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

The Food and Drug Administration (FDA) is canceling the meeting of the Cardiovascular and Renal Drugs Advisory Committee scheduled for April 5, 2005. This meeting was announced in the Federal Register of March 9, 2005 (70 FR 11678).

The Food and Drug Administration (FDA) is announcing the availability of three guidances for industry entitled ``Premarketing Risk Assessment,'' ``Development and Use of Risk Minimization Action Plans,'' and ``Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment.'' These guidances provide guidance to industry on risk management activities for drug products, including biological drug products, in the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). The guidances address, respectively, premarket risk assessment; the development, implementation, and evaluation of risk minimization action plans for drug products; and good pharmacovigilance practices and pharmacoepidemiologic assessment of observational data.

In accordance with section 10(a) of the Federal Advisory Committee Act, this notice announces a meeting of the National Advisory Council for Healthcare Research and Quality.

The Food and Drug Administration (FDA) is announcing the referral of KEMSTRO (baclofen) and DROXIA (hydroxyurea) to the Foundation for the National Institutes of Health (the Foundation) for the conduct of pediatric studies. FDA referred KEMSTRO (baclofen) and DROXIA (hydroxyurea) to the Foundation on September 1, 2004, and October 20, 2004, respectively. FDA is publishing this notice of the referrals in accordance with the Best Pharmaceuticals for Children Act (BCPA).

The Food and Drug Administration (FDA) is issuing an interim final rule to amend the color additive regulations by increasing the fees for certification services. The change in fees will allow FDA to continue to maintain an adequate color certification program as required by the Federal Food, Drug, and Cosmetic Act (the act). The fees are intended to recover the full costs of operation of FDA's color certification program.

The Administration on Aging (AoA) 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 the information collection requirements relating to State Annual Long-Term Care Ombudsman Report and instructions for Older Americans Act Title VII.

The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995 (the PRA).

The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.

In accordance with section 10(a) of the Federal Advisory Committee Act, this notice announces the first meeting of the Citizens' Health Care Working Group mandated by section 1014 of the Medicare Modernization Act.

The Food and Drug Administration (FDA) is correcting a final rule that appeared in the Federal Register of December 23, 2004 (69 FR 76844). The document amended the food additive regulations by establishing a new maximum permitted energy level of x rays for treating food of 7.5 million electron volts provided the x rays are generated from machine sources that use tantalum or gold as the target material, with no change in the maximum permitted dose levels or uses currently permitted by FDA's food additive regulations. The document was published with two errors in the preamble section. This document corrects those errors.

The Food and Drug Administration (FDA), in cooperation with the Drug Information Association (DIA), is announcing a public meeting to solicit views and provide an interactive forum for discussion of stakeholders' perspectives about, and experiences with, the legal and public health issues that arise when sponsors seek to develop or market a product of one type (device, drug, or biological product) that would be labeled for use with an already approved product of a different type, and the approved product's labeling would not be changed. The input received at the meeting and comments made to the docket after the meeting will be considered in developing draft guidance on this topic.

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 the information collection provisions of FDA's current good manufacturing practice (CGMP) regulations for finished pharmaceuticals.

The Food and Drug Administration (FDA) is announcing the availability of summaries of medical and clinical pharmacology reviews of pediatric studies submitted in supplements for PARAPLATIN (carboplatin), TRUSOPT (dorzolamide), CAMPTOSAR (irinotecan), PREVACID (lansoprazole), TAMIFLU (oseltamivir), VIOXX (rofecoxib), FERRLECIT (sodium ferric gluconate), IMITREX (sumatriptan), DETROL and DETROL LA (tolterodine). These summaries are being made available consistent with the Best Pharmaceuticals for Children Act (the BPCA). For all pediatric supplements submitted under the BPCA, the BPCA requires FDA to make available to the public a summary of the medical and clinical pharmacology reviews of the pediatric studies conducted for the supplement. In addition, the agency is also announcing the availability of summaries of medical and clinical pharmacology reviews of pediatric studies for the following antidepressants: CELAXA (citalopram), REMERON (mirtazapine), SERZONE (nefazodone), PAXIL (paroxetine), and ZOLOFT (sertraline). Studies for these drugs were submitted before the BPCA was implemented. Therefore, they are not subject to its requirements. However, due to the public's interest in these pediatric studies, FDA asked the sponsors to consent to the public disclosure of a summary of the medical and clinical pharmacology reviews for these studies. Based on sponsors' consent, FDA is making the summaries publicly available.

The Office of Public Health and Science, Department of Health and Human Services (HHS) solicits public comment on criteria that have been recommended to the Office for Human Research Protections (OHRP) for making determinations of whether procedures prescribed by institutions outside the United States afford protections that are at least equivalent to those provided in the Federal Policy for the Protection of Human Subjects (codified by HHS as 45 CFR part 46, subpart A, and equivalent regulations of 14 Departments and Agencies, collectively referred to as the Federal Policy or the Common Rule).

