37850^ Federal RegisU VoL 55, No>^8, / ..Thursday, Septemb 
"Appendix K^— Footnotes 
“1. The criteria in this grid address only the 
biological hazard associated with organisms 
containing recombinant DNA. Other hazards - 
accompanying the large scale cultivation of 
such organisms (e.g., toxic properties of 
products; physical, mechanical and chemical 
aspects of downstream processing) are not 
addressed and must be considered 
separately, albeit in conjunction with this 
grid. 
“2. Good Industrial Large Scale Practice as 
recommended by the Bioprocessing 
Committee of the Industrial Bioter^oiogy 
Association and Pharmaceutical 
Manufacturers Association. 
“3. While not required, standard industry 
practice recommends restricted access at 
BL2-LS and higher. 
"4. Contingency measures for containing 
significant spillage from systems is 
recommended. 
“5. While not required, standard industry 
practice recommends that exhaust air from 
BL3-LS facilities be HEPA-filtered, subjected 
to thermal oxidation, or otherwise treated to 
prevent release of viable organisms. 
"Appendix K — Definitions to 
Accompany Containment Grid and 
Proposed Modification of Appendix K 
“Accidental release— ^The 
unintentional discharge of a 
microbiological agent (i.e., 
microorganism or virus) or eukaryotic 
cell due to a failure in the containment 
system. 
“Biological barrier — An impediment 
(naturally occurring or introduced) to 
the infectivity and/or survival of a 
microbiological agent or eukaryotic cell 
once it has been released into the 
environment, 
“Closed system — A system, which by 
its design and proper operation, 
prevents release of a microbiological 
agent or eukarj'otic cell contained 
therein. 
“Containment — ^The confinement of a 
microbiological agent or eukaryotic cell 
that is being cultured, stored, 
manipulated, transported or destroyed 
in order to prevent or limit its contact 
with people and/or the environment. 
Methods used to achieve this include: 
physical and biological barriers and 
inactivation using physical or chemical 
means. 
"de minimis release — A release of 
viable microbiological agents or 
eukaryotic cells that does not result in 
the establishment of disease in healthy 
people, plants or animals or in 
uncontrolled proliferation of any 
microbiological agent. 
“Disinfection — A process by which 
viable microbiological agents are 
reduced to a level unlikely to produce 
disease in healthy people, plants or 
animals. 
“Good Industrial Large Scale Practice 
(GILSP) Organism — For an organism to 
qualify for GILSP consideration, it must 
meet the following criteria: [Reference: 
Organization for Economic Cooperation 
and Development,” Recombinant DNA 
Safety Considerations", 1987, p. 34-35] 
“a. The host organism should be non- 
pathogenic, should not contain 
adventitious agents and should have an 
extended history of safe industrial use 
or have built-in environmental 
limitations that permit optimum growth 
in the industrial setting but limited 
survival without adverse consequences 
in the environment. 
“b. The recombinant DNA-engineered 
organism should be non-pathogenic, 
should be as safe in the industrial 
setting as the host organism, and 
without adverse consequences in the 
environment. 
*‘c. The vector/insert should be well 
characterized and free from known 
harmful sequences: should be limited in 
size as much as possible to the DNA 
required to perform the intended 
function; should not increase the 
stability of the construct in the 
environment unless that is a 
requirement of the intended function; 
should be poorly mobilizable; and 
should not transfer any resistance 
markers to microorganisms not know'n 
to acquire them naturally if such 
acquisition could compromise the use of 
a dinig to control disease agents in 
human or veterinary medicine or 
agriculture. 
“Inactivation — Any process that 
reduces the ability of a specific 
microbiological agent or eukarj'otic cell 
to self-replicate. 
“Incidental release — ^The discharge of 
a microbiological agent or eukaryotic 
cell from a containment system that is 
expected when the system is 
appropriately designed and properly 
operated and maintained. 
“Minimization — The design and 
operation of containment systems in 
order that any incidental release is a de 
minimis release. 
“Pathogen — Any microbiological 
agent containing sufficient genetic 
information, which upon expression of 
such information is capable of producing 
disease in healthy people, plants or 
animals. 
"Physical barrier — Equipment, 
facilities and devices (e.g., fermenters, 
factories, filters, thermal oxidizers) 
designed to achieve containment. 
iS, 1990 / ‘Notices- 
“Release — The discharge of a 
microbiological agent or eukaryotic cell 
from a containment system. Discharges 
can be incidental or accidental. 
Incidental releases are de minimis in 
nature; accidental releases may be de 
minimis in nature.” 
II. Preliminary Review of the Regional 
Hearings Conducted by the 
Recombinant DNA Advisory Committee 
Since the seven regional hearings 
conclude on October 15, 1990, the 
Recombinant DNA Advisory Committee 
will have its first opportunity to review 
the public response tC questions poSed 
about the future role of this committee. 
Topics to be considered will include: A 
proposed new definition of recombinant 
DNA; possible reduction of central 
review of experiments with increasing 
responsibilities for the local Institutional 
Biosafety Committees; and orientation 
materials for review of human gene 
therapy experiments. 
OMB’s “Mandatory Information 
Requirements for Federal Assistance 
Program Armounceraents” (45 FR 39592, 
June 11, 1980) requires a statement 
concerning the official Government 
programs contained in the “Catalog of 
Federal Domestic Assistance.” Normally 
NIH lists in its announcements the 
number and title of affected individual 
programs for the guidance of the public. 
Because the guidance in this notice 
covers not only virtually every NIH 
program but also essentially every 
Federal research program in which DNA 
recombinant molecule techniques could 
be used,, it has been determined not to 
be cost effective or in the public interest 
to attempt to list these programs. Such a 
list would likely require several 
additional pages. In addition, NIH could 
not be certain that every Federal 
program would be included as many 
Federal agencies, as well as private 
organizations, both national and 
international, have elected to follow the 
“NIH Guidelines,” In lieu of the 
individual program listing, NIH invites 
readers to direct questions to the 
information address above about 
whether individual programs listed in 
the “Catalog of Federal Domestic 
Assistance” are affected. 
Dated: September 10. 1990. 
)ay Moskowitz, 
Associate Director for Science Policy and 
Legislation. 
(FR Doc. 90-21709 Filed 9-12-90; 8;45 amj 
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