24410 Federal Register / Vol. 68, No. 88 / Wednesday, May 7, 2003 / Proposed Rules Unfunded Mandates Reform Act The Unfunded Mandates Reform Act of 1995 ( 2 U. S. C. 1531   1538) requires Federal agencies to assess the effects of their discretionary regulatory actions. In particular, the Act addresses actions that may result in the expenditure by a State, local, or tribal government, in the aggregate, or by the private sector of $ 100,000,000 or more in any one year. Though this proposed rule would not result in such expenditure, we do discuss the effects of this rule elsewhere in this preamble.

Taking of Private Property This proposed rule would not effect a taking of private property or otherwise have taking implications under Executive Order 12630, Governmental Actions and Interference with Constitutionally Protected Property Rights.

Civil Justice Reform This proposed rule meets applicable standards in sections 3( a) and 3( b)( 2) of Executive Order 12988, Civil Justice Reform, to minimize litigation, eliminate ambiguity, and reduce burden.

Protection of Children We have analyzed this proposed rule under Executive Order 13045, Protection of Children from Environmental Health Risks and Safety Risks. This rule is not an economically significant rule and would not create an environmental risk to health or risk to safety that might disproportionately affect children.

Indian Tribal Governments This proposed rule does not have tribal implications under Executive Order 13175, Consultation and Coordination with Indian Tribal Governments, because it would not have a substantial direct effect on one or more Indian tribes, on the relationship between the Federal Government and Indian tribes, or on the distribution of power and responsibilities between the Federal Government and Indian tribes. We invite your comments on how this proposed rule might impact tribal governments, even if that impact may not constitute a `` tribal implication'' under the order.

Energy Effects We have analyzed this proposed rule under Executive Order 13211, Actions Concerning Regulations That Significantly Affect Energy Supply, Distribution, or Use. We have determined that it is not a `` significant energy action'' under that order because it is not a `` significant regulatory action'' under Executive Order 12866 and is not likely to have a significant adverse effect on the supply, distribution, or use of energy. It has not been designated by the Administrator of the Office of Information and Regulatory Affairs as a significant energy action. Therefore, it does not require a Statement of Energy Effects under Executive Order 13211.

Environment We have considered the environmental impact of this rule and concluded that under figure 2   1, paragraph ( 34)( g), of Commandant Instruction M16475. lD, this rule is categorically excluded from further environmental documentation because we are establishing a security zone. A `` Categorical Exclusion Determination'' and checklist are available in the docket for inspection or copying where indicated under ADDRESSES. Comments on this section will be considered before we make the final decision on whether the rule should be categorically excluded from further environmental review.

List of Subjects in 33 CFR Part 165 Harbors, Marine safety, Navigation ( water), Reporting and record keeping requirements, Security measures, Waterways. For the reasons discussed in the preamble, the Coast Guard proposes to amend 33 CFR part 165 as follows:

PART 165   REGULATED NAVIGATION AREAS AND LIMITED ACCESS AREAS 1. The authority citation for Part 165 continues to read as follows:

Authority: 33 U. S. C. 1231; 50 U. S. C. 191, 33 CFR 1.05   1( g), 6.04   1, 6.04   6, and 160.5; Department of Homeland Security Delegation No. 0170.

2. Add § 165.1109 to read as follows:

§ 165.1109 Security Zone; National City Marine Terminal, San Diego, CA.

( a) Location. The security zone consists of the navigable waters surrounding the National City Marine Terminal and encompassing Sweetwater Channel. The limits of this security zone are more specifically defined as the area enclosed by the following points: starting on shore at 32 ° 39  25  N 117 ° 07  15  W, then extending northerly to 32 ° 39  32  N 117 ° 07  16  W, then extending westerly to 32 ° 39  29  N 117 ° 07  36  W, then southerly to 32 ° 39  05  N 117 ° 07  34  W, and then easterly to shore at 32 ° 39  06  N 117 ° 07  14.5  W. All coordinates are North American Datum 1983. ( b) Regulations. ( 1) In accordance with the general regulations in § 165.33 of this part, entry into, transit through, or anchoring within the security zone by all vessels is prohibited during military outloads, unless authorized by the Captain of the Port, or his designated representative. All other general regulations of § 165.33 of this part apply in the security zone established by this section. ( 2) Persons desiring to transit the area of the security zone may contact the Captain of the Port on VHF channel 16 or VHF channel 21A to seek permission to transit the area. Additionally, the COTP representative may be reached at ( 619) 683   6470 ext 2. If permission is granted, all persons and vessels must comply with the instructions of the Captain of the Port or his or her designated representatives. ( c) Enforcement. The U. S. Coast Guard may be assisted in the patrol and enforcement of this security zone by the San Diego Harbor Police. ( d) Notice. Enforcement of the security zone will be announced via broadcast notice to mariners, local notice to mariners, or by any other means that is deemed appropriate. ( e) Authority. In addition to 33 U. S. C. 1231, the authority for this section includes 33 U. S. C. 1226.

Dated: April 17, 2003. Stephen P. Metruck, Commander, U. S. Coast Guard, Captain of the Port, San Diego, California. [ FR Doc. 03   11296 Filed 5   6   03; 8: 45 am]

BILLING CODE 4910   15   P ENVIRONMENTAL PROTECTION AGENCY 40 CFR Chapter I [ OPP   2003   0132; FRL   7302   8]

RIN: 2070   AD57 Human Testing; Advance Notice of Proposed Rulemaking AGENCY: Environmental Protection Agency ( EPA). ACTION: Advance notice of proposed rulemaking.

SUMMARY: This advance notice of proposed rulemaking announces EPA's plan to conduct rulemaking about criteria and standards EPA would apply in deciding the extent to which it will consider or rely on various types of research with human subjects to support its actions. This notice also initiates the rulemaking process by requesting public comments and suggestions on a broad range of issues relating to this subject.

VerDate Jan< 31> 2003 16: 34 May 06, 2003 Jkt 200001 PO 00000 Frm 00028 Fmt 4702 Sfmt 4702 E:\ FR\ FM\ 07MYP1. SGM 07MYP1 24411 Federal Register / Vol. 68, No. 88 / Wednesday, May 7, 2003 / Proposed Rules DATES: Comments must be received on or before August 5, 2003.

ADDRESSES: Submit your comments, identified by docket ID number OPP   2003   0132, online at http:// www. epa. gov/ edocket ( EPA's preferred method) or mailed to the Public Information and Records Integrity Branch ( PIRIB), ( 7502C), Office of Pesticide Programs ( OPP), Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460   0001. For additional submission methods and detailed instructions, go to Unit I. C. of the SUPPLEMENTARY INFORMATION.

FOR FURTHER INFORMATION CONTACT: William L. Jordan, Mail code 7501C, Office of Pesticide Programs, Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460; telephone number: ( 703) 305   1049, fax number: ( 703) 308   4776; e mail address: jordan. william@ epa. gov.

SUPPLEMENTARY INFORMATION: This Advance Notice of Proposed Rulemaking ( ANPR) is organized into four Units. Unit I. contains `` General Information'' about the applicability of this ANPR, how to obtain additional information, how to submit comments in response to the request for comments, and certain other related matters. Unit II. provides background and historic information pertaining to human subject research. Unit III. describes the rulemaking process, identifies relevant statutory provisions, and requests public comments and suggestions on a broad range of issues related to the Agency's consideration of or reliance on research with human subjects. Unit IV. describes procedures followed in the development of this ANPR and certain statutes and Executive Orders that the public may wish to consider in preparing comments.

