Department of Health and Human Services March 2005 – Federal Register Recent Federal Regulation Documents

The Food and Drug Administration (FDA) is announcing the availability of the guidance document entitled ``Class II Special Controls Guidance Document: Automated Fluorescence in situ Hybridization (FISH) Enumeration Systems.'' This guidance document describes a means by which automated FISH enumeration systems may comply with the requirements of special controls for class II devices. Elsewhere in this issue of the Federal Register, FDA is publishing a final rule to classify automated FISH enumeration systems into class II (special controls). This guidance document is immediately in effect as the special control for automated FISH enumeration systems, but it remains subject to comment in accordance with the agency's good guidance practices (GGPs).

The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Pharmacogenomic Data Submissions.'' The guidance provides recommendations to sponsors holding investigational new drug applications (INDs), new drug applications (NDAs), and biologics license applications (BLAs) on what pharmacogenomic data to submit to the agency during the drug development process, the format of submissions, and how the data will be used in regulatory decisionmaking. The guidance is intended to facilitate scientific progress in the area of pharmacogenomics.

Macrophage cholesterol accumulation in blood vessels leads to the development of atherosclerotic plaques, the cause of most heart attacks and strokes. Recently, research from Dr. Howard Kruth, head of the Experimental Atherosclerosis Section of NHLBI has elucidated a novel mechanism of receptor-independent macrophage cholesterol accumulation\1,2\. In this pathway, human macrophages take up low- density lipoprotein (LDL), the main carrier of blood cholesterol, by fluid-phase endocytosis, an uptake pathway that can be activated in macrophages. Activated macrophages show greatly stimulated uptake of fluid and LDL contained in the fluid through macropinocytosis, a fluid- phase endocytic uptake pathway unique to macrophages. This mechanism of LDL uptake and macrophage cholesterol accumulation does not depend on binding of LDL to receptors. Macrophage macropinocytosis of LDL produces levels of cholesterol accumulation similar to that observed for macrophages isolated from atherosclerotic plaques, something that does not occur when human macrophages take up LDL by receptor-mediated mechanisms in these macrophages. The NHLBI is seeking CRADA collaborators to work with investigators in the Experimental Atherosclerosis Section of NHLBI to identify inhibitors of this cholesterol uptake pathway. The collaborator will provide high throughput screening capabilities coupled with small molecule and/or siRNA libraries of test compounds, or other methodologies to identify potential inhibitors of this pathway. A cell- based screening assay that will have predictive value with human macrophages will be developed jointly by the NHLBI investigators and the collaborator based on published and unpublished research findings of the NHLBI investigators. The goal of this collaboration will be to identify compounds that selectively inhibit macrophage macropinocytosis and consequently macrophage uptake of LDL and cholesterol accumulation. Compounds identified will be further tested in a suitable animal model of atherosclerosis to determine their effect on macrophage cholesterol accumulation and atherosclerotic plaque development. Macropinocytosis also mediates entry of microorganisms such as HIV into macrophages. Thus, discovery of macropinocytosis inhibitors may be relevant not only to atherosclerosis treatment but also to certain infectious disease treatments.

This announcement governs the proposed award of formula grants under the Family Violence Prevention and Services Act to States (including Territories and Insular Areas). The purpose of these grants is to assist States in establishing, maintaining, and expanding programs and projects to prevent family violence and to provide immediate shelter and related assistance for victims of family violence and their dependents. This announcement sets forth the application requirements, the application process, and other administrative and fiscal requirements for grants in fiscal year (FY) 2005. CFDA Number: 93.671, Family Violence Prevention and Services.

The Food and Drug Administration (FDA) is requesting nominations for nonvoting industry representatives to serve on the National Mammography Quality Assurance Advisory Committee (NMQAAC) in the Center for Devices and Radiological Health (CDRH). FDA has a special interest in ensuring that women, minority groups, individuals with disabilities, and small businesses are adequately represented on its advisory committees. Therefore, the agency encourages nominations for appropriately qualified candidates from these groups.

This final rule clarifies our interpretation of the meaning of ``entity'' in the final rule titled ``Medicare Program; Establishment of the Medicare Advantage Program'' published in the Federal Register on January 28, 2005 (70 FR 4588). Subsequent to the publication of the Medicare Advantage (MA) final rule on January 28, 2005, we have received inquiries from parties interested in offering an MA Regional Plan concerning whether they could jointly enter into a contract with us to offer a single MA Regional Plan in a multistate region. The participating health plans wish to contract with each other to create a single ``joint enterprise.'' They have asked us whether such a joint enterprise could be considered an ``entity'' under sections 1859(a)(1) and 1855(a)(1) of the Social Security Act, for purposes of offering an MA Regional Plan. The MA final rule is scheduled to take effect on March 22, 2005. Our interpretation of the word ``entity'' that follows in the ``Supplementary Information'' section of this final rule is deemed to be included in that final rule.

In compliance with the requirements of section 3506(c)(2)(A) of the Paperwork Reduction Act of 1995, for opportunity for public comment on proposed data collection projects, the Office of Science Education, 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: The Effectiveness of the NIH Curriculum Supplements and Workshops Survey. Information Collection Request: New. Need and Use of Information Collection: The survey will attempt to assess the effectiveness of the NIH curriculum supplements in aiding teachers to teach science in a more engaging and interactive way. The supplements help k-12 educators teach science in more engaging and effective ways by featuring the latest NIH research. A typical supplement contains two weeks of student activities on the science behind a health topic, such as cancer, sleep or obesity. Web-based simulations, animations and experiments enhance the ``pencil and paper'' activities. In addition to developing and distributing the supplements, OSE conducts professional workshops to help teachers successfully implement these lessons with their students. Since January 2000, over 3,000 teachers have attended an OSE workshop. Assessing the effectiveness of the NIH Curriculum Supplements and teacher workshops is critical to determining if OSE is successfully fulfilling its mission. OSE has the database infrastructure in place to easily collect customer satisfaction data from supplement requesters and workshop attendees. At present, we do not have clearance to contact our customers to determine how NIH resources are meeting their educational needs.

Following the Senate Committee's recommendation, the Health Resources and Services Administration (HRSA) will give funding preference during the FY 2005 competition to current and former Healthy Start grantees, including those whose Healthy Start grant application was approved but not funded in FY 2004. Senate Report 108-345 at 54 (2004) accompanying the Consolidated Appropriations Act, 2005 (Pub. L. 108-447) states ``The Committee urges HRSA to give preference to current and former grantees with expiring or recently expired project periods. This should include grantees whose grant applications were approved but not funded during fiscal year 2004.''

The Food and Drug Administration (FDA) is amending the animal food additive regulations to correct the specifications for two food additives used in cattle feed. Incorrect symbols describing permitted levels of heavy metals such as lead and arsenic are being corrected with text to reflect the maximum permitted levels of these two impurities in these food additives. This action is being taken to improve the accuracy of the agency's regulations.