Department of Health and Human Services March 2008 – Federal Register Recent Federal Regulation Documents

In accordance with section 205 of the Health Insurance Portability and Accountability Act of 1996, this final rule amends the OIG regulations at 42 CFR part 1008 by (1) revising the process for advisory opinion requestors to submit payments for advisory opinion costs, and (2) clarifying that notices to the public announcing procedures for processing advisory opinion requests will be published on OIG's Web site.

The Food and Drug Administration (FDA) is amending its civil money penalties regulations to correct an inadvertent typographical error. This action is editorial in nature and is intended to improve the accuracy of the agency's regulations.

The Food and Drug Administration (FDA) is amending the animal drug regulations to reflect approval of a new animal drug application (NADA) filed by Alpharma, Inc. The NADA provides for use of approved, single-ingredient Type A medicated articles containing bacitracin methylene disalicylate and nicarbazin to formulate two-way combination drug Type C medicated feeds for broiler chickens.

The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed collection of certain information by the agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on requirements related to the recall of infant formula.

The Food and Drug Administration (FDA) is announcing an opportunity for public comment on the proposed collection of certain information by the agency. Under the Paperwork Reduction Act of 1995 (the PRA), Federal agencies are required to publish notice in the Federal Register concerning each proposed collection of information, including each proposed extension of an existing collection of information, and to allow 60 days for public comment in response to the notice. This notice solicits comments on information collection provisions relating to FDA's electronic records and electronic signatures.

The Food and Drug Administration (FDA) is announcing a public meeting entitled ``Preparation for ICH Meetings in Portland, Oregon'' to provide information and receive comments on the International Conference on Harmonization (ICH) as well as the upcoming meetings in Portland, Oregon. The topics to be discussed are the topics for discussion at the forthcoming ICH Steering Committee Meeting. The purpose of the meeting is to solicit public input prior to the next Steering Committee and Expert Working Groups meetings in Portland, Oregon, June 2-5, 2008, at which discussion of the topics underway and the future of ICH will continue. Date and Time: The meeting will be held on Friday April 4, 2008, from 12:30 pm to 5 p.m. Location: The meeting will be held at 5600 Fishers Lane, 3rd floor, Conference Room G and H, Rockville, MD 20857. For security reasons, all attendees are asked to arrive no later than 12:25 p.m., as you will be escorted from the front entrance of 5600 Fishers Lane to Conference Room G and H. Contact Person: All participants must register with Tammie Bell, Office of the Commissioner, Food and Drug Administration, 5600 Fishers Lane, Rockville, MD 20857, by e-mail: Tammie.bell@fda.hhs.gov or FAX: 301-480-0003. Registration and Requests for Oral Presentations: Send registration information (including name, title, firm name, address, telephone, and fax number), written material, and requests to make oral presentations, to the contact person by April 3, 2008. If you need special accommodations due to a disability, please contact Tammie Bell at least 7 days in advance.

NICEATM announces availability of the ICCVAM Test Method Evaluation Report: In Vitro Cytotoxicity Test Methods for Estimating Starting Doses for Acute Oral Systemic Toxicity Tests (NIH Publication 07-4519). The report describes two in vitro basal cytotoxicity neutral red uptake (NRU) test methods that can be used for estimating starting doses for acute oral toxicity tests. The report includes ICCVAM's (a) final test method recommendations on the use of these two test methods, (b) recommended test method protocols for future use, (c) recommendations for future studies to further characterize the usefulness and limitations of in vitro methods for assessing acute systemic toxicity, and (d) recommended performance standards for tests with similar scientific principles and that measure or predict acute oral systemic toxicity. The report recommends the use of these methods in a weight-of-evidence approach to determine starting doses for acute oral systemic toxicity tests with rodents. The report also recommends that these in vitro test methods be considered before using animals for acute oral systemic toxicity testing and used when determined appropriate. NICEATM also announces the availability of the final Background Review Document: In Vitro Cytotoxicity Test Methods for Estimating Acute Oral Systemic Toxicity (BRD) (NIH Publication 07-4518). The BRD provides data and analyses from a collaborative international validation study organized by NICEATM and the European Centre for the Validation of Alternative Methods (ECVAM) to evaluate the usefulness and limitations of two in vitro basal cytotoxicity NRU test methods using either BALB/c 3T3 mouse fibroblasts (3T3) or primary human epidermal keratinocytes (NHK) for estimating acute oral rodent toxicity. Electronic copies of the ICCVAM Test Method Evaluation Report and the BRD are available from the ICCVAM/NICEATM Web site at https:// iccvam.niehs.nih.gov or by contacting NICEATM (see FOR FURTHER INFORMATION CONTACT). The ICCVAM Test Method Evaluation Report and the final BRD have been forwarded to U.S. Federal agencies for regulatory and other acceptance considerations where applicable. Responses will be posted on the ICCVAM/NICEATM Web site as they are received.

