Federal Register / Vol, 55, No. 249 / Thursday December 27, 1990 / Notices 
53263 
“Appendix K — Footnotes 
"1. This table is derived from the text in 
appendices G and K and is not to be used in 
lieu of appendices G and K. 
"2. 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. 
“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 eukaryotic 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 agents or eukaryotic cells. 
“Disinfection — A process by which viable 
microbiological agents or eukaryotic cells are 
reduced to a level imlikely to produce disease 
in healthy people, plants or animals. 
“Good Large Scale Practice (GLSP) 
Organism — For an organism to qualify for 
GLSP 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 known to acquire them 
naturally if such acquisition could 
compromise the use of a drug to control 
disease agents in human or veterinary 
medicine or agriculture. 
"Inactivation — Any process that destroys 
the ability of a specific microbiological agent 
or eukaryotic 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 or 
eukaryotic cell 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., fermentors, factories, 
filters, thermal oxidizers) designed to achieve 
containment. 
"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.” 
IV. Amendment to Appendix B-I-B-1 of 
the “NIH Guidelines” regarding 
“Salmonella Typhimurium” LT2 
In a letter dated September 25, 1990, 
Dr. Robert A. La Rossa of the E. I. 
DuPont Agricultural Products Research 
Center requested that the 
biocontainment level for Salmonella 
typhimurium LT2 be reduced from 
Biosafety Level 2 to Biosafety Level 1. 
In his letter. Dr. La Rossa states: 
A large body of knowledge suggests 
that Salmonella typhimurium LT2 can 
be handled at Biological Safety Level 1. 
Support of this concept can be found in 
Advanced Bacterial Genetics (Davis, 
Roth and Botstein; Cold Spring Harbor 
Press, 1980) and Experimental 
Techniques in Bacterial Genetics 
(Maloy, Jones and Bartlett, 1990), 
Microbiological Reviews (42:471-519 
(1978)) and Infection and Immunity 
(15:491-499 (1977)). Indeed Jhese studies 
indicate that Salmonella typhimurium 
LT2 is at least 10^ less pathogenic 
towards mice than other Salmonellae. 
The informed consensus of experts in 
the field (see the Microbiological 
Reviews reference) is that this organism 
can be safely handled under conditions 
less stringent than BSL 1 that we are 
proposing. 
V. Report from the Planning 
Subcommittee in Charge of Reviewing 
Comments Received During the 
Regional Hearings Conducted by the 
Recombinant DNA Advisory Committee 
Concerning Future Role of this 
Committee 
The Recombinant DNA Advisory 
Committee conducted seven Regional 
Hearings in 1990. During the October 15- 
16, 1990, meeting, it was decided to 
establish a Planning Subcommittee to 
consider in detail the results of the 
regional hearings. Based on these 
findings, a series of recommendations 
will be made concerning: 
1. Changes in the definition of 
recombinant DNA; 
2. Relinquishing review of 
experiments involving environmental 
release of genetically modified 
organisms; 
3. Review of experiments that involve 
cloning of genes for biosynthesis of 
vertebrate toxins; 
4. Educational role of the 
Recombinant DNA Advisory Committee 
and its Human Gene Therapy 
Subcommittee with regard to human 
gene therapy protocols; and 
5. Other changes in the NIH 
Guidelines. 
The Planning Subcommittee met on 
December 6, 1990,,and formulated the 
following options to the Recombinant 
DNA Advisory Committee for 
consideration at the meeting on 
^binary 4, 1991. 
^The options are as follows: 
1. Consider restructuring the Human 
Gene Therapy Subcommittee as a free- 
standing committee. 
2. Merge the Human Gene Therapy 
Subcommittee with the Recombinant 
DNA Advisory Committee. 
3. Consider regional workshops on 
human gene therapy for the benefit of 
local institutional biosafety committees; 
consider having sessions on human gene 
therapy at various clinical research 
meetings. 
OMB’s “Mandatory Information 
Requirements for Federal Assistance 
Program Announcements" (45 FR 39592, 
June 11, 1980) requires a statement 
concerning the ofHcial government 
programs contained in the Catalog of 
Federal Domestic Assistance. Normally 
HIH 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 
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