14818 Federal Register / Vol. 72, No. 60 / Thursday, March 29, 2007 / Notices 

TABLE 1.—TESTING RECOMMENDATIONS FOR SUBSTANCES NOMINATED TO THE NTP FOR TOXICOLOGICAL STUDIES—

Continued 

Substance [CAS No.] Nominated by 1 Nomination rationale Preliminary study recommendations 2

Artificial butter flavoring mixture and certain components: Acetoin [513–86–0], 

Diacetyl [431–03–8].

United Food and 

Commercial 

Workers International Union.

Evidence of lung disease in exposed 

workers and respiratory toxicity in 

short-term animal toxicity studies.

—Chronic toxicity and carcinogenicity 

studies via inhalation in rats. 

—Mechanistic studies. 

Asbestos, naturally occurring and atypical forms [1332–21–4].National Center for 

Environmental 

Health/Agency 

for Toxic Substances and Disease Registry, 

U.S. Environmental Protection Agency.

Widespread community exposure in 

certain geographic locales; insufficient dose-response data to characterize risk from exposure to ‘‘unregulated’’ asbestiform mineral fibers 

and naturally occurring fibrous mineral ‘‘mixtures’’.

—Mineral characterization. 

—In vitro durability and toxicity studies. 

—Subchronic and chronic toxicity/carcinogenicity studies via inhalation. 

—Studies should utilize test materials 

representative of minerals identified 

in Libby, MT and at other Naturally 

Occurring Asbestos (NOA) sites. 

Diethyl phthalate [84–66–2] ................... National Institute of 

Environmental 

Health Sciences.

Widespread consumer exposure 

through use in cosmetics and personal care products; insufficient toxicity data to assess potential reproductive hazard.

—Multigeneration oral reproductive 

and developmental toxicity studies 

—Toxicokinetic studies (oral and dermal routes). 

2′,2′′-Dithiobisbenzanilide [135–57–9] .... NCI ........................ High production volume; potential 

worker and consumer exposures; 

lack of adequate toxicological data; 

suspicion of toxicity based on structure.

—Genotoxicity studies. 

—Metabolism studies. 

2-Methoxy-4-nitroaniline [97–52–9] ........ NCI ........................ High production volume; potential 

worker exposures; lack of adequate 

toxicological data; positive mutagenicity data; strong suspicion of toxicity and carcinogenicity based on 

structure.

—Toxicological characterization. 

—Short-term mechanistic studies to 

predict carcinogenic potential. 

Nanoscale materials Nanoscale gold 

[7440–57–5] Nanoscale silver [7440–

22–4].

U.S. Food and 

Drug Administration.

Widespread and increasing use in 

drug, food and cosmetic products; 

lack of adequate toxicological and 

pharmacokinetic data; need to 

evaluate whether the current required tests are adequate to detect 

adverse biological and toxicological 

events.

—Nanoscale materials characterization. 

—Metabolism and pharmacokinetic 

studies. 

—Acute, subacute and subchronic toxicity studies. 

—Mechanistic studies to assess the 

role of size and surface coating on 

biological disposition and toxicity. 

Pentaethylenehexamine [4067–16–7] .... NCI ........................ High production volume; potential 

worker exposures; lack of adequate 

toxicological data; positive mutagenicity data.

No studies at this time due to the irritant and corrosive nature of this 

compound. 

o-Phthalaldehyde [643–79–8] ................ National Institute 

for Occupational 

Safety and 

Health.

Widespread and increasing use as a 

disinfectant in health care settings; 

lack of adequate and publicly available toxicological data; potential skin 

and respiratory sensitizer.

—Toxicological characterization including studies to assess dermal irritation, dermal toxicity, and sensitization and asthmagenic potential. 

1 National Cancer Institute (NCI). 2 The term ‘‘toxicological characterization’’ in this table includes studies for genotoxicity, subchronic toxicity, and chronic toxicity/carcinogenicity 

as determined to be appropriate during the conceptualization and design of a research program to address toxicological data needs. Other types 

of studies (e.g., metabolism and disposition, immunotoxicity, and reproductive and developmental toxicity) may be conducted as part of a complete toxicological characterization; however, these types of studies are not listed unless they are specifically recommended. 

[FR Doc. E7–5831 Filed 3–28–07; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 1997E–0013] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; RETEVASE 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) has determined 

the regulatory review period for 

RETEVASE and is publishing this notice 

of that determination as required by 

law. FDA has made the determination 

because of the submission of an 

application to the Director of Patents 

and Trademarks, Department of 

Commerce, for the extension of a patent 

which claims that human biological 

product. 

ADDRESSES: Submit written comments 

and petitions to the Division of Dockets 


jlentini on PROD1PC65 with NOTICES
Federal Register / Vol. 72, No. 60 / Thursday, March 29, 2007 / Notices 14819 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to http:// 

www.fda.gov/dockets/ecomments. 

FOR FURTHER INFORMATION CONTACT: 

Beverly Friedman, Office of Regulatory 

Policy (HFD–7), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–594–2041. 

SUPPLEMENTARY INFORMATION: The Drug 

Price Competition and Patent Term 

Restoration Act of 1984 (Public Law 98–

417) and the Generic Animal Drug and 

Patent Term Restoration Act (Public 

Law 100–670) generally provide that a 

patent may be extended for a period of 

up to 5 years so long as the patented 

item (human drug product, animal drug 

product, medical device, food additive, 

or color additive) was subject to 

regulatory review by FDA before the 

item was marketed. Under these acts, a 

product’s regulatory review period 

forms the basis for determining the 

amount of extension an applicant may 

receive. 

