33054 
NOTICES 
cordingly. a special committee of 
safety and health experts was con- 
vened by W. Emmett Barkley. Ph. D.. 
Director of the Office of Research 
Safety. National Cancer Institute, to 
review and revise this supplementary 
Information. Several sections have 
been extensively rewritten, and new 
sections have been added on evalua- 
tion methods for P3 facilities, certifi- 
cation procedures for P4 facilities, cer- 
tification of biological safety cabinets, 
emergency control procedures, medical 
surveillance programs, and other 
topics. This document is separately 
available as Laboratory Safety Mono- 
graph— A Supplement to the NIH 
Guidelines for Recombinant DNA Re- 
search. ’’ 
Other comments. A number of addi- 
tional comments have been received 
from public commentators relating to 
proposed actions at specific levels of 
physical containment. 
It has been suggested that certain 
requirements at the PI level remain 
"permissive’’ rather than be changed 
to "mandatory ", l.e., that the language 
In the PRG-NIH read "should" rather 
than "shall.” NIH considers this incon- 
sistent with live stated principle of 
specifying requirements, and has 
therefore mandated adherence to 
these good microbiological practices. 
The EMBO Standing Advisory Com- 
mittee on Recombinant DNA Re- 
search has recommended that simple 
air exhaust cabinets be used at the PI 
level when there is likelihood of pro- 
ducing large amounts of aerosols. In 
the view of NIH such cabinets are un- 
necessary. as the agents used at tills 
level would not create aerosols hazard- 
ous to laboratory workera 
A recommendation has been received 
from the EMBO Standing Advisory 
Committee on Recombinant DNA Re- 
search to reclassify P2 With a class III 
cabinet as equivalent to P3 specifica- 
tions. While this option was permitted 
in the 1976 guidelines. It is no longer 
considered practical. The cost of fabri- 
cating and installing class III cabinets 
would far exceed the cost of installing 
a new exhaust-air system for the labo- 
ratory. It is considered more cosi-ef- 
fective and desirable to convert P 2 lao- 
oratories into P3 laboratories. The 
elimination of the 1976 option should 
be viewed as an encouragement to up- 
grade laboratories. 
It has been observed that many class 
II safety cabinets do not meet accept- 
ed standards. A recommendation has 
been made that the local IBC be au- 
thorized to certify these cabinets, and 
that such a requirement be included in 
the guidelines. It should be noted that 
the guidelines already authorize IBC's 
to certify safety practices and proce- 
dures; however, to respond more di- 
rectly to the above suggestion, a spe- 
cial section on certification of biologi- 
cal safety cabinets has been included 
in the supplement to the PRG-NLH 
entitled "Laboratory Safety Mono- 
graph.” 
The EMBO Standing Advisory Com- 
mittee on Recombinant DNA Re- 
search observes that in the case of a 
P3 facility, the proposed revisions do 
not speak to precautions against the 
contamination of the main water sup- 
plies by laboratory water systems. It is 
noted that building codes and labora- 
tory design standards require that pre- 
cautionary measures be taken to sepa- 
rate potable water systems from labo- 
ratory process water. Additional pre- 
cautions have been required at the P4 
level. Standard design practice is felt 
to be appropriate at the P3 level. 
Some commentators have pointed 
out that the PRG-RAC did not re- 
quire an autoclave in the P3 labora- 
tory itself, but only within the build- 
ing. The 1976 guidelines require that 
for P3 laboratories an autoclave be 
available ‘‘within the building and 
preferably within the controlled labo- 
ratory area." Some believe an auto- 
clave In the P3 laboratory should be 
required. One commentator felt that 
the autoclave should be "as close as 
possible" to the controlled area of the 
P3 laboratory, not merely available In 
the same building. He pointed out that 
from an operational point of view, the 
closer the autoclave can be to the solid 
waste, the better. This is especially 
true In the larger medical research 
complexes, where transport of wastes 
from the laboratory to the autoclave 
might Involve passage ‘‘via some 
rather sensitive patient areas of the 
institution." He prefers that the auto- 
clave be located either In the con- 
trolled area or as close to It as possi- 
ble. with such explicit language in the 
guidelines. The language in the 1976 
guidelines stating that in a P3 labora- 
tory “an autoclave shall be available 
within the building and preferably 
within the controlled laboratory area” 
has been reinserted in the PRG-NIH. 
