Investigational new drug applications; clinical holds; companion document to direct final rule--FDA. Proposed rule

The Food and Drug Administration (FDA) is proposing to amend its regulations governing investigational new drug applications (IND's) for human drug and biological products. This proposed action would amend the IND clinical hold requirements to state that the agency will respond in writing to a sponsor's request that a clinical hold be removed from an investigation within 30-calendar days of the agency's receipt of the request and the sponsor's complete response to the issue(s) that led to the clinical hold. This proposed action is being taken in accordance with provisions of the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). This proposed rule is a companion document to a direct final rule published elsewhere in this issue of the Federal Register. If FDA receives any significant adverse comment, the direct final rule will be withdrawn, and the comments will be considered in the development of a final rule using usual notice-and-comment rulemaking based on this proposed rule.     

Investigational new drug applications and new drug applications--FDA. Final rule

The Food and Drug Administration (FDA) is amending its regulations pertaining to new drug applications (NDA's) to clearly define in the NDA format and content regulations the requirement to present effectiveness and safety data for important demographic subgroups, specifically gender, age, and racial subgroups. FDA also is amending its regulations pertaining to investigational new drug applications (IND's) to require sponsors to tabulate in their annual reports the numbers of subjects enrolled to date in clinical studies for drug and biological products according to age group, gender, and race. This action is intended to alert sponsors as early as possible to potential demographic deficiencies in enrollment that could lead to avoidable deficiencies later in the NDA submission. This rule does not address the requirements for the conduct of clinical studies and does not require sponsors to conduct additional studies or collect additional data. It also does not require the inclusion of a particular number of individuals from specific subgroups in any study or overall. The rule refers only to the presentation of data already collected.     

Investigational new drug, antibiotic, and biological product applications; clinical hold and termination--FDA. Final rule

The Food and Drug Administration (FDA) is issuing a final regulation that provides additional grounds for placing an investigation on "clinical hold" and for terminating an investigational new drug application (IND). Under this rule, FDA may require sponsors to cease distributing an experimental drug in an open, nonconcurrently controlled investigation if any of several specified conditions exist. This final rule is part of the Public Health Service's(PHS's) efforts to make promising drugs widely available to people with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-related disease who lack satisfactory alternative therapies, while simultaneously ensuring that the adequate and well-controlled clinical trials essential to establishing a new drug's safety and effectiveness are expeditiously conducted.     

Skin protectant drug products for over-the-counter human use; astringent drug products; final monograph; direct final rule. Direct final rule

The Food and Drug Administration (FDA) is amending the regulation that established conditions under which over-the-counter (OTC) skin protectant astringent drug products are generally recognized as safe and effective and not misbranded. This action revises some labeling for astringent drug products to be consistent with the final rule for OTC skin protectant drug products (68 FR 33362, June 4, 2003) and adds labeling for certain small packages (styptic pencils). This action is part of FDA's ongoing review of OTC drug products. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule, under FDA's usual procedure for notice-and-comment rulemaking, to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comments and withdraws this direct final rule.     

Investigational new drug application; exception from informed consent; technical amendment--FDA. Final rule

The Food and Drug Administration (FDA) is amending its investigational new drug application (IND) regulations to clarify that, within 30 days after the receipt of an IND for any clinical investigation involving an exception from informed consent, FDA will provide a written determination as to whether the investigation may begin. This action is intended to clarify a recent amendment to the IND regulations for clinical investigations involving an exception from informed consent that states that FDA will provide a written authorization within 30 days of receipt of the IND.     

Investigational new drugs: export requirements for unapproved new drug products. Final rule

The Food and Drug Administration (FDA) is amending its regulations on the exportation of investigational new drugs, including biological products. The final rule describes four different mechanisms for exporting an investigational new drug product. These provisions implement changes in FDA's export authority resulting from the FDA Export Reform and Enhancement Act of 1996 and also simplify the existing requirements for exports of investigational new drugs.     

Investigational new drug applications; amendment to clinical hold regulations for products intended for life-threatening diseases and conditions. Food and Drug Administration, HHS. Final rule

The Food and Drug Administration (FDA) is amending the regulations governing investigational new drug applications (IND's) to permit FDA to place a clinical hold on one or more studies under an IND involving a drug that is intended to treat a life-threatening disease or condition affecting both genders. The amendments permit the agency to place a clinical hold on such studies if men or women with reproductive potential who have the disease or condition are otherwise eligible but are categorically excluded from participation solely because of a perceived risk or potential risk of reproductive or developmental toxicity from use of the investigational drug. This rule was developed in response to the past practice of excluding women with reproductive potential from early clinical trials because of a perceived risk or potential risk of reproductive or developmental toxicity. The final rule does not impose requirements to enroll or recruit a specific number of men or women with reproductive potential.     

