Federal Register / Vol. 59, No. 127 / Tuesday, July 5, 1994 / Notices 
34523 
I 
Department of Justice, Department of 
State, Department of Veterans Affairs, 
Agency for International Development, 
Environmental Protection Agency, 
National Aeronautics and Space 
Administration, and National Science 
Foundation. The Biotechnology 
Research Subcommittee will function in 
an advisor)' capacity to the Committee 
on Fundamental Science, the Director of 
the Office of Science and Technology 
Policy, and the Executive Office of the 
President. The Biotechnology Research 
Subcommittee will review the scientific 
aspects of proposed regulations and 
guidelines as they are developed. 
The primary responsibilities of the 
Biotec^ology Research Subcommittee 
are to: (i) Describe and review current 
Federal efforts in biotechnology 
research; (ii) identify and define the 
priority areas for future Federal 
biotechnology research, including areas 
needing greater emphasis, describing 
the role of each agency in those areas, 
and delineate where interagency 
cooperation would enhance progress in 
the biotechnology sciences, with an 
emphasis on integrated research efforts, 
where appropriate: (iii) assess major 
international efforts in the 
biotechnology sciences and develop 
mechanisms for international 
collaboration. For example, activities of 
the U.S. -European Community Task 
Force on Biotechnology have been 
coordinated through the Biotechnology 
Research Subcommittee; (iv) identify 
and review national and international 
policy issues (such as public education) 
associated with biotechnology; and (v) 
provide reviews, analyses, and 
recommendations to the Chairs of the 
Committee on Fundamental Science on 
scientific issues related to regulations 
and the applications of biotechnology 
research and biotechnology policies and 
issues. 
In 1990, the Biotechnology Research 
Subcommittee replaced the 
Biotechnology Sciences Coordinating 
Committee. Both the Biotechnology 
Research Subcommittee and the 
Biotechnology Sciences Coordinating 
Committee previously functioned under 
the Federal Coordinating Council on 
Science, Engineering, and Technology 
(FCCSET). While regulatory issues 
became the primary focus of the 
Biotechnology Sciences Coordinating 
Committee, the Biotechnology Research 
Subcommittee focuses on scientific 
issues, although it will still provide 
scientific support for regulatory 
responsibilities. 
Appendix K. Physical Containment for 
Large Scale Uses of Oiganisms 
Containing Recombinant DNA 
Molecules 
Appendix K specifies physical 
containment guidelines for large scale 
(greater than 10 liters of culture) 
research or production involving viable 
organisms containing recombinant DNA 
molecules. It shall apply to large scale 
research or production activities as 
specified in Section IIl-C-6. It is 
important to note that this appendix 
addresses 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, emd chemical aspects of 
downstream processing) are not 
addressed and shall be considered 
separately, albeit in conjunction with 
this appendix. 
All provisions shall apply to large 
scale research or production activities 
with the following modifications: (i) 
Appendix K shall supersede Appendix 
G when quantities in excess of 10 liters 
of culture are involved in research or 
production. Appendix K-Il applies to 
Good Large Scale Practice; (ii) the 
institution shall appoint a Biological 
Safety Officer if it engages in large scale 
research or production activities 
involving viable organisms containing 
recombinant DNA molecules. The 
duties of the Biological Safety Officer 
shall include those specified in Section 
rV-B-3; (iii) the institution shall 
establish and maintain a health 
surveillance program for personnel 
engaged in large scale research or 
production activities involving viable 
organisms containing recombinant DNA 
molecules which require Biosafety Level 
(BL) 3 containment at the laboratory 
scale. The program shall include: 
preassignment and periodic physical 
and medical examinations; collection, 
maintenance, and analysis of serum 
specimens for monitoring serologic 
changes that may result from the 
employee's work experience: and 
provisions for the investigation of any 
serious, unusual, or extended illnesses 
of employees to determine possible 
occupational origin. 
Appendix K-I. Selection of Physical 
Containment Levels 
The selection of the physical 
containment level required for 
recombinant DNA research or 
production involving more than 10 
liters of culture is based on the 
containment guidelines established in 
Section III. For purposes of large scale 
research or production, four physical 
containment levels are established. The 
four levels set containment conditions 
at those appropriate for the degree of 
hazard to health or the environment 
posed by the organism, judged by 
experience with similar organisms 
unmodified by recombinant DNA 
techniques and consistent with Good 
Large Scale Practice. The four biosafety 
levels of large scale physical 
containment are referred to as Good 
Large Scale Practice, BLl-Large Scale, 
BL2-Large Scale, and BL3-Large Scale. 
Good Large Scale Practice is 
recommended for large scale research or 
production involving viable, non- 
pathogenic, and non-toxigenic 
recombinant strains derived from host 
organisms that have an extended history 
of safe large scale use. Good Large Scale 
Practice is recommended for organisms 
such as those included in Appendix C 
which have built-in environmental 
limitations that permit optimum growth 
in the large scale setting but limited 
survival without adverse consequences 
in the environment. BLl-Large Scale is 
recommended for large scale research or 
production of viable organisms 
containing recombinant DNA molecules 
that require BLl containment at the 
laboratory scale and that do not qualify 
for Good Large Scale Practice. BL2- 
Large Scale is recommended for large 
scale research or production of viable 
organisms containing recombinant DNA 
molecules that require BL2 containment 
at the laboratory scale. BL3-Large Scale 
is recommended for large scale research 
or production of viable organisms 
containing recombinant DNA molecules 
that require BL3 containment at the 
laboratory scale. No provisions are made 
for large scale research or production of 
viable organisms containing 
recombinant DNA molecules that 
require BL4 containment at the 
laboratory scale. If necessary, these 
requirements will be established by NIH 
on an individual basis. 
Appendix K-ll. Good Large Scale 
Practice (GLSP) 
Appendix K-II-A. Institutional codes 
of practice shall be formulated and 
implemented to assure adequate control 
of health and safety matters. 
Appendix K-Il-B. Written 
instructions and training of personnel 
shall be provided to assure that cultures 
of viable organisms containing 
recombinant DNA molecules are 
handled prudently and that the 
workplace is kept clean and orderly. 
Appendix K-tl-C. In the interest of 
good personal hygiene, facilities (e.g., 
hand washing sink, shower, changing 
room) and protective clothing (e.g.. 
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Recombinant DNA Research, Volume 19 