However, an absolute requirement 
that the autoclave must be within the 
controlled area Is not considered ap- 
propriate. since contaminated materi- 
als can be safely transported. Such a 
requirement would exclude the use of 
autoclaves In waste staging areas that 
have been conveniently sited to sup- 
port an entire facility. 
The PRG-RAC states that P4 work 
can be done in either (l)a class III 
cabinet system or <2) a class I or class 
II cabinet system In a special area 
where all personnel wear one-piece, 
positive pressure suits. Some Investiga- 
tors apparently prefer use of pressure 
suits over work in the class III cabi- 
nets. NIH believes that the suits are 
especially useful in working with ex- 
perimental animals in a P4 facility or 
with large amounts of material. At 
present, however, most recombinant 
DNA studies are handled more practi- 
cally in a class III without need for a 
suit. 
In 1976. several commentators advo- 
cated that NIH arrange for sharing of 
P4 facilities, both by investigators 
from the NIH intramural program and 
from institutions supported through 
NIH awards. In response to these sug- 
gestions and those of recent commen- 
tators. we have arranged to make our 
recently established P4 facilities at the 
Frederick Cancer Research Center 
(Fort Dc trick) available to outside sci- 
entists. 
Shipment. Some commentators have 
urged that stricter controls be re- 
quired on shipping recombinant DNA 
molecules in or out of the country. It 
has been recommended, for example, 
that shipping procedures differentiate 
between types of substances being 
transported. We wish to emphasize 
that requirements for shipping organ- 
isms that con'aln recombinant DNA 
molecules are consistent with relevant 
Public Health Service. Department of 
Transportation, and Civil Aeronautics 
Board regulations, and are also in 
compliance with the World Health Or- 
ganization recommendations on the 
International shipment of biologic 
agents. It should be noted that organ- 
isms containing recombinant DNA 
molecules all require the same con- 
tainment conditions as for the most 
hazardous known agents. 
The EMBO Standing Advisory Com- 
mittee on Recombinant DNA Re- 
search recommends that before a ship- 
ment Is made, the recipients of organ- 
isms containing recombinant DNA 
molecules should affirm to the donors 
that they are following the safety 
standards and practices of their coun- 
try. NIH considers this a sound recom- 
mendation and reauires the following 
(as stated in the NIH Guide for grants 
and contracts); 
All memoranda of understanding and 
agreement (MUA’a) submitted with compet- 
ing and noncorr.peting applications involv- 
ing recombinant DNA research must indi 
cate that the principal investigator (pro- 
gram director, fellow, or candidate) agrees 
to comply with the NIH Guidelines and 
other specific NIH instructions pertaining 
to the proposed project. Included in the pro- 
visions are tne following pertaining to ship- 
ment or transfer or recombinant DNA mate- 
rials: 
A. Prior to shipment or transfer of recom- 
binant DNA materials to other Federally 
funded investigators within the United 
States, the sending laboratory shall obtain a 
letter from the requesting laboratory stat- 
ing that: 
1. Research involving recombinant DNA 
molecules shall be conducted in compliance 
with the NIH Guidelines and other NIH 
Instructions, and that the requesting labora- 
tory shall not transfer the recombinant 
DNA materials to other laboratories; 
2. The requesting laboratory has been re- 
viewed by its Institutional Biosafety Com- 
FEDERAl REGISTER. VOL 43. NO. 1*6— ERIDAT, JULY 28, 1978 
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