Medical devices; medical device reporting. Direct final rule

The Food and Drug Administration (FDA or we) is amending its regulation governing reporting of deaths, serious injuries, and certain malfunctions related to medical devices. We are revising the regulation into plain language to make the regulation easier to understand, and we are making technical corrections. Elsewhere in this issue of the Federal Register, we are publishing a companion proposed rule, under FDA's usual procedures for notice and comment, to provide a procedural framework to finalize the rule in the event we receive any significant adverse comment and withdraw the direct final rule.     

Medical devices; humanitarian use of devices--FDA. Direct final rule

The Food and Drug Administration (FDA) is amending the regulations governing humanitarian use devices. These amendments are being made to implement provisions of the Federal Food, Drug, and Cosmetic Act (the act) as amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA). Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule, under FDA's usual procedures for notice and comment, to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comment and withdraws the direct final rule.     

Beverages: bottled water. Direct final rule

The Food and Drug Administration (FDA) is amending its bottled water quality standard regulations by establishing an allowable level for the contaminant uranium. As a consequence, bottled water manufacturers are required to monitor their finished bottled water products for uranium at least once each year under the current good manufacturing practice (CGMP) regulations for bottled water. Bottled water manufacturers are also required to monitor their source water for uranium as often as necessary, but at least once every 4 years unless they meet the criteria for the source water monitoring exemptions under the CGMP regulations. FDA will retain the existing allowable levels for combined radium-226/-228, gross alpha particle radioactivity, and beta particle and photon radioactivity. This direct final rule will ensure that the minimum quality of bottled water, as affected by uranium, combined radium-226/-228, gross alpha particle radioactivity, and beta particle and photon radioactivity, remains comparable with the quality of public drinking water that meets the Environmental Protection Agency's (EPA's) standards. FDA is issuing a direct final rule for this action because the agency expects that there will be no significant adverse comment on this rule. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed, rule under the agency's usual procedure for notice-and-comment rulemaking, to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comments and withdraws this direct final rule. The companion proposed rule and direct final rule are substantively identical.     

Current good manufacturing practice regulation and investigational new drugs. Direct final rule

The Food and Drug Administration (FDA) is amending its current good manufacturing practice (CGMP) regulations for human drugs, including biological products, to exempt most investigational "Phase 1" drugs from complying with the requirements in FDA's regulations. FDA will instead exercise oversight of production of these drugs under the agency's general statutory CGMP authority and investigational new drug application (IND) authority. In addition, FDA is making available simultaneously with the publication of this direct final rule, a guidance document setting forth recommendations on approaches to CGMP compliance for the exempted Phase 1 drugs. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule, under FDA's usual procedure for notice-and-comment rulemaking, to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comments and withdraws this direct final rule. The companion proposed rule and direct final rule are substantively identical. Elsewhere in this issue of the Federal Register, FDA is announcing the availability of a draft guidance for industry entitled "INDs--Approaches to Complying With CGMP During Phase 1" to provide further guidance on the subject.     

Medical devices; medical device reporting; baseline reports. Direct final rule

The Food and Drug Administration (FDA) is amending its medical device reporting regulations to remove a requirement for baseline reports that the agency deems no longer necessary. Currently, manufacturers provide baseline reports to FDA that include the FDA product code and the premarket approval or premarket notification number. Because most of the information in these baseline reports is also submitted to FDA in individual adverse event reports, FDA is removing the requirement for baseline reports. The removal of this requirement will eliminate unnecessary duplication and reduce the manufacturer's reporting burden. FDA is amending the regulation in accordance with its direct final rule procedures. Elsewhere in this issue of the Federal Register, we are publishing a companion proposed rule under FDA's usual procedures for notice and comment to provide a procedural framework to finalize the rule in the event we receive a significant adverse comment and withdraw this direct final rule.     

Medical devices; humanitarian use of devices--FDA. Direct final rule; withdrawal

The Food and Drug Administration (FDA) published, in the Federal Register of April 17, 1998 (63 FR 19185), a direct final rule to implement the amendments to the humanitarian use devices provision of the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA). The comment period closed July 1, 1998. FDA is withdrawing the direct final rule because the agency received significant adverse comment.     

