Department of Health and Human Services June 2006 – Federal Register Recent Federal Regulation Documents

The Food and Drug Administration (FDA) is announcing its intention to take enforcement action against unapproved drug products containing carbinoxamine and persons who cause the manufacture of such products. Numerous drug products containing carbinoxamine are marketed without approved applications and many are inappropriately labeled for use in infants and young children. Drug products containing carbinoxamine are new drugs that require approved applications. One firm has approved applications to market products containing carbinoxamine. In addition, there is information showing that carbinoxamine should not be used in children under 2 years of age. Manufacturers who wish to market carbinoxamine products that do not already have FDA approval must obtain FDA approval of a new drug application (NDA) or an abbreviated new drug application (ANDA). Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a guidance entitled ``Marketed Unapproved Drugs Compliance Policy Guide.''

The Food and Drug Administration (FDA) has determined the regulatory review period for CETROTIDE and is publishing this notice of that determination as required by law. FDA has made the determination because of the submission of an application to the Director of Patents and Trademarks, Department of Commerce, for the extension of a patent that claims that human drug product.

Subtitle 2 of Title XXI of the Public Health Service Act, as enacted by the National Childhood Vaccine Injury Act of 1986, as amended (the Act), governs the National Vaccine Injury Compensation Program (VICP). The VICP, administered by the Secretary of Health and Human Services (the Secretary), provides that a proceeding for compensation for a vaccine-related injury or death shall be initiated by service upon the Secretary, and the filing of a petition with the United States Court of Federal Claims (the Court). In some cases, the injured individual may receive compensation for future lost earnings, less appropriate taxes and the ``average cost of a health insurance policy, as determined by the Secretary.'' The Secretary now proposes a new method of calculating the average cost of a health insurance policy.

The Food and Drug Administration (FDA) is announcing the withdrawal, without prejudice to a future filing, of a food additive petition (FAP 2253) proposing that the food additive regulations be amended to provide for the safe use of polyurethane polymer coating in ruminant feed.

The Food and Drug Administration (FDA) Minneapolis District, in cooperation with the Association of Clinical Research Professionals (ACRP), is announcing a workshop on FDA clinical trial statutory and regulatory requirements. This 2-day workshop for the clinical research community targets sponsors, monitors, clinical investigators, institutional review boards, and those who interact with them for the purpose of conducting FDA regulated clinical research. The workshop will include both industry and FDA perspectives on proper conduct of clinical trials regulated by FDA. Date and Time: The public workshop is scheduled for Wednesday, August 23, 2006, from 8 a.m. to 5 p.m. and Thursday, August 24, 2006, from 8:30 a.m. to 12 noon. Location: The public workshop will be held at The Northland Inn, 7025 Northland Dr., Brooklyn Park, MN 55428, 800-441-6422 or 763-536- 8300, FAX: 763-536-8790. Contact: Amy C. Johnson, Public Affairs Specialist, Food and Drug Administration, 212 3rd Ave. South Minneapolis, MN 55401, 612-758-7131, FAX: 612-334-4134, e-mail: amy.johnson@fda.hhs.gov. Registration: Send registration information (including name, title, firm name, address, telephone, and fax number) and the registration fee of $220 (ACRP Minnesota chapter member), $280 (nonmember), or $220 (Government employee). Make registration fee payable to ACRP, and mail to the attention of Paul Below, 441 Timberland Dr., Burnsville, MN 55337. To register via the Internet please go to https://mnacrp.org/ or contact the ACRP webmaster at webmaster@mnacrp.org. (FDA has verified the Web site address, but is not responsible for subsequent changes to the Web site after this document publishes in the Federal Register). The registrar will also accept payment by major credit cards. For more information on the meeting, or for questions on registration, contact Paul Below for ACRP at 441 Timberland Dr., Burnsville, MN 55337, 952-882-4083, FAX: 952-223-1665, e-mail: webmaster@mnacrp.org. Attendees are responsible for their own accommodations. To make reservations at the Northland Inn at a rate of $119.00 plus tax, please contact the Northland Inn (see Location). The registration fee will be used to offset the expenses of hosting the conference, including meals, refreshments, meeting rooms, and materials. Space is limited, therefore interested parties are encouraged to register early. Limited onsite registration may be available. Please arrive early to ensure prompt registration. If you need special accommodations due to a disability, please contact Amy Johnson (see Contact) at least 7 days in advance of the workshop.