The Food and Drug Administration (FDA) is announcing the availability of a final document that has been prepared by Study Group 4 of the Global Harmonization Task Force (GHTF). This document represents a harmonized proposal and recommendation from Study Group 4 of the GHTF that may be used by governments developing and updating their regulatory requirements for medical devices. This document is intended to provide information only and does not describe current regulatory requirements; elements of this document may not be consistent with current U.S. regulatory requirements.

This notice announces an administrative hearing to be held on May 7, 2008, at the CMS Dallas Regional Office, 1301 Young Street, Room 1196, Dallas, Texas 75202, to reconsider CMS' decision to disapprove Texas SPA 07-011. Closing Date: Requests to participate in the hearing as a party must be received by the presiding officer by April 8, 2008.

In compliance with the requirement of Section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, for opportunity for public comment on proposed data collection projects, the National Center for Research Resource (NCRR), the National Institutes of Health (NIH) will publish periodic summaries of proposed projects to be submitted to the Office of Management and Budget (OMB) for review and approval. Proposed Collection: Title: Inventory and Evaluation of Clinical Research Networks. Type of Information Collection Request: Revision of OMB 0925-0550. Expiration: 07/31/08. Need and Use of Information Collection: Through the original data collection, the IECRN project identified and surveyed clinical research networks to obtain data for two purposes: (1) To create a web-based inventory of clinical research networks that can be accessed by the clinical research community and the general public and (2) to prepare a detailed description of existing network practices from a sample of identified networks. The current request is to continue collecting data for the first purpose only. The instrument known as the Core Survey will be used to collect information to confirm that the respondent is truly a clinical research network, plus basic characteristics about each identified clinical research network to be included in the web-based inventory. The information for the inventory database includes the network's name, address, contact information, funding sources, age, geographic coverage, size, composition, and populations and diseases of focus. Permission to post the network's data in the web-based public inventory will be requested, and only those networks that agree will have their information posted. Currently the inventory includes ``network profiles'' for approximately 270 clinical research networks. While this number is believed to represent most of the existing networks, some networks have not yet been identified, are unaware of the existence of the inventory, or are newly formed since the original data collection occurred. In addition, each network in the inventory is requested annually to update the information posted in its ``network profile'' to ensure that the inventory is complete and accurate. Frequency of Response: Once (Core Survey), Annually (Network Updates). Affected Public: Individuals. Type of Respondents: Health Professionals (Physicians and others involved in research networks).