I. General Information A. Does this Action Apply to Me?

This action is directed to the public in general. This action may, however, be of particular interest to those who conduct testing of substances regulated by EPA. Since other entities may also be interested, the Agency has not attempted to describe all the specific entities that may be affected by this action. If you have any questions regarding the applicability of this action to a particular entity, consult the person listed under FOR FURTHER INFORMATION CONTACT. B. How Can I Get Copies of this Document and Other Related Information?

1. Docket. EPA has established an official public docket for this action under docket identification ( ID) number OPP   2003   0132. The official public docket consists of the documents specifically referenced in this action, any public comments received, and other information related to this action. Although a part of the official docket, the public docket does not include Confidential Business Information ( CBI) or other information whose disclosure is restricted by statute. The official public docket is the collection of materials that is available for public viewing at the Public Information and Records Integrity Branch ( PIRIB), Rm. 119, Crystal Mall # 2, 1921 Jefferson Davis Hwy., Arlington, VA. This docket facility is open from 8: 30 a. m. to 4 p. m., Monday through Friday, excluding legal holidays. The docket telephone number is ( 703) 305   5805. 2. Electronic access. You may access this Federal Register document electronically through the EPA Internet under the `` Federal Register'' listings at http:// www. epa. gov/ fedrgstr/. An electronic version of the public docket is available through EPA's electronic public docket and comment system, EPA Dockets. You may use EPA Dockets at http:// www. epa. gov/ edocket to submit or view public comments, access the index listing of the contents of the official public docket, and to access those documents in the public docket that are available electronically. Once in the system, select `` search,'' then key in the appropriate docket ID number. Certain types of information will not be placed in the EPA Dockets. Information claimed as CBI and other information whose disclosure is restricted by statute, which is not included in the official public docket, will not be available for public viewing in EPA's electronic public docket. EPA's policy is that copyrighted material will not be placed in EPA's electronic public docket but will be available only in printed, paper form in the official public docket. To the extent feasible, publicly available docket materials will be made available in EPA's electronic public docket. When a document is selected from the index list in EPA Dockets, the system will identify whether the document is available for viewing in EPA's electronic public docket. Although not all docket materials may be available electronically, you may still access any of the publicly available docket materials through the docket facility identified in Unit I. B. 1. EPA intends to work towards providing electronic access to all of the publicly available docket materials through EPA's electronic public docket. For public commenters, it is important to note that EPA's policy is that public comments, whether submitted electronically or on paper, will be made available for public viewing in EPA's electronic public docket as EPA receives them and without change, unless the comment contains copyrighted material, CBI, or other information whose disclosure is restricted by statute. When EPA identifies a comment containing copyrighted material, EPA will provide a reference to that material in the version of the comment that is placed in EPA's electronic public docket. The entire printed comment, including the copyrighted material, will be available in the public docket. Public comments submitted on computer disks that are mailed or delivered to the docket will be transferred to EPA's electronic public docket. Public comments that are mailed or delivered to the docket will be scanned and placed in EPA's electronic public docket. Where practical, physical objects will be photographed, and the photograph will be placed in EPA's electronic public docket along with a brief description written by the docket staff.

C. How and to Whom Do I Submit Comments? You may submit comments electronically, by mail, or through hand delivery/ courier. To ensure proper receipt by EPA, identify the appropriate docket ID number in the subject line on the first page of your comment. Please ensure that your comments are submitted within the specified comment period. Comments received after the close of the comment period will be marked `` late.'' EPA is not required to consider these late comments. If you wish to submit CBI or information that is otherwise protected by statute, please follow the instructions in Unit I. D. Do not use EPA Dockets or e mail to submit CBI or information protected by statute. 1. Electronically. If you submit an electronic comment as prescribed in this unit, EPA recommends that you include your name, mailing address, and an email address or other contact information in the body of your comment. Also include this contact information on the outside of any disk or CD ROM you submit, and in any cover letter accompanying the disk or CD ROM. This ensures that you can be identified as the submitter of the comment and allows EPA to contact you VerDate Jan< 31> 2003 16: 34 May 06, 2003 Jkt 200001 PO 00000 Frm 00029 Fmt 4702 Sfmt 4702 E:\ FR\ FM\ 07MYP1. SGM 07MYP1 24412 Federal Register / Vol. 68, No. 88 / Wednesday, May 7, 2003 / Proposed Rules in case EPA cannot read your comment due to technical difficulties or needs further information on the substance of your comment. EPA's policy is that EPA will not edit your comment, and any identifying or contact information provided in the body of a comment will be included as part of the comment that is placed in the official public docket, and made available in EPA's electronic public docket. If EPA cannot read your comment due to technical difficulties and cannot contact you for clarification, EPA may not be able to consider your comment. i. EPA Dockets. Your use of EPA's electronic public docket to submit comments to EPA electronically is EPA's preferred method for receiving comments. Go directly to EPA Dockets at http:// www. epa. gov/ edocket, and follow the online instructions for submitting comments. Once in the system, select `` search,'' and then key in docket ID number OPP   2003   0132. The system is an `` anonymous access'' system, which means EPA will not know your identity, e mail address, or other contact information unless you provide it in the body of your comment. ii. E mail. Comments may be sent by e mail to opp docket@ epa. gov, Attention: Docket ID Number OPP   2003   0132. In contrast to EPA's electronic public docket, EPA's e mail system is not an `` anonymous access'' system. If you send an e mail comment directly to the docket without going through EPA's electronic public docket, EPA's e mail system automatically captures your e mail address. E mail addresses that are automatically captured by EPA's e mail system are included as part of the comment that is placed in the official public docket, and made available in EPA's electronic public docket. iii. Disk or CD ROM. You may submit comments on a disk or CD ROM that you mail to the mailing address identified in Unit I. C. 2. These electronic submissions will be accepted in WordPerfect or ASCII file format. Avoid the use of special characters and any form of encryption. 2. By mail. Send your comments to: Public Information and Records Integrity Branch ( PIRIB), Office of Pesticide Programs ( OPP), Environmental Protection Agency ( 7502C), 1200 Pennsylvania Ave., NW., Washington, DC 20460   0001, Attention: Docket ID Number OPP   2003   0132. 3. By hand delivery or courier. Deliver your comments to: Public Information and Records Integrity Branch ( PIRIB), Office of Pesticide Programs ( OPP), Environmental Protection Agency, Rm. 119, Crystal Mall # 2, 1921 Jefferson Davis Hwy., Arlington, VA, Attention: Docket ID Number OPP   2003   0132. Such deliveries are only accepted during the docket's normal hours of operation as identified in Unit I. B. 1.

D. How Should I Submit CBI to the Agency?

Do not submit information that you consider to be CBI electronically through EPA's electronic public docket or by e mail. You may claim information that you submit to EPA as CBI by marking any part or all of that information as CBI ( if you submit CBI on disk or CD ROM, mark the outside of the disk or CD ROM as CBI and then identify electronically within the disk or CD ROM the specific information that is CBI). Information so marked will not be disclosed except in accordance with procedures set forth in 40 CFR part 2. In addition to one complete version of the comment that includes any information claimed as CBI, a copy of the comment that does not contain the information claimed as CBI must be submitted for inclusion in the public docket and EPA's electronic public docket. If you submit the copy that does not contain CBI on disk or CD ROM, mark the outside of the disk or CD ROM clearly that it does not contain CBI. Information not marked as CBI will be included in the public docket and EPA's electronic public docket without prior notice. If you have any questions about CBI or the procedures for claiming CBI, please consult the person listed under FOR FURTHER INFORMATION CONTACT.

