60134 
PROPOSED RULES 
[41 10-03-M] 
DEPARTMENT OF HEALTH, 
EDUCATION, AND WELFARE 
Food and Drug Administration 
[21 CFR Part 59] 
[Docket No. 78N-0012] 
RECOMBINANT DNA 
Intont to Propose Regulations 
AGENCY: Food and Drug Administra- 
tion. 
ACTION: Notice of Intent to Propose 
Regulations. 
SUMMARY: The Food and Drug Ad- 
ministration (FDA) intends to propose 
regulations to require assurances in 
future submissions to the agency that 
any recombinant deoxyribonucleic 
acid (DNA) work that has been or will 
be performed in connection with these 
submissions fully complies with the 
National Institutes of Health (NIH) 
Guidelines for Recombinant DNA Re- 
search. This notice Is being issued be- 
cause the Commissioner of Food and 
Drugs believes it would be helpful to 
invite public comment on whether 
such action would be appropriate and 
desirable. 
DATE: Comments by February 20. 
1979. 
ADDRESS: Written comments to the 
Hearing Clerk (HFA-305). Food and 
Drug Administration. Rm. 4-65. 5600 
Fishers Lane. Rockville, MD 20857. 
FOR FURTHER INFORMATION 
CONTACT: 
Irvin M. Asher. Office of Health Af- 
fairs (HFY-313), Food and Drug Ad- 
ministration. Department of Health. 
Education, and Welfare. 5600 Fish- 
ers Lane. Rockville, MD 20857 r 301- 
443-4490. 
SUPPLEMENTARY INFORMATION: 
"Recombinant DNA” molecules have 
been defined as either (1) molecules 
that are constructed outside living 
cells by Joining natural or synthetic 
DNA segments to DNA molecules that 
can replicate in a living cell, or (2) 
DNA molecules that result from the 
replication of such molecules. (See the 
Federal Register of July 28, 1978 (43 
FR 33042, at 33069).) The Food and 
Drug Administration has received in- 
quiries from pharmaceutical manufac- 
tures and others concerning the use of 
recombinant DNA techniques in re- 
search on, and development and man- 
ufacture of. products subject to FDA’s 
Jurisdiction. 
The Secretary of Health. Education, 
and Welfare (HEW) has recognized 
that newly developed techniques for 
creating and manipulating such mole- 
cules constitute scientific tools with 
unusual promise of bringing about a 
better understanding and improved 
treatment of human disease. As scien- 
tists in the field were the first to rec- 
ognize. however, the new techniques 
pose potential hazards. Should foreign 
DNA alter microorganisms in unpre- 
dictable. undesirable ways, and should 
those organisms escape from con- 
trolled settings, they could conceiv- 
ably harm individuals and the environ- 
ment. 
On June 23, 1976, NIH issued com- 
prehensive guidelines setting forth ap- 
propriate precautions for work with 
various types of recombinant DNA 
molecules (see the Federal Register 
of July 7. 1976 (41 FR 27902)). All Fed- 
eral agencies that conduct or sponsor 
research involving recombinant DNA 
subsequently endorsed the NIH guide- 
lines. At the time the 1976 guidelines 
were issued, the Director of NIH em- 
phasized that the guidelines were to 
remain flexible and subject to continu- 
ing review as new information relating 
to potential risks or safety aspects of 
the research program was developed 
(see the July 7. 1976 Federal Register 
at 41 FR 27905). 
Since the publication of the 1976 
guidelines, the Issues surrounding re- 
combinant DNA research have been 
widely discussed in congressional hear- 
ing. public hearings consucted by NIH, 
and in scientific journals. Proposed re- 
visions of the guidelines were recom- 
mended to the NIH Director by the 
NIH Recombinant DNA Advisory 
Committee and were published for 
public comment in the Federal Regis- 
ter. of September 27. 1977 (42 FR 
49596). After an extensive evaluation 
of the September 27 proposal and the 
comments received in response to that 
proposal, the NIH Director issued pro- 
posed revised guidelines on July 28, 
1978 (43 FR 33042). The comments re- 
ceived in response to the July 28 pro- 
posal were reviewed by a Department- 
al review committee established by the 
Secretary of HEW. That committee’s 
review of the comments, and the new 
guidelines, are being published in the 
Federal Register today. 
The Commissioner believes that the 
new NIH guidelines reflect the best 
available information on recombinant 
DNA research and constitute the most 
workable available guide to responsi- 
ble practice in this developing area of 
science. They represent the most so- 
phisticated attempt to date to harmo- 
nize freedom for scientific inquiry 
with protection of the public health 
and environment with respect to this 
research. The NIH guidelines have 
been subjected to scientific and public 
review and will continue to be updated 
as new information becomes available. 
Therefore, the Commissioner in- 
tends to propose regulations to require 
that any firm seeking approval of a 
product requiring the use of recombin- 
ant DNA methods in its development 
or manufacture demonstrate the 
firm’s compliance with the require- 
ments of the NIH guidelines (in effect 
at the time work involving recombin- 
ant DNA is commenced) in connection 
with any work it has done or will do 
relating to that product. Such assur- 
ance would be required, for example, 
in notices of claimed investigational 
exemption of a new drug (IND's), new 
drug applications (NDA’s), license ap- 
plications for biologic products, re- 
quests for certification for antibiotics, 
feed additive petitions, food additive 
petitions, and new animal drug appli- 
cations (NADA’s). Further, the Com- 
missioner intends to propose that the 
NIH guidelines be incorporated in 
good manufacturing practice regula- 
tions. should recombinant DNA tech- 
niques be proposed for the manufac- 
ture of products for commercial distri- 
bution. Although the details for assur- 
ing compliance with the NIH guide- 
lines have not yet been worked out, 
the Commissioner is considering a re- 
quirement that all recombinant DNA 
research being conducted for submis- 
sion to FDA be registered with FDA. 
In evaluating such research. FDA 
would utilize the expertise of NIH as 
necessary, and might refer specific 
protocols to NIH for review as to their 
compliance with the NIH guidelines. 
The Commissioner is aware that 
product-related research involving re- 
combinant DNA is in many cases re- 
garded as commercially sensitive, and 
is treated as confidential by persons 
who conduct or sponsor such research. 
FDA’s public information regulations 
broadly protect trade secret and com- 
mercial information that is privileged 
or confidential (see 21 CFR 20.61). 
The regulations (21 CFR 20.82(b)) ex- 
pressly provide that information 
within the scope of § 20.61 may not be 
disclosed. 
Moreover, specified types of confi- 
dential information are prohibited 
from disclosure by statute. Section 
301(j) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C 331(j)) prohib- 
its the disclosure, other than to De- 
partment employees and to the courts, 
of any information acquired under au- 
thority of specified sections of the act 
“concerning any method or process 
which as a trade secret is entitled to 
protection." The general Federal con- 
fidentiality statute, 18 U.S.C. 1905, 
prohibits the disclosure "in any 
manner or to any extent not author- 
ized by law” of any information ac- 
quired in the course of official duty 
concerning, among other things, 
“trade secrets, processes, operation, 
style of work, or apparatus" of any 
person (18 U.S.C. 1905). 
The regulations to be proposed 
would provide protections against 
public disclosure of information con- 
FEDERAl REGISTER, VOL 43. NO. 247— FRIDAY, DECEMBER 22, 1978 