Medical devices; hearing aids; technical data amendments. Direct final rule

The Food and Drug Administration (FDA) is amending its regulations governing hearing aid labeling to reference the most recent version of the consensus standard used to determine the technical data to be included in labeling for hearing aids. We are amending the regulations to require that manufacturers may use state-of-the-art methods to provide technical data in hearing aid labeling. FDA is also amending the regulations to update an address and remove an outdated requirement. FDA is amending the regulations in accordance with its direct final rule procedures. Elsewhere in this issue of the Federal Register, we are publishing a companion proposed rule under FDA's usual procedures for notice and comment rulemaking to provide a procedural framework to finalize the rule in the event we receive a significant adverse comment and withdraw this direct final rule.     

Medical devices; reports of corrections and removals--FDA. Direct final rule

The Food and Drug Administration (FDA) is amending its regulations that govern reports of corrections and removals of medical devices to eliminate the requirement for distributors to make such reports. The amendments are being made to implement provisions of the Federal Food, Drug, and Cosmetic Act (the act), as amended by the Food and Drug Administration Modernization Act of 1997 (FDAMA). FDA is publishing these amendments in accordance with its direct final rule procedures. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule under FDA's usual procedures for notice and comment to provide a procedural framework to finalize the rule in the event the agency receives any significant adverse comment and withdraws the direct final rule.     

Applications for Food and Drug Administration approval to market a new drug; postmarketing reports; reporting information about authorized generic drugs. Direct final rule

The Food and Drug Administration (FDA) is amending its regulations to require that the holder of a new drug application (NDA) submit certain information regarding authorized generic drugs in an annual report. We are taking this action as part of our implementation of the Food and Drug Administration Amendments Act of 2007 (FDAAA). FDAAA requires that FDA publish a list of all authorized generic drugs included in an annual report since 1999, and that the agency update the list quarterly. We are using direct final rulemaking for this action because the agency expects that there will be no significant adverse comment on the rule. In the proposed rule section of this issue of the Federal Register, we are concurrently proposing and soliciting comments on this rule. If significant adverse comments are received, we will withdraw this final rule and address the comments in a subsequent final rule. FDA will not provide additional opportunity for comment.     

Antiperspirant drug products for over-the-counter human use; final monograph. Final rule

The Food and Drug Administration (FDA) is issuing a final rule in the form of a final monograph establishing conditions under which over-the-counter (OTC) antiperspirant drug products are generally recognized as safe and effective and not misbranded as part of FDA's ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on its proposed regulation, issued as a tentative final monograph (TFM), and all new data and information on antiperspirant drug products that have come to the agency's attention.     

Exempting in-home video telehealth from copayments. Direct final rule

The Department of Veterans Affairs (VA) is taking final action to amend its regulation that governs VA services that are not subject to copayment requirements for inpatient hospital care or outpatient medical care. Specifically, the regulation is amended to exempt in-home video telehealth care from having any required copayment. This removes a barrier that may have previously discouraged veterans from choosing to use in-home video telehealth as a viable medical care option. In turn, VA hopes to make the home a preferred place of care, whenever medically appropriate and possible.     

Antidiarrheal drug products for over-the-counter human use; final monograph. Final rule

The Food and Drug Administration (FDA) is issuing a final rule in the form of a final monograph establishing conditions under which over-the-counter (OTC) antidiarrheal drug products (to control the symptoms of diarrhea) are generally recognized as safe and effective and not misbranded. This final rule is part of FDA's ongoing review of OTC drug products. FDA is issuing this final rule after considering public comments on the agency's proposed regulation, which was issued in the form of a tentative final monograph (TFM), and all new data and information on OTC antidiarrheal drug products that have come to the agency's attention. Also, this final rule amends the regulation that lists nonmonograph active ingredients by adding those OTC antidiarrheal active ingredients that have been found to be not generally recognized as safe and effective.     

Administrative practices and procedures; internal review of agency decisions---FDA. Direct final rule

The Food and Drug Administration (FDA) is amending its regulations governing the review of agency decisions by inserting a statement that sponsors, applicants, or manufacturers of drugs (including biologics) or devices may request review of a scientific controversy by an appropriate scientific advisory panel, or an advisory committee. This action is being taken to clarify the availability of review of scientific controversies by such advisory panels and committees. Elsewhere in this issue of the Federal Register, FDA is publishing a companion proposed rule. If any significant adverse comment is received, FDA will withdraw the direct final rule and will follow its usual procedures for notice-and-comment rulemaking based on the companion proposed rule.