Attachment II - Page 24 
50878 federal Register / Vol. 49. No. 252 / Monday. December 31, 1984 / Notices 
FOOD AND DRUG ADMINISTRATION 
Statement of Policy for Regulating 
Biotechnology Products 
AGENCY: Food and Drug Administration. 
action: Statement of Policy for 
Regulating Biotechnology Products. 
summary: This notice describes the 
regulatory policy of the Food and Drug 
Administration applicable to 
biotechnology in general. Public 
comment is requested on scientific and 
policy issues raised by this notice. 
ADDRESS: Written comments should be 
submitted to: Docket #84N-0431. 
Dockets Management Branch, Food and 
Drug Administration (HFA-305), Room 
4-62, 5600 Fishers Lane, Rockville, MD 
20857. 
FOR FURTHER INFbRMATION, CONTACT: 
Dr. Mary Ann Danello, Food and Drug 
Administration (HF-5), Room 14-90, 
5600 Fishers Lane, Rockville, MD 20857. 
Telephone: (301) 443-4650. 
Introduction 
A small but important and expanding 
fraction of the products the Food and 
Drug Administration (FDA) regulates 
represents the fruits of new 
technological achievements. These 
achievements are in areas as diverse as 
polymer chemistry, molecular biology, 
and micro-miniaturization. It is also 
noteworthy that technological 
advancement in a given area may give 
rise to very diverse product classes, 
some or all of which may be under 
FDA's regulatory jurisdiction. For 
example, new developments in 
recombinant DNA research can yield 
products as divergent as food additives, 
drugs, biologies, and medical devices. 
Although there are no statutory 
provisions or regulations that address 
biotechnology directly, the laws and 
regulations under which the Agency 
operates place the burden of proof of 
safety as well as effectiveness of 
products on the manufacturer, except for 
traditional foods and cosmetics. The 
adminsitrative review of products using 
biotechnology is based on the intended 
use of each product on a case-by-case 
basis. 
This notice describes the regulatory 
policy of the FDA applicable to 
biotechnology in general. The manner in 
which regulations for biotechnology are 
implemented in the United States could 
have a direct impact on the 
competitiveness of U.S. producers in 
both domestic and world markets. 
Inconsistent or duplicative domestic 
regulation will put U.S. producers at a 
competitive disadvantage. In addition, 
certification systems which favor 
domestic products, if adopted by our 
trading partners, could create 
substantial nontariff barriers to trade 
and block market access. Therefore 
during the development of the U.S. 
regulatory procedures for biotechnology 
products, attention is being paid to the 
need for achieving consistency in 
national regulation and international 
harmonization. With respect to 
international harmonization the U.S. is 
seeking to promote scientific 
cooperation, mutual understanding of 
regulatory approaches international 
agreement on a range of common 
technical problems such as the 
development of consistent test 
guidelines, laboratory practices and 
principles for assessing potential risks. 
In achieving national consistency and 
international harmonization, regulatory 
decisions can be made in a socially 
responsible manner, protecting human 
health and the environment, while 
allowing U.S. producers to remain 
competitive. 
The Agency possesses extensive 
experience with the administrative and 
regulatory regimens described as 
applied to the products of 
biotechnological processes, new and 
old, and proposes no new procedures or 
requirements for regulated industry or 
individuals. Public comment is 
requested on scientific and regulatory 
policy issues raised by this notice. 
The marketing of new drugs and 
biologies for human use, and new 
animal drugs, requires prior approval of 
an appropriate new drug application 
(NDA), license, or new animal drug 
application (NADA). For new medical 
devices, including diagnostic devices for 
human use either a premarket approval 
application or reclassification petition is 
required. If the device is determined to 
be equivalent to an already marketed 
device, a premarket notification under 
section 510(k) of the Federal Food, Drug, 
and Cosmetic Act (the act) is required. 
For food products, section 409 of the act 
requires FDA preclearance of food 
additives including those prepared using 
biotechnology. Section 706 of the act 
requires preclearance of color additives. 
The implementing regulations for food 
and color additive petitions and for 
affirming generally recognized as safe 
(GRAS) food substances are sufficiently 
comprehensive to apply to those 
involving new biotechnology. 
Genetic manipulations of plants or 
animals may enter FDA's jurisdiction in 
other ways: for example, the 
introduction into a plant of a gene 
coding for a pesticide or growth factor 
may constitute adulteration of the 
foodstuff derived from the plant, or the 
use of a new microorganism found in a 
food such as yogurt could be considered 
a food additive. Such situations will be 
evaluated case-by-case, and with 
cooperation with the U.S. Department of 
Agriculture (USDA), where appropriate. 
The Regulatory Process 
Congress has provided FDA authority 
under the act and the Public Health 
Service (PHS) Act to regulate products 
regardless of how they are 
manufactured. 
General Requirements far Human Drugs 
and Biologies 
A new drug is, in general terms, a drug 
not generally recognized by qualified 
scientific experts as safe and effective 
for the proposed use. New drugs may 
not be marketed unless they have been 
approved as safe and effective, and 
clinical investigations on human 
subjects by qualified experts are a 
prerequisite for determination of safety 
and effectiveness. Sponsors of 
investigations of new drugs or new drug 
uses of approved drugs file an 
Investigational New Drug Application 
(IND) to conduct clinical investigations 
on human subjects. The IND must 
contain information needed to 
demonstrate the safety of proceeding to 
test the drug in human subjects, 
including, for example, drug 
composition, manufacturing and 
controls data, results of animal testing, 
training and experience of investigators, 
and a plan for clinical investigation. In 
addition, assurance of informed consent 
and protection of the rights and safety of 
human subjects is required. FDA 
evaluates IND submissions and reviews 
ongoing clinical inveatig^ions. 
Significant chmiges in the conditions of 
the study, including changes in study 
design, drug manufacture or formulation, 
or proposals for additional studies, must 
be submitted to FDA as amendment to 
the IND. 
FDA approval of a New Drug 
Application (NDA) or an abbreviated 
New Drug Application (ANDA) is 
required before the new drug can be 
marketed. The NDA must contain: 
• Full reports of investigations, 
including the results of clinical 
investigations, that show whether or not 
the drug is safe and effective: 
• A list of components of the drug and 
a statement of the drug's quantitative 
composition; 
• A description of the methods used 
in, and the facilities and controls used 
for, the manufacturing, processing, and 
packaging of the drug; 
• Samples of the drug and drug 
components as may be required; and 
• Specimens of the proposed labeling. 
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