The Office of Population Affairs (OPA) requests applications for family planning service delivery improvement research grants. Applied research projects are encouraged in one or more of the following priority areas: (1) Quality of care in the delivery of family planning services; (2) effective approaches and interventions for addressing the reproductive health needs of adolescents and incorporating family members (particularly parents or guardians) into decisions of adolescents regarding relationships and sex; (3) reproductive health needs of males, prevention-related decisions by males and appropriate strategies for reaching male clients; (4) knowledge base for incorporating a ``couples'' perspective into the delivery of family planning services; (5) effective organizational approaches for delivery of family planning services in conjunction with related services, particularly HIV prevention services; (6) dissemination of findings and translation of service delivery research into practice; (7) factors associated with increasing costs and the impact of such increasing costs on service delivery; and (8) effectiveness of Title X non-clinical services with regard to information and education activities. Regulations pertaining to grants for research projects are set out at 42 CFR part 52. Section 1008 of the PHS Act provides that ``none of the funds appropriated under this title shall be used in programs where abortion is a method of family planning.''

This interim final rule with comment period adopts the substance of the April 15, 2004 temporary interim amendment (TIA) 00-1 (101), Alcohol Based Hand Rub Solutions, an amendment to the 2000 edition of the Life Safety Code, published by the National Fire Protection Association (NFPA). This amendment will allow certain health care facilities to place alcohol-based hand rub dispensers in egress corridors under specified conditions. This interim final rule with comment period also requires that nursing facilities install smoke detectors in resident rooms and public areas if they do not have a sprinkler system installed throughout the facility or a hard-wired smoke detection system in those areas.

This notice extends the comment period for a proposed rule published in the Federal Register on February 4, 2005, (70 FR 6086). In that rule, we proposed to establish new conditions for coverage for organ procurement organizations (OPOs), including multiple new outcome and process performance measures based on donor potential and other related factors in each service area of qualified OPOs. We are proposing new standards with the goal of improving OPO performance and increasing organ donation. The comment period is extended for 60 days.

This notice sets forth the procedures for filing with the Secretary of the Department of Health and Human Services a complaint of non-compliance by a covered entity with certain provisions of the administrative simplification rules under 45 CFR parts 160, 162, and 164. It also describes the procedures the Department employs to review the complaints. These procedures are intended to facilitate the investigation and resolution of these complaints.

This notice announces a public meeting of the Medicare Coverage Advisory Committee (MCAC). The Committee provides advice and recommendations about whether scientific evidence is adequate to determine whether certain medical items and services are reasonable and necessary under the Medicare statute. This meeting concerns the treatment of vertebral body compression fractures. Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. App. 2, section 10(a)).

This notice announces the Centers for Medicare & Medicaid Services' (CMS') reapproval of the American Osteopathic Association (AOA) as a national accreditation organization for hospitals that request participation in the Medicare program. We have determined that accreditation of hospitals by AOA demonstrates that all Medicare hospital conditions of participation are met or exceeded. Thus, CMS will continue to grant deemed status to those hospitals accredited by AOA.

This notice announces our decision to approve the Joint Commission on Accreditation of Healthcare Organizations for continued recognition as a national accreditation program for home health agencies seeking to participate in the Medicare or Medicaid programs.

Notice is hereby given that the Office of Research Integrity (ORI) and the Acting Assistant Secretary for Health have taken final action in the following case: Eric T. Poehlman, Ph.D., University of Vermont: Based on the report of an investigation conducted by the University of Vermont (Report), admissions made by the respondent, and additional analysis conducted by ORI in its oversight review, the U.S. Public Health Service (PHS) found that Eric T. Poehlman, Ph.D., former Professor, Department of Medicine at the University of Vermont College of Medicine, engaged in scientific misconduct in research. The research was supported by National Institutes of Health (NIH) grants from the National Institute of Aging (NIA), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and the National Center for Research Resources (NCRR). Specifically, PHS found that the respondent is responsible for scientific misconduct by engaging in the misleading and deceptive practices set forth herein below:

The Food and Drug Administration (FDA) is issuing an order under the Federal Food, Drug, and Cosmetic Act (the act) debarring Dr. Eduardo Caro Acevedo for 5 years from providing services in any capacity to a person that has an approved or pending drug product application. FDA bases this order on a finding that Dr. Caro was convicted of a felony under Federal law for engaging in a conspiracy to defraud the United States and has demonstrated a pattern of conduct sufficient to find that there is reason to believe that he may violate requirements under the act relating to drug products. Dr. Caro failed to request a hearing and, therefore, has waived his opportunity for a hearing concerning this action.

The Administration for Children and Families' (ACF), Administration on Children, Youth and Families' (ACYF), Child Care Bureau (CCB) announces the availability of funds to support new CCB Research Scholar projects in Fiscal Year 2005. The Research Scholar Grants are designed to increase the number of graduate students conducting dissertation research on child care issues that are consistent with the Bureau's research agenda.

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.