E. What Should I Consider as I Prepare My Comments for EPA?

You may find the following suggestions helpful for preparing your comments: 1. Explain your views as clearly as possible. 2. Describe any assumptions that you used. 3. Provide copies of any technical information and/ or data you used that support your views. 4. If you estimate potential burden or costs, explain how you arrived at the estimate that you provide. 5. Provide specific examples to illustrate your concerns. 6. Make sure to submit your comments by the deadline in this ANPR. 7. To ensure proper receipt by EPA, be sure to identify the docket control number assigned to this action in the subject line on the first page of your response. You may also provide the name, date, and Federal Register citation. II. Introduction A. Background on Federal Standards for Conducting Human Research Over the years, scientific research with human subjects has provided much valuable information to help characterize and control risks to public health, but its use has also raised particular ethical concerns for the welfare of the human participants in such research as well as scientific issues related to the role of such research in assessing risks. Society has responded to these concerns by defining general standards for conducting human research. In the United States, the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research issued in 1979 `` The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research.'' This document can be found on the web at http:// ohrp. osophs. dhhs. gov/ humansubjects/ guidance/ belmont. htm. For most federal agencies in the United States, the principles of the Belmont Report are implemented through the Common Rule, which was developed cooperatively by some 17 departments and agencies, including EPA, and which guides all research with human subjects conducted or supported by these departments and agencies of the federal government. The Common Rule as promulgated by EPA ( 40 CFR part 26) has guided human research conducted or supported by EPA since it was put in place in 1991. More broadly, the international medical research community has developed and maintains ethical standards documented in the Declaration of Helsinki, first issued by the World Medical Association in 1964 and revised several times since then. These standards apply to research on matters relating to the diagnosis and treatment of human disease, and to research that adds to understanding of the causes of disease and the biological mechanisms that explain the relationships between human exposures to environmental agents and disease. In addition, many public and private research and academic institutions and private companies, both in the United States and in other countries, including non federal U. S. and non U. S. governmental organizations, have their own specific policies related to the protection of human participants in research. Much of the scientific research supporting EPA's actions, including a significant portion of the research with human subjects submitted to the Agency or retrieved by the Agency from VerDate Jan< 31> 2003 16: 34 May 06, 2003 Jkt 200001 PO 00000 Frm 00030 Fmt 4702 Sfmt 4702 E:\ FR\ FM\ 07MYP1. SGM 07MYP1 24413 Federal Register / Vol. 68, No. 88 / Wednesday, May 7, 2003 / Proposed Rules published sources, is conducted by this broader research community, without direct participation or support by the U. S. government. Such research, referred to here as `` third party'' research, while it may be governed by specific institutional policies intended to protect research participants or may fall within the scope of the Declaration of Helsinki, is not subject to the Common Rule. In general, EPA cannot readily determine whether such policies are consistent with or as protective of human subjects as the Common Rule, nor the extent to which such policies or standards have been followed in the conduct of any particular study. Thus, even well conducted third party human studies may raise difficult questions for the Agency when it seeks to determine their acceptability for consideration.

B. Human Research Issues in EPA's Pesticide Program Questions about the Agency's consideration of and reliance on thirdparty human research studies have arisen most notably, but not exclusively, in EPA's pesticides program. Under the Federal Insecticide, Fungicide, and Rodenticide Act ( FIFRA), EPA may require pesticide companies to conduct studies with human subjects, for example, to measure potential exposure to pesticide users or to workers and others who re enter areas treated with pesticides, and to evaluate the effectiveness of pesticide products intended to repel insects and other pests from human skin. In addition, EPA sometimes encourages other research with human subjects, including tests of the potential for some pesticides generally those designed for prolonged contact with human skin to irritate or sensitize human skin, and tests of the metabolic fate of pesticides in the human system. These latter studies typically precede monitoring studies of agricultural workers and others to protect them from exposure to potentially dangerous levels of pesticide residues. In addition to these kinds of research which have been required or encouraged by EPA, other kinds of studies involving human subjects intentionally exposed to pesticides have occasionally been submitted to the agency voluntarily. Among these voluntarily submitted studies have been tests involving intentional dosing of human subjects to establish a No Observed Adverse Effect Level ( NOAEL) or No Observed Effect Level ( NOEL) for systemic toxicity of certain pesticides to humans. Before passage of the Food Quality Protection Act ( FQPA) in 1996, submission of such studies was rare. EPA considered and relied on human NOAEL/ NOEL studies in a few regulatory decisions on pesticides made prior to 1996. Since the passage of FQPA, submission of these types of studies to the Office of Pesticide Programs has increased; the Agency has received some 20 studies of this kind since 1996. In response to concerns about human testing expressed in a report of a nongovernmental advocacy organization, the Environmental Working Group, in July 1998, the Agency began a systematic review of its policy and practice. In a press statement on July 28, 1998, EPA noted that it had not relied on any such studies in any final decisions made under FQPA; this remains true today. In further response to growing public concern over pesticide research with human subjects, EPA convened an advisory committee under the joint auspices of the EPA Science Advisory Board ( SAB) and the FIFRA Scientific Advisory Panel ( SAP) to address issues of the scientific and ethical acceptability of such research. This advisory committee, known as the Data from Testing of Human Subjects Subcommittee ( DTHSS), met in December 1998 and November 1999, and completed its report in September 2000. Their report is available in the Docket cited above in this ANPR, and on the web at: http:// www. epa. gov/ science1/ pdf/ ec0017. pdf The DTHSS advisory committee heard many comments at their two public meetings, and further comments have been submitted in response to their published report. No clear consensus emerged from the advisory committee process on the acceptability of NOAEL or NOEL studies of systemic toxicity of pesticides to human subjects, and significant differences of opinion remain on both their scientific merit and ethical acceptability. A vigorous public debate continues about the extent to which EPA should accept, consider, or rely on third party intentional dosing human toxicity studies with pesticides.

C. EPA's Current Agency wide Focus on Human Research Issues EPA is now interested in addressing these issues more broadly, and in all Agency programs. In December 2001, EPA asked the advice of the National Academy of Sciences ( NAS) on the many difficult scientific and ethical issues raised by this debate, and also stated the Agency's interim approach on third party intentional dosing human subjects studies. The Agency's press release on this subject is on the web at http:// yosemite. epa. gov/ opa/ admpress. nsf/ b1ab9f485b098972 852562e7004dc686/ c232a45f5473 717085256b2200740ad4? OpenDocument. At that time the Agency committed that when it receives the NAS report, `` EPA will engage in an open and participatory process involving federal partners, interested parties and the public during its policy development and/ or rulemaking regarding future acceptance, consideration or regulatory reliance on such human studies.'' Since making that commitment, EPA has decided to initiate a rulemaking process by issuing this ANPR. In early 2002, various parties from the pesticide industry filed a petition with the U. S. Court of Appeals for the District of Columbia for review of EPA's December 2001 press release. These parties argued that the Agency's interim approach constituted a `` rule'' promulgated in violation of the procedural requirements of the Administrative Procedure Act and the Federal Food, Drug, and Cosmetic Act. The court has denied motions concerning emergency relief and other matters, briefs have been filed, and oral argument of the merits of the case occurred on March 17, 2003. Under a contract with EPA, the NAS has convened a committee to provide the requested advice. The committee met in December 2002, and again in January and March 2003. The membership, meeting schedule, and other information about the work of this committee can be found on the NAS website at: http:// www4. nas. edu/ webcr. nsf/ 5c50571a75df494485256a95007 a091e/ 9303f725c15902f685256c44005d8931? OpenDocument& Highlight= 0, EPA. The committee's final report is due in December 2003. Notwithstanding these many recent developments concerning human studies, some things have not changed. EPA remains committed to full compliance with the Common Rule for all research with human subjects conducted or supported by the Agency. This body of research has provided many important insights and has contributed significantly to the protection of human health. The Agency will continue to conduct and support such research, and to consider and rely on its results in Agency actions. EPA also remains committed to scientifically sound assessments of the hazards of environmental agents, taking into consideration available, relevant, and appropriate scientific research.

