various combina- 
tions of containment safeguards. For 
FEDERAL REGISTER. VOL 43, NO. 144 — FRIDAY, JULY 28, 1978 
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