The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. in accordance with 35 U.S.C. 207 to achieve expeditious commercialization of results of federally-funded research and development. Foreign patent applications are filed on selected inventions to extend market coverage for companies and may also be available for licensing.

The Food and Drug Administration (FDA) is announcing that a proposed collection of information has been submitted to the Office of Management and Budget (OMB) for review and clearance under the Paperwork Reduction Act of 1995.

Notice is hereby given that the Office of Research Integrity (ORI) and the Acting Assistant Secretary for Health have taken final action in the following case: Gary M. Kammer, M.D., Wake Forest University: Based on the Wake Forest University (WFU) Investigation Report, the respondent's admission, and additional analysis conducted by ORI in its oversight review, the U.S. Public Health Service (PHS) found that Gary M. Kammer, M.D., former Professor, Division of Rheumatology, Department of Internal Medicine, and Department of Microbiology and Immunology at the WFU School of Medicine, engaged in scientific misconduct by falsification and fabrication of research in grant application 2 R01 AR39501-12A1, ``T Lymphocyte Dysfunction in Lupus Erythematosus,'' submitted to the National Institute of Arthritis and Musculoskeletal Skin Diseases (NIAMS), National Institutes of Health (NIH), and in 1 R01 AI46526-01A2, ``Protein Kinase A-II in the Pathogenesis of Lupus,'' submitted to the National Institute of Allergy and Infectious Diseases (NIAID), NIH. Specifically, PHS found that: The respondent fabricated Families 2 and 3 in Figure 6 and related text in application 2 R01 AR39501-12A1 (pp. 29-30), entitled (``T Lymphocyte Dysfunction in Lupus Erythematosus'') by: a. Making up both of the pedigrees, b. Fabricating 13 PKA-I and 13 PKA-II values for these non-existent affected and unaffected family members, and c. Composing the false text describing these two fabricated families. The respondent falsified the text describing the results in Figure 20 (``Inhibition of c-fos luciferase activity in S49 T cells transiently transfected with pIRES2-RIIb-EGFP and treated with 8-Cl- cAMP'') in application 1 R01 AI46526-01A2 (p. 27), by falsely reporting N = 4, P less than 0.002, when the experiment had been performed only one time at the time that the application was submitted. PHS also concluded that the respondent further demonstrated a lack of present responsibility as a Principal Investigator by submitting NIH grant proposals with additional unsupported experimental results: The pedigree and data for the family reported in grant application 2 R01 AR39501-12 and for Family 1 in grant application 2 R01 AR39501-12A1 are incorrect and the data pertaining to this family that Dr. Kammer subsequently provided to WFU after the inquiry were not the data reported in the applications. Dr. Kammer stated that he did not recall who in his laboratory gave him this pedigree. ORI noted that the actual PKA data for the ``proof-of-principle'' family, while suggesting that low PKA values may be hereditary (the presence of low PKA-I values in three generations), do not support the claims of the fabricated and mixed up pedigree and data that show that low PKA-I values were associated with Systematic Lupus Erythematosus (SLE) (application 2R01 AR39501-12). In application, R01 AI39501-12A1, the following unsupported statement was also included: ``In both normal and disease controls, all T cells express CD59+ and there is no significant difference in its cell surface expression on CD4+, CD45RA+, CD4+, CD45RO+, CD8+, CD45RA+, CD8+, CD45RO+ subsets (n=4 each control group; data not shown).'' No data could be produced to support the information in the grant application about these control experiments. Dr. Kammer has entered into a Voluntary Exclusion Agreement (Agreement ) in which he has voluntarily agreed for a period of three (3) years, beginning on February 15, 2005: (1) To exclude himself from serving in any advisory capacity to PHS including but not limited to service on any PHS advisory committee, board, and/or peer review committee, or as a consultant, and (2) To exclude himself from any contracting or subcontracting with any agency of the United States Government and from eligibility or involvement in nonprocurement programs of the United States Government referred to as ``covered transactions'' as defined in the debarment regulations at 45 CFR part 76. This voluntary exclusion precludes the respondent from receiving Federal research, research training, or other research related funds from the Federal Government for three (3) years, but shall not apply to the respondent's participation in a Federal health care program as defined in section 1128B(f) of the Social Security Act and shall not apply to Federal funds used solely for purposes of teaching or training medical students, residents, or fellows in clinical medical matters.

The Office of Public Health and Science, DHHS, is seeking nominations of qualified candidates to be considered for appointment as a member of the Chronic Fatigue Syndrome Advisory Committee (CFSAC). CFSAC provides science-based advice and recommendations to the Secretary of Health and Human Services, through the Assistant Secretary for Health, on a broad range of issues and topics pertaining to chronic fatigue syndrome (CFS). CFSAC, which was formerly known as the Chronic Fatigue Syndrome Coordinating Committee, was established by the Secretary of Health and Human Services on September 5, 2002. The appointments of six Committee members are scheduled to end on September 30, 2005. Nominations of qualified candidates are being sought to fill these scheduled vacancies.