VerDate Jan< 31> 2003 16: 34 May 06, 2003 Jkt 200001 PO 00000 Frm 00031 Fmt 4702 Sfmt 4702 E:\ FR\ FM\ 07MYP1. SGM 07MYP1 24414 Federal Register / Vol. 68, No. 88 / Wednesday, May 7, 2003 / Proposed Rules III. EPA's Rulemaking Process and Request for Public Comment EPA intends to undertake notice andcomment rulemaking on the subject of its consideration of or reliance on research involving human subjects. The Agency will particularly focus on thirdparty intentional dosing human studies, but recognizes that the principles applicable to third party studies may also be relevant to studies conducted or supported by the federal government. The first step in this process is this ANPR which calls for comments and suggestions from all interested parties. The next step the Agency would expect to undertake would be to issue a proposed rule for public comment. In developing any proposed rule, EPA will consider the advice in the National Academy of Sciences committee report, along with comments received in response to this ANPR. Comments received on any proposed rule would then be taken into consideration in developing a final rule or policy. In general, the Agency expects that any rule or policy coming out of this process may do one or more of the following:   Specify, if and to the extent determined by EPA to be appropriate, whether EPA would accept, consider, or rely on results from particular types of studies involving intentional dosing of human subjects or from human studies with particular characteristics.   Establish minimum standards relating to the protection of human subjects which would be required to be met in the design and conduct of a study with human subjects, in order for EPA to accept, consider, or rely on the results of the study.   Establish procedures for ensuring that any minimum standards for the conduct of third party research with human subjects had been adhered to in the conduct of any such study that EPA intended to accept, consider, or rely on.

A. Legal Authority Section 25( a) of FIFRA gives the Administrator authority to `` prescribe regulations to carry out the purposes of [ FIFRA].'' Such a rule would implement EPA's authority to require data in support of registration of pesticides ( see, for example, FIFRA sections 3( c)( 1)( F) and 3( c)( 2)( B)) and to interpret the provision making it unlawful for any person `` to use any pesticide in tests on human beings unless such human beings ( i) are fully informed of the nature and purposes of the test and of any physical and mental health consequences which are reasonably foreseeable therefrom, and ( ii) freely volunteer to participate in the test.'' ( FIFRA section 12( a)( 2)( P)). In addition, section 408( e)( 1)( C) of the FFDCA authorizes the Administrator to issue a regulation establishing `` general procedures and requirements to implement this section.'' The Clean Air Act gives EPA general rulemaking authority in 42 U. S. C. 7601( a). The Clean Water Act, 33 U. S. C. 1361, authorizes the Administrator to promulgate regulations necessary to carry out the Agency's functions under that Act. Section 42 U. S. C. 9615 in the Comprehensive Environmental Response, Compensation, and Liability Act authorizes the President to establish regulations to implement the statute; this authority has been delegated to EPA by Executive Order 12580. The Emergency Planning and Community Right to Know Act also contains a general rulemaking provision, 42 U. S. C. 11048, authorizing the Administrator to promulgate rules necessary to carry out the Act. The Resource Conservation and Recovery Act specifically authorizes the Administrator to prescribe regulations necessary to carry out EPA's functions under the Act, 42 U. S. C. 6912. The Safe Drinking Water Act contains similar language, authorizing the Administrator to prescribe such regulations `` as are necessary and appropriate'' to carry out EPA's functions under the Act, 42 U. S. C. 300j 9. In addition, EPA has authority under 5 U. S. C. 301 and 42 U. S. C. 300v 1( b).