Under the provisions of Section 3507(a)(1)(D) of the Paperwork Reduction Act of 1995, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health has submitted to the Office of Management and Budget (OMB) a request for renewal of an information collection request. The original information collection request was approved (OMB Clearance 0925-0543) following publication in the Federal Register on January 9, 2004, page 1589 and December 2, 2004, page 70153. The proposed collection extension was previously published in the Federal Register on January 16, 2008, page 2925 and allowed 60 days for public comment. Only one public comment was received during the previous comment period. It was received via e-mail from a concerned citizen who stated that she felt that the study should no longer continue because it is not a good use of tax dollars. 5 CFR 1320.5 (General Requirements) Reporting and Recordkeeping Requirements: Final Rule requires that the agency inform the potential persons who are to respond to the collection of information that such persons are not required to respond to the collection of information unless it displays a currently valid OMB control number. This information is required to be stated in the 30-day Federal Register Notice. Proposed Collection: Title: Longitudinal Investigation of Fertility and the Environment (LIFE Study). Type of Information Collection Request: EXTENSION (OMB control number 0925-0543, expiration date, March 30, 2008). Need and Use of Information Collection: The purpose of the LIFE Study is to assess the impact of environmental factors, broadly defined to include lifestyle factors, on human reproduction and development. The LIFE Study is consistent with the mission of the Eunice Kennedy Shriver National Institute of Child Health and Human Development that includes conducting basic, clinical and epidemiologic research focusing on factors and processes associated with human reproduction and development thereby, ensuring the birth of healthy infants capable of reaching full adult potential unimpaired by physical or mental disabilities. This study will assess the relation between select environmental factors and human reproduction and development. This research originally proposed to recruit 960 couples who are interested in becoming pregnant and willing to participate in a longitudinal study. Fewer than expected couples were enrolled during the first three years of the project (n = 350), predominantly due to the fact that more couples were ineligible for participation than had been originally estimated. In light of this fact, the revised study plan is to enroll a total of 500 couples (i.e., 150 additional couples), a sample size that will not compromise the main study objectives. Couples will be selected from geographic regions that were chosen from peer reviewed competitive proposals. Fecundity will be measured by the time required for the couples to achieve pregnancy, while fertility will be measured by the ability of couples to have a live born infant. Infertility will be recognized for couples unable to conceive within 12 months of trying. The study's primary environmental exposures include: Organochlorine pesticides; polychlorinated biphenyls; polybrominated diphenyl ethers; metals; perfluorinated compounds; cotinine; and phytoestrogens. A growing body of literature suggests these compounds may exert adverse effects on human reproduction and development; however, definitive data are lacking especially for sensitive endpoints. Couples will participate in a 25- minute baseline interview and be instructed in the use of home fertility monitors and pregnancy kits for counting the time required for pregnancy and detecting pregnancy. Blood and urine samples will be collected at baseline from both partners of the couple for measurement of the environmental exposures. Two semen samples from male partners and two saliva samples from female partners also will be requested. Semen samples will be used to globally assess male fecundity as measured primarily by sperm concentration and morphology. Saliva samples will be used for the measurement of cortisol levels as a marker of stress among female partners so that the relation between environmental factors, stress and human reproduction can be assessed. The findings will provide valuable information regarding the effect of environmental contaminants on sensitive markers of human reproduction and development, filling critical data gaps. Moreover, these environmental exposures will be analyzed in the context of other lifestyle exposures such as use of cigarettes and alcohol, consistent with the manner in which human beings are exposed. Frequency of Response: Following the baseline interview (25 minutes), couples will each complete a 2-minute daily diary on select lifestyle factors. Women will perform daily fertility testing (7 minutes) approximately 11 days per cycle and pregnancy testing (4 minutes) at day of expected menses using a dipstick test in urine. Approximately 60% of women will become pregnant after 2 to 3 months, at which point they will switch to the less intensive portion of the protocol. Men will provide two semen samples, a month apart, requiring approximately 20 minutes for each collection, and women will collect two saliva samples, a month apart, requiring approximately 6 minutes each. Participating couples will be given a choice to submit their information by mail or to send it electronically to the Data Coordinating Center. This option will be available throughout data collection in the event couples change their minds about how they would like to submit information. Study participants will collect semen and saliva samples and forward them in prepaid delivery packages to the study's laboratories. Research nurses will collect blood and urine samples and return them to the study's laboratories. Affected Public: Individuals from participating communities. Type of Respondents: Men aged 18+ years and women aged 18-40 years. Estimated Number of Respondents: Approximately 500 couples enrolling (minimum of 400 completing the study). Estimated Number of Response Sets Per Respondent: 7 per woman and 4 per man over approximately two years. Average Burden Hours Per Response: (1) 0.17 hours for completing the screening instrument; (2) 0.42 hours for baseline interviews with men and women; (3) 2.5 hours for daily journal while attempting pregnancy for men and women; (4) 0.38 and 0.7 hours for biospecimen collection for women and men, respectively; (5) 2.6 hours for fertility monitors; (6) 0.27 hours for pregnancy testing for women; and (7) 0.29 hours for pregnancy journals for women. Estimated Total Annual Burden Hours Requested: 1,640 to 4,950 hours for female participants and 1,050 to 2,740 hours for male participants depending upon the length of time required for pregnancy. There is no cost to respondents. There are no Capital Costs, Operating Costs, and/or Maintenance Costs to report. Request for Comments: Written comments and/or suggestions from the public and affected agencies are invited on one or more of the following points: (1) Evaluate whether the proposed collection of information is necessary for the proper performance of the function of the agency, including whether the information will have practical utility; (2) Evaluate the accuracy of the agency's estimate of the burden of the proposed collection of information, including the validity of the methodology and assumptions used; (3) Enhance the quality, utility, and clarity of the information to be collected; and (4) Minimize the burden of the collection of information on those who are to respond, including the use of appropriate automated, electronic, mechanical, or other technological collection techniques or other forms of information technology. Direct Comments to OMB: Written comments and/or suggestions regarding the item(s) contained in this notice, especially regarding the estimated public burden and associated response time, should be directed to the: Office of Management and Budget, Office of Regulatory Affairs, OIRA_submission@omb.eop.gov, or by fax to 202-395-6974, Attention: Desk Officer for NIH. To request more information on the proposed project or to obtain a copy of the data collection plans and instruments, contact: Dr. Germaine M. Buck Louis, Epidemiology Branch, Division of Epidemiology, Statistics & Prevention Research, NICHD, 6100 Executive Blvd., Room 7B03, Rockville, MD 20852, 301-496-6155. You may also e-mail your request to louisg@mail.nih.gov. Comments Due Date: Comments regarding this information collection are best assured of having their full effect if received within 30 days of the date of this publication.

The Food and Drug Administration (FDA) is requesting comments and information regarding technologies used for the identification, validation, tracking and tracing, and authentication of prescription drugs. This request is related to FDA's implementation of the Food and Drug Administration Amendments Act of 2007 (FDAAA). Elsewhere in this issue of the Federal Register, FDA is publishing a related document entitled ``Standards for Standardized Numerical Identifier, Validation, Track and Trace, and Authentication for Prescription Drugs; Request for Comments.''

The Food and Drug Administration (FDA) is seeking information and comments on issues related to standards for identification, validation, tracking and tracing, and authentication for prescription drug products. Particularly, we are requesting information and comments from drug manufacturers, distributors, pharmacies, other supply chain stakeholders, foreign regulators, standards organizations, and other Federal agencies and interested parties. This request is related to FDA's implementation of the Food and Drug Administration Amendments Act of 2007 (FDAAA). Elsewhere in this issue of the Federal Register, FDA is publishing a related document entitled ``Technologies for Prescription Drug Identification, Validation, Track and Trace, or Authentication; Request for Information.''