Federal Register / Vol. 52, No. 163 / Monday. August 24. 1987 / Notices 
31849 
Health. The Preamble stales that. . .for 
contained federally funded research for 
biomedical and agricultural purposes, 
research approval will be granted by the 
funding agency .... Jurisdiction for release 
may be under SAE. NSF. APHIS, or EPA.” 
There is no mention in the June 28 Federal 
Register document of any requirement once 
approval for a recombinant DNA experiment 
is obtained from a Federal agency other than 
NIK for communication with the NIH Office 
of Recombinant ONA Activities. And indeed 
1 believe that the absence of such a 
requirement should be the'case: not omy for 
experiments covered by Section Hi- A of the 
Guidelines, but for all recombinant ONA 
experiments. 
Therefore. I propose the following changes 
in the NIH Guidelines for Research Involving 
Recombinant DNA Molecules. 
1. Delete from Section Ql-A of the 
Guidelines the following paragraph: 
If the experiments in this category are 
submitted for review to another Federal 
agency, the submitter shall notify ORDA; 
ORDA may then determine that such review 
serves the same purpose, and based on that 
determination, notify the submitter that no 
RAC review will take place, no NIH approval 
is necessary, and the experiment may 
proceed upon approval from the other 
Federal agency. 
2. Add at the end of Section l-A of the 
Guidelines the following paragraph 
Any recombinant DNA experiment which 
according to these Guidelines requires 
approval by the National Institutes of Health 
(NIH). may be sent by the submitter to the 
NIH or to another Federal agency that has 
Jurisdiction for review and approval. Once 
approval for a recombinant DNA experiment 
has been given by a Federal agency other 
than the NIH (whether referred to that agency 
by the NIH or salt directly there by the 
submitter), the experiment may proceed 
without the necessity for NIH review or 
approval. 
This proposal was published for 
comment in the Federal Register of 
December 19. 1988 (51 FR 45850). 
Eleven letters were received with 
comments on this proposal. Ten of the 
letters provided unqualified support for 
the proposal. One letter suggested an 
alternative mechanism in which NIH 
and another agency would confer and 
decide which agency would conduct the 
review. 
The RAC considered this proposal at 
the February 2. 1987. meeting. The RAC 
supported the proposal and 
recommended the incorporation of 
amendments proposed at the meeting. 
One RAC member moved that the 
following sentence be added at the end 
of proposed revised Section l-A: 
However, any experiment that involves the 
administration of gene therapy to human 
subjects (see Section III— A — : I of the 
Guidelines) may nol proceed without prior 
review by the NIH Recombinant DNA 
Adviaory Committee and NIH approval. 
Dr. Talbot supported the amendment. 
By a vote of 12 in favor, 1 opposed, and 
3 abstentions, the RAC accepted the 
amendment 
Another RAC member proposed that 
the second sentence of proposed revised 
Section l-A be amended to read as 
follows: 
Once approval or other applicable 
clearances, have been obtained from a 
Federal agency other than the NIH (whether 
the experiment is referred to that agency by 
the NIK or sent directly there by the 
aubmitter). the experiment may proceed 
without the necessity for NIH review or 
approval. 
The RAC then voted- 17 in favor, none 
opposed, and no abstentions to 
recommend approval of the proposal as 
amended. 
I accept this recommendation and 
Sections J-A and ID-A have been 
modified accordingly. 
B. Proposed Revisions of Appendices 
C-1I. C-llL and C-IV 
Dr. Frank E. Young. Commissioner of 
Food and Drugs, submitted in a letter 
dated December 4 . 1986. the following 
proposed revisions of Appendices C-U, 
C-m. and C-IV. and rationale: 
On June 28. 1988. a major statement of 
federal policy, the "Coordinated Framework 
for Regulation of Biotechnology." was 
published (51 FR 23301-93). We believe that 
important clarifications of regulatory policy 
are to be found there, but that tome minor 
changes in the NIH Guidelines are required 
for consistency and clarity. 