B. Request for Comments Neither this ANPR nor the specific questions presented below for public comment are intended to indicate that EPA now favors any particular policy approaches regarding the Agency's consideration of or reliance on thirdparty intentional dosing human studies. Similarly, neither this ANPR nor the specific questions presented below for public comment are intended to indicate that EPA has decided on a particular scope for any potential future rulemaking. Nor is this ANPR intended to impede or otherwise delay any Agency assessments or actions. Rather, this ANPR is designed to encourage public input from all interested parties on a broad range of issues that could help inform any rule or policy that EPA eventually promulgates or issues, respectively. The Agency fully appreciates the number, the range, and the interconnectedness of the scientific and ethical concerns raised especially by intentional dosing human studies of the wide range of environmental agents addressed by EPA's programs. Reflecting the breadth of issues that have been raised, the Agency has identified specific questions on which it particularly invites comment. These questions are intended to help organize and focus the discussion, but not to constrain it. Commenters should feel free to address any other relevant topics as well. 1. Applicability of existing standards   a. Is it appropriate to use a standard intended to guide the conduct of research ( e. g., the Common Rule, Declaration of Helsinki, or the Nuremberg Code) to assess the acceptability for review of completed research? b. Is it appropriate to use a standard intended to guide the conduct of therapeutic or diagnostic medical research or to clarify causes of disease, such as the Declaration of Helsinki, to assess the acceptability for review of other kinds of research without diagnostic or therapeutic intent, conducted with healthy subjects? c. Should the Agency apply the same standard of acceptability independent of the type of substance tested ( e. g., pharmaceutical, pesticide, pathogen, or environmental contaminant)? If not, how might differing standards be applied when a single substance has multiple uses, e. g., as both a pesticide and a drug? d. Does it matter who maintains a standard, or by what process it is maintained? For example, would it be appropriate for EPA to accept and apply a standard maintained by a private, nongovernmental organization, as is the Declaration of Helsinki? e. Should the Agency extend the requirements of the Common Rule to the conduct of third party research with human subjects intended for submission to EPA? What are the advantages and disadvantages of conducting a rulemaking or undertaking other Agency action for this purpose alone? 2. Should the standard of acceptability vary depending on the research design?   a. Should the Agency apply the same standard of acceptability independent of whether the research design involves intentional exposure? For example, should the same standard apply to research involving intentional exposures to human subjects, to research designed to follow up accidental exposure, and to studies of individuals occupationally or incidentally exposed? b. Should the Agency apply the same standard of acceptability independent of the level of exposure of the human subjects? For example, does it matter if the level of exposure to a chemical is below the Reference Dose or other established health standard designed to VerDate Jan< 31> 2003 16: 34 May 06, 2003 Jkt 200001 PO 00000 Frm 00032 Fmt 4702 Sfmt 4702 E:\ FR\ FM\ 07MYP1. SGM 07MYP1 24415 Federal Register / Vol. 68, No. 88 / Wednesday, May 7, 2003 / Proposed Rules protect the general public? Should the same standard apply if intentional exposure to an environmental pollutant occurs at ambient levels, or at elevated levels? If research involves intentional exposure to a pesticide, does it matter if exposure results from use of the pesticide in conformity with approved label directions? c. Should the Agency apply the same standard of acceptability independent of the pathway of exposure? For example, should the same standard apply when exposure is oral, or dermal, or by inhalation? d. Should the Agency apply the same standard of acceptability independent of the effects being evaluated? For example, should the same standard apply to a study measuring transitory changes in blood chemistry or levels of a substance in urine that applies to studies measuring longer lasting changes? Should the same standard apply to a study of localized skin irritation that applies to a study of systemic dermal toxicity? Should the same standard apply to studies measuring organoleptic effects, such as taste or smell, that applies to studies of toxic effects? Should the same standard apply to measurements of toxic effects and to measurements through genomic or proteomic assessments? e. Should conduct of research in compliance with the provisions of the Common Rule or another standard for the protection of human subjects be accepted as evidence of its ethical acceptability? f. Should the Agency consider whether research has been performed consistent with an EPA guideline for data development in determining its acceptability? For example, EPA has published guidelines for certain kinds of human studies required for pesticide registration; should conduct of a required study in compliance with an EPA guideline be accepted as evidence of its acceptability? g. Should the Agency apply the same standard of acceptability independent of a study's statistical power? h. Should the Agency apply the same standard of acceptability whether or not a human study design is able to measure the same endpoints in humans that have been observed in animal testing of the same substance? For example, if the most sensitive adverse effects shown in animal studies have been detected through histopathological evaluation of brain tissue, is subsequent research involving intentional exposure of human subjects acceptable? i. Should the Agency apply the same standard of acceptability to intentional dosing studies independent of whether there are alternative methods of obtaining data of comparable scientific merit that would not require deliberate exposure of humans? If not, to what extent, if any, should the cost of the alternate method be a factor? j. What special considerations, if any, should the Agency apply in judging the acceptability of studies when some or all of the subjects are from populations likely to be vulnerable to coercion or undue influence, such as children, prisoners, pregnant women, mentally disabled persons, or economically or educationally disadvantaged persons? 3. Should the standard of acceptability vary depending on the provenance of the research?   a. Should the Agency apply the same standard of acceptability without regard to who or what organization sponsors or supports the research? Since 1991, human research conducted or supported by the U. S. government has been subject to the Common Rule. Should the same standard apply to research conducted or supported by others? Should a single standard apply independent of whether the sponsor is a commercial enterprise, a non profit organization, another government in the United States ( such as state, tribal, or local), or the government in another country? Should the same standard apply without regard to the test sponsor's interest in a regulatory matter that could be affected by EPA's consideration of the data? b. Should the Agency apply the same standard of acceptability independent of who or what organization conducts the research? For example, a research organization public or private holding a `` Federal Wide Assurance'' from the Department of Health and Human Services's Office of Human Research Protections usually promises to comply with the Common Rule in all its human research. Should third party work conducted by a research organization holding a Federal Wide Assurance be assessed by the same standard that applies to other third party human research? c. Should the Agency apply the same standard of acceptability without regard to where the research was conducted? For example, does it matter whether research is conducted entirely in the United States or partially in the United States? If it is conducted outside the United States, does it matter in what country it is conducted? What are the advantages and disadvantages of judging the acceptability of human studies based on a single uniform standard versus prevailing local standards ( e. g., in different countries)? d. Should the Agency apply the same standard of acceptability without regard to the reasons the research was conducted? If not, how might the Agency determine intent? e. Should the Agency apply the same standard of acceptability to submitted research without regard to who submitted it? For example, should the same standard apply to submissions from regulated industry, from public interest groups, from the public, or from other governments? Should the Agency apply the same standard of acceptability independent of whether the study was submitted voluntarily, or in response to a particular regulatory requirement of EPA? f. Should the Agency apply the same standard of acceptability to human research which is not submitted, but which the Agency obtains at its own initiative from the scientific literature or other sources, independent of how or where EPA obtains it? 4. Should the standard of acceptability vary depending on EPA's potential use of the data?   a. Should the Agency apply the same standard of acceptability independent of whether the results of the study would support a more or less stringent regulatory position? For example, should the same standard apply whether the data indicate that the substance tested is more risky or less risky than is indicated by other available data? b. Should the Agency apply the same standard of acceptability without regard to how EPA intends to use the results, e. g., to reduce or remove the traditional tenfold interspecies uncertainty factor, to provide an endpoint for use in calculating a Reference Dose or Reference Concentration for the test substance, to provide a dose response function for use in quantitative risk assessment, or for some other purpose? 5. Should the standard of acceptability vary depending on EPA's assessment of the risks and benefits of the research to the subjects or to society?   a. Should the Agency apply a standard of acceptability based on a comparison of the anticipated benefits of the research in relation to the risks to human subjects, provided the risks are minimized and informed consent is obtained? b. Should the Agency independently assess the risks of the research to the subjects and the benefits of the research to the research subjects or to society, or should it defer to the judgment of Institutional Review Boards or similar oversight panels? c. If EPA were to assess independently the risks and benefits of human research, on what range of information should it base its assessment? How might EPA obtain VerDate Jan< 31> 2003 16: 34 May 06, 2003 Jkt 200001 PO 00000 Frm 00033 Fmt 4702 Sfmt 4702 E:\ FR\ FM\ 07MYP1. SGM 07MYP1 24416 Federal Register / Vol. 68, No. 88 / Wednesday, May 7, 2003 / Proposed Rules information relevant to such an assessment? 6. How should the Agency implement standards of acceptability?   a. To what extent and how should the submitter of research with human subjects to EPA be required to document or otherwise demonstrate compliance with appropriate standards for the protection of human research subjects, e. g., fully informed and fully voluntary participation, and independent oversight of research design and conduct by an Institutional Review Board or comparable entity? b. How should the Agency determine compliance with an appropriate standard for human research data which is not submitted, but which it obtains from the scientific literature or other sources? c. To what extent should new standards be applied to research which has already been conducted, or is underway? Should a different standard be applied to such research? Does fairness require a period of transition to any new rule or standards of acceptability, or do other considerations override that factor? d. Should the Agency apply the same standard of acceptability to research already submitted to or obtained by EPA and to research newly submitted to or obtained by EPA? Does it matter if the submitted research was conducted for the specific regulatory purpose at hand or for other purposes ( even though the study was conducted after EPA issued a policy on human testing)? Does fairness require a period of transition to any new rule or standards of acceptability, or do other considerations override that factor? e. Is rulemaking needed at all? Would it be better to address the issues surrounding acceptance of human research, or some of them, by other means, such as policy statements or internal guidelines?

IV. Statutory and Executive Order Reviews Under Executive Order 12866, entitled Regulatory Planning and Review ( 58 FR 51735, October 4, 1993), it has been determined that this ANPR is a `` significant regulatory action'' under section 3( f) of the Executive Order. The Agency therefore submitted this document to OMB for the 10   day review period afforded under this Executive Order. Any changes made in response to OMB comments during that review have been documented in the public docket as required by the Executive Order. Since this ANPR does not impose any requirements, and instead seeks comments and suggestions for the Agency to consider in developing a subsequent notice of proposed rulemaking, the various other review requirements that apply when an agency imposes requirements do not apply to this action. As part of your comments on this ANPR you may include any comments or information that you have regarding these requirements. In particular, any comments or information that would help the Agency to assess the potential impact of a rule on small entities pursuant to the Regulatory Flexibility Act ( RFA) ( 5 U. S. C. 601 et seq.); to consider voluntary consensus standards pursuant to section 12( d) of the National Technology Transfer and Advancement Act of 1995 ( NTTAA), Public Law 104   113, section 12( d) ( 15 U. S. C. 272 note); or to consider environmental health or safety effects on children pursuant to Executive Order 13045, entitled Protection of Children from Environmental Health Risks and Safety Risks ( 62 FR 19885, April 23, 1997). The Agency will consider such comments during the development of any subsequent notice of proposed rulemaking as it takes appropriate steps to address any applicable requirements.