Notice is hereby given that the Office of Research Integrity (ORJ) and the Assistant Secretary for Health have taken final action in the following case: Steven Anthony Leadon, Ph.D., University of North Carolina: Based on the report of an investigation conducted by the University of North Carolina (UNC) at Chapel Hill and additional analysis conducted by ORI in its oversight review, the U.S. Public Health Service (PHS) found that Steven Anthony Leadon, Ph.D., former Professor of Radiation Oncology, Department of Radiology, School of Medicine, UNC, engaged in scientific misconduct while supported by National Cancer Institute (NCI), National Institutes of Health (NIH), grant R01 CA40453-09 to 15. Specifically, PHS found that Dr. Landon engaged in scientific misconduct by falsifying DNA samples and constructing falsified figures for experiments done in his laboratory to support claimed findings of defects in a DNA repair process that involved rapid repair of DNA damage in the transcribed strand of active genes, included in four grant applications and in eight publications and one published manuscript, which were included as an Appendix to the Voluntary Exclusion Agreement entered into by Dr. Leadon and are as follows: Figures 1, 2, and 3 in the article by Gowen, L.C., Avrutskaya, A.V., Latour, A.M., Koller, B.H., & Leadon, S.A. ``BRCAI Required for Transcription-Coupled Repair of Oxidation DNA Damage.'' Science 281:109-1012, 1988. In grant application 2 R01 CA40453-14 (p. 9), this article was used as justification for proposed research on BRCA1 and related proteins that may be required for transcription-coupled DNA repair of oxidative DNA damage. Data from the research reported in this paper was also used as preliminary data (Figure 2, p. 16) to support proposed experiments on BRCA1. Figures 1A, 2A, and 3 in the article by Leadon, S.A. & Avrutskaya, A. ``Differential Involvement of the Human Mismatch Repair Proteins, hMLH1 and hMSH2 in Transcription-coupled Repair.'' Cancer Research 57:3784-3791, 1997. Figures 1 and 3 in the article by Leadon, S.A. & Avrutskaya, A.V. ``Requirement for DNA Mismatch Repair Proteins in the Transcription Coupled Repair of Thymine Glycols in Saccharomyces cerevisiae.'' Mutation Research 407:177-187, 1998. Figures 7B and 7C in the article by Cressman, V.L., Backlund, D.C., Avrutskaya, A.V., Leadon, S.A., & Koller, B.H. ``Growth retardation, DNA repair defects, and lack of spermatogenesis in BRCA1- deficient mice.'' Molecular and Cellular Biology 19:7061-7075, 1999. Figures 1 A-D, 3A, 3C, ajd 3D and graphs in the unpublished manuscript by Rauscher, F. J. III, Jensen, D.E., Patel, G., Fredericks, W.J., Schultz, D.C., Proctor, M., Sekido, Y., Minna, J., Chernova, T.A., Wilkinson, K.D., Avrutskaya, A.V., & Leadon, S.A. ``BRCA1-associated ubiquitin hydrolase required for transcription- coupled repair of oxidative DNA damage.'' Submitted to Science on May 16, 2001. In figure 4 in grant application 2 R01 CA40453-14 (pp. 17- 18), data from this unpublished manuscript was used regarding BAP1 defects in TCR. Figure 1A and 3A in the article by Cooper, P.K., Nouspikel, T., Clarkson, S.g., and Leadon, S.A., ``Defective transcription-coupled repair of oxidative base damage in Cockayne syndrome patients from XP group G,'' Science 275: 9907ndash993, 1997. In NIH grant application R01 CA40453-10A1, some of the same data for XPG or XP-G/CS cells from this Science article were included by Dr. Leadon as graphs (Figures 4 and 5, pp. 25-27) before the Science paper was published. Figure 1C, 2A and 2B in the article by LePage, F., Kwoh, E.E., Avrutskaya, A., Gentil, A., Leadon, S.A., Sarasin, A., & Cooper, P.K. ``Transcription-coupled repair of 8-oxoguanine: requirement for XPG, TFIIH, and CSB and implications for Cockayne Syndrome.'' Cell 101:159-171, 2000. Figure 7 in grant application 1 R01 CA092390-01. Figures 1 and 2 and Table 1 in the article by Leadon, S.A., Barbee, S.L., & Dunn, A.B. ``The yeast RAD2, but not RAD1, gene is involved in the transcription-coupled repair of thymine glycols.'' Mutation Research 337:169-178, 1995. Figure 6 in the article Nouspikel, T., Lalle, P., Leadon, S.A., Cooper, P.K., & Clarkson, S.g. ``A common mutational pattern in Cockayne syndrome patients from xeroderma pigmentosum group G: Implications for a second XPG function,'' Proc. Nat. Acad. Sci. USA 94, 3116-3121, 1997. Dr. Leadon's position is that he did not engage in scientific misconduct. His position is that a systematic error was introduced into the experiments in question and he recognizes that it could have influenced or accounted for the results. Dr. Leadon states that he has entered into a Voluntary Exclusion Agreement (Agreement) because he cannot sustain the significant financial burden of a legal proceeding to resolve the disagreements between his position and that of HHS. By entering into this Agreement, Dr. Leadon has voluntarily agreed: (1) To exclude himself from knowingly contracting or subcontracting with any agency of the United States Government and from eligibility or knowing 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 for a period of five (5) years, beginning on May 10, 2006; (2) 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 consultant for a period of five (5) years, beginning on May 10, 2006; and (3) To submit letters of retraction to the editors of the journals listed below within ten (10) business days from the effective date of this Agreement, stating as follows:

This notice announces the first forum of the Office of the National Coordinator for Health Information Technology to address the Nationwide Health Information Network functional requirements. The Forum is open to the public and will discuss the requirements needed for a Nationwide Health Information Network that facilitates the accurate, appropriate, timely, and secure exchange of health information.

The Food and Drug Administration (FDA) is announcing the availability of the guidance entitled ``Class II Special Controls Guidance Document: Olfactory Test Device.'' This guidance document describes a means by which the olfactory test device may comply with the requirement of special controls for class II devices. It includes recommendations for validation of device performance and labeling. Elsewhere in this issue of the Federal Register, FDA is publishing a final rule to classify these device types into class II (special controls).

The Food and Drug Administration (FDA) is issuing this interim final rule to amend its regulations to establish a new exception from the general requirements for informed consent, to permit the use of investigational in vitro diagnostic devices to identify chemical, biological, radiological, or nuclear agents without informed consent in certain circumstances. The agency is taking this action because it is concerned that, during a potential terrorism event or other potential public health emergency, delaying the testing of specimens to obtain informed consent may threaten the life of the subject. In many instances, there may also be others who have been exposed to, or who may be at risk of exposure to, a dangerous chemical, biological, radiological, or nuclear agent, thus necessitating identification of the agent as soon as possible. FDA is creating this exception to help ensure that individuals who may have been exposed to a chemical, biological, radiological, or nuclear agent are able to benefit from the timely use of the most appropriate diagnostic devices, including those that are investigational.