A regulatory review period consists of 

two periods of time: A testing phase and 

an approval phase. For human 

biological products, the testing phase 

begins when the exemption to permit 

the clinical investigations of the 

biological product becomes effective 

and runs until the approval phase 

begins. The approval phase starts with 

the initial submission of an application 

to market the human biological product 

and continues until FDA grants 

permission to market the biological 

product. Although only a portion of a 

regulatory review period may count 

toward the actual amount of extension 

that the Director of Patents and 

Trademarks may award (for example, 

half the testing phase must be 

subtracted as well as any time that may 

have occurred before the patent was 

issued), FDA’s determination of the 

length of a regulatory review period for 

a human biological product will include 

all of the testing phase and approval 

phase as specified in 35 U.S.C. 

156(g)(1)(B). 

FDA approved for marketing the 

human biological product RETEVASE 

(reteplase). RETEVASE is indicated in 

the management of acute myocardial 

infarction (AMI) in adults for the 

improvement of ventricular function 

following AMI, the reduction of the 

incidence of congestive heart failure and 

the reduction of mortality associated 

with AMI. Subsequent to this approval, 

the Patent and Trademark Office 

received a patent term restoration 

application for RETEVASE (U.S. Patent 

No. 5,223,256) from Boehringer 

Mannheim GmbH, and the Patent and 

Trademark Office requested FDA’s 

assistance in determining this patent’s 

eligibility for patent term restoration. In 

a letter dated February 6, 1997, FDA 

advised the Patent and Trademark 

Office that this human biological 

product had undergone a regulatory 

review period and that the approval of 

RETEVASE represented the first 

permitted commercial marketing or use 

of the product. On September 14, 2006, 

the Patent and Trademark Office 

requested that FDA determine the 

product’s regulatory review period. 

FDA has determined that the 

applicable regulatory review period for 

RETEVASE is 1,919 days. Of this time, 

1,430 days occurred during the testing 

phase of the regulatory review period, 

while 489 days occurred during the 

approval phase. These periods of time 

were derived from the following dates: 

1. The date an exemption under 

section 505(i) of the Federal Food, Drug, 

and Cosmetic Act (21 U.S.C. 355(i)) 

became effective: August 1, 1991. The 

applicant claims July 1, 1991, as the 

date the investigational new drug 

application (IND) became effective. 

However, FDA records indicate that the 

IND effective date was August 1, 1991, 

which was 30 days after FDA receipt of 

the IND. 

2. The date the application was 

initially submitted with respect to the 

human biological product under section 

351 of the Public Health Service Act (42 

U.S.C. 262): June 30, 1995. FDA has 

verified the applicant’s claim that the 

product license application (PLA) for 

Retevase (PLA 95–1167) was initially 

submitted on June 30, 1995. The PLA 

was renumbered as biologics license 

application (BLA) 103632/0. 

3. The date the application was 

approved: October 30, 1996. The 

applicant claims October 29, 1996, as 

the date the PLA was approved. 

However, FDA records indicate that 

PLA 95–1167 (BLA 103632/0) was 

approved on October 30, 1996. 

This determination of the regulatory 

review period establishes the maximum 

potential length of a patent extension. 

However, the U.S. Patent and 

Trademark Office applies several 

statutory limitations in its calculations 

of the actual period for patent extension. 

In its application for patent extension, 

this applicant seeks 123 days of patent 

term extension. 

Anyone with knowledge that any of 

the dates as published is incorrect may 

submit to the Division of Dockets 

Management (see ADDRESSES) written or 

electronic comments and ask for a 

redetermination by May 29, 2007. 

Furthermore, any interested person may 

petition FDA for a determination 

regarding whether the applicant for 

extension acted with due diligence 

during the regulatory review period by 

September 25, 2007. To meet its burden, 

the petition must contain sufficient facts 

to merit an FDA investigation. (See H. 

Rept. 857, part 1, 98th Cong., 2d sess., 

pp. 41–42, 1984.) Petitions should be in 

the format specified in 21 CFR 10.30. 

Comments and petitions should be 

submitted to the Division of Dockets 

Management. Three copies of any 

mailed information are to be submitted, 

except that individuals may submit one 

copy. Comments are to be identified 

with the docket number found in 

brackets in the heading of this 

document. Comments and petitions may 

be seen in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

Dated: March 12, 2007. 

Jane A. Axelrad, 

Associate Director for Policy, Center for Drug 

Evaluation and Research. 

[FR Doc. E7–5736 Filed 3–28–07; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

Food and Drug Administration 

[Docket No. 2006E–0354] 

Determination of Regulatory Review 

Period for Purposes of Patent 

Extension; VAPRISOL 

AGENCY: Food and Drug Administration, 

HHS. 

ACTION: Notice. 

SUMMARY: The Food and Drug 

Administration (FDA) has determined 

the regulatory review period for 

VAPRISOL and is publishing this notice 

of that determination as required by 

law. FDA has made the determination 

because of the submission of an 

application to the Director of Patents 

and Trademarks, Department of 

Commerce, for the extension of a patent 

that claims that human drug product. 

ADDRESSES: Submit written comments 

and petitions to the Division of Dockets 

Management (HFA–305), Food and Drug 

Administration, 5630 Fishers Lane, rm. 

1061, Rockville, MD 20852. Submit 

electronic comments to http:// 

www.fda.gov/dockets/ecomments. 

FOR FURTHER INFORMATION CONTACT: 

Beverly Friedman, Office of Regulatory 

Policy (HFD–7), Food and Drug 

Administration, 5600 Fishers Lane, 

Rockville, MD 20857, 301–594–2041. 


jlentini on PROD1PC65 with NOTICES