List of Subjects Environmental protection, Protection of human research subjects.

Dated: April 29, 2003. Christine T. Whitman, Administrator.

[ FR Doc. 03   11002 Filed 5   6   03; 8: 45 am]

BILLING CODE 6560   50   S ENVIRONMENTAL PROTECTION AGENCY 40 CFR Part 52 [ MD136   3091b; FRL   7484   1]

Approval and Promulgation of Air Quality Implementation Plans; Maryland; Amendments to State II Vapor Recovery at Gasoline Dispensing Facilities AGENCY: Environmental Protection Agency ( EPA). ACTION: Proposed rule.

SUMMARY: EPA proposes to approve the State Implementation Plan ( SIP) revision submitted by the State of Maryland for the purpose of amending the regulations pertaining to Stage II Vapor Recovery at Gasoline Dispensing Stations. In the Final Rules section of this Federal Register, EPA is approving the State's SIP submittal as a direct final rule without prior proposal because the Agency views this as a noncontroversial submittal and anticipates no adverse comments. A detailed rationale for the approval is set forth in the direct final rule. If no adverse comments are received in response to this action, no further activity is contemplated. If EPA receives adverse comments, the direct final rule will be withdrawn and all public comments received will be addressed in a subsequent final rule based on this proposed rule. EPA will not institute a second comment period. Any parties interested in commenting on this action should do so at this time.

DATES: Comments must be received in writing by June 6, 2003.

ADDRESSES: Written comments should be addressed to Makeba Morris, Acting Chief, Air Quality Planning and Information Services Branch, Mailcode 3AP21, U. S. Environmental Protection Agency, Region III, 1650 Arch Street, Philadelphia, Pennsylvania 19103. Copies of the documents relevant to this action are available for public inspection during normal business hours at the Air Protection Division, U. S. Environmental Protection Agency, Region III, 1650 Arch Street, Philadelphia, Pennsylvania 19103; and the Maryland Department of the Environment, 1800 Washington Boulevard, Suite 705, Baltimore, Maryland 21230.

FOR FURTHER INFORMATION CONTACT: Kathleen Anderson, ( 215) 814   2173, or by e mail at anderson. kathleen@ epa. gov.

SUPPLEMENTARY INFORMATION: For further information, please see the information provided in the direct final action, with the same title, that is located in the `` Rules and Regulations'' section of this Federal Register publication. Please note that if EPA receives adverse comment on an amendment, paragraph, or section of this rule and if that provision may be severed from the remainder of the rule, EPA may adopt as final those provisions of the rule that are not the subject of an adverse comment.

Dated: April 9, 2003.

James W. Newsom,

Regional Administrator, Region III. [ FR Doc. 03   11184 Filed 5   6   03; 8: 45 am]

BILLING CODE 6560   50   P VerDate Jan< 31> 2003 16: 34 May 06, 2003 Jkt 200001 PO 00000 Frm 00034 Fmt 4702 Sfmt 4702 E:\ FR\ FM\ 07MYP1. SGM 07MYP1


[Federal Register: April 10, 2007 (Volume 72, Number 68)]
[Notices]
[Page 17892-17893]
[DOCID:fr10ap07-70]

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ENVIRONMENTAL PROTECTION AGENCY

[EPA-HQ-OECA-2006-0720; FRL-8296-9]

Agency Information Collection Activities; Submission To OMB for
Review and Approval; Comment Request; NESHAP for Off-Site Waste and
Recovery Operations (Renewal), EPA ICR Number 1717.05, OMB Control
Number 2060-0313

AGENCY: Environmental Protection Agency (EPA).

ACTION: Notice.

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SUMMARY: In compliance with the Paperwork Reduction Act (44 U.S.C. 3501
et seq.), this document announces that an Information Collection
Request (ICR) has been forwarded to the Office of Management and Budget
(OMB) for review and approval. This is a request to renew an existing
approved collection. This ICR is scheduled to expire on May 31, 2007.
Under OMB regulations, the Agency may continue to conduct or sponsor
the collection of information while this submission is pending at OMB.
This ICR describes the nature of the information collection and its
estimated burden and cost.

DATES: Additional comments may be submitted on or before May 10, 2007.

ADDRESSES: Submit your comments, referencing docket ID number EPA-HQ-
OECA-2006-0720, to (1) EPA online using http://www.regulations.gov (our preferred method), by e-mail to<EMAIL_ADDRESS>or by mail to: EPA

Docket Center (EPA/DC), Environmental Protection Agency, Enforcement
and Compliance Docket and Information Center, Mail Code 2201T, 1200
Pennsylvania Avenue, NW., Washington, DC 20460, and (2) OMB at: Office
of Information and Regulatory Affairs, Office of Management and Budget
(OMB), Attention: Desk Officer for EPA, 725 17th Street, NW.,
Washington, DC 20503.

FOR FURTHER INFORMATION CONTACT: Learia Williams, Compliance Assessment
and Media Programs Division, Office of Compliance, Mail Code 2223A,
Environmental Protection Agency, 1200 Pennsylvania Avenue, NW.,
Washington, DC 20460; telephone number:<PHONE_NUMBER>; fax number:
(202) 564-0050; e-mail address<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: EPA has submitted the following ICR to OMB
for review and approval according to the procedures prescribed in 5 CFR
1320.12. On October 6, 2006 (71 FR 58853), EPA sought comments on this
ICR pursuant to 5 CFR 1320.8(d). EPA received no comments.
    EPA has established a public docket for this ICR under Docket ID
Number EPA-HQ-OECA-2006-0720, which is available for online viewing at
http://www.regulations.gov, or in person viewing at the Enforcement and

Compliance Docket and Information Center in the EPA Docket Center (EPA/
DC), EPA West, Room 3334, 1301 Constitution Avenue, NW., Washington,
DC. The EPA Docket Center Public Reading Room is open from 8:30 a.m. to
4:30 p.m., Monday through Friday,

excluding legal holidays. The telephone number for the Reading Room is
(202) 566-1744, and the telephone number for the Enforcement and
Compliance Docket Center is<PHONE_NUMBER>.
    Use EPA's electronic docket and comment system at http://www.epa.gov
, to submit or view public comments, access the index

listing of the contents of the docket, and to access those documents in
the docket that are available electronically. Once in the system,
select ``docket search, then key in the docket ID number identified
above. Please note that EPA's policy is that public comments, whether
submitted electronically or in paper, will be made available for public
viewing at http://www.regulations.gov, as EPA receives them and without

change, unless the comment contains copyrighted material, CBI, or other
information whose public disclosure is restricted by statute. For
further information about the electronic docket, go to http://www.regulations.gov
.

