Federal Register / Vo!. 55. No. 249 / Thursdaj' December 27, 1990 / Notices 53259 
Leu.kemia (AML) in First Complete 
Remission: Use of Marker Genes to 
investigate the Biology of Marrow 
Reconstitution and the Mechanism oi 
Relapse.” 
The protocol was reviewed by the 
t iyman Gene Therapy Subcommittee 
curing its November 30, 1990, meeting. 
The subcommittee recommended 
provisional approval pending receipt of 
the following additional information. 
The consent form should include 
statements about patipnt confidentiality. 
There should be additional information 
in Lhe consent form about long-term 
patient reevaluaiion. There should be 
more specific detail about the 
transduction protocol and more detail 
about the molecular identification of 
biasi colonies. assent form should be 
developed i'or use with patients over the 
ace <5r 
Tha ttauain Gens Therapy 
Subconmutire focwa.''ded the protocol to 
the Recombinant Advisory 
CoirUTJttee for consideration during its 
February 4. meeting. 
III. Reiision of .Appendix K of the “NIH 
Guidelines'' Regarding Establishment of 
Guidelines for Love! of Containment 
Appropriate to Good Industrial Large 
Seals Practices (GILSP) 
Revision of appendix K of the NIH 
oevys/Znes Regarding Establishment of 
Guidelines for Level of Containment 
Appropriate to Good Industrial Large 
Scale Practices (GILSP). In a letter dated 
June 28, 1990, the Industrial 
Biotechnology Association (IBAJ and the 
PhaiTOaceutical 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. In 
attachments to this request, there are 
proposed definitions and requirements 
pertaintng to the requested changes. 
Duiing the RAC meeting omGetoberlfif 
1990, they considered the 
reconmiendations made.hy the Revision 
of the NIH Guidelines Subcommittee. : 
Following a discussion, it Was dedded . 
that fiiitlrer nmdificatibns of appendix K 
were necessary. Accordingly, the matter 
was refeited back to the subcomnuttee. 
The Revision qf the Guidelines ; 
Subconunittee met on December 7, 199Q. 
, with the fptlowdng recommendations to 
the Recombinant DNA Advisory 
GonunUtee for their meeting on February 
.4..1994.- ■ ^ ; 
> Proposed revision of appendix K 
reads as follows: 
“Appendix K — Physical Containment for 
Large-Scale Uses of Organisms 
Containing Recombinant D.NA 
Moiacules 
“This par! of the Guidelines specifies 
physic.=il containment guidelines for 
large — scale (greater than 10 liters of 
culture) research or production invobdug 
viable organisms containing 
recombinant DNA molecules. It shall . 
apply to large-scale research or 
production activities as specified in 
section IiI-rB-5 of the Guidelines. It i.s 
important to note that this appendix 
addres.ses only the biological hazard 
associated w'ith organisms containing 
recombinant DNA^ Other hazards 
accompanying the large scale cultivation 
of such organisms (e.g., toxic propeirties 
of products; physical, mechanical and 
chemical aspects of downstream 
processing) are not addre.ssed and must 
be considered separately, albeit in 
CGnjunction with this appendix ’* 
“Aii 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 are involved m 
research or production. Appendix K-II 
applies to GLSP; Appendice.s G-I and G- ' 
II, as, indicated in accompanying table, 
apply to Biosafety Levels (BL) BLl-I.S, 
BL2^LS, and BL3-LS.” 
(Remainder of Introduction remains 
unchanged.] 
“Appendix K-I — Selection of Physical 
Containment Levels. 
“I'he 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 Part III of the 
Guidelines. For purposes of large-scrfle 
reseaixh or production, four physical 
containment levels are established. 'Fhe 
foui' levels set containment conditions a i 
those appropriate for the de^fee of 
'^hazardToheaitb or the environment^': ' ' 
posed bj' the organismt," judged by ■ : T . 
experience with similar .organisms 
; manodiSed by recombinant DNA : ^ 
i techniques and consistent: with good - 
large scale. practices. These . axe referred 
:toasGLSR,BLl-LS.BL2--LS.andBL3-- 
15. The GtSP (Good Large-Scale; 
Practice) level of physical contaimnexit 
; is recommended for largerscale research ■ 
, or production involving viable, nod- ^ 
pathogenic, and non-tpxigenic . • ; ' • : ■' ; 
recombinant strains derived fi:bm host , 
^ : Organisms that have an extended histoiy . 
of .safe iaige scale use. Ukewibev the T; 
: GiSPdevel of physical containment, is; 
recommended for organisms such as 
those included in appendix C that have 
built-in environmental lirriitations that 
por.miit optimum grow'fb in li;e large 
scale setting but limited survival without 
adverse consequences in he 
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 
Lsboiatory scale. The BL2-1S (Biosafety 
Level 2 — I.ajge Scale) level of physical 
containment is required for large-scale 
research or production of viable 
organisms containing recombinant DNA 
molecules that require BI..2 containment 
at title laboratory scale. The BL3-LS 
(Biosafety Level 3— Large Scale) level of 
physical containment is required for 
large-scale research or productian os' 
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 
requlreinents will be established by NIH 
on an individual basis. 
“Appendix K-II-- GLSP Level. 
“Appendix K-II-A*. Insfitutional codes 
of practice shall be formulated and 
implemented to assure adequate control 
of health and safety matters. 
"Appendix K-II-B. Written 
instructions and training of personnel 
shall be provided to assure that cultures 
of viable organisms containing 
recombinant DNA molecules are hauled 
pnide’htiy arid that the workplace is kept 
clean and orderly. 
“Appendix K-II-G. In the interest of 
good personal hygiene, facilities (e g., 
handwashing sink, shower, changing . 
room) and protective clothing (e.g., 
mrifqriqsr laboratory coats) shall be' 
, , provided that are appropriate for die 
risk of exposure to viable organisms 
, containing reconibinant DNA molecules.. 
In addition, eating, drinking, smoking, ,, 
applying cosmetics and mouth pipetting 
shall be prohibited in the work area. 
‘’Appendix K-II-D- Cultures of viable 
organisms containing reconibinant DNA 
molecules shall be handled in facilities 
intended to safeguard health during , 
work with microorganisms that do not. . 
reqwrP'Containin,ent. . ! , 
« "Appendix K-41-^E- Discharges ; 
coataining-viable recombifiant ; 
organisms shall be handled in .. 
aOcoidance 'with applicable 
Recombinant DNA Research, Volume 14 
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