Aa noted on page 23304 of the June 28 
document Appendices C-U. C-IIL and C-IV 
of the NIH Guidelines contain the statement 
that: 
For large scale (LS) fermentation 
experiments BLl-LS physical containment 
conditions are recommended. However, 
following review by the IBC of appropriate 
data for a particular host-vector system, some 
latitude in the application of BLl-LS 
requirements as outlined in Appendices K— II— 
A through K-Il-F ia permitted. 
The document continues: 
The appropriate large-scale conlainment 
requirements of many low-risk (r|DNA 
derived industral microorganisms will be no 
greater than those appropriate for the 
unmodified parental organisms. 
Together, these statements imply that the 
actions of IBCs should ensure that 
requirements for physical containment of 
low-risk microorganisms should be 
appropriately minimal, i.e.. only those that 
are employed routinely for organisms such as 
E. coli K-12. B. subtilis. or Socchoromyces 
cerevisiae. It should be noted that industrial 
fermentation has a long and distinguished 
history and currently accounts for products 
valued at more than S2 billion annually. . . . 
All but a minuscule proportion of this 
production employs non-pathogenic 
organisms and is carried out safely under 
conditions significantly less restrictive than 
the NIH Guidelines' BLl-LS. which requires 
that recombinant organisms be handled in a 
closed system, that culture fluids containing 
viable organisms not be removed from a 
closed system, that exhaust gases removed 
from a closed system be treated by filters 
equivalent to HEPA filters, etc. 
To ensure compliance with the NIH 
Guidelines, the E. coli and Socchoromyces 
cerevisiae production organisms used to 
manufacture the five DNA-derived 
pharmaceuticals approved by FDA (human 
insulin, human growth hormone, two alpha- 
interferons. and hepatitis B vaccine), are 
indeed grown under containment conditions 
at least BLl-LS. This degree of containment 
is expensive, unwieldy and unnecessary. 
Despite the interpretation discussed above 
of the language in the June 28 document. FDA 
has received numerous inquiries and requesis 
from academics, industrial representatives, 
and others who have found the language in 
the June 20 document and the NIH Guidelines 
not explicit enough for purposes of strategic 
planning. Therefore, we propose Ihe 
following amendment to the NIH Guidelines: 
In Appendices C-IL C-UL and C-IV, delete 
the following language: 
For these exempt laboratory experiments. 
BLl physical containment conditions are 
recommended. 
For large-scale (LS) fermentation 
experiments BLl-LS physical containment 
conditions are recommended. However, 
following review by the IBC of appropriate 
data for a particular host-vector system, some 
latitude in the application of BLl-LS 
requirements as outlined in Appendices K— II— 
A through K-II-F is permitted. 
And substitute: For these exempt 
laboratory experiments, the appropriate 
physical containment conditions need be no 
greater than those for the host organism 
unmodified by recombinant DNA techniques. 
For large-scale (LS) fermentation 
experiments, the appropriate physical 
containment conditions need be no greater 
than those for the host organism unmodified 
by recombinant DNA techniques. 
This proposal was published for 
comment in the Federal Register of 
December 19. 1986 (51 FR 45650). 
Eighteen letters were received with 
comments on this proposal. Comments 
in sixteen letters supported adoption of 
the proposal. One letter questioned why 
BLl containment should be relaxed for 
laboratory experiments covered by 
Appendices C— II. C— III. and C-IV, and 
suggested that "unwieldy, expensive, 
and unnecessary” requirements for 
large-scale containment could be 
replaced by less stringent requirements. 
One letter opposed the lessening of Bl.l- 
LS containment for large-scale 
experiments. 
The RAC considered this proposal at 
the February 2, 1987. meeting. It was 
noted that there are two aspects to the 
proposal. One deals with containment 
recommended for exempt laboratory 
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