    Title: NESHAP for Off-Site Waste and Recovery Operations (Renewal).
    ICR Numbers: EPA ICR Number 1717.05; OMB Control Number 2060-0313.
    ICR Status: This ICR is scheduled to expire on May 31, 2007. Under
OMB regulations, the Agency may continue to conduct or sponsor the
collection of information while this submission is pending at OMB. An
Agency may not conduct or sponsor, and a person is not required to
respond to, a collection of information unless it displays a currently
valid OMB control number. The OMB control numbers for EPA's regulations
in title 40 of the CFR, after appearing in the Federal Register when
approved, are listed in 40 CFR part 9, are displayed either by
publication in the Federal Register or by other appropriate means, such
as on the related collection instrument or form, if applicable. The
display of OMB control numbers in certain EPA regulations is
consolidated in 40 CFR part 9.
    Abstract: The National Emission Standards for Hazardous Air
Pollutants (NESHAP) for Off-Site Waste and Recovery Operations (40 CFR
part 63, subpart DD) were proposed on October 13, 1994, and promulgated
on July 1, 1996. These standards apply to hazardous air pollutants
(HAP) emissions from selected facilities involved in waste management
and recovery operations that are not subject to Federal air standards
under other subparts in part 63 commencing construction, modification
or reconstruction after the date of proposal if the facility is a
``major source'' of HAP emissions as defined in general provisions to
40 CFR part 63 or the facility has the potential to emit more than 10
tons per year for a single HAP or more than 25 tons per year for
multiple HAP. In addition, subpart DD cross-references control
requirements to be applied to specific types of affected sources:
tanks-level 1, containers, surface impoundments, individual drain
systems, oil-water separators and organic water separators, loading,
transfer, and storage systems. This information is being collected to
assure compliance with 40 CFR part 63, subpart DD. Organic HAP
emissions are the pollutants regulated under this subpart.
    Owners or operators of the affected facilities described must make
one-time-only notifications. Owners or operators are also required to
maintain records of the occurrence and duration of any startup,
shutdown, or malfunction in the operation of an affected facility, or
any period during which the monitoring system is inoperative.
Semiannual reports of excess emissions (or reports certifying that no
exceedances have occurred) are required. These notifications, reports,
and records are essential in determining compliance; and are required,
in general, of all sources subject to NESHAP.
    Any owner or operator subject to the provisions of this part shall
maintain a file of these measurements, and retain the file for at least
five years following the date of such measurements, maintain reports,
and records. All reports are sent to the delegated state or local
authority. In the event that there is no such delegated authority, the
reports are sent directly to the EPA regional office. This information
is being collected to assure compliance with 40 CFR part 63, subpart DD
as authorized in section 112 and 114(a) of the Clean Air Act. The
required information consists of emissions data and other information
that have been determined not to be private.
    An agency may not conduct or sponsor, and a person is not required
to respond to, a collection of information unless it displays a
currently valid OMB Control Number. The OMB control numbers for EPA's
regulations are listed in 40 CFR part 9 and 48 CFR chapter 15, and are
identified on the form and/or instrument, if applicable.
    Burden Statement: The annual public reporting and recordkeeping
burden for this collection of information is estimated to average
approximately 218 hours per response. Burden means the total time,
effort, or financial resources expended by persons to generate,
maintain, retain, or disclose or provide information to or for a
Federal agency. This includes the time needed to review instructions;
develop, acquire, install, and utilize technology and systems for the
purposes of collecting, validating, and verifying information,
processing and maintaining information, and disclosing and providing
information; adjust the existing ways to comply with any previously
applicable instructions and requirements; train personnel to be able to
respond to a collection of information; search data sources; complete
and review the collection of information; and transmit or otherwise
disclose the information.
    Respondents/Affected Entities: Off-Site Waste and Recovery
Operations.
    Estimated Number of Respondents: 236.
    Frequency of Response: Initially, on occasion, and semiannually.
    Estimated Total Annual Hour Burden: 154,306 hours.
    Estimated Total Costs: $9,928,473, which includes $0 annualized
Capital Startup Costs, $5,000 annualized Operations & Maintenance (O&M)
Costs and $9,923,473 annualized labor costs.
    Changes in the Estimates: There is no change in the labor hours in
this ICR compared to the previous ICR. This is due to two
considerations. First, the regulations have not changed over the past
three years and are not anticipated to change over the next three
years. Secondly, the growth rate for the industry is very low, negative
or non-existent, so there is no significant change in the overall
burden. There is a $5,000 correction to the burden cost to cover
operations and maintenance costs for photocopying and postage which
were not included in the previous ICR approval.

    Dated: April 2, 2007.
Robert Gunter,
Acting Director, Collection Strategies Division.
[FR Doc. E7-6708 Filed 4-9-07; 8:45 am]

BILLING CODE 6560-50-P


[Federal Register Volume 81, Number 244 (Tuesday, December 20, 2016)]
[Notices]
[Pages 92832-92833]
[FR Doc No: 2016-30528]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2016-E-0626]

Determination of Regulatory Review Period for Purposes of Patent
Extension; COSENTYX

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) has determined the
regulatory review period for COSENTYX 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 the U.S.
Patent and Trademark Office (USPTO), Department of Commerce, for the
extension of a patent which claims that human biological product.

DATES: Anyone with knowledge that any of the dates as published (see
the SUPPLEMENTARY INFORMATION section) are incorrect may submit either
electronic or written comments and ask for a redetermination by
February 21, 2017. 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 June 19,
2017. See ``Petitions'' in the SUPPLEMENTARY INFORMATION section for
more information.

ADDRESSES: You may submit comments as follows:

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments. Comments submitted
electronically, including attachments, to http://www.regulations.gov
will be posted to the docket unchanged. Because your comment will be
made public, you are solely responsible for ensuring that your comment
does not include any confidential information that you or a third party
may not wish to be posted, such as medical information, your or anyone
else's Social Security number, or confidential business information,
such as a manufacturing process. Please note that if you include your
name, contact information, or other information that identifies you in
the body of your comments, that information will be posted on http://www.regulations.gov.
     If you want to submit a comment with confidential
information that you do not wish to be made available to the public,
submit the comment as a written/paper submission and in the manner
detailed (see ``Written/Paper Submissions'' and ``Instructions'').

Written/Paper Submissions

    Submit written/paper submissions as follows:
     Mail/Hand delivery/Courier (for written/paper
submissions): Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
     For written/paper comments submitted to the Division of
Dockets Management, FDA will post your comment, as well as any
attachments, except for information submitted, marked and identified,
as confidential, if submitted as detailed in ``Instructions.''
    Instructions: All submissions received must include the Docket No.
FDA-2016-E-0626 for ``Determination of Regulatory Review Period for
Purposes of Patent Extension; COSENTYX.'' Received comments will be
placed in the docket and, except for those submitted as ``Confidential
Submissions,'' publicly viewable at http://www.regulations.gov or at
the Division of Dockets Management between 9 a.m. and 4 p.m., Monday
through Friday.
     Confidential Submissions--To submit a comment with
confidential information that you do not wish to be made publicly
available, submit your comments only as a written/paper

submission. You should submit two copies total. One copy will include
the information you claim to be confidential with a heading or cover
note that states ``THIS DOCUMENT CONTAINS CONFIDENTIAL INFORMATION.''
The Agency will review this copy, including the claimed confidential
information, in its consideration of comments. The second copy, which
will have the claimed confidential information redacted/blacked out,
will be available for public viewing and posted on http://www.regulations.gov. Submit both copies to the Division of Dockets
Management. If you do not wish your name and contact information to be
made publicly available, you can provide this information on the cover
sheet and not in the body of your comments and you must identify this
information as ``confidential.'' Any information marked as
``confidential'' will not be disclosed except in accordance with 21 CFR
10.20 and other applicable disclosure law. For more information about
FDA's posting of comments to public dockets, see 80 FR 56469, September
18, 2015, or access the information at: http://www.fda.gov/regulatoryinformation/dockets/default.htm.
    Docket: For access to the docket to read background documents or
the electronic and written/paper comments received, go to http://www.regulations.gov and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Division of Dockets Management, 5630 Fishers
Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Beverly Friedman, Office of Regulatory
Policy, Food and Drug Administration, 10903 New Hampshire Ave., Bldg.
51, Rm. 6250, Silver Spring, MD 20993,<PHONE_NUMBER>.

