33174 
Federal Register / Vol. 56. No. 138 / Thursday. July 18, 1991 / Notices 
DEPARTMENT OF HEALTH AND 
HUMAN SERVICES 
National Institutes of Health 
Recombinant DNA Research: Actions 
Under the Guidelines 
agency: National Institutes of Health. 
PHS. DHHS. 
action: Notice of Actions Under the 
NIH Guidelines for Research Involving 
Recombinant DNA Molecules. 
suMr;iARY: This nodce sets forth seven 
actions to be taken by the Director. 
NadonaJ Institutes of Health (NIH). 
under the May 7, 1988, NIH GuideUnes 
for Research Involving Recombinant 
DNA Molecules (51 FR 16958). 
EFFECTIVE DATE: July 18, 1991. 
FOR FURTHER INFORMATION CONTACT: 
Additional information can be obtained 
from Dr. Nelson A. WiveL Director, 
Office of Recombinant DNA Activities, 
Office of Science Policy and Legislation, 
National Institutes of Health, Building 
31, room 4B11. Bethesda, Maryland 
20892 (301) 496-983a 
SUPPUEMENTARY INFORMATION: Today 
seven actions on being promulgated 
under the NIH Guidelines for Research 
Involving Recombinant DNA Molecules. 
These seven actions were published for 
comment in the Federal Register of 
September 13. 1990 (55 FR 37846). 
December 27. 1990 (55 FR 53258). and 
April 29. 1991 (56 FR 19776). and 
reviewed and recommended for 
approval by the NIH Recombinant D.NA 
Advisory Committee (RAC) at its 
meetings on October 16. 1990. February 
4. 1990. and May 30-31. 1991 
L Background infonnation and 
Decisions on Actions Under the “NIH 
Guidelines" 
A. Revision of Appendix K of the ’"NIH 
Guidelines” Regarding Establishment of 
Guidelines for Level of Containment 
Appropriate to Good Industrial Large 
Scale Practices (GILSP) 
Revision of appendix K of the NIH 
Guidelines Regarding Establishment of 
Guidelines for Level of Cor.tairunent 
Appropriate to Good Industrial Large 
Scale Practices (GILSP). In a letter dated 
June 28, 1990, the Industrial 
Biotechnology Association (IBA) and the 
Pharmaceutical Manufacturers 
Association (PMA) requested that the 
Recombinant DNA Advisory Committee 
revise appendix K of the NIH Guidelines 
to reflect a formalization of suitable 
containment practices and facilities for 
the conduct of large-scale experiments 
involving recombinant DNA-derived 
industrial microorganisms. This request 
included proposed definitions and 
requirementa pertaining to the requested 
changes. 
This request was published for 
comment in the Federal Register on 
September 13. 1990 (55 FR 37848). 
During the RAC meeting on October 
16. 1990, the members considered the 
recommendations made by the Revision 
of the NIH Guidelines Subcommittee. 
Following a discussion, it was dedded 
that further modifications of appendix K 
were necessary. Accordingly, the matter 
was referred back to the subcommittee. 
The Revision of the NIH Guidelines 
Subcommittee met on December 7. 1990, 
and developed recommendations to the- 
Recombinant DNA Advisory Committee 
for their meeting on February 4, 1991. 
This request was published in die 
Federal Register for comment on 
December 27, 1990 (55 FR 53258), 
At the meeting of February 4, 1991. the 
Recombinant DNA Advisory Committee 
considered the recommendations of the 
Revision of the NIH Guidelines 
Subcommittee. The RAC, by a vote of 15 
in favor, none opposed, and one 
abstention, approved a revision of 
appendix K wUch reads as follows. 
Appendix K. Physical Containment for Large* 
S^e Uses of Organisms Containing 
Recombinant DNA Molecules 
This part of the Guidelines 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 OI-B-S of the Guidelines. 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 and chemical 
aspects of downstream processing] are not 
addressed and muat be considered 
separately, albeit in conjunction with this 
appendix. 
All provisions of the Guidelines shall apply 
to large-scale research or production with the 
following modifications: 
• Appendix K shall replace portions of ‘ 
Appendix G when quantities in excess of 10 
liters of culture ere involved in research or 
production. Appendix K-II applies to GLSP; 
appendices G^ and G-fi. as indicated in 
accompanying table, apply to Biosafety 
Levels (BL) BLl-LS. BL2-LS, and BL3-LS. 
• The institution shall appoint a Biological 
Safety Officer (BSO) if it engages in large- 
scale research or production activities 
involving viable organisms containing 
recombinant DNA molecules. The duties of 
the BSO shall include those specified in 
section IV-B-4 of the Guidelines. 
• 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 BL3 containment at 
the laboratory scale. The program shall 
include: Preassignment and periodic physical 
and medical examinations; collectioa 
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 
colture is based on the containment 
guidelines established in part m of the 
Gnldelines. 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 
«nd consistent with good large scale 
practices. These are referred to as GLSP. 
BU-LS, BL2^ and BL3-LS. The GLSP 
(Good Large-Scale Practice] level of physical 
containment 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. 
Likewise, the GLSP level of physical 
containment is recommended for organisms 
sudi as those included in Appendix C that 
have built-in environmental limitations that 
permit optimum growth in the large scale 
setting but limit^ survival without adverse 
consequences in the environmenL For those 
organisms that do not qualify for GLSP. the 
BLl-LS (Biosafety Level 1 — Large-Scale) level 
of physical containment is recommended for 
large-scale research or production of viable 
organisms containing recombinant DNA 
molecules that require BLl containment at 
the laboratory scale. The BL2-LS (Biosafety 
Level 2 — Large Scale) level of physical 
containment is required for large-scale 
research or production of viable organisms 
containing recombinant DNA molecules that 
require BL2 contaiiunent at the laboratory 
scale, the BL3-LS (Biosafety Level 3— Large 
Scale) level of physical contaiiunent is 
required for large-scale research or 
production of viable organisms contaming 
recombinant DNA molecules that require BL3 
contaiiunent 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-IL GLSP Level 
Appendix K-O-A Institutional codes of 
practice shall be formulated and 
implemented to assure adequate control of 
health and safety matters. 
Recombinant DNA Research, Volume 14 
[867] 