SUPPLEMENTARY INFORMATION:

I. Background

    The Drug Price Competition and Patent Term Restoration Act of 1984
(Pub. L. 98-417) and the Generic Animal Drug and Patent Term
Restoration Act (Pub. L. 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 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 USPTO 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 has approved for marketing the human biologic product COSENTYX
(secukinumab). COSENTYX is indicated for treatment of moderate to
severe plaque psoriasis in adult patients who are candidates for
systemic therapy or phototherapy. Subsequent to this approval, the
USPTO received a patent term restoration application for COSENTYX (U.S.
Patent No. 7,807,155) from Novartis AG, and the USPTO requested FDA's
assistance in determining this patent's eligibility for patent term
restoration. In a letter dated May 2, 2016, FDA advised the USPTO that
this human biological product had undergone a regulatory review period
and that the approval of COSENTYX represented the first permitted
commercial marketing or use of the product. Thereafter, the USPTO
requested that FDA determine the product's regulatory review period.

II. Determination of Regulatory Review Period

    FDA has determined that the applicable regulatory review period for
COSENTYX is 3,381 days. Of this time, 2,926 days occurred during the
testing phase of the regulatory review period, while 455 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: October 21,
2005. The applicant claims December 17, 2006, as the date the
investigational new drug application (IND) became effective. However,
FDA records indicate that the IND effective date was October 21, 2005,
which was thirty days after FDA receipt of an earlier 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): October 24, 2013. FDA has verified the
applicant's claim that the biologics license application (BLA) for
COSENTYX (BLA 125504/0) was initially submitted on October 24, 2013.
    3. The date the application was approved: January 21, 2015. FDA has
verified the applicant's claim that BLA 125504/0 was approved on
January 21, 2015.
    This determination of the regulatory review period establishes the
maximum potential length of a patent extension. However, the USPTO
applies several statutory limitations in its calculations of the actual
period for patent extension. In its application for patent extension,
this applicant seeks 629 days of patent term extension.

III. Petitions

    Anyone with knowledge that any of the dates as published are
incorrect may submit either electronic or written comments and ask for
a redetermination (see DATES). 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.
To meet its burden, the petition must be timely (see DATES) and 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.
    Submit petitions electronically to http://www.regulations.gov at
Docket No. FDA-2013-S-0610. Submit written petitions (two copies are
required) to the Division of Dockets Management (HFA-305), Food and
Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

    Dated: December 14, 2016.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2016-30528 Filed 12-19-16; 8:45 am]
 BILLING CODE 4164-01-P


[Federal Register Volume 77, Number 18 (Friday, January 27, 2012)]
[Rules and Regulations]
[Page 4225]
[FR Doc No: 2012-1744]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 520

[Docket No. FDA-2011-N-0003]

Oral Dosage Form New Animal Drugs; Milbemycin Oxime, Lufenuron,
and Praziquantel

AGENCY: Food and Drug Administration, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA) is amending the animal
drug regulations to reflect approval of a new animal drug application
(NADA) filed by Novartis Animal Health US, Inc. The NADA provides for
the veterinary prescription use of milbemycin oxime, lufenuron, and
praziquantel for the prevention of heartworm disease, for prevention
and control of fleas, and for the treatment and control of various
internal parasites in dogs.

DATES: This rule is effective January 27, 2012.

FOR FURTHER INFORMATION CONTACT: Steven Fleischer, Center for
Veterinary Medicine (HFV-110), Food and Drug Administration, 7500
Standish Pl., Rockville, MD 20855,<PHONE_NUMBER>, email:
<EMAIL_ADDRESS>
SUPPLEMENTARY INFORMATION: Novartis Animal Health US, Inc., 3200
Northline Ave., Suite 300, Greensboro, NC 27408, filed NADA 141-333
that provides for the veterinary prescription use of SENTINEL SPECTRUM
(milbemycin oxime/lufenuron/praziquantel) Tablets for the prevention of
heartworm disease, for the prevention and control of flea populations,
and for the treatment and control of adult roundworm, adult hookworm,
adult whipworm, and adult tapeworm infections in dogs and puppies 2
pounds of body weight or greater and 6 weeks of age and older. The NADA
is approved as of December 8, 2011, and 21 CFR part 520 is amended by
adding new Sec.  520.1447 to reflect the approval.
    A summary of safety and effectiveness data and information
submitted to support approval of this application may be seen in the
Division of Dockets Management (HFA-305), Food and Drug Administration,
5630 Fishers Lane, Rm. 1061, Rockville, MD 20852, between 9 a.m. and 4
p.m., Monday through Friday.
    Under section 512(c)(2)(F)(ii) of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 360b(c)(2)(F)(ii)), this approval qualifies for
3 years of marketing exclusivity beginning on the date of approval.
    The Agency has determined under 21 CFR 25.33 that this action is of
a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
    This rule does not meet the definition of ``rule'' in 5 U.S.C.
804(3)(A) because it is a rule of ``particular applicability.''
Therefore, it is not subject to the congressional review requirements
in 5 U.S.C. 801-808.

List of Subjects in 21 CFR Part 520

    Animal drugs.

    Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs and
redelegated to the Center for Veterinary Medicine, 21 CFR part 520 is
amended as follows:

PART 520--ORAL DOSAGE FORM NEW ANIMAL DRUGS

0
1. The authority citation for 21 CFR part 520 continues to read as
follows:

    Authority: 21 U.S.C. 360b.

0
2. Add Sec.  520.1447 to read as follows:

Sec.  520.1447  Milbemycin oxime, lufenuron, and praziquantel tablets.

    (a) Specifications. Each tablet contains:
    (1) 2.3 milligrams (mg) milbemycin oxime, 46 mg lufenuron, and 22.8
mg praziquantel;
    (2) 5.75 mg milbemycin oxime, 115 mg lufenuron, and 57 mg
praziquantel;
    (3) 11.5 mg milbemycin oxime, 230 mg lufenuron, and 114 mg
praziquantel; or
    (4) 23 mg milbemycin oxime, 460 mg lufenuron, and 228 mg
praziquantel.
    (b) Sponsor. See No. 058198 in Sec.  510.600(c) of this chapter.
    (c) [Reserved]
    (d) Conditions of use--(1) Dogs--(i) Amount. 0.5 mg milbemycin
oxime, 10 mg lufenuron, and 5 mg of praziquantel per kilogram of body
weight, once a month.
    (ii) Indications for use. For the prevention of heartworm disease
caused by Dirofilaria immitis; for the prevention and control of flea
populations (Ctenocephalides felis); and for the treatment and control
of adult roundworm (Toxocara canis, Toxascaris leonina), adult hookworm
(Ancylostoma caninum), adult whipworm (Trichuris vulpis), and adult
tapeworm (Taenia pisiformis, Echinococcus multilocularis, and E.
granulosus) infections in dogs and puppies 2 pounds of body weight or
greater and 6 weeks of age and older.
    (iii) Limitations. Federal law restricts this drug to use by or on
the order of a licensed veterinarian.
    (2) [Reserved]

    Dated: January 23, 2012.
William T. Flynn,
Acting Director, Center for Veterinary Medicine.
[FR Doc. 2012-1744 Filed 1-26-12; 8:45 am]
BILLING CODE 4160-01-P